JHON MURTAGH Flashcards
Peak age incidence 10–30 years >40 years
Clinical differentiation between type 1 and type 2 diabetes
Age of onset
Usually young <20
Usually middle-aged >40
Clinical differentiation between type 1 and type 2 diabetes
Onset
Rapid
Insidious/slow
Clinical differentiation between type 1 and type 2 diabetes
___________ is also known as juvenile onset diabetes or insulin dependent diabetes mellitus
(IDDM).
Type 1
________ is also known as maturity onset diabetes or non-insulin dependent diabetes mellitus
(NIDDM).
Type 2
Type 1 has an autoimmune causation which is also responsible for a late-onset form known as
_______________________
late onset autoimmune diabetes in adults (LADA).
Drug-induced diabetes (transient)
Thiazide diuretics
Oestrogen therapy (high dose—not with low-dose HRT)
Corticosteroids
In Australians older than 25 years the prevalence of diabetes is __________, with
another 10.6% having impaired glucose tolerance
7.5%
About 30% of those with impaired glucose tolerance will develop clinical diabetes
within ________
10 years
Many people with type 2 diabetes are ______
asymptomatic
___________ may be temporarily elevated during acute illness, after trauma or
surgery.
Blood glucose
The classic symptoms of uncontrolled diabetes are:
polyuria polydipsia loss of weight (type 1) tiredness and fatigue propensity for infections, especially of the skin and genitals (vaginal thrush)
DxT thirst + polyuria + weight loss →
The young person with type 1 diabetes
Symptoms of complications (may be presenting feature) include:
staphylococcal skin infections
polyneuropathy: tingling or numbness in feet, pain (can be severe if present)
impotence
arterial disease: myocardial ischaemia, peripheral vascular disease
The young person with type 1 diabetes
Examination
The physical examination should ideally follow the protocol for annual review.
Initial screening for suspected diabetes should include:
general inspection, including skin
BMI (weight/height)
waist circumference
visual acuity
diabetes
blood pressure—lying and standing
test for peripheral neuropathy: tendon reflexes, sensation (e.g. cotton wool, 10 g
monofilament, Neurotips)
urinalysis: glucose, albumin, ketones, nitrites
diabetes
Initial: fasting or random blood sugar, follow-up oral glucose tolerance test (OGTT) or glycated haemoglobin (HbA1c) if indicated Other tests according to clinical assessment (e.g. lipids, kidney function, urine albumin– creatinine ratio (ACR), ECG)
diabetes
Age >40 years
Family history
Overweight/obesity
Sedentary lifestyle
History of gestational diabetes, pancreatitis
Women with polycystic ovarian syndrome (PCOS)
Hypertension/ischaemic heart disease
Medication causing hyperglycaemia
Ethnic/cultural groups: Aboriginal and Torres Strait Islanders, Pacific Islanders, people from
Indian subcontinent, Chinese, Afro-Caribbeans
Risk factors for DIABETES
People with known impaired fasting glucose/glucose tolerance (‘prediabetes’)
Age >40 years, or younger age (e.g. >30 years) with: family history (first-degree relative with
T2D), obesity (BMI >30), high-prevalence ethnic groups
Age >18 years in Aboriginal and Torres Strait Islander people
Previous gestational diabetes
People on long-term steroids or antipsychotics
Screening (type 2)
Polycystic ovarian syndrome, especially if overweight
Previous cardiovascular event
Screening (type 2)
The optimal frequency is every 3 years from age 40 years using AUSDRISK
Screening (type 2)
If score ≥12, do fasting blood glucose or
HbA1c. Screen annually in very high-risk groups, including Aboriginal and Torres Strait Islander
people and those with ‘prediabetes’.5
Screening (type 2)
If symptomatic (at least two of polydipsia, polyuria, frequent skin infections or frequent
genital thrush):
fasting venous blood glucose (VBG) ≥7.0 mmol/L
or
random VBG (at least 2 hours after last eating) ≥11.1 mmol/L
or
HbAIc >____________
6.5% (>48 mmol/mol)
If asymptomatic:
at least two separate elevated values, either fasting, 2 or more hours postprandial, or the two
values from ____________________________
an oral glucose tolerance test (OGTT)
If random or fasting VBG lies in an uncertain range (5.5–11.0 mmol/L) in either a
symptomatic patient or a patient with risk factors (over 50 years, overweight, firstdegree
relative with T2D), perform ___________________.
an OGTT
The 2-hour blood sugar on an OGTT is still the gold standard for the diagnosis of uncertain
diabetes, i.e. ____________________
> 11.1 mmol/L.
The OGTT should be reserved for true borderline cases and for diagnosing gestational diabetes,
where a 75 mg OGTT is recommended at _____________________________
24–28 weeks’ gestation
Diabetic ulcer, allergic to penicillin, debridement done. Next?allergic to pencillin so can’t give ________________
Ticarcillin is an extended-spectrum penicillin
Elderly pt with “painful bones, renal stones, abdominal groans, and psychic moans
Hyperparathyroidism
This is the condition where the VPG is elevated above the normal range (i.e. 6.1–6.9) but does
not satisfy the type 2 diagnostic criteria.
Prediabetes
This is the condition where the VPG is elevated above the normal range (i.e. 6.1–6.9) but does
not satisfy the type 2 diagnostic criteria. It includes two states:
impaired fasting glucose (IFG)
impaired glucose tolerance (IGT)
A diagnosis of prediabetes is not a call to start medication, but it increases the urgency of
promoting lifestyle changes such as weight reduction and ______________________.
increased physical activity
______________is unreliable in diagnosis since glycosuria occurs at different plasma glucose values in
patients with different kidney thresholds.
Urinalysis
Venous blood glucose concentration fasting up to 6 mmol/L
Normal
Venous blood glucose concentration fasting up to 6.1–6.9 mmol/L
Intermediate
hyperglycaemia
Venous blood glucose concentration fasting up to ≥7 mmol/L
Diabetes
Venous blood glucose concentration random up to 6 mmol/L
Normal
Venous blood glucose concentration random up to ≥11.1 mmol/L
Diabetes
Oral glucose tolerance test 2-hour venous blood glucose concentration up to 7.7 mmol/L
Normal
Oral glucose tolerance test 2-hour venous blood glucose concentration up to 7.8–11 mmol/L
Intermediate
hyperglycaemia
Oral glucose tolerance test 2-hour venous blood glucose concentration up to 7.8–11 mmol/L
≥11.1 mmol/L
HbA1c ≥48 mmol/mol (
Gestational diabetes is the new onset of abnormal glucose tolerance during ___________.
pregnancy
Pregnancy is diabetogenic for those with a genetic predisposition
Gestational diabetes
All pregnant women should be
screened at 24–28 weeks with _________________
a 75 g oral glucose tolerance test (OGTT).
gestational diabetes is a fasting plasma glucose of
≥5.1 mmol/L, or a post-75 g oral glucose load at 1 hour ≥10.0, or at 2 hours _____________
8.5–11.0
The incidence of diabetes rises with _________
age
On day discharge FBS
OGTT at 6-12 weeks
If normal then _____________
3 yearly FBS
Prevention of CAD in DM patients include control of BP, Blood sugar and LDL, AceI/Arbs in high risk and ___________________
smoking cessation
Meticulous foot care is very important in _____________
diabetic patients
IgA-TG2 (immunoglobulin A-tissue transglutaminase 2) antibody is the preferred single test for ___________ at any age. Concurrently measure total IgA level with serology testing to determine whether IgA levels are sufficient.
CD detection
Most common cause of secondary PPH
Retained products of conception
because gdm cause macrosomia and prolonged labour may result in cervical laceration and __________________
traumatic birth
This is a secondary post-partum bleeding and cannot possibly be from cervical laceration. Moreover, the presence of blood clots suggests it is ___________________
intrauterine bleeding.
because ulcer is localised and not severe.
In severe case( systemic involvement) __________________
I/v ticarcillin.
for deep and non-healing wound, do MRI to exclude osteomyelitis first, then tx with _______________
antibiotics
Says 3 mm deep ulcer is an indication for further evaluation for osteomyelitis. Here,the Q says purulent ulcer,non healing and 1 cm DEEP. So no doubt the next mx will be ______________.
MRI
rifampicin is enzyme inducer it will decrease efficacy ,rifampicin and ____________pill
contraceptive
poorly controlled sugar levels in the mother leads to hyperglycaemia in the fetus, which causes more release of Insulin, IGFs and Growth Hormone in the fetus and hence there’s more adipose deposition and ___________.
Macrosomia
The mainstay of treatment in diabetic patients with new onset proteinuria to aggressively control blood pressure, ideally below 130/80 mmHg. _________________ are therefore first-line therapy, angiotensin receptor blockers
can also be used.
ACE inhibitors (D)
ischaemic/coronary heart disease
cerebrovascular disease
peripheral vascular disease
Macrovascular complications include:
death (24%) myocardial infarction (22%) stroke (33%) cardiovascular death (37%) overt nephropathy (24%)
An analysis of type 2 diabetes in the HOPE study12,13 showed a benefit of ramipril to reduce the
risk of:
Kidney Nerves Infection Vessels Eyes Skin
Consider organs/problems affected by diabetes under the mnemonic ‘KNIVES’:
The small vessels most affected from a clinical viewpoint are the retina, nerve sheath and kidney
glomerulus. In younger people it takes about 10 to 20 years after diagnosis for the problems of
diabetic retinopathy, neuropathy and nephropathy to manifest.
Microvascular disease
Prevention of diabetic nephropathy is an essential goal of treatment. Early detection of the
yardstick, which is microalbuminuria, is important as the process can be reversed with optimal
control, particularly of _____________________
blood pressure.
The dipstick method is unreliable and the preferred
hospital method of 24-hour urine collection is considered impractical in general practice
diabetic nephropathy
Screening is done simply by a first morning urine sample to determine the albumin–creatinine
ratio
diabetic nephropathy
ACE inhibitors (or angiotensin II receptor blockers if a cough develops) should be used for evidence of hypertension.
diabetic nephropathy
Retinopathy develops as a consequence of ________________disease of the retina
microvascular
Assessment of the fundus by an expert is recommended every 1–2 years, via direct
ophthalmoscopy (with dilated pupils), retinal photography or, if necessary, fluorescein
angiography.
Retinopathy and maculopathy
Early diagnosis of serious retinopathy is vital since the early use of laser
photocoagulation may delay and prevent ________________
visual loss.
radiculopathy (diabetic lumbosacral radiculoplexopathy)
sensory polyneuropathy
isolated or multiple mononeuropathy
isolated peripheral nerve lesions (e.g. median nerve)
cranial nerve palsies (e.g. III, VI)
amyotrophy
diabetic Neuropathy
autonomic neuropathy, which may lead to:
erectile dysfunction
postural hypotension and syncope
impaired gastric emptying (gastroparesis)
diabetic Neuropathy
diarrhoea
delayed or incomplete bladder emptying
loss of cardiac pain → ‘silent’ ischaemia
hypoglycaemic ‘unawareness’
sudden arrest, especially under anaesthetic
diabetic Neuropathy
skin: mucocutaneous candidiasis (e.g. balanitis, vulvovaginitis), staphylococcal infections (e.g.
folliculitis)
poorly controlled diabetes
urinary tract: cystitis (women), pyelonephritis and perinephric abscess
poorly controlled diabetes
lungs: pneumonia (staphylococcal, streptococcal pneumonia), tuberculosis
poorly controlled diabetes
Hypoglycaemia
Diabetic ketoacidosis
Hyperosmolar hyperglycaemia
Lactic acidosis
Diabetic metabolic complications
Cataracts Refractive errors of eye Sleep apnoea Depression Musculoskeletal: neuropathic joint damage (Charcot-type arthropathy), tendon rupture Foot ulcers (related to neuropathy)
Diabetic complications
intensive lifestyle intervention in individuals who are
overweight with impaired glucose tolerance or raised fasting blood glucose
Prevention of diabetes
reduction of ‘lifestyle’ risks—weight, smoking, low physical activity
Management of diabetes
strict glycaemic control as measured by HbA1c (target varies with circumstance, but usually
≤7%)
Management of diabetes
blood pressure control (≤140/90 mmHg, lower if tolerated)
Management of diabetes
control of blood lipid levels
Management of diabetes
four times a day (before meals and before bedtime) at first and for problems
twice a day (at least once)
may settle for 1–2 times a week (if good control)
Blood glucose monitoring at home
Type 1 diabetes
important for those on insulin, not routinely recommended for oral medication (monitor
with HbA1c instead, in most circumstances)
more useful for pregnant women, frail elderly, heavy machinery operators or symptomatic
hypoglycaemia
Blood glucose monitoring at home
Type 2 diabetes
which normally comprises 4–6% of the total haemoglobin, is abnormally abundant in
those with persistent hyperglycaemia, reflecting suboptimal metabolic control.
HbA1c,
__________________have a long half-life and their measure reflects the mean plasma glucose
levels over the past 2–3 months and hence provides a good method of assessing overall diabetes
management.
Glycohaemoglobins
__________ should be checked every 3–6 months
HbA1c
rapid-acting and short duration (ultra-short)
insulin lispro, insulin aspart
short-acting—neutral
regular, soluble
intermediate-acting
isophane (NPH) or lente
long-acting
ultralente, insulin detemir, insulin glargine
diet therapy
exercise program
weight loss
Type 2 diabetes
First-line treatment
Most symptoms improve within 1–4 weeks on diet and exercise
Type 2 diabetes
First-line treatment
If unsatisfactory control persists after 3–6 months, consider adding an oral
hypoglycaemic agent
Type 2 diabetes
First-line treatment
The usual first-line agent is metformin, which reduces
_________________.
insulin resistance
If glycaemic targets are not achieved on monotherapy, usual practice is to add
in a secretagogue, such as a sulfonylurea, which increases _____________________
insulin production
newer agents SGLT2 inhibitors (the gliflozins) and GLP-1 receptor agonists (injected) should be
considered for their ___________________________
cardioprotective and renoprotective effects
12 (also slowrelease daily dosage) 0.5–3 g Side effects: GIT disturbances (e.g. diarrhoea, a/n/v)
Metformin
a biguanide
Hypoglycaemia
most common side
effect
Gliclazide
Dubious mortality
benefit. Caution with
heart failure.
Thiazolidinediones
glitazones
Oedema, weight
gain, heart failure
Thiazolidinediones
glitazones
horners syndrome triad includes ptosis,anhidrosis,miosis .It is associated with
pancoast tumor
___________ should be painless haematuria
Bladder Ca
Precipitating factor insulin insufficient, interrupted insulin therapy, infection,infection, stress, alcohol
DkA
If no thyroid swelling but features of hyperthyroidism then __________ first then RIU scan.
TSH-R Ab
Multiple myeloma is present with fatigue lethargy and ______________
hypercalcemia
indepamide cause __________ work as diuretics
hyponatramia
indapamide causing
Hyponatremia results in ____________
confusion
Hypoglycaemia is theoretically defined as blood glucose falling below __________
4.0 mmol/L
Classic warning symptoms: sweating, tremor, palpitations, hunger, peri-oral paraesthesia
Hypoglycaemia
30 mL 50% glucose slow IV push
Treatment (reduced conscious state or unconscious)
Usually 10 mL in children. 50% glucose slow IV push
Treatment (reduced conscious state or unconscious)
This life-threatening emergency requires intensive management. It usually occurs during an
illness (e.g. gastroenteritis) when insulin is omitted. It can also occur in type 2 diabetes.
Diabetic ketoacidosis24
Develops over a few days, but may occur in a few hours in ‘brittle’ diabetics
Diabetic ketoacidosis
Hyperglycaemia (often >20 mmol/L, lower or normal if on SGLT2 inhibitor)
Diabetic ketoacidosis
Preceded by polyuria, polydipsia, drowsiness
Diabetic ketoacidosis
Vomiting and abdominal pain, dehydration
Diabetic ketoacidosis
Hyperventilation—severe acidosis (acidotic breathing): ↓BP, ↑pulse, ↑resp. rate
Diabetic ketoacidosis
Ketosis (blood and urine)
Diabetic ketoacidosis
Arrange urgent hospital admission
Diabetic ketoacidosis
Early IV fluids—normal saline fast first litre, then caution
Diabetic ketoacidosis
IV insulin—slow, e.g. 10 U in first hour
Diabetic ketoacidosis
ECG—arrhythmia in electrolyte disturbances
Diabetic ketoacidosis
Diabetic ketoacidosis with __________requires fluid, sodium (eventually 3 L N saline), potassium
(KCl) and insulin.
coma
People with this problem may present with an altered conscious state varying from stupor to
coma and with marked dehydration
Hyperosmolar hyperglycaemia
The onset may be insidious over a period of weeks, with
fatigue, polyuria and polydipsia.
Hyperosmolar hyperglycaemia4
The key features are marked hyperglycaemia and dehydration without ketoacidosis
Hyperosmolar hyperglycaemia4
It occurs typically in uncontrolled type 2 diabetes, especially in elderly
patients.
Hyperosmolar hyperglycaemia4
There may be evidence of an
underlying disorder such as pneumonia or a urinary infection
Hyperosmolar hyperglycaemia4
The essential findings are extreme
hyperglycaemia and high plasma osmolarity
Hyperosmolar hyperglycaemia4
The condition has a high mortality—even higher
than ketoacidosis.
Hyperosmolar hyperglycaemia4
IV fluids, e.g. normal to ½ normal saline, given slowly
Insulin—relatively lower doses than acidosis
Hyperosmolar hyperglycaemia4
Patients with ____________ present with marked hyperventilation ‘air hunger’ and confusion
lactic acidosis
has a high mortality rate and must be considered in the very ill person taking metformin,
especially if kidney function is impaired
Lactic acidosis
Investigations reveal blood acidosis (low pH), low bicarbonate,
high serum lactate, absent serum ketones and a large anion gap
Lactic acidosis
Treatment is based on removal
of the cause, rehydration and alkalinisation with IV sodium bicarbonate
Lactic acidosis
The prevalence of erectile dysfunction in men with type 2 diabetes over 40 years may be as high
as __________. It may be caused by macrovascular disease, pelvic autonomic neuropathy or
psychological causes.
50%
Autonomic ___________-related postural hypotension may be compounded by medication,
including antihypertensives and anti-angina agents.
neuropathy
Symptoms of gastroparesis (due to autonomic neuropathy) with decreased gastric emptying
include a sensation of fullness, dysphagia, reflux or recurrent nausea and vomiting, especially
________________.
after meals
Treatment options include medication with domperidone, cisapride or erythromycin
Gastroparesis
Injections of botulinum toxin type A into the pylorus via gastroscopy may facilitate gastric
emptying.
Gastroparesis
In general terms, people controlled by diet alone have no restrictions
for driving whereas those on ____________may obtain a conditional licence subject to annual or 2-
yearly review.
insulin
Long-acting reversible contraceptives (e.g. Implanon, Mirena) or the combined oral
contraceptive pill are appropriate options for birth control in women not interested in permanent
sterilisation. Bear in mind the possibility of polycystic ovarian syndrome
Contraception IN DIATEICS
requires specialist evaluation and then 1- to 2-yearly review
Type 1 diabetes
For _____________screening: every 2 years to inspect retina (or use retinal photography)
ophthalmological
Many cases of type 2 diabetes remain _____________, so vigilance is important.
undiagnosed
__________is a common cause of tiredness. If elderly people with type 2
diabetes are very tired, think of _____________
Hyperglycaemia
If a person with diabetes (particularly type 1) is very drowsy and looks sick,
consider first the diagnosis of ______________
ketoacidosis
__________ is vital: always examine the feet when the person comes in for review
Foot care
Treat associated hypertension with ACE inhibitors or a calcium-channel blocker
(also good in combination).
DIABETES
‘Never let the sun go down on pus in a diabetic foot’—______________
admit to hospital
If a foot ulcer hasn’t healed in 6 weeks, exclude osteomyelitis. Arrange for __________
and investigate the vasculature.
an MRI
Diabetes control: _____-monthly review
3
hyperuricaemia due to
thiazide diuretics
___________________________, which should be used in conjunction with an educational
support program, has been proved to be effective and is available as chewing gum, inhaler, oral
spray, lozenges, sublingual tablets or transdermal patches (the preferred method). Ideally the
nicotine should not be used longer than 3 months
Nicotine replacement therapy (NRT)
This oral agent has a similar effectiveness to NRT.
Bupropion (Zyban)
Adverse effects include insomnia and dry mouth (both common), with serious effects, such as
allergic reactions and increased seizure risk.7 It is contraindicated in persons with a history of
epilepsy.
Recommended dose: 150 mg (o) daily for 3 days then bd for 12 weeks.
Bupropion (Zyban)
It is an effective agent but there are several adverse side effects, especially nausea with a concern
about neuropsychiatric effects
Varenicline tartrate
serum _________: elevated in chronic drinkers (returns to normal with cessation of intake)
GGT
abnormal liver function tests (other than GGT)
alcohol
__________________-deficient transferrin (quite specific—dependent on an enzyme induced by
alcohol)
carbohydrate
is a serious life-threatening withdrawal state. It has a high mortality rate if inadequately
treated and hospitalisation is always necessary.
Alcohol withdrawal delirium (delirium tremens)
May be precipitated by intercurrent infection or trauma
1–5 days after withdrawal (usually 3–4 days)
Disorientation, agitation
Clouding of consciousness
Marked tremor
Visual hallucinations (e.g. spiders, pink elephants)
Sweating, tachycardia, pyrexia
Signs of dehydration
Alcohol withdrawal delirium (delirium tremens)
Hospitalisation with alcohol specialist advisory service
Correct fluid and electrolyte imbalance with IV therapy
Treat any systemic infection
Thiamine (vitamin B1) 300 mg IM or IV daily for 3–5 days, then thiamine 300 mg (o) daily
Diazepam 20 mg (o) every 2 hours (up to max. 100 mg daily)
Alcohol withdrawal delirium (delirium tremens)
Chlorpromazine is not recommended because of its potential to lower seizure threshold.
Diazepam and haloperidol may worsen the symptoms of hepatic toxicity
Alcohol withdrawal delirium (delirium tremens)
Overdose is potentially fatal. The average lethal blood alcohol concentration is about 0.45–0.5%.
Alcohol overdose
Loss of appetite, nausea (possibly vomiting) Lacrimation/rhinorrhoea Tiredness/insomnia Muscle aches and cramps Abdominal colic Diarrhoea
Opioid withdrawal effects19,20
Maximum withdrawal symptoms
usually occur between 36 and 72 hours and tend to subside after 10 days
Opioid withdrawal effects19,20
Buprenorphine controlled withdrawal (short term) is used to prevent the emergence of a
withdrawal syndrome
Opioid withdrawal
In Australia, most people with anaemia will have ___________ ranging from up
to 5% for children to 20% for menstruating females
iron deficiency
The remainder will mainly have anaemia of ______________
chronic disorders
probably the best test to monitor iron-deficiency anaemia
The serum ferritin level, which is low in cases of iron-deficiency anaemia
DxT fatigue + palpitations + exertional dyspnoea →
anaemia
tiredness/fatigue muscle weakness headache and tinnitus lack of concentration faintness/dizziness dyspnoea on exertion palpitations angina on effort intermittent claudication pica—usually brittle and crunchy food
anaemia
inadequate diet, pregnancy, GIT loss, menorrhagia, NSAID and anticoagulant
ingestion
iron deficiency
inadequate diet especially with pregnancy and alcoholism, small bowel
disease
folate deficiency
previous gastric surgery, ileal disease or surgery, pernicious anaemia, selective diets (e.g. vegetarian, fad)
vitamin B12 deficiency
abrupt onset anaemia with mild jaundice
haemolysis
MCV ≤ 80 fL
microcytic
MCV >100 fL
macrocytic
MCV 80–100 fL
normocytic
Iron deficiency
Thalassaemia
Anaemia of chronic disease
Sideroblastic anaemia
Microcytic (MCV < 80 fL)
Vitamin B12 deficiency Folate deficiency Myelodysplastic disorders Cytotoxic drugs Liver disease/alcoholism
Microcytic (MCV > 100 fL)
Kidney disease Anaemia of chronic disease Endocrine failure/hypothyroidism Haemolysis Aplastic anaemia
Normocytic (MCV 80–100 fL)
Microcytic anaemia Serum ferritin level low (NR: F 15–200 mcg/L: M 30–300 mcg/L) Serum iron level low Increased transferrin level Microcytic hypochromic red cells MCV ↓, MCH ↓, MCHC ↓ Reduced transferrin saturation Response to iron therapy
Iron-deficiency anaemia3
Angular cheilosis/stomatitis Glossitis Oesophageal webs Atrophic gastritis Brittle nails and koilonychias
Non-haematological effects of chronic iron deficiency
Menorrhagia Gastrointestinal bleeding (e.g. carcinoma, haemorrhoids, peptic ulcer, hiatus hernia, GORD,NSAID therapy) Frequent blood donations Malignancy Hookworm (common in tropics)
iron deficiency Causes1
Microcytic, hypochromic red cells
Anisocytosis (variation in size), poikilocytosis (shape)—pencil-shaped rods
Low serum iron level
Raised iron-binding capacity
Serum ferritin level low (the most useful index)
Haematological investigations:
Oral iron is continued for __________ months to replenish stores.
