Long Cases Flashcards
Most common CF infections in younger children
- Staph
- Pseudomonas
- Haemophilus
- E.Coli
- Strep pneumoniae
Most common CF infections in older children/adolescents
- Burkholderia cepacia
- Achromobacter Xylosoxidans
- Stenotrophomonas maltophilia
- Klebsiella
- Enterobacter
- Fungal - aspergillus fumigatus
- Non TB mycobacteria
What is the CFTR protein
Cyclic-AMP regulated chloride channel on the apical surface of epithelial cells - lack of this leads to dehydration of both mucous and airway surface liquid, and disturbance of mucociliary clearance
CFTR modulator drugs
- Lumacaftor and Ivacaftor (Orkambi) used in F508del patients - helps with protein folding
Which CF mutation is associated with pancreatic insufficiency in 99%?
Phe508del (F508del)
Discuss the different CF class mutations
- Class I (3%) - no protein e.g. G542X. Stop mutation, nonsense, short protein which is deleted, therefore no function.
- Class II (90%) - no trafficking e.e F508del. Abnormal folding, trafficking defect, therefore no traffic to cell membrane.
- Class III (5%) - no function. e.g. G551D. Gating defect, protein can get to cell wall but Cl- cannot get out of cell.
- Class IV - less function
- Class V - less protein
- Class VI - less stable
CF monitoring of disease progression
- Infants usually seen weekly
- As get older usually review 3 monthly, and annual review for disease progression with:
- Sputum culture, CXR, nutritional assessment, lung function tests, LFTs, FBC, vitamin levels, total IgE (ABPA)
- Oral glucose tolerance test from age 10yrs or earlier if symptoms or decline in lung function tests
- High res CT scan in primary/secondary school to look for bronchiectasis
Treatment of pseudomonas infection in CF
Ciprofloxacin (but develop rapid resistance) + nebulised antibiotics e.g. tobramycin or colistin (usually alternating month on and off neb antibiotics in chronic pseudomonas to avoid AB resistance). IV = tazocin or ceftazidime
3 significant factors for poor outcome post lung transplant for CF:
repeat transplant, mechanical ventilation at time of transplant, co-existing congenital heart disease
3 main causes of death post lung transplant for CF:
early graft dysfunction, infection, bronchiolitis obliterans
Treatment of DIOS
Nasogastric decompression, IV hydration, enema. If incomplete obstruction then paraffin oil, stool softeners, osmotic laxatives, low residue diet, enema. Can also use NAC, gastrografin.
Predisposing factors for DIOS
Pancreatic insufficiency, under replacement of PERT, meconium ileus, dehydration
Causes of weight loss in CF
Non compliance, insufficient calories, insufficient PERT, CF related diabetes, chest infection, coeliac disease/IBD
Risks of indomethicin treatment
Renal impairment and NEC
Risks of TPN therapy in premature infants
- Extravasation
- Line infections
- Thrombosis
- Conjugated hyperbilirubinaemia (TPN associated liver disease)
Risk of infections in nephrotic syndrome
- Due to loss of immunoglobulins and complement in urine, and steroid treatment
- Especially pneumococcal and streptococcal infections
- Peritonitis and septicaemia
- Treat with oral penicillin prophylaxis while have proteinuria
- Remember immunisations including pneumococcal and influenza
- High dose steroids may mask signs of infection
- Risk of chickenpox and measles
Risk of thrombosis in nephrotic syndrome
- Due to renal loss of antithrombin 3, hyperviscosity, and hypovolaemia
- Can present as macrosopic haematuria (renal vein thrombosis)
- Decreased risk with being well hydrated and mobilsing
High risk groups for subacute bacterial endocarditis?
- Patients with multiple interventions e.g. chronic line placements
- Immunocompromised (immunodeficiency, sickle cell, chemotherapy etc)
- Unrepaired congenital cyanotic heart disease and those with prosthetic materials
- Older patients with CHD
What is appropriate SBE prophylaxis?
Amoxycillin 1hr prior to procedure (1.5g <10y, 3g 10y). If allergic then cephalosporin. May add aminoglycoside if prosthetic heart valve.
How do ACE inhibitors work in cardiac failure?
Reduce afterload (mainly) and preload
What are the important side effects of ACE inhibitors?
Hypotension, renal impairment, hyperkalaemia
When should T21 children have ECHOs?
After diagnosis/birth and again at 6 weeks of age
Down Syndrome adolescents have increased risk of what cardiac diseases?
- 50% develop mitral valve prolapse
- Can also get aortic incompetence
- Hypertension and atheroma risk is low despite obesity and unfavourable lipids
Rates of hearing loss in T21 children and adults?
- 50-80% children
- 90% of adults
- Conductive, sensorineural, or mixed
- Small pinna, narrow canals, impacted ear wax, middle-ear fluid
When should children with T21 see an ophthalmologist?
By 6-12 months of age, and then yearly. High risk of multiple eye issues (refractive, strabismus, nystagmus, cataracts, glaucoma etc)
What are the behavioral issues seen in Down Syndrome?
- ADHD-like, autism, conduct/oppositional defiant disorder, aggressive behaviour
- Autism diagnosis often made later than in non DS kids. Can present as atypical behaviour in infancy, or autistic regression age 3-7 years
What screening bloods should be done in children with Down Syndrome?
- T4 + TSH at birth, 6 months, then yearly
- Coeliac screen at age 2, no consensus on when to repeat
- FBC for TMD and leukaemia
What haematological abnormalities are seen in Down Syndrome?
- Neonatal polycythaemia and macrocytosis
- Transient myeloproliferative disorder
- ALL, AML
What autoimmune diseases are associated with T1DM?
Coeliac disease (6%) Hashimoto's thyroiditis (3%) Grave's disease Addison's disease Primary ovarian failure Vitiligo Ulcerative colitis
What is the risk of developing T1DM:
- Identical twin
- Sibling
- If mother +ve
- If father +ve
- If both parents +ve
What is the risk of developing T1DM:
- Identical twin - 40-50%
- Sibling - 1-2%
- If mother +ve - 2-3%
- If father +ve - 5-6%
- If both parents +ve - 30%
When should screening for complications of T1DM begin and what should you do?
- From age 12 onwards, yearly:
- Fundoscopy (retinopathy)
- Clinical exam (neuropathy)
- Urine albumin:creatinine ratio (nephropathy) - if positive then ACE- and 24 hours BP monitor (loss of night-time dip)
- Discussion around smoking
- Monitoring of hypertension and lipid profiles
How do you diagnose T1DM?
- Classic: polyuria, polydipsia, weight loss, random BSL >11.8
- Asymptomatic: fasting BSL >7.0 and 2hr postprandial BSL >11
- Presentation with DKA (30-40% cases)
Discuss the ages at which NF1 changes occur
- Any age:developmental delay, plexiform neuromas
- diffuse plexiform fibromas before age 1
- birth to 8 optic pathway rumours
- birth to 2 CALMs
- bony anomalies first 2 years
- 2 years onwards hypertension
- 3 to 5 years freckling
- 5 year onwards neurofibromas
- 5-10 years lisch nodules
- 6-10 years scoliosis
Discuss the ages at which NF1 changes occur
- Any age:developmental delay, plexiform neuromas
- diffuse plexiform fibromas before age 1
- birth to 8 optic pathway rumours
- birth to 2 CALMs
- bony anomalies first 2 years
- 2 years onwards hypertension
- 3 to 5 years freckling
- 5 year onwards neurofibromas
- 5-10 years lisch nodules
- 6-10 years scoliosis
Management of acne
- Avoid triggers + picking
- Regular cleansing
- Topical antibiotics (clindamycin/erythromycin)
- Oral antibiotics min 3m (doxycycline)
- OCP (Estelle: cyproterone acetate) if premenstrual flares
- Topical isotretinoin
- Systemic isotretinoin (roaccutane) - dermatologist, cystic acne, teratogenic/dry skin/sun sensitivity
What does HEADSSS stand for?
