Conditions Flashcards

Question

How are ASDs managed?

Answer 1

Children with significant ASDs significant enough to cause right ventricle dilation will require treatment. For secundum ASDs this is by cardiac catheterisation with insertion of an occlusion device, but for partial AVSD, surgical correction is required. Treatment is undertaken at about 3 to 5 years of age in order to prevent right heart failure and arrythmias in later life.

Answer 2

Common, accounting for 30% of all cases of congenital heart disease. There is a defect anywhere in the ventricular septum, perimembranous (adjacent to the tricuspid valve) or muscular (completely surrounded by muscles). They can most conveniently be considered according to the size of the lesion - small (smaller than the aortic valve, up to 3mm) or large (same size or bigger than the aortic valve) VSDs.

Answer 3

Small: -Usually asymptomatic -Loud pansystolic murmur at lower left sternal edge (loud murmur implies smaller defect) -Quiet pulmonary second sound Large: -Heart failure with breathlessness and faltering growth after 1 week old -Recurrent chest infections -Tachypnoea, Tachycardia and enlarged liver from heart failure -Soft pansystolic murmur or no murmur at all (implying a large defect) -Apical mid-diastolic murmur (from increased flow over the mitral valve after the blood has circulated through the lungs) -Loud pulmonary second sound from raised pulmonary arterial pressure

Answer 4

CXR - may be normal with a small lesion or show cardiomegaly, enlarged pulmonary arteries, increased pulmonary vascular markings or pulmonary oedema with a large lesion ECG - may be normal with a small lesion or show biventricular hypertrophy by two months of age with a large lesion Echocardiography - Demonstrates the precise anatomy of the defect so is diagnostic. Often there is no pulmonary hypertension with a small defect but with a large defect there will be pulmonary hypertension due to high flow.

Answer 5

Small VSDs: lesions close spontaneously, while the defect is present prevention of bacterial endocarditis is by maintaining good oral hygiene. Large VSDs: Diuretics are given combined with captopril (ACE-i). Additional calorie input is required. Surgery is usually performed at 3-6 months of age in order to manage heart failure and faltering growth and to prevent permanent lung damage from pulmonary hypertension and high blood flow

Answer 6

The ductus arteriosus connects the pulmonary artery to the descending aorta. In term infants, it normally closes shortly after birth. In PDA it has failed to close by 1 month after the expected date of delivery due to a defect in the constrictor mechanism of the duct. The flow of blood across a PDA is then from the aorta to the pulmonary artery (i.e. left to right), following the fall in pulmonary vascular resistance after birth. In the preterm infant, the presence of a PDA is not from congenital heart disease but due to prematurity.

Answer 7

Most children present with a continuous murmur beneath the left clavicle. The murmur continues into diastole because the pressure in the pulmonary artery is lower than that in the aorta throughout the cardiac cycle. The pulse pressure is increased, causing a collapsing or bounding pulse. Symptoms are unusual, but when the duct is large there will be increased pulmonary blood flow with heart failure and pulmonary hypertension.

Answer 8

The chest radiograph and ECG are usually normal, but if the PDA is large and symptomatic the features on chest radiograph and ECG are indistinguishable from those seen in a patient with a large VSD (cardiomegaly, enlarged pulmonary arteries, increased pulmonary vascular markings, pulmonary oedema). However, the duct is readily identified on echocardiography.

Answer 9

Closure is recommended to abolish the lifelong risk of bacterial endocarditis and of pulmonary vascular disease. Closure is with a coil or occlusion device introduced via a cardiac catheter at about 1 year of age. Occasionally, surgical ligation is required.

Answer 10

-Tetralogy of fallot -Transposition of the great arteries Presentation is with cyanosis (blue, oxygen saturations <94%, or collapsed), usually in the first week of life.

Answer 11

The Hyperoxia (Nitrogen washout) test The infant is place in 100% oxygen (headbox or ventilator) for 10 minutes. If the right radial arterial partial pressure of oxygen (PaO2) from a blood gas remains low (<15 kPa, 113 mmHg) after this time, a diagnosis of ‘cyanotic’ congenital heart disease can be made if lung disease and persistent pulmonary hypertension of the newborn have been excluded. If the PaO2 is over 20kPa, it is not cyanotic heart disease. Blood gas analysis must be performed as oxygen saturations are not reliable enough in this range of values.

Answer 12

-Stabilize the airway, breathing, and circulation (ABC), with artificial ventilation if necessary. -Start prostaglandin infusion (5ng/kg per min). Most infants with cyanotic heart disease presenting in the first few days of life are duct dependent, i.e. there is reduced mixing between the pink oxygenated blood returning from the lungs and the blue deoxygenated blood from the body. Maintenance of ductal patency is the key to early survival of these children. Observe for potential side-effects of prostaglandin – apnoea, jitteriness and seizures, flushing, vasodilatation and hypotension.

Answer 13

1. Large VSD 2. Overriding of the aorta with respect to the ventricular septum 3. Subpulmonary stenosis causing right ventricular outflow tract obstruction 4. Right ventricular hypertrophy as a result

Answer 14

Symptoms Most are diagnosed: * antenatally or * following the identification of a murmur in the first 2 months of life. Cyanosis at this stage may not be obvious, although a few present with severe cyanosis in the first few days of life. The classical description of severe cyanosis, hypercyanotic spells and squatting on exercise developing in late infancy, is now rare in developed countries, but still common where access to the necessary paediatric cardiac services is not available. It is important to recognize hypercyanotic spells, as they may lead to myocardial infarction, cerebrovascular accidents and even death if left untreated. They are characterized by a rapid increase in cyanosis, usually associated with irritability or inconsolable crying because of severe hypoxia and breathlessness and pallor because of tissue acidosis. On auscultation, there is a very short murmur during a spell. Signs * Clubbing of the fingers and toes will develop in older children. * A loud harsh ejection systolic murmur at the left sternal edge from day 1 of life. With increasing right ventricular outflow tract obstruction, which is predominantly muscular and below the pulmonary valve the murmur will shorten and cyanosis will increase.

Answer 15

CXR: Relatively small heart, possibly with an uptilted apex (boot shaped) due to right ventricular hypertrophy, more prominent in the older child. There may be a right-sided aortic arch, but characteristically there is a pulmonary artery ‘bay’, a concavity on the left heart border where the convex-shaped main pulmonary artery and right ventricular outflow tract would normally be profiled. There may also be decreased pulmonary vascular markings reflecting reduced pulmonary blood flow. ECG: Normal at birth. Right ventricular hypertrophy when older. Echocardiography: This will demonstrate the cardinal features, but cardiac catheterization may be required to show the detailed anatomy of the coronary arteries.

Answer 16

* Initial management is medical, with definitive surgery at around 6 months of age. It involves closing the VSD and relieving right ventricular outflow tract obstruction, sometimes with an artificial patch which extends across the pulmonary valve. * Infants who are very cyanosed in the neonatal period require a shunt to increase pulmonary blood flow. This is usually done by surgical placement of an artificial tube between the subclavian artery and the pulmonary artery (a modified Blalock–Taussig shunt), or sometimes by balloon dilatation of the right ventricular outflow tract. * Hypercyanotic spells are usually self-limiting and followed by a period of sleep. If prolonged (beyond about 15 min), they should be given prompt treatment, according to need, with: – sedation and pain relief (morphine is excellent) – intravenous propranolol (or an α adrenoceptor agonist), which probably works both as a peripheral vasoconstrictor and by relieving the subpulmonary muscular obstruction that is the cause of reduced pulmonary blood flow – intravenous volume administration – bicarbonate to correct acidosis – muscle paralysis and artificial ventilation in order to reduce metabolic oxygen demand.

Answer 17

The aorta is connected to the right ventricle and the pulmonary artery is connected to the left ventricle (discordant ventriculo–arterial connection). The blue blood is therefore returned to the body and the pink blood is returned to the lungs. There are two parallel circulations – unless there is mixing of blood between them, this condition is incompatible with life. Fortunately, there are a number of naturally occurring associated anomalies, e.g. VSD, ASD and PDA as well as therapeutic interventions which can achieve this mixing in the short term.

Answer 18

Cyanosis is the predominant symptom. It may be profound and life-threatening. Presentation is usually on day 2 of life when ductal closure leads to a marked reduction in mixing of the desaturated and saturated blood. Cyanosis will be less severe and presentation delayed if there is more mixing of blood from associated anomalies, e.g. an ASD. Physical signs: * Cyanosis is always present. * The second heart sound is often loud and single. * Usually no murmur, but may be a systolic murmur from increased flow or stenosis within the left ventricular (pulmonary) outflow tract.

Answer 19

CXR: This may reveal the classic findings of a narrow upper mediastinum with an ‘egg on side’ appearance of the cardiac shadow (due to the anteroposterior relationship of the great vessels, narrow vascular pedicle, and hypertrophied right ventricle, respectively). Increased pulmonary vascular markings are common due to increased pulmonary blood flow. ECG: This is usually normal. Echocardiography: This is essential to demonstrate the abnormal arterial connections and associated abnormalities

Answer 20

* In the sick cyanosed neonate, the key is to improve mixing. * Maintaining the patency of the ductus arteriosus with a prostaglandin infusion is mandatory. * A balloon atrial septostomy may be a life-saving procedure, which may need to be performed in 20% of those with transposition of the great arteries. A catheter with an inflatable balloon at its tip is passed through the umbilical or femoral vein and then on through the right atrium and foramen ovale. The balloon is inflated within the left atrium and then pulled back through the atrial septum. This tears the atrial septum, renders the flap valve of the foramen ovale incompetent and so allows mixing of the systemic and pulmonary venous blood within the atrium. * All patients with transposition of the great arteries will require surgery, which is usually the arterial switch procedure in the neonatal period. In this operation, performed in the first few days of life, the pulmonary artery and aorta are transected above the arterial valves and switched over. In addition, the coronary arteries have to be transferred across to the new aorta.

Answer 21

If high pulmonary blood flow due to a large left-to-right shunt or common mixing is not treated at an early stage, then the pulmonary arteries become thick walled and the resistance to flow increases. Gradually, those children that survive become less symptomatic as the shunt decreases. Eventually, at about 10–15 years of age, the shunt reverses and the teenager becomes blue, which is Eisenmenger syndrome. This situation is progressive and the adult will die in right heart failure at a variable age, usually in the fourth or fifth decade of life. Treatment is aimed at prevention of this condition, with early intervention for high pulmonary blood flow. Transplantation is not easily available although there are now medicines to palliate such pulmonary vascular disease eg inhaled nitric oxide, intravenous magnesium sulfate, oral phosphodiesterase inhibitors including sildenafil, prostacyclin or inhaled iloprost.

Answer 22

-Complete AVSD -Complex congenital heart disease eg tricuspid atresia

Answer 23

This is most commonly seen in children with Down syndrome. A complete AVSD is a defect in the middle of the heart with a single five-leaflet (common) valve between the atria and ventricles, which stretches across the entire atrioventricular junction and tends to leak. As there is a large defect there is pulmonary hypertension. Features of a complete AVSD are: * presentation on antenatal ultrasound screening * cyanosis at birth or heart failure at 2 weeks to 3 weeks of life * no murmur heard, the lesion being detected on routine echocardiography screening in a newborn baby with Down syndrome * there is always a superior axis on the ECG * management is to treat heart failure medically (as for large VSD) and surgical repair at 3 months to 6 months of age.

Answer 24

-Tricuspid atresia -Mitral atresia -Double inlet left ventricle -Common arterial trunk (truncus arteriosus) Their main presenting feature depends on whether cyanosis or heart failure is more predominant. Tricuspid atresia is the most common.

Answer 25

In tricuspid atresia, only the left ventricle is effective, the right being small and nonfunctional. Clinical features: There is ‘common mixing’ of systemic and pulmonary venous return in the left atrium. Presentation is with cyanosis in the newborn period if duct dependent, or the child may be well at birth and become cyanosed or breathless.

Answer 26

Early palliation (as with all the common mixing complex diseases) is performed to maintain a secure supply of blood to the lungs at low pressure, by: - A Blalock–Taussig shunt insertion (between the subclavian and pulmonary arteries) in children who are severely cyanosed - Pulmonary artery banding operation to reduce pulmonary blood flow if breathless. Completely corrective surgery is not possible with most, as there is often only one effective functioning ventricle. Palliation is performed (Glenn or hemi-Fontan operation connecting the superior vena cava to the pulmonary artery after 6 months of age and a Fontan operation to also connect the inferior vena cava to the pulmonary artery at 3–5 years of age). Thus the left ventricle drives blood around the body and systemic venous pressure supplies blood to the lungs. The Fontan operation results in a less than ideal functional outcome, but has the advantages of relieving cyanosis and removing the long-term volume load on the single functional ventricle.

Answer 27

These lesions are: * Aortic stenosis * Pulmonary stenosis * Adult-type coarctation of the aorta

Answer 28

The aortic valve leaflets are partly fused together, giving a restrictive exit from the left ventricle. There may be one to three aortic leaflets. Aortic stenosis may not be an isolated lesion. It is often associated with mitral valve stenosis and coarctation of the aorta, and their presence should always be excluded. Clinical features: -Most present with an asymptomatic murmur. -Those with severe stenosis may present with reduced exercise tolerance, chest pain on exertion, or syncope. -In the neonatal period, those with critical aortic stenosis and a duct-dependent systemic circulation may present with severe heart failure leading to shock. Physical signs * Small volume, slow rising pulses. * Carotid thrill (always) * Ejection systolic murmur maximal at the upper right sternal edge radiating to the neck. * Delayed and soft aortic second sound. * Apical ejection click

Answer 29

Investigations CXR: Normal or prominent left ventricle with post-stenotic dilatation of the ascending aorta. ECG: There may be left ventricular hypertrophy. Management In children, regular clinical and echocardiographic assessment is required in order to assess when to intervene. Children with symptoms on exercise or who have a high resting pressure gradient (>64 mmHg) across the aortic valve will undergo balloon valvotomy. Balloon dilatation in older children is generally safe and uncomplicated, but in neonates this is much more difficult and dangerous. Most neonates and children with significant aortic valve stenosis requiring treatment in the first few years of life will eventually require aortic valve replacement. Early treatment is therefore palliative and directed towards delaying this for as long as possible.

Answer 30

The pulmonary valve leaflets are partly fused together, giving a restrictive exit from the right ventricle. Clinical features Most are asymptomatic. It is diagnosed clinically. A small number of neonates with critical pulmonary stenosis have a duct-dependent pulmonary circulation and present in the first few days of life with cyanosis. Physical signs * An ejection systolic murmur best heard at the upper left sternal edge; thrill may be present. * An ejection click best heard at the upper left sternal edge. * When severe, there is a prominent right ventricular impulse (heave).

Answer 31

CXR: Normal or post-stenotic dilatation of the pulmonary artery. ECG: Shows evidence of right ventricular hypertrophy (upright T wave in V1). Management Most children are asymptomatic and when the pressure gradient across the pulmonary valve becomes markedly increased (>about 64 mmHg), intervention will be required. Transcatheter balloon dilatation is the treatment of choice in most children.

Answer 32

This uncommon lesion is not duct dependent. It gradually becomes more severe over many years. Clinical features * Asymptomatic. * Systemic hypertension in the right arm. * Ejection systolic murmur at upper sternal edge. * Collaterals heard with continuous murmur at the back. * Radio-femoral delay. This is due to blood bypassing the obstruction via collateral vessels in the chest wall and hence the pulse in the legs is delayed. Investigations CXR: * ‘Rib notching’ due to the development of large collateral intercostal arteries running under the ribs posteriorly to bypass the obstruction. * ‘3’ sign, with visible notch in the descending aorta at site of the coarctation. ECG: * Left ventricular hypertrophy Management When the condition becomes severe, as assessed by echocardiography, a stent may be inserted at cardiac catheter. Sometimes surgical repair is required.

Answer 33

These lesions include: * Coarctation of the aorta * Interruption of the aortic arch * Hypoplastic left heart syndrome. Clinical features are: * In all of these children, they usually present sick with heart failure and shock in the neonatal period, unless diagnosed on antenatal ultrasound Management is: * resuscitate (ABC) * prostaglandin should be commenced at the earliest opportunity * referral is made to a cardiac centre for early surgical intervention.

Answer 34

This is due to arterial duct tissue encircling the aorta just at the point of insertion of the duct. When the duct closes, the aorta also constricts, causing severe obstruction to the left ventricular outflow. This is the most common cause of collapse due to left outflow obstruction. Clinical features Examination on the first day of life is usually normal. The neonates usually present with acute circulatory collapse at 2-days of age when the duct closes. Physical signs * A sick baby, with severe heart failure. * Absent femoral pulses. * Severe metabolic acidosis. Investigations CXR: Cardiomegaly from heart failure and shock. ECG: Normal. Management * resuscitate (ABC) * prostaglandin should be commenced at the earliest opportunity * referral is made to a cardiac centre for early surgical intervention. *Surgical repair is performed soon after diagnosis.

Answer 35

* Uncommon, with no connection between the proximal aorta and distal to the arterial duct, so that the cardiac output is dependent on right-to-left shunt via the duct * A VSD is usually present. * Presentation is with shock in the neonatal period . * Complete correction with closure of the VSD and repair of the aortic arch is usually performed within the first few days of life. * Association with other conditions (DiGeorge syndrome – absence of thymus, palatal defects, immunodeficiency and hypocalcaemia, and chromosome 22q11.2 microdeletion).

Answer 36

In this condition there is underdevelopment of the entire left side of the heart. The mitral valve is small or atretic, the left ventricle is diminutive, and there is usually aortic valve atresia. The ascending aorta is very small, and there is almost invariably coarctation of the aorta. Clinical features These children may be detected antenatally at ultrasound screening. This allows for effective counselling and prevents the child from becoming sick after birth. If they do present after birth, they are the sickest of all neonates presenting with a duct-dependent systemic circulation. There is no flow through the left side of the heart, so ductal constriction leads to profound acidosis and rapid cardiovascular collapse. There is weakness or absence of all peripheral pulses, in contrast to weak femoral pulses in coarctation of the aorta. Management The management of this condition consists of a difficult neonatal operation called the Norwood procedure. Children who have complex lesions or are small for gestational age undergo hybrid procedures that are a combination of cardiac catheter and surgical operation. This is followed by a further operation (Glenn or hemi-Fontan) at about 6 months of age and again (Fontan) at about 3 years of age.

Answer 37

The most common reason for this is replacement of artificial valves and relief of postsurgical suture line stenosis, e.g. re-coarctation or pulmonary artery stenosis.

Answer 38

-SVT -Congenital complete heart block -Long QT syndrome Atrial fibrillation, atrial flutter, ectopic atrial tachycardia, ventricular tachycardia and ventricular fibrillation occur in children, but all are rare. They are most often seen in children who have undergone surgery for complex congenital heart disease.

Answer 39

This is the most common childhood arrhythmia. The heart rate is rapid, between 250–300 beats/min. It can cause poor cardiac output and pulmonary oedema. It typically presents with symptoms of heart failure in the neonate or young infant. It is a cause of hydrops fetalis and intrauterine death. The term re-entry tachycardia is used because a circuit of conduction is set up, with premature activation of the atrium via an accessory pathway. There is rarely a structural heart problem, but an echocardiogram should be performed. Investigation The ECG will generally show a narrow complex tachycardia of 250–300 beats/min. It may be possible to discern a P wave after the QRS complex due to retrograde activation of the atrium via the accessory pathway. If heart failure is severe, there may be changes suggestive of myocardial ischaemia, with T-wave inversion in the lateral precordial leads. When in sinus rhythm, a short P–R interval may be discernible. In the Wolff–Parkinson–White syndrome, the early antegrade activation of the ventricle via the pathway results in a short P–R interval and a delta wave. Management In the severely ill child, prompt restoration of sinus rhythm is the key to improvement. This is achieved by: * Circulatory and respiratory support – tissue acidosis is corrected, positive pressure ventilation if required * Vagal stimulating manoeuvres, e.g. carotid sinus massage or cold ice pack to face, successful in about 80% * Intravenous adenosine – the treatment of choice. This is safe and effective, inducing atrioventricular block after rapid bolus injection. It terminates the tachycardia by breaking the re-entry circuit that is set up between the atrioventricular node and accessory pathway. It is given incrementally in increasing doses * Electrical cardioversion with a synchronized direct current shock (0.5–2 J/kg body weight) if adenosine fails. Once sinus rhythm is restored, maintenance therapy will be required, e.g. with flecainide or sotalol. Digoxin can be used on its own when there is no overt pre-excitation wave (delta wave) on the resting ECG, but propranolol can be added in the presence of pre-excitation. Even though the resting ECG may remain abnormal, 90% of children will have no further attacks after infancy. Treatment is therefore stopped at 1 year of age. Those who have Wolff–Parkinson–White syndrome need to be assessed to ensure they cannot conduct quickly and this may be undertaken in teenage life, with atrial pacing. This will reduce the small chance of sudden death in such patients. Those who relapse or are at risk are usually treated with percutaneous radiofrequency ablation or cryoablation of the accessory pathway.

Answer 40

This is a rare condition that is usually related to the presence of anti-Ro or anti-La antibodies in maternal serum. These mothers will have either manifest or latent connective tissue disorders. Subsequent pregnancies are often affected. This antibody appears to prevent normal development of the electrical conduction system in the developing heart, with atrophy and fibrosis of the atrioventricular node. It may cause fetal hydrops, death in utero and heart failure in the neonatal period. However, most remain symptom free for many years, but a few become symptomatic with presyncope or syncope. All children with symptoms require insertion of an endocardial pacemaker. There are other rare causes of complete heart block.

Answer 41

Long QT syndrome may be associated with sudden loss of consciousness during exercise, stress or emotion, usually in late childhood. It may be mistakenly diagnosed as epilepsy. If unrecognized, sudden death from ventricular tachycardia may occur. Inheritance is autosomal dominant; there are several phenotypes. It has been associated with erythromycin therapy, electrolyte disorders and head injury. It is one of the group of channelopathies caused by specific gene mutations. Abnormalities of the sodium, potassium or calcium channels lead to gain or loss of function. Anyone with a family history of sudden unexplained death or a history of syncope on exertion should be assessed.

Answer 42

Transient loss of consciousness is usually due to syncope, when it is associated with a loss of postural tone with spontaneous recovery. It is caused by a transient impairment of brain oxygen delivery, generally due to impaired cerebral perfusion. This is common in adolescents and is usually benign, but rarely it is due to cardiac disease, which may be life-threatening. The causes are: * Neurally mediated syncope – is in response to a range of provocations and stressors. These may be from just standing up too quickly (a symptom of ‘orthostatic intolerance’), to the sight of blood or needles or to a sudden unexpected pain. There is usually a prodrome of dizziness and light-headed feeling and abnormal vision often with nausea, sweating, or pallor. When associated with jerking movements, it can easily be misdiagnosed as epilepsy. In most episodes there is a maladaptive drop in blood pressure; in a significant minority there is a marked fall in heart rate and in a few there is asystole * Cardiac syncope – may be arrhythmic, from heart block, supraventricular tachycardia, ventricular tachycardia, e.g. associated with long QT syndrome or structural, associated with aortic stenosis, hypertrophic cardiomyopathy. Features suggestive of a cardiac cause are: * Symptoms on exercise – potentially dangerous * family history of sudden unexplained death * palpitations. Check blood pressure and for signs of cardiac disease (murmur, femoral pulses, signs of Marfan syndrome). Investigate all presenting with transient loss of consciousness with a standard 12-lead ECG, and check the corrected Q-T interval.

Answer 43

Acute rheumatic fever is a short-lived, multisystem autoimmune response to a preceding infection with group A β-haemolytic streptococcus. The disease mainly affects children aged 5–15 years. It progresses to chronic rheumatic heart disease in up to 80% of cases. After a latent interval of 2–6 weeks following a pharyngeal or skin infection, polyarthritis, mild fever and malaise develop. Jones criteria for diagnosis of rheumatic fever = Two major, or one major and two minor, criteria plus supportive evidence of preceding group A streptococcal infection (markedly raised or rising ASO titre or positive rapid streptococcal antigen test or positive group A streptococcus on throat culture) Major manifestations: -Migratory arthritis (80%): Ankles, knees, and wrists, Exquisite tenderness, moderate rednes, and swelling. 'Flitting', lasting <1 week in a joint, but migrating to other joints over 1–2 months -Carditis (50%); Endocarditis - significant murmur, valvular dysfunction. Myocarditis - may lead to heart failure and death Pericarditis - pericardial friction rub, pericardial effusion, tamponade -Sydenham chorea (10%): 2–6 months after the streptococcal infection. Involuntary movements and emotional lability for 3–6 months -Erythema marginatum (<5%): Uncommon, early manifestation. Rash on trunk and limbs Pink macules spread outwards, causing pink border with fading centre. Borders may unite to give a maplike outline. - Subcutaneous nodules (rare): Painless, pea-sized, hard. Mainly on extensor surfaces Minor manifestations: Fever Polyarthralgia Raised acute-phase reactants: ESR, C-reactive protein, leucocytosis Prolonged P–R interval on ECG

Answer 44

The most common form of long-term damage from scarring and fibrosis of the valve tissue of the heart is mitral stenosis. If there have been repeated attacks of rheumatic fever with carditis, this may occur as early as the second decade of life, but usually symptoms do not develop until early adult life. Although the mitral valve is the most frequently affected, aortic, tricuspid and rarely, pulmonary valve disease may occur.

Answer 45

Acute rheumatic fever is usually treated with bed rest and anti-inflammatory agents. While there is evidence of active myocarditis (echocardiographic changes with a raised erythrocyte sedimentation rate), bed rest and limitation of exercise are essential. Aspirin is very effective at suppressing the inflammatory response of the joints and heart. It needs to be given in high dosage and serum levels monitored. If the fever and inflammation do not resolve rapidly, corticosteroids may be required. Symptomatic heart failure is treated with diuretics and ACE inhibitors, and significant pericardial effusions will require pericardiocentesis. Anti-streptococcal antibiotics may be given if there is any evidence of persisting infection. Following resolution of the acute episode, recurrence should be prevented. Monthly injections of benzathine penicillin is the most effective prophylaxis. Alternatively, penicillin can be given orally every day, but it is less effective and compliance may be a problem. Oral erythromycin can be substituted in those sensitive to penicillin. Most recommend prophylaxis for either 10 years after the last episode of acute rheumatic fever or until the age of 21 years, whichever is the longer, or lifelong prophylaxis if there is severe valvular disease. The severity of eventual rheumatic valvular disease relates to the number of childhood episodes of rheumatic fever. Symptomatic patients are given medical therapy to relieve symptoms and disease progression, but surgical intervention with valvular repair or replacement may be required, but carry significant risk.

Answer 46

All children of any age with congenital heart disease (except secundum ASD), including neonates, are at risk of infective endocarditis. The risk is highest when there is a turbulent jet of blood, as with a VSD, coarctation of the aorta and PDA or if prosthetic material has been inserted at surgery. It may be difficult to diagnose, but should be suspected in any child or adult with a sustained fever, malaise, raised ESR, unexplained anaemia or haematuria. The presence of the classical peripheral stigmata of infective endocarditis should not be relied upon. Clinical signs * Fever * Anaemia and pallor * Splinter haemorrhages in nailbed * Clubbing (late) * Necrotic skin lesions * Changing cardiac signs * Splenomegaly * Neurological signs from cerebral infarction * Retinal infarcts * Arthritis/arthralgia * Haematuria (microscopic). Diagnosis Multiple blood cultures should be taken before antibiotics are started. Detailed cross-sectional echocardiography may confirm the diagnosis by identification of vegetations but can never exclude it. The vegetations consist of fibrin and platelets and contain infecting organisms. Acute-phase reactants are raised and can be useful to monitor response to treatment. Treatment The most common causative organism is α-haemolytic streptococcus (Streptococcus viridans). Bacterial endocarditis is usually treated with high-dose penicillin in combination with an aminoglycoside, giving 6 weeks of intravenous therapy and checking that the serum level of the antibiotic will kill the organism. If there is infected prosthetic material, e.g. prosthetic valves, VSD patches or shunts, there is less chance of complete eradication and surgical removal may be required. Prophylaxis The most important factor in prophylaxis against endocarditis is good dental hygiene that should be strongly encouraged in all children with congenital heart disease along with avoidance of body piercing and tattoos. Antibiotic prophylaxis is no longer recommended in the UK, but may be required in other countries for: * dental treatment, however, trivial * surgery which is likely to be associated with bacteraemia.

Answer 47

Dilated cardiomyopathy (a large, poorly contracting heart) may be inherited, secondary to metabolic disease or may result from a direct viral infection of the myocardium. It should be suspected in any child with an enlarged heart and heart failure who has previously been well. The diagnosis is readily made on echocardiography. Treatment is symptomatic with diuretics and ACE inhibitors and carvedilol, a beta-blocker. The role of steroids and immunoglobulin infusion is controversial.

Answer 48

This mainly affects children of 6 months to 5 years of age. An echocardiogram is performed at diagnosis that may show a pericardial effusion, myocardial disease (poor contractility), endocardial disease (valve regurgitation) or coronary disease with aneurysm formation, which can be giant (>8 mm in diameter). If the coronary arteries are abnormal, angiography or magnetic resonance imaging will be required.

Answer 49

Causes: -Pulmonary arterial hypertension *Idiopathic: sporadic or familial *Post-tricuspid shunts (e.g. VSD, AVSD, PDA) *HIV infection *Persistent pulmonary hypertension of the newborn -Pulmonary venous hypertension *Left-sided heart disease *Pulmonary vein stenosis or compression -Pulmonary hypertension with respiratory disease *Chronic obstructive lung disease or bronchopulmonary dysplasia in preterm infants *Interstitial lung disease *Obstructive sleep apnoea or upper airway obstruction - Pulmonary thromboembolic disease -Pulmonary inflammatory or capillary disease. From the cardiac perspective, most children with pulmonary hypertension (high pulmonary artery pressure, mean >25 mmHg) have a large post-tricuspid shunt with high pulmonary blood flow and low resistance, e.g. VSD, AVSD or PDA. The pressure falls to normal if the defect is corrected by surgery within 6 months of age. If these children are left untreated, however, the high flow and pressure cause irreversible damage to the pulmonary vascular bed (pulmonary vascular disease), which is not correctable other than by heart/lung transplantation. Many medical therapies are now available, which may act on the pulmonary vasculature on the cyclic guanosine monophosphate pathway (e.g. inhaled nitric oxide, intravenous magnesium sulphate and oral phosphodiesterase inhibitors including sildenafil) or on the cyclic adenosine monophosphate pathway (intravenous prostacyclin or inhaled iloprost). In addition, endothelin receptor antagonists are valuable but expensive therapy, e.g. oral bosentan. Anticoagulation is often given with heparin, aspirin or warfarin. These medications allow transplantation to be delayed for many years.

Answer 50

Presentation of respiratory disorders in children is with: * upper respiratory tract symptoms of coryza, sore throat, earache, sinusitis or stridor * lower respiratory tract symptoms of cough, wheeze and respiratory distress.

Answer 51

As children, especially infants, have compliant chest walls and poorly developed respiratory muscles, they are particularly susceptible to respiratory failure, and early detection and prevention are the cornerstone of management. Infants may develop signs of respiratory distress from most respiratory disorders. Its features are: * moderate – tachypnoea, tachycardia, nasal flaring, use of accessory respiratory muscles, intercostal and subcostal recession, head retraction and inability to feed * severe – cyanosis, tiring because of increased work of breathing, reduced conscious level, oxygen saturation < 92% despite oxygen therapy.

Answer 52

Ex-preterm infants with bronchopulmonary dysplasia, those with haemodynamically significant congenital heart disease or disorders causing muscle weakness, cystic fibrosis (CF) or immunodeficiency. Susceptibility to specific acute respiratory infections varies with age.

Answer 53

A review of the respiratory physiology explains why stridor, from extrathoracic airway obstruction in the trachea and larynx, is predominantly inspiratory, and wheeze, from intrathoracic airway narrowing, is predominantly expiratory. Inspiration is an active process in which the contraction and downward movement of the diaphragm combines with the upward and outward movement of the ribs to generate a negative pressure in the thoracic cavity, which sucks air into the lungs through the tube of the extrathoracic airways. A gradient of negative pressure is formed from the alveoli to the upper airway. Within the thoracic cavity the airway walls are pulled outwards by the negative intrathoracic pressure. Above the thoracic inlet, where the external pressure is atmospheric, the negative pressure within the airways leads to a degree of inward collapse during inspiration. The reverse happens during expiration, when the recoil pressure of the chest wall generates a positive intrathoracic pressure and pushes air out from the alveoli to the upper airway, compressing the intrathoracic airways but distending the extrathoracic airway. These changes are exaggerated during any form of airway obstruction, since the pressures generated to overcome the obstruction are even higher. As a result, obstruction to the extrathoracic airways is worse during inspiration (causing stridor), whereas obstruction to the intrathoracic airways is worse during expiration (causing crepitations and wheeze). Narrowing of the airway due to inflammation is a feature of many respiratory pathologies. Snoring is also inspiratory, but because it is caused by variable partial upper airway obstruction, it is a rough inspiratory noise (stertor).