3 to 6
significant microcytosis quite out
of proportion to the normal Hb or slight anaemia, and confirmed by finding a raised HbA2 on Hb
electrophoresis.
diagnosis of heterozygous thalassaemia minor
Treatment of ______________ is transfusion to a high normal Hb with packed cells plus
desferrioxamine.
thalassaemia major
Each individually, or in combination, leads to macrocytosis with or without anaemia
Alcohol and liver disease
It is usually caused by lack of intrinsic factor due to autoimmune atrophic changes
and by gastrectomy
Vitamin B12 deficiency pernicious anaemia
is found in the normal diet but only in foods of animal origin and
consequently very strict vegetarians may eventually develop deficiency.
Vitamin B12 (cobalamin)
atrophic gastritis H. pylori infection H2 receptor blockers PPI drugs other drugs, e.g. OCP, metformin chronic alcoholism HIV strict vegan diet
Causes of food vitamin
B12 deficiency are
The main cause is poor intake associated with old age, poverty and malnutrition, usually
associated with alcoholism. It may be seen in malabsorption and regular medication with antiepileptic
drugs such as phenytoin
Folic acid deficiency
Oral __________5 mg/day to replenish body stores (5–10 mg). This takes about 4 weeks but continue
for 4 months.
folate
This is the most common cause of normocytic anaemia and is usually due to haematemesis
and/or melaena.
Acute haemorrhage
This is often associated with anaemia due to failure of erythropoietin secretion and is
unresponsive to treatment
Kidney failure
if there is a reticulocytosis, mild macrocytosis, reduced haptoglobin,
increased bilirubin and urobilinogen.
Suspect haemolytic anaemia
The more
common of the congenital ones are hereditary spherocytosis, sickle-cell anaemia and deficiencies
of the red cell enzymes, pyruvate kinase and G-6-PD, although most cases of G-6-PD deficiency
haemolyse
haemolytic anaemia
clinical features of anaemia (Hb ↓), infection (WCC ↓) or bleeding (platelets
↓).
Aplastic anaemia
Diagnosis is by bone marrow examination.
Aplastic anaemia
_______deficiency is present in up to 10–30% of children in high-risk groups
Iron
High-risk groups include those infants <6 months who are premature and/or with low
birthweight; toddlers 6–36 months with a diet high in cow’s milk and low in iron-containing
foods
Iron deficiency in children10
Introduce _______-containing solids early—at 4 to 5 months, e.g. cereals, vegetables, egg and
meat.
iron
Encourage breastfeeding and avoid cow’s milk in the first 12 months
Iron deficiency in children
__________ anaemia is blood-loss anaemia until proved otherwise
Iron-deficiency
__________ anaemia is usually due to menorrhagia or gastrointestinal loss until
proved otherwise.
Blood-loss
Serum free tri-iodothyronine (T3) measurement and serum free thyroxine (T4) can be useful in
suspected ____________
T3 toxicosis
TSH receptor antibodies (TR Ab):
Graves disease
Thyroid peroxidase antibodies (TPO Ab):
Hashimoto disease
Thyroglobulin antibody (Tg Ab):
Hashimoto disease
This is the single most cost-effective investigation in the diagnosis of thyroid nodules
Fine-needle aspiration
It is the
best way to assess a nodule for malignancy
Fine-needle aspiration
The scan may help in the differential diagnosis of thyroid nodules and in causes of
hyperthyroidism.
Thyroid nuclear scan and imaging
A functioning nodule is said to be less likely to be malignant than a nonfunctioning
nodule (cyst, colloid nodule, haemorrhage are non-functioning; carcinoma is usually
non-functioning).
Thyroid nuclear scan and imaging
A thyroid ultrasound is usually more sensitive in the detection of thyroid nodules
Thyroid ultrasound
__________goitre may be diagnosed on ultrasound while the clinical impression may be that of
a solitary nodule
multinodular
_________________ may be used particularly to determine if there is significant compression
in the neck from a large multinodular goitre with retrosternal extension
CT scan of the thyroid
The term __________refers to the accumulation of mucopolysaccharide in subcutaneous
tissues.
myxoedema
Transient causes include subacute thyroiditis, postpartum thyroiditis and silent thyroiditis.
Hypothyroidism
Common causes of primary hypothyroidism include
radioactive iodine treatment, thyroid surgery
and Hashimoto thyroiditis
autoimmune disorders (e.g. autoimmune lymphocytic thyroiditis, rheumatoid arthritis, type 1 diabetes)
Hypothyroidism
cold intolerance tiredness/lethargy/somnolence physical slowing mental slowing depression huskiness of voice puffiness of face and eyes pallor loss of hair weight gain
Hypothyroidism
DxT tiredness + husky voice + cold intolerance →
myxoedema
sinus bradycardia delayed reflexes (normal muscular contraction, slow relaxation) coarse, dry and brittle hair thinning of outer third of eyebrows dry, cool skin skin pallor or yellowing obesity goitre
Hypothyroidism
________________, or lymphocytic thyroiditis, which is an autoimmune thyroiditis, is the
commonest cause of bilateral non-thyrotoxic goitre in Australia
Hashimoto thyroiditis
bilateral goitre
classically described as firm and rubbery
patients may be hypothyroid or euthyroid with a possible early period of
thyrotoxicosis
Diagnosis is confirmed by a strongly positive antithyroid microsomal antibody (TPO Ab) titre
and/or fine-needle aspiration cytology
Hashimoto thyroiditis
T4—subnormal
TSH—elevated (>10 is clear gland failure)
Laboratory diagnosis of hypothyroidism
If T4 is low and TSH is low or normal, consider pituitary dysfunction
secondary
hypothyroidism) or sick euthyroid syndrome
A raised TSH and T4 in normal range denotes
‘subclinical’ hypothyroidism
Serum cholesterol level elevated
Anaemia: usually normocytic; may be macrocytic
ECG: sinus bradycardia, low voltage, flat T waves
hypothyroidism
Confirm the diagnosis, provide appropriate patient education and refer the patient
where appropriate.
hypothyroidism
Levothyroxine (thyroxine) 50–100 mcg daily, increasing by 25 mcg up to 100–200 mcg if
required
hypothyroidism
Start with low doses (25–50 mcg daily) in >60 years and those with ischaemic heart
disease and 50–100 mcg in others
hypothyroidism
Monitor TSH levels 6–8 weeks at first. As euthyroidism is achieved, monitoring may be less
frequent (e.g. 2–3 months). When stable on optimum dose of T4, monitor every 2–3 years.
Thyroid medication
Rapid thyroxine replacement can precipitate myocardial infarction,
especially in the elderly
Ischaemic heart disease
Continue thyroxine during pregnancy; watch for hypothyroidism
(an increased dose of T4 is often required).
Pregnancy and postpartum
If euthyroid, can stop thyroxine for one week. If subthyroid, defer surgery
until euthyroid.
Elective surgery
Urgent hospitalisation under specialist care is required. Intensive treatment
is required, which may involve parenteral T4 or T3 as liothyronine or thyroxine by slow IV
injection.
Myxoedema coma
This is a life-threatening emergency with coma, extreme hyperthermia, areflexia and respiratory
depression. Precipitating factors include illness, infection, trauma and cold.
Myxoedema coma
Treatment is
supportive care, IV thyroxine or liothyronine and corticosteroids. Convert to oral T4 when stable.
Myxoedema coma
Misdiagnosing this serious condition leads to failure to thrive, retarded growth and poor school
performance.
Neonatal hypothyroidism
If untreated it leads to permanent intellectual damage (cretinism).
Neonatal hypothyroidism
The clinical
features of the newborn include coarse features, dry skin, supra-orbital oedema, jaundice, harsh
cry, slow feeding and umbilical hernia
Neonatal hypothyroidism
It is detected by routine neonatal heel-prick blood testing
Neonatal hypothyroidism
Thyroxine replacement should be started as soon as possible
Neonatal hypothyroidism
is also relatively common and may affect up to 2% of women, who are affected
four to five times more often than men
Hyperthyroidism (thyrotoxicosis)
Graves disease is the most common
cause, followed closely by nodular thyroid disease
Hyperthyroidism (thyrotoxicosis)
Autonomous functioning nodules/toxic adenoma
Hyperthyroidism (thyrotoxicosis)
Subacute thyroiditis (de Quervain thyroiditis)—viral origin
Hyperthyroidism (thyrotoxicosis)
Excessive intake of thyroid hormones—thyrotoxicosis factitia
Hyperthyroidism (thyrotoxicosis)
Heat intolerance
Sweating of hands
Muscle weakness
Weight loss despite normal or increased appetite
Emotional lability, especially anxiety, irritability
Palpitations
Frequent loose bowel motions
Hyperthyroidism (thyrotoxicosis)
DxT anxiety + weight loss + weakness →
thyrotoxicosis
agitated, restless patient warm and sweaty hands fine tremor (place paper on hands) goitre proximal myopathy hyperactive reflexes bounding peripheral pulse ± atrial fibrillation
Hyperthyroidism (thyrotoxicosis)
Lid retraction (small area of sclera seen above iris)
Lid lag
Exophthalmos
Ophthalmoplegia in severe cases
Hyperthyroidism (thyrotoxicosis)
T4 (and T3) elevated
TSH level suppressed
Radioisotope scan
Antithyroid peroxidase (TPO Ab)—often positive
Hyperthyroidism (thyrotoxicosis)
The isotope scan enables a diagnosis of Graves disease to be made when the scan shows uniform
increased uptake
Hyperthyroidism (thyrotoxicosis)
Increased irregular uptake would suggest a toxic multinodular goitre, while
there is poor or no uptake with de Quervain thyroiditis and thyrotoxicosis factitia
Hyperthyroidism (thyrotoxicosis)
Establish the precise cause before initiating treatment.
Refer to an endocrinologist to guide treatment.
Educate patients and emphasise the possibility of development of recurrent hyperthyroidism or
hypothyroidism and the need for lifelong monitoring.
Monitor for cardiovascular complications, osteoporosis and eye problems
Hyperthyroidism (thyrotoxicosis)
Radioactive iodine therapy (131I)
Thionamide antithyroid drugs (initial doses)
carbimazole 10–45 mg (o) daily starting with 10–20 mg in divided doses depending on
disease activity
or
propylthiouracil 200–600 mg (o) daily in divided doses or methimazole
Hyperthyroidism (thyrotoxicosis)
Adjunctive drugs
beta blockers (for symptoms in acute florid phase, e.g. propranolol 10–40 mg, 6 to 8
hourly); diltiazem or atenolol are alternatives
lithium carbonate (rarely used when there is intolerance to thionamides)
Lugol’s iodine: mainly used prior to surgery
Surgery
Hyperthyroidism (thyrotoxicosis)
Younger patients with small goitres and mild case—18-month course antithyroid drugs
Treatment (Graves disease)
Large goitres or moderate-to-severe cases—antithyroid drugs until euthyroid, then surgery or
Treatment (Graves disease)
Control hyperthyroidism with antithyroid drugs, then surgery or 131I. Long-term
remissions on antithyroid drugs in a toxic nodular goitre are rare.
Treatment (Graves disease)
Because there is chance of hematoma, so I think we should remove the ___________first
staples
Hypertension with hypokalemia
Could be primary hyper aldosteronism or secondary hyper aldosteronism
Primary is ___________ in which renin is decreased and 2’o is RTA in which renin is increased
conn’s synd
aldosterone is elevated. But doing plasma __________level will differentiate between primary hyperaldosteronism and renal artery stenosis.
renin
hyperaldosteronism, initial inx should be plasma ____________
aldosterone/renin ratio
________________ is the treatment of choice in any woman with Graves disease planning pregnancy or in the first trimester as carbimazole is associated with a rare embryopathy.
Propylthiouracil (PTU)
In the second and third trimesters, switching to ________________has been suggested due to the risk of fulminant hepatitis with PTU
carbimazole
_____________ with hypokalemic myopathy
Conn disease
Presence of High Bp and Hypokalemia
Conn’s disease
Initial and best plasma free _____________then urinary VMA
metanephrin
next -24 hour urinary metanephrines
Best - plasma metanephrines
pheochromocytoma
____________goiter is most common
Multinodular
on __________If GH not suppressed: this confirmes acromegaly
OGTT
conduct pituitary MRI to determine the source of _______________ later.
excess GH
the best initial test is level of IGF-1, most accurate is glucose suppression test .
acromegaly
but it’s was mentioned in class to increase the dose by 1.5 times
Pregnant woman with hypothyroidism
Wermer’s syndrome
Pitiuitary tumor
Parathyroid adenoma
Pancreas( gastrinoma, vipnoma, insulinoma)
Men1
is the most accurate test for acromegaly, but initial inx for acromegaly is IGF-1
Oral glucose tolerance
The best would be treating by __________________ and defer her pregnancy till cure which usually takes 6 months
radio active iodine
Primary hyperparathyroidism
Most common cause parathyroid adenoma
Next common cause _________________
parathyroid hyperplasia
first, then USG or radioactive thyroid scan depends on the TSH level
Thyroid function test
Pt has ___________blood culture
Best is duplex Doppler
fever
history of DVT, rule out DVT first; it can also be cellulitis, but even it’s cellulitis, blood culture is very limited and not routinely performed cuz ____________________
the positive rate is very low
-1.5-2.5 score
osteopenia
Ca and vit d
Hypothyroidism. Most common cause _________________
hashimoto
Most common ca is papillary but in this case as tsh is high it means it’s hypo and hushimoto is most common in hypothyroidism leading to ____________
goitre
here ACTH is releasing due to secondary cause, paraneoplastic syndrome vaiya, secreting Ectopic ACTH which is stimulating melanocyte (cause adrenal gland is fine itself) and causing _______________.
pigmentation
If zolendronic is in options that would be more gud one as __________is no more used
strontium
cant give alendronate as gerd.and not HRT and ca,vit D as already _____________
osteoporosis
Here pt has got GERD , so we can’t choose (A) Alendronate because it causes / aggravates ____________
oesophagitis
When you don’t find out the exact cause of bleeding, go for _____________
capsule endoscopy
amedex says in overt bleeding: melana, hematochezia, blood loss go for _______________
CT ANGIOGRAPHY
Occult bleeding : iron deficiency anemia and +fecal occlude blood test go for ____________
capsule
Capsule endo when __________positive
FOBt
100% sc as the cord was involved , we just wait cuz all theatres are busy ,, always cord involved means ________
SC
first give magnesium till you find a theatre then deliver by SC ,, the next after _________is SC
magnesium
Non specific back pain caused by lifting weights. Encourage activity and analgesics. ________________ here so no imaging is warranted
No red flags
Imaging is done if there are red flags e.g ________________ or cancer etc
neurological deficits
____________for pain and encourage normal activity
Analgesics
Nsaids not given in someone with _____________
nephropathy
Allopurinol is not started in acute gout. But if the patient has an acute attack of gout while on allopurinol, we can continue the drug. But ________________ will not help with the pain or the swelling.
increasing the dose
no change of dose of allupurinol during a cute stage , we can increase the dose of allupurionol to prevent _______________ not during the attack
acute attack
Acute episode + nephropathy
Steroid
dose of allopurinol should not be changed in acute attack._____________ u can
once it settles
Acute gout- ___________contraindicated
allopurinol
Acute on top chronic gout in impaired renal
answer : ___________> D
steroid
In patients with tumors less than 1 cm located in the appendix, ____________is the treatment of choice.
appendectomy
_____________________ is indicated for tumors larger than 2 cm, lymphatic invasion, lymph node involvement
More extensive surgery
Radiculopathy with no red flag signs, so advice simple _____________and review in 1-2 wk
analgesics
Bilateral loss of pain and sensation and hx of trauma favours ________________
syringomyelia
____________common in obese young females
Pseudomotor
MS . hence _______is the investigation
MRI
Mnd there will be no ___________
numbness
If inr less than 4.5 \_\_ reduce or skip next dose of warfarin # if inr more than \_\_\_\_\_\_ \_\_ *stop dose of warfarin. *Check inr after 24 hrs. *Resume warfarin at reduced dose depending on results.
4.5
Upon commencing antidepressants, patients with bipolar disorder should be
closely monitored for symptoms of mania, and if these emerge then
antidepressant therapy should be ______________.
discontinued
________ infarct will have effect on upper limb and face
And it won’t cause dysphagia and dysarthria rather will cause aphasia due to broca’s and wernicke’s
Mca
excluded as dysarthria does not occur with MCA infarction ___________occurs.
Dysphasia
_____________________.as both upper and lower motor neuron lesion sign is present
amyotropic lateral sclerosis
_________but ALS diagnosis is clinical
EMG
___________________ supportive only, if hs than add acyclovir
viral meningitis
supportive for viral meningitis, if it’s caused by herpes, then add ____________
aciclovir
history of infection, now presenting headache, fever, neuro focal symptoms, suspect _____________
brain abscess
________ presents with ascending bilateral weakness
GBS
Brain tumor will represent more features of raised icp over long period of time without ______________
fever
Pneumonia— _______cough sputum
fever
In ______________there is fever headache raised icp low immune
abscess
Eye opening to pain=2
Withdraws from pain=________
Incomprehensible sound=2
4
If patient is in ER we place a transcutaneous pacemaker, and refer to cardiology unit for ___________________________
permanent pacemaker placement.
Monte & ______ are preventors against its pathology
SCG
Depends upon age of pt if less than 5 _sodium cromiglycate
If 5 or more -______________
inhaled corticosteroids
Presbyacusis… sensorial neural deafness.. bilateral…in ______________ its unilateral
acoustic neuroma
First reduce displacement, then __________
wound debridement
bulging fontanelle is ___________for LP
contraindicated
LP is _____________in raised ICP
contraindicated
Hyperthyroidism is usually transient for 1–2 months, and follows a surge of thyroxine after a
viral-type illness, then followed by hypothyroidism for 4–6 months.
Subacute thyroiditis (de Quervain thyroiditis)
Symptoms include pain
and/or tenderness over the goitre (especially on swallowing), fever, ESR elevated,
Subacute thyroiditis (de Quervain thyroiditis
Release of thyroid hormone from autoimmune destruction of thyroid
Painless postpartum thyroiditis
Treat with beta blockers for symptoms and thyroxine for
hypothyroid phase.
Painless postpartum thyroiditis
Clinical features are marked anxiety, weight loss, weakness, proximal muscle weakness,
hyperpyrexia, tachycardia (>150 per minute), heart failure and arrhythmias
Thyroid crisis (thyroid storm)
It requires urgent intensive hospital management with antithyroid drugs; IV saline infusion, IV
corticosteroids, anti-heart failure and antiarrhythmia therapy, especially beta blockers.
Thyroid crisis (thyroid storm)
Thyroid enlargement may be diffuse or multinodular.
Goitre
Diffuse causes include physiological,
Graves disease, thyroiditis (Hashimoto or de Quervain), iodine deficiency or it can be hereditary.
Goitre
Investigations include TFTs, needle biopsy, ultrasound and CXR.
Goitre
defined as a discrete lesion on palpation and/or ultrasonography that is
distinct from the rest of the thyroid gland.
A thyroid nodule
True solitary nodule: adenoma, carcinoma (papillary or follicular)
Thyroid nodules
Ultrasound imaging
Fine-needle aspiration cytology
Thyroid function tests
Thyroid nodules
The main presentations are a painless nodule, a hard nodule in an enlarged gland or
lymphadenopathy. Papillary carcinoma is the most common malignancy
Thyroid carcinoma8
This often involves total thyroidectomy, ablative 131I treatment, thyroxine
replacement and follow-up with serum thyroglobulin measurements, 131I/thallium scanning and
neck ultrasound. Fine-needle aspiration is the investigation of choice.
Thyroid carcinoma8
Fine-needle aspiration is the investigation of choice
Thyroid carcinoma
These account for 10% of intracranial tumours and are invariably benign adenomas
Pituitary tumours
They can
present with hormone deficiencies, features of hypersecretory syndromes (e.g. prolactin, GH,
ACTH) or by local tumour mass symptoms (e.g. headache, visual field loss, seizures, cranial
nerve 3, 4, 6 palsy).
Pituitary tumours
The main causes (of many) are a pituitary adenoma (prolactinoma; micro- or macro),
pituitary stalk damage, drugs—such as antipsychotics, various antidepressants, metoclopramide,
cimetidine, oestrogens, opiates, marijuana—and physiological causes such as pregnancy and
breastfeeding.
Hyperprolactinaemia11
Symptoms common to males and females: reduced libido, subfertility, galactorrhoea (mainly
females)
Hyperprolactinaemia
Females: amenorrhoea/oligomenorrhoea
Males: erectile dysfunction, reduced facial hair
Hyperprolactinaemia
Serum prolactin and macroprolactin assays
Hyperprolactinaemia
Refer for management, which may include a dopamine agonist such as cabergoline or
bromocriptine, surgical resection (rarely necessary) or radiotherapy.
Hyperprolactinaemia
excessive growth of hands (increased glove size)
excessive growth of tissues (e.g. nose, lips, face)
excessive growth of feet (increased shoe size)
increased size of jaw and tongue; kyphosis
Acromegaly
general: weakness, sweating, headaches sexual changes, including amenorrhoea and loss of libido disruptive snoring (sleep apnoea)
Acromegaly
DxT nasal problems + fitting problems (e.g. rings, shoes) + sweating →
acromegaly
Plasma growth hormone excess
Elevated insulin-like growth factor 1 (IGF-1) (somatomedin)—the key test
X-ray skull and hands
MRI scanning pituitary
acromegaly
Consider associated impaired glucose tolerance/diabetes
Obtain old photographs (if possible).
Treatment options: transsphenoidal pituitary microsurgery, drugs and radiotherapy.
acromegaly
Impaired secretion of vasopressin (antidiuretic hormone) from the posterior pituitary leads to polyuria, nocturia and compensatory polydipsia, resulting in the passage of 3–20 L of dilute
urine per day.
diabetes insipidus
There are several causes of ________________, the commonest being
postoperative (hypothalamic-pituitary), which is usually transient only. Other causes of cranial
DI include tumours, infections and infiltrations
diabetes insipidus (DI)
In nephrogenic DI the kidney tubules are
insensitive to _____________.
vasopressin
_____________________________is caused by
cancer (e.g. lung, lymphomas, kidney, pancreas), pulmonary disorders, various intracranial
lesions and drugs such as carbamazepine and many antipsychotic agents
The syndrome of secretion of inappropriate antidiuretic hormone (SIADH)
Management of
SIADH is essentially ______________
fluid restriction
The treatment of _____ is desmopressin, usually given twice daily intranasally
DI
DxT weakness + polyuria + polydipsia →
diabetes insipidus
a history of postpartum haemorrhage or head injury
symptoms of hypothyroidism
symptoms of adrenal insufficiency
symptoms suggestive of a pituitary tumour
thin, wrinkled skin: ‘monkey face’
pale ‘alabaster’ skin/hairlessness
Hypopituitarism
Causes: pituitary adenoma, other parasellar tumours and inflammatory/infiltrative lesions.
Hypopituitarism
DxT (female): amenorrhoea + loss of axillary and pubic hair + breast
atrophy →
hypopituitarism
DxT (male): ↓ libido + impotence + loss of body hair →
hypopituitarism
Investigate with serum pituitary hormones, imaging (MRI) and triple stimulation test.
hypopituitarism
Treatment includes HRT, surgery or radiotherapy.
hypopituitarism
Zona ___________—mineral corticoids, especially aldosterone
glomerulosa
Zona ____________—glucocorticoids
fasciculata
Zona ____________—androgens, especially DHEA
reticularis
Catecholamines—epinepherine, norepinephrine
Medulla
deficiency of cortisol and aldosterone
chronic adrenal insufficiency (Addison disease)—
cortisol excess
Cushing syndrome
Autoimmune destruction of the adrenals is the most common cause; others are infection, e.g. TB
or fungal.
Addison disease
Lethargy/excessive fatigue/weakness
Anorexia and nausea
Diarrhoea/abdominal pain
Weight loss
Dizziness/funny turns, syncope: hypoglycaemia (rare); postural hypotension (common)
Hyperpigmentation, especially mucous membranes of mouth and hard palate, skin creases of
hands
Addison disease
remains undiagnosed, wasting leading to death may occur. Severe
dehydration can be a feature.