Home Education/employment Activities Drugs and alcohol Sexuality/relationships Suicide risk/mood Safety (behaviour + environment)
Managing behavioural issues in children
- Prioritise and identify 2 most important
- Clear boundaries, Consistency, Consequences
- 4-pronged approach: environmental modulation, time-out, ignore other behaviours, praise for good behaviours
What are the risk factors for osteopenia?
- Immobility/reduced weight bearing
- Diet - especially in adolescence (dieting)
- Reduced sun exposure/dark skinned
- Delayed puberty and amenorrhea
- Antiepileptics/steroids/warfarin
- Liver failure/fat malabsorption
- Renal failure
Side effects of bisphosphonates
- Initially hypocalcaemia
- Myalgia
- Bone pain
- Fevers
- Avascular necrosis of TMJ
- Renal impairment
Investigations for osteoporosis
- Ca, Phos, ALP, VIt D +/- PTH
- X-rays
- DEXA scan (bone mineral density hip + lumbar spine)
Treatment of osteoporosis
- Calcium supplements
- Vitamin D - cholecalciferol, calcitriol
- Hormonal therapy
- Reduce fracture risk
- Exercise program
- Bisphosphonates
What are the indications for bisphosphonate therapy?
- Z score <2.0 +
- > 1 vertebral compression fractures
- > 2 long bone fractures
- Significant # in low mobility (eg CP) or low tone condition (eg DMD)
- OI with fractures
OR hypercalcaemia, or AVN+bone pain
What are the two standard cognitive tests?
- < 6yo WIPSI (Wechsler preschool and primary scale of intelligence)
- > 6yo WISC (Wechsler intelligence scale for children)
Assisted communication strategies
- Ensure have had formal assessment of hearing and vision
- Glasses and hearing aids
- Environmental modifications
- Non-aided: gestures, facial expressions, key word signs from Makaton vocabulary
- Aided: printed words or pictures, feeling boards, cored boards/PODD book, switches, sound picture boards
Ways to increase compliance in adolescents
- Explain that poor adherence is common
- Identify barriers (lack of understanding of complications, side effects, doesn’t fit into lifestyle, bullying, forgetfulness, depression)
- Start increasing their autonomy (see independently, discuss confidentiality, re-educate about disease and medications, explore understanding)
- Simplify regime (decrease number and frequency of meds, avoid school-time meds, be flexible)
- Increase compliance (written instructions, routine/alarms, negotiate role of parents)
- Set short term goals e.g. 1 month, and regular review
Organic causes of constipation
- CMPI
- Hirschsprung’s disease
- Coeliac
- Hypothyroidism
- Hypercalcaemia
- Spinal cord pathology
How do ACE inhibitors work
ACE inhibitors decrease the production of angiotensin II and thereby decrease the vasoconstriction (or increased after-load) against which the left ventricle needs to pump. This results in decreased myocardial work, thus improving cardiac output.
What medications would you use in heart failure
ACE inhibitor (captopril, enalapril) Beta blocker (not when acute or decompensated) Frusemide
Key activities of daily living to ask about
○ Feeding - breast, bottle, solids, nutritional supplements, feeding supports (NG, PEG)
○ Toileting - nappies (day/night), support with toileting, enuresis, constipation
○ Dressing - self/assisted, orthotics
○ Mobility - supports, issues, limitations on activities
○ Communication - speech, vision, hearing
○ Equipment (hoists, wheelchair, walking frames)
○ Puberty management (older child, especially periods)
○ Sleep
○ Dental
What medical issues are related with Spina Bifida
- Mobility
- Incontinence - urinary and faecal
- Hydrocephalus (90%) - may require VP shunt. Arnold Chiari II malformation
- Syringomyelia and tethered cord
- Cognitive, developmental delays
- Orthopaedic: scoliosis, kyphosis, deformity
- Decreased bone mineral density, fractures
- Sleep-disordered breathing
- Pressure ulcers, latex allergy
- Vision and hearing
- Growth and development including precocious puberty, GH deficiency, short stature, obesity - HP axis disruption
- Seizures
- Low self esteem and depression
What are the indications for intermittent urinary catheterisation in spina bifida?
High pressure systems:
- UTI
- Hydronephrosis
- VUR
- Incomplete emptying
Start from 2 weeks age, with 3-4 times per day
What are the complications of VP shunts?
- Infection
- Obstruction (under-drainage) - raised ICP symptoms, neurological deterioration
- Low pressure syndrome (over-drainage) - headache (worse with getting up), dizziness, fainting
- Seizures
What is an Arnold Chiari 2 malformation
- Downward displacement of the cerebellar tonsils
and vermis through the foramen magnum - Elongation and kinking of medulla
- Caudal displacement of spinal cord and medulla
- Obliteration of the cisterna magna
Can lead to compression of brainstem, dysfunction of cerebellum cranial nerve IX+X abnormalities and hydrocephalus
Symptoms of an Arnold Chiari 2 malformation
- Swallowing difficulties with choking on foods, nasal regurgitation, GOR
- Aspiration pneumonia
- Dysarthria
- OSA, cyanosis, stridor
- Hoarse or high-pitched cry
- Weakness or spasticity of upper limbs
- Headaches
- Scoliosis
- Dizziness, clumsiness, poor coordination (cerebellar)
Treatment of an Arnold Chiari 2 malformation
- Decompression of medulla and upper cervical cord
- Duraplasty to increase size of dural sac
- Cervical laminectomy below the lowest level of the cerebellar tonsils
- Leads to improvement in cerebellar function and upper limb weakness
What are the features of syringomyelia
- Upper limb weakness
- Back pain
- Scoliosis
- Spasticity or motor loss in the lower limbs
- Similar symptoms to Arnold Chiari 2 malformation. Present in 80% of myelomeningocele patients, but only symptomatic in 2-5%
Discuss the complications and management of scoliosis in Spina Bifida
- The higher the lesion the more likely scoliosis
- Due to spinal muscle weakness
- Increases with age
- Curves > 30 degrees require formal surgical interventions
- Can lead to decreased lung capacity, recurrent infections, cor pulmonale, impairment of height, pressure sores, need for surgery (rods, or spinal fusion if at full height
Signs of a tethered cord
- Often appear during periods of growth e.g. adolescence
- Present in nearly all children with repaired myelomeningocele (scar tissue)
- Gait changes - crouched
- Lower limb pain
- Worsening of motor function (decr muscle strength + inc tone)
- Change in sensory level
- Change in bowel or urinary habit
- Progressive foot deformities
Management of worsening scoliosis in spina bifida
- Especially during adolescence/increased growth
- Need to rule out syringomyelia/tethered cord/Chiari malformation/failure of VP shunt as the cause
Most common tumours in NF1?