Answer 54

Children have a median of five upper respiratory tract infections (URTIs) per year in the first few years of life, but some toddlers and primary school-aged children have as many as 10–12 per year. Approximately 80% of all respiratory infections involve only the nose, throat, ears or sinuses. The term URTI embraces a number of different conditions: * common cold (coryza) * sore throat (pharyngitis, including tonsillitis) * acute otitis media * sinusitis (relatively uncommon). The most common presentation is a child with a combination of these conditions. Cough may be troublesome and in URTI may be secondary to postnasal drip or attempts to clear upper airway secretions. URTIs may cause: * difficulty in feeding in infants as their noses are blocked and this obstructs breathing * febrile seizures * acute exacerbations of asthma. Hospital admission is rarely required but may be necessary if feeding and fluid intake is inadequate.

Answer 55

This is the most common infection of childhood. Classical features include a clear or mucopurulent nasal discharge and nasal blockage. The most common pathogens are viruses: –Rhinoviruses (of which there are >100 different serotypes), -Coronaviruses -Respiratory syncytial virus (RSV). Health education to advise parents that colds are self-limiting and have no specific curative treatment may reduce anxiety and save unnecessary visits to doctors. Pain is best treated with paracetamol or ibuprofen. Antibiotics are of no benefit as the common cold is viral in origin and secondary bacterial infection is very uncommon. Cough may persist for up to 4 weeks after a common cold.

Answer 56

In pharyngitis, the pharynx and soft palate are inflamed and local lymph nodes are enlarged and tender. It is usually due to viral infection (mostly adenoviruses, enteroviruses, as well as rhinoviruses). In the older child, group A β-haemolytic streptococcus is a common pathogen.

Answer 57

Tonsillitis is a form of pharyngitis where there is intense inflammation of the tonsils, often with a purulent exudate. Common pathogens are: -group A β-haemolytic streptococci -Epstein–Barr virus (infectious mononucleosis). It is not possible to distinguish clinically between viral and bacterial causes. Marked constitutional disturbance, such as headache, apathy and abdominal pain, white tonsillar exudate and cervical lymphadenopathy, is more common with bacterial infection

Answer 58

Antibiotics (e.g. penicillin V or erythromycin if there is penicillin allergy) are often prescribed for severe pharyngitis and tonsillitis even though only a third are caused by bacteria. They may hasten recovery from streptococcal infection. In order to eradicate the organism completely (and prevent rheumatic fever) 10 days of antibiotic treatment is required for pharyngitis or tonsillitis. Rarely, in severe cases, children may require hospital admission for intravenous fluid administration and analgesia if they are unable to swallow solids or liquids. (Amoxicillin is best avoided as it may cause a widespread maculopapular rash if the tonsillitis is due to infectious mononucleosis). Occasionally, group A streptococcal infection results in scarlet fever, which is most common in children aged 5–12 years. Fever usually precedes the presence of headache and tonsillitis by 2–3 days. The appearance of the rash is variable, although a typical appearance will include a ‘sandpaper-like’ maculopapular rash with flushed cheeks and perioral sparing. The tongue is often white and coated and may be sore or swollen. This is the only childhood exanthema caused by a bacterium, and requires treatment with antibiotics (penicillin V or erythromycin) to prevent complications including acute glomerulonephritis or, very rarely in high-income countries, rheumatic fever.

Answer 59

Most children will have at least one episode of acute otitis media. This is most common at 6–12 months of age. Up to 20% will have three or more episodes. Infants and young children are prone to acute otitis media because their Eustachian tubes are short, horizontal, and function poorly. There is pain in the ear and fever. Every child with a fever must have his/her tympanic membranes examined. In acute otitis media, the tympanic membrane is seen to be bright red and bulging with loss of the normal light reflection. Occasionally, there is acute perforation of the eardrum with pus visible in the external canal.

Answer 60

Pathogens include viruses, especially RSV and rhinovirus, and bacteria including pneumococcus, nontypeable Haemophilus influenzae and Moraxella catarrhalis. Serious complications are mastoiditis and meningitis, but these are now uncommon. Recurrent infections may lead to glue ear and hearing loss, causing speech and learning difficulties.

Answer 61

Pain should be treated with an analgesic such as paracetamol or ibuprofen. Regular analgesia is more effective than intermittent (as required) and may be needed for up to a week until the acute inflammation has resolved. Most cases of acute otitis media resolve spontaneously. Antibiotics marginally shorten the duration of pain but have not been shown to reduce the risk of hearing loss. A reasonable approach is to give the parents a prescription but ask them to use it only if the child remains unwell after 2–3 days. Amoxicillin is widely used. Neither decongestants nor antihistamines are beneficial.

Answer 62

Recurrent ear infections can lead to otitis media with effusion. Children are usually asymptomatic apart from possible decreased hearing. The eardrum is seen to be dull and retracted, often with a fluid level visible. Otitis media with effusion is very common between the ages of 2–7 years, with peak incidence between 2.5–5 years of age. It usually resolves spontaneously, but may cause conductive hearing loss as shown on pure tone audiometry (possible if >4 years old) or a flat trace on tympanometry hearing testing in younger children.

Answer 63

There is no evidence for the longterm benefit from the use of antibiotics, steroids, or decongestants. Otitis media with effusion is the most common cause of conductive hearing loss in children and can interfere with normal speech development and result in learning difficulties in school. In such children, insertion of ventilation tubes (grommets) is often performed, but benefits do not last more than 12 months. In practice, children with recurrent URTIs and chronic otitis media with effusion (glue ear) that does not resolve with conservative measures often also undergo grommet insertion. If problems recur after grommet extrusion, then reinsertion of grommets with adjuvant adenoidectomy is often advocated, as there is some evidence that adenoidectomy can offer more long-term benefit.

Answer 64

Infection of the paranasal sinuses may occur with viral URTIs. Occasionally, there is secondary bacterial infection, with pain, swelling and tenderness over the cheek from infection of the maxillary sinus. As the frontal sinuses do not develop until late childhood, frontal sinusitis is uncommon in the first decade of life. Antibiotics and analgesia are used for acute sinusitis.

Answer 65

The indications for tonsillectomy are controversial, and must be balanced against the risks of surgery, but include: * Recurrent severe tonsillitis (as opposed to recurrent URTIs) – tonsillectomy reduces the number of episodes of tonsillitis by a third, e.g. from three to two per year but is unlikely to benefit mild symptoms * A peritonsillar abscess (quinsy) * Obstructive sleep apnoea (the adenoids will also often be removed).

Answer 66

In young children, the adenoids grow proportionately faster than the airway, so that their effect of narrowing the airway lumen is greatest between ages 2–8 years. They may narrow the posterior nasal space sufficiently to justify adenoidectomy. Indications for the removal of both the tonsils and adenoids are controversial but include: * Recurrent otitis media with effusion with hearing loss, where it gives a significant long-term additional benefit * Obstructive sleep apnoea (an absolute indication).

Answer 67

Stridor is a harsh, muscial sound due to partial obstruction of the lower portion of the upper airway including the upper trachea and the larynx. By far the most common cause is laryngeal and tracheal infection, where mucosal inflammation and swelling can rapidly cause life-threatening obstruction of the airway in young children. Common causes: -Viral laryngotracheobronchitis (‘croup’) Rare causes: -Epiglottitis -Bacterial tracheitis -Laryngeal or oesophageal foreign body -Allergic laryngeal angioedema (seen in anaphylaxis and recurrent croup) -Inhalation of smoke and hot fumes in fires -Trauma to the throat -Retropharyngeal abscess -Hypocalcaemia -Severe lymph node swelling (tuberculosis, infectious mononucleosis, malignancy) -Measles -Diphtheria -Psychological – vocal cord dysfunction

Answer 68

The severity of upper airways obstruction is best assessed clinically by characteristics of the stridor (none, only on crying, at rest, or biphasic) and the degree of chest retraction (none, only on crying, at rest). Severe obstruction also leads to increasing respiratory rate, heart rate, and agitation. Central cyanosis, drooling or reduced level of consciousness suggest impending complete airway obstruction. The most reliable objective measure of hypoxaemia is by measuring the oxygen saturation by pulse oximetry, but, in contrast to lung disease, is a late feature of upper airways obstruction. Total obstruction of the upper airway may be precipitated by examination of the throat using a spatula. One must avoid looking at the throat of a child with upper airways obstruction unless full resuscitation equipment and personnel are at hand.

Answer 69

Viral croup accounts for over 95% of laryngotracheal infections. Parainfluenza viruses are the most common cause, but other viruses, such as rhinovirus, RSV and influenza, can produce a similar clinical picture. Croup typically occurs from 6 months to 6 years of age but the peak incidence is in the 2nd year of life. It is most common in the autumn.

Answer 70

The typical features are coryza and fever followed by: * Hoarseness due to inflammation of the vocal cords * A barking cough, like a sea lion, due to tracheal oedema and collapse * Harsh stridor * Variable degree of difficulty breathing with chest retraction * The symptoms often start, and are worse, at night.

Answer 71

When the upper airway obstruction is mild, the stridor and chest recession disappear when the child is at rest and the child can usually be managed at home. The parents should observe the child closely for signs of increasing severity. The decision to manage the child at home or in hospital is influenced not only by the severity of the illness but also by the time of day, ease of access to hospital, the child’s age (with a low threshold for admission for those <12 months old due to their narrow airway calibre) and parental understanding and confidence about the disorder. Oral dexamethasone, oral prednisolone, or nebulized steroids (budesonide) reduce the severity and duration of croup and are first-line therapy for croup causing chest recession at rest. They have been shown to reduce the need for hospitalization. In severe upper airways obstruction, nebulized epinephrine (adrenaline) with oxygen by face mask provides rapid but transient improvement. The child must continue to be observed closely for 2–3 hours after administration as the effects wear off. Intubation for viral croup has become extremely unusual since the introduction of steroid therapy. Some children have a pattern of recurrent croup, which may be related to atopy.

Answer 72

In acute epiglottitis there is intense swelling of the epiglottis and surrounding tissues associated with septicaemia. It is a life-threatening emergency due to the high risk of respiratory obstruction. It is caused by H. influenzae type b (Hib). In the UK and many other countries, the introduction of universal Hib immunization in infancy has led to more than 99% reduction in the incidence of epiglottitis and other invasive Hib infections.

Answer 73

1. Onset: Days (c) vs hours (e) 2. Preceding coryza: present (c) vs not present (e) 3. Cough: Severe barking (c) vs absent/slight (e) 4. Able to drink: Yes (c) vs No (e) 5. Drooling saliva: No (c) vs yes (e) 6. Appearance: unwell (c) vs toxic or very ill (e) 7. Fever: <38.5 degrees (c) vs >38.5 degrees (e) 8. Stridor: Harsh, rasping (c) vs muffled, reluctant to speak (e)

Answer 74

Epiglottitis is most common in children aged 1–6 years but affects all age groups. It is important to distinguish clinically between epiglottitis and croup as they require quite different treatment. The onset of epiglottitis is usually very acute with: * High fever in a very ill, toxic-looking child * An intensely painful throat that prevents the child from speaking or swallowing; saliva drools down the chin * Soft inspiratory stridor and rapidly increasing respiratory difficulty over hours * The child sitting immobile, upright, with an open mouth to optimize the airway. In contrast to viral croup, cough is minimal or absent.

Answer 75

Attempts to lie the child down or examine the throat with a spatula or perform a lateral neck X-ray to identify a swollen epiglottis and surrounding tissues must not be undertaken as they can precipitate total airway obstruction and death. If the diagnosis of epiglottitis is suspected, urgent hospital admission and treatment are required. A senior anaesthetist, paediatrician, and ENT surgeon should be summoned and treatment initiated without delay. The child should be transferred directly to the intensive care unit or an anaesthetic room, and must be accompanied by senior medical staff in case respiratory obstruction occurs. The child should be intubated under controlled conditions with a general anaesthetic. Rarely, this is impossible and urgent tracheostomy is life-saving. Only after the airway is secured should blood be taken for culture and intravenous antibiotics such as cefuroxime started. The tracheal tube can usually be removed after 24 hours and antibiotics given for 3–5 days. With appropriate treatment, most children recover completely within 2–3 days. As with other serious H. influenzae infections, prophylaxis with rifampicin is offered to close household contacts.

Answer 76

Also known as pseudomembranous croup. This rare but dangerous condition is similar to severe epiglottitis in that the child has a high fever, appears very ill, and has rapidly progressive airways obstruction with copious thick airway secretions. It is typically caused by infection with Staphylococcus aureus. Management is by intravenous antibiotics and intubation and ventilation if required.

Answer 77

When a child with acute stridor presents with atypical features or a poor response to treatment, other causes need to be considered (Box 17.1). If a child has an abrupt onset of stridor without apparent infection, consider anaphylaxis or inhaled foreign body. Chronic stridor is usually due to a structural problem, either from intrinsic narrowing or collapse of the laryngotracheal airway, e.g. subglottic stenosis, laryngomalacia (floppy larynx), or external compression (e.g. vascular ring, lymph nodes, tumours). Investigations are required to determine the cause.

Answer 78

Acute wheeze is due to a partial obstruction of the intrathoracic airways. This is from mucosal inflammation and swelling as in bronchiolitis or bronchoconstriction as in asthma or mechanical obstruction (e.g. with foreign body or mucus). It may occur as a combination of all three.

Answer 79

RSV is the pathogen in 80%, the remainder are accounted for by parainfluenza virus, rhinovirus, adenovirus, influenza virus, and human metapneumovirus. There is evidence that co-infection with more than one virus, particularly RSV and human metapneumovirus may lead to a more severe illness. Coryzal symptoms precede a dry cough and increasing breathlessness. Feeding difficulty associated with increasing dyspnoea is often the reason for admission to hospital. Recurrent apnoea is a serious complication, especially in young infants. Infants born prematurely who develop bronchopulmonary dysplasia or with other underlying lung disease, such as cystic fibrosis, or have congenital heart disease are most at risk from severe bronchiolitis. The characteristic findings on examination are: * Dry wheezy cough * Tachypnoea and tachycardia * Subcostal and intercostal recession * Hyperinflation of the chest * Fine end-inspiratory crackles * High-pitched wheezes – expiratory > inspiratory

Answer 80

Pulse oximetry should be performed on all children with suspected bronchiolitis. No other investigations are routinely recommended. In particular, chest X-ray or blood gases are only indicated if respiratory failure is suspected. Hospital admission is indicated if any of the following are present: * Apnoea (observed or reported) * Persistent oxygen saturation of < 90% when breathing air * Inadequate oral fluid intake (50–75% of usual volume) * Severe respiratory distress – grunting, marked chest recession, or a respiratory rate over 70 breaths/minute.

Answer 81

This is supportive. Humidified oxygen is either delivered via nasal cannulae or using a head box; the concentration required is determined by pulse oximetry. The infant is monitored for apnoea. NB: No evidence for reducing severity or illness duration has been shown from use of mist, nebulized hypertonic saline, antibiotics, corticosteroids or nebulized bronchodilators, such as salbutamol or ipratropium. Fluids may need to be given by nasogastric tube or intravenously. Assisted ventilation in the form of non-invasive respiratory support with CPAP (continuous positive airway pressure) or else mechanical ventilation is required in a small percentage of infants admitted to hospital. RSV is highly infectious, and infection control measures, particularly good hand hygiene, cohort nursing, and gowns and gloves, have been shown to prevent cross-infection to other infants in hospital. Most infants recover from the acute infection within 2 weeks. However, as many as half will have recurrent episodes of cough and wheeze. Rarely, usually following adenovirus infection, the illness may result in permanent damage to the airways (bronchiolitis obliterans).

Answer 82

A monoclonal antibody to RSV (palivizumab, given monthly by intramuscular injection) reduces the number of hospital admissions in high-risk preterm infants, although 17 babies need to be treated to avoid one admission. Its use is limited by cost and the need for multiple intramuscular injections.

Answer 83

- Viral episodic wheezing – wheeze only in response to viral infections - Multiple trigger wheeze – in response to multiple triggers and which is more likely to develop into asthma over time - Asthma.

Answer 84

Most wheezy preschool children have viral episodic wheeze. This is thought to result from small airways being more likely to narrow and obstruct due to inflammation and aberrant immune responses to viral infection. This gives the condition its episodic nature, being triggered by viruses that cause the common cold. Studies have found that sufferers often have reduced small airway diameter from birth. Risk factors include maternal smoking during and/or after pregnancy and prematurity. A family history of asthma or allergy is not a risk factor, but a family history of early viral wheezing is common. Viral episodic wheezing is more common in males and usually resolves by 5 years of age, presumably from increase in airway size.

Answer 85

Some children, both preschool and school aged, have frequent wheeze triggered by many stimuli, not just viruses but also cold air, dust, animal dander and exercise. This has been called multiple-trigger wheeze. In the preschool age group, where a formal diagnosis of asthma may be unjustified, this distinction is helpful as many children in this group benefit from asthma preventer therapy and a significant proportion go on to have asthma.

Answer 86

When recurrent wheezing is associated with symptoms between viral infections (interval symptoms) and evidence of allergy to one or more inhaled allergens such as house dust mite, pollens or pets, it is called ‘atopic asthma’. Evidence of allergy may be accompanied by positive skin-prick testing or presence of IgE on blood testing. Atopic asthma is strongly associated with other atopic diseases such as eczema, rhinoconjunctivitis and food allergy, and is more common in those with a family history of such diseases.

Answer 87

-Viral episodic wheeze -Multiple trigger wheeze -Asthma -Recurrent anaphylaxis (e.g. in food allergy) -Chronic aspiration -Cystic fibrosis -Bronchopulmonary dysplasia -Bronchiolitis obliterans -Tracheo-bronchomalacia

Answer 88

Genetic predisposition, atopy, and environmental triggers (Upper respiratory tract infections, Allergens [e.g. house dust mite, grass pollens, pets], Smoking (active or passive), Cold air, Exercise, Emotional upset or anxiety, Chemical irritants [e.g. paint, aerosols]) all lead to: Bronchial inflammation With oedema, excessive mucus production, infiltration with cells, eosinophils, mast cells, neutrophils and lymphocytes There is Bronchial Hyperresponsiveness - exaggerated twitchiness to inhaled stimuli This leads to airway narrowing with reversible airflow obstruction (eg peak flow variability) This causes wheeze, cough, breathlessness and chest tightness.

Answer 89

Asthma should be suspected in any child with wheezing on more than one occasion, particularly if there are interval symptoms. Asthmatic wheeze is a polyphonic (multiple pitch) noise coming from the airways. It is believed to represent many airways of different sizes vibrating from abnormal narrowing. Key features associated with a high probability of a child having asthma include: * Symptoms worse at night and in the early morning * Symptoms that have nonviral triggers * Interval symptoms, i.e. symptoms between acute exacerbations * Personal or family history of an atopic disease * Positive response to asthma therapy. Examination of the chest is usually normal between attacks. In long-standing asthma there may be hyperinflation of the chest, generalized polyphonic expiratory wheeze with a prolonged expiratory phase. Onset of the disease in early childhood may result in Harrison’s sulci. Evidence of eczema should be sought, as should examination of the nasal mucosa for allergic rhinitis. (The presence of a wet cough or sputum production, finger clubbing or poor growth suggests a condition characterized by chronic infection such as cystic fibrosis or bronchiectasis)

Answer 90

In younger children, asthma is usually diagnosed from history and examination alone. Parental description of the symptoms and response to treatment is the cornerstone to diagnosis. Sometimes, specific investigations are required to confirm the diagnosis, or determine the severity and phenotype in more detail. -Skin-prick testing for common allergens may be performed to aid the diagnosis of atopy and to identify allergens, which may be acting as triggers. - If there is uncertainty in the diagnosis or disease severity needs to be monitored, peak expiratory flow rate (PEFR) may be measured or spirometry performed. Peak flow is less sensitive to changes in airway calibre than spirometry but is portable and therefore helpful for serial measurements. Most children over 5 years of age can use a peak flow meter or undertake spirometry. Poorly controlled asthma leads to increased variability in peak flow, with both diurnal variability (morning usually lower than evening peak flow) and day-to-day variability. Spirometry involves measurement of forced expiratory volume in 1 second blowing out as hard and as fast as possible (FEV1). This provides a non-invasive measure of flow through the larger airways (to the bronchioles). Often, response to a bronchodilator is the most helpful investigation. This can be demonstrated as an improvement in peak flow rate or in FEV1 before and after inhaling a bronchodilator (an improvement of 12% or more confirms bronchodilator reversibility and is characteristic of asthma). Following treatment, this reversibility often reduces or disappears completely.

Answer 91

Inhaled β2-agonists are the most commonly used and most effective bronchodilators. Short-acting β2-agonists (often called relievers) such as salbutamol or terbutaline have a rapid onset of action (maximum effects after 10–15 min), are effective for 2–4 hours and have few side-effects. They are used “as required” for increased symptoms and in high doses for acute asthma attacks. By contrast, long-acting β2-agonists (LABAs) such as salmeterol or formoterol are effective for 12 hours. They are not used in acute asthma and should not be used without an inhaled corticosteroid. LABAs are useful in exercise-induced asthma. Ipratropium bromide, an anticholinergic bronchodilator, is sometimes given to young infants when other bronchodilators are found to be ineffective or in the treatment of severe acute asthma.

Answer 92

1. LABAs eg Salmeterol and Formoterol for bronchodilation. (First choice in children over 5 years) 2. Inhaled corticosteroids eg Budesonide, Beclometasone, Fluticasone, Mometasone Inhaled corticosteroids (often called preventers) are the most effective inhaled prophylactic therapy. They decrease airway inflammation, resulting in decreased symptoms, asthma exacerbations and bronchial hyperactivity. They are often used in conjunction with an inhaled LABA or leukotriene receptor antagonist. 3. Leukotriene receptor antagonists (LTRA) eg Montelukast as add-on therapy (first choice in children under 5 years but can be used in older children when symptoms are not controlled by the addition of a LABA) 4. Methylxanthines eg Theophylline is an alternative add-on therapy , however it has a high incidence of side effects (vomiting, insomnia, headahces, poor concentration) so is not often used in children. 5. Oral steroids, prednisolone, usually given on alternate days to minimize the adverse effect on growth, is required only in severe persistent asthma where other treatment has failed. All children on this therapy must be managed by a specialist in childhood asthma 6. Anti-IgE therapy (omalizumab) is an injectable monoclonal antibody that acts against IgE, the natural antibody that mediates allergy. It is used for the treatment of severe atopic asthma, and should also only be administered by a specialist in childhood asthma.

Answer 93

They have no clinically significant side-effects when given in low dose, although they can cause mild reduction in height velocity, but this is usually followed by catch-up growth in late childhood. Systemic side effects, including impaired growth, adrenal suppression and altered bone metabolism may be seen when high doses are used. To reduce the risk of unwanted side effects, treatment with inhaled corticosteroids should always be at the lowest dose possible. Treatment for many children is effective at very low doses

Answer 94

Complete control is defined as the absence of daytime or night-time symptoms, no limit on activities (including exercise), no need for reliever use, normal lung function and no exacerbations (need for hospitalization or oral steroids) in the previous 6 months

Answer 95

Treatment increases through the steps and is stepped down when control is good. STEP 1 (Mild intermittent asthma) = Short acting beta agonist, SABA STEP 2 (Regular preventer therapy) = Add inhaled corticosteroid (200 micrograms/day or 400 for adolescents) or in those <5 years consider leukotriene receptor antagonist if steroids cannot be used. STEP 3 (Initial add-on therapy) = -In <5 years: add LTRA, if poor response increase ICS dose (400 micrograms/day -In >5 years and young adults: initially add LABA. Assess the response: if good continue, if partial increase the ICS dose (400 or 800 in adolescents), if poor stop the LABA & increase the ICS & consider LTRA and/or slow release theophylline. STEP 4 (persistent poor control) = -In <5 years: refere to resp paediatrician -In 5-12 years: increase ICS dose to 800 micrograms/day -In adolescents: increase ICS to 1600 and consider LTRA or slow release theophylline. (Issue steroid replacement warning card) STEP 5 (Continuous or frequent use of oral steroids) = -In 5-12 years: Maintain ICS at 800. Use lowest possible daily dose of oral steroids to maintain adequate control. Refer. -In adolescents: Maintain ICS at 1600. Use lowest possible daily dose of oral steroids to maintain adequate control. Refer.

Answer 96

Parental smoking cessation Psychological intervention may be useful in chronic severe asthma

Answer 97

With each acute attack, the duration of symptoms, the treatment already given, and the course of previous attacks should be noted. Determine the severity of the attack based on clinical features (Mild, moderate, severe, life-threatening) 1. Increased work of breathing Chest recession: * Moderate – some intercostal recession * Severe – use of accessory neck muscles * Life-threatening – poor respiratory effort Auscultation: * Wheeze * Silent chest – poor air entry from poor expiratory effort or exhaustion in life-threatening 2. Cardiovascular: * Tachycardia – varies with age; better guide to severity than respiratory rate but affected by β2-agonists * Arrythmia, hypotension – life-threatening 3. Altered consciousness, agitation or confusion – in life-threatening Exhaustion – life-threatening 4. Tongue: * Cyanosis in life-threatening 5. Peak flow (% predicted or best or usual measurement): * Moderate >50% * Severe 33–50% * Life-threatening <33% 6. O2 saturation: * Moderate >92% * Severe or life-threatening <92% 7. Is there a trigger for the attack?: * URTI or other viral illness * Allergen, e.g. animal dander * Exercise * Cold air

Answer 98

* Asthma * Pneumonia or lower respiratory tract infection * Foreign body * Anaphylaxis * Pneumothorax or pleural effusion * Metabolic acidosis – diabetic ketoacidosis, inborn error of metabolism, lactic acidosis * Severe anaemia * Heart failure * Panic attacks (hyperventilation)

Answer 99

Children require hospital admission if, after high-dose inhaled bronchodilator therapy, they: * Have not responded adequately clinically, i.e. there is persisting breathlessness or tachypnoea * Are becoming exhausted * Still have a marked reduction in their predicted (or usual best) peak flow rate or FEV1 (<50%) * Have a reduced oxygen saturation (<92% in air). A chest X-ray is indicated only if there are unusual features (e.g. asymmetry of chest signs suggesting pneumothorax, lobar collapse) or signs of severe infection. In children, blood gases are only indicated in life-threatening or refractory cases and often are normal until the child is in extremis.

Answer 100

High-dose inhaled bronchodilators, steroids, and oxygen form the foundation of therapy of severe acute asthma. 1. As soon as the diagnosis has been made, the child should be given oxygen if the oxygen saturation is <92%. 2. All children should be given a β2-bronchodilator, the dose and frequency increasing according to severity of the attack, the child’s age and response to therapy. It should be given via a spacer, as used by the child at home, unless the attack is severe to life-threatening when a nebulizer driven by high-flow oxygen may be indicated. The addition of nebulized ipratropium to the initial therapy in severe asthma is beneficial. 3. A short course (3–7 days) of oral prednisolone expedites the recovery from moderate or severe acute asthma. - Inhaled therapies are not always be successful as the drugs may be delivered in suboptimal doses to areas of the lung that are poorly ventilated. Intravenous therapy therefore has a role in the minority of children who fail to respond adequately to inhaled bronchodilator therapy. -IV hydrocortisone -Magnesium sulphate: has the least side-effects and most evidence of benefit, and is increasingly being used as the first choice for intravenous therapy. OR -Aminophylline: a loading dose is given over 20 minutes, followed by continuous infusion. Seizures, severe vomiting and fatal cardiac arrhythmias may follow a rapid infusion. If the child is already on oral theophylline, the loading dose should be omitted. Monitor ECG and blood electrolytes. OR -Intravenous salbutamol: monitor ECG and blood electrolytes Occasionally, these measures are insufficient and mechanical ventilation is required.

Answer 101

* Atypical pneumonia – although pneumococcal pneumonia rarely causes wheezing, atypical pneumonia caused by Mycoplasma, Chlamydia or adenovirus can do so. * Foreign body inhalation – abrupt onset of cough followed by wheeze in a previously well child. On passing below the glottis, a foreign body generally impacts in a main or lobar bronchus and may initially cause unilateral wheezing and air trapping. A chest X-ray performed during expiration will show persistent hyperinflation of the lung distal to the obstruction. Eventually, airway swelling causes complete obstruction and lobar collapse is seen. * Anaphylaxis – suspect if acute urticaria, facial swelling, stridor, or previous reaction to an allergen.

Answer 102

1. Dry with prolonged expiratory phase: some narrowing of the small-sized to moderate-sized airways 2. Barking cough: degree of tracheal inflammation, narrowing or collapse 3. Moist: increased mucus secretion or infection in the lower airway

Answer 103

This is a highly contagious respiratory infection caused by Bordetella pertussis. 1. Catarrhal phase: usually a week of coryza 2. Paroxysmal phase: paroxysmal or spasmodic cough followed by a characteristic inspiratory whoop. The spasms of cough are often worse at night and may culminate in vomiting. During a paroxysm, the child goes red or blue in the face, and mucus flows from the nose and mouth. The whoop may be absent in infants, but apnoea is common at this age. Epistaxis and subconjunctival haemorrhages can occur after vigorous coughing. The paroxysmal phase lasts up to 3 months. 3. Convalescent phase: The symptoms gradually decrease but may persist for many months. Complications such as pneumonia, seizures and bronchiectasis are uncommon but there is still a significant mortality, particularly in infants who have not yet completed their primary vaccinations at 4 months. Infants and young children suffering severe spasms of cough or cyanotic attacks should be admitted to hospital and isolated from other children.

Answer 104

The organism (Bordetella pertussis) can be identified early in the disease from culture of a pernasal swab, although PCR is more sensitive. Characteristically, there is a marked lymphocytosis on a blood count.

Answer 105

Although macrolide antibiotics (Azithromycin, clarithromycin, erythromycin) eradicate the organism, they decrease symptoms only if started during the catarrhal phase. Siblings, parents and school contacts may develop a similar cough, and close contacts should receive macrolide prophylaxis. Unimmunized infant contacts should be vaccinated. Immunization reduces the risk of developing pertussis and the severity of disease in those affected but does not guarantee protection. The level of protection declines steadily during childhood. Reimmunization of mothers during pregnancy reduces the risk of pertussis in her infant during the first few months of life when it is particularly dangerous. It is currently recommended in the UK; this followed the re-emergence of pertussis in infants in the community.

Answer 106

* Recurrent respiratory infections * Following specific respiratory infections (e.g. pertussis, respiratory syncytial virus, Mycoplasma) * Asthma * Persistent lobar collapse following pneumonia * Suppurative lung diseases (e.g. cystic fibrosis, ciliary dyskinesia or immune deficiency) * Recurrent aspiration (±gastro-oesophageal reflux) * Persistent bacterial bronchitis * Inhaled foreign body * Cigarette smoking (active or passive) * Tuberculosis (in a child with severe, persistent cough, TB should be considered) * Habit cough * Airway anomalies (e.g. tracheo-bronchomalacia, tracheo-oesophageal fistula)

Answer 107

Viruses are the most common cause in younger children, whereas bacteria are more common in older children, 1. Newborns: -Group B Streptococcus -Gram-negative enterococci -Gram negative bacilli (Klebsiella, pseudomonas aeruginosa, E. coli) 2. Infants and young children -Respiratory viruses, particularly RSV, - Streptococcus pneumoniae - H. influenzae - Bordetella pertussis - Chlamydia trachomatis - Staphylococcus aureus (Infrequent bit serious). 3. Children over 5 years: - Mycoplasma pneumoniae - Streptococcus pneumoniae - Chlamydia pneumoniae At all ages Mycobacterium tuberculosis should be considered.

Answer 108

Fever, cough and rapid breathing are the most common presenting symptoms. These are usually preceded by a URTI. Other symptoms include lethargy, poor feeding, and an ‘unwell’ child. Some children do not have a cough at presentation. Localized chest, abdominal, or neck pain is a feature of pleural irritation and suggests bacterial infection. Examination reveals tachypnoea, nasal flaring and chest indrawing. In contrast to asthma, the most sensitive clinical sign of pneumonia in children is increased respiratory rate, and pneumonia can sometimes be missed if the respiratory rate is not measured in a febrile child (so-called silent pneumonia). There may be end-inspiratory coarse crackles over the affected area but the classic signs of consolidation with dullness on percussion, decreased breath sounds and bronchial breathing over the affected area are often absent in young children. Oxygen saturation may be decreased.

Answer 109

A chest X-ray may confirm the diagnosis but cannot reliably differentiate between bacterial and viral pneumonia. In younger children, a nasopharyngeal aspirate may identify viral causes, but blood tests, including full blood count and acute phase reactants are generally unhelpful in differentiating between a viral and bacterial cause. In a small proportion of children the pneumonia is associated with a pleural effusion, where there may be blunting of the costophrenic angle on the chest X-ray. Some of these effusions develop into empyema and fibrin strands may form, leading to septations.