Addison disease
DxT fatigue + a/n/v + abdominal pain (± skin discolouration)→
Addison
disease
Elevated serum potassium, low serum sodium
Low plasma cortisol level (fails to respond to synthetic adrenocorticotropic hormone [ACTH])
The short synacthen stimulation test is the definitive test
Consider adrenal autoantibodies and imaging? calcification of adrenals
Addison
disease
Treatment: corticosteroid replacement—hydrocortisone/fludrocortisone acetate, other options
Addison
disease
Age is important
Old age cystoscopy
And usg done according to protocol ua should be done prior __________
usg
An ________________ develops because of an inability to increase cortisol in response to stress,
which may include intercurrent infection, surgery or trauma.
Addisonian crisis
Nausea and vomiting
Acute abdominal pain
Severe hypotension progressing to shock
Weakness, drowsiness progressing to coma
Addisonian crisis
Establish IV line with IV fluids
Hydrocortisone sodium succinate 100 mg IV initially and 50–100 mg 4–6 hourly until stable
Arrange urgent hospital admission
Addisonian crisis
iatrogenic—chronic corticosteroid administration
pituitary ACTH excess (Cushing disease)
bilateral adrenal hyperplasia
adrenal tumour (adenoma, adenocarcinoma)
ectopic ACTH or (rarely) corticotrophin-releasing hormone (CRH) from non-endocrine
tumours (e.g. oat cell carcinoma of lung)
The clinical features are caused by the effects of excess cortisol and/or adrenal androgens
Cushing syndrome8
Proximal muscle wasting and weakness Central obesity, buffalo hump on neck Cushing facies: plethora, moon face, acne Weakness Hirsutism Abdominal striae Thin skin, easy bruising Hypertension Hyperglycaemia (30%) Menstrual changes (e.g. amenorrhoea) Osteoporosis Psychiatric changes
Cushing syndrome8
DxT plethoric moon face + thin extremities + muscle weakness →
Cushing syndrome
Cortisol excess (plasma or 24-hour urinary cortisol)
Dexamethasone suppression test
Late night salivary cortisol (2 measurements)
Inferior petrosal sinus sampling
Serum ACTH
Radiological localisation: MRI for ACTH-producing pituitary tumours; CT scanning for
adrenal tumours
Cushing syndrome
transsphenoidal excision of pituitary tumour. Pharmacological blockade of corticosteroid
production may be necessary, ketoconazole (o) is first line.
Cushing syndrome
Most commonly due to an adrenal adenoma.
Primary hyperaldosteronism
Usually asymptomatic and hypertensive but any symptoms are features of hypokalaemia
Conn syndrome
weakness, headaches palpitations cramps paraesthesia polyuria and polydipsia
Conn syndrome
Aldosterone (serum and urine) ↑ Plasma renin ↓ Plasma aldosterone to renin activity ratio Na ↑, K ↓, alkalosis Imaging (MRI or CT scan) of adrenals
Conn syndrome
Refer for treatment including possible surgery to excise adenoma. prepare for
surgery.
Conn syndrome
A dangerous tumour of the adrenal medulla. Clinical features are paroxysms or spells of: anxiety hypertension headache (throbbing); tremor sweating palpitations pallor/skin blanching rising sensation of tightness in upper chest and throat (angina can occur)
Phaeochromocytoma
DxT episodic headache + sweating + tachycardia →
phaeochromocytoma
Series of three 24-hour free catecholamines ↑ VMA
Abdominal CT or MRI scan (both highly sensitive)
phaeochromocytoma
Excise tumour, cover with alpha and beta blockers
phaeochromocytoma
condition with 21-hydroxylase deficiency being the most common of several forms.
Congenital adrenal hyperplasia (adrenogenital
syndrome)6,8
There is inadequate synthesis of cortisol and aldosterone with increased androgenisation
Congenital adrenal hyperplasia (adrenogenital
syndrome)
Congenital adrenal hyperplasia (adrenogenital
syndrome)
may present with failure to thrive or vomiting and
dehydration (SLS)
Most of those detected by abdominal imaging are benign and termed ‘incidentalomas’ but serious tumours include adrenal carcinoma, phaeochromocytoma, neuroblastoma, glucocorticoid
or a mineralocorticoid secreting tumour.
Adrenal tumours
Rule: tumours >4 cm require thorough assessment as malignant tumours are large.
Excision is usually advisable.
Adrenal tumours9
These are adrenal tumours ≥1 cm. Most are benign and non-functioning. An important issue is
malignancy, and if this is the case, whether it is primary, secondary or functional (hormone
secreting).
Incidentalomas
Investigations to consider include electrolytes, aldosterone/renin ratio, catecholamines,
testosterone, DHEAs, dexamethasone suppression test, CT scan. Surgical excision should be
considered under specialist guidance.
Incidentalomas
Suspect hypercalcaemia if there is weakness, tiredness, malaise, anorexia, nausea or vomiting,
abdominal pain, loin pain, constipation, thirst, fever, polyuria, drowsiness, dizziness, personality
changes, muscle aches and pains, visual disturbances
Hypercalcaemia
Measure urea and electrolytes (especially
calcium), creatinine, albumin.
Hypercalcaemia
Primary hyperparathyroidism, familial hypercalciuric hypercalcaemia and neoplasia, especially
carcinoma of lung and breast (with metastases to bone), account for over 90% of cases.
Hypercalcaemia
Other
causes include Paget disease, Williams syndrome, prolonged immobilisation, dehydration,
sarcoidosis and milk-alkali syndrome.
Hypercalcaemia
Investigations include ESR, serum parathyroid hormone
(N: 1.0–7 pmol/L), serum ACE levels, serum alkaline phosphatase, chest X-ray, Sestamibi scan
and bone scan. Requires specialist referral.
Hypercalcaemia
DxT weakness + constipation + polyuria →
Hypercalcaemia
DxT cramps + confusion + tetany →
hypocalcaemia
is caused by an excessive secretion of parathyroid hormone and is usually
due to a parathyroid adenoma.
Primary hyperparathyroidism
Classic mnemonic: bones, moans, stones, abdominal groans
Primary hyperparathyroidism
Exclusion of other causes of hypercalcaemia
Serum parathyroid hormone (elevated)
TC-99m Sestamibi scan to detect tumour
Primary hyperparathyroidism
Refer for possible surgical management
Primary hyperparathyroidism
Most appropriate is sputum for _________
AFB
______ is for latent TB
IGRA
next _____________ ,most appropriate sputum culture
chest x ray
dx NSTEMI with AF (which has occured as a complication of MI)
____________will help to deal with both NSTEMI and AF(due to non valvular lesion)
Antiplatelet
Inverted T wave means _______
PE
Causes include parathyroid injury, autoimmune hyperparathyroidism, severe vitamin D
deficiency and neonates of mothers with hypercalcaemia.
Hypocalcaemia
This usually presents with tetany or
more generalised neuromuscular hyperexcitability and neuropsychiatric manifestations
Hypocalcaemia
The
sensory equivalents are paraesthesia in the hands, feet and around the mouth (distinguish from
tetany seen in the respiratory alkalosis of hyperventilation).
Hypocalcaemia
There may be seizures and cramps.
The diagnosis is by measurement of serum total calcium concentration in relation to serum
albumin (s. calcium <2.10 mmol/L).
Hypocalcaemia
Two important signs are:
Trousseau sign: occlusion of the brachial artery with BP cuff precipitates carpopedal spasm
(wrist flexion and fingers drawn together)
Chvostek sign: tapping over parotid (facial nerve) causes twitching in facial muscles
Hypocalcaemia
Treatment involves careful adjustments in dosage of calcitriol and calcium to correct
hypocalcaemia and avoid hypercalcaemia and hypercalciuria (the latter may lead to kidney
impairment).
Hypocalcaemia
is the most common cause of hypocalcaemia. Causes include postoperative
thyroidectomy and parathyroidectomy, congenital deficiency (DiGeorge syndrome) and
idiopathic (autoimmune) hypoparathyroidism.
Hypoparathyroidism
The main features are neuromuscular
hyperexcitability, tetany and neuropsychiatric manifestations.
Hypoparathyroidism
Water depletion (e.g. diabetes insipidus)
Water and sodium depletion (e.g. diarrhoea)
Corticosteroid excess (e.g. Cushing syndrome, Conn syndrome)
Iatrogenic: excess IV hypertonic Na solutions
Hypernatraemia Na+ >145 mmol/L
Thirst, confusion, lethargy, weakness, irritability, oliguria
Orthostatic hypotension
Muscle twitching or cramps
Signs of dehydration
Severe: seizures, delirium, hyperthermia, coma
Hypernatraemia Na+ >145 mmol/L
Water retention (e.g. CCF, hypoalbuminaemia)
Kidney failure to conserve salt (e.g. nephritis, diabetes mellitus, Addison disease)
Gastrointestinal loss of Na+ (e.g. vomiting, diarrhoea)
Drugs (e.g. diuretic excess, ACE inhibitors)
Hyponatraemia Na+ <135 mmol/L
Asymptomatic when mild
Anorexia, nausea, lethargy, confusion, headache, ataxia, mental changes (e.g. in personality)
Severe: convulsions, coma, death
Hyponatraemia Na+ <135 mmol/L
The first sign of ________________ (e.g. >6) may be a cardiac arrest. A medical emergency if >6.5.
hyperkalaemia
Oliguria, kidney failure
Acidosis (especially metabolic)
Mineralocorticoid deficiency: Addison disease, aldosterone antagonists
Excessive intake of K+ (e.g. IV fluids with K)
Drugs (e.g. ACE inhibitors, NSAIDs, suxamethonium)
Consider artefact, e.g. haemolysed sample
Hyperkalaemia K+ >5.5 mmol/L
Malaise, muscle weakness, flaccid paralysis (rare)
May be asymptomatic until cardiac toxicity
May cause cardiac arrest—asystole or fibrillation
ECG: peaked T waves, ↓ QT, ↑ PR interval → arrhythmias
Hyperkalaemia K+ >5.5 mmol/L
If <2.5 severe symptoms, seek urgent attention.
Hypokalaemia K+ <3.5 mmol/L
Kidney disease
Gastrointestinal loss: vomiting, diarrhoea
Alkalosis
Mineralocorticoid excess
Loss of extracellular fluid to intracellular (e.g. burns, other trauma, pyloric stenosis)
Drugs (e.g. diuretics: frusemide, thiazides), purgatives, liquorice abuse
Reduced intake of K+
Hypokalaemia K+ <3.5 mmol/L
Lethargy, muscle weakness and cramps, mental lethargy and confusion
Severe flaccid paralysis, tetany, coma
ECG: prominent U waves, depressed ST segment, T waves, arrhythmias
Hypokalaemia K+ <3.5 mmol/L
neck pain neck stiffness headache ‘migraine’-like headache facial pain arm pain (referred or radicular) myelopathy (sensory and motor changes in arms and legs) ipsilateral sensory changes of scalp ear pain (peri-auricular) scapular pain anterior chest pain torticollis dizziness/vertigo visual dysfunction
Clinical problems of cervical spinal origin
The most common pathogens are the bacteria Escherichia coli (E. coli),
Staphylococcus saprophyticus, Proteus, Klebsiella and Enterococcus spp.
Urinary tract infection (UTI)
Of great concern is the
worldwide emergence of multidrug-resistant strains of E. coli.
Urinary tract infection (UTI)
The morbidity of urinary
infections in both children and adults is well known but it is vital to recognise the potential for
progressive kidney damage, ending in chronic kidney failure.
Urinary tract infection (UTI)
The main task in the prevention of
chronic pyelonephritis is the early identification of patients with additional factors, such as reflux
or obstruction, which could lead to progressive kidney damage.
Urinary tract infection (UTI)
frequency, dysuria and
loin pain.
Urinary tract infection (UTI)
Screening of asymptomatic women has shown that about 5% have bacterial
UTI.
Urinary tract infection (UTI)
UTIs are largely caused by organisms from the bowel that colonise the perineum
and reach the bladder via the urethra.
Urinary tract infection (UTI)
In many young women, infections are
precipitated by sexual intercourse. Ascending infection accounts for 93% of UTIs
Urinary tract infection (UTI)
Always consider any family history of urinary tract abnormalities
Urinary tract infection (UTI)
Infants less than 6 months old with a UTI have a significant risk of bacteraemia
Urinary tract infection (UTI)
Female sex
Sexual intercourse
Diabetes mellitus
Vesicoureteral reflux (VUR)
Urinary tract obstruction/malformation/stricture
Pregnancy
Immunosuppression
Menopause
Diaphragm contraception or spermicidal exposure
Instrumentation
Bladder polyps, carcinoma, diverticula, stones
Urinary tract infection (UTI)
Sterile pyuria
Urinary tract infection (UTI)
contamination of poorly collected urine specimens
urinary infections being treated by antibiotics, i.e. inadequately treated infections
genital infections (e.g. chlamydia urethritis)
analgesic nephropathy
staghorn calculi
other kidney disorders (e.g. polycystic kidney)
bladder tumours
tuberculosis
chemical cystitis (e.g. cytotoxic therapy)
appendicitis
Sterile pyuria
This is defined as the presence of a significant growth of bacteria in the urine (concentration
>108 colony forming units/L), which has not produced symptoms requiring consultation
Asymptomatic bacteriuria
pregnant women because of the risk of pyelonephritis and pregnancy complications (see
CHAPTER 100 )
patients before elective urological procedures (e.g. TURP)
Asymptomatic bacteriuria
the presence of frequency, dysuria and loin pain alone or in combination,
together with a significant growth of organisms on urine culture
symptomatic bacteriuria
If not pregnant —-> xray pelvis
If pregnant —>_____
usg
debridement comes first then ________
reduction
______________are teratogenic we avoid in young age
Bisphosphonate
ok that means no bisphosphonates before __________________
menupause
reproductive age group avoid ____
BSP
Always correct __________ before bispoh
vit d
First correct vit D, then _________
alendronate
Tophaceous gout ….________
prednisolone
Pt. is already on Aspirin prophylaxis and developed stroke. CEA is recommended in symptomatic stenosis of >50% and asymptomatic stenosis of __________
> 70%.
In alcohol aST to alt ratio _____
2:1
temperature is 38, child’s age is 4. It could be perthes tenosynovitis or septic arthritis based on age, I chose septic arthritis coz of ___________
fever
______________ in stable Abdominal trauma
CT abdomen
fever and ryt iliac fossa pain >__________
abscess
In a case of infertility,always do ________analysis first
semen
Diagnosis here is ________if timolol and pilocarpine in option will choose that from these options
galucoma
Suspend breast feeding for 24 hour than checkin __________
bilirubin
If conjugated bilirubin is >10% of total bilirubin from the options given its
____________
Biliary atresia
If we stop warfarin or giving vit K it will take about ___days time
4
if emergency Sx give ffp/prothrombin concetrate (B)…if Sx can be delayed above method of stopping or reversing the action of effect of ________________
anticoagulant
apple core lesion is significant for colon ca here patient having obstructive symptoms so if no options of Prothrombin then we will go with ____
ffp
symptoms of acute abdomen, so we will do __________ASAP
intervention
if history of snake bite present and even no fangs sign present utill unless always consider snake is poisonus so reffer to _________________
tertitory hospital
yes dont give ____________untill collapse aur cardiac arrest inr more than 1.3 opthalmoplegia aur paralysis events
antivenom
___________to find out gross hematuria cause
Cystoscopy
gross haematuria in less than 55 yrs initial ________then CT scan to rule out renal CA..
UA
gross hematuria in middle aged ,initial ure then ____to rule out rcc
ct
investigation for ______________ should be done frst as chest pain and travel h/o are present
pul. Embolism
early syphilis-benz penicilin single dose IM, or doxycyline incase of pen allergy. should contact all sexual partners in past 3 month. ________________ at 3 months, 3 monthly
repeat serology
Asymptomatic pts with more than 70% stenosis have modest risk and should be treated ____________
conservatively
carotid endarterectomy indicated when stenosis is __________ with symptoms.
75%
Sjogren > mx is supportive
complaint for this pt is dry eyes so
C . ______________
artificial eye drop
_________for mild pneumonia in children
Amox
after excluding adjustment disorder- major stress or absent, autism excluded coz- _____________.
speech normal
Post operative confusion,always think about hypoxia 1st.so pulse oxymetry.__________ should be more appropriate
ABG
because warfarin should be stopped _____________ before elective surgry
4-5 days
Intrahepatic cholestasis of pregnancy-develop in late pregnancy ,no rash ,worse itching at night,____________typically develops 1-4 weeks after onset of pruritus
jaundice
Scabies must have burrows
Pruritus in 3rd trimester goes in favour of ______________
cholestasis of pregnancy
zolendronic acid is generally _____
iv
______________( a common side effect after covid vaccine) especially in below 50 yrs and younger age groups.
myocarditis
_______________ can elevated in PE and myocarditis
Troponin
no fetal heart sounds, so to deliver the dead baby-do ___________
amniotomy
apple core appearance _________
CA colon
IV antibiotics ( for all infants below 3 months).
Urinary tract infection
Iv antibiotics then Usg
urinary tract infection (UTI) in young children
paroxetine contraindicated in ___________
pregnancy
Patient takung ACEI since long withiut any angioneurosis …. & amoxycillin since 2 days &s/s after amoxy angioneuresis appeared …so I will blame ___________
Amoxy
Polymyalgia Rheumatica with Giantcell arteritis.
__________would be better as next step.
ESR
____________because its excercise induced asthma, Ref JM 7the edition, still check the latest 8th edition once
salbutamol
initially SABA given , if not working than we choose __________
SCG or ICS
it shuld be ______________coin like apperaence is due to hypercalcemia leads to calcification which causes coin like asralra are present due to pul htn whixh is present in all others so b
sarcidiosis
Inflammation of the bladder and/or urethra is associated with dysuria (pain or scalding with
micturition) and/or urinary frequency
Acute cystitis (dysuria-frequency syndrome)
Acute bacterial infection of the kidney produces loin pain and constitutional upset, with fever,
rigors, nausea and sometimes vomiting
Acute pyelonephritis1
The symptoms of acute cystitis are often also present.
The differential diagnosis includes causes of the acute abdomen, such as appendicitis,
cholecystitis and acute tubal or ovarian diseases. The presence of pyuria and absence of
rebound tenderness are helpful in distinction.
Acute pyelonephritis1
This is cystitis occurring in the uninstrumented non-pregnant female without structural or
neurological abnormalities. Acute infection is most commonly caused by E. coli and
Staphylococcus saprophyticus.
Uncomplicated urinary tract infection
This is associated with anatomical or functional abnormalities (e.g. diabetes, urinary calculi) that increase the risk of serious complications or treatment failure.
Complicated urinary tract infection5
The laboratory diagnosis of ___________ depends on careful collection, examination and culture of urine
UTI
It is not mandatory for non-pregnant
women with suspected cystitis when empirical treatment may be appropriate.
The laboratory diagnosis of UTI
It is best to collect the first urine passed in the morning, when it is highly concentrated and any
bacteria have been incubated in the bladder overnight
Collection of urine1
Preferably the urine should be taken to the
laboratory immediately, but it can be stored for up to 24 hours at 4°C to prevent bacterial
multiplication.
Collection of urine1
Clean catch midstream specimen of urine (MSU). This is best collected from a full bladder, to
allow at least 100 mL of urine to be passed before collection of the MSU
Collection of urine1
Catheter specimen of urine (CSU). In women who have difficulty with collecting an
uncontaminated MSU (as is commonly the case in the elderly, the infirm and the grossly
obese), a short open-ended catheter can be inserted and a specimen collected after 200 mL has
flushed the catheter.
Collection of urine1
Suprapubic aspirate of urine (SPA). This is an extremely reliable way to detect bacteriuria in
neonates and in patients where UTI is suspected but cannot be confirmed because of low
colony counts or contamination in an MSU.
Collection of urine
All children with a UTI require a urine specimen. It is diagnosed by significant growth on MSU,
CSU, MCC or SPA.
Urine specimen collection in children
____________ of urinary leucocytes or nitrite are suggestive of UTI and may be an
indication for empirical treatment if symptomatic
Dipstick findings
The urine is examined under a microscope to detect pyuria (more than 10 pus cells—WBCs—per
high-powered field) but should be examined in a counting chamber to calculate the number of
WBCs/mL of urine.
Microscopic examination
The nature and number of organisms present in the urine are the most useful indicators of UTI
Culture of the urine
Most common are enteric organisms. E. coli (especially) and Staphylococcus saprophyticus
are responsible for over 90% of UTIs, with other Gram-negative organisms (Klebsiella sp. and
Proteus sp.), Enterococcus sp. and Gram-positive cocci (Streptococcus faecalis and other
staphylococci) also responsible.
Culture of the urine
Infections due to organisms other than E. coli (e.g. Pseudomonas sp.) are suggestive of an
underlying kidney tract abnormality.
Culture of the urine
If >105 colony forming units (cfu) per mL of bacteria are present in an MSU, it is highly likely
that the patient has a UTI.
Culture of the urine
On the other hand, it is most important to realise that up to 30% of women with acute bacterial
cystitis have less than 105 cfu/mL in the MSU. For this reason, it is reasonable to treat women
with dysuria and frequency even if they have <105 cfu/mL of organisms in an MSU
Culture of the urine
Significant levels for UTI:
Microscopy: WBC >10 per mL (10 × 106/L)
Culture: counts >105 cfu/mL (108/L)
Summary: MCU (microscopy and culture urine)
Keep yourself rested.
Drink a lot of fluid: 2–3 cups of water at first and then 1 cup every 30 minutes.
Try to empty your bladder completely each time.
Use analgesics such as paracetamol for pain.
Make the urine alkaline by taking sodium citrotartrate (4 g orally 6 hourly)—not if taking
nitrofurantoin.
Acute uncomplicated cystitis
Urine dipstick Urine microscopy and culture First-line antibiotics—trimethoprim or cephalexin Alkaliniser for severe dysuria High fluid intake Check sensitivity—leave or change ABs
UTI: basic management
Use for 10 days in women with known urinary tract abnormality:
trimethoprim 300 mg (o) daily for 3 days (first choice)
or
cephalexin 500 mg (o) 12 hourly for 5 days
or
amoxicillin + clavulanate 500/125 mg (o) 12 hourly for 5 days
or
nitrofurantoin 100 mg (o) 6 hourly for 5 days
or
norfloxacin 400 mg (o) 12 hourly for 3 days (if resistance to above agents proven and if
susceptible, Caution about tendinopathy and tendon rupture.)
No follow-up is required if women remain asymptomatic after treatment
Treatment (non-pregnant women)3,7
Avoid using important quinolones—norfloxacin or ciprofloxacin—as first-line agents.
Cotrimoxazole is not first line because it has no advantage over trimethoprim and has more
side effects.
Treatment failures are usually due to a resistant organism or an underlying
Treatment (non-pregnant women)3,7
Treatment of acute cystitis (empirical):
cephalexin 500 mg (o) 12 hourly for 5 days
or
nitrofurantoin 100 mg (o) 6 hourly for 5 days
or
amoxicillin + clavulanate 500/125 mg (o) 12 hourly for 5 days
Repeat MCU 1–2 weeks after completion.
Pregnant women8,9
UTI in pregnant women requires careful surveillance
Consider the cause (see risk factors above).
Investigations: MCU, U&E, ultrasound.
Treatment (empirical, while awaiting investigation):
trimethoprim 300 mg (o) daily for 7 days
or
cephalexin 500 mg (o) 12 hourly for 7 days
or
amoxicillin + clavulanate 500/125 mg (o) 12 hourly for 7 days
or
nitrofurantoin 100 mg (o) 6 hourly for 7 days
or
norfloxacin 400mg (o) 12 hourly for 7 days
Note: All males with a UTI should be investigated to exclude an underlying abnormality, e.g
Adult males7
_______________ is a treatable condition that most commonly happens in uncircumcised males.
Balanitis
____________ specificity is high in SLE
Anti-dsDNA
combination of 3rd gen cephalosporins+azithro is needed to cover resident ________________even in the absence of Chlamydia
gonorrhoea
Thiamine infusion should be given before _______________
dextrose infusion
patient under 55 highly risk for CPTA scan
V/Q
Suspected Ca. Prostate. Initial: DRE/PSA - TRUS guided biopsy. ___________indicated in fracture spine d/t mets.