Benign neurofibromas (Schwann cell tumours)
Optic gliomas
Brain tumours (brainstem and cerebellar gliomas)
Malignant peripheral nerve sheath tumours (in 10%)
Pheochromocytoma
Management of optic glioma in NF1
- Children under age 7 most at risk from symptomatic optic gliomas
- Develop in 15%
- Chemo (vincristine, cisplatin), surgery for debulking
Learning and behavioural difficulties in NF1
- ADHD, ASD
- Executive planning, problem-solving, speech intelligibility
- Self-esteem, anxiety, depression
MSK issues in NF1
- Dystrophic scoliosis - requires surgery and ant/post fusion, doesn’t respond to bracing
- Tibial pseudarthrosis - complex and difficult management. Early bracing to prevent fractures. May require amputations if poor blood supply + fractures
- Osteoporosis - doesn’t respond to calcium/Vit D. Trials underway with bisphosphonates
Causes and treatment of hypertension in NF1
- Essential hypertension
- Renal artery stenosis
- Pheochromocytoma
- Coarctation of aorta
- Lifestyle (weight loss, salt restriction, manage OSA)
- ACE inhibitors, sartans, beta blockers, frusemide
- If BP is elevated then 24-hour urinary excretion of catecholamines and metabolites
Cardiac disease in NF1
- Pulmonary stenosis most common (2%) (NF1-Noonan syndrome)
- Coarctation of the aorta
- Aortic valve stenosis
Management of secretions/drooling
- Common in CP and neurodevelopmental - due to difficulty managing, not excessive production
- SLT input, video swallow if aspiration concerns
- Can cause skin irritation, embarrassment, aspiration
- Conservative: seating, positioning, using straw more to help learn suck, bibs, clothing
- Meds: anticholinergics (hyoscine patch and glycopyrrolate) - SEs drowsiness, constipation, urinary retention, thick secretions with aspiration risk
- Botox injections into parotid gland
- Surgical excision sublingual glands and transplant submandibular glands to back of mouth
Managemnet of nocturnal enuresis
- 10% 5yr olds, 7% 7yr olds, 5% 10 yr olds, 1-2% 15yr olds
- Rule out secondary causes
- Behavioural: scheduled awakenings, alarms/bells
- DDAVP short term fix, can use for 3/12 with pad if failed previously
- No blame
- Parental reassurance
- Imipramine (TCA), no longer used
DMD genetic counselling
- Mum’s relatives need counselling as may be carriers
- Check mum’s creatinine - if high then carrier. If normal could be mosaicism, may need genetic testing
- Carriers can get cardiomyopathy
Which conditions can you do pre-implantation genetic diagnosis for?
- Via PCR/FISH
- CF, DMD, thalassaemia, haemophilia, sickle cell, SMA, fragile X, huntington’s, retinoblastoma
What are side effects of growth hormone therapy?
- SUFE
- Headaches, benign ICH
- Reversible hypothyroidism
- N+V
- Gynaecomastia
- Peripheral oedema
Causes of failure to thrive
- Inorganic 90%
- Poor intake - oral aversion, nausea, pain, GOR
- Malabsorption - coeliac, CF
- Increased expenditure - hyperthyroid, chronic illness e.g. renal failure, CF
- Increased output/losses - diabetes insipidus, diarrhoea, vomiting
Investigations for failure to thrive
- Plot weight, height, HC
- Assessment of nutritional stores
- FBC, U+Es, LFTs, TFTs, coeliac screen, ESR, micronutrients (B12, folate, iron, vitamins)
- Urine (proteinuria), faecal calprotectin if older
- Consider metabolic work up, sweat test
Causes of sensorineural hearing loss
- AR in 50%, connexin 26 mutation
- Syndromes: Usher, Pendred, Goldenhaar, Treacher collins (usually conductive), NF2, Alports, Waardenburg
- Infections: rubella, meningitis, mastoiditis, TB
- Drugs: gentamicin, frusemide
- Bilirubin
- Tumours
Investigations in SN hearing loss
- TFTs (Pendreds)
- U+Es, urinalysis (Alports)
- Connexin 26
- ECG (Jervell-Lange-Neilson)
- Rubella serology on Guthrie card
- CT/MRI - exclude vestibular aqueduct, avoid contact sports
Management of hearing loss
- Monitor linguistic and social development, may need SLT input
- Reduce OM - early antibiotics, reduce smoking/daycare/dummies
- Grommets short term benefit - if bilat >30db conductive loss and recurrent OME
- Environmental - quiet background noise, talk loudly, ear plugs with loud noises to protect hearing
- Amplification if 50db loss
- Hearing aids (conductive or SN)
- Cochlear implants age <2y
- Alternative forms of communication if 80db loss, lip reading/signing
Side effects of mycophenolate
- Myelosuppression: leukopenia, increased risk of infection
- Malignancy: haematological, esp lymphoma
- Gut effects: diarrhoea, bleed, perforation
Side effects of methotrexate
- Hair loss
- Mucositis
- Nausea, vomiting, diarrhoea - may need ondansetron
- Hepatotoxicity
- Bone marrow suppression
- If bad side effects can use folic acid
Side effects of tacrolimus
T - tremor, tingling A - alimentary, diarrhoea, anorexia, vomiting, anaemia C - cancer risk increased R - renal impairment O - osteoporosis L - lymphoproliferative disease I - increased BP and K+ M - magnesium low U - urea high S - sugar diabetes
Side effects of cyclosporine
- Renal impairment
- Paresthesia (25%)
- Hypertrichosis
- Gingival hyperplasia
- Hypertension
Treatment of higher risk Crohn’s disease
- High risk: younger age of onset, extensive small bowel disease, deep colonic ulcers, perianal disease, early need for corticosteroid
- Top-down approach, rather than escalation of therapy
- Early use of immunomodulators and biological agents
Recommended vaccinations prior to starting immunosuppresants
- Check VZV and measles serology
- Influenza, pneumococcal polysaccharide, Hep B, HPV, VZV
Extraintestinal manifestations of IBD
- Arthralgia
- Erythema nodosum (CD), pyoderma gangrenosum (UC)
- Uveitis
- Aphthous ulcers (mouth)
- Primary sclerosing cholangitis (UC), chronic active hepatitis
- Sacroiliitis, ankylosing spondylitis, peripheral arthritis (CD)
Remission induction in CD (BEENSAS)
Remission induction in UC (BASS)
Maintenance (BIAS)
CD
- Biologics (infliximab/adalimumab)
- EEN
- Steroids
- Antibiotics
- Surgery
UC
- Biologics
- Aminosalicylates (5-ASA, eg. mesalazine - Asacol, Pentasa)
- Steroids
- Surgery
- If refractory can use infliximab or cyclosporin/tacrolimus for rescue therapy to avoid emergency colectomy
Maintenance of remission: - Biologics - Immunomodulators (AZA/6-MP/MTX) - Aminosalicylates - Supplementary enteral nutrition (CD) - Surgery (UC) (no steroids or antibiotics to maintain remission)
Investigations for IBD
- Faecal PCR, calprotectin, a1at level (protein loss), C-diff
- Bloods: FBC, CRP, ESR, LFTs, B12+folate, Vit ADEK, C/M/P/iron, U+Es
- TPMT level in case use thiopurines
- Yersinia serology (bowel + arthritis symptoms)
- Coeliac serology
- Imms status
- Serological biomarkers: pANCAs (UC), ASCAs (CD), low sense and specificity
- Imaging: MRI and US are best modalities
- Upper and lower endoscopy
Features differentiating CD and UC
- CD: transmural, proximal small bowel or terminal ileum, skip lesions, ulcerations, cobblestone pattern
- UC: perianal disease, rectal upwards, mucosal, strictures, oedematous hyperaemic friable mucosa,
What is the purpose of cholestyramine in short gut syndrome?
- The bile acid sequestering agent cholestyramine may be useful in decreasing bile salt related diarrhea (binds excess bile salts)
- Binds lipids so risk of causing steatorrhoea
Discuss the use of infliximab in IBD
- Monoclonal antibody, anti-TNF alpha. Neutralises cytokines and stops inflammation
- Response rate in over 80%
- Give at 0, 2, and 6 weeks, then every 8-12 weeks (half life is 3 weeks)
- Risk of developing antibodies in 20% (human-antichimeric antibodies), reduce risk with concurrent AZA or 6-MP treatment
- Is eaten up by disease, therefore if not working well can do surgery to reduce disease burden and then will work more effectively
- Can also use adalimumab (also anti-TNFa), half life 14 days
Side effects of infliximab/adalimumab reported in adults
- Autoimmune-like syndromes
- Malignancy, especially lymphoma
- Pancytopenia, neutropenia
- Elevated LFTs
- Eczema and psoriasis
- Heart failure
- Infections
- Guillain Barre, optic neuritis
- TB
- Poor wound healing
Discuss the use of AZA and 6-MP in IBD (+TPMT)
- AZA is metabolised to 6-MP
- Slow onset (3-4m) so use in combination with steroids + EEN for induction
- High relapse rate if stopped within first year of treatment
- Bone marrow suppression in 2-5%
- Need to know TPMT status prior to treatment (catalyses conversion of 6-MP to 6-MMP). If activity is reduced then produced more toxic 6-TG which causes bone marrow depression and leukopenia. Higher TPMT activity leads to hepatotoxicity.