Answer 110

Most affected children can be managed at home but indications for admission include oxygen saturation <92%, recurrent apnoea, grunting and/or an inability to maintain adequate fluid/feed intake. General supportive care should include oxygen for hypoxia and analgesia if there is pain. Intravenous fluids should be given if necessary to correct dehydration and maintain adequate hydration and sodium balance. The choice of antibiotic is determined by the child’s age and the severity of illness: - Newborns require broad spectrum intravenous antibiotics. - Most older infants can be managed with oral amoxicillin, with broader spectrum antibiotics such as co-amoxiclav reserved for complicated or unresponsive pneumonia. - For children over 5 years of age, either amoxicillin or an oral macrolide such as erythromycin is the treatment of choice. There is no advantage in giving intravenous rather than oral treatment in mild/moderate pneumonia.

Answer 111

Small parapneumonic effusions occur in up to one third of children with pneumonia and may resolve with appropriate antibiotics, but persistent fever despite 48 hours of antibiotics suggests a pleural collection which requires drainage. This should be done with ultrasound guidance. The percutaneous placement of a small-bore chest drain and regular instillation of a fibrinolytic agent to break down the fibrin strands are usually effective, but more aggressive intervention such as video-assisted thoracoscopic surgery or even thoracotomy and decortication is sometimes necessary in refractory cases.

Answer 112

Any child with a persistent cough that sounds ‘wet’ (i.e. sounds like there is excess sputum in the chest) or is productive requires further investigations. 1. Persistent bacterial bronchitis, where there is persistent inflammation of the lower airways driven by chronic infection, is increasingly recognized as a cause of chronic wet cough in children. Common organisms are Haemophilus influenzae and Moraxella catarrhalis. It may be a precursor to bronchiectasis if investigations and treatment are not instituted. Bacterial growth from sputum or bronchial lavage is consistent with the diagnosis. Treatment is with a high dose of antibiotic such as co-amoxiclav, coupled with physiotherapy. 2. Bronchiectasis (permanent dilatation of the bronchi). It may be generalized or restricted to a single lobe. - Generalized bronchiectasis may be due to cystic fibrosis, primary ciliary dyskinesia, immunodeficiency, or chronic aspiration. - Focal bronchiectasis is due to previous severe pneumonia, congenital lung abnormality, or obstruction by a foreign body. A plain chest X-ray may show gross bronchiectasis, but often it is not possible to identify it. It is best identified on a CT scan of the chest. To investigate focal disease, bronchoscopy is usually indicated to exclude a structural cause.

Answer 113

CF is the most common life-limiting autosomal recessive condition in Caucasians, with an incidence of 1 in 2500 live births and carrier rate of 1 in 25. It is well recognized but less common in other ethnic groups. Average life expectancy has increased from a few years to the mid-30s, with a projected life expectancy for current newborns into the 40s. The fundamental problem in CF is a defective protein called the CF transmembrane conductance regulator (CFTR). This is a cyclic AMP-dependent chloride channel found in the membrane of cells. The gene for CFTR is located on chromosome 7. Over 900 different gene mutations have been discovered that cause a number of distinct defects in CFTR, but by far the most frequent mutation (about 78%) in the UK is ΔF508. Identification of the gene mutation involved within a family allows prenatal diagnosis and carrier detection in the wider family. Some genotypes are known to be associated with milder disease and pancreatic sufficiency.

Answer 114

CF is a multisystem disorder, which results mainly from abnormal ion transport across epithelial cells. In the airways this leads to reduction in the airway surface liquid layer and consequent impaired ciliary function and retention of mucopurulent secretions. Chronic endobronchial infection with specific organisms such as Pseudomonas aeruginosa ensues. Defective CFTR also causes dysregulation of inflammation and defence against infection. In the intestine, thick viscid meconium is produced, leading to meconium ileus in 10–20% of infants. The pancreatic ducts also become blocked by thick secretions, leading to pancreatic enzyme deficiency and malabsorption. Abnormal function of the sweat glands results in excessive concentrations of sodium and chloride in the sweat.

Answer 115

Newborn: * Diagnosed through newborn screening * Meconium ileus Infancy: * Prolonged neonatal jaundice * Growth faltering * Recurrent chest infections * Malabsorption, steatorrhoea Young child: * Bronchiectasis * Rectal prolapse * Nasal polyp * Sinusitis Older child and adolescent: * Allergic bronchopulmonary aspergillosis * Diabetes mellitus * Cirrhosis and portal hypertension * Distal intestinal obstruction (meconium ileus equivalent) * Pneumothorax or recurrent haemoptysis * Sterility in males

Answer 116

Heel prick tests are taken for biochemical screening. Infants with CF have raised Immunoreactive trypsinogen (IRT). These samples are then screened for common CF gene mutations and infants with two mutations have a sweat test to confirm the diagnosis.

Answer 117

Chronic infection with specific bacteria – initially Staphylococcus aureus and Haemophilus influenzae and subsequently with Pseudomonas aeruginosa or Burkholderia species results from viscid mucus in the smaller airways of the lungs. This leads to damage of the bronchial wall, bronchiectasis and abscess formation.

Answer 118

The child has a persistent, ‘wet’ cough, productive of purulent sputum. On examination there is hyperinflation of the chest due to air trapping, coarse inspiratory crepitations, and/or expiratory wheeze. With established disease, there is finger clubbing.

Answer 119

Over 90% of children with CF have pancreatic exocrine insufficiency (lipase, amylase, and proteases), resulting in maldigestion and malabsorption. Untreated, this leads to faltering growth with frequent large, pale, and greasy stools (steatorrhoea). Pancreatic insufficiency can be diagnosed by demonstrating low faecal elastase. About 10–20% of infants with CF present in the neonatal period with meconium ileus, in which inspissated meconium causes intestinal obstruction. Typically, there is vomiting, abdominal distension, and failure to pass meconium in the first few days of life. Surgery is usually required, but gastrografin enema may relieve the obstruction.

Answer 120

The essential diagnostic procedure is the sweat test, to confirm that the concentration of chloride in sweat is markedly elevated (Cl 60–125 mmol/L in CF, 10–40 mmol/L in normal children). Sweating is stimulated by applying a low-voltage current to pilocarpine applied to the skin. The sweat is collected into a special capillary tube or absorbed onto a weighed piece of filter paper. Diagnostic errors are common if there is an inadequate volume of sweat collected. Confirmation of diagnosis can be made by testing for gene abnormalities in the CFTR protein.

Answer 121

Recurrent and persistent bacterial chest infection is the major problem. In younger children, respiratory monitoring is based on symptoms; older children should have their lung function measured regularly by spirometry. The FEV1 expressed as a percentage predicted for age, sex, and height, is an indicator of clinical severity and declines with disease progression. 1. Physiotherapy: From diagnosis, children should have physiotherapy at least twice a day, aiming to clear the airways of secretions. In younger children, parents are taught to perform airway clearance at home using chest percussion and postural drainage. Older patients perform controlled deep breathing exercises and use a variety of physiotherapy devices for airway clearance. Physical exercise is beneficial and is encouraged. 2. Antibiotics Many CF specialists recommend continuous prophylactic oral antibiotics (usually flucloxacillin), with additional rescue oral antibiotics for any increase in respiratory symptoms or decline in lung function. Persisting symptoms or signs require prompt and vigorous intravenous therapy to limit lung damage, usually administered for 14 days via a PIC (peripherally inserted central) line. Increasingly, parents are taught to administer courses of intravenous antibiotics at home, to decrease disruption of school and other activities. Chronic Pseudomonas infection is associated with a more rapid decline in lung function, which is slowed by the use of daily nebulized antipseudomonal antibiotics (penicillins, cephalosporins, aminoglycosides, carbapenems). The macrolide antibiotic azithromycin, given regularly, decreases respiratory exacerbations. If venous access becomes troublesome, implantation of a central venous catheter with a subcutaneous access port (e.g. Portacath) simplifies venous access, although they require monthly flushing and complications may develop. 3. Nebulised saline (and DNase) Nebulized DNase or hypertonic saline may be helpful to decrease the viscosity of sputum and to increase its clearance. Regular, nebulized hypertonic saline may decrease the number of respiratory exacerbations. 4. Bilateral sequential lung transplantation is the only therapeutic option for end-stage CF lung disease. Outcomes following lung transplantation continue to improve, with over 50% survival at 10 years.

Answer 122

Dietary status should be assessed regularly. Pancreatic insufficiency is treated with oral enteric-coated pancreatic replacement therapy taken with all meals and snacks. Dosage is adjusted according to clinical response. A high-calorie diet is essential, and dietary intake is recommended at 150% of normal. To achieve this, overnight feeding via a gastrostomy is increasingly used. Most patients require fat-soluble vitamin supplements.

Answer 123

Most children with CF survive into adult life. With increasing age come increased complications, 1. Diabetes mellitus: due to decreasing pancreatic endocrine function. 2. Liver disease: Up to one-third of adolescent patients will have evidence of liver disease with hepatomegaly on liver palpation, abnormal liver function on blood tests, or an abnormal ultrasound. Regular ursodeoxycholic acid, to improve flow of bile, may be beneficial. Rarely, the liver disease progresses to cirrhosis, portal hypertension, and ultimately liver failure. Liver transplant is generally very successful in CF-related liver failure. 3. Distal intestinal obstruction syndrome (DIOS, meconium ileus equivalent): viscid mucofaeculent material obstructs the bowel. This is usually cleared by a combination of oral laxative agents. 4. Increasing chest infections, as well as other late respiratory complications including pneumothorax and life-threatening haemoptysis. There is increasing concern over transmission of virulent strains of Pseudomonasand Burkholderia cepacia between patients, causing rapid decline in lung function. Consequently, patients are often segregated and advised not to socialise with other people with CF. 5. Infertility: Females have normal fertility, and unless they have severe lung disease, tolerate pregnancy well. Males are virtually always infertile due to absence of the vas deferens, although they can father children through intracytoplasmic sperm injection.

Answer 124

In primary ciliary dyskinesia there is congenital abnormality in the structure or function of cilia lining the respiratory tract. This leads to impaired mucociliary clearance. Affected children have recurrent infection of the upper and lower respiratory tracts, which if untreated may lead to severe bronchiectasis. They characteristically have a recurrent productive cough, purulent nasal discharge, and chronic ear infections. Since ciliary action is responsible for normal organ situs, 50% have dextrocardia and situs inversus (Kartagener syndrome, where major organs are in mirror position of normal). The diagnosis is made by examination of the structure and function of the cilia of nasal epithelial cells brushed from the nose. The cornerstones of management are daily physiotherapy to clear secretions, proactive treatment of infections with antibiotics, and appropriate ENT follow-up.

Answer 125

During REM (rapid eye movement) sleep, the control of breathing becomes unstable and there is relaxation of voluntary muscles in the upper airway and chest. This makes upper airway collapse more likely. Sleep-disordered breathing occurs either due to airway obstruction, central hypoventilation or a combination of these.

Answer 126

Key aspects of the history include loud snoring, witnessed pauses in breathing (apnoeas), restlessness, and disturbed sleep. Obstructive sleep apnoea leads to excessive daytime sleepiness or hyperactivity, learning and behaviour problems, faltering growth, and in severe cases, pulmonary hypertension. In childhood, it is usually due to: Upper airway obstruction secondary to adenotonsillar hypertrophy. Predisposing causes of sleep-disordered breathing are: - Neuromuscular disease (e.g. Duchenne muscular dystrophy) - Craniofacial abnormalities (e.g. Pierre Robin sequence, achondroplasia) - Dystonia of upper airway muscles (e.g. cerebral palsy) - Severe obesity. - Children with Down syndrome have anatomical upper airway restriction as well as hypotonia and are particularly at risk. These high-risk groups should be screened for sleep-disordered breathing. Congenital central hypoventilation syndrome is a rare congenital condition resulting in disordered central control of breathing as well as other autonomic dysfunction. In severe cases, life-threatening hypoventilation occurs during sleep, which may result in death in infancy. Long-term ventilation, either continuous or only during sleep is the mainstay of treatment.

Answer 127

The most basic assessment is overnight pulse oximetry, which can be performed in the child’s home. The frequency and severity of periods of desaturation can be quantified. Normal oximetry does not exclude the condition, but means that severe physical consequences are unlikely. Polysomnography is required in more complex cases. This should include monitoring of heart rate, respiratory effort, airflow, CO2 measurement and video recording. This provides more information about gas exchange and can distinguish between central and obstructive events. Sometimes more detailed electrophysiological assessment is needed to assess neurological arousals and sleep staging.

Answer 128

In children with adenotonsillar hypertrophy, adenotonsillectomy usually dramatically improves their condition. Before surgery for obstructive sleep apnoea, overnight oximetry should be performed to identify severe hypoxaemia, which may increase the risk of perioperative complications. For children with other sleep-related breathing disorders, nasal or face mask continuous positive pressure (CPAP) or BiPAP (bilevel positive airway pressure) to maintain their upper airway may be required at night.

Answer 129

1. Narrow upper airways: - Subglottic stenosis - Laryngeal anomalies (e.g. atresia, haemangiomas, webs) - Pierre Robin sequence (small jaw and cleft palate) - Other craniofacial anomalies (e.g. Crouzon disease) 2. Lower airway anomalies - Severe tracheobronchomalacia 3. Long-term ventilation - Muscle weakness - Head or spinal injury 4. Wean from ventilation - Any prolonged period of ventilation 5. Airway protection - To facilitate clearance of secretions

Answer 130

If a child with a tracheostomy develops sudden and severe breathing difficulties, it may be that the tracheostomy tube is blocked with secretions and needs urgent suction or needs changing immediately. If this does not relieve the difficulty in breathing, respiratory support is given via the tracheostomy tube. All children with a tracheostomy should have a spare tracheostomy tube with them at all times, and a carer competent to change it.

Answer 131

Vomiting is the forceful ejection of gastric contents. Posseting and regurgitation are terms used to describe the non-forceful return of milk, but differ in degree. Posseting describes the small amounts of milk that often accompany the return of swallowed air (wind), whereas regurgitation describes larger, more frequent losses. Posseting occurs in nearly all babies from time to time, whereas regurgitation may indicate the presence of more significant gastro-oesophageal reflux. Vomiting is the forceful ejection of gastric content

Answer 132

1. Bile-stained vomit - Intestinal obstruction 2. Haematemesis - Oesophagitis - Peptic ulceration - Oral/nasal bleeding - Oesophageal variceal bleeding 3. Projectile vomiting, in first few weeks of life - Pyloric stenosis 4. Vomiting at the end of paroxysmal coughing - Whooping cough (pertussis) 5. Abdominal tenderness/abdominal pain on movement - Surgical abdomen 6. Abdominal distension - Intestinal obstruction - Strangulated inguinal hernia 7. Hepatosplenomegaly -Chronic liver disease -Inborn error of metabolism 8. Blood in the stool -Intussusception -Bacterial gastroenteritis 9. Severe dehydration, Shock - Severe gastroenteritis - Systemic infection (urinary tract infection, meningitis) - Diabetic ketoacidosis 10. Bulging fontanelle or seizures - Raised intracranial pressure 11. Faltering growth - Gastro-oesophageal reflux disease - Coeliac disease - Chronic gastrointestinal conditions

Answer 133

1. Gastro-oesophageal reflux 2. Feeding problems 3. Infection: * Gastroenteritis * Respiratory tract/otitismedia * Whooping cough (pertussis) * Urinary tract * Meningitis 4. Food allergy and food intolerance 5. Eosinophilic oesophagitis 6. Intestinal obstruction: * Plyoric stenosis * Atresia – duodenal, other sites * Intussusception * Malrotation * Volvulus * Duplication cysts * Strangulated inguinalhernia * Hirschsprung disease 7. Inborn errors of metabolism 8. Congenital adrenal hyperplasia 9. Renal failure

Answer 134

1. Gastroenteritis 2. Infection: * Respiratory tract/otitis media * Urinary tract * Meningitis * Whooping cough (pertussis) 3. Appendicitis 4. Intestinal obstruction: * Intussusception * Malrotation * Volvulus * Adhesions * Foreign body – bezoar 5. Raised intracranial pressure 6. Coeliac disease 7. Renal failure 8. Inborn errors of metabolism 9. Torsion of the testis

Answer 135

1. Gastroenteritis 2. Infection - Pyelonephritis - Septicaemia - Meningitis 3. Peptic ulceration and H. pylori infection 4. Appendicitis 5. Migraine 6. Raised intracranial pressure 7. Coeliac disease 8. Renal failure 9. Diabetic ketoacidosis 10. Alcohol/drug ingestion or medications 11. Cyclical vomiting syndrome 12. Bulimia/anorexia nervosa 13. Pregnancy 14. Torsion of the testis

Answer 136

Gastro-oesophageal reflux is the involuntary passage of gastric contents into the oesophagus. It is extremely common in infancy. It is caused by inappropriate relaxation of the lower oesophageal sphincter as a result of functional immaturity. A predominantly fluid diet, a mainly horizontal posture and a short intraabdominal length of oesophagus all contribute. While common in the 1st year of life, nearly all symptomatic reflux resolves spontaneously by 12 months of age. This is probably due to a combination of maturation of the lower oesophageal sphincter, assumption of an upright posture and more solids in the diet. Most infants with gastro-oesophageal reflux have recurrent regurgitation or vomiting but are putting on weight normally and are otherwise well. Gastro-oesophageal reflux is usually a benign, self-limited condition but when it becomes a significant problem it becomes gastro-oesophageal reflux disease (GORD) and needs treatment.

Answer 137

Gastro-oesophageal reflux disease is more common in: * Children with cerebral palsy or other neurodevelopmental disorders * Preterm infants, especially in those with bronchopulmonary dysplasia * Following surgery for oesophageal atresia or diaphragmatic hernia.

Answer 138

* Faltering growth from severe vomiting * Oesophagitis – haematemesis, discomfort on feeding or heartburn, iron-deficiency anaemia * Recurrent pulmonary aspiration – recurrent pneumonia, cough or wheeze, apnoea in preterm infants * Dystonic neck posturing (Sandifer syndrome) * Apparent life-threatening events

Answer 139

Gastro-oesophageal reflux is usually diagnosed clinically and no investigations are required. However, they may be indicated if the history is atypical, complications are present, or there is failure to respond to treatment. Investigations include: * 24-hour oesophageal pH monitoring to quantify the degree of acid reflux * 24-hour impedance monitoring which is available in some centres. Weakly acidic or nonacid reflux, which may cause disease, is also measured * Endoscopy with oesophageal biopsies to identify oesophagitis and exclude other causes of vomiting Contrast studies of the upper gastrointestinal tract may support the diagnosis but are neither sensitive nor specific. They may be required in gastro-oesophageal disease to exclude underlying anatomical abnormalities in the oesophagus, stomach, and duodenum, and to identify malrotation.

Answer 140

Uncomplicated gastro-oesophageal reflux has an excellent prognosis and can be managed by parental reassurance, adding inert thickening agents to feeds (e.g. Carobel), and smaller, more frequent feeds. Significant gastro-oesophageal reflux disease is managed with acid suppression with either hydrogen receptor antagonists (e.g. ranitidine) or proton-pump inhibitors (e.g. omeprazole). These drugs reduce the volume of gastric contents and treat acid-related oesophagitis. If the child fails to respond to these measures, other diagnoses such as cow’s milk protein allergy should be considered and further investigations performed. Surgical management is reserved for children with complications unresponsive to intensive medical treatment or oesophageal stricture. A Nissen fundoplication, in which the fundus of the stomach is wrapped around the intra-abdominal oesophagus, is performed either as an abdominal or as a laparoscopic procedure.

Answer 141

In pyloric stenosis, there is hypertrophy of the pyloric muscle causing gastric outlet obstruction. It presents at 2–8 weeks of age, irrespective of gestational age. It is more common in boys (4 : 1), particularly firstborn, and there may be a family history, especially on the maternal side. Clinical features are: * Vomiting, which increases in frequency and forcefulness over time, ultimately becoming projectile * Hunger after vomiting until dehydration leads to loss of interest in feeding * Weight loss if presentation is delayed. A hypochloraemic metabolic alkalosis with a low plasma sodium and potassium occurs as a result of vomiting stomach contents.

Answer 142

Unless immediate fluid resuscitation is required, a test feed is performed. The baby is given a milk feed, which will calm the hungry infant, allowing examination. Gastric peristalsis may be seen as a wave moving from left to right across the abdomen. The pyloric mass, which feels like an olive, is usually palpable in the right upper quadrant. If the stomach is overdistended with air, it will need to be emptied by a nasogastric tube to allow palpation. Ultrasound examination may be helpful to confirm the diagnosis prior to surgery.

Answer 143

The initial priority is to correct any fluid and electrolyte disturbance with intravenous fluids. Once hydration and acid–base and electrolytes are normal, definitive treatment by pyloromyotomy can be performed. This involves division of the hypertrophied muscle down to, but not including, the mucosa. The operation can be performed either as an open procedure via a periumbilical incision or laparoscopically. Postoperatively, the child can usually be fed within 6 hours and discharged within 2 days of surgery.

Answer 144

The term ‘colic’ is used to describe a common symptom complex that occurs during the first few months of life. Paroxysmal, inconsolable crying or screaming often accompanied by drawing up of the knees and passage of excessive flatus takes place several times a day. There is no firm evidence that the cause is gastrointestinal, but this is often suspected. The condition occurs in up to 40% of babies. It typically occurs in the first few weeks of life and resolves gradually from 3–12 months of age. The condition is benign but it is very frustrating and worrying for parents and may precipitate non-accidental injury in infants already at risk. Support and reassurance should be given. ‘Gripe water’ is often recommended but is of unproven benefit. If severe and persistent, it may be due to a cow’s milk protein allergy and an empirical 2-week trial of a protein hydrolysate formula (cow’s milk protein free) may be considered and continued if symptoms improve. If they do not, then a trial of gastro-oesophageal reflux treatment may be considered.

Answer 145

1. Surgical -Acute appendicitis -Intestinal obstruction including intussusception -Inguinal hernia -Peritonitis -Inflamed Meckel diverticulum -Pancreatitis -Trauma 2. Medical - Gastroenteritis - Urinary tract: * Urinary tract infection * Acute pyelonephritis * Hydronephrosis * Renal calculus -Henoch–Schönlein purpura -Diabetic ketoacidosis -Sickle cell disease -Hepatitis -Inflammatory bowel disease -Constipation -Gynaecological in pubertal females -Psychological -Lead poisoning -Acute porphyria (rare) 3. Extra-abdominal -Upper respiratory tract infection -Lower lobe pneumonia -Torsion of the testis -Hip and spine

Answer 146

Acute appendicitis is the most common cause of abdominal pain in childhood requiring surgical intervention. Although it may occur at any age, it is very uncommon in children under 3 years of age. The clinical features of acute uncomplicated appendicitis are: * Symptoms – Anorexia – Vomiting – Abdominal pain, initially central and colicky (appendicular midgut colic), but then localizing to the right iliac fossa (from localized peritoneal inflammation) * Signs – Fever – Abdominal pain aggravated by movement, e.g. on walking, coughing, jumping, bumps on the road during a car journey – Persistent tenderness with guarding in the right iliac fossa (McBurney’s point). However, with a retrocaecal appendix, localized guarding may be absent, and in a pelvic appendix there may be few abdominal signs. In preschool children: * The diagnosis is more difficult, particularly early in the disease. * Faecoliths are more common and can be seen on a plain abdominal X-ray. * Perforation may be rapid, as the omentum is less well developed and fails to surround the appendix, and the signs are easy to underestimate at this age

Answer 147

Appendicitis is a progressive condition and so repeated observation and clinical review every few hours are key to making the correct diagnosis, avoiding delay on the one hand and unnecessary laparotomy on the other. No laboratory investigation or imaging is consistently helpful in making the diagnosis. A neutrophilia is not always present on a full blood count. White blood cells or organisms in the urine are not uncommon in appendicitis as the inflamed appendix may be adjacent to the ureter or bladder. Although ultrasound is no substitute for regular clinical review, it may support the clinical diagnosis (thickened, non-compressible appendix with increased blood flow), and demonstrate associated complications such as an abscess, perforation or an appendix mass, and may exclude other pathology causing the symptoms. In some centres, laparoscopy is available to see whether or not the appendix is inflamed.

Answer 148

Appendicectomy is straightforward in uncomplicated appendicitis. Complicated appendicitis includes the presence of an appendix mass, an abscess, or perforation. If there is generalized guarding consistent with perforation, fluid resuscitation and intravenous antibiotics are given prior to laparotomy. If there is a palpable mass in the right iliac fossa and there are no signs of generalized peritonitis, it may be reasonable to elect for conservative management with intravenous antibiotics, with appendicectomy being performed after several weeks. If symptoms progress, laparotomy is indicated.

Answer 149

Intussusception describes the invagination of proximal bowel into a distal segment. It most commonly involves ileum passing into the caecum through the ileocaecal valve. Intussusception is the most common cause of intestinal obstruction in infants after the neonatal period.

Answer 150

Although it may occur at any age, the peak age of presentation is 3 months – 2 years of age. Presentation is typically with: * Paroxysmal, severe colicky pain with pallor – during episodes of pain, the child becomes pale, especially around the mouth, and draws up the legs. There is recovery between the painful episodes but subsequently the child may become increasingly lethargic. * May refuse feeds, may vomit, which may become bile stained depending on the site of the intussusception. * A sausage-shaped mass – often palpable in the abdomen. * Passage of a characteristic redcurrant jelly stool comprising blood-stained mucus – this is a characteristic sign but tends to occur later in the illness and may be first seen after a rectal examination. * Abdominal distension and shock.

Answer 151

The most serious complication is stretching and constriction of the mesentery resulting in venous obstruction, causing engorgement and bleeding from the bowel mucosa, fluid loss, and subsequently bowel perforation, peritonitis and gut necrosis. Prompt diagnosis, immediate fluid resuscitation and urgent reduction of the intussusception are essential to avoid complications.

Answer 152

Usually, no underlying intestinal cause for the intussusception is found, although there is some evidence that viral infection leading to enlargement of Peyer’s patches may form the lead point of the intussusception. An identifiable lead point such as a Meckel diverticulum or polyp is more likely to be present in children over 2 years of age. Intravenous fluid resuscitation is likely to be required immediately, as there is often pooling of fluid in the gut, which may lead to hypovolaemic shock.

Answer 153

An X-ray of the abdomen may show distended small bowel and absence of gas in the distal colon or rectum. Sometimes the outline of the intussusception itself can be visualized. Abdominal ultrasound is helpful both to confirm the diagnosis (the so-called target/doughnut sign) and to check response to treatment.

Answer 154

Unless there are signs of peritonitis, reduction of the intussusception by rectal air insufflation is usually attempted by a radiologist. This procedure should only be carried out once the child has been resuscitated and is under the supervision of a paediatric surgeon in case the procedure is unsuccessful or bowel perforation occurs. The success rate of this procedure is about 75%. The remaining 25% require operative reduction. Recurrence of the intussusception occurs in less than 5% but is more frequent after hydrostatic reduction.

Answer 155

Around 2% of individuals have an ileal remnant of the vitello-intestinal duct, a Meckel diverticulum, which contains ectopic gastric mucosa or pancreatic tissue. Most are asymptomatic but they may present with: - Severe rectal bleeding, which is classically neither bright red nor true melaena. - Acute reduction in haemoglobin. - Intussusception - Volvulus (twisting of the bowel) - Diverticulitis, when inflammation of the diverticulum mimics appendicitis. A technetium scan will demonstrate increased uptake by ectopic gastric mucosa in 70% of cases. Treatment is by surgical resection.

Answer 156

During rotation of the small bowel in fetal life, if the mesentery is not fixed at the duodenojejunal flexure or in the ileocaecal region, its base is shorter than normal, and is predisposed to volvulus. Ladd bands are peritoneal bands that may cross the duodenum, often anteriorly. There are two presentations: * Obstruction (from ladd bands obstructing the duodenum or from volvulus) * Obstruction with a compromised blood supply. Obstruction with bilious vomiting is the usual presentation in the first few days of life but can be seen at a later age. There is often abdominal pain and tenderness from peritonitis or ischaemic bowel.

Answer 157

Any child with dark green vomiting needs an urgent upper gastrointestinal contrast study to assess intestinal rotation, unless signs of vascular compromise are present, when an urgent laparotomy is needed. This is a surgical emergency as, when a volvulus occurs, the superior mesenteric arterial blood supply to the small intestine and proximal large intestine is compromised and unless it is corrected will lead to infarction of these areas. At operation, the volvulus is untwisted, the duodenum mobilized, and the bowel placed in the non-rotated position with the duodenojejunal flexure on the right and the caecum and appendix on the left. The malrotation is not ‘corrected’, but the mesentery broadened. The appendix is generally removed to avoid diagnostic confusion should the child subsequently have symptoms suggestive of appendicitis.

Answer 158

The aim is to identify any serious cause without subjecting the child to unnecessary investigation, while providing reassurance to the child and parents. To do this, a full history and thorough examination is required, which includes inspection of the perineum for anal fissures. The child’s growth should be checked. A urine microscopy and culture is mandatory as urinary tract infections may cause pain in the absence of other symptoms or signs. An abdominal ultrasound is particularly helpful in excluding gall stones and pelvi-ureteric junction obstruction. Although there are many potential organic causes, most are rare. Coeliac antibodies and thyroid function tests should be checked, but further investigations should be performed only if clinically indicated. The long-term prognosis is that: * About half of affected children rapidly become free of symptoms * In one-quarter, the symptoms take some months to resolve * In one-quarter, symptoms continue or return in adulthood as migraine, irritable bowel syndrome or functional dyspepsia

Answer 159

Abdominal migraine is often associated with abdominal pain in addition to headaches, and in some children the abdominal pain predominates. The attacks of abdominal pain are midline associated with vomiting and facial pallor. There is usually a personal or family history of migraine. The history is characteristic with long periods (often weeks) of no symptoms and then a shorter period (12–48 hours) of non-specific abdominal pain and pallor, with or without vomiting. Treatment with anti-migraine medication (eg Triptans) may be of benefit if the problem causes school absence.

Answer 160

This disorder, also common in adults, is associated with altered gastrointestinal motility and an abnormal sensation of intra-abdominal events. Symptoms may be precipitated by a gastro-intestinal infection. Studies of pressure changes within the small intestine of children with irritable bowel syndrome suggest that abnormally forceful contractions occur. These factors are usually modulated by psychosocial factors such as stress and anxiety. There is often a positive family history and a characteristic set of symptoms, although not all patients experience every symptom: * Non-specific abdominal pain, often peri-umbilical, may be worse before or relieved by defaecation * Explosive, loose, or mucousy stools * Bloating * Feeling of incomplete defecation * Constipation (often alternating with normal or loose stools). Some children and adults with irritable bowel symptoms have coeliac disease, which is why coeliac antibody serology must be checked.

Answer 161

H. pylori causes a nodular antral gastritis, which may be associated with abdominal pain and nausea. It is usually identified in gastric antral biopsies. The organism produces urease, which forms the basis for a laboratory test on biopsies and the 13C breath test following the administration of 13C-labelled urea by mouth. Stool antigen for H. pylori may be positive in infected children. Serological tests are less reliable in young children but may be helpful in older children. Children in whom peptic ulceration is suspected should be treated with proton-pump inhibitors, e.g. omeprazole, and if investigations suggest they have an H. pylori infection, eradication therapy should be given (amoxicillin and metronidazole or clarithromycin). Those who fail to respond to treatment or whose symptoms recur on stopping treatment should have an upper gastrointestinal endoscopy and, if this is normal, functional dyspepsia is diagnosed.

Answer 162

>90% no structural cause identified 1. Gastrointestinal * Irritable bowel syndrome * Constipation * Non-ulcer dyspepsia * Abdominal migraine * Gastritis and peptic ulceration * Eosinophilic oesophagitis * Inflammatory bowel disease * Malrotation 2. Gynaecological * Dysmenorrhoea * Ovarian cysts * Pelvic inflammatory disease 3. Hepatobility/pancreatic * Hepatitis * Gall stones * Pancreatitis 4. Urinary tract * Urinary tract infection * Pelvi-ureteric junction (PUJ) obstruction 5. Psychosocial – bullying, abuse, stress, etc. – a small proportion

Answer 163

* Epigastric pain at night, haematemesis (duodenal ulcer) * Diarrhoea, weight loss, growth failure, blood in stools (inflammatory bowel disease) * Vomiting (pancreatitis) * Jaundice (liver disease) * Dysuria, secondary enuresis (urinary tract infection) * Bilious vomiting and abdominal distension (malrotation)

Answer 164

Eosinophilic oesophagitis is an inflammatory condition affecting the oesophagus caused by activation of eosinophils within the mucosa and submucosa. It can present with vomiting, discomfort on swallowing or bolus dysphagia, when food “sticks in the upper chest”. There may be difficulty feeding, weight loss and failure to thrive. It is probably an allergic phenomenon although the precise pathophysiology is unclear. It is more common in children with other features of atopy (asthma, eczema, and hay fever). Diagnosis is by endoscopy where macroscopically, linear furrows and trachealization of the oesophagus may be seen, and microscopically, eosinophilic infiltration is identified. Treatment is with swallowed corticosteroids in the form of fluticasone or viscous budesonide. Exclusion diets may be of benefit in young children.