MRI
___________works similar to terlipressin as vasoactive agent. Next is to scope to r/o variceal bleed
Octreotide
salt restriction - frst lifestyle modification for all ___________pts
ascites
first we do urinalysis and then creatinine and urine cytology is considered in _____________
hematuria
DRE -> UA -> sCr -> _________
US KUB
__________ to see soft tissues damage like ligaments or tendon
MRI
Patients with a level 2.5 – 4 mEq/L should have hemodialysis if they have severe symptoms such as neurologic deterioration, hemodynamic instability, acute kidney injury or ventricular arrhythmia.
lithium
Febeile convulsion -___________
no need anything
Patients presenting with acute neurological ischaemia or amaurosis initial aspirin and the best ________
surgery
bcoz risk of transmission to baby less even if symptomatic.do serology once pt is ___________
symptomatic
Urine microscopy and culture is mandatory. Mild cases can be treated with oral therapy alone for
a longer duration than the recommended course for uncomplicated cystitis
Acute pyelonephritis
For empirical
therapy, use amoxicillin/clavulanate (875/125 mg (o) 12 hourly) for 10–14 days or ciprofloxacin
(500 mg (o) 12 hourly) for 7 days.
Acute pyelonephritis
For severe infection with suspected septicaemia, admit to hospital and treat initially with
parenteral antibiotics after taking urine for microscopy and culture, and blood for culture. It is a
particular problem if acquired in pregnancy.
Acute pyelonephritis
amoxicillin/ampicillin 2g IV 6 hourly
plus
gentamicin 4–6 mg/kg/day, single daily IV dose
Follow with oral therapy for a total of 14 days.
Drug levels of gentamicin require monitoring. Gentamicin can be replaced with IV cefotaxime or
ceftriaxone.
Acute pyelonephritis
Consider investigation for an underlying urinary tract abnormality, especially in men and in
patients that remain unwell after 72 hours of treatment
Acute pyelonephritis
Persistent (chronic) UTIs indicate that the organism
is resistant to the antimicrobial agents employed or that there is an underlying abnormality such
as a kidney stone or a chronically infected prostate in the male patient
Recurrent or chronic urinary tract infections
Treat an acute episode of recurrent UTI as for cystitis or pyelonephritis
Recurrent or chronic urinary tract infections
__________ in infants and very young children is often kidney in nature and may be associated with
generalised symptoms such as fever, vomiting, diarrhoea and failure to thrive.
UTI
Causes of ‘smelly’ urine in children are urinary infection and/or ___________,
especially with gastroenteritis
dehydration
In a girl or boy (rare
presentation) with symptoms of dysuria and frequency, an underlying abnormality may be
present with a reported incidence of __________________ as high as 40% and scarred
kidneys (reflux nephropathy) in 27%
vesicoureteric reflux (VUR)
Thus the early detection of children with VUR and control of recurrent kidney infection could
prevent the development of scars, hypertension and ____________________
chronic kidney failure
Radiological
investigation of children with UTIs shows normal kidneys in approximately 66% and _____________in
approximately 33%.
reflux
<1 year—ultrasound; consider ___________________ if US
abnormal
micturating cystourethrogram (MCUG)
Treat empirically in children one month or more while awaiting culture results. If less than one
month, treatment with IV antibiotics is advisable.
Treatment (mild infection in children)
Treatment should be taken orally for 3–7 days:
trimethoprim 4 mg/kg (max. 150 mg) bd (suspension is 50 mg/5 mL)
or
cephalexin 12.5 mg/kg (max. 500 mg) bd
or
trimethoprim/sulfamethoxazole 4/20 mg/kg (max. 160/800 mg) bd
Treatment (mild infection in children)
For empirical treatment in those ≥12 months who appear septic or are vomiting, and
infants <12 months, give gentamicin IV + amoxi/ampicillin IV.
Severe infections in children
can affect women of any age, it is more prevalent in girls between 2 and
8 years. It can be confused with a UTI where there is dysuria, which is a common symptom in
this type of dermatitis
Vulvovaginitis
Consider bacterial ____________in men with few urinary symptoms (frequency, urgency and
dysuria), flu-like illness, fever, low backache and perineal pain
prostatitis
The prostate is exquisitely tender
on rectal examination. For mild to moderate infection, give trimethoprim
prostatitis
3-day course of trimethoprim 300 mg daily is a suitable first choice for acute
uncomplicated __________in women.
cystitis
In males the prostate is the most common source of ___________UTI
recurrent
UTI is commonly associated with __________________
microscopic haematuria
The six most common causes of death from cancer in
Australia are cancer of the lung, colorectal, lymphoma, ____________, breast and pancreas
prostate
Lump or mass, especially neck or stomach Unusual bleeding, bruising or rash White eye Persistent nausea and vomiting Constant illness Constant tiredness and/or pallor Headache, especially early morning Continuing unexplained weight loss Recurrent or persistent fever Changes which occur suddenly and persist
Red flags for childhood cancer
the Philadelphia chromosome for _________________
chronic myeloid leukaemia
(elevated in trophoblastic tumours and germ cell
neoplasms of the testes and ovaries)
human chorionic gonadotrophin (HCG)
Testicular cancer (non-seminomatous)
Hepatocellular carcinoma
GIT cancers with and without liver metastases
AFP
Ovarian cancer (non-mucinous), breast
CA-125
CA-15-3 ___________
Breast
CA-19-9 ____________
Pancreas, colon, ovary
CEA
Colorectal cancer
Pancreatic, breast, lung, small intestine, stomach,
ovaries
PSA*
Prostate cancer
hCG
Choriocarcinoma
Hydatidiform mole
Trophoblastic diseases
DxT malaise + weight loss + cough →
lung cancer
________ cancer is one of the most common cancers in
Australia in terms of both incidence and death, accounting for at least 20% of cancer deaths
lung
___________________ include hypercalcaemia, Cushing syndrome, carcinoid syndrome,
dermatomyositis, visual loss progressing to blindness from retinal degeneration, cerebellar
degeneration and encephalitis.
The paraneoplastic syndromes
haematuria (60%)
loin pain (40%)
loin mass (palpable kidney)
signs of anaemia
left supraclavicular lymphadenopathy (Virchow node)
varicocele (left side)
hypertension
symptoms of metastases (to liver, lungs, brain, bones): respiratory symptoms, neurological
symptoms and signs, bone pain, pathological fracture (vertebral collapse)
urinalysis—67% positive for blood
Kidney cell cancer
Diagnosis is confirmed by imaging, e.g. CT/MRI.
Refer for radical nephrectomy.
Kidney cell cancer
DxT haematuria + loin pain + palpable kidney mass →
kidney cell cancer
is responsible for 10% of all childhood malignancies.
Wilms tumour (nephroblastoma)
Clinical features include:4 peak incidence 2–3 years general symptoms of neoplasia palpable mass 80% abdominal pain 30% haematuria 25%
Wilms tumour (nephroblastoma)
Diagnosis is confirmed by urine cytology, ultrasound or CT/MRI scan.
Wilms tumour (nephroblastoma)
Early diagnosis with nephrectomy and chemotherapy leads to a very favourable prognosis (90%
5-year survival).
Wilms tumour (nephroblastoma)
DxT haematuria + abdominal mass + malaise →
Wilms tumour (nephroblastoma)
Probably the most common cancer in infancy (usually <2–3 years). 90% present under
5 years.
Neuroblastoma7
It is a tumour of the adrenal medulla (50%) and sympathetic nervous system, especially
retroperitoneal neural tissue in abdomen (30%) but also in chest and neck
Neuroblastoma7
fatigue, anorexia, nausea, fever
abdominal pain, abdominal swelling
anaemia and weight loss
May present with metastases, e.g. bone pain.
Diagnosis: CT scan, skeletal survey; biopsy required
Neuroblastoma7
Treatment is based on surgical resection then chemotherapy ± localised radiotherapy. Good
response to therapy especially if <18 months.
Neuroblastoma7
has the highest mortality rate of all the gynaecological cancers because the
majority of patients present in the late stage of the disease.
Ovarian cancer8
It is responsible for 5% of deaths in
females.
Ovarian cancer8
It is usually asymptomatic prior to the development of metastases
Ovarian cancer8
Epithelial tumours
are the most common of malignant ovarian tumours
Ovarian cancer
They are uncommon under 40 years of age
and the average age of diagnosis is 50 years
Ovarian cancer
The most common presentation is abdominal swelling (mass and/or ascites), abdominal bloating
or discomfort.
Ovarian cancer
Non-specific symptoms, which may be present for a long time before diagnosis,
include abnormal uterine bleeding, urinary frequency, weight loss, abdominal discomfort,
reduced capacity for food, diarrhoea, anorexia, nausea and vomiting
Ovarian cancer
Diagnosis is supported by pelvic ultrasound and serum CA-125 tumour marker
Ovarian cancer
A new test is the
OvPlex serum test, which measures five serum markers.
Ovarian cancer
DxT abdominal discomfort + anorexia + abdominal bloating/distension →
Ovarian cancer
Malignancy in this area is more likely to present with symptoms of anaemia without the patient
noting obvious blood in the faeces or alteration of bowel habit
Carcinoma of caecum and ascending colon5
DxT blood in stools + abdominal discomfort + change in bowel habit →
Carcinoma of caecum and ascending colon
This is another cancer with vague symptoms, metastasising early and late presentation
Pancreatic cancer
It is
mainly ductal adenocarcinoma, which, if in the head of the pancreas, presents with painless
jaundice and if in the body and/or tail presents with epigastric pain radiating to the back, relieved
by sitting forward
Pancreatic cancer
DxT jaundice + anorexia + abdominal discomfort/pain →
Pancreatic cancer
are caused by an acquired malignant transformation in the stem cell in the
haemopoietic system.
The leukaemias
The usual age range for acute lymphatic leukaemia (ALL) is 2–10 years with a second peak at
about ______________.
40 years
Symptoms of anaemia
Susceptibility to infection (e.g. sore throat, mouth ulceration, chest infection)
Easy bruising and bleeding (e.g. epistaxis, gingival bleeding)
Bone pain (notably in children with ALL) and joint pain
Symptoms due to infiltration of tissues with blast cells (e.g. gingival hypertrophy in AML)
Acute leukaemia
DxT malaise + pallor + bone pain →
ALL
DxT malaise + pallor + oral problems →
AML
Pallor of anaemia Petechiae, bruising Gum hypertrophy/gingivitis/stomatitis Signs of infection Variable enlargement of liver, spleen and lymph nodes Bone tenderness, especially sternum
Acute leukaemia
FBE and film: normochromic/normocytic anaemia; pancytopenia with circulatory blast cells; platelets: usually reduced Bone marrow examination PCR studies Cytogenetics
Acute leukaemia
Treatment: chemotherapy, immunotherapy, stem cell therapy
Acute leukaemia
As a rule, relapse of acute leukaemia means imminent death unless bone marrow
transplantation is successful. The mean 5-year survival rate for childhood ALL is about 75–80%;
for adult ALL 30%;
Acute leukaemia
A disorder of middle age, typically 40–60 years
Insidious onset
Constitutional symptoms: malaise, weight loss, fever, night sweats
Symptoms of anaemia
Splenomegaly (very large); abdominal discomfort
Priapism
Gout
Markedly elevated white cell count (granulocytes)
Marked left shift in myeloid series
Presence of Philadelphia chr
Chronic myeloid leukaemia (CML)
A disorder of late middle age and elderly
Insidious onset
Constitutional symptoms: malaise, weight loss, fever, night sweats
Lymphadenopathy (large rubbery nodes)—neck, axilla, groin (80%)
Moderately enlarged spleen and liver (about 50%)
Mild anaemia
Lymphocytosis >15 × 109/L
‘Mature’ appearance of lymphocytes
Chronic lymphocytic leukaemia (CLL)
DxT fatigue + weight loss + fever/night sweats + lymphadenopathy →
CLL
which are malignant tumours of lymphoid tissue, are classified as Hodgkin
lymphoma and non-Hodgkin lymphoma on the basis of histological appearance of the involved
lymph tissue.
The lymphomas6
Painless (rubbery) lymphadenopathy, especially cervical nodes
Constitutional symptoms (e.g. malaise, weakness, weight loss)
Fever and drenching night sweats—undulant (Pel–Ebstein) fever
Pruritus
Alcohol-induced pain in any enlarged lymph nodes
Possible enlarged spleen and liver
Hodgkin lymphoma
Diagnosis is by lymph node biopsy with histological confirmation. Other tests: FBE,
CXR, CT/MRI (to stage), bone marrow biopsy, functional isotopic scanning. Staging is
by using Ann Arbor nomenclature (IA to IVB). Treatment includes chemotherapy,
immunotherapy and radiotherapy.
Hodgkin lymphoma
DxT malaise + fever/night sweats + pruritus →
Hodgkin lymphoma
are a heterogeneous group of cancers of lymphocytes derived from the
malignant clones of B or T cells
Non-Hodgkin lymphomas
Painless lymphadenopathy—localised or widespread
Constitutional symptoms possible, especially sweating
Pruritus is uncommon
Extra nodal sites of disease (e.g. CNS, bone, skin, GIT)
Possible enlarged liver and spleen
Possible nodular infiltration of skin (e.g. mycosis fungoides)
Diagnosis is by lymph node biopsy.
CXR and CT abdomen to stage.
non-Hodgkin
lymphoma
DxT malaise + fever/night sweats + lymphadenopathy →
non-Hodgkin
lymphoma
is a clonal malignancy of the differentiated β lymphocyte—the plasma cell.
Multiple myeloma
It
is regarded as a disease of the elderly, the mean age of presentation being 65 years
Multiple myeloma
he classic presenting triad in an older person is anaemia, back pain and elevated ESR, which helps to differentiate it from monoclonal gammopathy of uncertain significance (MGUS).
Multiple myeloma
Other investigations include serum protein electrophoresis and immunofixation, Sestamibi scan
Multiple myeloma
Bone pain (e.g. backache)—in more than 80% of patients (possible pathological fracture)
Bone tenderness, e.g. femur, ribs, spine
Weakness, tiredness, increased thirst
Anorexia and weight loss
Recurrent infections, e.g. chest infection
Symptoms of anaemia
Bleeding tendency
Replacement of bone marrow by malignant plasma cells
Multiple myeloma
Impaired renal failure → kidney failure
Associated with amyloidosis and hypercalcaemia
Multiple myeloma
DxT weakness + unexplained back pain + susceptibility to infection →
Multiple myeloma
Diagnostic criteria comprise the presence of:7
paraprotein in serum (on electrophoresis)
Bence–Jones protein in urine
bony lytic lesions on skeletal survey
Multiple myeloma
Treatment is with chemotherapy including thalidomide or lenalidomide: 5-year survival rate is
50% or longer if diagnosed earlier
Multiple myeloma
primary macroglobulinaemia due to a type of malignant plasma cell
abnormality.
Waldenstrom macroglobulinaemia
This uncommon but difficult-to-diagnose disorder caused by the deposition of amyloid
protein is classified as primary, familial or secondary (from chronic infection, e.g. TB,
inflammation, RA, some cancers, others). It may be localised or generalised. Clinical features
depend on the organ targeted such as the heart (CCF), kidney (nephrotic syndrome), GIT
(malabsorption), brain (dementia) and peripheral nerves (e.g. CTS). Diagnosis
Amyloidosis
Hormone secretion by carcinoid cells causes the characteristic carcinoid syndrome long before
local growth or metastatic spread of the tumour is apparent (80% metastasise). Most carcinoid
tumours are asymptomatic.
Carcinoid tumours and syndrome
Classic triad: skin flushing (especially face), diarrhoea (with abdominal cramps), valvular
heart disease
Other possible features: wheezing, telangiectasia, hypotension, cyanosis
Sites of tumours: appendix/ileum, stomach, bronchi
Carcinoid tumours and syndrome
24-hour urine 5-hydroxyindoleacetic acid
Plasma chromogranin A/hepatic ultrasound
Carcinoid tumours and syndrome
Surgery or other ablation: octreotide/others
Carcinoid tumours and syndrome
This is a malignant proliferation of RBCs and also WBCs and platelets
Polycythaemia vera
Older person Fatigue Headache, dizziness, tinnitus Pruritus after hot bath, shower Epistaxis Facial plethora Splenomegaly Thrombosis
Polycythaemia vera
FBE and haematocrit
Bone marrow biopsy
Genetic mutations—JAK2 mutation
Polycythaemia vera
Testicular 98 Prostate 95 Thyroid 92 Melanoma 91 Breast (female) 91 Hodgkin lymphoma 87 Uterus 84 Bladder 77 Non-Hodgkin lymphoma 72 Colon 72 Ovary 41 Stomach 33 Liver 20 Lung 19 Pancreas
Common cancers and their 5-year survival rates (a collation of surveys)
Common sites of metastatic presentation are the lymph nodes, liver, lung, mediastinum and bone. Other sites include the brain, bone marrow, peritoneum, retroperitoneum, skin and the
spinal cord.
Metastatic tumours
Bone. Breast, prostate, lung, Hodgkin lymphoma, kidney, thyroid, melanoma
important sites (listed below) are followed by likely primary sources
Brain. Breast, lung, colorectal, lymphoma, kidney, melanoma, prostate
These important sites (listed below) are followed by likely primary sources, with the most likely
listed first.
Liver. Colon, pancreas, liver, stomach, breast, lung, melanoma
These important sites (listed below) are followed by likely primary sources, with the most likely
listed first.
Lung and mediastinum. Breast, lung, colorectal, kidney, testes, cervix/uterus, Hodgkin
lymphoma, melanoma
These important sites (listed below) are followed by likely primary sources, with the most likely
listed first.
DxT anorexia + weight loss + jaundice (± epigastric pain) →
pancreatic
cancer
DxT fatigue + dysphagia + weight loss →
oesophageal cancer
DxT anorexia + dyspepsia + weight loss →
stomach cancer
DxT headache + a/n/v + ataxia →
medulloblastoma (children)
DxT fever + malaise (extreme) + a/n/v (± anaemia) →
neuroblastoma
DxT mental dysfunction + vomiting + (waking) headache →
cerebral
tumour (late)
DxT indrawn eye + small pupil + ptosis (± anhydrosis) →
Horner
syndrome (?lung cancer)
are well known for their adverse intra-uterine effects on the fetus.
The TORCH organisms (TORCH being an acronym for toxoplasmosis, rubella, CMV and
herpes)
The mosquito-borne infections causing encephalitis and haemorrhagic fevers are mainly viral,
apart from the protozoan causing malaria, and are of particular significance in ______________________
travellers
returning from endemic areas
blood: malaria, trypanosomiasis
GIT: giardiasis, amoebiasis, cryptosporidium
tissues: toxoplasmosis, leishmaniasis, babesiosis
The major protozoal diseases of humans are:
Most of the world’s serious _______________infections—malaria, African trypanosomiasis,
leishmaniasis, amoebiasis—occur in tropical areas
protozoal
is a febrile illness caused by the human herpes virus 4 (Epstein–Barr) virus, one of the
eight known herpes viruses.
Epstein–Barr mononucleosis
It is often called ‘the great imitator’ because of its multisystem
involvement.
Epstein–Barr mononucleosis
It can mimic diseases such as HIV primary infection, streptococcal tonsillitis, viral
hepatitis and acute lymphatic leukaemia.
Epstein–Barr mononucleosis
There are three forms: the febrile, the anginose (with
sore throat, see FIG. 18.1 ) and the glandular (with lymphadenopathy).
Epstein–Barr mononucleosis
It may occur at any age but usually between 10 and 35 years; it is commonest in the 15–25 years
age group.
Epstein–Barr mononucleosis
it usually
affects people in their late teenage years or early 20s. It is endemic in most countries, affecting
over 95% of the adult population worldwide. Subclinical infection is common in young children.
The incubation period is at least 1 month but data are insufficient to define it accurately
Epstein–Barr mononucleosis
is excreted in oropharyngeal secretions during the illness and for some months (sometimes
years) after the clinical infection.
EBV
Slow-onset malaise 1–6 weeks Fever Myalgia Headaches, anorexia Blocked nose—mouth breathing Nasal quality to voice Sore throat (85%) Anorexia, nausea ± vomiting Rash—primary 5% Dyspepsia
Epstein–Barr mononucleosis
DxT malaise + sore throat + fever + lymphadenopathy →
EBM
WCC shows absolute lymphocytosis.
Blood film shows atypical lymphocytes.
Paul–Bunnell or Monospot test for heterophile antibody is positive (although positivity can be
delayed or absent in 10% of cases; 85% positive in adults and older children).
Diagnosis confirmed (if necessary) by EBV-specific antibodies, viral capsid antigen (VCA)
antibodies—IgM, IgG and EB nuclear antigen (EBN-A).
Consider throat culture to rule out streptococcal pharyngitis.
Culture for EBV and tests for specific viral antibodies are not performed routinely
Epstein–Barr mononucleosis
Supportive measures (no specific treatment)
Rest (the best treatment) during the acute stage, preferably at home and indoors
NSAIDs or paracetamol to relieve discomfort
Gargle soluble aspirin or 30% glucose or saline to soothe the throat
Advise against alcohol, fatty foods, continued activity, especially contact sports, for 8 weeks
(risk of splenic rupture)
Ensure adequate hydration
Corticosteroids reserved for: neurological involvement, thrombocytopenia, threatened airway
obstruction (not recommended for uncomplicated cases)
Epstein–Barr mononucleosis
Intra-uterine infection may cause serious abnormalities in the fetus, including CNS
involvement (microcephaly, hearing defects, motor disturbances), jaundice,
hepatosplenomegaly, haemolytic anaemia and thrombocytopenia.
Cytomegalovirus infection
In healthy adults, ___________produces an illness similar to EBM with fever, malaise, arthralgia and
myalgia, generalised lymphadenopathy and hepatomegaly
CMV
In the patient with normal immunity no treatment apart from supportive measures is required, as
the infection is usually self-limiting.
Cytomegalovirus infection
which is caused by Toxoplasma gondii, an obligate intracellular protozoan, is a
worldwide, albeit rare, infection
Toxoplasmosis
The definitive host in its life cycle is the cat (or pig or sheep)
and the human is an intermediate host.
Toxoplasmosis
caused by Mycobacterium tuberculosis, still has a worldwide distribution
with a very high prevalence in Asian countries where 60–80% of children below the age of 14
years are affected
Tuberculosis
This has special implication in Australia, where large numbers of Asian
migrants are settling.
Tuberculosis
Cough Sputum: initially mucoid, later purulent Haemoptysis Dyspnoea (esp. with complications Pleuritic pain
Tuberculosis
Anorexia Fatigue Weight loss Fever (low grade) Night sweats
Tuberculosis
May be no respiratory signs or may be signs of fibrosis, consolidation or cavitation (amphoric
breathing)
Finger clubbing
Tuberculosis
High-risk people/situations Newborn and infants Adults over 60 years Patients with HIV/AIDS Chronic disease, e.g. diabetes Crowded or unsanitary living conditions People affected by alcohol and drugs Immigrants and refugees from endemic countries (especially Indian subcontinent, Papua New Guinea, South-East Asia, Sub Sahara and South Africa)
pulmonary TB
DxT malaise + cough + weight loss ± fever/night sweats + haemoptysis →
pulmonary TB
The primary infection usually involves the lungs. Transmission is by droplet infection.
The focus is usually subpleural in the upper to mid zones and is almost always accompanied by
lymph node involvement.
pulmonary TB
Erythema nodosum may accompany the primary infection
pulmonary TB
is the presence of infection without evidence of active disease (contained by the immune
system) and inability to transmit the infection.
Latent TB infection (LTBI)
Most cases of ________in adults are due to reactivation of disease some years later
TB
The main sites of extrapulmonary disease (in order of frequency in Australia) are the lymph
nodes (the commonest, especially in young adults and children), genitourinary tract (kidney,
epididymis, Fallopian tubes), pleura and pericardium, the skeletal system (arthritis and
osteomyelitis with cold abscess formation), CNS (meningitis and tuberculomas), the eye
(choroiditis, iridocyclitis), the skin (lupus vulgaris), the adrenal glands (Addison disease—see
CHAPTER 14 ) and the GIT (ileocaecal area and peritoneum).
Extrapulmonary TB
This disorder follows diffuse dissemination of tubercle bacilli via the bloodstream,
especially in those with chronic disease and immunosuppression
Miliary tuberculosis
Children living in close contact with people with smear-positive pulmonary TB are highly
vulnerable to acquiring the primary infection. A possible complication is miliary TB
TB in children2
Primary disease is the more common form in young children. Reactivation is more common in
adolescents.
TB
chest X-ray; CT scan if doubtful
sputum or bronchial excretion or gastric aspirates for stain (acid-fast bacilli) and
culture (takes about 6–8 weeks but important); ideally requires 3 specimens over 3
days including one early morning
immunochromatographic finger-prick test (new and promising)
interferon gamma release assay (IGRA)
QuantiFERON–TB Gold blood test
NAAT/PCR test—less sensitive than culture
biopsies on lesions/lymph nodes may be necessary; the hallmark is caseating granulomata
fibre-optic bronchoscopy to obtain sputum may be necessary
consider HIV studies
diagnosis of TB.