- ASAs (aminosalicylates) and methotrexate inhibit TPMT and lead to bone marrow suppression
Side effects of sulfasalazine
- Rashes
- Bone marrow depression
- Nephrotoxicity
Discuss infantile spasms
- Average onset 5 months
- EEG hypsarrhythmia
- Developmental regression
- Prognosis depends on underlying cause
- Tx: steroids, vigabatrin (esp if TS), ACTH
- Flexor jack-knife seizures of extensor moro. Up to 30 clusters per day
- Causes: cerebral malformations, tuberous sclerosis, lissencephaly, ischaemia, infections, cerebrovascular accidents, Downs, metabolic disorders, Aicardi syndrome (agenesis corpus callosum)
Familial risk of epilepsy
- Depends on cause/underlying epilepsy syndrome
- Risk to siblings: generalised epilepsy approx 10%, focal approx 5%, febrile seizures approx 8%
Which AEDs can you measure serum levels for?
- Carbamazepine
- Phenytoin
- Phenobarbitone
- Lamotrigine
- Topiramate
- Can measure benzodiazepine + valproate levels but do not correlate to clinical efficacy or toxicity - useful if suspect non-compliance
Discuss the genetics of Rett syndrome
- Most caused by mutations in MECP2 gene
- X-linked dominant
- Sporadic in 99%
- Most are females (affected males die in utero)
Main features of Rett syndrome
- Slowing of development between 6-18 months of age then regression and then stabilisation
- Stereotypical movements of hands
- Disordered breathing when awake with hypoventilation/hyperventilation episodes and apnoeas
- Abnormalities of gait
- Intellectual impairment
- Epilepsy
- Progressive microcephaly
- Progressive disorder
- Scoliosis
- Decreased bone density, increased fractures
- Hypoplastic cold hands and feet
- Sleep disturbance, nocturnal awakening, laughing or screaming episodes during night
Diagnostic criteria for Rett syndrome
- Regression followed by stabilisation AND - Loss of speech - Loss of purposeful hand movements - Abnormal dyspraxic gait - Development of stereotypic hand movements
Exclude:
- Significantly abnormal development in first 6 months
- Cerebral injury leading to neurological impairment
Other features:
- Breathing abnormalities, bruxism
- Abnormal muscle tone
- Screaming and laughing spells, scoliosis, small cold peripheries, sleep pattern disturbed
- Eye pointing
- Deceleration of head growth, then height and weight, decreased pain response
4 stages of Rett syndrome (DRUM)
1) - Delay or arrest in development - age 6-18m, gross motor delay, decreased eye contact, deceleration of head growth. Ask about key milestones.
2) - Regression in development/destructive phase - 1-4yrs, loss of acquired purposeful hand skills and language/communication. Loss of social interaction. Stereotypic hand movements, gait abnormalities. 90% learn to sit, 50% learn to walk.
3) - Unapparent slow deterioration/static period - 2-10yrs, some restoration of communication, return of abilities. Epilepsy (multiple types of seizures, can be intractable, abnormal EEG, lamotrigine, epilim, carbamazepine) and apraxia, intense eye communication, dystonic posturing
4) - Motor deterioration - teenage years, scoliosis, ambulation stops, wheelchair dependent, can last decades, muscle wasting. Early life hypotonia, then spasticity/rigidity later
Differential diagnosis for Rett syndrome (PLACED)
- Pitt Hopkins syndrome (develop delay, hypervent, apnoeas)
- Lennox-Gastaut, leukodystrophies
- Autism, Angelman, Ataxias
- Cerebral palsy
- Encephalitis
- Deletion (microdeletion) syndromes, deafness, disturbed vision
Steroid potency comparison (dex, pred, hydrocort, methylpred)
Hydrocort = 1 (=100mg) Prednisolone = 4-6x (=20mg) Methylpred = 6-8x (=15mg) Dexamethasone = 80-120x (=1.5mg)
Discuss the duration of different insulins
Rapid acting - insulin analogues
- Novorapid (insulin aspart), apidra, humalog
- Used in pumps
- Useful in toddlers as can be given post-food (fussy eaters)
- Onset 5-15min, peak effect 30-120min, duration 3.5-6hrs
- Hypoglycaemia less common
Short acting - standard human insulins
- Actrapid, humulin R
- Onset 30-60min, peak effect 2-5hrs, duration 6-8hrs
Intermediate acting
- Protophane, humulin N
- Onset 1-2hrs, peak effect 4-12hrs, duration 16-24hrs
Long acting
- Lantus (insulin glargine), levermir (insulin determir)
- Onset 30-60min, peakless basal insulin, half life 12hrs, duration 16-24hrs
Biphasic (mixed) insulins
- 30% short acting, 70% intermediate acting
- Onset 30min, peak 1-12hrs, duration 16-24hrs
Symptoms of TSH deficiency
fatigue, weight gain, brittle hair and nails, cold intolerance, constipation, depression
Symptoms of LH/FSH deficiency
pubertal delay, fatigue, altered mood, menstrual disorders
Symptoms of ACTH deficiency
weight loss, postural dizziness, weakness, fatigue, anorexia, nausea, hypoglycaemia, anaemia
Symptoms of GH deficiency
short stature, reduced energy
Symptoms of ADH deficiency
polyuria, polydipsia, nocturia
Causes of short stature with obesity
- Cushing’s
- Hypothyroidism
- Hypopituitarism
- GH deficiency
- Pseudohypoparathyroidism
Complications of congenital cardiac disease
Complications due to cyanosis:
- Growth, puberty and nutrition
- Retinal bleeds
- Renal impairment
- Reduced exercise tolerance
Complications of cardiac surgery:
Shunts
- Increased pulmonary blood flow
- Reduced pulses
- Limb atrophy
- Protein losing enteropathy (with Fontan)
- Persistent stenosis or subsequent regurgitation
- CHF
- Arrhythmias
- Central nervous system complications - stroke (endocarditis, polycythaemia, post operative)
Operative complications:
- Right laryngeal nerve palsy - voice changes, poor cough
- Horner’s syndrome (30% with BT shunts)
- Diaphragm
- Scar
Drug complications:
- Anticoagulants
- Immunosuppressives
Causes of hypertension
Renal (most young children have renal cause)
- Nephritis – PSGN, IgA nephropathy, SLE, HSP, SBE, HUS
- Congenital renal anomalies - PCKD, hydronephrosis, dysplastic kidneys
- Reflux nephropathy (proteinuria)
- Nephrotic syndrome
- Renal artery stenosis, renal vein thrombosis (bruits)
Endocrine:
- Cushing’s, hyperthyroidism, hyperparathyroid, hyperaldosteronism (Conn’s syndrome), CAH
- Phaeochromocytoma
Cardiac:
- Coarctation of the aorta, PDA, supravalvular AS
- AV fistula
Drugs:
- Steroids, sympathomimetics, stimulants
- OCP
- Cocaine, phencyclidine (PCP), licorice, nicotine, caffeine
Syndromal - Turner’s
Neurological:
- Raised ICP
- Guillain-Barre syndrome (from autonomic dysfunction)
- TS, NF (due to RAS/phaeo)
Tumours: Wilm’s, neuroblastoma, phaeochromocytoma
Psychological: mental stress, anxiety
Likely cases:
- Renal artery stenosis (RAS) with bruits;
- NF-1
- Infantile polycystic kidneys with large kidneys and liver
- Portal hypertension
- Previous portosystemic shunts.