Answer 165

The most frequent cause of gastroenteritis in developed countries is rotavirus infection, which accounts for up to 60% of cases in children under 2 years of age, particularly during the winter and early spring. Other viruses, particularly adenovirus, norovirus, calicivirus, coronavirus and astrovirus may cause outbreaks. Bacterial causes are less common in developed countries but may be suggested by the presence of blood in the stools. -Campylobacter jejuni infection, the most common of the bacterial infections in developed countries, is often associated with severe abdominal pain. -Shigella and some salmonellae produce a dysenteric type of infection, with blood and pus in the stool, pain and tenesmus. Shigella infection may be accompanied by high fever. -Cholera and enterotoxigenic Escherichia coli infection are associated with profuse, rapidly dehydrating diarrhoea. However, clinical features act as a poor guide to the pathogen. The third cause of gastroenteritis is protozoan parasite infection such as Giardia and Cryptosporidium In gastroenteritis there is a sudden change to loose or watery stools often accompanied by vomiting. There may be contact with a person with diarrhoea and/or vomiting or recent travel abroad.

Answer 166

Dehydration leading to shock is the most serious complication and its prevention or correction is the main aim of treatment. The following children are at increased risk of dehydration: * Infants, particularly those under 6 months of age or those born with low birthweight * If they have passed six or more diarrhoeal stools in the previous 24 hours * If they have vomited three or more times in the previous 24 hours * If they have been unable to tolerate (or not been offered) extra fluids * If they have malnutrition. Infants are at particular risk of dehydration because they have a greater surface area-to-weight ratio than older children, leading to greater insensible water losses. They also have higher basal fluid requirements and immature renal tubular reabsorption. In addition, they are unable to obtain fluids for themselves when thirsty.

Answer 167

The most accurate measure of dehydration is the degree of weight loss during the diarrhoeal illness. A recent weight measurement is useful but is often not available and may be misleading if the child had clothes on or the different measuring scales are not accurate. The history and examination are used to assess the degree of dehydration as: * No clinically detectable dehydration (usually <5% loss of body weight) * Clinical dehydration (usually 5-10% loss of body weight) * Shock (usually >10% loss of body weight)

Answer 168

In dehydration, there is a total body deficit of sodium and water. In most instances, the losses of sodium and water are proportional and plasma sodium remains within the normal range (isonatraemic dehydration). When children with diarrhoea drink large quantities of water or other hypotonic solutions, there is a greater net loss of sodium than water, leading to a fall in plasma sodium (hyponatraemic dehydration). This leads to a shift of water from extracellular to intracellular compartments. The increase in intracellular volume leads to an increase in brain volume, which may result in seizures, whereas the marked extracellular depletion leads to a greater degree of shock per unit of water loss. This form of dehydration is more common in poorly nourished infants in developing countries.

Answer 169

Infrequently, water loss exceeds the relative sodium loss and plasma sodium concentration increases (hypernatraemic dehydration). This usually results from high insensible water losses (high fever or hot, dry environment) or from profuse, low-sodium diarrhoea. The extracellular fluid becomes hypertonic with respect to the intracellular fluid, which leads to a shift of water into the extracellular space from the intracellular compartment. Signs of extracellular fluid depletion are therefore less per unit of fluid loss, and depression of the fontanelle, reduced tissue elasticity, and sunken eyes are less obvious. This makes this form of dehydration more difficult to recognize clinically, particularly in an obese infant. It is a particularly dangerous form of dehydration as water is drawn out of the brain and cerebral shrinkage within a rigid skull may lead to jittery movements, increased muscle tone with hyperreflexia, altered consciousness, seizures, and multiple, small cerebral haemorrhages. Transient hyperglycaemia occurs in some patients with hypernatraemic dehydration; it is self-correcting and does not require insulin.

Answer 170

- Decreased level of consciousness - Pale or mottled skin - Hypotension - Sunken fontanelle - Eyes sunken and tearless - Dry mucous membranes - Tachypnoea - Prolonged capillary refill time - Tachycardia, weak peripheral pulses - Reduced tissue turgor - Reduced urine output - Sudden weight loss - Cold extremities

Answer 171

Usually, no investigations are indicated. Stool culture is required if the child appears septic, if there is blood or mucus in the stools, or the child is immunocompromised. It may be indicated following recent foreign travel, if the diarrhoea has not improved by day 7, or if the diagnosis is uncertain. Plasma electrolytes, urea, creatinine, and glucose should be checked if intravenous fluids are required or there are features suggestive of hypernatraemia. If antibiotics are started, a blood culture should be taken.

Answer 172

1. Management of dehydration. Where clinical dehydration is not present, the aim is its prevention. 2. Antibiotics are not routinely required to treat gastroenteritis, even if there is a bacterial cause. They are only indicated for: - Suspected or confirmed sepsis - Extraintestinal spread of bacterial infection - Salmonella gastroenteritis if aged under 6 months - Malnourished or immunocompromised children - Specific bacterial or protozoal infections (e.g. Clostridium difficile associated with pseudomembranous colitis, cholera, shigellosis, giardiasis). 3. Nutrition In developing countries, multiple episodes of diarrhoea are a major contributing factor to the development of malnutrition. Following diarrhoea, nutritional intake should be increased. Diarrhoea may be associated with zinc deficiency and supplementation may be helpful in both acute diarrhoea and as prophylaxis.

Answer 173

There is no place for medications for the vomiting or diarrhoea of gastroenteritis in children as they: * Are ineffective * May prolong the excretion of bacteria in stools * Can be associated with side-effects * Add unnecessarily to cost * Focus attention away from oral rehydration.

Answer 174

- Continue breastfeeding and other milk feeds - Encourage fluid intake to compensate for increased gastrointestinal losses - Discourage fruit juices and carbonated drinks - Oral rehydration solution (ORS) as supplemental fluid if at increased risk of dehydration

Answer 175

- Oral rehydration solution (contains sodium, potassium and glucose), give often and in small amounts - Give fluid deficit replacement (50 ml/kg) over 4 hours as well as maintenance fluid requirement. - Continue breastfeeding - Consider supplementing ORS with usual fluids if inadequate intake of ORS - If inadequate fluid intake or vomits persistently, consider giving ORS via nasogastric tube If there is deterioration or persistent vomiting then intravenous therapy may be required.

Answer 176

Intravenous therapy - Give bolus of 0.9% sodium chloride solution. Repeat if necessary. When symptoms/signs of shock improve move to IV therapy for rehydration: - Replace fluid deficit over 24 hours in most cases and give maintenance fluids - Unless a recent weight measurement is available, clinical estimation of hydration status is difficult. Consider fluid deficit to be 100 ml/kg (10% body weight) if shock is present and 50 ml/kg (5% body weight) if not in shock - Give 0.9% sodium chloride solution or 0.9% sodium chloride solution with 5% glucose - Monitor plasma electrolytes, urea, creatinine, and glucose. - Consider intravenous potassium supplementation - Continue breastfeeding if possible

Answer 177

Oral rehydration solution should be used to rehydrate hypernatraemic children with clinical dehydration. If intravenous fluids are required, a rapid reduction in plasma sodium concentration and osmolality will lead to a shift of water into cerebral cells and may result in seizures and cerebral oedema. The reduction in plasma sodium should therefore be slow. The fluid deficit should be replaced over at least 48 hours (with 0.9% or 0.45% saline) and the plasma sodium measured regularly, aiming to reduce it at less than 0.5 mmol/l per hour.

Answer 178

Infrequently, following an episode of gastroenteritis, the introduction of a normal diet results in a return of watery diarrhoea. In such cases, oral rehydration therapy should be restarted.

Answer 179

Disorders affecting the digestion or absorption of nutrients manifest as: * Abnormal stools * Poor weight gain or faltering growth in most but not all cases * Specific nutrient deficiencies, either singly or in combination. In general, parents know when their children’s stools have become abnormal. The true malabsorption stool is difficult to flush down the toilet and has an odour that pervades the whole house. In general, colour is a poor guide to abnormality. Some disorders affecting the small intestinal mucosa or pancreas (chronic pancreatic insufficiency) may lead to the malabsorption of many nutrients (pan-malabsorption), whereas others are highly specific, e.g. zinc malabsorption in acrodermatitis enteropathica.

Answer 180

Coeliac disease is an enteropathy in which the gliadin fraction of gluten and other related prolamines in wheat, barley, and rye provoke a damaging immunological response in the proximal small intestinal mucosa. As a result, the rate of migration of absorptive cells moving up the villi (enterocytes) from the crypts is massively increased but is insufficient to compensate for increased cell loss from the villous tips. Villi become progressively shorter and then absent, leaving a flat mucosa. The age at presentation is partly influenced by the age of introduction of gluten into the diet. The classical presentation is of a profound malabsorptive syndrome at 8–24 months of age after the introduction of wheat-containing weaning foods. There is: - Faltering growth - Abdominal distension and buttock wasting - Abnormal stools - General irritability However, this ‘classical’ form is no longer the most common presentation and children are now more likely to present less acutely in later childhood. The clinical features of coeliac disease can be highly variable and include: - Mild, non-specific gastrointestinal symptoms - Anaemia (iron and/or folate deficiency) and growth faltering. Alternatively, it is identified on screening of children at increased risk (type 1 diabetes mellitus, autoimmune thyroid disease, Down syndrome) and first-degree relatives of individuals with known coeliac disease.

Answer 181

1. Serological screening tests: anti-tTG (immunoglobulin A tissue transglutaminase antibodies) and EMA (endomysial antibodies). 2. Mucosal changes: Although the diagnosis is strongly suggested by positive serology, confirmation depends upon the demonstration of mucosal changes (increased intraepithelial lymphocytes and a variable degree of villous atrophy and crypt hypertrophy) on small intestinal biopsy performed endoscopically followed by the resolution of symptoms and catch-up growth upon gluten withdrawal.

Answer 182

All products containing wheat, rye, and barley are removed from the diet and this results in resolution of symptoms. Supervision by a dietician is essential. In children in whom the initial biopsy or the response to gluten withdrawal is doubtful, a gluten challenge may be required in later childhood to demonstrate continuing susceptibility of the small intestinal mucosa to damage by gluten. The gluten-free diet should be adhered to for life. Non-adherence to the diet risks the development of micronutrient deficiency, especially osteopenia, and there is a small but definite increased risk in bowel malignancy, especially small bowel lymphoma.

Answer 183

1. Cholestatic liver disease or biliary atresia: Bile salts no longer enter the duodenum in the bile. This leads to defective solubilization of the products of triglyceride hydrolysis. Fat and fat-soluble malabsorption result 2. Exocrine pancreatic dysfunction, e.g. cystic fibrosis: Absent lipase, proteases, and amylase lead to defective digestion of triglyceride, protein, and starch (’pan-nutrient malabsorption’) 3. Lymphatic leakage or obstruction: Chylomicrons (containing absorbed lipids) unable to reach thoracic duct and the systemic circulation, e.g. intestinal lymphangiectasia (abnormal lymphatics) 4. Small-intestinal mucosal disease: * Loss of absorptive surface area, e.g. coeliac disease * Specific enzyme defects, e.g. transient lactase deficiency following gastroenteritis, but is uncommon * Specific transport defects, e.g. glucose–galactose malabsorption (severe life-threatening diarrhoea with first milk feed), acrodermatitis enteropathica (zinc malabsorption, also erythematous rash around mouth and anus) 5. Loss of terminal ileal function: e.g. resection or Crohn's disease Absent bile acid and vitamin B12 absorption 6. Short bowel syndrome: Small-intestinal resection, due to congenital anomalies or necrotizing enterocolitis, leads to nutrient, water and electrolyte malabsorption

Answer 184

This condition, previously known as toddler diarrhoea, is the most common cause of persistent loose stools in preschool children. Characteristically, the stools are of varying consistency, sometimes well formed, sometimes explosive and loose. The presence of undigested vegetables in the stools is common. Affected children are well and thriving. In a proportion of children the diarrhoea may result from undiagnosed coeliac disease or excessive ingestion of fruit juice, especially apple juice. Occasionally the cause is temporary cow’s milk allergy following gastroenteritis, when a trial of a cow’s milk protein free diet may be helpful. Once possible underlying causes have been excluded, in the majority of cases the loose stools probably result from dysmotility of the gut (a form of irritable bowel syndrome) and fast-transit diarrhoea; it almost always improves with age.

Answer 185

Crohn’s disease can affect any part of the gastrointestinal tract from mouth to anus, whereas in ulcerative colitis the inflammation is confined to the colon.

Answer 186

1. Growth failure 2. Puberty delayed 3. General ill health: * Fever * Lethargy * Weight loss 4. Classical presentation (25%): * Abdominal pain * Diarrhoea * Weight loss 5. Extra-intestinal manifestations: * Oral lesions or perianal skin tags * Uveitis * Arthralgia * Erythema nodosum

Answer 187

The presence of raised inflammatory markers (platelet count, ESR, and CRP), iron-deficiency anaemia, and low serum albumin are helpful in both making a diagnosis and confirming a relapse. Diagnosis is based on endoscopic and histological findings on biopsy. Upper gastrointestinal endoscopy, ileocolonoscopy and small bowel imaging are required. The histological hallmark is the presence of non-caseating epithelioid cell granulomata, although this is not identified in up to 30% at presentation. Small bowel imaging may reveal narrowing, fissuring, mucosal irregularities and bowel wall thickening.

Answer 188

Crohn’s disease is a transmural, focal, subacute, or chronic inflammatory disease, most commonly affecting the distal ileum and proximal colon. Initially, there are areas of acutely inflamed, thickened bowel. Subsequently, strictures of the bowel and fistulae may develop between adjacent loops of bowel, between bowel and skin or to other organs (e.g. vagina, bladder).

Answer 189

Remission is induced with nutritional therapy, when the normal diet is replaced by whole protein modular feeds (polymeric diet) for 6–8 weeks. This is effective in 75% of cases. Systemic steroids are required if ineffective. Relapse is common and immunosuppressant medication (azathioprine, mercaptopurine or methotrexate) is almost always required to maintain remission. Anti-tumour necrosis factor agents (infliximab or adalimumab) may be needed when conventional treatments have failed. Long-term supplemental enteral nutrition (often with overnight nasogastric or gastrostomy feeds) may be helpful in correcting growth failure. Surgery is necessary for complications of Crohn’s disease – obstruction, fistulae, abscess formation or severe localized disease unresponsive to medical treatment, often manifesting as growth failure.

Answer 190

Ulcerative colitis is a recurrent, inflammatory and ulcerating disease involving the mucosa of the colon. Characteristically, the disease presents with rectal bleeding, diarrhoea and colicky pain. Weight loss and growth failure may occur, although this is less frequent than in Crohn’s disease. Extra-intestinal complications include erythema nodosum and arthritis.

Answer 191

The diagnosis is made on endoscopy (upper and ileocolonoscopy) and on the histological features, after exclusion of infective causes of colitis. There is a confluent colitis extending from the rectum proximally for a variable length. In contrast to adults, in whom the colitis is usually confined to the distal colon, 90% of children have pancolitis. Histology reveals mucosal inflammation, crypt damage (cryptitis, architectural distortion, abscesses and crypt loss), and ulceration. Small bowel imaging is required to check that extra-colonic inflammation suggestive of Crohn’s disease is not present

Answer 192

In mild disease, aminosalicylates (e.g. mesalazine) are used for induction and maintenance therapy. Disease confined to the rectum and sigmoid colon (rare in children) may be managed with topical steroids. More aggressive or extensive disease requires systemic steroids for acute exacerbations and immunomodulatory therapy, e.g. azathioprine alone to maintain remission or in combination with low-dose corticosteroid therapy. There is a role for biological therapies such as infliximab or ciclosporin in patients with resistant disease, but if ineffective, surgery should not be delayed. Severe fulminating disease is a medical emergency and requires treatment with intravenous fluids and steroids. If this fails to induce remission, ciclosporin may be used. Colectomy with an ileostomy or ileorectal pouch is undertaken for severe fulminating disease, which may be complicated by a toxic megacolon, or for chronic poorly controlled disease. There is an increased incidence of adenocarcinoma of the colon in adults. Regular colonoscopic screening is performed after 10 years from diagnosis

Answer 193

1. Failure to pass meconium within 24 hours of life: Hirschsprung disease 2. Faltering growth/growth failure: Hypothyroidism, coeliac disease, other causes 3. Gross abdominal distension: Hirschsprung disease or other gastrointestinal dysmotility 4. Abnormal lower limb neurology or deformity, e.g. talipes or secondary urinary incontinence: Lumbosacral pathology 5. Sacral dimple above natal cleft, over the spine – naevus, hairy patch, central pit, or discoloured skin: Spina bifida occulta 6. Abnormal appearance/ position/ patency of anus: Abnormal anorectal anatomy 7. Perianal bruising or multiple fissures: Sexual abuse 8. Perianal fistulae, abscesses, or fissures: Perianal Crohn's disease

Answer 194

In more long-standing constipation, the rectum becomes overdistended, with a subsequent loss of feeling the need to defecate. Involuntary soiling may occur as contractions of the full rectum inhibit the internal sphincter, leading to overflow. It should be explained to the child and the parents that the soiling is involuntary and that recovery of normal rectal size and sensation can be achieved but may take a long time.

Answer 195

Ensure adequate oral fluid intake and encourage good toileting habits. 1. Osmotic laxative: Polyethylene glycol (movicol) + electrolytes (give the low-dose regimen in mild disease or the disimpaction regimen with an escalating dose over 1-2 weeks if constipation with impaction) [Lactulose can be substituted if not tolerated] +/- 2. Stimulant laxative e.g. sodium picosulphate or senna if response inadequate Continue the laxative therapy for a minimum of 6 months to ensure regular stooling, titrating the dose. Occasionally, the faecal retention is so severe that evacuation is only possible using enemas or by manual evacuation under an anaesthetic. They should only be performed under specialist supervision, paying particular attention to avoiding distress and embarrassment for the child. Dietary interventions alone are of little or no benefit in managing constipation in this situation, although the child should receive sufficient fluid and a balanced diet. The addition of extra fibre to the diet is not helpful, and may make stools larger and more difficult to pass. The child should be encouraged to sit on the toilet after mealtimes to utilize the physiological gastrocolic reflex and improve the likelihood of success.

Answer 196

The absence of ganglion cells from the myenteric and submucosal plexuses of part of the large bowel results in a narrow, contracted segment. The abnormal bowel extends from the rectum for a variable distance proximally, ending in a normally innervated, dilated colon. In 75% of cases, the lesion is confined to the rectosigmoid, but in 10% the entire colon is involved. Presentation is usually in the neonatal period with intestinal obstruction heralded by failure to pass meconium within the first 24 hours of life. Abdominal distension and later bile-stained vomiting develop. Occasionally, infants present with severe, life-threatening Hirschsprung enterocolitis during the first few weeks of life. In later childhood, presentation is with chronic constipation, usually profound, and associated with abdominal distension but usually without soiling. Growth failure may also be present.

Answer 197

Rectal examination may reveal a narrowed segment and withdrawal of the examining finger often releases a gush of liquid stool and flatus. Temporary improvement in the obstruction following the dilatation caused by the rectal examination can lead to a delay in diagnosis. Diagnosis is made by demonstrating the absence of ganglion cells, together with the presence of large, acetylcholinesterase-positive nerve trunks on a suction rectal biopsy. Anorectal manometry or barium studies may be useful in giving the surgeon an idea of the length of the aganglionic segment but are unreliable for diagnostic purposes. Management is surgical and usually involves an initial colostomy followed by anastomozing normally innervated bowel to the anus.

Answer 198

1. Faltering growth and malnutrition 2. Jaundice 3. Ascites 4. Cholestasis: * Fat malabsorption * Deficiency of fat-soluble vitamins * Pruritus * Pale stools * Dark urine 5. Spider naevi 6. Bruising and petechiae 7. Palmar erythema 8. Varices with portal hypertension 9. Clubbing 10. Hypersplenism 11. Splenomegaly with portal hypertension 12. Muscle wasting from malnutrition 13. Loss of fat stores secondary to malnutrition 14. Peripheral neuropathy 15. Encephalopathy 16. Hepatorenal failure 17. Hypotonia 18. Epistaxis 19. Rickets secondary to vitamin D deficiency

Answer 199

Physiological jaundice in newborns is common but 90% will have resolved by 2 weeks (3 weeks if preterm). Prolonged (or persistent) neonatal jaundice requires prompt investigation to distinguish unconjugated (resolves spontaneously) from conjugated which indicates liver disease. Unconjugated causes: * Breastmilk jaundice * Infection (particularly urinary tract) * Haemolytic anaemia, e.g. G6PD deficiency * Hypothyroidism * High gastrointestinal obstruction * Crigler–Najjar syndrome Conjugated causes: 1. Bile duct obstruction * Biliary atresia * Choledochal cyst 2. Neonatal hepatitis syndrome * Congenital infection * Inborn errors of metabolism * α1-Antitrypsin deficiency * Galactosaemia * Tyrosinaemia (type 1) * Errors of bile acid synthesis * Progressive familial intrahepatic cholestasis * Cystic fibrosis * Intestinal failure-associated liver disease – associated with long-term parenteral nutrition 3. Intrahepatic biliary hypoplasia * Alagille syndrome

Answer 200

There is progressive fibrosis and obliteration of the extrahepatic and intrahepatic biliary tree. Without intervention, chronic liver failure develops and death occurs within 2 years. The exact aetiology is unknown. Clinical presentation is with mild jaundice and pale stools (the colour may fluctuate but becomes increasingly pale as the disease progresses). They have normal birthweight followed by faltering growth. Hepatomegaly is often present initially. Splenomegaly develops due to portal hypertension.

Answer 201

There is a raised conjugated bilirubin and abnormal liver function test. A fasting abdominal ultrasound may demonstrate a contracted or absent gallbladder, though it may be normal. The diagnosis is confirmed by a cholangiogram (ERCP - endoscopic retrograde cholangiopancreatography), which fails to outline a normal biliary tree. Liver biopsy initially demonstrates neonatal hepatitis with features of extrahepatic biliary obstruction developing with time.

Answer 202

Palliative surgery with a Kasai hepatoportoenterostomy (a loop of jejunum is anastomosed to the cut surface of the porta hepatis) bypasses the fibrotic ducts and facilitates drainage of bile from any remaining patent ductules. Early surgery increases the success rate, with 80% clearing the jaundice if performed before 60 days. Even with successful clearance of jaundice, the disease progresses in most children who may develop cholangitis and cirrhosis with portal hypertension. Nutrition and fat-soluble vitamin supplementation is essential. If the Kasai is unsuccessful, liver transplantation is considered. Biliary atresia is the single most common indication for liver transplantation in the paediatric age group.

Answer 203

These are cystic dilatations of the extrahepatic biliary system. They may be detected on antenatal ultrasound scan, present with neonatal jaundice or, in older children, presentation is with abdominal pain, a palpable mass, jaundice, or cholangitis (possibly due to reflux of enteric contents into the cyst and biliary tree). The diagnosis is established by ultrasound or magnetic resonance cholangiopancreatography. Treatment is by surgical excision of the cyst with the formation of a Roux-en-Y anastomosis to the biliary duct. Future complications include cholangitis and a 2% risk of malignancy, which may develop in any part of the biliary tree.

Answer 204

In neonatal hepatitis syndrome, there is prolonged neonatal jaundice and hepatic inflammation. It is termed idiopathic if no specific cause can be found. Causes include: * Congenital infection * Inborn errors of metabolism * α1-Antitrypsin deficiency * Galactosaemia * Tyrosinaemia (type 1) * Errors of bile acid synthesis * Progressive familial intrahepatic cholestasis * Cystic fibrosis * Intestinal failure-associated liver disease – associated with long-term parenteral nutrition

Answer 205

Prolonged neonatal jaundice and hepatic inflammation. Babies may have a low birthweight and faltering growth. Other clinical features depend on the diagnosis. Jaundice may be severe and differentiation from biliary atresia is essential. Liver biopsy is often nonspecific but shows giant cell hepatitis.

Answer 206

This is a rare autosomal dominant condition with widely varying penetrance even within families. Clinical presentation is with a characteristic triangular facies, skeletal abnormalities (including butterfly vertebrae), congenital heart disease (classically peripheral pulmonary stenosis), renal tubular disorders, and defects in the eye. Infants may be profoundly cholestatic with severe pruritus and faltering growth. Identifying the gene mutations confirms the diagnosis. Treatment is to provide nutrition and fat-soluble vitamins. Pruritus is profound and difficult to manage. A small number will require liver transplant, but most survive into adult life. Mortality is most likely secondary to the cardiac disease.

Answer 207

These autosomal recessive disorders all affect bile salt transport. Clinical presentation is with jaundice, intense pruritus, faltering growth, rickets, and in some cases diarrhoea and hearing loss. Older children may present with gallstones. The diagnosis is confirmed by identifying mutations in bile salt transport genes. Treatment is with nutritional support and fat-soluble vitamins. Pruritus can be severe. Progression of fibrosis is usual with most requiring liver transplantation.

Answer 208

A form of neonatal metabolic liver disease. It is inherited as an autosomal recessive disorder. There are many phenotypes of the protease inhibitor (Pi) which are coded on chromosome 14, with liver disease primarily associated with the protein phenotype PiZZ. Abnormal folding of the protease α1-antitrypsin is associated with accumulation of the protein within the hepatocytes and hence liver disease in infancy and childhood. The lack of circulating α1-antitrypsin results in emphysema in adults. The majority of children who present with α1-antitrysin deficiency will either have prolonged neonatal jaundice or, less commonly, bleeding due to vitamin K deficiency (haemorrhagic disease of the newborn). Hepatomegaly is present. Splenomegaly develops with cirrhosis and portal hypertension. The disorder can be diagnosed antenatally. The diagnosis is confirmed by estimating the level of α1-antitrypsin in the plasma and identifying the protein phenotype. Approximately 50% of children have a good prognosis, but the remainder will develop liver disease and may require transplantation. Pulmonary disease is not significant in childhood, but is likely to develop in adult life. Advice to avoid smoking (both active and passive) should be given.

Answer 209

A form of neonatal metabolic liver disease. A hereditary disorder of carbohydrate metabolism that affects the body's ability to convert galactose to glucose. The infants develop poor feeding, vomiting, jaundice, and hepatomegaly when fed milk. Liver failure, cataracts, and developmental delay are inevitable if it is untreated. A rapidly fatal course with shock, haemorrhage, and disseminated intravascular coagulation, often due to Gram-negative sepsis, may occur. On investigating prolonged (persistent) jaundice, it can be identified by detecting galactose, a reducing substance, in the urine. The diagnosis is made by measuring the enzyme galactose-1-phosphate-uridyl transferase in red cells. A recent blood transfusion may mask the diagnosis. A galactose-free diet prevents progression of liver disease, but ovarian failure and learning difficulties may occur later.

Answer 210

The clinical features of acute viral hepatitis include nausea, vomiting, abdominal pain, lethargy, and jaundice; however, 30% to 50% of children do not develop jaundice. A large tender liver is common and 30% will have splenomegaly. The liver transaminases are usually markedly elevated. Coagulation is usually normal.

Answer 211

Hepatitis A virus is an RNA virus which is spread by faecal–oral transmission. Vaccination is required for travellers to endemic areas (often where sanitation and food hygiene are generally poor eg parts of Africa, Indian subcontinent, far east, middle east, south america) The disease may be asymptomatic, but the majority of children have a mild illness and recover both clinically and biochemically within 2 weeks to 4 weeks. Some may develop prolonged cholestatic hepatitis (which is self-limiting), or fulminant hepatitis. Chronic liver disease does not occur. Diagnosis can be confirmed by detecting IgM antibody to the virus (anti-HAV). There is no treatment and no evidence that bed rest or change of diet is effective. Close contacts should be vaccinated within 2 weeks of the onset of the illness. In those at increased risk e.g. chronic liver disease, HNIG (human normal immunoglobulin) should be considered.

Answer 212

Hepatitis B virus (HBV) is a DNA virus that is an important cause of acute and chronic liver disease worldwide, with high prevalence and carrier rates in sub-Saharan Africa and the Far East. HBV is transmitted by: * Perinatal transmission from carrier mothers or horizontal spread within families * Inoculation with infected blood via blood transfusion, needlestick injuries, or renal dialysis * Among adults it can also be transmitted sexually. Infants who contract HBV perinatally are asymptomatic, but at least 90% become chronic carriers. Older children who contract HBV may be asymptomatic or have classical features of acute hepatitis. The majority will resolve spontaneously, but 1-2% develop fulminant hepatic failure, while 5% to 10% become chronic carriers. The diagnosis is made by detecting HBV antigens and antibodies. IgM antibodies to the core antigen (anti-HBc) are positive in acute infection. Hepatitis B surface antigen (HBsAg) denotes ongoing infectivity. There is no treatment for acute HBV infection.

Answer 213

Approximately 30% to 50% of asymptomatic carrier children will develop chronic HBV liver disease, which may progress to cirrhosis in 10%. There is a long-term risk of cirrhosis and hepatocellular carcinoma. Current treatment regimens for chronic HBV have poor efficacy. Interferon or pegylated interferon (a long acting formulation) treatment for chronic hepatitis B is successful in 50% of children infected horizontally and 30% of children infected perinatally. (Interferons are antiviral cytokines) Oral antiviral therapy such as lamivudine and adefovir is effective in 25% but may be limited by the development of resistance. Newer drugs (such as entecavir, tenofovir, and telbivudine) may be more effective. Prevention of HBV infection is important. All pregnant women should have antenatal screening for HBsAg. Babies of all HBsAg-positive mothers should receive a course of hepatitis B vaccination (given routinely to all infants in many countries), with hepatitis B immunoglobulin also being given if the mother is also hepatitis B e antigen (HBeAg)-positive. (this antigen exists during the early phase of hepB infection soon after detectable surface antigen) Antibody response to the vaccination course should be checked in high-risk infants at 12 months as 5% require further vaccination. Other members of the family should also be vaccinated. There is evidence that effective neonatal vaccination reduces the incidence of HBV-related cancer.

Answer 214

Hepatitis C virus (HCV) is an RNA virus that was responsible for 90% of post-transfusion hepatitis until the screening of donor blood was introduced. The prevalence is high among intravenous drug users. Vertical transmission is now the most common cause of HCV transmission in children. Six percent of transmission occurs from infected mothers, but is twice as common if there is coinfection with HIV. It seldom causes an acute infection, but the majority become chronic carriers, with a 20% to 25% lifetime risk of progression to cirrhosis or hepatocellular carcinoma. Standard treatment with a combination of pegylated interferon and ribavirin (antiviral) is successful. Recent developments with oral antiviral drugs such as sofosbuvir are likely to be 100% curative, thus increasing the need to screen high risk children, such as the children of drug abusers. Treatment is not undertaken before 3 years of age, as HCV may resolve spontaneously following vertically acquired infections.

Answer 215

Hepatitis D virus (HDV) is a defective RNA virus that depends on hepatitis B virus for replication. It occurs as a coinfection with hepatitis B virus or as a superinfection causing an acute exacerbation of chronic hepatitis B virus infection. Cirrhosis develops in 50% to 70% of those who develop chronic HDV infection.

Answer 216

This is an RNA virus that is enterally transmitted, usually by contaminated water. It is found worldwide but is more prevalent in low-income countries. Hepatitis E virus causes a mild self-limiting illness in most people and is known to be transmitted by blood transfusion or eating infected pork. In pregnant women it causes fulminant hepatic failure with a high mortality rate.

Answer 217

Clinical presentation is similar to hepatitis A. When a viral aetiology of hepatitis is suspected but not identified, it is known as seronegative hepatitis.

Answer 218

The disease is uncommon, but has a high mortality. Most are caused by infection and metabolic conditions. Acute liver failure in children is the development of massive hepatic necrosis with subsequent loss of liver function, with or without hepatic encephalopathy. The child may present within hours or weeks with jaundice, encephalopathy, coagulopathy, hypoglycaemia, and electrolyte disturbance. Early signs of encephalopathy include alternate periods of irritability and confusion with drowsiness. Older children may be aggressive and unusually difficult. Complications include cerebral oedema, haemorrhage from gastritis or coagulopathy, sepsis and pancreatitis.