<5 mm—negative (note: may be negative in presence of very active pulmonary infection)
5–10 mm—typical of past BCG vaccination
>5 mm—significant in immunocompromised, close contacts and HIV infection
>10 mm—positive = tuberculosis infection (active or inactive)
>15 mm—highly significant for ‘normal’ people
Tuberculin (Mantoux) testing and BCG vaccination
Aboriginal and Torres Strait Islander neonates in regions of high incidence
neonates born to patients with leprosy or family history of leprosy
children <5 years travelling for long periods to countries of high TB prevalence
BCG vaccination is recommended for:
The current antimicrobial treatment is the
standard short-course therapy with four antituberculous drugs initially (rifampicin + isoniazid +
pyrazinamide + ethambutol) daily for 2 months, then rifampicin + isoniazid daily for a further 4
months.
pulmonary TB
Pyridoxine 25 mg daily is
recommended for adults taking isoniazid. A 3-times-weekly regimen is also an option if DOT is
employed. Corticosteroids may be prescribed.
pulmonary TB
extremely common in certain Indigenous groups and is frequently acquired from sexual
contacts overseas
Syphilis
It presents either as a primary lesion or through the chance finding of positive syphilis serology
(reagin tests, treponemal antibody tests, PCR).
Syphilis
The primary lesion or chancre usually develops at the point of inoculation after an incubation
period averaging 21 days.
Primary syphilis
The adjacent lymph nodes are discretely enlarged, firm and non-suppurating. Any
anorectal ulcer or sore should be considered as syphilis until proved otherwise.
Primary syphilis
The interval between the appearance of the primary chancre and the onset of secondary
manifestations varies from 6 to 12 weeks after infection
Primary syphilis
The most common feature of the secondary stage of infection is a rash, which is present in about
80% of cases. The rash is typically a symmetrical, generalised, coppery-red maculopapular
eruption on the face, trunk, palms and soles and is neither itchy nor tender
Primary syphilis
Positive serology in a patient without symptoms or signs of disease is referred to as latent
syphilis and is the commonest presentation of syphilis in Australia today.
Latent syphilis
Spirochaetes can be demonstrated by microscopic examination of smears from early lesions
using dark field techniques and provide an immediate diagnosis in symptomatic syphilis. The
direct fluorescent antibody techniques (FTAABS) can be used on this smear.
Dark field examination8
Serological tests provide indirect evidence of infection, and the diagnosis of asymptomatic
syphilis relies heavily on these tests. The main types of tests are
reagin tests (VDRL and RPR)—not specific for syphilis but useful for screening treponemal tests (TPPA, TPI, EIA, FTAABS)—specific tests, with the latter being sensitive and widely used PCR (blood or CSF)—very sensitive
It is based on parenteral benzylpenicillin or procaine penicillin
syphilis
fever,
especially in patients with a history of cardiac valvular disorders.
Infective endocarditis
It is caused by microbial
infection of the cardiac valves or endocardium.
Infective endocarditis
more invasive
procedures, IV drug use and increased cardiac catheterisation
Infective endocarditis
DxT FUO + cardiac murmur + embolism →
Infective endocarditis
Past history of endocarditis Rheumatically abnormal valves, especially Aboriginal and Torres Strait Islander people Congenitally abnormal valves Mitral valve prolapse Calcified aortic valve Congenital cardiac defects (e.g. VSD, PDA) Prosthetic valves, shunts, conduits IV drug use Central venous catheters
Infective endocarditis
Streptococcus viridans (50% of cases) most susceptible to penicillin
Streptococcus bovis
Enterococcus faecalis
Infective endocarditis
The ‘classic tetrad’ of clinical features:9 signs of infection, signs of heart disease,
signs of embolism, immunological phenomena
Infective endocarditis
Culture the blood of every patient who has a fever and a heart murmur.
Infective endocarditis
FBE and ESR: ESR ↑, anaemia and leukocytosis
urine: proteinuria and microscopic haematuria
blood culture: positive in about 75%8 (at least 3 sets of samples—aerobic and anaerobic
culture)
echocardiography—to visualise vegetations (TOE more sensitive than TTE)
chest X-ray
ECG
Infective endocarditis
Bactericidal antibiotics are chosen on the basis of the results of the blood culture and
antibiotic sensitivities.
Infective endocarditis
treatment must be given IV for at least 2 weeks
treatment is prolonged—usually 4–6 weeks
Infective endocarditis
Benzylpenicillin + gentamicin + di(flu)cloxacillin are recommended
Vancomycin needs to be considered if hospital acquired, MRSA suspected or prosthetic
cardiac valve
Infective endocarditis
Consider Q fever, leptospirosis, orf, anthrax
Meat workers
______________(undulant fever, Malta fever) has diminished in prevalence since the
campaign to eradicate it from cattle.
Brucellosis
DxT malaise + headache + undulant fever →
brucellosis
Brucella agglutination test (rising titre)—acute and convalescent (3–4 weeks) samples
Brucella PCR testing—sensitive and rapid
brucellosis
Adults: doxycycline 100 mg (o) bd for 6 weeks + rifampicin 600 mg (o) daily for 6 weeks
or
gentamicin 4–6 mg/kg/day IV statim then daily for 2 weeks (monitor)
Children: cotrimoxazole + rifampicin
brucellosis
_______________ is a zoonosis due to Coxiella burnetii. It is the most common abattoir-associated infection in Australia and can also occur in farmers and hunters
Q fever
It usually resolves
spontaneously within 2 weeks. Rash is not a major feature but can occur if the infection persists
without treatment. It is transmitted by inhaled dust, animals (wild or domestic) and unpasteurised
milk.
Q fever
Incubation period 1–3 weeks Sudden onset fever, rigors and myalgia Dry cough (may be pneumonia in 20%)14 Petechial rash (if persisting infection) ± Abdominal pain
Q fever
DxT fever + headache + prostration →
Q fever
Coxiella burnetii PCR is effective
Q fever
The disease can be prevented in abattoir workers by using Q fever vaccine
Q fever
follows contamination of abraded or cut skin or mucous membranes with Page 194
Leptospira-infected urine of many animals including pigs, cattle, horses, rats and dogs.
Leptospirosis
There is a risk to dairy farmers
splashed with urine during milking, especially if through open cuts or sores. Early diagnosis is
important to prevent it passing into the immune phase.
Leptospirosis
DxT abrupt fever + headache + conjunctivitis →
leptospirosis
Clinical pattern especially rash of erythema migrans + serology and PCR
Lyme and lyme-like disease
spirochaete, Borrelia burgdorferi, and transmitted by Ixodes ticks, so that people living and
working in the bush are susceptible
Lyme and lyme-like disease
Remove tick
A typical regimen for adults is doxycycline 100 mg bd for 21 days or amoxicillin
Lyme and lyme-like disease
Most patients are bird fanciers. Psittacosis accounts for 1–5% of hospital admissions for
pneumonia.
Psittacosis (‘bird fancier’s disease’)
It is indistinguishable from other atypical
pneumonias except for history of contact with birds.
Psittacosis (‘bird fancier’s disease’)
Serology—rising antibody and PCR
Chest X-ray
Psittacosis (‘bird fancier’s disease’)
is caused by Listeria monocytogenes, a bacterium widespread in nature that
can contaminate food and has been found in many fresh (e.g. fruit and vegetables) and processed
foods (e.g. dairy products, especially unpasteurised milk, soft cheese, processed meats and
smoked seafood).
Listeriosis
influenza-like illness (usually mild) food poisoning, gastroenteritis (atypical) meningitis, especially infants, elderly septicaemia (in susceptible) pneumonia (in susceptible)
Listeriosis
Infections from bites and scratches
cat-scratch disorder, rat bite fever
This sometimes misdiagnosed bacterial infection (Clostridium tetani) can appear from one day to
several months after the injury, which may have been forgotten
Tetanus
Prodrome: fever, malaise, headache
Trismus (patient cannot open mouth)
Risus sardonicus (a grin-like effect from hypertonic facial muscles)
Opisthotonos (arched trunk with hyperextended neck)
Spasms, precipitated by minimal stimuli
Tetanus
Give tetanus antitoxin and human tetanus immunoglobin
Tetanus
(necrotising soft tissue infection) can involve skin and subcutaneous fat, fascia and
muscle.
Gangrene/gas gangrene5
(clostridial myonecrosis) is caused by entry of one of several clostridia organisms,
for example, Clostridium perfringens, into devitalised tissue, such as exists following severe
trauma to a leg.
Gangrene/gas gangrene
Refer immediately to surgical centre for debridement
Start benzylpenicillin 2.4 g IV, 4 hourly + clindamycin
Hyperbaric oxygen if available
Gangrene/gas gangrene
Sudden onset of pain and swelling in the contaminated wound Brownish serous exudate Gas in the tissue on palpation or X-ray Prostration and systemic toxicity Circulatory failure (‘shock’)
Gangrene/gas gangrene
is food poisoning caused by the neurotoxin of Clostridium botulinum
Botulism5
From 12 to 36 hours after ingesting the toxin
from canned, smoked or vacuum-packed food (e.g. home-canned vegetables or meat) visual
problems such as diplopia suddenly appear. Suspect botulism if cranial nerve weakness with
normal sensation.
Botulism
Fever, malaise
Headache
Minimal respiratory symptoms, non-productive cough
Signs of consolidation absent
Chest X-ray (diffuse infiltration) incompatible with chest signs
atypical pneumonia
DxT ‘flu’ + headache + dry cough →
atypical pneumonia
Blood tests and PCR tests are available for all the following causative organisms:
Mycoplasma pneumoniae (the commonest)
Adolescents and young adults: treat with doxycycline (first line) 200 mg statim then 100 mg
daily for 14 days
or
roxithromycin 300 mg (o) daily for 14 days
atypical pneumonia
Related to cooling systems in large buildings
Incubation 2–10 days
Diagnostic criteria include: prodromal-like illness; a dry cough, influenza-like illness,
confusion or diarrhoea; lymphopenia with marked leukocytosis; hyponatraemia; PCR test and
urinary antigen assay
Treatment for mild disease: azithromycin 500 mg (o) daily for 5 days or doxycycline 100 mg
(o) 12 hourly for 10–14 days
Legionella pneumophila (legionnaire disease)
is inflammation of the meninges (pia and arachnoid) and the cerebrospinal fluid
(CSF).
Meningitis
The classic triad is: headache photophobia neck stiffness Other symptoms include malaise, vomiting, fever and drowsiness
Meningitis
Streptococcus pneumoniae, Haemophilus influenzae (especially children), Neisseria
meningitides (the big three)
Listeria monocytogenes, Mycobacterium tuberculosis, Group B Streptococcus, Strep.
agalactiae (common in newborn), Staphylococcus spp., Gram –ve bacilli, such as Escherichia
coli, Borrelia burgdorferi, Treponema pallidum
Meningitis
Enteroviruses (Coxsackie, echovirus, poliovirus); mumps; herpes simplex HSV type 1, 2 or 6;
varicella zoster virus; EBV; HIV (primary infection)
Meningitis
Cryptococcus neoformans or C. gattii
Histoplasma capsulatum
Meningitis
Lumbar puncture (see TABLE 20.1 )
CT scan
Blood culture—all patients with suspected meningitis
CSF microculture/PCR (PCR useful even if antibiotics given)
Specific serology, e.g. HIV, EBV
Note: If significant delay with these investigations, do not withhold treatment
Meningitis
is basically a childhood infection. Neonates and children aged 6–12 months
are at greatest risk.
Bacterial meningitis2
Most cases begin as septicaemia, usually via the nasopharynx
Bacterial meningitis
Fever, pallor, vomiting ± altered conscious and mental state Lethargy Increasing irritability with drowsiness Refusal to feed, indifference to mother Neck stiffness (not always present) Cold extremities (a reliable sign) May be bulging fontanelle Kernig sign (see FIG. 20.1 ): unreliable Brudzinski sign (see FIG. 20.2 ): more reliable sign of meningeal irritation Opisthotonos
Bacterial meningitis
Kernig sign: pain in hamstrings with inability to straighten leg on
passive knee extension with hip flexed at 90°
Bacterial meningitis
Brudzinski sign: neck flexion causes involuntary flexion of hip
and knee
Bacterial meningitis
Meningeal irritation more obvious (e.g. headache, fever, vomiting, neck stiffness)
Later: delirium, altered conscious state
Bacterial meningitis
First: oxygen + IV access and consult
Take blood for culture (within 30 minutes of assessment)—ideally prior to hospitalisation
For child give bolus of 10–20 mL/kg of N saline with added bolus up to total 60 ml/kg if signs
of hypoperfusion
Admit to hospital for lumbar puncture (preliminary CT scan to assess safety of LP in adults)
Dexamethasone 0.15 mg/kg up to 10 mg IV (start at same time as or 15 minutes before
antibiotics—controversial but shown to improve outcome)5
Ceftriaxone 2 g (child >1 month: 50 mg/kg up to 2 g) IV statim then 12 hourly for 4
days
or
cefotaxime 2 g (child: 50 mg/kg up to 2 g) IV
Bacterial meningitis
Treatment is extremely urgent once suspected (e.g. petechial or purpuric rash on trunk and limbs)
(see FIG. 20.4 ). It should be given before reaching hospital. Empirical treatment is:
benzylpenicillin 2.4 g (child: 60 mg/kg IV up to 2.4 g) statim (continue for 5 days)
if IV access not possible give IM or (especially if hypersensitive to penicillin)
Bacterial meningitis
Meningococcal vaccines—B and ACWY given separately
Bacterial meningitis
This is basically a childhood infection. The most common causes are human herpes virus 6 (the
cause of roseola infantum) and enteroviruses (Coxsackie and echovirus).
Viral meningitis
Most cases are benign and self-limiting, but the clinical presentation can mimic bacterial
meningitis, although there are fewer obvious signs of meningeal irritation
Viral meningitis1,6
Lumbar puncture is
important for diagnosis and also PCR for enterovirus. If positive, it can allow early cessation of
antibiotics if commenced empirically.2 Treatment which is symptomatic includes rehydration
and analgesics. Aciclovir is given for herpes meningitis. The immunocompromised require
special management.
Viral meningitis1,6
Very cold hands? Think .
Viral meningitis
is inflammation of the brain parenchyma. It is mainly caused by viruses, although
other organisms including some bacteria, Mycoplasma, Rickettsia and Histoplasma can cause
encephalitis. Suspect it when a viral prodrome is followed by irrational behaviour, altered
conscious state and possibly cranial nerve lesions.
Encephalitis
These can vary from mild to severe.
Constitutional: fever (not inevitable), malaise, myalgia
Meningeal features: headache, photophobia, neck stiffness
Cerebral dysfunction: altered consciousness—confusion, drowsiness, personality changes,
irrational behaviour, seizures, coma
Focal neurological deficit
Encephalitis
A protozoal infection seen in immunocompromised patients, especially HIV. Refer for specialist
advice.
Toxoplasma gondii
Lumbar puncture: CSF (usually aseptic meningitis)
CSF PCR for viral studies, esp. HSV, toxoplasma
CT scan—often shows cerebral oedema
Gadolinium-enhanced MRI
EEG—characteristic waves
Toxoplasma gondii
is a focal area of infection in the cerebrum or cerebellum.
A brain (cerebral) abscess
It presents
as a space-occupying intracerebral lesion
A brain (cerebral) abscess
Suspect in any patient with a raised intracranial
pressure.
A brain (cerebral) abscess
The infection can reach the brain by local spread or via the bloodstream; for example,
endocarditis or bronchiectasis.
A brain (cerebral) abscess
There may be no clue to a focus of infection elsewhere but it can
follow ear, sinus, dental, periodontal or other infection and also a skull fracture. The organisms
are polymicrobial, especially microaerophilic cocci and anaerobic bacteria in the nonimmunosuppressed.
In the immunosuppressed, Toxoplasma, Nocardia sp. and fungi.
A brain (cerebral) abscess
Raised intracranial pressure Headache Nausea and vomiting Altered conscious state Papilloedema
A brain (cerebral) abscess
Focal neurological signs such as hemiplegia, dysphasia, ataxia
Seizures (30%)
Fever (may be absent)
Signs of sepsis elsewhere, e.g. teeth, endocarditis
A brain (cerebral) abscess
MRI (if available) or CT scan
FBE, ESR/CRP, blood culture
Note: Lumbar puncture is contraindicated.
Consider endocarditis
A brain (cerebral) abscess
Management is urgent neurosurgical referral. Aspiration or biopsy is essential to guide
antimicrobial treatment, which may (empirically) include metronidazole IV and a cephalosporin,
e.g. ceftriaxone IV. Nocardiosis is treated with other antibiotics
A brain (cerebral) abscess
These uncommon focal infections can be extremely difficult to diagnose so an index of suspicion
is required to consider such an abscess. The usual organism is Staphylococcus aureus.
Spinal subdural or epidural abscess
Back pain (increasing) ± radiculopathy
Percussion tenderness over spine
Evolving neurological deficit, e.g. gradual leg weakness and sensory loss ± fever (may be
absent)
Spinal subdural or epidural abscess
Associated infection: furuncle, decubitus ulcer, adjacent osteomyelitis, discitis, other
Spinal subdural or epidural abscess
Back trauma with haematoma
Post-subdural or epidural anaesthetic block
One-third is spontaneous
Spinal subdural or epidural abscess
Blood culture
MRI scan to localise abscess and spinal cord pressure
Spinal subdural or epidural abscess
Urgent neurosurgical referral. Empirical therapy while awaiting culture results may include
di/flucloxacillin IV + gentamicin IV or vancomycin IV.
Spinal subdural or epidural abscess
DxT fatigue + psychiatric symptoms + myoclonus →
CJD
Progressive dementia (starts with personality change and memory loss—eventual loss of
speech)
Myoclonus/muscle spasms
Fatigue and somnolence
Variable neurological features (e.g. ataxia, chorea)
Creutzfeldt–Jakob disease
MRI: high signal intensity in thalami
CSF: positive 14-3-3 protein immunoassay
EEG
Brain biopsy after death (ultimate confirmation)
Creutzfeldt–Jakob disease
is a highly contagious enterovirus (picornavirus) transmitted through the faeco-oral route
and is a specific spinal cord anterior horn cell enterovirus. It remains endemic in the tropics.
Most infections (95%) are asymptomatic. Note: Myelitis means inflammation of the spinal cord
Poliomyelitis
Flu-like syndrome, with fever and sore throat, then
‘Pre-paralytic’ stage: nausea and vomiting, headache, stiff neck (meningeal irritation)
Paralytic (0.1%): LMN lesion (flaccid paralysis)—may include spinal polio especially of
lower limbs and/or bulbar polio ± respiratory failure. No sensory loss.
There are 2 levels of polio: minor (recovery in a few days) and major.
Poliomyelitis
Viral studies of throat and faeces—culture and PCR
Serology
CSF: leucocytosis, esp. lymphocytes
Poliomyelitis
Symptomatic paralytic patients should be referred to hospital. Prevention is through vaccination
Poliomyelitis
can present at any stage of syphilis. The main syphilitic syndromes affecting the
CNS are:
Neurosyphilis
Asymptomatic syphilis: present during the interval between the secondary and tertiary stages
of syphilis.
Meningitis including acute basal meningitis and meningovascular syphilis. The latter can
present with a cerebrovascular accident.
Tabes dorsalis causing meningoradiculitis with degeneration of the parenchyma of the spinal
columns of the spinal cord and involvement of the pupils. Features include lightning pains,
Charcot joints, ataxia and neurotrophic ulcers, Argyll Robertson pupils.
General paralysis of the insane with marked personality change, dementia, dysarthria and
seizures
Neurosyphilis
may include tuberculosis meningitis, tuberculoma (presenting as a cerebral
abscess), spinal arachnoiditis and spinal involvement (Pott disease). Treatment with multiple
antimicrobial agents is usually complex and prolonged.
Neurological TB
Worm infestations that can (rarely) cause intracerebral lesions through the formation of cysts or
granulomas include cysticercosis (tapeworms, e.g. Taenia solium), Echinococcus (hydatid) and
Schistosoma.
Helminthic infections
High sensitivity 95%, low specificity for SLE
Antinuclear antibody (ANA)
High sensitivity and specificity for SLE (60%):
found in rheumatoid arthritis
Anti-dsDNA
Highly specific for SLE
Smith (Sm)
Common in Sjögren syndrome and SLE
Common in Sjögren syndrome, SLE (15%)
Ro (SSA)
La (SSB)
Common in 20–30% of patients with
scleroderma
Scl-70 (antitopoisomerase)
Common in 30% of patients with polymyositis
Jo1
High sensitivity and specificity for CREST
syndrome
Anticentromere lc
High sensitivity and specificity for Wegener
granulomatosis
Antineutrophil cytoplasm
ANCA
Diagnostic in antiphospholipid syndrome
Antiphospholipids
Anticardiolipin
Anti-β2-GP1 antibodies
This syndrome may occur with SLE or in isolation and is responsible for recurrent arterial and/or
venous thromboembolism, recurrent spontaneous abortions or thrombocytopenia in the presence
of antiphospholipid antibodies but without features of SLE. Livedo reticularis, skin ulcers and
neuropsychiatric disturbances have also been noted. If suspected, commence aspirin 150–300 mg
(o) daily and refer to a consultant, especially during pregnancy
Antiphospholipid antibody syndrome
which is the commonest of the connective tissue disorders, is described as the
‘great pretender’.3 It is a multisystem autoimmune disorder with a wide variety of clinical
features that are due to vasculitis (see FIG. 21.2 ). Arthritis is the commonest feature of SLE
(90% of cases). Milder manifestations outnumber more severe forms.
Systemic lupus erythematosus
Prevalence about 1 in 1000 of population
Mainly affects women in ‘high oestrogen’ period (90% of cases)
Peak onset between 15 and 45 years
Systemic lupus erythematosus
Fever, malaise, tiredness common
Multiple drug allergies, e.g. sulfonamides
Problems with oral contraceptive pill and pregnancy
Course of remission and flares
Systemic lupus erythematosus
DxT polyarthritis + fatigue + skin lesions →
Systemic lupus erythematosus
Malar (butterfly) rash
Discoid rash
Photosensitivity
Arthritis (symmetric non-erosive arthritis in ≥2 peripheral joints)
Oral ulcers (usually painless)
Serositis (pleurisy or pericarditis)
Kidney features (proteinuria or cellular casts)
Neurological features (intractable headache, seizures or psychosis)
Haematological features (haemolytic anaemia, leucopenia, lymphopenia or thrombocytopenia)
Immunological features (positive anti-dsDNA, antiphospholipid antibodies, anticardiolipin or
anti-Sm tests and false-positive syphilis serology)
Positive antinuclear antibody (ANA) test
SLE
ESR/CRP—elevated in proportion to disease activity
ANA test—positive in 95% (perform first) (key test) but poor specificity
SLE
dsDNA antibodies—90% specific for SLE but present in only 60% (key test)
ENA antibodies, especially Sm—highly specific
Rheumatoid factor—positive in 50%
LE cell test—inefficient and not used
SLE
For suspected SLE, the recommended approach is to perform an ANA test. If positive,
then order dsDNA and ENA antibodies
SLE
Mild: NSAIDs (for arthralgia)
Moderate (especially skin, joint serosa involved): low-dose antimalarials (e.g.
hydroxychloroquine up to 6 mg/kg once daily) (e.g. 400 mg (o) daily for 3 months, then
200 mg daily long term)
SLE,
Rule: treat early and avoid long-term and unnecessary steroid use.
SLE,
Severe: corticosteroids are the mainstay (e.g. prednisolone initially 25–60 mg (o) daily then
7.5–15 mg (o) daily); immunosuppressive steroid-sparing drugs (e.g. azathioprine,
methotrexate with folic acid, bDMARDs (e.g. rituximab, belimumab) may be used for severe
arthralgia and IV or oral cyclophosphamide for organ damage
SLE
This can present as a polyarthritis affecting the fingers in 25% of patients, especially in the early
stages. Soft tissue swelling produces a ‘sausage finger’ pattern. Scleroderma mainly affects the
skin with fibrotic thickening. It presents with Raynaud phenomenon in over 85% of patients
Systemic sclerosis (scleroderma)
There are three clinical variants:
1 limited cutaneous disease, e.g. morphea
2 cutaneous with limited organ involvement (CREST)
3 diffuse systemic disease (systemic sclerosis)
Systemic sclerosis (scleroderma)
Female to male ratio = 3:1
A progressive disease of multiple organs
Raynaud phenomenon
Stiffness and tightness of fingers and other skin areas (see FIG. 21.4 )
‘Bird-like’ facies (mouth puckered)
Dysphagia and diarrhoea (malabsorption)
Oesophageal dysmotility
Respiratory symptoms: pulmonary fibrosis
Cardiac symptoms: vasculopathy, pericarditis, pulmonary arterial hypertension, etc.