Specific signs:
- Pheochromocytoma – weight loss, flushing, sweating, tachycardia, blurred vision, dilated cardiomyopathy, increased ESR & BSL, urinary catecholamines
- Alport’s – sensorineural hearing loss, eye problems (cataracts, peri macular degeneration)
- Wilm’s tumour – WAGR (aniridia, genitourinary abnormalities, mental retardation)
- Henoch Schonlein purpura
- Renal disease
- General - short stature, nutritional deficiency, scratch marks, anaemia, uraemia, peripheral neuropathy
- Biochemical – renal osteodystrophy, hyperparathyroidism and hypercalcaemia, rickets, hyperkalaemia (arrhythmia, paraesthesia, flaccid paralysis)
What are the complications of hypertension?
CNS - stroke
Eyes - retinal bleeds, hypertensive retinopathy
Heart - left ventricular hypertrophy
Complications of treatment - ACE inhibitors (cough, hernia
What are the investigations for hypertension?
- FBC (reduced lymphocytes with Cushing’s)
- UEC and creatinine (low potassium and alkalosis with Conn’s)
- TSH (thyroid)
- BSL (Cushing’s, pheochromocytoma)
- +/- Calcium
- Urine - protein, blood, culture, catecholamines
- CXR/ECG
2nd line:
- Cortisol (Cushing’s)
- PTH (hyperparathyroidism)
- 17-OH progesterone (CAH)
- Imaging - renal USS + doppler
- Specials - VMA and HVA for pheochromocytoma
What are the causes of obesity?
Genetic:
- Prader Willi syndrome - develop delay, small hands, hypogonadism, dysmorphism (almond eyes, narrow bitemporal diameter, thin upper lip, flattened philtrum)
- Laurence Moon Biedl - develop delay, renal issues, visual problems (retinitis pigmentosa), polydactyly, hypogonadism
- Down’s
- Turner’s
- Alstrom - nystagmus, pigmentary changes, deafness, obese, DM, renal failure
Endocrine: Short and overweight: - Cushing’s syndrome (adrenal) or disease (pituitary) - Hypothyroidism - Hypopituitarism - Growth hormone deficiency - Pseudohypoparathyroidism Tall and overweight: - Simple obesity/ nutritional - Klinefelter’s - euchnoid, hypogonadism, gynaecomastia If normal height and overweight - IDDM
Drugs:
- Prednisolone - Cushing’s
- Megace (progesterone)
- Sulfonylureas
- Tricyclic antidepressants
What are the complications of obesity?
CNS:
- Idiopathic ICH
- Depression
CVS:
- Hypertension
- Raised cholesterol
Respiratory:
- Increased risk of obstructive sleep apnoea
- Peripheral hypoventilation
Abdominal - fatty liver
Bones:
- SUFE
- Bowing of tibia and femurs - overgrowth of proximal metaphysis (Blount disease)
- Increased risk of osteoporosis (sedentary lifestyle)
Endocrine:
- Insulin resistance
- Acanthosis nigricans
- PCOS - hyperandrogenic profile in girls
- Precocious puberty
- Acne
Features and management of Prader-Willi syndrome
Prader Willi syndrome results from a missing paternal copy of 15q11. Diagnosis is via DNA methylation studies and FISH for microdeletion.
Clinical features
- Obesity from 6 months
- Hypotonia at birth
- Mental retardation
- Short stature
- Facial features – narrow bifrontal diameter, almond shaped palpebral fissures, narrow nasal bridge and down turned mouth
- Strabismus
- Small hands and feet
- Small penis, cryptorchidism, hypogonadism
- Premature pubic and axillary hair growth
- Obstructive sleep apnoea
- Osteoporosis
Management:
- Early intervention
- Monitor and restrict diet
- Growth hormone
- Testosterone/oestrogen for puberty
Causes of delayed bone age
- Constitutional delay of growth and puberty
- Decreased androgens/oestrogens (delayed puberty)
- Emotional deprivation
- Increased cortisol
- Poor nutrition
- Chronic disease
- GH deficiency
- Turner syndrome
Causes of advanced bone age
- Precocious puberty
- Hyperthyroidism
- Sotos syndrome (cerebral gigantism)
- Weaver syndrome
What are the side effects of lamotrigine?
Skin rash (including SJS, esp if with valproate) - start dose low and slow, need to stop if skin rash. Risk highest in first 8 weeks of treatment
Insomnia
Double vision
Dizziness, ataxia, drowsiness
Interactions with valproate, but together have improved efficacy
What are the side effects of vigabatrin?
Risk of peripheral visual field loss which can be irreversible
Sedation
Fatigue
Weight gain
Agitation
Muscle spasms
AED of choice in infantile spasms in tuberous sclerosis
What are the side effects of carbamazapine?
Rash/SJS (esp Han Chinese, test for HLAB15) Drowsiness Thrombocytopenia and haemolytic anaemia Headache Nausea
What are the side effects of sodium valproate?
Weight gain Liver toxicity (monitor LFTs) Thrombocytopenia (monitor FBC) Teratogenic (NTDs) Nausea and vomiting Gingival hyperplasia
What are the side effects of clobazam?
Dowsiness Ataxia/unsteadiness Confusion Amnesia Paradoxical aggression Muscle weakness
New medications in CF + SEs
Ivacaftor - class 3 - G551D - good effects.
Orkambi (ivacaftor + lumacaftor) - class 2 - homozygous delta 508. Only modest effect.
Trikafta (tezacaftor, izacaftor, elexacaftor) - class 2 - delta 508 homozygous or heterozygous - good effects.
SEs: monitor LFTs + yearly opthal review for cataracts. Processed by cytochrome P450 so monitor for drug interactions, small inc BP.
Not a cure - other therapies and surveillance still required.
Treatment of ABPA
Steroids
Anti-fungals
Omalizumab
Discuss the use of pulmozyme in CF
- Cleaves extracellular DNA which usually increases viscosity
- Also called dornase alpha
- Reduces risk of exacerbations and maintains lung function
- Nebulised once/day
Treatment of pancreatic insufficiency in CF
- CREON / PERT - helps with absorption of fats and proteins
- Vitadeck (Vit A, D, E, K) - fat soluble vitamins
- High calorie diet
Treatment of chronic rhinosinusitis and polyps in CF
- Difficult to treat effectively and recur
- Surgical excision, hypertonic saline, antibiotics, nasal steroids
Meconium ileus, constipation, DIOS in CF
- Partly due to bicarbonate flow
- Meconium ileus - medical/surgical treatment - can lead to resection + short gut syndrome
- DIOS - increased risk warmer temperatures, lack of CREON, ensure adequate hydration and salt
- Constipation is common
Discuss CF-related diabetes
- Insulin deficiency +/- resistance, use of steroids
- 10% adolescents, 30% by 30 years
- Can cause lung function deterioration
- Screening: OGTT, continuous glucose monitor
- Treatment: insulin, exercise, taking PERT, good nutrition
Discuss CF-related liver disease
- Universal at autopsy
- Monitor with LFTs and USS - 3 yearly and then yearly adolescents
- 10% significant disease with 10% of these requiring transplant
- Good nutritional status is key and Vitadeck supplements
- Ursodeoxycholic acid improves LFTs but unclear long term benefit
Discuss CF-related bone disease
- Due to reduced lean tissue mass leading to low bone mass accrual
- Adequate nutrition is vital
- Screen patients if: poor nutrition, CF diabetes or liver disease, poor lung function
Discuss fertility in CF
- Males - CBAVD 99% - can use ICSI and IVF
- From age 14 discuss normal sexual function, reduced ejaculate, adult clinics can check for sperm, importance of still using barrier contraception for pregnancy/infection risk
- Females - increasing number have families, outcome depends on health
Screening tools for developmental delay
- Parents
- Clinician
- ASD
- ADHD
- Parents: ages and stages questionnaire (ASQ, 3m-5y), parent evaluation of developmental stages (PEDS)
- Clinician: Bayley infant neurodevelopmental screen (BINS), Brigant screen (0-7y)
- ASD: ADOS, sensory profile
- ADHD: Connor’s
What are BEST?