Answer 219

Children <2 years: - Infection (most common is herpes simplex) -Metabolic disease -Seronegative hepatitis -Drug induced -Neonatal haemochromatosis Children >2 years: -Seronegative hepatitis -Paracetamol overdose -Mitochondrial disease -Wilson disease -Autoimmune hepatitis

Answer 220

Diagnosis Bilirubin may be normal in the early stages, particularly with metabolic disease. Transaminases are greatly elevated (10–100 times normal), alkaline phosphatase is increased, coagulation is very abnormal and plasma ammonia is elevated. It is essential to monitor the acid–base balance, blood glucose and coagulation times. An EEG will show acute hepatic encephalopathy and a CT scan may demonstrate cerebral oedema. Management Early referral to a national paediatric liver centre is essential Steps to stabilize the child prior to transfer include: * Maintaining the blood glucose (>4 mmol/L) with intravenous dextrose * Preventing sepsis with broad-spectrum antibiotics and antifungal agents * Preventing haemorrhage, particularly from the gastrointestinal tract, with intravenous vitamin K and H2-blocking drugs or proton pump inhibitors * Prevent cerebral oedema by fluid restriction and mannitol diuresis if oedema develops. Features suggestive of a poor prognosis are a shrinking liver, rising bilirubin with falling transaminases, a worsening coagulopathy, or progression to coma. Without liver transplantation, 70% of children who progress to coma will die.

Answer 221

-Postviral hepatitis B, C -Autoimmune hepatitis and sclerosing cholangitis -Drug-induced liver disease (NSAIDs) -Cystic fibrosis -Wilson disease -Fibropolycystic liver disease -Non-alcoholic fatty liver disease -α1-Antitrypsin deficiency

Answer 222

The clinical presentation varies from an apparent acute hepatitis to the insidious development of hepatosplenomegaly, cirrhosis, and portal hypertension with lethargy and malnutrition.

Answer 223

These conditions are often prevalent as an overlap syndrome (Autoimmune sclerosing cholangitis - ASC) AIH: Inflammatory disease of the liver of unknown cause characterised by abnormal T-cell function and autoantibodies directed against hepatocyte surface antigens. PSC: progressive cholestasis with bile duct inflammation

Answer 224

The mean age of presentation is 7 years to 10 years. It is more common in girls. It may present as an acute hepatitis, as fulminant hepatic failure or chronic liver disease with autoimmune features such as skin rash, arthritis, haemolytic anaemia, or nephritis. Diagnosis is based on elevated total protein, hypergammaglobulinaemia (IgG >20 g/L); positive autoantibodies (SMA, ANCA, ASMA), a low serum complement (C4); and typical histology. Autoimmune hepatitis may occur in isolation or in association with inflammatory bowel disease, coeliac disease, or other autoimmune diseases. Some 90% of children with autoimmune hepatitis will respond to prednisolone and azathioprine. Sclerosing cholangitis is treated with ursodeoxycholic acid.

Answer 225

Liver disease is the second most common cause of death after respiratory disease in cystic fibrosis. The most common liver abnormality is hepatic steatosis (fatty liver). It may be associated with protein energy malnutrition or micronutrient deficiencies. Steatosis does not generally progress and treatment involves ensuring optimal nutritional support. More significant liver disease arises from thick tenacious bile with abnormal bile acid concentration leading to progressive biliary fibrosis. Cirrhosis and portal hypertension develop in 20% of children by mid-adolescence. Early liver disease is difficult to detect by biochemistry, ultrasound or radioisotope scanning. Liver histology includes fatty liver, focal biliary fibrosis, or focal nodular cirrhosis. Supportive therapy includes endoscopic treatment of varices and nutritional therapy and treatment with ursodeoxycholic acid. Liver transplantation may be considered for those with end-stage liver disease, either alone or in combination with a heart–lung transplant.

Answer 226

Wilson disease is an autosomal recessive disorder. The basic genetic defect is a combination of reduced synthesis of caeruloplasmin (the copper-binding protein) and defective excretion of copper in the bile, which leads to an accumulation of copper in the liver, brain, kidney, and cornea. Wilson disease rarely presents in children under the age of 3 years. In those presenting in childhood, a hepatic presentation is more likely. They may present with almost any form of liver disease, including acute hepatitis, fulminant hepatitis, cirrhosis, and portal hypertension. Neuropsychiatric features are more common in those presenting from the second decade onwards and include deterioration in school performance, mood and behaviour change, and extrapyramidal signs such as incoordination, tremor, and dysarthria. Renal tubular dysfunction, with vitamin D-resistant rickets, and haemolytic anaemia also occur. Copper accumulation in the cornea (Kayser–Fleischer rings) is not seen before 7 years of age.

Answer 227

A low serum caeruloplasmin and copper is characteristic, but not universal. Urinary copper excretion is increased and this further increases after administering the chelating agent penicillamine. However, the diagnosis is confirmed by the finding of elevated hepatic copper on liver biopsy or identification of the gene mutation. Treatment is with penicillamine or trientine. Both promote urinary copper excretion, reducing hepatic and central nervous system copper. Zinc is given to reduce copper absorption. Pyridoxine is given to prevent peripheral neuropathy. Zinc is used in asymptomatic children identified by screening families with an index case. Neurological improvement may take up to 12 months of therapy. About 30% of children with Wilson disease will die from hepatic complications if untreated. Liver transplantation is considered for children with acute liver failure or severe end-stage liver disease.

Answer 228

This is a range of inherited conditions affecting the development of the intrahepatic biliary tree. Presentation is with liver cystic disease or fibrosis and renal disease. Congenital hepatic fibrosis presents in children over 2 years old with hepatosplenomegaly, abdominal distension, and portal hypertension. It differs from cirrhosis in that liver function tests are normal in the early stage. Liver histology shows large bands of hepatic fibrosis containing abnormal bile ductules. Complications include portal hypertension with varices and recurrent cholangitis. Cystic renal disease may coexist and may cause hypertension or renal dysfunction. Indications for liver transplant include severe recurrent cholangitis or deterioration of renal function requiring renal transplant, in which case a combined transplant would be offered.

Answer 229

It is a spectrum of disease, ranging from simple fatty deposition (steatosis) through to inflammation (steatohepatitis), fibrosis, cirrhosis, and end-stage liver failure. In childhood, it may be associated with a metabolic syndrome or with obesity. The pathogenesis is not fully understood but may be linked to insulin resistance. The prognosis in childhood is uncertain; few develop cirrhosis in childhood in contrast to 8% to 17% of adults. They are usually asymptomatic, although some complain of vague right upper quadrant abdominal pain or lethargy. The diagnosis is often suspected following the incidental finding of an echogenic liver on ultrasound or mildly elevated transaminases carried out for some other reason. Liver biopsy demonstrates marked steatosis with or without inflammation or fibrosis. Treatment targets weight loss through diet and exercise, which may lead to liver function tests returning to normal

Answer 230

1. Nutrition - Fat malabsorption – long chain fat is not effectively absorbed without bile. Therefore, medium chain triglyceride-containing milk is required if children are persistently cholestatic, as it does not require bile micelles for absorption. - Fat-soluble vitamins (KADE) are carried on the long chain fats and hence deficiency is common unless these vitamins are supplemented. (K deficiency = bleeding incl intracranial, A deficiency = retinal changes or blindness, D = rickets and fractures, E = peripheral neuropathy, haemolysis, ataxia) - Protein malnutrition – poor intake combined with high catabolic rate of the diseased liver. Protein intake should not be restricted unless the child is encephalopathic. 2. Pruritus: Severe pruritus is associated with cholestasis, although the aetiology is not clear. Treatment includes: * Loose cotton clothing, avoiding overheating, keep nails short. * Moisturising the skin with emollients. * Medication: phenobarbital to stimulate bile flow; cholestyramine, a bile salt resin to absorb bile salts; ursodeoxycholic acid, an oral bile acid to solubilise the bile; rifampicin, an enzyme inducer 3. Encephalopathy: occurs in end-stage liver disease and may be precipitated by gastrointestinal haemorrhage, sepsis, sedatives, renal failure, or electrolyte imbalance. Infants present with irritability and sleepiness, while older children present with abnormalities in mood, sleep rhythm, intellectual performance, and behaviour. Plasma ammonia may be elevated and an EEG is always abnormal. Oral lactulose and a nonabsorbable oral antibiotic (e.g. rifaximin) will help reduce the ammonia by lowering the colonic pH and increasing gut transit time. 4/5. Cirrhosis and portal hypertension: extensive fibrosis with regenerative nodules. It may be secondary to hepatocellular disease or to chronic bile duct obstruction (biliary cirrhosis). The main pathophysiological effects of cirrhosis are diminished hepatic function and portal hypertension with splenomegaly, varices, and ascites. Hepatocellular carcinoma may develop. Children with compensated cirrhosis may be asymptomatic if liver function is adequate. They will not be jaundiced and may have normal liver function tests. As the cirrhosis increases, however, the results of deteriorating liver function and portal hypertension become obvious. Physical signs include jaundice, palmar and plantar erythema, telangiectasia and spider naevi, malnutrition, and hypotonia. Dilated abdominal veins and splenomegaly suggest portal hypertension, although the liver may be shrunken and impalpable. 6. Oesophageal varices: These are an inevitable consequence of portal hypertension and may develop rapidly in children. They are best diagnosed by upper gastrointestinal endoscopy. Acute bleeding is treated conservatively with blood transfusions and H2-blockers (e.g. ranitidine) or omeprazole. If bleeding persists, octreotide infusion, vasopressin analogues, endoscopic band ligation, or sclerotherapy may be effective. Portacaval shunts may preclude liver transplantation, but radiological placement of a stent between the hepatic and portal veins can be used as a temporary measure if transplantation is being considered. 7. Ascites: The pathophysiology of ascites is uncertain, but contributory factors include hypoalbuminaemia, sodium retention, renal impairment and fluid redistribution. It is treated by sodium and fluid restriction and diuretics. Additional therapy for refractory ascites includes albumin infusions or paracentesis. 8. Spontaneous bacterial peritonitis: This should always be considered if there is undiagnosed fever, abdominal pain, tenderness, or an unexplained deterioration in hepatic or renal function. A diagnostic paracentesis should be performed and the fluid sent for white cell count and differential and culture. Treatment is with broad-spectrum antibiotics. 9. Renal failure: This may be secondary to renal tubular acidosis, acute tubular necrosis, or functional renal failure (hepatorenal syndrome).

Answer 231

Investigations include: * Screening for the known causes of chronic liver disease * Upper gastrointestinal endoscopy to detect the presence of oesophageal varices and/or erosive gastritis * Abdominal ultrasound – may show a shrunken liver and splenomegaly with gastric and oesophageal varices * Liver biopsy – may be difficult because of increased fibrosis but may indicate the aetiology (e.g. typical changes in congenital hepatic fibrosis, copper storage). As cirrhosis decompensates, biochemical tests may demonstrate an elevation of aminotransferases and alkaline phosphatase. The plasma albumin falls and the prothrombin time becomes increasingly prolonged.

Answer 232

The indications for transplantation in chronic liver failure are: * Severe malnutrition unresponsive to intensive nutritional therapy * Complications refractory to medical management (bleeding varices, resistant ascites) * Failure of growth and development * Poor quality of life. Liver transplant evaluation includes assessment of the vascular anatomy of the liver and exclusion of irreversible disease in other systems. Absolute contraindications include sepsis, untreatable cardiopulmonary disease or cerebrovascular disease. There is considerable difficulty in obtaining small organs for children. Most children receive part of an adult’s liver, either a cadaveric graft or more recently from a living related donor. A cadaveric organ may either be reduced to fit the child’s abdomen (reduction hepatectomy) or split (shared between an adult and child).

Answer 233

1. Plasma creatinine concentration: Main test of renal function. Rises progressively throughout childhood according to height and muscle bulk. May not be outside laboratory ‘normal range’ until renal function has fallen to less than half normal. 2.eGFR: Better measure of renal function than creatinine and useful to monitor renal function serially in children with renal impairment 3. Inulin or EDTA (ethylenediaminetetraacetic acid) glomerular filtration rate: More accurate as clearance from the plasma of substances freely filtered at the glomerulus, and is not secreted or reabsorbed by the tubules. Need for repeated blood sampling over several hours limits use in children 4. Creatinine clearance: Requires timed urine collection and blood tests. Rarely done in children as inconvenient and often becomes inaccurate 5. Plasma urea concentration: Increased in renal failure, often before creatinine starts rising, and raised levels may be symptomatic. Urea levels also increased by high protein diet, in catabolic states, or due to gastrointestinal bleeding

Answer 234

1. Ultrasound: Standard imaging procedure of the kidneys and urinary tract provides anatomical assessment but not function. Excellent at visualizing urinary tract dilatation, stones, and nephrocalcinosis (small, multiple calcium deposits within renal parenchyma) - Advantages: noninvasive, mobile - Disadvantages: operator dependent, will not detect all renal scars, Static scan of the renal cortex 2. DMSA scan (99mTc dimercaptosuccinic acid): Detects functional defects, such as scars or areas of nonfunctioning renal tissue, but very sensitive, so need to wait at least 2 months after a urinary tract infection to avoid diagnosing false ‘scars’ 3. Micturating cystourethrogram (MCUG): Contrast introduced into the bladder through urethral catheter. Can visualize bladder and urethral anatomy. Detects vesicoureteric reflux (VUR) and urethral obstruction - Disadvantages: invasive and unpleasant investigation especially beyond infancy, high radiation dose, and can introduce infection 4. MAG3 renogram (mercapto-acetyltriglycine, labelled with 99mTc): Dynamic scan, isotope-labelled substance MAG3 excreted from the blood into the urine. Measures drainage, best performed with a high urine flow so furosemide often given/ In children old enough to cooperate (usually >4 years of age), scan during micturition is used to identify VUR (indirect cystogram) 5. Plain abdominal X-ray: Identifies unsuspected spinal abnormalities May identify renal stones, but poor at showing nephrocalcinosis

Answer 235

1. Absence of both kidneys (renal agenesis) – As amniotic fluid is mainly derived from fetal urine, there is severe oligohydramnios resulting in Potter syndrome, which is fatal (low amniotic fluid causes fetal compression causing characteristic facies, lung hypoplasia, severe talipes). 2. Multicystic dysplastic kidney – Results from the failure of union of the ureteric bud (which forms the ureter, pelvis, calyces, and collecting ducts) with the nephrogenic mesenchyme. It is a non-functioning structure with large fluid-filled cysts with no renal tissue and no connection with the bladder. Half will have involuted by 2 years of age, and nephrectomy is indicated only if it remains very large or hypertension develops, but this is rare. Because they produce no urine, Potter syndrome will result if the lesion is bilateral. Other causes of large cystic kidneys are: 3. Autosomal recessive polycystic kidney disease (ARPKD): diffuse bilateral enlargement of both kidneys 4. Autosomal dominant polycystic kidney disease (ADPKD): Separate cysts of varying size between normal renal parenchyma, the kidneys are enlarged. Causes htn and renal failure in late adulthood, associated with cysts in the liver and pancreas, cerebral aneurysms, and mitral valve prolapse. 5. Tuberous sclerosis. In contrast to a multicystic dysplastic kidney, in these disorders some or normal renal function is maintained but both kidneys are always affected. 6. Pelvic/Horseshoe kidney: Caused by abnormal caudal migration. The lower poles are fused in the midline. The abnormal position may predispose to infection or obstruction of urinary drainage. 7. Duplex kidney: Premature division of the ureteric bud gives rise to a duplex system, which can vary from simply a bifid renal pelvis to complete division with two ureters. These ureters frequently have an abnormal drainage so that the ureter from the lower pole moiety often refluxes, whereas the upper pole ureter may drain ectopically into the urethra or vagina or may prolapse into the bladder (ureterocele) and urine flow may be obstructed. 8. Bladder exstrophy: Failure of fusion of the infraumbilical midline structures results in exposed bladder mucosa. Absence or severe deficiency of the anterior abdominal wall muscles is frequently associated with a large bladder and dilated ureters (megacystis-megaureter) and cryptorchidism, the prune-belly syndrome (absent musculature syndrome). 9. Hydronephrosis/Urinary tract obstruction: Obstruction to urine flow may occur at the: - Pelviureteric or - Vesicoureteric junction (both causing unilateral hydronephrosis), or at the - Bladder neck (e.g. due to disruption of the nerve supply, neuropathic bladder), or - Posterior urethra in a boy due to mucosal folds or a membrane, known as posterior urethral valves (both causing bilateral hydronephrosis). Obstruction to urine flow results in dilatation of the urinary tract proximal to the site of obstruction (eg hydronephrosis or hydroureters) At worst, this results in a dysplastic kidney which is small, poorly functioning, and may contain cysts. In the most severe and bilateral cases Potter syndrome is present.

Answer 236

Prophylactic antibiotics may be started at birth to try to prevent urinary tract infection (UTI), although practice varies between centres. In urinary tract obstruction, a urethral catheter can be inserted. As the newborn kidney has a low GFR, urine flow is low and mild outflow obstruction may not be evident in the first few days of life. An ultrasound scan should therefore be delayed for a few weeks. -Unilateral hydronephrosis in a male or any anomaly in a female should be investigated with an ultrasound at 4-6 weeks and if this is normal, Abx can be stopped and the ultrasound repeated after 2-3 months. If abnormal, further investigation is required. However, - Bilateral hydronephrosis in a male infant warrants investigations including an ultrasound and micturating cystourethrogram (MCUG) shortly after birth to exclude posterior urethral valves, which always requires urological intervention such as cystoscopic ablation.

Answer 237

* Up to half of patients have a structural abnormality of their urinary tract * Pyelonephritis may damage the growing kidney by forming a scar, predisposing to hypertension and to progressive chronic kidney disease if the scarring is bilateral.

Answer 238

Infants * Fever * Vomiting * Lethargy or irritability * Poor feeding/ faltering growth * Jaundice * Septicaemia * Offensive urine * Febrile seizure (>6 months) Children * Dysuria, frequency and urgency * Abdominal pain or loin tenderness * Fever with or without rigors (exaggerated shivering) * Lethargy and anorexia * Vomiting, diarrhoea * Haematuria * Offensive/cloudy urine * Febrile seizure * Recurrence of enuresis

Answer 239

For the child in nappies, urine can be collected by: * A ‘clean-catch’ sample into a waiting clean pot when the nappy is removed. This is the recommended method * An adhesive plastic bag applied to the perineum after careful washing, although there may be contamination from the skin * A urethral catheter if there is urgency in obtaining a sample and no urine has been passed * Suprapubic aspiration, when a fine needle attached to a syringe is inserted directly into the bladder just above the symphysis pubis under ultrasound guidance; it may be used in severely ill infants requiring urgent diagnosis and treatment, but it is an invasive procedure, and is increasingly replaced by urethral catheter sampling. In the older child, urine can be obtained by collecting a midstream sample. Careful cleaning and collection are necessary, as contamination with both white cells and bacteria can occur from under the foreskin in boys, and from reflux of urine into the vagina during voiding in girls.

Answer 240

Urine sample for microscopy and cultures. Urinary white cells are not a reliable feature of a UTI, as they may lyse during storage and may be present in febrile children without a UTI and in children with balanitis or vulvovaginitis. Dipsticks can be used as a screening test. (Urine culture should still be performed unless both leucocyte esterase and nitrite are negative or if the clinical symptoms and dipstick tests do not correlate). A bacterial culture of more than 105 colony-forming units (CFU) of a single organism per millilitre in a properly collected specimen gives a 90% probability of infection. If the same result is found in a second sample, the probability rises to 95%. A growth of mixed organisms usually represents contamination, but if there is doubt, another sample should be collected. Any bacterial growth of a single organism per millilitre in a catheter sample or suprapubic aspirate is considered diagnostic of infection. ** A urine sample should be tested in all infants with an unexplained fever >38°C

Answer 241

1. Nitrite stick testing - Positive result useful as very likely to indicate a true UTI (but some children with a UTI are nitrite negative) 2. Leucocyte esterase stick testing (for white blood cells) - May be present in children with UTI but may also be negative - Present in children with febrile illness without UTIs - Positive in balanitis and vulvovaginitis Interpretation of results: - Both positive: Regard as UTI - Nitrite positive and leucocyte esterase negative: Start antibiotic treatment if clinical evidence of UTI, Diagnosis depends on urine culture - Nitrite negative and leucocyte esterase positive: Only start antibiotic treatment if clinical evidence of UTI, Diagnosis depends on urine culture - Both negative: UTI unlikely. Repeat or send urine for culture if clinical history suggests UTI - Blood, protein, and glucose present on stick testing: Useful in any unwell child to identify other diseases, e.g. nephritis, diabetes mellitus, but will not discriminate between children with and without UTIs

Answer 242

UTI is usually the result of bowel flora entering the urinary tract via the urethra, although it can be haematogenous, e.g. in the newborn. The most common organism is Escherichia coli, followed by Klebsiella, Proteus, Pseudomonas, and Streptococcus faecalis. Proteus infection is more commonly diagnosed in boys than in girls, possibly because of its presence under the prepuce. Proteus infection predisposes to the formation of phosphate stones by splitting urea to ammonia, and thus alkalinizing the urine. Pseudomonas infection may indicate the presence of some structural abnormality in the urinary tract affecting drainage and it is also more common in children with plastic catheters.

Answer 243

* Infrequent voiding, resulting in bladder enlargement * Vulvitis * Incomplete micturition with residual postmicturition bladder volumes * Obstruction by a loaded rectum from constipation * Neuropathic bladder * Vesicoureteric reflux.

Answer 244

VUR is a developmental anomaly of the vesicoureteric junctions. The ureters are displaced laterally and enter directly into the bladder rather than at an angle, with a shortened or absent intramural course. Severe cases may be associated with renal dysplasia. It is familial, with a 30-50% chance of occurring in first-degree relatives. It may also occur with bladder pathology, e.g. a neuropathic bladder or urethral obstruction, or temporarily after a UTI. Its severity varies from reflux into the lower end of an undilated ureter during micturition to the severest form with reflux during bladder filling and voiding, with a distended ureter, renal pelvis, and clubbed calyces. Mild reflux is unlikely to be of significance, but the more severe degrees of VUR may be associated with intrarenal reflux, which is the backflow of urine from the renal pelvis into the papillary collecting ducts and is associated with a particularly high risk of renal scarring if UTIs occur. The incidence of renal defects increases with increasing severity of reflux. There is considerable controversy as to whether renal scarring is a congenital abnormality already present in children with reflux and which predisposes to infection or if children with reflux have normal kidneys at birth which are damaged by UTIs and that preventing UTIs in these children prevents scars.

Answer 245

VUR tends to resolve with age, especially lower grades of VUR. VUR-associated ureteric dilatation is important as: * Urine returning to the bladder from the ureters after voiding results in incomplete bladder emptying which encourages infection * The kidneys may become infected (pyelonephritis) especially if there is intrarenal reflux *Bladder voiding pressure is transmitted to the renal papillae which may contribute to renal damage if voiding pressures are high. Infection may destroy renal tissue, leaving a scar, resulting in a shrunken, poorly functioning segment of kidney (reflux nephropathy). If scarring is bilateral and severe, progressive chronic kidney disease may develop.

Answer 246

There has been a move away from extensive investigation of all children with UTIs to those who have had atypical or recurrent UTIs. Atypical UTI includes: * Seriously ill or septicaemia * Poor urine flow * Abdominal or bladder mass * Raised creatinine * Failure to respond to suitable antibiotics within 48 hours * Infection with atypical (non-E. coli) organisms. An initial ultrasound will identify: * Serious structural abnormalities and urinary obstruction * Renal defects (although it is not the gold standard for detecting renal scars) Subsequent investigations will depend on the results of the ultrasound. - If urethral obstruction is suspected (abnormal bladder in a boy), MCUG should be performed promptly. - Functional scans should be deferred for 3 months after a UTI, unless the ultrasound is suggestive of obstruction, to avoid missing a newly developed scar and because of false-positive results from transient inflammation.

Answer 247

- All infants under 3 months of age with suspicion of a UTI or if seriously ill should be referred immediately to hospital. They require intravenous antibiotic therapy (e.g. co-amoxiclav) for at least 5–7 days at which point oral prophylaxis can then be commenced. - Infants aged over 3 months and children with acute pyelonephritis/ upper UTI (bacteriuria and fever ≥38°C or bacteriuria and loin pain/tenderness even if fever is <38°C) are usually treated with oral antibiotics (e.g. trimethoprim for 7 days); or else intravenous antibiotics, e.g. co-amoxiclav, are given for 2–4 days followed by oral antibiotics for a total of 7–10 days. The choice of antibiotic is adjusted according to sensitivity on urine culture. - Children with cystitis/lower UTI (dysuria but no systemic symptoms or signs) can be treated with oral antibiotics such as trimethoprim or nitrofurantoin for 3 days.

Answer 248

The aim is to ensure washout of organisms that ascend into the bladder from the perineum; and to reduce the presence of aggressive organisms in the stool, perineum, and under the foreskin: * High fluid intake to produce a high urine output * Regular voiding * Ensure complete bladder emptying by encouraging the child to try a second time to empty his bladder after a minute or two, commonly known as double voiding, which empties any urine residue or refluxed urine returning to the bladder * Treatment and/or prevention of constipation * Good perineal hygiene * Lactobacillus acidophilus, a probiotic to encourage colonization of the gut by this organism and reduce the number of pathogenic organisms that might potentially cause invasive disease * Antibiotic prophylaxis, although this is controversial. It is often used in those under 2-3 years of age with a congenital abnormality of the kidneys or urinary tract or who have had an upper UTI and those with severe reflux until out of nappies. Trimethoprim (2 mg/kg at night) is used most often, but nitrofurantoin or cephalexin may be given. Broad-spectrum, poorly absorbed antibiotics such as amoxicillin should be avoided.

Answer 249

In these children: * Urine should be dipsticked with any nonspecific illness in case it is caused by a UTI and urine sent for microscopy and culture if suggestive of UTI * Long-term, low-dose antibiotic prophylaxis can be used. There is no evidence for when antibiotic prophylaxis should be stopped * Circumcision in boys may sometimes be considered as there is evidence that it reduces the incidence of UTI * Anti-VUR surgery may be indicated if there is progression of scarring with ongoing VUR but it has not been shown to improve outcome in mild VUR * Blood pressure should be checked annually if renal defects are present * Urinalysis to check for proteinuria which is indicative of progressive chronic kidney disease * Regular assessment of renal growth and function is necessary if there are bilateral defects because of the risk of progressive chronic kidney disease. If there are further symptomatic UTIs in younger children, investigations may be required to determine whether there is new scar formation and if so whether there is ongoing VUR, which may require prophylactic antibiotic therapy or surgical anti-VUR treatment.

Answer 250

This is a lack of bladder control during the day in a child old enough to be continent (over the age of 3–5 years). Nocturnal enuresis is also usually present. It may be caused by: * Lack of attention to bladder sensation: a manifestation of a developmental or psychogenic problem, although it may occur in otherwise normal children who are too preoccupied with what they are doing to respond to the sensation of a full bladder * Detrusor instability (sudden, urgent urge to void induced by sudden bladder contractions) * Bladder neck weakness * A neuropathic bladder (bladder is enlarged and fails to empty properly, irregular thick wall, and is associated with spina bifida and other neurological conditions) * A UTI (rarely in the absence of other symptoms) * Constipation * An ectopic ureter, causes constant dribbling and child is always damp.

Answer 251

Examination may reveal evidence of a neuropathic bladder, i.e. the bladder may be distended, there may be abnormal perineal sensation and anal tone, or abnormal leg reflexes and gait. Sensory loss in the distribution of the S2, S3, and S4 dermatomes should besought. A spinal lesion may be present. Girls who are dry at night but wet on getting up are likely to have pooling of urine from an ectopic ureter opening into the vagina. A urine sample should be examined for microscopy, culture, and sensitivity. Other investigations are performed if indicated. An ultrasound may show bladder pathology, with incomplete bladder emptying or thickening of the bladder wall. Urodynamic studies may be required. An X-ray of the spine may reveal a vertebral anomaly. A MRI scan may be required to confirm or exclude a spinal defect such as tethering of the cord.

Answer 252

Affected children in whom a neurological cause has been excluded may benefit from star charts, bladder training, and pelvic floor exercises. Constipation should be treated. A small portable alarm with a pad in the pants, which is activated by urine, can be used when there is lack of attention to bladder sensation. Anticholinergic drugs, such as oxybutynin, to dampen down bladder contractions, may be helpful if other measures fail.

Answer 253

The loss of previously achieved urinary continence may be due to: * Emotional upset, which is the most common cause * UTI * Polyuria from an osmotic diuresis in diabetes mellitus or a renal concentrating disorder, e.g. sickle cell disease or chronic kidney disease or very rarely diabetes insipidus, which can be central or nephrogenic.

Answer 254

Investigation should include: * Testing a urine sample for infection, glycosuria, and proteinuria using a dipstick * Assessment of urinary concentrating ability by measuring the osmolality of an early morning urine sample. Rarely, a formal water deprivation test may be needed to exclude a urinary concentrating defect * Ultrasound of the renal tract.

Answer 255

By measuring the urine protein-to-creatinine ratio in an early morning sample (normal protein-to-creatinine ratio <20 mg/mmol).

Answer 256

* Orthostatic proteinuria (found only when the child is upright during the day) * Glomerular abnormalities – Minimal change disease – Glomerulonephritis – Abnormal glomerular basement membrane (familial nephritides) * Increased glomerular filtration pressure * Reduced renal mass in chronic kidney disease * Hypertension * Tubular proteinuria

Answer 257

In nephrotic syndrome, heavy proteinuria results in a low plasma albumin and oedema. The cause of the condition is unknown, but a few cases are secondary to systemic diseases such as Henoch–Schönlein purpura and other vasculitides, e.g. SLE, infections (e.g. malaria) or allergens (e.g. bee sting). Clinical signs of the nephrotic syndrome are: * Periorbital oedema (particularly on waking) which is often the earliest sign * Scrotal or vulval, leg, and ankle oedema * Ascites * Breathlessness due to pleural effusions and abdominal distension * Infection such as peritonitis, septic arthritis, or sepsis due to loss of protective immunoglobulins in the urine.

Answer 258

* Urine protein – on test strips (dipstick) * FBC and ESR * Urea, electrolytes, creatinine, albumin * Complement levels – C3, C4 * Antistreptolysin O or anti-DNAse B titres and throat swab * Urine microscopy and culture * Urinary sodium concentration * Hepatitis B and hepatitis C screen * Malaria screen if travel abroad

Answer 259

In 85–90% of children with nephrotic syndrome, the proteinuria resolves with corticosteroid therapy (steroid-sensitive nephrotic syndrome). These children do not progress to chronic kidney disease. It is more common in boys than in girls, in Asian children than in Caucasians, and there is an association with atopy. It is often precipitated by respiratory infections. Features suggesting steroid-sensitive nephrotic syndrome are: * Age between 1–10 years * No macroscopic haematuria * Normal blood pressure * Normal complement levels * Normal renal function.

Answer 260

The most widely used protocol is to initially give oral corticosteroids (60 mg/m2 per day of prednisolone), unless there are atypical features. After 4 weeks, the dose is reduced to 40 mg/m2 on alternate days for 4 weeks and then weaned or stopped. The median time for the urine to become free of protein is 11 days. However, there is now good evidence that extending the initial course of steroids by gradually tapering the alternate day part of the course leads to a marked reduction in the proportion of children who develop a frequently relapsing or steroid-dependent course, although there are increased side-effects from steroid treatment. Children who do not respond to 4–6 weeks of corticosteroid therapy or have atypical features may have a more complex diagnosis and require a renal biopsy. 1/3 will resolve directly, 1/3 will have infrequent relapses and 1/3 will develop a frequent relapsing or steroid-dependent disease

Answer 261

Renal histology in steroid-sensitive nephrotic syndrome is usually normal on light microscopy but fusion of podocytes with foot process effacement is seen on electron microscopy. For this reason, it is called minimal change disease.

Answer 262

* Hypovolaemia – during the initial phase of oedema formation, the intravascular compartment may become volume depleted. The child who becomes hypovolaemic characteristically complains of abdominal pain and may feel faint. There is peripheral vasoconstriction and urinary sodium retention. A low urinary sodium (<10 mmol/L) and a high packed cell volume of red blood cells are indications of hypovolaemia, which requires urgent treatment with intravenous fluid (0.9% saline or 4.5% albumin solution) as the child is at risk of vascular thrombosis and shock. Increasingly peripheral oedema, assessed clinically and by daily weight, may cause discomfort and respiratory compromise. If severe, this may need treatment with intravenous 20% albumin infusion with furosemide. Care must be taken with the use of 20% albumin as it may precipitate pulmonary oedema and hypertension from fluid overload, and also with diuretics, which may cause or worsen hypovolaemia. * Thrombosis – a hypercoagulable state, due to urinary losses of antithrombin III, thrombocytosis which may be exacerbated by steroid therapy, increased synthesis of clotting factors, and increased blood viscosity from the raised haematocrit, all predispose to thrombosis. This may affect the lungs, brain, limbs, and splanchnic circulation with potentially catastrophic results. * Infection – children in relapse are at risk of infection with capsulated bacteria, especially Pneumococcus. Spontaneous peritonitis may occur. Pneumococcal and seasonal influenza vaccination is widely recommended. Chickenpox and shingles should be treated with aciclovir. * Hypercholesterolaemia – this correlates inversely with the serum albumin, but the cause of the hyperlipidaemia is not fully understood.