Look for tight skin on chest (Roman breastplate)
Systemic sclerosis (scleroderma)
DxT finger discomfort + arthralgia + GORD (± skin tightness) →
Systemic sclerosis (scleroderma)
ESR may be raised
Normocytic normochromic anaemia may be present
ANA test—up to 90% positive (relatively specific)
Rheumatoid factor—positive in 30%
Anticentromere antibodies—specific (positive in 90% with limited disease and 5% with
diffuse)
Antitopoisomerase I (anti-Scl-70) antibody is specific but only positive in 20–30%
Skin biopsy—increase in dermal collagen
Systemic sclerosis (scleroderma)
Empathic explanation, patient education
Analgesics and NSAIDs for pain
Avoid vasospasm (no smoking, beta blockers, ergotamine); calcium-channel blockers such as
nifedipine may help Raynaud
Monitor blood pressure
Treat malabsorption if present; skin emollients
D-penicillamine can help if there is significant systemic or cutaneous involvement
Systemic sclerosis (scleroderma)
Calcinosis Raynaud phenomenon Oesophageal dysmotility Sclerodactyly Telangiectasia Anticentromere antibody (invariably positive)
CREST syndrome
is an uncommon systemic disorder with inflammation of skin and muscle whose
main feature is symmetrical muscle weakness and wasting involving the proximal muscles of the
shoulder and pelvic girdles.
Polymyositis
Any age group
Peak incidence 40–60 years
Female to male ratio = 2:1
Muscle weakness and wasting proximal limb muscles
Main complaint is weakness
Muscle pain and tenderness in about 50%
Arthralgia or arthritis in about 50% (resembles distribution of rheumatoid arthritis)
Dysphagia in about 50% due to oesophageal involvement
Raynaud phenomenon
Consider associated malignancy: lung and ovary
Polymyositis
DxT weakness + joint and muscle pain + violaceous facial rash →
dermatomyositis
rash shows features of photosensitivity. There is heliotrope (violet) discolouration
of the eyelids (see FIG. 21.5 ), forehead and cheeks, and possible erythema resembling sunburn
and peri-orbital oedema. A classic sign is a macular rash over the upper chest, back and
shoulders. There is a characteristic rash on the hands, especially the fingers and nail folds. The
knees and elbows are commonly involved.
dermatomyositis
Muscle enzyme studies (serum creatine kinase and aldolase)
Antibody associations, e.g. anti-Jo1
dermatomyositis
Biopsies—skin and muscle
EMG studies—show characteristic pattern
dermatomyositis
Treatment includes corticosteroids, hydroxychloroquine and cytotoxic drugs. Early referral is
appropriate. Malignancy surveillance is important due to an increased risk of common cancers.
dermatomyositis
The underdiagnosed syndrome of dry eyes (keratoconjunctivitis sicca) in the absence of
rheumatoid arthritis or any other autoimmune disease is known as primary Sjögren syndrome
(SS). There is lymphoid infiltration of the exocrine glands
Sjögren syndrome
primary SS—limited or multisystem
secondary SS—occurs in association with other CTDs including rheumatoid arthritis (accounts
for 50%) or systemic sclerosis
Sjögren syndrome
Fatigue
Sicca (xerostomia, dry eyes, dry vagina)
Difficulty swallowing food
Increased dental caries; denture dysfunction
Salivary gland enlargement; reduced salivation
Xerotrachea → chronic dry cough; hoarseness
Dyspareunia
Arthralgia ± non-erosive arthritis
Sjögren syndrome
DxT dry eyes + dry mouth + arthritis →
Sjögren syndrome
Autoantibody tests—positive ANA(ENA), Ro (SSA), La (ss-B)
Elevated ESR, +ve RA factor, possibly anaemia
Sjögren syndrome
Schirmer tear test (measures conjunctival dryness)
Sjögren syndrome
Referral to rheumatologist
Treatment is symptomatic for dry eyes, mouth and vagina; arthralgia
NSAIDs, hydroxychloroquine or steroids for arthritis
Sjögren syndrome
It is classified as either primary (without associated disease) or secondary (when associated with
any CTD).
Raynaud phenomenon
Patients with primary Raynaud may progress to a CTD but the likelihood is low (5–15%) and the
delay to diagnosis is long (average of 10 years).2 The more severe the Raynaud, the more likely
it is to progress to systemic disease.
Raynaud phenomenon
is a clinical syndrome of episodic arteriolar vasospasm usually involving the fingers and toes (one or two at a time).
Raynaud phenomenon
are a heterogeneous group of disorders involving
inflammation and necrosis of blood vessels, the clinical effects and classification depending on
the size of the vessels involved
The vasculitides or vasculitis syndromes
Small vessel vasculitis is the common type encountered in practice. Medium vessel vasculitis
includes polyarteritis nodosa and large vessel vasculitis includes giant cell arteritis
The vasculitides or vasculitis syndromes
Symptoms suggestive of vasculitis include systemic (malaise, fever, weight loss, arthralgia), skin
lesions (e.g. purpura, ulcers, infarction), respiratory (wheeze, cough, dyspnoea), ENT (epistaxis,
sinusitis, nasal crusting), chest pain (angina), kidney (haematuria, proteinuria, CKF) and
neurological (various, e.g. sensorimotor).
The vasculitides or vasculitis syndromes
This is associated with many important disorders, such as rheumatoid arthritis, SLE, bacterial
endocarditis, Henoch–Schönlein purpura and hepatitis B. Skin lesions are usually associated with
these disorders and the most common presentation is painless, palpable purpura, such as occurs
with Henoch–Schönlein purpura.
Small vessel vasculitis
disease is suspected, early diagnosis is life-saving
because of sinister kidney damage. Perform a urine examination for haematuria and
proteinuria. If positive, order an ANCA test. If positive, refer urgently
If a serious ANCA-associated
Known as ‘pulseless disease’ or ‘aortic arch syndrome’, this vasculitis involves the aortic arch
and other major arteries. It typically affects young Japanese female adults. Features include
absence of peripheral pulses and hypertension
Takayasu arteritis2
The hallmark of PN is necrotising vasculitis of the small and medium arteries leading to skin
nodules, infarctive ulcers and other serious manifestations. The cause is unknown but
associations are found with drug abusers (especially adulterated drugs), B-cell lymphomas, other
drugs and hepatitis B surface antigen. It should be suspected in any multisystemic disease of
obscure aetiology
Polyarteritis nodosa
Young to middle-aged men
Constitutional symptoms: fever, malaise, myalgia, weight loss
Migratory arthralgia or polyarthritis
Subcutaneous nodules along arterial lines
Livedo reticularis and skin ulcers
Kidney impairment and hypertension
Cardiac disorders: arrhythmia, failure, infarction
Diagnosis confirmed by biopsy or angiogram
ESR raised
Treatment is with corticosteroids and immunosuppressants. Refer for specialist care.
Meticulous control of blood pressure is essential
Polyarteritis nodosa
DxT arthralgia + weight loss + fever (± skin lesions) →
polyarteritis nodosa
The basic pathology of this very important disease complex is GCA (synonyms: temporal
arteritis, cranial arteritis).
Giant cell arteritis
The clinical manifestations of polymyalgia rheumatica invariably precede those of
temporal arteritis, of which there is about a 50% association. The diagnosis is based on clinical
grounds. No definite cause has been found.
Giant cell arteritis and polymyalgia rheumatica
Pain and stiffness in proximal muscles of shoulder and pelvic girdle, cervical spine (refer
FIG. 21.7 )
Symmetrical distribution
Typical ages 60–70 years (rare <50)
Both sexes: more common in women
Early morning stiffness lasting >45 minutes
May be systemic symptoms: weight loss, malaise, anorexia, fever
Clinical features (polymyalgia rheumatica)
Painful restriction of movement of shoulders and hips (other joints not usually involved)
Signs may be absent later in day
ESR typically >40 but may be normal
Clinical features (polymyalgia rheumatica)
DxT malaise + painful shoulder girdle + morning stiffness (>50 years) →
Clinical features (polymyalgia rheumatica)
Age >50 New headache—unilateral, throbbing (see CHAPTER 45 ) Visual symptoms, e.g. diplopia Temporal artery tenderness Polymyalgia rheumatica Loss of pulsation of temporal artery Jaw claudication Biopsy of temporal artery (5 cm) is diagnostic
Clinical features (temporal arteritis)
DxT fatigue/malaise + headache + jaw claudication →
Clinical features (temporal arteritis)
No specific test for polymyalgia rheumatica
ESR—extremely high, >50 mm/hr
C-reactive protein—elevated
Mild anaemia (normochromic, normocytic)
polymyalgia rheumatica
Refer any patient with suspected _________urgently.
GCA
Prednisolone
Starting dose:
____________________: 1 mg/kg (usually 60 mg) (o) daily initially for 4 weeks (+
aspirin 100 mg/day) then gradual reduction according to ESR/CRP
temporal (giant cell) arteritis
Prednisolone
____________________: 15 mg (o) daily for 4 weeks, then reduce daily dose by 2–5 mg
every 4 weeks to 10 mg/day, then 1 mg every 4–8 weeks to zero
polymyalgia rheumatica
Taper down gradually to the minimum effective dose (often <5 mg daily) according to the
clinical response and the ESR and CRP. Aim for treatment for 2 years. Relapses are common.
If complicated (e.g. evolving visual loss) give IV methylprednisolone for 3 days prior to oral
agents.
Prednisolone
Azathioprine or methotrexate can be used as steroid-sparing agents.
Giant cell arteritis and polymyalgia rheumatica
In ____________________, a delay in diagnosis after presenting with amaurosis fugax and
non-specific symptoms can have tragic consequences, in the form of ischaemic
events such as blindness and strokes.
giant cell arteritis
is a systemic (multiorgan) vasculitis of unknown aetiology, affecting veins and
arteries of all sizes. The main feature is painful oral ulceration and the hallmark is the ‘pathergy’
reaction whereby simple trauma such as a pinprick can cause a papule or pustule to form within a
few hours at the site.
Behçet syndrome2
Male to female ratio = 2:1 Recurrent oral and/or genital ulceration Arthritis (usually knees) Skin changes, e.g. erythema nodosum Ocular symptoms—pain, reduced vision, floaters (ocular inflammation) There is no specific diagnostic test.
Behçet syndrome2
Associated problems/complications: repeated uveitis and retinitis → blindness, colitis, venous
thrombosis, meningoencephalitis.
Treatment: high-dose steroids and specific ulcer treatment. DMARDs or bDMARDs may be
required.
Behçet syndrome
Patients with Behçet eye disease should be referred promptly for an
ophthalmological opinion, which may be sight-saving
Behçet syndrome
this rare vasculitis of unknown cause has a classic
triad: upper respiratory tract (URT) granuloma, fleeting pulmonary shadows (nodules) and
glomerulonephritis. Without treatment it is invariably fatal and sometimes the initial diagnosis is
that made at autopsy. It is difficult to diagnose, especially as the patient (usually young to
middle-aged) presents with a febrile illness and respiratory symptoms, but early diagnosis is
essential. It usually gets confused with benign nasal conditions.
Granulomatosis2 with polyangiitis
Adolescence to elderly, mean age 40–45 years
Constitutional symptoms (as for PN)
Lower respiratory tract (LRT) symptoms (e.g. cough, dyspnoea)
Oral ulcers
Upper respiratory symptoms: rhinorrhoea, epistaxis, sinus pain, nasal septum loss, ear
dysfunction
Eye involvement—orbital mass
Polyarthritis
Kidney involvement—usually not clinically apparent (about 75% get glomerulonephritis)
Chest X-ray points to diagnosis—multiple nodes, cavitations
Antineutrophil antibodies (c-ANCA) are a useful diagnostic marker (not specific)
Diagnosis confirmed by biopsy, usually an open l
Granulomatosis2 with polyangiitis
DxT malaise + URTs (e.g. rhinitis, sinusitis) + LRTs (e.g. wheeze, cough)
→
Granulomatosis2 with polyangiitis
DxT asthma + rhinitis + vasculitis + hypereosinophilia →
Churg−Strauss
vasculitis
It is invariably binocular, which usually results from extraocular muscular
imbalance or weakness.
Diplopia
Test for double vision with each eye occluded. If diplopia persists, it is uniocular. If, however,
double vision disappears when either eye is covered, there is a defect of one of the muscles
moving the eyeball. Determine whether diplopia occurs in any particular direction of gaze. It is
most marked when moved in the direction of action of the weak muscle. Ask the patient to
follow your finger, red pin or penlight with both eyes and move it in an H pattern.
3rd nerve—eye turned out: divergent squint
6th nerve—failure to abduct: convergent squint (see FIG. 22.1 )
Diplopia
signs occur when a lesion has interrupted a neural pathway at a level above the anterior
horn cell.2 Examples include lesions in motor pathways in the cerebral cortex, internal capsule,
brain stem or spinal cord.
UMN
Clinical examples include stroke (thrombosis, embolism or haemorrhage in the brain), tumours
of the various pathways, demyelinating disease (e.g. multiple sclerosis)
UMN signs
occur when a lesion interrupts peripheral neural pathways from the anterior horn cell,
that is, the spinal reflex arc.
Lower motor neurone lesions
Clinical examples include peripheral neuropathy, Guillain–Barré syndrome, poliomyelitis and a
thickened peripheral nerve (e.g. leprosy).
Lower motor neurone lesions
is a progressive neuromuscular disorder resulting in muscular limb and bulbar weakness
due to death of motor neurones in the brain, brain stem and spinal cord
Motor neurone disease (MND)
The sensory system is not involved, nor the cranial nerves to the eye muscles.
Motor neurone disease (MND)
Five to 10% of MND is inherited with an
autosomal dominant pattern; the rest is sporadic.
Motor neurone disease (MND)
amyotrophic lateral sclerosis (Lou Gehrig disease)—combined LMN muscle atrophy plus
UMN hyper-reflexia, leading to progressive spasticity. This is the most common type.
Motor neurone disease (MND)
progressive muscle atrophy—wasting beginning in the distal muscles; widespread
fasciculation
Motor neurone disease (MND)
progressive bulbar (LMN) palsy and pseudobulbar palsy (LMN lesions in the brain stem
motor nuclei). Results in wasted fibrillating tongue, weakness of chewing and swallowing, and
of facial muscles.
Motor neurone disease (MND)
Weakness or muscle wasting—first noticed in hands (weak grip) or feet
Stumbling (spastic gait, foot drop)
Difficulty with swallowing
Difficulty with speech, for example, slurring, hoarseness
Fasciculation (twitching) of skeletal muscles and fibrillating tongue
Cramps
Emotional instability, depression
± Muscle pain
Motor neurone disease (MND)
is incurable and progresses to death usually within 3–5 years from ventilatory
failure/aspiration pneumonia.
Motor neurone disease (MND)
No treatment is proven to influence outcome although riluzole, a sodium channel blocker,
appears to slow progression slightly. Baclofen 10 mg bd may help symptoms of cramp.
Botulinum toxin may help spasticity and propantheline or amitriptyline for drooling.
Multidisciplinary care is essential. Management is supportive.
Motor neurone disease (MND)
The tremor of PD is present at rest. The hand tremor is most marked with the arms supported on
the lap and during walking. The characteristic movement is ‘pill-rolling’ where movement of the
fingers at the metacarpophalangeal joints is combined with movements of the thumb.
Resting tremor—Parkinsonian
The resting
tremor decreases on finger–nose testing. The best way to evoke the tremor is to distract the
patient, such as focusing attention on the left hand with a view to ‘examining’ the right hand or
by asking the patient to turn the head from side to side.
Resting tremor—Parkinsonian
This fine tremor is noted by examining the patient with the arms outstretched and the fingers
apart. The tremor may be rendered more obvious if a sheet of paper is placed over the dorsum of
the hands. The tremor is present throughout movement, being accentuated by voluntary
contraction.
Action or postural tremor
Essential tremor (also called familial tremor or benign essential tremor)
Senile tremor
Physiological
Anxiety/emotional
Hyperthyroidism
Alcohol
Drugs, for example, drug withdrawal (e.g. heroin, cocaine, alcohol), amphetamines, lithium,
sympathomimetics (bronchodilators), sodium valproate, heavy metals (e.g. mercury), caffeine,
amiodarone
Phaeochromocytoma
Action or postural tremor
This coarse oscillating tremor is absent at rest but exacerbated by action and increases as the
target is approached. It is tested by ‘finger–nose–finger’ touching or running the heel down the
opposite shin, and past pointing of the nose is a feature. It occurs in cerebellar lobe disease, with
lesions of cerebellar connections and with some medications.
Intention tremor (cerebellar disease)
A flapping or ‘wing-beating’ tremor is observed when the arms are extended with
hyperextension of the wrists. It involves slow, coarse and jerky movements of flexion and
extension at the wrists.
Note: Flapping (asterixis) is not strictly a tremor
Flapping (metabolic tremor)
Wilson syndrome Hepatic encephalopathy Uraemia Respiratory failure Lesions of the red nucleus of the midbrain (the classic cause of a flap)
Flapping (metabolic tremor)
which is probably the most common movement disorder (2–5% prevalence),
has been variously called benign, familial, senile or juvenile tremor.
Essential tremor
Autosomal dominant disorder (variable penetrance)
Often begins in early adult life, even adolescence
Usually begins with a slight tremor in both hands
May involve head (titubation), chin and tongue and rarely trunk and legs
Interferes with writing (not micrographic), handling cups of tea and spoons, etc.
Tremor most marked when arms held out (postural tremor); less evident at rest
Tremor exacerbated by anxiety
May affect speech if it involves bulbar musculature
Relieved by alcohol
Can swing arm and gait normal
Essential tremor
Positive family history
Tremor with little disability
Normal gait
Essential tremor
This is not always easy as a postural tremor can be present in PD, although the hand tremor is
most marked at rest with the arms supported on the lap. Parkinsonian tremor is slower at 4–6 Hz
while essential tremor is much faster at around 8–13 Hz. Imaging is unnecessary
Distinguishing essential tremor from Parkinson disease
A most useful way to differentiate the two causes is to observe the gait. It is normal in essential
tremor but in PD there may be loss of arm swing and the step is usually shortened with stooped
posture and shuffling gait.
Distinguishing essential tremor from Parkinson disease
use propranolol (first choice) or primidone 62.5 mg nocte (up to 250 mg).3 A typical
starting dose of propranolol is 10–20 mg bd; many require 120–240 mg/day.3 If the tremor is
only intrusive at times of increased emotional stress, intermittent use of benzodiazepines (e.g.
lorazepam 1 mg) 30 minutes before exposure to the stress may be all that is required. Modest
alcohol intake (e.g. a glass of whisky) is very effective. A standard drink of alcohol often
alleviates the tremor. Larger doses of alcohol have no additional effect. If drugs fail, deep brain
stimulation to the thalamus can be used.
Essential tremor
is a disorder of the automatic processor of the brain which relies on
dopamine to maintain movements at a selected size and speed. Loss of dopamine causes
movements to become smaller and slower. The pathological features are loss of dopamineproducing
neurones from the substantia nigra in the brain stem together with Lewy bodies in the
neurones.4 Genetic factors occur in 5% of individuals.
Parkinson disease
One of the most important clinical aspects of PD, which has a slow and insidious onset, is the
ability to make an early diagnosis. Sometimes this can be very difficult, especially when the
tremor is absent or mild, as occurs with the atherosclerotic degenerative type of Parkinsonism.
The lack of any specific abnormality on special investigation leaves the responsibility for a
diagnosis based on the history and examination. As a general rule of thumb the diagnosis of PD
is restricted to those who respond to levodopa (L-dopa)—the rest are termed Parkinsonism or
‘Parkinson plus’.
Parkinson disease
- Tremor (at rest)
- Rigidity
- Bradykinesia/hypokinesia
- Postural instability
- Gait freezing
≥2 signs = Parkinson disease
Parkinson disease
PD is a most common and disabling chronic neurological disorder. About 90%
are idiopathic.
The prevalence in Australia is 120–150 per 100 000.5 Lifetime risk is 1 in 40.
Parkinson disease
The incidence rises sharply over 70 years of age (peak 65 years).5
The diagnosis is based on the history and examination.
Always think of PD in an older person presenting with falls.
A reduced sense of smell is one of the first symptoms. Others that may precede
PD include constipation, REM sleep disorders and orthostatic hypotension.
Non-motor automatic dysfunctions: cognition, behaviour, mood.
Hemi-parkinsonism can occur; all the signs are confined to one side and thus
must be differentiated from hemiparesis. In fact, most cases of PD start
unilaterally.
Always consider drug-induced Parkinsonism. The usual drugs are
phenothiazines, butyrophenones and reserpine. Tremor is uncommon but rigidity
and bradykinesia may be severe.
Other causes include vascular (atherosclerosis) and normal pressure
hydrocephalus.
Parkinson disease
Power, reflexes and sensation are usually normal.
Muscle tone is increased: patients display cogwheel or lead-pipe rigidity when tested at wrist.
The earliest abnormal physical signs to appear are loss of dexterity of rapid alternating
movements and absence of arm swing, in addition to increased tone with distraction.
Positive frontal lobe signs, such as grasp and glabellar taps (only allow three blinks), are more
common with Parkinsonism.
Note: There is no laboratory test for PD—it is a clinical diagnosis. Hypothyroidism and
depression, which also cause slowness of movement, may cause confusion with diagnosis.
Note: The Steele–Richardson–Olszewksi syndrome (also known as progressive supranuclear
palsy—PSP parkinsonism, mild dementia and vertical gaze dysfunction) is worth considering
Parkinson disease
Walking sticks (which spread the centre of gravity) with appropriate education into their use may be necessary to help prevent falls, and constant care is required. Admission to a nursing home for end-stage disease may be appropriate. Correct dopamine deficiency and/or block cholinergic excess in the brain
Parkinson disease
Avoid postponing treatment. It should be commenced as soon as symptoms interfere with
working capacity or the patient’s enjoyment of life. This will be apparent only if the correct
questions are asked as the patient may accept impaired enjoyment without appreciating that it is
due to PD. Start low—L-dopa 100/25 (½ tab bd) and go slow. There is usually no difference
between the L-dopa preparations. The dosage should be tailored so that the patient neither
develops side effects nor is on an inadequate dose of medication without significant therapeutic
benefit (see TABLE 22.6 ). The dose usually progresses to 1 tab bd, then consider add-on
therapy.
Parkinson disease
The older drugs, such as anticholinergics and amantadine, still have a place in modernmanagement but L-dopa, which basically counters bradykinesia, is the best drug and the baseline
of treatment. With the onset of disability (motor disturbances), L-dopa in combination with a
decarboxylase inhibitor (carbidopa or benserazide) in a 4:1 ratio should be introduced. L-dopa
therapy does not significantly improve tremor but improves rigidity, dyskinesia and gait disorder.
It is preferred in those >70 years.10 Consider benzhexol or benztropine if tremor is the feature,
especially in young patients.
The new non-ergot derivative dopamine agonists (e.g. pramipexole and rotigotine) can be used in
treatment, especially with the L-dopa ‘on–off’ phenomenon (fluctuations throughout the day),
and also as first-line monotherapy in early PD in certain circumstances and with caution.8 They
are preferred to the ergot derivatives because of a superior adverse effect profile. They appear to
be most effective when used in combination. The ergot derivatives can have serious adverse
effects, including cardiac valve damage, and are no longer recommended. Selegiline is an
effective second-line drug, especially in combination with Sinemet. If there is associated pain,
depression or insomnia, the tricyclic agents (e.g. amitriptyline) can be effective
Parkinson disease
Mild (minimal disability):
L-dopa preparation (low dose), e.g. L-dopa 100 mg + carbidopa 25 mg (½ tab bd—increase
gradually as necessary to 1 tab (o) tds)
or
amantadine 100 mg (o) daily may help the young or the elderly for up to 12 months—if
inadequate response
selegiline up to 5 mg bd can be added to L-dopa if necessary
Moderate (independent but disabled, e.g. writing, movements, gait):
L-dopa preparation
selegiline 1 mg bd
and/or
add if necessary—non-ergot
Parkinson disease
Severe (disabled, dependent on others):
L-dopa (to maximum tolerated dose) + non-ergot dopamine agent
add entacapone 200 mg (o) with each dose of L-dopa, e.g. Stalevo
consider antidepressants
Parkinson disease
After 3–5 years of L-dopa treatment, side effects may appear in about one-half of patients:5
involuntary movements—dyskinesia
end-of-dose failure (reduced duration of effect to 2–3 hours only)—consider entacapone
‘on–off’ phenomenon (sudden inability to move, with recovery in 30–90 minutes)
early morning dystonia, such as clawing of toes (due to disease—not a side effect)
Specialist advice is appropriate.