Behavioural education support teams
For students who are not ORS funded but with difficult behaviours to manage at school
Causes of jaundice
PREHEPATIC CAUSES (unconjugated)
Congenital: Gilbert’s disease Crigler-Najjar syndrome Alagille Haemolysis
Congenital Red Cell Defects: Hereditary spherocytosis Sickle cell disease G6PD ThalassaemiaMalaria HBO incompatibility AutoimmuneHemolytic disease of the newborn Absorbing large haematoma
Acquired:
Hypersplenism
Metabolic – a1antitrypsin deficiency, CF, Wilson’s, hereditary fructose intolerance
HEPATIC CAUSES
Acute liver disease: Hepatitis – ABC, EBV/CMV Toxoplasmosis Drugs – Paracetamol Toxin – Carbon tetrachloride Autoimmune
Chronic liver disease: Chronic viral hepatitis Chronic autoimmune hepatitis ESLD – cirrhosis, haemochromatosis Wilson’s disease
CHOLESATIC CAUSES
Intrahepatic:
Drugs – chlorpromazine
Primary biliary cirrhosis
Viral hepatitis
Extrahepatic (obstructive): Gallstones Congenital biliary atresia Cholangiocarcinoma Stricture – inflammatory, postop Cholangitis Choledochal cyst Carcinoma pancreas, ampulla of Vater Chronic pancreatitis
What are the causes and complicaitons of splenomegaly?
Haematological: Hereditary spherocytosis (autosomal dominant) G6PD deficiency (X-linked recessive)
Infective:
Subacute bacterial endocarditis
Typhoid
Portal hypertension
Complications of splenomegaly:
- Hypersplenism – thrombocytopenia
- Functional asplenism – immunodeficiency and infection by encapsulated organisms
- Splenic infarction – tenderness
- Early satiety – growth charts
What are the main complications of CKD?
Hypertension Hyperparathyroidism Vitamin D deficiency Anaemia Acidosis Hypoalbuminaemia Hyperphosphatemia
Hypertension management in CKD
- Treat when >90th centile
- Aiming for <50th centile - better long term outcomes
- Lifestyle modifications, weight reduction, low salt diet - these will lower BP by 5-10mmHg (same as taking one medication)
- Tx: ACE - or ARB (esp if have proteinuria, as been shown to have reno-protective effect), beta blocker, CCB (e.g. amlodipine, diltiazem), diuretics
Issues with ACE- or ARB treatment for hypertension
- Risk of hypotension - take at night time to decrease symptoms
- Risk of hyperkalaemia, esp in later stage CKD
- Risk of AKI - make sure adequate fluid intake, and stop with acute gastro illness
- Check bloods 2-3 weeks post starting to make sure creat not inc. by more than 20%, and not developed hyperkalaemia
Causes of anaemia in CKD
- EPO deficiency
- Uraemia suppresses bone marrow
- ACE inhibitors
- Blood loss
- Shortened RBC life span
- CKD mineral and bone disorder
- Iron, B12 and folate deficiency (malnutrition and poor absorption)
Treatment of anaemia in CKD
- Target Hb 100-120
- Erythropoiesis stimulating agent - darbepoetin (SC) or erythropoietin weekly or monthly
- Only works if good iron stores. Aim ferritin 200-500, transferrin saturation 20-30%
- May need iron transfusion (oral iron adherence is poor)
Discuss mineral bone disease in CKD
- Abnormalities of C, P, PTH, Vit D
- Abnormalities in bone turnover, mineralisation, volume, strength
- Vascular or other soft tissue calcification
- CKD leads to reduced renal phosphorous clearance
- This causes hyperphosphatemia
- This inhibits activation of vitamin D and there is also resistance to Vit D effects
- This leads to hypocalcemia
- This causes secondary hyperparathyroidism
Management of mineral bone disease in CKD
- Low dietary phosphate and use of phosphate binders
- Can use calcitriol (activated vitamin D) to treat hypocalcaemia and reduce PTH
- Maintain PTH below twice normal range (don’t want too low)
- Manage acidosis with oral bicarbonate
Nutrition in CKD
- Low potassium, low phosphate diet
- Need adequate calories
- Need adequate protein (extra in peritoneal dialysis patients)
- May need supplemental gastrostomy feeds esp if anorexia or vomiting e.g. Kindergen (infant formula - high salt, low K, high calories)
- Fluid restrict if oligoanuric and fluid target if polyuric
Growth in CKD
- Need to ensure adequate nutrition
- Growth hormone supplementation criteria:
- 1 year post renal transplant (have stopped GH during kidney transplant, can’t start until at least 1 yr later)
- GFR <30
- Height and height velocity <25th centile
Management of CKD post kidney transplant
Risk of infections:
- PCP - cotrimoxazole prophylaxis
- CMV - valganciclovir proph. if donor CMV +ve, for first 6m
- BK virus - nephropathy, graft dysfunction, blood level surveillance for first 1-2 years
- Varicella - need VZIg as prophylaxis
Risk of malignancy (2nd biggest cause of death):
- PTLD - post transplant lymphoproliferative disorder = EBV-driven lymphoma. Presents in first 1-2yrs post transplant, esp when need higher levels of immunosuppression with rejection
Triple immunosuppression: - Tacrolimus - Mycophenolate - Prednisolone ( + induction prior to transplant with IV methylpred and IL-2 blocking agent)
Findings in renal osteodystrophy
Hyperphosphatemia, inc FGF23 + low Vit D, hypocalcemia, secondary hyperparathyroidism
Bone pain and deformity
Muscle weakness
Bow-legs and knock knees
Growth restriction
Dental anomalies - defective enamel, malformed teeth
Can develop soft tissue calcification if Ca+ too high
X-rays: widened growth plates, fraying and cupping of metaphysis (renal rickets), subperiosteal bone resorption, osteopenia (secondary hyperparathyroidism)
Tx:
Calcitriol (active Vit D, OD) - aim for serum PTH to be twice the upper limit of normal, also monitor ALP
Calcium supps (calcium carbonate)
Low phosphate diet (avoid ice cream, milk, dairy) and phosphate binders (e.g. calcium carbonate, needs to be given with food)
Bone monitoring in CKD
- Phos, Vit D3, Ca, PTH, ALP
- Annual x-rays - bone age, x-rays hip/knee/ankle (weight bearing joints) looking for renal rickets and osteopenia
Causes of poor growth in CKD
- Deficient caloric intake
- Salt wasting and polyuria
- CKD from infancy (-3 SDS height)
- Chronic steroid use
- Abnormalities in IGF-1
- GH resistance
- Poor protein synthesis
- CKD mineral and bone disease
- Acidosis
- Infection
- The lower the GFR, the lower the height percentile.
- In younger children, maximise caloric intake.