Answer 263

Relapses are identified by parents on urine testing. The side-effects of corticosteroid therapy may be reduced by an alternate-day regimen. If relapses are frequent, or if a high maintenance dose is required, involvement of a paediatric nephrologist is advisable as steroid-sparing agents may be considered to enable reduction in steroid use. Possible steroid-sparing agents include the immunomodulator levamisole, alkylating agents (e.g. cyclophosphamide), calcineurin inhibitors such as tacrolimus and cyclosporin A, the immunosuppressant mycophenolate mofetil, and for difficult cases the anti-B-cell monoclonal antibody rituximab.

Answer 264

- Focal segmental glomerulosclerosis: Most common, Familial or idiopathic, 30% progress to end-stage renal failure in 5 years; 20% respond to cyclophosphamide, cyclosporin, tacrolimus, or rituximab, Recurrence post-transplant is common - Mesangiocapillary glomerulonephritis (membranoproliferative glomerulonephritis): More common in older children, Haematuria and low complement level present, Decline in renal function over many years - Membranous nephropathy: Associated with hepatitis B, May precede SLE, Most remit spontaneously within 5 years

Answer 265

Management of the oedema is by diuretic therapy, salt restriction, angiotensin-converting enzyme inhibitors, and sometimes nonsteroidal anti-inflammatory drugs, which may reduce proteinuria. Genetic testing for steroid-resistant nephrotic syndrome is available and helps in the management of children, e.g. withdrawal of immunosuppression or supplementation of CoQ10 if there is a CoQ10 pathway defect.

Answer 266

Congenital nephrotic syndrome presents in the first 3 months of life. It is rare. The most common kind is recessively inherited and the gene frequency is particularly high in Finns (congenital nephrotic syndrome of the finnish type). In the UK, it is more common in consanguineous families. It is associated with a high mortality, usually due to complications of hypoalbuminaemia rather than progressive chronic kidney disease. The albuminuria is so severe that unilateral nephrectomy may be necessary for its control, followed by dialysis for stage 5 (most severe) chronic kidney disease, which is continued until the child is no longer nephrotic and old enough for renal transplantation.

Answer 267

Urine that is red in colour or tests positive for haemoglobin on urine sticks should be examined under the microscope to confirm haematuria (>10 red blood cells per high-power field). Glomerular haematuria is suggested by brown urine, the presence of deformed red cells (which occurs as they pass through the basement membrane), and casts, and is often accompanied by proteinuria. Lower urinary tract haematuria is usually red, occurs at the beginning or end of the urinary stream, is not accompanied by proteinuria, and is unusual in children.

Answer 268

-Non-glomerular * Infection (bacterial, viral, tuberculosis, schistosomiasis) * Trauma to genitalia, urinary tract, or kidneys * Stones * Tumours * Sickle cell disease * Bleeding disorders * Renal vein thrombosis * Hypercalciuria -Glomerular * Acute glomerulonephritis (usually with proteinuria eg poststreptococcal glomerulonephritis) * Chronic glomerulonephritis (usually with proteinuria) * IgA nephropathy * Familial nephritis, e.g. Alport syndrome * Thin basement membrane disease

Answer 269

* Urine microscopy (with phase contrast) and culture * Protein and calcium excretion * Kidney and urinary tract ultrasound * Plasma urea, electrolytes, creatinine, calcium, phosphate, albumin * FBC, platelets, coagulation screen, sickle cell screen If suggestive of glomerular haematuria * ESR, complement levels, and anti-DNA antibodies * Throat swab and antistreptolysin O/anti-DNAse B titres (both indicative of recent Strep A infection) * Hepatitis B and C screen * Renal biopsy if indicated * Test mother’s urine for blood (if Alport syndrome suspected) * Hearing test (if Alport syndrome suspected)

Answer 270

A renal biopsy may be indicated if: * There is significant persistent proteinuria * There is recurrent macroscopic haematuria * Renal function is abnormal * The complement levels are persistently abnormal.

Answer 271

* Post-infectious (including streptococcus) * Vasculitis (HSP or SLE, Wegener granulomatosis, microscopic polyarteritis, polyarteritis nodosa) * IgA nephropathy and mesangiocapillary glomerulonephritis * Antiglomerular basement membrane disease (Goodpasture syndrome) – very rare

Answer 272

Increased glomerular cellularity restricts glomerular blood flow, and therefore glomerular filtration is decreased. This leads to: * Decreased urine output and volume overload * Hypertension, which may cause seizures * Oedema, characteristically initially periorbital * Haematuria and proteinuria. Management is by attention to both water and electrolyte balance and the use of diuretics when necessary. Rarely, there may be a rapid deterioration in renal function (rapidly progressive glomerulonephritis). This may occur with any cause of acute nephritis, but is uncommon when the cause is poststreptococcal. If left untreated, irreversible chronic kidney disease may occur over weeks or months, so renal biopsy and subsequent treatment with immunosuppression and plasma exchange may be necessary.

Answer 273

Usually follows a streptococcal sore throat or skin infection and is diagnosed by evidence of a recent streptococcal infection (culture of the organism, raised ASO/anti-DNAse B titres), and low complement C3 levels that return to normal after 3 weeks to 4 weeks.

Answer 274

Henoch–Schönlein purpura is the combination of some of the following features: * Characteristic skin rash on extensor surfaces * Arthralgia * Periarticular oedema * Abdominal pain * Glomerulonephritis. It usually occurs between the ages of 3–10 years, is twice as common in boys, peaks during the winter months, and is often preceded by an upper respiratory infection. Despite much research, the cause is unknown. It is postulated that genetic predisposition and antigen exposure increase circulating IgA levels and disrupt IgG synthesis. The IgA and IgG interact to produce complexes that activate complement and are deposited in affected organs, precipitating an inflammatory response with vasculitis.

Answer 275

- At presentation, affected children often have a fever. - The rash is the most obvious feature. It is symmetrically distributed over the buttocks, the extensor surfaces of the arms and legs, and the ankles. The trunk is usually spared. The rash may initially be urticarial, rapidly becoming maculopapular and purpuric, is characteristically palpable, and may recur over several weeks. The rash is the first clinical feature in about 50% and is the cornerstone of the diagnosis, which is clinical. - Joint pain occurs in two-thirds of patients, particularly of the knees and ankles. There is periarticular oedema. Long-term damage to the joints does not occur, and symptoms usually resolve before the rash goes. - Colicky abdominal pain occurs in many children and, if severe, can be treated with corticosteroids. Gastrointestinal involvement can cause haematemesis and melaena. Intussusception can occur and can be particularly difficult to diagnose under these circumstances. - Ileus, protein-losing enteropathy, orchitis, and occasionally central nervous system involvement are other rare complications. - Renal involvement is common, but is rarely the first symptom. Over 80% have microscopic or macroscopic haematuria or mild proteinuria. These children usually make a complete recovery. If proteinuria is more severe, nephrotic syndrome may result. Risk factors for progressive chronic kidney disease are heavy proteinuria, oedema, hypertension, and deteriorating renal function, when a renal biopsy will determine if treatment is necessary. All children with Henoch–Schönlein purpura should be followed for a year to detect those with persisting haematuria or proteinuria (5–10%). Children who have persistent renal involvement or required treatment for Henoch– Schönlein purpura nephritis require long-term follow-up. This is necessary as hypertension and progressive chronic kidney disease may develop after an interval of several years.

Answer 276

Autoimmune disease causing a build-up of IgA in the kidneys, leading to inflammation and kidney damage. This may present with episodes of macroscopic haematuria, commonly in association with upper respiratory tract infections. Histological findings and management are as for Henoch–Schönlein purpura, which may be a variant of the same pathological process but not restricted to the kidney. The prognosis in children is better than that in adults.

Answer 277

The most common familial nephritis is Alport syndrome. This is usually an X-linked recessive disorder that progresses to progressive end-stage chronic kidney disease by early adult life in males and is associated with nerve deafness and ocular defects. The mother may have haematuria. The differential diagnosis is thin basement membrane disease, which also required long-term follow-up to detect proteinuria and chronic kidney disease, which rarely develops in later life.

Answer 278

The most common vasculitis to involve the kidney is Henoch–Schönlein purpura. However, renal involvement may occur in rarer vasculitides such as polyarteritis nodosa, microscopic polyarteritis, and granulomatosis with polyangiitis (formerly known as Wegener granulomatosis). Characteristic symptoms are fever, malaise, weight loss, skin rash, and arthropathy with prominent involvement of the respiratory tract in granulomatosis with polyangiitis. ANCA (antineutrophil cytoplasm antibodies) are present and diagnostic in these diseases. Renal arteriography, to demonstrate the presence of aneurysms, will diagnose polyarteritis nodosa. Renal involvement may be severe and rapidly progressive. Treatment is with corticosteroids, plasma exchange, and intravenous cyclophosphamide, which may need to be continued for many months.

Answer 279

Blood pressure increases with age and height and readings should be plotted on a centile chart. Hypertension is blood pressure above 95th percentile for height, age, and sex. Children who are overweight or obese are at increased risk. Symptomatic hypertension in children is usually secondary to renal, cardiac, or endocrine causes. Presentation includes vomiting, headaches, facial palsy, hypertensive retinopathy, convulsions, or proteinuria. Faltering growth and cardiac failure are the most common features in infants. Pheochromocytoma may also cause paroxysmal palpitations and sweating. Some causes are correctable, e.g. nephrectomy for unilateral scarring, angioplasty for renal artery stenosis, surgical repair of coarctation of the aorta, resection of a pheochromocytoma, but in most cases medical treatment is necessary with antihypertensive medications. Early detection of hypertension is important. All children with a renal tract abnormality should have their blood pressure checked annually throughout life. Children with a family history of essential hypertension should be encouraged to restrict their salt intake, avoid obesity, and have their blood pressure checked regularly.

Answer 280

1. Renal – Renal parenchymal disease – Renovascular, e.g. renal artery stenosis – Polycystic kidney disease (autosomal recessive polycystic kidney disease and autosomal dominant polycystic kidney disease) – Renal tumours 2. Coarctation of the aorta 3. Catecholamine excess – Pheochromocytoma – Neuroblastoma 4. Endocrine – Congenital adrenal hyperplasia – Cushing syndrome or corticosteroid therapy – Hyperthyroidism 5. Essential hypertension – A diagnosis of exclusion.

Answer 281

Unilateral * Multicystic kidney * Compensatory hypertrophy * Obstructed hydronephrosis * Renal tumour (Wilms tumour) * Renal vein thrombosis Bilateral * Autosomal recessive polycystic kidneys * Autosomal dominant polycystic kidneys * Tuberous sclerosis * Renal vein thrombosis

Answer 282

* UTI * Structural anomalies of the urinary tract * Metabolic abnormalities.

Answer 283

- The most common are phosphate stones associated with infection, especially with Proteus. - Calcium-containing stones occur in idiopathic hypercalciuria, the most common metabolic abnormality, and with increased urinary urate and oxalate excretion. Deposition of calcium in the parenchyma (nephrocalcinosis) may occur with hypercalciuria, hyperoxaluria, and distal renal tubular acidosis. Nephrocalcinosis may be a complication of furosemide therapy in the neonate. - Cystine and xanthine stones are rare. Presentation may be with haematuria, loin or abdominal pain, UTI, or passage of a stone. Stones that are not passed spontaneously should be removed, by either lithotripsy or surgery, and any predisposing structural anomaly repaired if possible. A high fluid intake is recommended in all affected children. If the cause is a metabolic abnormality, specific therapy may be possible.

Answer 284

Proximal tubule cells are among the most metabolically active in the body, so are especially vulnerable to cellular damage. The cardinal features are excessive urinary loss of amino acids, glucose, phosphate, bicarbonate, sodium, calcium, potassium, and magnesium. Fanconi syndrome should be considered in a child presenting with: * Polydipsia and polyuria * Salt depletion and dehydration * Hyperchloraemic metabolic acidosis * Rickets * Faltering or poor growth.

Answer 285

1. Idiopathic 2. Secondary to inborn errors of metabolism * Cystinosis (an autosomal recessive disorder causing intracellular accumulation of cystine) * Glycogen storage disorders * Lowe syndrome (oculocerebrorenal dystrophy) * Galactosaemia * Fructose intolerance * Tyrosinaemia * Wilson disease 3. Acquired * Heavy metals * Drugs and toxins * Vitamin D deficiency

Answer 286

1. Proximal tubule - Low glucose resorption = glycosuria, usually asymptomatic - Low cystine and dibasic amino acid resorption = Cystinuria, may cause renal calculi - Low phosphate resorption = phosphaturia, may be seen in rickets (vitamin-D resistant rickets) - High phosphate resorption = pseudohypoparathyroidism, may see obesity, a depressed nasal bridge and short 2nd, 4th and 5th fingers - High secretion or low resorption of uric acid = hyperuricosuria, may cause renal calculi - Low resorption of bicarbonate = renal tubular acidosis type 2, causes metabolic acidosis, alkaline urine and faltering growth - Low resorption of calcium = hypercalcuria, may cause nephrocalcinosis or renal stones 2. Distal tubule/Collecting duct - Low resorption of chloride = Bartter syndrome, causes hypokalaemia, metabolic alkalosis, hypercalciuria, normal BP with increased renin, polydipsia and poluria, faltering growth - Low resorption of water = nephrogenic diabetes insipidus, polydipsia and polyuria, fever, faltering growth - Low H+ secretion = renal tubular acidosis type 1, metabolic acidosis, alkaline urine, faltering growth and nephrocalcinosis

Answer 287

Acute kidney injury has acute renal failure at the most severe end of the spectrum where there is a sudden, potentially reversible, reduction in renal function. Oliguria (<0.5 ml/kg per hour) is usually present. It can be classified as: * Prerenal: the most common cause in children * Renal: there is salt and water retention; blood, protein, and casts are often present in the urine; and there may be symptoms specific to an accompanying disease [e.g. haemolytic uraemic syndrome (HUS)] * Postrenal: from urinary obstruction. Acute-on-chronic renal failure is suggested by the child having growth failure, anaemia, and disordered bone mineralization (renal osteodystrophy).

Answer 288

1. Prerenal * Hypovolaemia: – Gastroenteritis – Burns – Sepsis – Haemorrhage – Nephrotic syndrome * Circulatory failure 2. Renal * Vascular: – Haemolytic uraemic syndrome – Vasculitis – Embolus – Renal vein thrombosis * Tubular: – Acute tubular necrosis – Ischaemic – Toxic – Obstructive * Glomerular: – Glomerulonephritis * Interstitial: – Interstitial nephritis – Pyelonephritis 3. Postrenal * Obstruction: – Congenital, e.g. posterior urethral valves – Acquired, e.g. blocked urinary catheter

Answer 289

1. Prerenal failure This is suggested by hypovolaemia. The fractional excretion of sodium is very low as the body tries to retain volume. The hypovolaemia needs to be urgently corrected with fluid replacement and circulatory support if acute tubular injury and necrosis are to be avoided. 2. Renal failure If there is circulatory overload, restriction of fluid intake and challenge with a diuretic may increase urine output sufficiently to allow gradual correction of sodium and water balance. A high-calorie, normal protein feed will decrease catabolism, uraemia, and hyperkalaemia. Emergency management of metabolic acidosis, hyperkalaemia, and hyperphosphataemia may be required. If the cause of renal failure is not obvious, a renal biopsy should be performed to identify rapidly progressive glomerulonephritis, as this may need immediate treatment with immunosuppression. The two most common renal causes of acute renal failure in children in the UK are haemolytic uraemic syndrome and acute tubular necrosis, the latter usually in the setting of multisystem failure in the intensive care unit or following cardiac surgery. 3. Postrenal failure This requires assessment of the site of obstruction and relief by nephrostomy or bladder catheterization. Surgery can be performed once fluid volume and electrolyte abnormalities have been corrected.

Answer 290

1. Metabolic acidosis: - Sodium bicarbonate 2. Hyperphosphataemia: -Calcium carbonate -Dietary restriction 3. Hyperkalaemia: -Calcium gluconate if ECG changes -Salbutamol (nebulized or intravenous) -Calcium exchange resin -Glucose and insulin -Dietary restriction -Dialysis

Answer 291

Dialysis in acute kidney injury is indicated when there is: * Failure of conservative management * Hyperkalaemia * Severe hyponatraemia or hypernatraemia * Pulmonary oedema or severe hypertension due to volume overload * Severe metabolic acidosis * Multisystem failure. Peritoneal dialysis or haemodialysis can be undertaken for acute kidney injury. If plasma exchange is part of the treatment (e.g. in vasculitis), haemodialysis is used. If there is cardiac decompensation or hypercatabolism, continuous arteriovenous or venovenous haemofiltration provides gentle, continuous dialysis and fluid removal.

Answer 292

HUS is a triad of acute renal failure, microangiopathic haemolytic anaemia, and thrombocytopenia. Typical HUS is secondary to gastrointestinal infection with verocytotoxin-producing E. coli O157:H7, acquired through contact with farm animals or eating uncooked beef, or, less often, Shigella. It follows a prodrome of bloody diarrhoea. The toxin from these organisms enters the gastrointestinal mucosa and preferentially localizes to the endothelial cells of the kidney where it causes intravascular thrombogenesis. Coagulation cascade is activated and clotting is normal (unlike in disseminated intravascular coagulation). Platelets are consumed in this process and microangiopathic haemolytic anaemia results from damage to red blood cells as they circulate through the microcirculation, which is occluded. Other organs such as the brain, pancreas, and heart may also be involved.

Answer 293

With early supportive therapy, including dialysis, the typical diarrhoea-associated HUS usually has a good prognosis, although long-term follow-up is necessary as there may be persistent proteinuria and the development of hypertension and progressive chronic kidney disease in subsequent years. By contrast, atypical HUS has no diarrhoeal prodrome, may be familial, and frequently relapses. It has a high risk of hypertension and progressive chronic kidney disease with a high mortality. A new treatment, the monoclonal anti-terminal complement antibody eculizumab, has greatly improved the prognosis of this condition although it is very expensive, and therefore plasma exchange is still used in many cases, especially in cerebral atypical HUS.

Answer 294

Stage 1: >90 ml/min per 1.73 m2 Normal renal function but structural abnormality or persistent haematuria or proteinuria Stage 2: 60–89 ml/min per 1.73 m2 Mildly reduced function, asymptomatic Stage 3: 30–59 ml/min per 1.73 m2 Moderately reduced renal function, renal osteodystrophy Stage 4: 15–29 ml/min per 1.73 m2 Severely reduced renal function with metabolic derangements and anaemia. Need to make plans for renal replacement therapy Stage 5: <15 ml/min per 1.73 m2 End stage renal failure, renal replacement therapy required

Answer 295

From most common to least: 1. Renal dysplasia ± reflux 2. Obstructive uropathy 3. Glomerular disease 4. Congenital nephrotic syndrome 5. Tubulointerstitial diseases 6. Renovascular disease 7. Polycystic kidney disease 8. Metabolic

Answer 296

Stage 4 and stage 5 chronic kidney disease presents with: * Anorexia and lethargy * Polydipsia and polyuria * Faltering growth/growth failure * Bony deformities from renal osteodystrophy (renal rickets) * Hypertension * Acute-on-chronic renal failure (precipitated by infection or dehydration) * Incidental finding of proteinuria * Unexplained normochromic, normocytic anaemia Many children with chronic kidney disease have had their renal disease detected before birth by antenatal ultrasound or have previously identified renal disease. Symptoms rarely develop before renal function falls to less than one-third of normal or chronic kidney disease stage 4.

Answer 297

The aims of management are to prevent the symptoms and metabolic abnormalities of chronic kidney disease, to allow normal growth and development, and to preserve residual renal function. 1. Diet Anorexia and vomiting are common. Improving nutrition using calorie supplements and nasogastric or gastrostomy feeding is often necessary to optimize growth. Protein intake should be sufficient to maintain growth and a normal albumin, whilst preventing the accumulation of toxic metabolic by-products. 2. Prevention of renal osteodystrophy Phosphate retention and hypocalcaemia due to decreased activation of vitamin D lead to secondary hyperparathyroidism, which results in osteitis fibrosa and osteomalacia of the bones. Phosphate restriction by decreasing the dietary intake of milk products, calcium carbonate as a phosphate binder, and activated vitamin D supplements help to prevent renal osteodystrophy. 3. Control of salt and water balance and acidosis Many children with chronic kidney disease caused by congenital structural malformations and renal dysplasia have an obligatory loss of salt and water. They need salt supplements and free access to water. Treatment with bicarbonate supplements is necessary to prevent acidosis. 4. Anaemia Reduced production of erythropoietin and circulation of metabolites that are toxic to the bone marrow result in anaemia. This responds well to the administration of recombinant human erythropoietin which is administered subcutaneously. 5. Hormonal abnormalities Many hormonal abnormalities occur in progressive chronic kidney disease. Most importantly, there is growth hormone resistance with high growth hormone levels but poor growth. Recombinant human growth hormone has been shown to be effective in improving growth for up to 5 years of treatment, but whether it improves final height remains unknown. Many children with stage 4 and stage 5 chronic kidney disease have delayed puberty and a subnormal pubertal growth spurt.

Answer 298

It is now possible for all children to enter renal replacement therapy programmes when stage 5 chronic kidney disease is reached. The optimum management is by renal transplantation. Technically, this is difficult in very small children and a minimum weight, e.g. 10 kg, needs to be reached before transplantation to avoid renal vein thrombosis. Kidneys obtained from living related donors have a higher success rate than deceased donor kidneys, which are matched as far as possible to the recipient’s HLA (human leukocyte antigen) type. Patient survival is high and first-year graft survival is around 95% for living related and 96% for deceased kidneys in the UK. Graft losses from both acute and chronic rejection or recurrent disease mean that the 5-year graft survival is reduced to 94% for living related kidneys and 84% for deceased donor kidney transplants and some children need retransplantation. Current immunosuppression is mainly with combinations of tacrolimus and mycophenolate mofetil and prednisolone and there is increasing use of minimal steroid regimens which improve growth. Ideally, a child is transplanted before dialysis is required, but if this is not possible, a period of dialysis may be necessary. Peritoneal dialysis, either by cycling overnight using a machine (continuous cycling peritoneal dialysis) or by manual exchanges over 24 hours (continuous ambulatory peritoneal dialysis), can be done by the parents at home and is therefore less disruptive to family life and the child’s schooling. Haemodialysis is an alternative and is usually done in hospital three to four times a week

Answer 299

1. Primary headaches: four main groups, comprising migraine, tension-type headache, cluster headache (and other trigeminal autonomic cephalalgias), and other primary headaches (such as primary stabbing headache). They are thought to be due to a primary malfunction of neurons and theirnetworks. 2. Secondary headaches: symptomatic of some underlying pathology, e.g. *Medication overuse headache *Head and/or neck trauma *Cranial or cervical vascular disorder – vascular malformation or intracranial haemorrhage *Non-vascular intracranial disorder – raised intracranial pressure, idiopathic intracranial hypertension *A substance or its withdrawal – alcohol, solvent or drug abuse *Infection – meningitis, encephalitis, abcess *Disorder of homeostasis – hypercapnia or hypertension *Disorder of facial or cranial structures – acute sinusitis * Associated with emotional disorders 3. Trigeminal and other cranial neuralgias and other headaches including root pain from herpes zoster.

Answer 300

This is a symmetrical headache of gradual onset, often described as tightness, a band or pressure. There are usually no other symptoms.

Answer 301

1. Migraine without aura This accounts for 90% of migraine. In children, episodes may last 1–72 hours; the headache is commonly bilateral but may be unilateral. Characteristically pulsatile, over the temporal or frontal area, it is often accompanied by unpleasant gastrointestinal disturbance such as nausea, vomiting, abdominal pain, photophobia and phonophobia (sensitivity to sounds). It is typically aggravated by physical activity and relieved by sleep. 2. Migraine with aura Accounts for 10% of migraine. The headache is preceded by an aura (visual, sensory, or motor), although the aura may occur without a headache. Features are the absence of problems between episodes and the frequent presence of premonitory symptoms (tiredness, difficulty concentrating, autonomic features, etc.). The most common aura comprises visual disturbance, which may include: *Negative phenomena, such as hemianopia (loss of half the visual field) or scotoma (small areas of visual loss) *Positive phenomena such as fortification spectra(seeing zigzag lines). Rarely, there are unilateral sensory or motor symptoms (e.g hemiplegic migraine). Migraine attacks usually last for a few hours, during which time children often prefer to lie down in a quiet, dark place. Symptoms of tension-type headache or a migraine often overlap. They are probably part of the same pathophysiological continuum, with evidence that both result from primary neuronal dysfunction, including channelopathies, with vascular phenomena as secondary events. There is a genetic predisposition, with first-degree and second-degree relatives often also affected. Bouts are often triggered by a disturbance of inherent biorhythms, such as late nights or early rises, stress, or winding down after stress at home or school. Certain foods, e.g. cheese, chocolate, and caffeine, are only rarely a reliable trigger. In girls, headaches can be related to menstruation and the oral contraceptive pill. 3. Uncommon forms of migraine These include * Familial hemiplegic migraine –caused by a calcium channel defect, dominantly inherited. * Sporadic hemiplegic migraine. * Basilar-type migraine – vomiting with nystagmus and/or cerebellar signs. * Periodic syndromes – often precursors of migraine and include: – Cyclical vomiting – recurrent stereotyped episodes of vomiting and intense nausea associated with pallor and lethargy. The child is well in between episodes – Abdominal migraine – an idiopathic recurrent disorder characterised by episodic midline abdominal pain in bouts lasting 1–72 hours. Pain is moderate to severe in intensity and associated with vasomotor symptoms, nausea, and vomiting. The child is well in between episodes – Benign paroxysmal vertigo of childhood – is characterized by recurrent brief episodes of vertigo occurring without warning and resolving spontaneously in otherwise healthy children. Between episodes, neurological examination, audiometric and vestibular function tests are normal

Answer 302

Headaches often raise the fear of brain tumours; this may well be the reason for parents to consult a doctor. Headaches due to a space-occupying lesion are worse when lying down or with coughing and straining and morning vomiting is characteristic. The headaches may also cause night-time waking. There is often a change in mood, personality, or educational performance. Other features suggestive of a space-occupying lesion are: *Visual field defects – from lesions pressing on the optic pathways, e.g. craniopharyngioma (a pituitary tumour) *Cranial nerve abnormalities causing diplopia, new-onset squint or facial nerve palsy. The VIth (abducens) cranial nerve has a long intracranial course and is often affected when there is raised pressure, resulting in a squint with diplopia and inability to abduct the eye beyond the midline. It is a false localising sign. Other nerves are affected depending on the site of lesion, e.g. pontine lesions may affect the VIIth (facial) cranial nerve and cause a facial nerve palsy *Abnormal gait *Torticollis (tilting of the head) *Growth failure, e.g. craniopharyngioma or hypothalamic lesion *Papilloedema – a late feature *Cranial bruits – may be heard in arteriovenous malformations but theselesions are rare *Early or late puberty.

Answer 303

A seizure is a paroxysmal abnormality of motor, sensory, autonomic, and/or cognitive function, due to transient brain dysfunction. The term includes epileptic, syncopal (anoxic), brainstem (hydrocephalic, coning), emotional or functional (psychogenic pseudo-seizures), and as yet undetermined. Regarding seizures as epileptic or non-epileptic will guard against the misdiagnosis of epilepsy, which is common. - Epileptic seizures are due to excessive and hypersynchronous electrical activity, typically in neural networks in all or part of the cerebral cortex

Answer 304

A convulsion is a seizure (epileptic or non-epileptic) with motor components, particularly stiff (tonic), a massive jerk (myoclonic), jerking (clonic), trembling (vibratory), thrashing about (hypermotor); as opposed to a non-convulsive seizure with motor arrest, e.g. an unresponsive stare (as in generalized epileptic absence seizures and some focal epileptic seizures), or drop attack (as in an epileptic atonic seizure).

Answer 305

Epilepsies: An epilepsy is a brain disorder that predisposes the patient to have unprovoked epileptic seizures. Generally, an epilepsy can be recognized after two or more unprovoked epileptic seizures have occurred. Acute symptomatic epileptic seizures: When epileptic seizures are provoked by an acute brain injury, e.g. from acute cortical ischaemia during arterial ischaemic stroke, or from a cerebral contusion during a traumatic brain injury, or cortical inflammation during meningitis. They do not constitute an epilepsy, even if there were recurrent injuries. These are called acute symptomatic epileptic seizures.

Answer 306

Epilepsies * Genetic (70–80%) – also called “idiopathic”, caused by alleles at several loci together ratherthan a single gene, so inheritance is “complex” * Structural, metabolic – Cerebral dysgenesis/malformation – Cerebral vascular occlusion – Cerebral damage, e.g. congenital infection, hypoxic-ischaemic encephalopathy, intraventricular haemorrhage/ischaemia – Cerebral tumour – Neurodegenerative disorders – Neurocutaneous syndromes e.g. Tuberous Sclerosis

Answer 307

* Due to any cortical brain injury or insult, at the time of the trauma or illness – Stroke, traumatic brain injury, intracranial infection – Hypoglycaemia, hypocalcaemia, hypomagnesaemia, hyponatraemia/ hypernatraemia, – Poisons/toxins

Answer 308

* Convulsive syncope – Cardiac syncope e.g. prolonged Q-T syndrome – Neurally mediated syncope: cardio-inhibitory e.g. reflex asystolic syncope (reflex anoxic seizures); vasodepressor or mixed (vasovagal syncope) – Expiratory apnoea syncope (“blue breath-holding spells”) – Hypovolaemic syncope e.g. with haemorrhage, dehydration or anaphylaxis * Sudden rise in intracranial pressure e.g. hydrocephalic attack, haemorrhage * Sleep disorders e.g. benign neonatal sleep myoclonus, hypnic jerks * Functional/medically unexplained e.g. dissociative states

Answer 309

A “febrile seizure” or “febrile convulsion” is an epileptic seizure accompanied by a fever in the absence of intracranial infection. These occur in 3% of children, between the ages of 6 months and 6 years. There is a genetic predisposition, with a 10% risk if the child has a first-degree relative with febrile seizures. The seizure usually occurs early in a viral infection when the temperature is rising rapidly. They are usually brief generalized tonic-clonic seizures. About 30–40% will have further febrile seizures. This is more likely the younger the child, the shorter the duration of illness before the seizure, the lower the temperature at the time of seizure and if there is a positive family history. Simple febrile seizures do not cause brain damage. There is a 1–2% chance of subsequentally developing an epilepsy, similar to the risk for all children. However, complex febrile seizures; i.e. those which are focal, prolonged, or repeated in the same illness, have an increased risk of 4–12% of subsequent epilepsy. Treat as per acute seizure management. Examination should focus on the cause of the fever, which is usually a viral illness, but a bacterial infection including meningitis should always be considered. The classical features of meningitis such as neck stiffness and photophobia may not be as apparent in children less than 18 months of age, so an infection screen (including blood cultures, urine culture, and lumbar puncture for cerebrospinal fluid) may be necessary. If the child is unconscious or has cardiovascular instability, lumbar puncture is contraindicated and antibiotics should be started immediately. Parents need reassurance and information. Advice sheets are usually given to parents. Antipyretics may be given but have not been shown to prevent febrile seizures. The family should be taught the first aid management of seizures. If there is a history of prolonged seizures (>5 min), rescue therapy with buccal midazolam can be supplied. Oral prophylactic antiepileptic drugs are not used as they do not reduce the recurrence rate of seizures, and have a relatively high risk of adverse effects. An EEG is not indicated as it does not predict seizure recurrence.

Answer 310

1. Blue breath-holding' spells: Occur in some toddlers when they are upset. The child cries, holds his breath in expiration and goes blue. Sometimes children will briefly lose consciousness but rapidly recover fully. Drug therapy is unhelpful. Attacks resolve spontaneously, but behaviour modification therapy with distraction, may help. 2. Reflex asystolic syncope: Also called reflex anoxic seizures. Occur in infants or toddlers. Many have a first-degree relative with a history of faints. Commonest triggers are pain or discomfort, particularly from minor head trauma, cold food (such as ice-cream or cold drinks), fright or fever. After the triggering event, the child becomes very pale and falls to the floor. The hypoxia may induce a generalised tonic–clonic seizure. The episodes are due to cardiac asystole from vagal inhibition. The seizure is brief and the child rapidly recovers. Ocular compression under controlled conditions often leads to asystole and paroxysmal slow-wave discharge on the EEG. 3. Syncope (transient loss of consciousness): Children may faint if in a hot and stuffy environment, on standing for long periods, or from fear. Clonic movements lasting a few seconds are common. 4. Migraine: May sometimes lead to paroxysmal headache involving unsteadiness or light-headedness as well as the more common visual or gastrointestinal disturbance. In some young people these episodes occur without headache. 5. Benign paroxysmal vertigo: This is characterised by recurrent episodes of vertigo, lasting from one to several minutes, associated with nystagmus, unsteadiness or even falling. It is a primary headache disorder of childhood occasionally due to a viral labyrinthitis. 6. Other causes: - Cardiac arrhythmia – prolonged QT interval may rarely cause collapse or cardiac syncope which may be related to exercise - Tics, daydreaming, night terrors - Non-epileptic attack disorder (NEAD)/functional seizures/medically unexplained seizures/ dissociative states - Pseudoseizures – when children feign seizures - Fabricated – seizures are fabricated by parent - Induced illness (nonaccidental injury) – e.g. seizures, from hypoglycaemia from an adult deliberately injecting insulin - Paroxysmal movement disorders – well-circumscribed episodes, genetically determined, no loss of consciousness.