Parkinson disease
apomorphine can be used for severe akinesia not responsive to L-dopa
for nausea and vomiting side effects: domperidone 20 mg (o) tds 24 hours prior to
apomorphine
better control may also be achieved with: amantadine 100 mg (o) bd
duodopa—levodopa into jejunum
Parkinson disease
The preferred method is high-frequency deep brain stimulation via electrodes into the
subthalamic nucleus, which may benefit all major features of the disease. The indication for
surgery such as thalamotomy is erratic and disabling responses to prolonged L-dopa therapy,
especially for annoying dyskinesias. It is considered more appropriate for younger patients with a
unilateral tremor
Parkinson disease
One of the simplest diagnostic tools for PD, as compared with Parkinsonism, is a
trial of therapy with L-dopa. The response is excellent while that for Parkinsonism
is poor.
L-dopa is the gold standard for therapy.
Ensure that a distinction is made between drug-induced involuntary movements
and the tremor of PD.
Keep the dose of L-dopa as low as possible to avoid these drug-induced
involuntary movements.
Practice tips for Parkinson disease
In the elderly with a fractured hip always consider PD (a manifestation of
disequilibrium).
Remember the balance of psychosis and PD in treatment.
Keep in mind the ‘sundown’ effect—patients often go psychotic as the sun goes
down.
Don’t fail to attend to the needs of the family, who often suffer in silence.
If drugs are to be withdrawn they should be withdrawn slowly.
Practice tips for Parkinson disease
is the most common cause of progressive neurological disability in the
20–50 year age group
Multiple sclerosis (MS)
It is generally accepted that MS is an autoimmune disorder. Genetic and
environmental factors are believed to play a role
Multiple sclerosis (MS)
Early diagnosis is difficult because MS is
characterised by widespread neurologic lesions that cannot be explained by a single anatomical
lesion, and the various symptoms and signs are subject to irregular exacerbations and remissions.
Multiple sclerosis (MS)
The lesions are ‘separated in time and space’. The most important issue in diagnosis is the need
for a high index of suspicion. The use of MRI has revolutionised the diagnosis of MS.
Multiple sclerosis (MS)
is a primary demyelinating disorder with demyelination occurring in plaques throughout the
white and grey matter of the brain, brain stem, spinal cord and optic nerves. The clinical features
depend on their location. There is a loss of brain volume
Multiple sclerosis (MS)
There is a variety of types of MS—relapsing remitting (most common), secondary progressive,
progressive relapsing and primary progressive—together with ‘benign’ and ‘malignant’ forms.
Multiple sclerosis (MS)
More common in females (3:1)
Peak age of onset is in the fourth decade
Transient motor and sensory disturbances
UMN signs
Symptoms develop over several days but can be sudden
Monosymptomatic initially in about 80%
Only 20% have a benign disease
multiple sclerosis
Multiple symptoms initially in about 20%
Common initial symptoms include:
visual disturbances of optic neuritis (blurred vision or loss of vision in one eye—sometimes
both); central scotoma with pain on eye movement (looks like unilateral papilloedema)
diplopia (brain-stem lesion)
weakness in one or both legs, paraparesis or monoparesis
sensory impairment in the lower limbs and trunk: numbness, paraesthesia; band-like
sensations; clumsiness of limb (loss of position sense); feeling as though walking on cotton
wool
vertigo (brain-stem lesion)
multiple sclerosis
Subsequent remissions and exacerbations that vary from one individual to another
80% have a relapsing remitting disease
There is a progressive form, esp. in women around 50 years
Anxiety, depression and other mood disorders are common
multiple sclerosis
Bladder disturbances, including retention of urine and urgency
‘Useless hand’ due to loss of position sense
Facial palsy
Trigeminal neuralgia
Psychiatric symptoms
In established disease, common symptoms are fatigue, impotence and bladder disturbances
multiple sclerosis
The diagnosis is clinical along with the MRI and depends on the following determinants
multiple sclerosis
Lesions are invariably UMN.
>1 part of CNS is involved, although not necessarily at time of presentation.
Episodes are separated in time and space.
Practically MS can only be diagnosed after a second relapse or when the MRI shows new
lesions.11
An early diagnosis requires evidence of contrast-enhancing lesions or new T2 lesions on the
MRI indicating dissemination in time.
The diagnostic criteria is based on the internationally accepted 2010 McDonald criteria
multiple sclerosis
Lumbar puncture: oligoclonal IgG detected in CSF in 90% of cases14 (only if necessary)
Visual evoked potentials: abnormal in about 90% of cases
MRI scan: usually abnormal, demonstrating MS lesions in about 90% of cases14
multiple sclerosis
The course is variable and difficult to predict. An early onset (<30 years) is usually ‘benign’
while a late onset (≥50 years) is often ‘malignant’.
MS follows a classic history of relapses and remissions in 80–85% of patients.14
The rate of relapse is about once in 2 years.
About 20% have a progressive course from the onset with a progressive spastic paraparesis
(applies mainly to late-age onset).
The average duration of MS is about 40 years from diagnosis to death.14
A ‘benign’ course occurs in about 30% of patients with 10–20% never suffering major
disability.
The median time to needing a walking aid is 15 years.8
The likelihood of developing MS after a single episode of optic neuritis is about 60%.
multiple sclerosis
All patients should be referred to a neurologist for confirmation of the diagnosis, which must
be accurate.
Explanation about the disorder and its natural history should be given.
Acute relapses require treatment if causing significant disability.
Depression and anxiety, which are common, require early treatment, e.g. paroxetine.
CBT or mindfulness-based interventions.
multiple sclerosis
Mild relapses
Mild symptoms, such as numbness and tingling, require only confirmation, rest and reassurance.
Moderate relapses
Prednisolone—in outpatient setting
Severe relapses or attacks8,15
These attacks include optic neuritis, paraplegia or brain-stem signs. Admit to hospital for IV
therapy:
methylprednisolone 1 g in 200 mL saline by slow IV infusion (1 hour) daily for 3 days
Plasma exchange may be used.
Observe carefully for cardiac arrhythmias
multiple sclerosis
Currently first-line immunomodulators are the interferons, glatiramer acetate and the monoclonal
antibodies natalizumab and alemtuzumab, or others.
Interferon beta-1b (SC injection) and beta-1a (IM injection) appear to be effective (but
expensive) for those with frequent and severe attacks.
New agents being evaluated include teriflunomide, siponimod, daclizumab, ocrelizumab and
Biotin.
multiple sclerosis
Physiotherapy Baclofen 10–25 mg (o) nocte For continuous drug therapy: baclofen 5 mg (o) tds, increasing to 25 mg (o) tds + diazepam 2–10 mg (o) tds An alternative is dantrolene Paroxysmal (e.g. neuralgias) Carbamazepine or gabapentin
multiple sclerosis
The reported efficacy of the cannabis-based medicine Sativex for relaxation, pain and bladder function is still being debated. One RCT showed a positive effect on detrusor activity
multiple sclerosis
refers to all conditions causing nerve damage outside the central
nervous system.
Peripheral neuropathy
It can be a mononeuropathy, such as carpal tunnel syndrome; mononeuropathy
multiplex involving multiple single nerves in an asymmetric pattern (as in vasculitides); or a
polyneuropathy, which is a diffuse symmetric disorder best referred to as PN. It can be classified
according to clinical progression as acute, subacute or chronic. The manifestations can be
sensory, motor, autonomic or mixed (sensorimotor).
Peripheral neuropathy
Sensory symptoms: tingling, burning, numbness in extremities, unsteady gait (loss of position
sense)
Motor symptoms (LMN): weakness or clumsiness in hands, foot/wrist drop
Signs: may be classic ‘glove and stocking’ sensory loss, sensory ataxia, LMN signs—distal
muscle wasting, muscle weakness, reflexes absent or depressed, fasciculations
Peripheral neuropathy
Mostly sensory: diabetes mellitus, vitamin deficiency (folate, B1, B6, B12), alcohol, various
neurotoxic drugs, leprosy, uraemia (CKF), amyloidosis, malignancy
Mostly motor: lead poisoning, porphyria, various neurotoxic drugs, Charcot–Marie–Tooth
syndrome (peroneal muscle atrophy), acquired inflammatory polyneuropathies—acute
(Guillain–Barré syndrome) and chronic (chronic inflammatory demyelinating polyneuropathy)
Peripheral neuropathy
which is a rapidly progressive and treatable cause of PN or ascending
radiculopathy, is potentially fatal. Early diagnosis of this serious disease by the family doctor is
crucial as respiratory paralysis may lead to death. The underlying pathology is segmental
demyelination of the peripheral nerves and nerve roots
Acute inflammatory polyradiculoneuropathy (Guillain–
Barré syndrome)
Weakness in the limbs (usually symmetrical)
Paraesthesia or pain in the limbs (less common)
Both proximal and distal muscles affected, usually starts peripherally and moves proximally
Facial and bulbar paralysis (rare)
Weakness of extraocular muscles (rarely)
Reflexes depressed or absent
Variable sensory loss but rare
Within 3–4 weeks the motor neuropathy, which is the main feature, progresses to a maximum
disability, possibly with complete quadriparesis and respiratory paralysis
Acute inflammatory polyradiculoneuropathy (Guillain–
Barré syndrome)
CSF protein is elevated; cells are usually normal.
Motor nerve conduction studies are abnormal
Acute inflammatory polyradiculoneuropathy (Guillain–
Barré syndrome)
Admit to hospital.
Respiratory function (vital capacity) should be measured regularly (2–4 hours at first).
Tracheostomy and artificial ventilation may be necessary.
Physiotherapy to prevent foot and wrist drop and other general care should be provided.
Acute inflammatory polyradiculoneuropathy (Guillain–
Barré syndrome)
Treatment is with plasma exchange or IV immunoglobulin (0.4 g/kg/day for 5 days), which
may need to be continued monthly.8
Corticosteroids are not generally recommended.
Acute inflammatory polyradiculoneuropathy (Guillain–
Barré syndrome)
About 80% of patients recover without significant disability. Approximately 5% relapse
Acute inflammatory polyradiculoneuropathy (Guillain–
Barré syndrome)
This is an inherited autosomal dominant polyneuropathy with an insidious onset from puberty.
Clinical features include weakness in the legs, variable distal sensory loss and muscle atrophy
giving the ‘inverted champagne bottle’ appearance of the legs. The features vary according to the
various subgroups. Refer for electrodiagnostic studies and specific genetic testing.
Charcot–Marie–Tooth syndrome
is an acquired autoimmune disorder that usually affects muscle
strength. Patients have fluctuating symptoms and variable distribution of muscle weakness. All
degrees of severity, ranging from occasional mild ptosis to fulminant quadriplegia and
respiratory arrest, can occur20 (see TABLE 22.8 ). It is associated with thymic tumour and other
autoimmune diseases, for example, RA, SLE, thyroid and pernicious anaemia.
Myasthenia gravis
Painless fatigue with exercise
Weakness also precipitated by emotional stress, pregnancy, infection, surgery
Variable distribution of weakness:
ocular: ptosis (60%) and diplopia (see FIG. 22.7 ); ocular myasthenia only remains in
about 10%
bulbar: weakness of chewing, swallowing, speech (ask to count to 100), whistling and head
lolling
limbs (proximal and distal)
generalised
respiratory: breathlessness, ventilatory failure
Note: The classic MG image is ‘the thinker’—the hand used to hold the mouth closed and the
head up.
Myasthenia gravis
Serum anti-acetylcholine receptor antibodies
Electrophysiological tests if antibody test negative
CT scan to detect thymoma
Edrophonium test still useful but potentially dangerous (atropine is the antidote)
Myasthenia gravis
Refer for consultant management.
Detect possible presence of thymoma with CT or MR scan of thorax. If present, removal is
recommended.
Thymectomy is recommended early for generalised myasthenia, especially in all younger
patients with hyperplasia of the thymus, even if not confirmed preoperatively.
Plasmapheresis is useful for acute crisis or where temporary improvement is required or
patients are resistant to treatment.
Avoid drugs that are relatively contraindicated.
Pharmacological agents:
anticholinesterase inhibitor drugs, first-line (e.g. pyridostigmine, neostigmine or
distigmine), should be used only for mild-to-moderate symptoms
corticosteroids are useful for all
Myasthenia gravis
The combination of ocular and facial weakness should alert the family doctor to
the possibility of a neuromuscular disorder, especially MG or mitochondrial
myopathy.19 Look for weakness and fatigue.
Beware of facioscapulohumeral dystrophy.
Practice tips for myasthenia gravis
Ptosis may develop only after looking upwards for a minute or longer.
Smiling may have a characteristic snarling quality.
Practice tips for myasthenia gravis
It is worth remembering that the four major causes of ptosis are:
1. 3rd cranial nerve palsy—ptosis, eye facing ‘down and out’, dilated pupil, sluggish light reflex
2. Horner syndrome—ptosis, miosis (constricted pupil), ipsilateral loss of sweating
3. Mitochondrial myopathy—progressive external ophthalmoplegia or limb weakness, induced
by activity—no pupil involvement
4. Myasthenia gravis—ptosis and diplopia, no pupil involvement
Ptosis
are sustained or intermittent abnormal repetitive movements or postures resulting from
alterations in muscle tone. The dystonic spasms may affect one (focal) or more (segmental) parts
of the body or the whole body (generalised).
Dystonia
Misdiagnosis is common as transient symptoms may be mistaken for an
emotional or psychiatric disorder. Many cases take years to diagnose.
Dystonias are often regarded as nervous tics.
The cause is thought to be disorders of the basal ganglia of the brain, but mainly
there is no known specific cause.
Neuroleptic and dopamine receptor blocking agents (e.g. L-dopa,
metoclopramide) can induce a severe generalised dystonia (e.g. oculogyric
crisis) which is treated with benztropine 1–2 mg IM or IV.8 However, L-dopa is
the drug of choice in some L-dopa responsive dystonias
Dystonia
Motor and vocal tics are a feature of Tourette disorder. If socially disabling, treat with:
haloperidol 0.25 mg (o) nocte, very gradually increasing to 2 g (max.) daily7
or
clonidine 25 mcg (o) bd for 2 weeks, then 50–75 mcg bd
Tics
Idiopathic facial (7th nerve) palsy, which is an acute unilateral lower motor neurone paresis or
paralysis, is the commonest cranial neuropathy. The classic type is Bell palsy, which is usually idiopathic although attributed to an inflammatory swelling involving the facial nerve in the bony
facial canal. In Ramsay–Hunt syndrome, which is due to infection with herpes zoster causing
facial nerve palsy, vesicles may be seen on the ipsilateral ear.
Facial nerve (Bell) palsy15
Associations: herpes simplex virus (postulated) diabetes mellitus hypertension thyroid disorder, e.g. hyperthyroidism
Facial nerve (Bell) palsy
Abrupt onset (can worsen over 2–5 days)
Weakness in the face (complete or incomplete)
Preceding pain in or behind the ear
Impaired blinking
Bell phenomenon—when closing the eye it turns up under the half-closed lid
Less common:
difficulty eating
loss of taste—anterior two-thirds of tongue
hyperacusis
Facial nerve (Bell) palsy
prednisolone 1 mg/kg (o) up to 75 mg (usually 60 mg) daily in the morning for 5 days (start
within 48 hours of onset)
Note: This is controversial, but recent randomised trials and a Cochrane review support the use
of prednis(ol) one. No good evidence for antiviral drugs, but low-grade evidence for benefit if
combining with a corticosteroid.
Patient education and reassurance
Adhesive patch or tape over eye if corneal exposure (e.g. windy or dusty conditions, during
sleep)
Artificial tears if eye is dry and at bedtime
Facial nerve (Bell) palsy
Massage and facial exercises during recovery
Note:
At least 70–80% achieve full spontaneous recovery; higher if mild. Remission should begin
within 1 week of onset.
Electromyography and nerve excitability or conduction studies are a prognostic guide only.
No evidence that nucleoside analogue, for example, aciclovir, is useful but should be used for
Ramsay–Hunt syndrome.
No evidence that surgical procedures to decompress the nerve are beneficial
Facial nerve (Bell) palsy
dysarthria + intention tremor + nystagmus
→ cerebellar disease
typical of MS
visual disturbance (blurred or transient loss) + weakness in limbs ± paraesthesia in limbs
→ multiple sclerosis
rigidity + bradykinesia + resting tremor
→ Parkinson disease
tremor (postural or action) + head tremor + absence of
Parkinsonian features
→ essential tremor
fatiguable and weakness of eyelids and eye
movements + limbs + bulbar muscles (speech and
swallowing)
→ myasthenia gravis
ascending weakness of limbs + of face + areflexia*
→ Guillain–Barré
syndrome (GBS)
(episodic) vertigo + tinnitus + hearing loss
→ Ménière syndrome
dementia + myoclonus + ataxia
→ Creutzfeldt–Jakob
disease
drowsiness + vomiting + headache (waking)
→ ↑ intracerebral
pressure
enophthalmos + meiosis + ptosis ± anhydrosis
→ Horner syndrome
blank spell + lip-smacking (or similar automation) +
olfactory/gustatory hallucination
→ complex partial
seizure
gradual spread (Jacksonian march) of focal jerking
(mouth, arm or leg) or sensory disturbance or (rarely)
visual field disturbance
→ simple partial
seizure
↑ intracranial pressure +/or focal signs +/or epilepsy
→ cerebral tumour
dysphagia + dysphonia/dysarthria + spastic tongue
→ pseudobulbar
palsy
recurrent: headache (often unilateral) + nausea (±
vomiting) + visual aura*
→ migraine with aura
(formerly ‘classical
recurrent: severe retro-orbital headache + rhinorrhoea
+ lacrimation*
→ cluster headache
instantaneous: headache ± vomiting ± neck stiffness
→ subarachnoid
haemorrhage until
disproven
headache + visual obscurations + papilloedema (often
in obese young female)
→ benign intracranial
hypertension
acute and transient: amaurosis fugax or dysphasia or
hemiplegia*
→ TIA (carotid)
typical facies (temporalis atropy and frontal balding) + muscle weakness esp. hands (± myotonia) + cataracts
→ dystrophia
myotonica (myotonic
dystrophy)
vertigo + provoked by movement (especially rolling in
bed) + Hallpike test +ve
→ BPPV
UMN signs + LMN signs + fasciculations
→ motor neurone
disease
leg weakness + ataxic gait + clumsiness (appears
about 12 years)
→ Friedreich ataxia
limb weakness + flaccid paralysis (day after exercise in
a young person)
→ familial periodic
paralysis
which is a disorder of iron overload, is the most common
serious single gene genetic disorder in our population.
Hereditary haemochromatosis (HHC),
It is a common condition in which the total body iron concentration is increased to 20–60 g
(normal 4 g). The excess iron is deposited in and can damage several organs:
liver—cirrhosis (10% develop cancer)
pancreas—‘bronze’ diabetes
Hereditary haemochromatosis (HHC),
skin—bronze or leaden grey colour
heart—restrictive cardiomyopathy
pituitary—hypogonadism, impotence
joints—arthralgia (especially hands), chondrocalcinosis
It is usually hereditary (autosomal recessive = AR) or may be secondary to chronic haemolysis
and multiple transfusions.
Note: Hereditary haemochromatosis is the genetic condition; haemosiderosis is the secondary
condition.
Hereditary haemochromatosis (HHC),
Being an autosomal recessive disorder, the patient must inherit two altered (mutated) copies of
the gene. It is a problem mainly affecting Caucasians, usually from middle age onwards. About 1
in 10 people are silent carriers of one mutated gene, while 1 in 200 are homozygous and are at
risk of developing haemochromatosis. These people can have it to a variable extent (the
penetrance factor), and some are asymptomatic while others have a serious problem. It is rare for
symptoms to manifest before the third decade.
Hereditary haemochromatosis (HHC),
homozygous C282Y—high risk for HHC
homozygous H63D—unlikely to develop clinical HHC
heterozygous C282Y and H63D—milder form of HHC
The key diagnostic sensitive markers are serum transferrin saturation and the serum ferritin level.
The serum iron level is not a good indicator. An elevated ferritin level is not diagnostic of HHC
but is the best serum marker of iron overload.
Hereditary haemochromatosis (HHC),
Most patients are asymptomatic but may have extreme lethargy, abdominal discomfort, signs of
chronic liver disease, polyuria and polydipsia, arthralgia, erectile dysfunction, loss of libido and
joint signs.
Signs: look for hepatomegaly, very tanned skin, cardiac arrhythmias, joint swelling, testicular
atrophy.
Hereditary haemochromatosis (HHC),
Increased serum transferrin saturation: >50% (F); >60% (M)
Hereditary haemochromatosis (HHC),
Increased serum ferritin level: >200 mcg/L (F); >300 mcg/L (M) (see CHAPTER 13 )
CT, MRI or FerriScan—increased iron deposition in liver
Liver biopsy (if liver function test enzymes are abnormal or ferritin >1000 mcg/L or
hepatomegaly)—FerriScan now preferred
Genetic studies: HFE gene—a C282Y and/or H63D mutation
Screen first-degree relatives (serum ferritin levels and serum transferrin saturation in older
relatives and genetic testing in younger ones). No need to screen before adulthood. HbEPG
gene for pregnant patient and partner.
Routine screening not recommended
Note: Full blood count (FBE) and erythrocyte sedimentation rate are normal.
Hereditary haemochromatosis (HHC),
Refer for specialist care
Weekly venesection 500 mL (250 mg iron) until serum iron stores are normal (may take at
least 2 years), then every 3–4 months to keep serum ferritin level <100 mcg/L (usually
40–80 mcg/L), serum transferrin saturation <50% and iron levels normal
Desferrioxamine can be used but not as effective as venesection
Normal, healthy low-iron diet
Avoid or limit alcohol
Avoid iron tablets and vitamin C
Life expectancy is normal if treated before cirrhosis or diabetes develops
Hereditary haemochromatosis (HHC),
is the result of a defect in an ion channel protein, the cystic fibrosis
transmembrane receptor, which is found in the membranes of cells lining the exocrine ducts. The
defect affects the normal transport of chloride ions, leading to a decreased sodium and water
transfer, thus causing viscid secretions that affect the lungs, pancreas and gut.
Cystic fibrosis
The most common AR paediatric illness
About 1 in 2500 Caucasians affected
Cystic fibrosis
About 1 in 20–25 are carriers A mutation (δ-F508) of chromosome 7 is the most common of some 500 possible mutations of the gene. This deletes a single phenylalanine residue from a 1480-amino acid chain.
Cystic fibrosis
General: malaise, failure to thrive, exercise intolerance
Chronic respiratory problems: cough, recurrent pneumonia, bronchiectasis, sinus tenderness,
nasal polyps
Gastrointestinal: malabsorption, pale loose bulky stools, jaundice (pancreatic effect),
meconium ileus (10% of newborn babies)
Infertility in males (atrophy of vas deferens)
Pancreatic insufficiency
Early mortality but improving survival rates (mean age now 31 years)
Cystic fibrosis
DxT failure to thrive + chronic cough + loose bowel actions →
Cystic fibrosis
Screening for immunoreactive trypsin/trypsinogen in newborns detects 75%
Sweat test for elevated chloride and sodium levels
DNA testing for carriers identifies only the most common mutations (70–75%)
cystic fibrosis
Early diagnosis and multidisciplinary team care are important
Physiotherapy for drainage of airway secretions
Hypertonic saline solution (by nebuliser) preceded by a bronchodilator
Treatment of infections: therapeutic and prophylactic antibiotics
Oral pancreatic enzyme replacement
Dietary manipulation
Lung and liver transplantation are considerations
cystic fibrosis
NF1—peripheral neurofibromatosis (von Recklinghausen disorder)
NF2—central type, bilateral acoustic neuromas (schwannomas) (rare)
The gene for NF1 is carried on chromosome 17 and NF2 on chromosome 22. Diagnostic genetic
testing is not routinely available. Diagnosis is by clinical examination.
Neurofibromatosis
DxT light-brown skin patches + skin tumours + axillary freckles →
NF1
Six or more café-au-lait spots (increasing with age)
Freckling in the axillary or inguinal regions
Flesh-coloured cutaneous tumours (appear at puberty)
Hypertension
Eye features (iris hamartomas)
Learning difficulty
Musculoskeletal problems (e.g. scoliosis, fibrous dysplasia, pseudoarthrosis)
Optic nerve gliomas
NF1
Six or more café-au-lait spots (increasing with age)
Freckling in the axillary or inguinal regions
Flesh-coloured cutaneous tumours (appear at puberty)
Hypertension
Eye features (iris hamartomas)
Learning difficulty
Musculoskeletal problems (e.g. scoliosis, fibrous dysplasia, pseudoarthrosis)
Optic nerve gliomas
NF1
One-third asymptomatic, only have skin stigmata
One-third minor problems, mainly cosmetic
One-third significant problems (e.g. neurological tumours)
NF1
No special treatment available
Surgical excisions of neurofibromas as appropriate
Refer to a special clinic, including neurofibroma clinic
Careful surveillance—report new symptoms
Yearly examination for children and adults, including blood pressure, neurological, skeletal
and ophthalmological examination
NF1
is a progressive proximal muscle weakness disorder with replacement of muscle by
connective tissue. Becker muscular dystrophy is a less severe variant. Early diagnosis is
important. First signs are delayed motor development, speech and language.