- Other children need GH replacement (esp if <3rd centile or -2 SDS)
- Need to optimise nutrition, monitor bone disease, correct acidosis and anaemia, avoid high dose steroids, provision of adequate salt
What are the side effects of EPO
Hypertension
Hyperkalaemia
Vascular access thrombosis
Iron deficiency
Complications of peritoneal dialysis
Peritonitis (usually staph epi + aureus) - treat with IP cefazolin and gentamicin
Exit site and catheter tunnel infections
Catheter blockage
What is the transplant work up in CKD
- Adding to waiting list for cadaveric donor
- Monthly bloods
- ABO blood typing and HLA tissue typing in child and prospective family donors
- Pre-transplant immunisation esp Varicella
- Viral surveillance: HSV, Hep B, C, CMV, HIV, EBV. Can give valganciclovir prophylaxis for CMV
- Assess bladder for VUR and outlet obstruction
- Adequate nutrition, must weigh at least 10 kg
Side effects of sirolimus
Mouth ulcers
Hypercholesterolaemia
Pneumonia
Rash
Findings + treatment in renal transplant rejection
Tenderness over graft Fever Rising serum creatinine Leukocytosis -> confirm on renal biopsy -> treat with high dose IV steroids +/- thymoglobulin
Acute and late complications post transplant
- Acute: infection, rejection
- Late: skin cancers and lymphomas, decreasing renal function (50% renal survival at 15yrs), cardiovascular disease (LV hypertrophy, hypertension, hypercholesterol) leading to stroke and IHD
- Can get chronic rejection, acute rejection, vascular thrombosis, recurrent disease in transplant (esp in FSGS and MPGN)
Follow-up/monitoring in CKD
- Growth
- BP and oedema
- U+Es, creat, urea, C/M/Vit D/PTH/ALP
- FBC
- Bone age + joint x-rays
- Cholesterol
- CXR
- Calculated GFR
What are the most common causes of nephrotic syndrome?
- Minimal change disease (80-90%)
- FSGS - 2nd most common cause of ESRD. Can be idiopathic or secondary e.g. after PSGN. Most frequent diagnosis in steroid-resistant nephrotic syndrome
- Mesangial proliferative glomerulonephritis - usually idiopathic but can be from sickle cell or SLE or post transplant
Discuss in nephrotic syndrome:
- Remission
- Relapse
- Frequent relapsing
- Steroid dependence
- Steroid resistance
- Remission: negative protein >3 consecutive days
- Relapse: 2+ protein > 3 days
- Frequent relapsing: 2 in 6m or 4 in 12m
- Steroid dependence: 2 consecutive relapses on steroids or first 2 weeks ceasing steroid
- Steroid resistance: failed response after 8 weeks of 2mg/kg steroid
Complications of Nephrotic Syndrome
- Complications of treatment: steroid side effects, poor growth, SEs of steroid sparing medications
- Infection - esp cellulitis, peritonitis, UTI. Due to urinary loss of immunoglobulin, opsonising factors, and complement, chronic immunosuppression with steroids, oedema and ascites. Risk with encapsulated bacteria (strep, haemophilus, E. Coli)
- Growth - urinary loss of IGF-binding protein, decreasing levels of active IGF-1 + side effect of steroids
- Oedema - with rapid onset NS usually intravascularly deplete therefore treat with albumin + frusemide. In chronic, usually overfilled therefore treat with frusemide and spironolactone alone.
- Thrombosis and embolism - increased hepatic synthesis of clotting factors, urine loss of antithrombin 3 and protein S, thrombocytosis, increased blood viscosity, decreased blood flow. Usually venous, renal vein thrombosis or sagittal sinus. Treat with LMWH +/- warfarin.
- Hyperlipidaemia and CVD risk - reversed quite quickly, usually not a clinical concern. Inc risk coronary arterial disease in unremitting NS.
- Hypothyroidism - due to loss of thyroid-binding protein in urine, common problem
- Hypocalcemia - due to loss of vitamin D-binding protein in urine. Long term leads to bone demineralisation
- ESKD - most at risk are steroid-resistant FSGS, up to 10% of these develop ESKD.
Initial investigations in nephrotic syndrome
- Urinalysis: protein, transient microscopic haematuria, cellular casts (don’t occur in MCD), protein:creatinine ratio
- Bloods: U+Es, albumin, FBC, complement, Hep B and C serology
Indications for renal biopsy in nephrotic syndrome
<1 year age, older children, steroid-resistant, persistently low complement C3, nephritic features (haematuria, hypertension, raised creatinine)
Steroid treatment in first presentation of nephrotic syndrome
- 60mg/m2/day for 4 weeks
- 40mg/m2 alternate days for 4 weeks
- Wean over next 4-6 weeks
- Total duration treatment is 3 months
Side effects of cyclophosphamide
- Bone marrow suppression, risk of viral infections e.g. varicella, measles
- Infertility
- Malignancy
Treatment in nephrotic syndrome
- SSNS: steroids initially + for relapses. 2nd line options are cyclophosphamide, mycophenolate, tacrolimus, levamisole, rituximab
- SRNS: tacrolimus and ACE-, can try IV methylpred, rituximab
- Antibiotics: PO penicillin during initial illness + relapses. If unwell then cefotaxime + ampicillin
- Immunisations: no live vaccines, need VZIg if at risk of VZV. Can give pneumococcal PCV13 + 23PPV + haemophilus vaccine + flu
- Severe oedema (anasarca) - IV concentrated albumin 20% with IV frusemide after first hour. Risk of overload, hypertension, pulmonary oedema.
- Hypertension - most won’t have hypertension. ACE- or ARB as they delay deterioration of renal function with ongoing proteinuria
- Diet: normal protein, salt restriction during relapses (otherwise no added salt). No fluid restriction except when oedematous, adequate calcium and vit D intake, risk obesity with steroids so require healthy diet + exercise plan
What are the features of Alagille disease?
- AD, JAG1/NOTCH 2
- Facies: prominent forehead, triangular facies, deep set eyes, long straight nose, small low set ears)
- Cardiac: peripheral pulmonary stenosis, ToF, right sided and septal defects
- Liver: intrahepatic biliary hypoplasia -> liver transplant in 15% due to intractable pruritus or cirrhosis and portal hypertension. Treat with ursodeoxycholic acid, cholestyramine. Can use rifampicin and naltrexone for itch
- Renal: PUJ obstruction, parenchymal defects
- Skeletal: butterfly vertebrae
- Ocular: posterior embryotoxon, peripheral corneal opacification
- Cerebral aneurysms
- Delayed gross motor milestones
Metabolic causes of liver disease (WATCH)
- Wilson’s disease
- A1AT deficiency
- Tyrosinemia type 1
- CF
- Hereditary fructose intolerance
Discuss Wilson’s disease
- Most common cause fulminant liver failure in >3y age
- AR, disorder of copper metabolism, copper unable to be excreted into the bile
- Copper accumulation in liver, brain (basal ganglia - movement disorder and dystonia in adolescence), kidneys (protein, blood, Fanconi syndrome), bones, cornea (Kayser-Fleischer rings), joints (arthritis), heart (cardiomyopathy, arrhythmia)
- Low serum copper and ceruloplasmin, raised urinary copper
- Rare to present before age 3
- Tx: copper chelating agents - penicillamine and zinc, low copper diet (no brain, liver, shellfish, chocolate), liver transplant if unresponsive to treatment, does not recur in new liver
Discuss A1AT liver disease
- 2nd most common cause of liver transplant
- PiZZ phenotype, accumulates in liver and causes destruction
- Presents <6m age with cholestasis, FTT, Vit K-responsive coagulopathy. Can then develop paucity intrahepatic bile ducts and jaundice
- 1/3rd recover, 1/3rd cirrhosis, 1/3rd transplant
- No other treatments exist for liver disease
- Cured with transplant, does not recur
Treatment of primary sclerosing cholangitis or autoimmune hepatitis
- 1st line: prednisolone or azathioprine
- 2nd line: cyclosporine or tacrolimus
- Liver transplant if these fail, or fulminant hepatic failure. AIH can recur after transplant
Complications of cirrhosis (HEPATIC)
- Hypersplenism
- Encephalopathy and esophageal varices
- Portal hypertension, protein calorie malnutrition
- Ascites
- Thrombosis of portal vein
- Infection (SB peritonitis)
- Coagulopathy, carcinoma (HCC)
Management of chronic liver disease
- General: monitor weight, LFTs, albumin, cogs, bilirubin
- Nutrition: high energy, moderately high protein, may need enteral feeding, Vitabdeck, zinc, iron, calcium supps
- Ascites: restrict salt, aim negative salt balance and lose 250g per day, treat with spironolactone, frusemide, if renal involvement may need dialysis
- Hepatic encephalopathy: can be vague such as lack of energy, drowsiness, regression in school work. Can be precipitated by infection, excess protein intake, electrolyte imbalance. Treat with protein restriction, lactulose, neomycin. Get toxic metabolites and altered BBB.