Answer 311

GENERALISED SEIZURES: Onset in both hemispheres. In generalised seizures, there is: * Loss of consciousness if > 3 seconds duration * No warning * Symmetrical seizure * Bilaterally synchronous seizure discharge on EEG 1. Absence seizures: Transient LOC, with an abrupt onset and termination, unaccompanied by motor phenomena except for some flickering of the eyelids and minor alteration in muscle tone. Absences can often be precipitated by hyperventilation. 2. Myoclonic seizures: Brief, often repetitive, jerking movements of the limbs, neck or trunk Non-epileptic myoclonic movements are also seen physiologically in hiccoughs (myoclonus of the diaphragm) or on passing through stage II sleep (sleep myoclonus) 3. Tonic seizures: Generalised increase in tone 4. Tonic–clonic seizures: Rhythmical contraction of muscle groups following the tonic phase. In the rigid tonic phase, children may fall to the ground, sometimes injuring themselves. They do not breathe and become cyanosed. This is followed by the clonic phase, with jerking of the limbs. Breathing is irregular, cyanosis persists and saliva may accumulate in the mouth. There may be biting of the tongue and incontinence of urine. The seizure usually lasts from a few seconds to minutes, followed by unconsciousness or deep sleep for up to several hours 5. Atonic seizures: Often combined with a myoclonic jerk, followed by a transient loss of muscle tone causing a sudden fall to the floor or drop of the head FOCAL SEIZURES: Onset in neural network limited to one cerebral hemisphere. Focal seizures: * Originate in a relatively small group of dysfunctional neurones in one of the cerebral hemispheres * May be heralded by an aura (the sensory symptoms) which reflects the site of origin * May or may not be associated with change in consciousness or evolve to generalised tonic-clonic seizure 6. Focal seizures - Frontal seizures – motor phenomena such as clonic movements or a tonic seizure with both upper limbs raised high for several seconds. Some assymetrical tonic seizures may be seen. - Temporal lobe seizures – auditory or sensory (smell or taste) phenomena: Aura. May spread to motor cortex and cause lip-smacking, plucking at one's clothing and walking in a non-purposeful manner. Often deja-vu feelings and impaired consciousness. - Occipital – positive or negative visual phenomena, stereotypically visual hallucinations - Parietal lobe seizures – contralateral altered sensation (dysaesthesia)

Answer 312

The diagnosis of an epilepsy is primarily based on a detailed history from the child and eyewitnesses, substantiated by a video if available. Particular attention is focussed on any specific triggers and if the child has any impairments, as there may be educational, psychological, or social problems. Clinical examination should include checking for skin markers for a neurocutaneous syndrome or neurological abnormalities. Investigation: 1. ECG - It is recommended that a 12-lead standard ECG is done in all children with seizures, especially convulsive seizures, even when an epilepsy seems most likely, as the consequences of missing convulsive syncope due to an arrhythmia, e.g. long-QT syndrome, can be an avoidable fatality. 2. EEG - An inter-ictal EEG is indicated whenever an epilepsy is diagnosed. It can help categorize the epilepsy type and severity. If seizures are frequent then an ictal EEG can make the diagnosis, e.g. in suspected childhood absence epilepsy and suspected infantile spasms (West syndrome). If the standard interictal EEG is normal, a sleep or sleep-deprived record can be helpful. Additional techniques are 24 hour ambulatory EEG or a 5-day video-telemetry EEG. 3. Brain imaging * Structural - MRI and CT brain scans are generally required routinely for childhood epilepsies unless there is a characteristic history of childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and childhood rolandic epilepsy. * Functional - While it is not always possible to see structural lesions, techniques have advanced to allow functional imaging to detect areas of abnormal metabolism suggestive of epileptogenic zones. These include PET (positron emission tomography) and SPECT (single photon emission computed tomography), which use isotopes and ligands injected and taken up by metabolically active cells. Both can be used between seizures to detect areas of hypometabolism in epileptogenic lesions. They are used in the work up of patients for possible epilepsy surgery. 4. Other investigations - Metabolic investigations will be indicated if there is developmental arrest or regression, or seizures are related to feeds or fasting, and should be considered in epilepsies (i.e. not including febrile seizures) starting in the first 2 years of life. Genetic tests are becoming increasingly useful, especially in intractable epilepsies with developmental arrest or delay (“epileptic encephalopathies”)

Answer 313

Age of onset: 3–12 months Violent flexor spasms of the head, trunk, and limbs followed by extension of the arms, last 1–2 s, often multiple bursts of 20–30, often on waking or many times a day. May be misinterpreted as colic. Social interaction often deteriorates – a useful marker in the history Most have underlying neurological cause. EEG – hypsarrhythmia. Treatment is vigabatrin and/or corticosteroids; good initial response in 60–70%, but unwanted side effects of therapy, and relapses common. Most will lose skills and develop learning disability and continuing epilepsy.

Answer 314

Age of onset: 1–3 years Multiple seizure types, but mostly atonic, atypical (subtle) absences, and tonic seizures in sleep. Also neurodevelopmental arrest or regression and behaviour disorder. Many causes, and often other complex neurological problems or history of infantile spasms. EEG shows slow generalized spike and wave (1–3 Hz). Prognosis is poor.

Answer 315

Age of onset: 4–12 years Momentary unresponsive stare with motor arrest, may twitch their eyelids or a hand or mouth minimally. Sudden onset, lasts only a few seconds (<30 s). Child has no recall except realises they have missed something and may look puzzled or say ‘pardon’ on regaining consciousness. Developmentally normal but can interfere with schooling. Accounts for only 2% of childhood epilepsy. Two-thirds are female. Episodes can be induced by hyperventilation. The EEG shows fast generalised spike and wave (3–4 Hz) discharges, bilaterally synchronous during and sometimes between absences. Prognosis good with 80% remission in adolescence; a few evolve into juvenile absence or juvenile myoclonic epilepsy.

Answer 316

Benign epilepsy with centro-temporal spikes Age of onset: 4–10 years Tonic-clonic seizures in sleep, or simple focal seizures with awareness of abnormal feelings in the tongue and distortion of the face (supplied by the rolandic (centro-temporal) area of the brain). 15% of all childhood epilepsies. EEG shows focal sharp waves from the rolandic area. Important to recognise as relatively benign and may not require AEDs. Remits in adolescence.

Answer 317

(Early-onset benign occipital epilepsy) Age of onset: 1–5 years Autonomic features with vomiting and unresponsive staring in sleep, with head and eye deviation, progressing sometimes to a convulsive seizure. Comprises 5% of childhood epilepsies. EEG shows posterior focal sharp waves and occipital discharges when eyes are shut. Remits in childhood. Some have specific learning difficulties.

Answer 318

Juvenile absence epilepsy Age of onset: 10–20 years Absences, and generalised tonic-clonic seizures, often with photosensitivity. Learning is unimpaired. Characteristic EEG. Response to treatment is usually good but lifelong. Remission unlikely

Answer 319

Age of onset: 10–20 years Myoclonic seizures, generalized tonic-clonic seizures, and absences may occur, mostly shortly after waking. A typical history is throwing drinks or cereal about in the morning as myoclonus occurs at this time. Learning is unimpaired. Characteristic EEG. Response to treatment is usually good but lifelong. Remission unlikely

Answer 320

The decision whether to treat or not is related to the risk of recurrence, how dangerous or impairing, and how upsetting further seizures would be, in the context of the child or young person’s life. It is common practice not to institute treatment for typical childhood rolandic epilepsy, and treatment of childhood absence epilepsy is aimed at maximizing their educational potential and supporting their social development. Antiepileptic drug therapy Principles governing use are: * Not all children with epileptic seizures require antiepileptic drug (AED) therapy. The decision should be based on the seizure type, epilepsy type, frequency, and the social and educational consequences of the seizures set against the possibility of unwanted effects of the AED * Choose an appropriate AED for the seizure and epilepsy. Inappropriate AEDs may be detrimental, e.g. carbamazepine can make absence and myoclonic seizures worse * Monotherapy at the minimum dosage to prevent the seizures without adverse effects is the desired goal, although in practice more than one AED may be required * All AEDs have potential unwanted effects and these should be discussed with the child and parent * AED levels are not measured routinely, but may be useful to check for concordance (adherence) or to see if a dose increase could be considered if a high dose is not working * Children with prolonged epileptic seizures (convulsive epileptic seizures with loss of consciousness >5 min) are given rescue therapy to keep with them. This is usually buccal midazolam * AED therapy may be discontinued after 2 years free of seizures, but should usually be continued indefinitely in young people with juvenile absence epilepsy or juvenile myoclonic epilepsy. Other treatment options: In children with intractable epilepsies, there are a number of other treatment options. * Ketogenic (low-carb, fat-based) diets may be helpful in some children. * Vagal nerve stimulation, delivered using externally programmable stimulation of a wire implanted around the afferent (left) vagal nerve, may be helpful in some children. * Epilepsy surgery. Cessation of seizures and AED therapy may be achieved in some children whose epilepsy has a well-localised structural cause or epileptogenic zone, as demonstrated by good concordance between ictal EEG, MRI, and functional imaging findings. The main procedure is temporal lobectomy for mesial temporal sclerosis, but other procedures include hemispherotomy (disconnection of the hemisphere) and other focal resections.

Answer 321

1. Tonic-clonic -Sodium Valproate (not used in women with child-bearing potential) - Lamotrigine or Levetiracetam (for women of child-bearing potential or if first choice unsuccessful. Be aware that lamotrigine may exacerbate seizures in people with myoclonic seizures) If this monotherapy is unsuccessful, consider adding any of the above or: - Clobazam, topiramate or perampanel. 2. Absence seizures - Ethosuximide as first-line treatment - Sodium Valproate/ Lamotrigine/ Levetiracetam as second line or as add-on therapy 3. Myoclonic seizures - Valproate/ Levetiracetam as first-line If unsuccessful either monotherapy or add-on therapy with: Clobazam, Lamotrigine, Topiramate 4. Focal seizures - Lamotrigine or levetiracetam If both are unsuccessful, second-line monotherapy with: - Carbamazepine - Oxcarbazepine - Zonisamide (The first two of these may exacerbate seizures in people with absence or myoclonic seizures, including in juvenile myoclonic epilepsy)

Answer 322

1. Valproate: Weight gain, hair loss, teratogenic, rare idiosyncratic liver failure 2. Carbamazepine: Rash, hyponatraemia, ataxia, liver enzyme induction, can interfere with other medication including oral contraception 3. Lamotrigine: Rash, insomnia, ataxia 4. Ethosuximide: Nausea and vomiting 5. Levetiracetam: Irritability 6. Topiramate: Weight loss, depression, parasthesia

Answer 323

The aim is to promote independence and confidence. Some children with epilepsy and their families need psychological help to adjust to the condition. -The school needs to be aware of the child’s problem and teachers advised on the management of seizures. Unrecognized absences may interfere with learning, which is an indication for being vigilant about ‘odd episodes’ which may be epileptic seizures. - Relatively few restrictions are required, but situations where having a seizure could lead to injury or death should be avoided. This includes avoiding deep baths (showers are preferable) and not swimming unsupervised. For adolescents, there will be issues to discuss around driving (only after 1 year free of seizures), contraception and pregnancy. There may also be issues with concordance (adherence) and the precipitation of seizures by alcohol and poor sleep routines. Sudden unexpected death in epilepsy, (SUDEP), is very rare in childhood, but may be discussed and its rarity emphasised. Information is available from self-help groups and organisations such as Epilepsy Action. Children with epilepsy do less well educationally, with social outcomes and with future employment than those with other chronic illnesses such as diabetes. Two-thirds of children with epilepsy go to a mainstream school, but some require educational help for associated learning difficulties. One-third attend a special school, but they often have multiple disabilities and their epilepsy is part of a severe brain disorder. A few children require residential schooling where there are facilities and expertise in monitoring and treating intractable epilepsies.

Answer 324

Status epilepticus, an epileptic seizure lasting 30 minutes or repeated epileptic seizures for 30 minutes without recovery of consciousness.

Answer 325

1. Motor cortex Lying along the precentral gyrus (the homunculus reflects the body upside down, legs superiorly and face inferiorly, just above the Sylvian fissure, with large areas to govern fine movements of the tongue, fingers and thumb). * Corticospinal (pyramidal) tract disorders – there is weakness with a pattern of adduction at the shoulder, flexion at the elbow and pronation of the forearm; adduction and internal rotation at the hip, flexion at hip and knee, and plantar flexion at the ankle with brisk hyper-reflexia and extensor plantar reflexes. Fine finger movement will be lost. Information from here passes down the corticospinal (pyramidal) tracts to link with the basal ganglia. 2. Basal ganglia Deep grey matter structures, store patterns of movement so that we need not put conscious effort into every movement we make. * Basal ganglia disorders – will lead either to difficulty initiating movement, with fluctuating (largely increased) tone – a ‘dystonia’ or a ‘dyskinesia’ where packets of movement information are released to give jerky movement (chorea) or writhing movement (athetosis). 3. Cerebellum Controls posture, balance, coordination and speech. * Cerebellar disorders – will lead to difficulty holding a posture; past-pointing (dysmetria); poor alternating movements (dysdiadochokinesis). The gait is wide-based and ataxic. Posterior-column sensory pathway problems may give a similar clinical picture (but with even worse ataxia when the eyes are closed), but are much rarer in childhood. Associated nystagmus and a characteristic scanning dysarthria may be seen.

Answer 326

1. Corticospinal (pyramidal) tract disorders - Cerebral dysgenesis, e.g. neuronal migration disorder - Global hypoxia–ischaemia - Arterial ischaemic stroke - Cerebral tumour - Acute disseminated encephalomyelitis - Postictal paresis - Hemiplegic migraine 2. Basal ganglia disorders - Acquired brain injury: * Acute and profound hypoxia-ischaemia * Carbon monoxide poisoning * Post-cardiopulmonary bypass chorea - Post-streptococcal chorea (rheumatic fever) - Mitochondrial cytopathies - Wilson disease - Huntington disease - Vitamin E deficiency - Pontocerebellar hypoplasia 3. Cerebellar disorders - Acute – medication and drugs, including alcohol and solvent abuse - Postviral – particularly varicella infection - Posterior fossa lesions or tumours, e.g. medulloblastoma - Genetic and degenerative disorders, e.g. Friedreich ataxia and ataxia telangiectasia

Answer 327

1. Disorders of the anterior horn cell * Spinal muscular atrophy * Poliomyelitis 2. Disorders of the peripheral nerve * Hereditary motor sensory neuropathies * Acute post-infectious polyneuropathy (Guillain-Barré) * Bell palsy 3. Disorders of neuromuscular transmission * Myasthenia gravis 4. Muscle disorders * Muscle dystrophies - Duchenne/Becker/congenital * Inflammatory myopathies - Benign acute myositis - Polymyositis/dermatomyositis * Myotonic disorders - Dystrophia myotonica * Metabolic myopathies * Congenital myopathies

Answer 328

The key clinical feature of a neuromuscular disorder is weakness, which may be progressive or static. Affected children may present with: * Hypotonia (floppiness) * Delayed motor milestones * Muscle weakness * Unsteady/abnormal gait * Fatiguability * Muscle cramps (suggesting a metabolic myopathy). Children with myopathy often show a waddling gait or positive Gowers’ sign suggestive of proximal muscle weakness. Gowers’ sign is the need to turn prone to rise to a standing from a supine position. This is normal until the age of 3 years. It is only when children have become very weak that they ‘climb up the legs with the hands’ to gain the standing position. A pattern of more distal wasting and weakness, particularly in the presence of pes cavus, suggests a hereditary motor sensory neuropathy. Increasing fatiguability through the day, often with ophthalmoplegia and ptosis, would be more consistent with a disorder of the motor end-plate/neuromuscular junction e.g. myasthenia gravis

Answer 329

* Anterior horn cell – there are signs of denervation: weakness, loss of reflexes, fasciculation and wasting as the nerve supply to the muscle fails * Neuropathy – often longer nerves affected. Motor neuropathy will give weakness, sensory neuropathy will give impaired perception of pain and temperature or touch, with a loss of reflexes in either * Myopathy – there is weakness (often proximal), wasting, gait disturbance * Neuromuscular junction – as end-plate acetylcholine stores become depleted, there is diurnal worsening through the day, leading to fatiguability.

Answer 330

1. Myopathy: * Plasma creatine kinase – markedly elevated in Duchenne and Becker muscular dystrophy, congenital muscular dystrophy, many limb girdle muscular dystrophies and inflammatory myopathies. * Muscle biopsy, usually taken with an open technique – modern histochemical techniques often enable a definitive diagnosis. * DNA testing – to identify abnormal genes. * Ultrasound and MRI of muscles – used to diagnose and monitor progress. 2. Neuropathy: * Nerve conduction studies – to identify delayed motor and sensory nerve conduction velocities seen in neuropathy. * DNA testing – for abnormal genes. * Nerve biopsy – occasionally performed by removing a segment of sural nerve in the leg. * EMG (electromyography) helps in differentiating myopathic from neuropathic disorders, e.g. fatiguability on repetitive nerve stimulation in myasthenia. Diagnosis of neuromuscular disorders has been made easier by advances in genetic (DNA) testing, e.g. for spinal muscular atrophy (SMA), Duchenne muscular dystrophy, myotonic dystrophy, the congenital muscular dystrophies, limb girdle muscular dystrophies and hereditary neuropathies.

Answer 331

Presentation is with weakness, wasting and absent reflexes. 1. Poliomyelitis (has almost been eradicated globally by immunization). 2. Spinal muscular atrophy (SMA)

Answer 332

This is an autosomal recessive degeneration of the anterior horn cells, leading to progressive weakness and wasting of skeletal muscles due to mutations in the survival motor neurone (SMN1) gene. This is the second most common cause of neuromuscular disease in the UK after Duchenne muscular dystrophy. A number of phenotypes are recognised. Spinal muscular atrophy type 1 (Werdnig– Hoffmann disease): A very severe progressive disorder presenting from birth to 3 months of age. Diminished fetal movements are often noticed during pregnancy and there may be arthrogryposis (positional deformities of the limbs with contractures of at least two joints) at birth. Typical signs include: * Alert expression * Fasciculation of the tongue * Symmetrical flaccid paralysis * Absent deep tendon reflexes * Intercostal recession * Weakness of bulbar muscles causing weak cry and poor suck with pooling of secretions. These children never sit unaided. Death is from respiratory failure within about 12 months of age. There are milder forms of the disorder with a later onset. Children with type 2 spinal muscular atrophy present at age 3 months to 15 months, can sit but never walk independently. Those with the milder type 3 (Kugelberg–Welander) present after 1 year of age and do learn to walk. The most severe form is SMA type 0 and is diagnosed in newborn infants that are born so weak that their survival is limited to only a few weeks.

Answer 333

1. Charcot-Marie-Tooth disease (the hereditary motor sensory neuropathies) 2. Guillain-Barre syndrome (acute post-infectious polyneuropathy) 3. Bell's palsy and facial nerve palsies

Answer 334

There are many forms of Charcot–Marie–Tooth (CMT) disease, which typically lead to symmetrical, slowly progressive distal muscular wasting. They are caused by mutations in myelin genes. CMT1A accounts for 70–80% and is inherited in an autosomal dominant manner in two thirds, one third developing the mutation de novo. The other types of CMT disease can be inherited by autosomal dominant, recessive or X-linked modes. Children may present in preschool with tripping from bilateral foot drop. Examination shows loss of ankle reflexes progressing to loss of knee reflexes. Pes cavus may be present, the lower limbs being affected more than the upper. Nerve conduction studies show a motor and sensory neuropathy. Affected nerves may be hypertrophic due to demyelination followed by attempts at remyelination. Nerve biopsy typically shows ‘onion bulb formation’ due to these two processes. The disease is chronic but only rarely do those affected lose the ability to walk.

Answer 335

Can occur at any age, and typically presents 2–3 weeks after an upper respiratory tract infection or campylobacter gastroenteritis, with an ascending, progressive, symmetrical weakness over a few days to 2 weeks. The maximum muscle weakness may occur only 2–4 weeks after the onset of illness. There is sometimes: - Loss of tendon reflexes - Autonomic involvement. - Sensory symptoms, usually in the distal limbs or trunk, (less striking than the weakness but can be unpleasant.) - Bilateral facial weakness is easily missed in young children. - Involvement of bulbar muscles leads to difficulty with chewing and swallowing and the risk of aspiration. - Dysautonomia occurs in 70% and manifests as tachycardia, bradycardia and other arrhythmias, hypertension and orthostatic hypotension, urinary retention, ileus and loss of sweating. Hypoventilation can require artificial ventilation, best started before established respiratory failure. Although full recovery can be expected in 90% of cases, this may take up to 2 years. Investigation: - MRI of the spinal cord (or brain and spinal cord) is the most useful acute investigation, to identify or exclude a spinal cord lesion e.g. a bleed, tumour, or inflammatory transverse myelitis. - The CSF white count is not raised, but CSF protein is characteristically markedly raised, but this may not be seen until the second week of illness. - Nerve conduction studies typically show reduced velocities but this may not be evident until after the second week. Management is supportive, particularly of respiration. The disorder is probably due to the formation of antibody attaching itself to protein components of myelin. Corticosteroids have no beneficial effect and may delay recovery. Controlled trials indicate the ventilator-dependent period can be significantly reduced by intravenous immunoglobulin infusion or plasma exchange.

Answer 336

Bell palsy is an isolated lower motor neurone paresis of the VIIth cranial nerve leading to facial weakness. Although the aetiology is unclear, it may be post-infectious with an association with herpes simplex virus or Lyme disease. The herpes virus may invade the geniculate ganglion and give painful vesicles on the tonsillar fauces and external ear, along with a facial nerve paresis. - If herpes is the suspected cause, treatment is with aciclovir. - Corticosteroids can reduce oedema in the facial canal if given during the first week and speed full recovery. Recovery is complete in the majority of cases but may take several months. The main complication is conjunctival infection due to incomplete eye closure on blinking. This may require the eye to be protected with lubricating drops or ointment, a patch or even tarsorrhaphy. There are important differential diagnoses. If there is also a recent 6th nerve paresis, or ipsilateral cerebellar signs, or contralateral upper motor neurone signs, suspect a brain stem lesion. If there are symptoms of a recent 8th nerve paresis, the most likely diagnosis is a compressive lesion in the cerebellopontine angle. Hypertension should be excluded, as there is an association between Bell palsy and coarctation of the aorta and renal failure.

Answer 337

Myasthenia gravis presents as abnormal muscle fatiguability which improves with rest or anticholinesterase drugs. Juvenile myasthenia is similar to adult autoimmune myasthenia gravis and is due to binding of antibody to acetylcholine receptors on the postsynaptic membrane of the neuromuscular junction. This reduces the number of functional receptors. Presentation is usually after 10 years of age with ophthalmoplegia and ptosis, loss of facial expression and difficulty chewing. Generalised, especially proximal, weakness may be seen. Diagnosis is made by observing improvement following the administration of intravenous edrophonium over a few minutes or oral pyridostigmine or neostigmine over days. (Acetylcholinesterase inhibitors) Identifying acetylcholine receptor antibodies (seen in 60–80%) or, more rarely, anti-MuSK (antimuscle-specific kinase) antibodies will confirm the diagnosis and direct treatment decisions. Treatment is with the choline esterase inhibitors pyridostigmine or neostigmine and immunosuppressive therapy. Immune-modulating drugs such as prednisolone, azathioprine or mycophenolate mofetilis, or even monoclonal antibodies (“biologicals”) e.g. rituximab are of value. Thymectomy is indicated if a thymoma is present or in young antibody positive patients with a very acute, severe presentation affecting more than just ocular muscles. Plasma exchange is used for crises

Answer 338

1. Duchenne 2. Becker 3. Limb girdle 4. Congenital

Answer 339

Duchenne muscular dystrophy is the most common muscular dystrophy. It is inherited as an X-linked recessive disorder, although about a third have de novo mutations. It results from a deletion of the gene for dystrophin, which connects the cytoskeleton of a muscle fibre to the surrounding extracellular matrix through the cell membrane. Where it is deficient, there is an influx of calcium ions, a breakdown of the calcium calmodulin complex and an excess of free radicals, ultimately leading to myofibre necrosis. The plasma creatine kinase (CK) is markedly elevated. Some countries have neonatal screening; affected children are detected by an elevated creatine kinase. Children present with a waddling gait and/or language delay; they have to mount stairs one by one and run slowly compared with their peers. Although the average age of diagnosis remains 5 years, children often become symptomatic much earlier. They will show Gowers sign (the need to turn prone to rise). There is pseudohypertrophy of the calves because of replacement of muscle fibres by fat and fibrous tissue. In the early school years, affected boys tend to be slower and clumsier than their peers. The progressive muscle atrophy and weakness means that they are no longer ambulant by the age of about 10–14 years. Life expectancy is reduced to the late twenties from respiratory failure or the associated cardiomyopathy. About one-third of affected children have learning difficulties. Scoliosis is a common complication

Answer 340

Psoriasis is a chronic autoimmune condition that causes recurrent symptoms of psoriatic skin lesions. There is a large variation in how severely patients are affected with psoriasis. There appears to be a genetic component but no clear genetic inheritance has been established. Around a third of patients have a first degree relative with psoriasis. The symptoms start in childhood in a third of patients. Patches of psoriasis are dry, flaky, scaly, faintly erythematous skin lesions that appear in raised and rough plaques, commonly over the extensor surfaces of the elbows and knees and on the scalp. These skin changes are caused by the rapid generation of new skin cells, resulting in an abnormal buildup and thickening of the skin in those areas.

Answer 341

1. Plaque psoriasis features the thickened erythematous plaques with silver scales, commonly seen on the extensor surfaces and scalp. The plaques are 1cm – 10cm in diameter. This is the most common form of psoriasis in adults. 2. Guttate psoriasis is the second most common form of psoriasis and commonly occurs in children. It presents with many small raised papules across the trunk and limbs. The papules are mildly erythematous and can be slightly scaly. Over time the papules in guttate psoriasis can turn into plaques. Guttate psoriasis is often triggered by a streptococcal throat infection, stress or medications. It often resolves spontaneously within 3 – 4 months. 3. Pustular psoriasis is a rare severe form of psoriasis where pustules form under areas of erythematous skin. The pus in these areas is not infectious. Patients can be systemically unwell. It should be treated as a medical emergency and patients with pustular psoriasis initially require admission to hospital. 4. Erythrodermic psoriasis is a rare severe form of psoriasis with extensive erythematous inflamed areas covering most of the surface area of the skin. The skin comes away in large patches (exfoliation) resulting in raw exposed areas. It should be treated as a medical emergency and patients require admission.

Answer 342

In children the distribution and presentation of psoriasis may differ from adults. Guttate psoriasis is more common in children, often triggered by a throat infection. Plaques of psoriasis are likely to be smaller, softer and less prominent. There are a few specific signs suggestive of psoriasis: - Auspitz sign refers to small points of bleeding when plaques are scraped off - Koebner phenomenon refers to the development of psoriatic lesions to areas of skin affected by trauma - Residual pigmentation of the skin after the lesions resolve The diagnosis can be made based on the clinical appearance of the lesions. Associations Nail psoriasis describes the nail changes that can occur in patients with psoriasis. These include nail pitting, thickening, discolouration, ridging and onycholysis (separation of the nail from the nail bed). Psoriatic arthritis occurs in 10 – 20% of patients with psoriasis and usually occurs within 10 years of developing the skin changes. It typically affects people in middle age but can occur at any age. Psychosocial implications of having chronic skin lesions, which may affect mood, self esteem and social acceptance and cause depression and anxiety. Other co-morbidities that increase the risk of cardiovascular disease are associated with psoriasis, particularly obesity, hyperlipidaemia, hypertension and type 2 diabetes.

Answer 343

Management depends on the severity of the condition. Psoriasis in children is usually managed and followed up by a specialist. It can be difficult to treat and psychosocial support is very important. The treatment options include: - Topical steroids - Topical vitamin D analogues (calcipotriol) - Topical dithranol - Topical calcineurin inhibitors (tacrolimus) are usually only used in adults - Phototherapy with narrow band ultraviolet B light is particularly useful in extensive guttate psoriasis Rarely, where topical treatments fail with severe and difficult to control psoriasis, children may be started on unlicensed systemic treatment under the guidance of an experienced specialist. This might include methotrexate, cyclosporine, retinoids or biologic medications. There are two products that contain both a potent steroid and vitamin D analogue that are commonly prescribed and worth being aware of. These not licensed in children and will be guided by a specialist. - Dovobet - Enstilar

Answer 344

-Deafness -Blindness -Congenital heart disease

Answer 345

Parvovirus B19 is also known as fifth disease, slapped cheek syndrome and erythema infectiosum. It is caused by the parvovirus B19 virus. Parvovirus infection starts with mild fever, coryza and non-specific viral symptoms such as muscle aches and lethargy. After 2 – 5 days the rash appears quite rapidly as a diffuse bright red rash on both cheeks, as though they have “slapped cheeks”. A few days later a reticular mildly erythematous rash affecting the trunk and limbs appears that can be raised and itchy. Reticular means net-like. The illness is self limiting and the rash and symptoms usually fade over 1 – 2 weeks. Healthy children and adults have a low risk of any complications and are managed supportively with plenty of fluids and simple analgesia. It is infectious prior to the rash forming, but once the rash has formed they are no longer infectious and do not need to stay off school.

Answer 346

Patients that are at risk of complications include immunocompromised patients, pregnant women and patients with haematological conditions such as sickle cell anaemia, thalassaemia, hereditary spherocytosis and haemolytic anaemia. These patients require serology testing for parvovirus to confirm the diagnosis and checking of the full blood count and reticulocyte count for aplastic anaemia. People that would be at risk of complications that have come in contact with someone with parvovirus prior to the rash forming, should be informed and may need investigations. Complications: Aplastic anaemia Encephalitis or meningitis Pregnancy complications including fetal death Rarely hepatitis, myocarditis or nephritis

Answer 347

Erythema multiforme is an erythematous rash caused by a hypersensitivity reaction. The most common causes are viral infections and medications. It is also notably associated with the herpes simplex virus (causing coldsores) and mycoplasma pneumonia. Presentation Erythema multiforme produces a widespread, itchy, erythematous rash. It produces characteristic “target lesions”. Target lesions are red rings within larger red rings, with the darkest red at the centre, similar to a bulls-eye target. It does not usually affect the mucous membranes but can cause a sore mouth (stomatitis). The symptoms come on abruptly over a few days. It may be associated with other symptoms of mild fever, stomatitis, muscle and joint aches, headaches and general flu-like symptoms. Management The diagnosis is made clinically based on the appearance of the rash. It is important to identify the underlying cause. Where there is a clear underlying cause, for example a recent coldsore or treatment with penicillin, it may be managed supportively. Where there is no clear underlying cause it may be worth investigating further, for example doing a chest xray to look for mycoplasma pneumonia. Most of the time erythema multiforme is mild and resolves spontaneously within one to four weeks without any treatment or lasting effects. Cases may be recurrent, particularly associated with recurrent coldsores. Severe cases may require admission to hospital, particularly where it affects the oral mucosa. Treatments used in severe cases include IV fluids, analgesia and steroids (systemic or topical). The use of systemic steroids is controversial. Antibiotics or antivirals may be used where infection is present.

Answer 348

Urticaria are also known as hives. They are small itchy lumps that appear on the skin. They may be associated with a patchy erythematous rash. This can be localised to a specific area or widespread. They may be associated with angioedema and flushing of the skin. Urticaria can be classified as acute urticaria or chronic urticaria. Pathophysiology Urticaria are caused the release of histamine and other pro-inflammatory chemicals by mast cells in the skin. This may be part of an allergic reaction in acute urticaria or an autoimmune reaction in chronic idiopathic urticaria. Causes of Acute Urticaria Acute urticaria is typically triggered by something that stimulates the mast cells to release histamine. This may be: - Allergies to food, medications or animals - Contact with chemicals, latex or stinging nettles - Medications - Viral infections - Insect bites - Dermatographism (rubbing of the skin)

Answer 349

Chronic urticaria is an autoimmune condition, where autoantibodies target mast cells and trigger them to release histamines and other chemicals. It can be sub-classified depending on the cause: 1. Chronic idiopathic urticaria 2. Chronic inducible urticaria 3. Autoimmune urticaria Chronic idiopathic urticaria describes recurrent episodes of chronic urticaria without a clear underlying cause or trigger. Chronic inducible urticaria describes episodes of chronic urticaria that can be induced by certain triggers, such as: - Sunlight - Temperature change - Exercise - Strong emotions - Hot or cold weather - Pressure (dermatographism) Autoimmune urticaria describes chronic urticaria associated with an underlying autoimmune condition, such as systemic lupus erythematosus.