Duchenne muscular dystrophy (DMD)
DMD is an X-linked recessive condition. It is caused by a mutation in the gene coding for
dystrophin, a protein found inside the muscle cell membrane.
Duchenne muscular dystrophy (DMD)
Usually diagnosed from 2–5 years
Weakness in hip and shoulder girdles
Walking problems: delayed onset or starting in boys aged 3–7
Waddling gait, falls, difficulty standing and climbing steps
Pseudohypertrophy of muscles, especially calves
Most in wheelchair by age 10–12
± Intellectual retardation/learning difficulties
Most die of respiratory problems by age 25
Gower sign: patient uses ‘trick’ method by using hands to climb up his or her legs when rising
to an erect position from the floor
Duchenne muscular dystrophy (DMD)
DxT male child + gait disorder + bulky calves →
Duchenne muscular dystrophy (DMD)
Elevated serum creatinine kinase level
Electromyography
Direct dystrophin gene testing
Muscle biopsy
Duchenne muscular dystrophy (DMD)
Counselling, especially genetic counselling, education, screening (especially mother)
No specific treatment available; support; corticosteroids delay progression
Duchenne muscular dystrophy (DMD)
Claimed to be the leading genetic cause of infant death, SMA includes several types, all
manifesting as progressive muscle wasting and leading to early death in the more severe types
Spinal muscular atrophy (SMA)
SMA is autosomal recessive and due to mutation in SMN1 gene on chromosome 5. Prevalence 1
in 6000–10 000; carriers 1 in 40.
Spinal muscular atrophy (SMA)
Muscle weakness, poor tone and floppiness
Feeding difficulties and feeble cry in babies
Weak swallowing, coughing and breathing
Normal intelligence and sensory modalities
Diagnosis is by DNA screening at birth and EEG studies. There is no cure at present and
treatment is mainly supportive. Zolgensma gene therapy is given as a single IV injection into
children <2 years before symptoms appear. Intrathecal injections of nusinersen are available.
Spinal muscular atrophy (SMA)
About 1 in 25 Ashkenazi Jews is a carrier of Tay–Sachs disease (gangliosidosis), an AR disorder
caused by a total deficiency of hexosaminidase A resulting in an accumulation of gangliosides in
the brain.
Tay–Sachs disease
This autosomal recessive disorder of the catabolism of the amino acid, phenylalanine, is caused
by a deficiency of phenylalanine hydroxylase activity, leading to an elevation of plasma
phenylalanine, which if untreated can cause intellectual disability (often very severe) and other
neurological symptoms, such as seizures. Neonatal screening for high blood phenylalanine levels
(the Guthrie test) is performed routinely.
Phenylketonuria (PKU)10
Tourette syndrome appears to be a genetic condition since a child of a person with TS has a 50%
chance of developing it (possibly AD with variable penetrance).
Tourette syndrome
Inherited as an AD disorder.
The responsible mutant gene has been located on the short arm of chromosome 4.
One genetic mutation accounts for the vast majority of cases, which means that there is an
accurate diagnostic test.
Both sexes are equally affected.
Huntington disease10
DxT chorea + abnormal behaviour + dementia + family history →
Huntington disease
Insidious onset and progression of chorea
Onset most often between 35 and 55 years
Mental changes—change in behaviour (can be as early as childhood or in very late life),
intellectual deterioration leading to dementia
Family history present in the majority
Motor symptoms: flicking movements of arms, lilting gait, facial grimacing, ataxia, dystonia
Usually a fatal outcome 15–20 years from onset
Huntington disease
This is available, sensitive and important because offspring have a 1 in 2 risk and the onset may
be late—after child-bearing years. It is appropriate to refer to expert centres for those seeking it.
Of interest is that only 20% have undergone testing since it became available, indicating that
those at risk generally prefer the uncertainty of not knowing the reality.
Huntington disease
Early-onset familial Alzheimer disease (EoFAD), which accounts for less than 1% of all
Alzheimer disease, is defined as the presence of two or more affected people with onset age <65
years in more than one generation of a family, with postmortem pathologically proven Alzheimer
disease in at least one person. There are two forms of FAD: early onset (EoFAD <65 years) and
late onset (LoFAD). Mutations in any one of three different forms (alleles) of the susceptible
APOE gene are known to cause FAD
Familial Alzheimer disease (FAD)
Most cases are sporadic, and the majority of cases with a family history do not have a clear
inheritance pattern and could be the result of several factors including a genetic predisposition or
simply a chance aggregation. Consider referral to a neurogenetics clinic for families with unusual
features, such as familial aggregation and/or early-onset Parkinson disease.
Parkinson disease
Five to 10% of motor neurone disease is inherited, with an autosomal dominant inheritance
pattern. Inherited MND shows familial aggregation and an earlier age of onset than average (40s
or younger); otherwise clinical features are essentially the same as the sporadic form (see
CHAPTER 22 ). If more than one family member presents with MND consider referral to a
neurogenetic clinic.
Motor neurone disease (MND) (amyotrophic lateral
sclerosis)
the most common human single-gene disorders in the world, are a group of
hereditary disorders characterised by a defect in the synthesis of one or more of the globin chains
(α or β)—there are two of each (α2, β2). This causes defective haemoglobin synthesis leading to
hypochromic microcytic anaemia. α-thalassaemia is usually seen in people of Asian origin while
β-thalassaemia is seen in certain ethnic groups from the Mediterranean, the Middle East, South-
East Asia and the Indian subcontinent. However, in our multicultural communities one cannot
assume a person’s origins. It is recommended that all women of child-bearing age be screened
for thalassaemia. The thalassaemias are described as ‘trait’ when there are laboratory features
without clinical expression.
Thalassaemia
α-thalassaemia is usually due to the deletion of one or more of the four genes for α-globin, the
severity depending on the number of genes deleted: deletion of all four genes—α-thalassaemia
(hydrops fetalis); of three genes—haemoglobin H disease, which results in lifelong anaemia of
mild-to-moderate degree; of one or two genes—a symptomless carrier.
In β-thalassaemia, the β-chains are produced in decreased quantity rather than having large
deletions. People who have two mutations (one in each β-globin gene) have β-thalassaemia
major.
β-thalassaemia minor—a single mutation (heterozygous)—the carrier or trait state
β-thalassaemia major—two mutations (homozygous)—the person who has the disorder
Thalassaemia
If both parents are carriers, there is a 1 in 4 chance that their child will have the disorder.
Clinical features
Carriers are clinically asymptomatic and do not need treatment apart from counselling. Patients
with thalassaemia major present with symptoms of severe anaemia (haemolytic anaemia).
Without treatment, children with thalassaemia major are lethargic and inactive, show a failure to
thrive or to grow normally, and delayed puberty, hepatosplenomegaly and jaundice. Signs
usually appear after 6 months and death from cardiac failure used to be common but with regular
blood transfusions and iron-chelating treatment people can now live in good health
Thalassaemia
DxT pallor + jaundice + hepatosplenomegaly →
thalassaemia major
FBE: in most carriers the mean corpuscular haemoglobin/mean corpuscular volume is low but
can be normal. There is usually mild hypochromic microcytic anaemia but this is severe with
the homozygous type.
Haemoglobin electrophoresis: measures relative amounts of normal adult haemoglobin (HbA)
and other variants (e.g. HbA2, HbF). This will detect most carriers.
Serum ferritin level: helps distinguish from iron deficiency, which has a similar blood film.
DNA analysis: for mutation detection (mainly used to detect or confirm carriers).
thalassaemia major
Treatment is based on a regular blood transfusion schedule for anaemia. Avoid iron supplements.
Folate supplementation and a low-iron diet are advisable. Excess iron is removed by iron
chelation (e.g. desferrioxamine). Allogeneic bone marrow transplantation has been used with
success.16 Splenectomy may be appropriate.
Treatment for thalassaemia major
The most important abnormality in the haemoglobin (Hb) chain is sickle-cell haemoglobin
(HbS), which results from a single base mutation of adenine to thymine, leading to a substitution
of valine for glutamine at position 6 on the β-globin chain. The defective Hb causes the red cells
to become deformed in shape—‘sickled’. The sickled cells tend to flow poorly and clog the
microcirculation, resulting in hypoxia, which compounds the sickling. Such attacks, which result
in tissue infarction, are called ‘crises’. Sickling is precipitated by infection, hypoxia, dehydration,
cold and acidosis, and may complicate operations. The autosomal recessive disorder occurs
mainly in Africans (25% carry the gene), but it is also found in India, South-East Asia, the
Middle East and southern Europe.
Sickle-cell disorders
Heterozygous state for HbS = sickle-cell trait
Homozygous state = sickle-cell anaemia/disease
Sickle-cell disorders
This varies from being mild or asymptomatic to a severe haemolytic anaemia and recurrent
painful crises. It may present in children with anaemia and mild jaundice. Children may develop
digits of varying lengths from the hand-and-foot syndrome due to infarcts of small bones.
Features of infarctive sickle crises include:
bone pain (usually limb bones)
abdominal pain
chest—pleuritic pain
kidney—haematuria
spleen—painful infarcts
precipitated by cold, hypoxia, dehydration or infection
Hb electrophoresis is needed to confirm the diagnosis.
Sickle-cell anaemia
Hb electrophoresis is needed to confirm the diagnosis.
Long-term problems include chronic leg ulcers, susceptibility to infection, aseptic necrosis of
bone (especially head of femur), blindness and chronic kidney disease. The prognosis is variable.
Children in Africa often die within the first year of life. Infection is the commonest cause of
death.
Sickle-cell anaemia
People with this usually have no symptoms unless they are exposed to prolonged hypoxia, such
as anaesthesia and flying in non-pressurised aircraft. The disorder is protective against malaria
Sickle-cell trait
This is the commonest cause of inherited haemolytic anaemia in northern Europeans. It is an
autosomal dominant disorder of variable severity, although in 25% of patients neither parent is
affected, suggesting spontaneous mutation in some instances. Jaundice may present at birth or be
delayed or occur not at all. Splenomegaly is a feature and splenectomy is considered to be the
treatment of choice in severe cases. Maintenance of folic acid levels is important
Hereditary spherocytosis
is a common disorder affecting over 400 million people worldwide. It is the most common red cell enzyme defect that causes episodic haemolytic anaemia because of the
decreased ability of red blood cells to cope with oxidative stresses. It is an X-linked recessive
inherited disorder with a high prevalence among people of African, Mediterranean or Asian
ancestry. In some countries such as Malaysia there is a national screening program.
Glucose-6-phosphate dehydrogenase deficiency
The important clinical features are:
asymptomatic in many
neonatal jaundice—infants at risk should be observed after delivery (at least 5 days)
episodic acute haemolytic anaemia—triggered by antioxidants and infections, and drugs,
especially antimalarials, sulfonamides, nitrofurantoin, quinolones, traditional medicines,
vitamins C and K, high dose aspirin, fava (broad) beans and naphthalene (e.g. moth balls)
There is no specific treatment. Known precipitants should be avoided. Avoid penicillin and
probenecid.
Diagnosis is by G6PD assay and a blood film during an attack.
Glucose-6-phosphate dehydrogenase deficiency
is an inborn error of metabolism in which the body is unable to metabolise
galactose to glucose. There are three clinical syndromes caused by differing enzyme deficiencies,
one of which is galactose-1-phosphate uridyl transferase, which causes the classic syndrome. It is
an autosomal recessive disorder with an incidence of about 1 in 60 000 births. As lactose is the
major source of galactose, the infant becomes anorexic and jaundiced within a few days or weeks
of taking breast milk or lactose-containing formula. It can be rapidly fatal. Management is with a
galactose (mainly lactose)-free formula such as soy with added calcium and vitamins.
Galactosaemia
In inherited bleeding deficiency disorders, there are deficiencies of vital factors (see
CHAPTER 29 ). The common significant disorders are:
haemophilia A (factor VIII deficiency)—X-linked recessive
haemophilia B (factor IX deficiency)—X-linked recessive
von Willebrand disease (deficiency of factor VIII:C + defective platelet factor)—autosomal
dominant
Others to consider are:
hereditary haemorrhagic telangiectasia (Osler–Weber–Rendu disease)
inherited thrombocytopenia
Bleeding disorders
This is an autosomal dominant disorder of the development of vasculature. A strong family
history aids diagnosis.
Key features:
mucocutaneous telangiectasia (Osler–Weber–Rendu syndrome)
recurrent epistaxis in children and adolescents
visceral arteriovenous malformations, e.g. GIT, lips
diagnosis is clinical, aided by imaging to detect AVMs
Hereditary haemorrhagic telangiectasia
This should be considered in patients with a past and/or family history of DVT or other
thrombotic episodes (see CHAPTER 122 ). There are several causes, including important
inherited factors, which are:
factor V Leiden gene mutation (activated protein C resistance)
prothrombin gene mutation
protein C deficiency
protein S deficiency
antithrombin deficiency
It is important to be aware of these factors, especially in people with a past history of
unexplained thrombotic episodes. Prescribing the oral contraceptive pill (OCP) is an issue but
preliminary screening for thrombophilias is not recommended. In factor V Leiden, the most
common factor in this group, there is a 35-fold increased risk of thrombosis for those taking the
OCP.
Thrombophilia
______________________ is based on typical facial features (flat facies, slanting eyes,
prominent epicanthic folds, small ears), hypotonia, intellectual disability and a single palmar
crease.
Down syndrome (trisomy 21)
DxT typical facies + hypotonia + single palmar crease →
Down syndrome
95% have extra chromosome of maternal origin (trisomy 21)
Remainder due to either unbalances, translocations or mosaicism
Prenatal screening tests include early ultrasound (nuchal translucency) and maternal serum
screening in first trimester (serum maternal and fetal DNA). Karyotyping of chorionic villus
sampling on amniocytes for pregnancies at risk is available.
Prevalence 1 in 650 live births
Down syndrome
Seizures (usually later onset) Impaired hearing Leukaemia Hypothyroidism Congenital anomalies (e.g. heart, duodenal atresia, Hirschsprung, TOF) Alzheimer-like dementia (fourth–fifth decade) Atlantoaxial instability Coeliac disease Diabetes
Down syndrome
Assess child’s capabilities
Refer to agencies for assessment (e.g. hearing, vision, developmental disability unit)
Advise on sexuality, especially for females (i.e. menstrual management, contraception) as
fertility must be presumed
Down syndrome
Trisomy 18
Clinical features
These include:
incidence 1 in 2000 live births (approx.)
microcephaly
facial abnormalities, e.g. cleft lip/palate
malformations of major organs, e.g. heart
malformations of hands and feet—clenched hand posture
neural tube defect
Prognosis is poor—about one-third die in first month, <10% live beyond 12 months.
Prenatal diagnosis is available
Edward syndrome10
Trisomy 13 Clinical features These include: incidence 1 in 7000 (approx.) microcephaly brain and heart malformation
Patau syndrome10
presents as a classic physical phenotype with large prominent ears, long narrow face,
macro-orchidism and intellectual disability. It is the most common inherited cause known of
developmental disability and should always be considered. The cause is the result of an increase
in the size of a trinucleotide repeat in the FMR-I gene on the X chromosome (the number of
sequences determines carrier or full mutant status). Any individual with significant development
delay should be tested for FXS.
Fragile X syndrome (FXS)
DxT characteristic facies + intellectual disability + large testes →
FXS
M:F ratio 2:1
Prevalence of full mutation 1 in 4000
Variable spectrum of characteristic features, making detection difficult in some cases
1 in 250 are pre-mutation carriers
Family history of intellectual disability
Affects all ethnic groups
Females may appear normal but may be affected
FXS
Cytogenetic testing (karyotyping) DNA test (specific for full mutation as well as carriers)
FXS
Autism or autistic-like behaviour Attention deficit in 10% (with or without hyperactivity) Seizures (20%) Connective tissue abnormalities Learning disability and speech delay Coordination difficulty Primary ovarian insufficiency Late-onset tremor/ataxia syndrome
FXS
Careful genetic appraisal and counselling
Assessment of child’s capabilities
Multidisciplinary assessment, including developmental disability unit
Referral for integration of speech and language therapy, special education, behaviour
management
Pharmacological treatment of any epilepsy, or attention or mood behaviour disorders
Medications may determine whether the child remains in the community or not
FXS
This uncommon disorder (1 in 10 000–15 000) has classic features, especially a bizarre appetite
and eating habits, of which the GP should be aware. It is probable that there are many
undiagnosed cases in the community. The most common cause is a deletion of the short arm of
chromosome 15.
Prader–Willi syndrome
DxT neonatal hypotonia + failure to thrive + obesity (later) →
Prader–Willi syndrome
Hypotonic infants with weak suction and failure to thrive, then voracious appetite causing
morbid obesity
Usually manifests at 3 years
Prader–Willi syndrome
Intellectual disability
Narrow forehead and turned-down mouth
Small hands and feet
Hypogonadism
Prader–Willi syndrome
Early diagnosis and referral
Multidisciplinary approach
Expert dietetic control
With proper care and support, longevity into the eighth decade is a reality
Prader–Willi syndrome
This is a systemic connective tissue disorder characterised by abnormalities of the skeletal,
cardiovascular and ocular systems. It has variable expressions and is a potentially lethal disorder.
If untreated, death in the 30s and 40s is common.
Marfan syndrome10
DxT tall stature + dislocated lens and myopia + aortic root dilatation →
Marfan syndrome
Mutations in the fibrillin gene on chromosome 15
Autosomal dominant
Marfan syndrome
Disproportionally tall and thin Long digits—arachnodactyly Kyphoscoliosis Joint laxity (e.g. genu recurvatum) Myopia and ectopic ocular lens High arched palate Aortic dilatation and dissection Mitral valve prolapse
Marfan syndrome
Needs surveillance of eyes, heart and thoracic aorta
Echocardiography, possibly aortic root dilatation
Long-term beta blockade therapy reduces rate of dilatation
Consider prophylactic cardiovascular surgery
Genetic counselling for the family
Marfan syndrome
This is an AD disorder with mutation of chromosome 11. It has been described as a male Turner
syndrome but affects both sexes
Noonan syndrome
DxT facies + short stature + pulmonary stenosis →
Noonan syndrome
Characteristic facies—down-slanting palpebral fissures, widespread eyes, low-set ears ± ptosis
Short stature
Noonan syndrome
Pulmonary valve stenosis Webbed neck Failure to thrive, usually mild Abnormalities of cardiac conduction and rhythm ± Intellectual disability
Noonan syndrome
This is due to an extra X chromosome, resulting in a male phenotype and occurring in 1 in 800
live births. Approximately 2 out of 3 are never recognised.
Klinefelter syndrome10
DxT lanky men + small testes + infertility →
Klinefelter syndrome10
47, XXY genotype
The extra X chromosome is usually of maternal origin
About 30 or more variants of the disorder
Klinefelter syndrome
tall men with long limbs
small firm testes ≤2 cm (10 mL)
infertility (azoospermia)
There may be:
sparse facial hair
reduced libido
learning difficulties, especially reading
intellectual ability may range from normal to disability
increased risk of DVT, breast cancer and diabetes (screening indicated)
Klinefelter syndrome
Increased gonadotrophin, low to normal testosterone
Klinefelter syndrome
Transdermal testosterone
Klinefelter syndrome
This is due to only one X chromosome, occurring in 1 in 4000 live female newborns; 99% of
conceptions are miscarried.
Turner syndrome (gonadal dysgenesis)
DxT short stature + webbed neck + facies →
Turner syndrome
45 chromosomes of XO karyotype (typical Turner karyotype in 50% of cases)
Many are mosaics (e.g. 45X/46XX chromosomes)
Phenotypes vary
Turner syndrome
Short stature—average adult height 143 cm
Primary amenorrhoea in XO patient; infertility
Webbing of neck
Typical facies: micrognathia, low hairline
Lymphoedema of extremities
Cardiac defects (e.g. coarctation of aorta)
Mental deficiency is rare.
Turner syndrome
Hormone-based (e.g. growth hormone, hormone replacement therapy)
Turner syndrome
DxT abnormal facies + growth retardation + microcephaly + history of
alcohol intake during pregnancy →
fetal alcohol spectrum disorder
Markedly underweight until puberty Learning difficulties Microcephaly Characteristic facies (needs 2 of *) shortened palpebral fissures* long, smooth featureless philtrum
Fetal alcohol syndrome
Hyperactivity
Congenital heart disease often seen
Skeletal abnormalities
Diagnosis based on alcohol history in pregnancy
Fetal alcohol syndrome
This is an autosomal dominant condition with predisposition to ventricular arrhythmias,
syncopal/fainting spells and sudden death, particularly during exercise. Confirm or exclude by
ECG when suspected—interval 0.5–0.7 seconds. Management includes sports restrictions, beta
blockers and pacemaker or AICD.
Congenital long QT syndrome
This is an AD disorder with several genetic mutations. It is the most common cause of sudden
cardiac death among athletes.
Familial hypertrophic cardiomyopathy
Fatigue
Exertional dyspnoea and chest pain
Palpitations
Dizziness/syncope
Diagnosis by ECG (LV hypertrophy) and doppler echocardiography.
Insertion of AICD may prevent sudden death.
Familial hypertrophic cardiomyopathy
There are several types of genetic disorder of lipid metabolism including the better-known
familial hypercholesterolaemia and familial combined hyperlipidaemia. The former is identified
by elevated cholesterol, corneal arcus juvenalis, tendon xanthomas in the patient or their firstand
second-degree relatives and also by a DNA mutation. Homozygous patients present with
atherosclerosis disease in childhood and early death from myocardial infarction. Heterozygotes
may develop the disorder in their 30s or 40s
Familial hyperlipoproteinaemia20
Mutations in either of the two genes—BRCA1 and BRCA2—result in a strong predisposition
for both breast and ovarian cancer
Mutations present in about 1 in 800 of the general population (male and female), who are
carriers
Dominant inheritance
The risk of developing breast cancer is 10-fold and 40–80% of cases occur before the age of
70 years22
The prognosis in these women is the same as for sporadic cases
Early age of onset of breast cancer
Male breast cancer (6% in males with BRCA2 gene mutation)
Coexistence of ovarian and breast cancer in the same family
Carriers of mutations may be at an increased risk of prostate cancer, pancreatic cancer and
colorectal cancer, although this is controversial for the latter two
Features of breast–ovarian cancer syndrome
Two first-degree or second-degree relatives on one side of the family with cancer
Individuals with age of onset of cancer <50 years
Individuals with bilateral or multifocal breast cancer
Individuals with ovarian cancer
Breast cancer in a male relative
Jewish ancestry
Risk indicators for familial breast–ovarian cancer
Both sexes have a risk of approximately 5% of developing bowel cancer in their lifetime. In some this risk is increased due to an inherited predisposition.
The two key disorders are HNPCC and FAP.
Colorectal cancer21
Caused by a defect in one of the genes responsible for DNA mismatch repair
Affects 1 in 1000 individuals
Autosomal dominant
Early age of onset
Increased risk of certain extracolonic cancers, including endometrial, stomach, ovary and
kidney tract cancers
Screening should occur every 1–2 years from 25 years of age or 5 years earlier than affected
family member developed it
Lynch syndrome (hereditary non-polyposis colorectal cancer)
Less common than HNPCC; affects about 1 in 10 000
Caused by a mutation in the APC gene
Usually hundreds or thousands of polyps
Eventually almost 100% of cases develop colon cancer without prophylactic colectomy
Median age of diagnosis 40 years
Small increased risk of other cancers (e.g. thyroid, cerebral)
Screening should occur annually from between 12–15 and 30–35 years of age, and then every
3 years
Familial adenomatous polyposis
For Lynch syndrome (HNPCC):
Three or more close relatives with bowel cancer
Two or more close relatives with bowel cancer and:
more than one bowel cancer in same relative
Individuals at risk Familial adenomatous polyposis
an inherited mutation in certain genes (e.g. BRAF gene) is considered to be
involved in up to 5% of melanomas. Having a first-degree relative affected almost doubles a
person’s risk.
Melanoma:
family history is a risk factor; some genes (e.g. BRAC1 and BRAC2) are susceptible.
Refer if a significant family history
Prostate:
which is due to a deficiency of the lysosomal enzyme glucocerebrosidase, leads
to anaemia and thrombocytopenia as a result primarily of hypersplenism. There is chronic bone
pain and ‘crises’ of bone pain. Consider it in children with fatigue, bone pain, delayed growth,
epistaxis, easy bruising and hepatosplenomegaly. Replacement enzyme therapy is available.
Gaucher disease