- Portal hypertension: leading to oesophageal varices, can bleed and be life-threatening. Band ligation or sclerotherapy, balloon tamponade. Avoid splenectomy if possible as inc risk infection and makes risk of variceal bleeding higher.
- Pruritus: use ursodeoxycholic acid +/- rifampicin, cholestyramine
Complications of liver transplant
- Graft rejection - raised ALT+AST, fever, malaise, jaundice. Responds to pulsed steroids, increase tacrolimus and addition of mycophenolate. Can develop autoimmune hepatitis (tx with azathioprine and prednisolone)
- Infection: early infections are bacterial or fungal (intra-abdominal or line infections). Late are viral e.g. CMV, EBV, VZV
- Biliary complications: up to 6 years later. Cholangitis, strictures, may require surgical revision, balloon dilation, re-transplant
- Hepatic vascular compromise: hepatic artery/vein or portal vein stenosis or occlusion. Portal vein stenosis leads to portal hypertension. Hepatic artery thrombosis can lead to urgent re-transplant, peritonitis, strictures. Balloon, stent, surgical re-construction.
- Post-transplant lymphoproliferative disease (EBV driven B cell proliferation) - ranges from lymphohyperplasia to true lymphoma. Occurs 3-12m post transplant. Monitor EBV PCR. Tx by decreasing immunosuppression, start ganciclovir, acyclovir and CMV hyperimmunoglobulin. Can also use rituximab.
Most common causes of malabsorption/maldigestion
- CF
- Coeliac disease
- Post-gastroenteritis syndrome
- Giardiasis
- Bacterial overgrowth (post prev surgeries or congenital gut anomalies)
- IBD
- Pancreatic insufficiency: Shwachman-Diamond syndrome
- Short gut syndrome <100cm e.g. post NED
- CLD with cholestasis
- Intestinal lymphangiectasia and abetalipoproteinemia
Digestive and absorptive causes of malnutrition
Digestive:
- Insufficient pancreatic enzymes: CF, Shwachman-Diamond Syndrome
- Lack of functioning bile salts: liver disease, ileal resection
- Brush border enzymes e.g. lactose intolerance
Absorptive factors:
- Congenital villi defects
- Reduced surface area e.g. short gut
- Inflammation: coeliac disease, post gastroenteritis, CMPI
- Lymphatic issues e.g. lymphangiectasia
Biopsy findings in coeliac disease
Villous atrophy
Crypt hyperplasia
Increased intraepithelial lymphocytes
HLA associated with coeliac disease
HLA-DQ2 and DQ8
Present in >50% of population
Their absence effectively excludes the diagnosis of coeliac disease
Testing in coeliac disease
- DQ2 and DQ8
- tTG IGA antibodies
- Total IgA (if low then need to test tTG IgG antibodies)
- Endomysial antibodies
- Small bowel biopsy
Need to be on gluten containing diet, may need to be re-trialled on glute (2 slices bread per day for 6-8 weeks)
Testing in new diabetic patients
GAD antibodies & IA2 antibodies
Causes of increased faecal A1AT excretion
- Mucosal inflammation
- Coeliac disease and IBD
- Protein losing enteropathy
Investigations in FTT/malabsorption/maldigestion
- Stool: PCR, giardiasis, blood/pus, calprotectin, fat globules and crystals, reducing substances, A1AT excretion
- Bloods: FBC + film, CRP, ESR, U+Es, LFTs, B12/folate/iron, coeliac (tTG + EMA), Vit ADEK, C/M/P
- Sweat test
- Imaging: bone age, bowel contrast studies, liver USS
- Small bowel biopsy is gold standard for coeliac disease
Most common causes of weight loss in older children
Anorexia nervosa Inflammatory bowel disease CF Hyperthyroidism Addison disease Wilson disease Malignancies Coeliac disease
Most common presenting features in SLE
Arthritis 50% - symmetrical PA, morning stiffness + swelling Malar rash 30% Nephropathy 25% - hypertension, oedema, haematuria Fever Lymphadenopathy Hepatosplenomegaly Fatigue/malaise Weight loss
Drug side effects: Cushing’s
Less common:
- neuropsychiatric disease (headache, seizures, chorea, depression, anxiety, psychosis)
- pulmonary (infection, pleuritic chest pain)
- GI (pancreatitis, diabetes)
- cardiac disease (Raynaud’s, myocarditis, serositis)
Predictive markers in SLE
dsDNA - predictor for haemolytic anaemia and nephritis
Lupus anticoagulant - predictor for antiphospholipid syndrome
Causes of failure of upward gaze
Supranuclear ophthalmoplegia Hydrocephalus with sunsetting of eyes Midbrain abnormality Pineal tumour Multiple sclerosis
Parenting courses
Triple PPP - diff age groups, and disability options
Incredible years
Family works
ToolBox - adolescent parenting curse
Brainwave trust - unravelling the adolescent brain
Anxiety resources
Smiling Mind
Reachout.au
Sparx - online free CBT resource for those >10yo through UoA
Sitting like a frog (child)
Centre for Youth Health - Kapiti Youth support, Evolve Youth Health
Causes of diabetes insipidus
Familial Posterior pituitary deficits - can be absent Panhypopituitarism Langerhans cell histiocytosis Post brain injury/bleed
Treatment of SLE
- Steroids
- Then maintenance agent so can wean steroids e.g. methotrexate, azathioprine, or mycophenolate.
- Hydroxychloroquine is useful for skin involvement and protection against cardiovascular events
Side effects of azathioprine
Bone marrow suppression
Liver toxicity
Hypersensitivity reaction - rash, vomiting, dizziness
Ophthalmology screening + treatment of uveitis in JIA
- 3-4 monthly for those at high risk
- 6-12 monthly for lower risk
- Active uveitis - steroid eye drops and mydriatics (pupillary dilation)
- Methotrexate has therapeutic effect, as well as infliximab and adalimumab
Treatment in Turner’s syndrome
- Managing lymphoedema
- Initially yearly screening aortic root dilation then 5 yearly
- Growth hormone once <5th centile on normal growth chart. Continue as long as possible before starting oestrogen (closes growth plates)
- Puberty induction - oestrogen from 12-14y of age (alternate day oestradiol valerate) until feminisation complete (approx 2-3 years). Check bone density near end of puberty. Add progestin (medroxyprogesterone) after 2 years of treatment to enable regular withdrawal bleeding. Monitor Tanner staging, BP, growth. Check FSH + oestradiol every 3-6 months
- Renal: renal USS every 5 years
- Eyes: yearly ophthalmology
- Hearing: risk of conductive and sensorineural hearing loss. Often need T+As and grommets
- Thyroid screening: yearly from age 10 (T4, TSH, anti-thyroid antibodies)
- Coeliac: screen from mid-childhood every 2 years
- Osteopenia risk: even with GH and oestrogen. Encourage exercise, calcium and vitamin D
What are the thyroid autoantibodies found in:
- Grave’s disease
- Hashimoto’s disease
- Grave’s: thyroid-stimulating antibody, TSH-binding inhibiting antibodies
- Hashimoto’s: antithyroglobulin antibody