Answer 350

Antihistamines are the main treatment for urticaria. Fexofenadine is usually the antihistamine of choice for chronic urticaria. Oral steroids may be considered as a short course for severe flares. In very problematic cases referral to a specialist may be required to consider treatment with: Anti-leukotrienes such as montelukast Omalizumab, which targets IgE Cyclosporin

Answer 351

Molluscum contagiosum is a viral skin infection caused by the molluscum contagiosum virus, which is a type of poxvirus. Features Molluscum contagiosum is characterised by small, flesh coloured papules (raised individual bumps on the skin) that characteristically have a central dimple. They typically appear in “crops” of multiple lesions in a local area. It is spread through direct contact or by sharing items like towels or bedsheets. The papules resolve by themselves without any treatment, however this can take up to 18 months. Once they resolve the skin returns to normal. Scratching or picking the lesions should be avoided as it can lead to spreading, scarring and infection. Management No treatment or change in lifestyle is required and children can continue all their normal activities. They should avoid sharing towels or other close contact with the lesions to minimise the risk of spreading the infection. Usually just simple reassurance and education is enough. Rarely, if bacterial superinfection infection occurs in the lesions as a result of scratching, this may require treatment with antibiotics. Options include topical fuscidic acid or oral flucloxacillin. Immunocompromised patients and those with very extensive lesions or lesions in problematic areas such as the eyelid or anogenital area may require referral to a specialist. Specialist treatment options include: - Topical potassium hydroxide, benzoyl peroxide, podophyllotoxin, imiquimod or tretinoin - Surgical removal and cryotherapy (freezing with liquid nitrogen) is an option but can lead to scarring

Answer 352

Pityriasis rosea a generalised, self limiting rash that has an unknown cause. It often occurs in adolescents and young adults. It may be caused by a virus such as human herpes virus (HHV-6 or HHV-7), but no definitive causative organism had been established. Presentation There may be prodromal symptoms prior to the rash developing. These include headache, tiredness, loss of appetite and flu-like symptoms. The rash starts with a characteristic herald patch. This is a faint red or pink, scaly, oval shaped lesion that is 2cm or more in diameter, usually occurring somewhere on the torso. It appears 2 or more days prior to the rest of the rash. If you suspect pityriasis, ask and look for a herald patch. Most, but not all, patients have a herald patch. The rash consists of widespread faint red or pink, slightly scaly, oval shaped lesions, usually less than 2 cm in diameter. On the torso they can be arranged in a characteristic “christmas tree” fashion, following the lines of the ribs. In dark skinned patients the lesions can be grey coloured, lighter or darker than their skin colour. Other symptoms may be present: - Generalised itch - Low grade pyrexia - Headache - Lethargy Disease Course The rash resolves without treatment within 3 months. It can leave a discolouration of the skin where the lesions were, however these will also resolved within another few months. Management There is no treatment for the rash. It will resolve spontaneously without any long term effects. Patient education and reassurance is all that is required. It is not contagious and they can continue all their normal activities. They may require symptomatic treatment if bothered by itching. This may include emollients, topical steroids or sedating antihistamines at night to help with sleep (e.g. chlorphenamine).

Answer 353

Head lice are the Pediculus humanus capitis parasite, which causes infestations of the scalp, most commonly in school aged children. Head lice are commonly known as nits, however nits are egg shells that have hatched or contain unviable embryos and not the lice themselves. Head lice are spread by close contact with someone that has head lice, usually in schools or amongst family members. Transmission is by head to head contact or by sharing equipment like combs or towels. Presentation Infestation causes an itchy scalp. Often the nits (eggs) and even lice themselves are visible when examining the scalp. Management Dimeticone 4% lotion can be applied to the hair and left to dry. This is left on for 8 hours (i.e. overnight), then washed off. This process is repeated 7 days later to kill any head lice that have hatched since treatment. Special fine combs can be used to systematically comb the nits and lice out of the hair. They can be used for detection combing to check the success of treatment. NICE clinical knowledge summaries recommend The Bug Buster kit.

Answer 354

Meningococcal septicaemia or other bacterial sepsis: This presents with a feverish unwell child. Any features of meningococcal septicaemia indicate emergency management with immediate antibiotics. This can lead to significant morbidity and mortality if treatment is delayed. Henoch-Schonlein purpura (HSP): This typically presents as a purpuric rash on the legs and buttocks and may have associated abdominal or joint pain. Idiopathic thrombocytopenic purpura (ITP): This develops over several days in an otherwise well child. Acute leukaemias: This presents with a gradual development of petechiae, potentially with other signs such as anaemia, lymphadenopathy and hepatosplenomegaly. Haemolytic uraemic syndrome (HUS): This is associated with oliguria (very low urine output) and signs of anaemia. This often presents in a child with recent diarrhoea. Mechanical: Strong coughing, vomiting or breath holding can produce petechiae in a “superior vena cava distribution”, above the neck and most prominently around the eyes. Traumatic: Tight pressure on the skin, for example in non-accidental injury, or occlusion of blood in an area of skin can lead to traumatic petechiae. Viral illness: This is often the explanation when other causes and serious illness are excluded. Typical causes are influenza and enterovirus.

Answer 355

Erythema nodosum is a condition where red lumps appear across the patient’s shins. Erythema means red and nodosum directly translates from Latin as “knots”, referring to lumps. It is caused by inflammation of the subcutaneous fat on the shins. Inflammation of fat is called panniculitis. It is caused by a hypersensitivity reaction. In around half of patients there is no identifiable cause. It is associated with a number of triggers and underlying conditions. Associations Erythema nodosum is caused by a hypersensitivity reaction, and there is often an identifiable cause: - Streptococcal throat infections - Gastroenteritis - Mycoplasma pneumoniae - Tuberculosis - Pregnancy - Medications, such as the oral contraceptive pill and NSAIDs It is also associated with chronic diseases: - Inflammatory bowel disease - Sarcoidosis - Lymphoma - Leukaemia

Answer 356

Staphylococcal scalded skin syndrome (SSSS) is a condition caused by a type of staphylococcus aureus bacteria that produces epidermolytic toxins. These toxins are protease enzymes that break down the proteins that hold skin cells together. When a skin infection occurs and these toxins are produced, the skin is damaged and breaks down. This condition usually affects children under 5 years. Older children and adults have usually developed immunity to the epidermolytic toxins. Presentation SSSS usually starts with generalised patches of erythema on the skin. Then the skin looks thin and wrinkled. This is followed by the formation of fluid filled blisters called bullae, which burst and leave very sore, erythematous skin below. This has a similar appearance to a burn or scald. Nikolsky sign is where very gentle rubbing of the skin causes it to peel away. This is positive in SSSS. Systemic symptoms include fever, irritability, lethargy and dehydration. If untreated it can lead to sepsis and potentially death.

Answer 357

Most patients will require admission and treatment with IV antibiotics. Fluid and electrolyte balance is key to management as patients are prone to dehydration. When adequately treated, children usually make a full recovery without scarring.

Answer 358

Type 1: IgE antibodies to a specific allergen trigger mast cells and basophils to release histamines and other cytokines. This causes an immediate reaction. Typical food allergy reactions, where exposure to the allergen leads to an acute reaction, range from itching, facial swelling and urticaria to anaphylaxis. Type 2: IgG and IgM antibodies react to an allergen and activate the complement system, leading to direct damage to the local cells. Examples are haemolytic disease of the newborn and transfusion reactions. Type 3: Immune complexes accumulate and cause damage to local tissues. Examples are autoimmune conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis and Henoch-Schönlein purpura (HSP) Type 4: Cell mediated hypersensitivity reactions caused by T lymphocytes. T-cells are inappropriately activated, causing inflammation and damage to local tissues. Examples are organ transplant rejection and contact dermatitis.

Answer 359

Anaphylaxis is a life-threatening medical emergency. It is caused by a severe type 1 hypersensitivity reaction. Immunoglobulin E (IgE) stimulates mast cells to rapidly release histamine and other pro-inflammatory chemicals. This is called mast cell degranulation. This causes a rapid onset of symptoms, with airway, breathing and/or circulation compromise. The key feature that differentiates anaphylaxis from a non-anaphylactic allergic reaction is compromise of the airway, breathing or circulation. Presentation Patients present with a history of exposure to an allergen (although it can be idiopathic). There will be rapid onset of allergic symptoms: - Urticaria - Itching - Angio-oedema, with swelling around lips and eyes - Abdominal pain Additional symptoms that indicate anaphylaxis are: - Shortness of breath - Wheeze - Swelling of the larynx, causing stridor - Tachycardia - Lightheadedness - Collapse

Answer 360

Anaphylaxis requires immediate medical attention and management. It should be managed by an experienced paediatrician. Call for help early. Refer to the resuscitation guidelines for full management guidelines. Initial assessment of acutely unwell child is with an ABCDE approach, assessing and treating: A – Airway: Secure the airway B – Breathing: Provide oxygen if required. Salbutamol can help with wheezing. C – Circulation: Provide an IV bolus of fluids D – Disability: Lie the patient flat to improve cerebral perfusion E – Exposure: Look for flushing, urticaria and angio-oedema Once a diagnosis of anaphylaxis is established, there are three medications given to treat the reaction: Intramuscular adrenalin, repeated after 5 minutes if required Antihistamines, such as oral chlorphenamine or cetirizine Steroids, usually intravenous hydrocortisone After the Event All children should have a period of assessment and observation after an anaphylactic reaction, as biphasic reactions can occur, meaning they can have a second anaphylactic reaction after successful treatment of the first. Children should be admitted to the paediatric unit for observation. Anaphylaxis can be confirmed by measuring the serum mast cell tryptase within 6 hours of the event. Tryptase is released during mast cell degranulation and stays in the blood for 6 hours before gradually disappearing. Education and follow-up of the family and child is essential. They need to be educated about allergy, how to avoid allergens and how to spot the signs of anaphylaxis. Parents should be trained in basic life support. Specialist referral should be made in all children with anaphylaxis for diagnosis, education, follow up and training in how to use an adrenalin auto-injector.

Answer 361

Allergic rhinitis is a condition caused by an IgE-mediated type 1 hypersensitivity reaction. Environmental allergens cause an allergic inflammatory response in the nasal mucosa. It is very common and can significantly affect sleep, mood, hobbies, work and school performance and quality of life. Allergic rhinitis may be: - Seasonal, for example hay fever - Perennial (year round), for example house dust mite allergy - Occupational, associated with the school or work environment Presentation Allergic rhinitis typically causes: - Runny, blocked and itchy nose - Sneezing - Itchy, red and swollen eyes Allergic rhinitis is associated with a personal or family history of other allergic conditions (atopy). Diagnosis is usually made based on the history. Skin prick testing can be useful, particularly testing for pollen, animals and house dust mite allergy. Triggers - Tree pollen or grass allergy leads to seasonal symptoms (hay fever) - House dust mites and pets can lead to persistent symptoms, often worse in dusty rooms at night. Pillows can be full of house dust mites. - Pets can lead to persistent symptoms when the pet or their hair, skin or saliva is present - Other allergens lead to symptoms after exposure (e.g. mould)

Answer 362

Avoid the trigger. Hoovering and changing pillows regularly and allowing good ventilation of the home can help with house dust mite allergy. Staying indoors during high pollen counts can help with hay fever symptoms. Minimise contact with pets that are known to trigger allergies. Oral antihistamines are taken prior to exposure to reduce allergic symptoms: - Non-sedating antihistamines include cetirizine, loratadine and fexofenadine - Sedating antihistamines include chlorphenamine (Piriton) and promethazine Nasal corticosteroid sprays such as fluticasone and mometasone can be taken regularly to suppress local allergic symptoms. Nasal antihistamines may be a good option for rapid onset symptoms in response to a trigger. Referral to an immunologist may be necessary if symptoms are still unmanageable.

Answer 363

DiGeorge syndrome, also called 22q11.2 deletion syndrome, results from a microdeletion in a portion of chromosome 22 that leads to a developmental defect in the third pharyngeal pouch and third branchial cleft. One of the consequences of this is incomplete development of the thymus gland. An underdeveloped thymus gland results in an inability to create functional T cells. Features of DiGeorge syndrome can be remembered with the CATCH-22 mnemonic: C – Congenital heart disease A – Abnormal facies (characteristic facial appearance) T – Thymus gland incompletely developed C – Cleft palate H – Hypoparathyroidism and resulting Hypocalcaemia 22nd chromosome affected

Answer 364

Complement disorders affect the complement proteins that make up the complement system, which helps destroy pathogenic cells. Complement proteins are most important in dealing with encapsulated organisms, such as: - Haemophilus influenza B - Streptococcus pneumonia - Neisseria meningitidis Complement Deficiencies Deficiencies in complement proteins result in a vulnerability to certain infective organisms, leading to recurrent infections with these organisms. Complement deficiencies make children particularly susceptible to infections of the respiratory tract, ears and throat. Complement deficiencies are also associated with immune complex disorders, such as systemic lupus erythematous, as an incomplete complement cascade leads to immune complexes building up and being deposited in tissues, leading to chronic inflammation. C2 deficiency is the most common complement deficiency. Vaccination against encapsulated organisms is very important in patients with complement deficiencies.

Answer 365

Bradykinin is part of the inflammatory response. It is responsible for promoting blood vessel dilatation and increased vascular permeability, leading to angioedema. Part of the action of C1 esterase is to inhibit bradykinin. An absence of C1 esterase causes intermittent angioedema in response to minor triggers, such as viral infections or stress, or without any clear trigger at all. Angioedema often affects the lips or face but can occur anywhere on the body, including the respiratory and gastrointestinal tract. The swelling can last several few days before self resolving. Angioedema can occur in the larynx and compromise the patients airway. Patients can be treated with intravenous C-1 esterase inhibitor as prophylaxis before dental or surgical procedures or in response to acute attacks of angioedema. *A key test for hereditary angioedema (C1 esterase inhibitor deficiency) is to check the levels of C4 (compliment 4). C4 levels will be low in the condition. The exam question describe a patient with episodes of unexplained lip swelling and ask what test to perform. The answer is C4 levels.

Answer 366

The causative pathogens are recognised by macrophages, lymphocytes and mast cells. These cells release vast amounts of cytokines, such as interleukins and tumor necrosis factor, to alert the immune system to the invader. These cytokines activate other parts of the immune system. This immune activation leads to further release of chemicals such as nitrous oxide that causes vasodilation. The immune response causes inflammation throughout the body. Many of these cytokines cause the endothelial lining of blood vessels to become more permeable. This causes fluid to leak out of the blood into the extracellular space, leading to oedema and a reduction in intravascular volume. The oedema around blood vessels creates a space between the blood and the tissues, reducing the amount of oxygen that reaches the tissues. Activation of the coagulation system leads to deposition of fibrin throughout the circulation, further compromising organ and tissue perfusion. It also leads to consumption of platelets and clotting factors, as they are being used up to form the blood clots. This leads to thrombocytopenia, haemorrhages and an inability to form clots and stop bleeding. This is called disseminated intravascular coagulopathy (DIC). Blood lactate rises as a result of anaerobic respiration in the hypo-perfused tissues with an inadequate oxygen. A waste product of anaerobic respiration is lactate. Septic Shock Septic shock is diagnosed when sepsis has lead to cardiovascular dysfunction. The arterial blood pressure falls, resulting in organ hypo-perfusion. This leads to a rise in blood lactate as the organs begin anaerobic respiration. Septic shock should be treated aggressively with IV fluids to improve the blood pressure and tissue perfusion. If IV fluid boluses fail to improve the blood pressure and lactate level, children should be escalated to the high dependency or intensive care unit where medication called inotropes (such as noradrenalin) can be considered. Inotropes stimulate the cardiovascular system and improve blood pressure and tissue perfusion.

Answer 367

Kernig’s test Brudzinski’s test Kernig’s test involves lying the patient on their back, flexing one hip and knee to 90 degrees and then slowly straightening the knee whilst keeping the hip flexed at 90 degrees. This creates a slight stretch in the meninges. Where there is meningitis it will produce spinal pain or resistance to movement. Brudzinski’s test involves lying the patient flat on their back and gently using your hands to lift their head and neck off the bed and flex their chin to their chest. In a positive test this causes the patient to involuntarily flex their hips and knees.

Answer 368

The most common causes of viral meningitis are herpes simplex virus (HSV), enterovirus and varicella zoster virus (VZV). A sample of the CSF from the lumbar puncture should be sent for viral PCR testing. Viral meningitis tends to be milder than bacterial and often only requires supportive treatment. Aciclovir can be used to treat suspected or confirmed HSV or VZV infection.

Answer 369

Bacterial: Cloudy High protein Low glucose High neutrophils (polymorphs) Clear Mildly raised or normal protein Normal glucose High lymphocytes

Answer 370

Encephalitis means inflammation of the brain. This can be the result of infective or non-infective causes. Non-infective causes are autoimmune, meaning antibodies are created that target brain tissue. The most common cause is infection with a virus. Bacterial and fungal encephalitis is also possible although much more rare in the UK. The most common viral cause is herpes simplex virus (HSV). In children the most common cause is herpes simple type 1 (HSV-1) from cold sores. In neonates it is herpes simplex type 2 (HSV-2) from genital herpes, contracted during birth. Other viral causes include varicella zoster virus (VZV) associated with chickenpox, cytomegalovirus associated with immunodeficiency, Epstein-Barr virus associated with infectious mononucleosis, enterovirus, adenovirus and influenza virus. It is important to ask about vaccinations, as the polio, mumps, rubella and measles viruses can cause encephalitis as well.

Answer 371

Presentation Altered consciousness Altered cognition Unusual behaviour Acute onset of focal neurological symptoms Acute onset of focal seizures Fever Diagnosis Children with features of encephalitis need some key investigations to establish the diagnosis: Lumbar puncture, sending cerebrospinal fluid for viral PCR testing CT scan if a lumbar puncture is contraindicated MRI scan after the lumbar puncture to visualise the brain in detail EEG recording can be helpful in mild or ambiguous symptoms but is not always routinely required Swabs of other areas can help establish the causative organism, such as throat and vesicle swabs HIV testing is recommended in all patients with encephalitis Contraindications to a lumbar puncture include a GCS below 9, haemodynamically unstable, active seizures or post-ictal.

Answer 372

Management Intravenous antiviral medications are used to treat the suspected or confirmed underlying cause: Aciclovir treats herpes simplex virus (HSV) and varicella zoster virus (VZV) Ganciclovir treat cytomegalovirus (CMV) Repeat lumbar puncture is usually performed to ensure successful treatment prior to stopping antivirals Aciclovir is usually started empirically in suspected encephalitis until results are available. Other viral causes have no effective treatment and management is supportive. Followup, support and rehabilitation is required after encephalitis, with help managing the complications. - Complications of Encephalitis Lasting fatigue and prolonged recovery - Change in personality or mood - Changes to memory and cognition - Learning disability - Headaches - Chronic pain - Movement disorders - Sensory disturbance - Seizures - Hormonal imbalance

Answer 373

Infectious mononucleosis (IM) is a condition caused by infection with the Epstein Barr virus (EBV). It is commonly known as the “kissing disease”, “glandular fever” or “mono”. This virus is found in the saliva of infected individuals. Infection may be spread by kissing or by sharing cups, toothbrushes and other equipment that transmits saliva. EBV is secreted in the saliva of infected individuals and can be infectious several weeks before the illness begins and intermittently for the remainder of the patient’s life. Most people are infected with EBV as children, when it causes very few symptoms. When infection occurs in teenagers or young adults, it causes more severe symptoms. It is the symptomatic infection with EBV that is called infectious mononucleosis. Typical symptoms are fever, sore throat and fatigue. TOM TIP: Look out for the exam question that describes an adolescent with a sore throat, who develops an itchy rash after taking amoxicillin. Mononucleosis causes an intensely itchy maculopapular rash in response to amoxicillin or cefalosporins. Features Fever Sore throat Fatigue Lymphadenopathy (swollen lymph nodes) Tonsillar enlargement Splenomegaly and in rare cases splenic rupture

Answer 374

In certain diseases (such as HIV) we can test for specific antibodies to the disease. That way we know the body has come in contact with the disease and launched an immune response to it. In infectious mononucleosis, the body produces something called heterophile antibodies, which are antibodies that are more multipurpose and not specific to the EBV antigens. It takes up to 6 weeks for these antibodies to be produced. We can test for these heterophile antibodies using two tests: Monospot test: this introduces the patient’s blood to red blood cells from horses. Heterophile antibodies (if present) will react to the horse red blood cells and give a positive result. Paul-Bunnell test: this is similar to the monospot test but uses red blood cells from sheep. These tests are almost 100% specific for infectious mononucleosis, however not everyone who has IM produces heterophile antibodies, and it can take up to six weeks for the antibodies to be produced. Therefore they are only 70 – 80% sensitive. Specific Antibody Tests It is possible to test for specific EBV antibodies. These antibodies target something called viral capsid antigen (VCA): The IgM antibody rises early and suggests acute infection The IgG antibody persists after the condition and suggests immunity

Answer 375

Squint refers to misalignment of the eyes. It is is also known as strabismus. When the eyes are not aligned, the images on the retina do not match and the person will experience double vision. When this occurs in childhood, before the eyes have fully established their connections with the brain, the brain will cope with this misalignment by reducing the signal from the less dominant eye. This results in one eye they use to see (the dominant eye) and one eye they ignore (the “lazy eye”). If this is not treated, this “lazy eye” becomes progressively more disconnected from the brain and over time the problem becomes worse. This is called amblyopia. Concomitant squints are due to differences in the control of the extra ocular muscles. The severity of the squint can vary. Paralytic squints are rare. They are due to paralysis in one or more of the extra ocular muscles. Definitions Strabismus: the eyes are misaligned Amblyopia: the affected eye becomes passive and has reduced function compared to the other dominant eye Esotropia: inward positioned squint (affected eye towards the nose) Exotropia: outward positioned squint (affected eye towards the ear) Hypertropia: upward moving affected eye Hypotropia: downward moving affected eye

Answer 376

Causes Cases of squint in otherwise healthy children are usually idiopathic, meaning there is not a specific underlying cause. Other causes of squint include: Hydrocephalus Cerebral palsy Space occupying lesions, for example retinoblastoma Trauma Management Up until the age of 8 years the visual fields are still developing, therefore treatment needs to start before 8 years. The earlier the better. Delayed treatment increases the risk of the squint becoming permanent. An occlusive patch can be used to cover the good eye and force the weaker eye to develop. An alternative to the patch may involve using atropine drops in the good eye, causing vision in that eye to be blurred. Management is coordinated by an ophthalmologist. It will be important to treat any underlying pathology, such as cataracts. Refractive errors can be corrected with corrective lenses.

Answer 377

Craniosynostosis occurs when the skull sutures close prematurely. This results in abnormal head shapes and restriction to the growth of the brain. If left untreated it will lead to raised intracranial pressure, with resulting symptoms of developmental delay, cognitive impairment, vomiting, irritability, visual impairment, neurological symptoms and seizures. Investigations Where there are suspicions about craniosynostosis the patient should be referred to a specialist for further investigations. The first line investigation is a skull xray. CT head with bone views is used to confirm the diagnosis or exclude it if there is doubt on the xray. Management Mild cases may be monitored and followed up over time. More severe cases require surgery for surgical reconstruction of the skull. The prognosis is usually good with proper management. They will have a lifelong scar on the scalp where the surgery was performed.

Answer 378

Diabetic ketoacidosis occurs in type 1 diabetes, where the person is not producing adequate insulin themselves and is not injecting adequate insulin to compensate for this. It occurs when they body does not have enough insulin to use and process glucose. The main problems are ketoacidosis, dehydration and potassium imbalance. Ketoacidosis When the cells in the body have no fuel and think they are starving, they initiate the process of ketogenesis so they have a usable fuel. Over time the glucose and ketone levels get higher and higher. Initially the kidneys produce bicarbonate to buffer the ketone acids in the blood and maintain a normal pH. Over time the ketone acids use up the bicarbonate and the blood starts to become acidic. This is called ketoacidosis. Dehydration Hyperglycaemia overwhelms the kidneys and glucose starts being filtered into the urine. The glucose in the urine draws water out with it in a process called osmotic diuresis. This causes the patient to urinate a lot (polyuria). This results in severe dehydration. The dehydration stimulates the thirst centre to tell the patient to drink lots of water. This excessive thirst is called polydipsia. Potassium Imbalance Insulin normally drives potassium into cells. Without insulin, potassium is not added to and stored in cells. Serum potassium can be high or normal in diabetic ketoacidosis, as the kidneys continue to balance blood potassium with the potassium excreted in the urine, however total body potassium is low because no potassium is stored in the cells. When treatment with insulin starts, patients can develop severe hypokalaemia (low serum potassium) very quickly, and this can lead to fatal arrhythmias. The most dangerous aspects of DKA are dehydration, potassium imbalance and acidosis. These are what will kill the patient. Therefore the priority is fluid resuscitation to correct the dehydration, electrolyte disturbance and acidosis. This is followed by an insulin infusion to allow the cells to start taking up and using glucose and stop producing ketones. Cerebral Oedema Children with DKA are at high risk of developing cerebral oedema. Dehydration and high blood sugar concentration cause water to move from the intracellular space in the brain to the extracellular space. This causes the brain cells to shrink and become dehydrated. Rapid correction of dehydration and hyperglycaemia (with fluids and insulin) causes a rapid shift in water from the extracellular space to the intracellular space in the brain cells. This causes the brain to swell and become oedematous, which can lead to brain cell destruction and death. Neurological observations (i.e. GCS) should be monitored very closely (e.g. hourly) to look for signs of cerebral oedema. Be concerned when patients being treated for diabetic ketoacidosis develop headaches, altered behaviour, bradycardia or changes to consciousness. Management options for cerebral oedema are slowing IV fluids, IV mannitol and IV hypertonic saline. These should be guided by an experienced paediatrician.

Answer 379

Follow local treatment protocols and involve senior paediatricians. The two pillars of correcting DKA are: Correct dehydration evenly over 48 hours. This will correct the dehydration and dilute the hyperglycaemia and the ketones. Correcting it faster increases the risk of cerebral oedema. Give a fixed rate insulin infusion. This allows cells to start using glucose again. This in turn switches off the production of ketones. Other important principles: Avoid fluid boluses to minimise the risk of cerebral oedema, unless required for resuscitation. Treat underlying triggers, for example with antibiotics for septic patients. Prevent hypoglycaemia with IV dextrose once blood glucose falls below 14mmol/l. Add potassium to IV fluids and monitor serum potassium closely. Monitor for signs of cerebral oedema. Monitor glucose, ketones and pH to assess their progress and determine when to switch to subcutaneous insulin.

Answer 380

21-hydroxylase is the enzyme responsible for converting progesterone into aldosterone and cortisol. Progesterone is also used to create testosterone, but this conversion does not rely on the 21-hydroxylase enzyme. In CAH, there is a defect in the 21-hydroxylase enzyme. Therefore, because there is extra progesterone floating about that cannot be converted to aldosterone or cortisol, it gets converted to testosterone instead. The result is a patient with low aldosterone, low cortisol and abnormally high testosterone.

Answer 381

Growth hormone is produced by the anterior pituitary gland. It is responsible for stimulating cell reproduction and the growth of organs, muscles, bones and height. It stimulates the release of insulin-like growth factor 1 (IGF-1) by the liver, which is also important in promoting growth in children and adolescents. Congenital growth hormone deficiency results from a disruption to the growth hormone axis at the hypothalamus or pituitary gland. It can be due to a known genetic mutation such as the GH1 (growth hormone 1) or GHRHR (growth hormone releasing hormone receptor) genes, or due to another condition such as empty sella syndrome where the pituitary gland is under-developed or damaged. Acquired growth hormone deficiency can be secondary to infection, trauma or interventions such as surgery. Growth hormone deficiency can occur in isolation or in combination with other pituitary hormone deficiencies like hypothyroidism, adrenal insufficiency and deficiencies of the gonadotrophins (LH and FSH). When the pituitary does not produce a number of pituitary hormones this is called hypopituitarism or multiple pituitary hormone deficiency.

Answer 382

Presentation Growth hormone deficiency may present at birth or in neonates with: Micropenis (in males) Hypoglycaemia Severe jaundice Older infants and children can present with: Poor growth, usually stopping or severely slowing from age 2-3 Short stature Slow development of movement and strength Delayed puberty Investigations Investigation, diagnosis and management will be made by specialists in paediatric endocrinology. Growth hormone stimulation test: Growth hormone stimulation tests involve measuring the response to medications that normally stimulate the release of growth hormone. Examples of these medications include glucagon, insulin, arginine and clonidine. Growth hormone levels are monitored regularly for 2-4 hours after administering the medication to assess the hormonal response. In growth hormone deficiency there will be a poor response to stimulation. Other investigations: Test for other associated hormone deficiencies, for example thyroid and adrenal deficiency MRI brain for structural pituitary or hypothalamus abnormalities Genetic testing for associated genetic conditions such as Turner syndrome and Prader–Willi syndrome Xray (usually of the wrist) or a DEXA scan can determine bone age and help predict final height

Answer 383

Children with growth hormone deficiency will be managed and followed up by a paediatric endocrinologist. Daily subcutaneous injections of growth hormone (somatropin) Treatment of other associated hormone deficiencies Close monitoring of height and development

Answer 384

Congenital hypothyroidism is where the child is born with an underactive thyroid gland. This occurs in around 1 in 3000 newborns. It can be the result of an underdeveloped thyroid gland (dysgenesis) or a fully developed gland that does not produce enough hormone (dyshormonogenesis). Very rarely it can be the result of a problem with the pituitary or hypothalamus. This usually occurs without any other problems and the cause is not clear. Congenital hypothyroidism is screened for on the newborn blood spot screening test. Where it is not picked up a birth, patients can present with: Prolonged neonatal jaundice Poor feeding Constipation Increased sleeping Reduced activity Slow growth and development

Answer 385

Acquired hypothyroidism is where a child or adolescent develops an underactive thyroid gland when previously it was functioning normally. The most common cause of acquired hypothyroidism is autoimmune thyroiditis, also known as Hashimoto’s thyroiditis. This causes autoimmune inflammation of the thyroid gland and subsequent under activity of the gland. It is associated with antithyroid peroxidase (anti-TPO) antibodies and antithyroglobulin antibodies. There is an association with other autoimmune conditions, particularly type 1 diabetes and coeliac disease. This can lead to symptoms of: Fatigue and low energy Poor growth Weight gain Poor school performance Constipation Dry skin and hair loss

Answer 386

Children will be managed and followed up by a paediatric endocrinologist. Investigations include full thyroid function blood tests (TSH, T3 and T4), thyroid ultrasound and thyroid antibodies. Levothyroxine orally once a day is used to replace the normal thyroid hormones. Doses are titrated based on thyroid function tests and symptoms.

Answer 387

Inadequate Nutritional Intake: Maternal malabsorption if breastfeeding Iron deficiency anaemia Family or parental problems Neglect Availability of food (i.e. poverty) Difficulty Feeding: Poor suck, for example due to cerebral palsy Cleft lip or palate Genetic conditions with an abnormal facial structure Pyloric stenosis Malabsorption: Cystic fibrosis Coeliac disease Cows milk intolerance Chronic diarrhoea Inflammatory bowel disease Increased Energy Requirements: Hyperthyroidism Chronic disease, for example congenital heart disease and cystic fibrosis Malignancy Chronic infections, for example HIV or immunodeficiency Inability to Process Nutrients Properly: Inborn errors of metabolism Type 1 diabetes

Answer 388

The aim of assessment is to establish the cause of the failure to thrive. This involves taking a full history, examining the child and completing relevant investigations. Key areas need to be assessed: Pregnancy, birth, developmental and social history Feeding or eating history Observe feeding Mums physical and mental health Parent-child interactions Height, weight and BMI (if older than 2 years) and plotting these on a growth chart Calculate the mid-parental height centile A feeding history involves asking about breast or bottle feeding, feeding times, volume and frequency and any difficulties with feeding. An eating history involves asking about food choices, food aversion, meal time routines and appetite in children. Asking the parent to keep a food diary can be helpful. BMI is calculated as: (weight in kg) / (height in meters)2. Mid parental height is calculated as: (height of mum + height of dad) / 2. Outcomes from the assessment that would suggest inadequate nutrition or a growth disorder are: Height more than 2 centile spaces below the mid-parental height centile BMI below the 2nd centile

Conditions Flashcards

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