Category Archives: General paediatrics

Wilson’s disease

Gastro, General paediatrics, Genetics, Neurology

= hepatolenticular degeneration. Autosomal recessive condition with copper accumulation due to impairment of biliary excretion. Leads to cirrhosis, via a stage indistinguishable from chronic active hepatitis, plus neurological disease. Caused by mutations of the ATP7B gene that codes for a copper transporting ATPase – over 300 mutations known, varying geographically.

Clinical Presentation

Usually presents in late teens but has been described as young as 3yrs. Neurological presentation tends to be older (by 5 years) although they usually have subclinical liver disease. Hepatic disease varies from elevated aminotransferases, through chronic liver disease to fulminant hepatic failure (often with Coombs negative haemolytic anaemia), about 5% of presentations.

Basal ganglia involvement leads to movement disorders viz:

  • Tremor
  • Chorea
  • Parkinsonism
  • Gait disturbances
  • Dysarthria

Other neurological signs are:

  • Psychiatric symptoms
  • Depression
  • Neuroses
  • Personality changes
  • Psychosis

It can also cause:

  • Epilepsy
  • Sunflower cataracts
  • Aminoaciduria
  • Renal stones
  • Osteomalacia with spontaneous fractures

Diagnosis

Can be tricky given multisystem disorder and limited sensitivity/specificity of tests. Heterozygotes may also have borderline results. If typical presentation then diagnosis can be made on basis of:

  • Kayser-Fleischer rings
  • Low serum ceruloplasmin levels (<0.2g/L)
  • Genetic screening of limited utility due to number of known mutations

May require extensive tests of copper metabolism especially with severe hepatic presentation, where up to 50% can have normal ceruloplasmin (an acute phase reactant) eg

  • Non-caeruloplasmin-bound serum copper
  • 24-h urinary copper excretion – can be abnormal in other chronic liver diseases, however. Excretion of >25micromol/24hr after penicillamine is a diagnostic test in children.
  • Liver copper content (>250mcg/g dry weight) – best test when others ambiguous.

In fulminant hepatic failure the following features may suggest diagnosis:

  • Haemolysis (Coombs negative)
  • Alkaline phosphatase surprisingly low viz ALP:Bilirubin ratio of less than 1 has 86% sensitivity and 50% specificity in children

Treatment

  • Diet – chocolate, liver, nuts, mushrooms, and shellfish are high in copper
  • Zinc – reduces copper absorption from gut. Monotherapy is an option for maintenance therapy.
  • Chelation
    • D-penicillamine – but note side effects, and some patients with neurological disease deteriorate on starting treatment
    • Trientine – perhaps less side effects
  • Liver transplantation – curative, except for long-standing neurological disease. Indicated for fulminant hepatic failure.

Monitoring

  • Neurological function
  • Liver function tests
  • 24hr urinary copper excretion (aim for less than 2 micromol/d)
  • Non-ceruloplasmin bound copper of 50-150mcg/L

Liver failure

Gastro, General paediatrics

Jaundice

Clinical, Gastro, General paediatrics

ie raised blood bilirubin.

First decide if conjugated or unconjugated.  Conjugated suggests a biliary problem, ie obstruction to bile flow, usually associated with raised gamma glucuronyl transferase (gamma GT).  Unconjugated (as measured in split bilirubin) implies haemolysis or else hepatocellular damage (transaminases also go up ie AST, ALT).  Unconjugated can also go up in conjugated disease, presumably competition for conjugation sites, or else because of secondary or mixed hepatocellular damage.

History – maternal if baby, immunisations, transfusions, outdoor activities, pets, holidays, drugs, tattoos. Family history (haemolytic conditions, in particular).

Look for signs of liver failure, lymphadenopathy, eyes (Wilsons – best with slit lamp), dysmorphic (Alagille’s).

Consider:

So do:

  • USS abdo – exclude obstruction.  Common bile duct stones can be obscured on USS by bowel gas.
  • FBC, U&Es, LFTs (including GGT, AST if not routinely done), CRP
  • Prothrombin time, glucose, ammonia, lactate – to monitor for failure
  • Amylase
  • Coombs test and reticulocytes – haemolytic anaemia seen in Wilsons
  • Paracetamol level
  • Cholesterol/TGs
  • Urate
  • ANA, anti SMA/LKM ab’s, Immunogloblulins
  • Ca/Phosph/Mg
  • Copper, caeruloplasmin (but not great for Wilsons if acute)
  • COVID, HHV6, HSV, HCV, CMV, EBV PCR
  • HBsAg
  • Hep A&E, Parvo B19, CMV, EBV Serology incl HIV, IM test
  • Viral throat swab (extended screen)
  • Alpha 1 AT if chronic
  • Slit lamps examination – (Wilson’s, also Alagille’s (posterior embryotoxin)
  • CXR to look for butterfly vertebrae (Alagille’s)
  • TTG ab
  • C3/4
  • Alfa fetoprotein
  • Urine amino/organic acids if under 5

If PT>15, give IV vitamin K (0.3mg/kg, max 10mg) and check daily. If resistant then refer.

Button battery ingestion

Gastro, General paediatrics

Damage is from sodium hydroxide generated by electric current, not from leakage!

Should be recognised as a medical emergency, deaths have occurred.

Haematemesis, haemoptysis and respiratory difficulties can manifest up to 28 days after ingestion of the battery, so easy to miss or ignore. Given the age of the children involved, they are unlikely to tell you! Catastrophic aortooesophageal fistula possible, as in the case of Hugh McMahon in Lanarkshire.  Earliest perforation has been at 12 hours – median is 5 days. [Am J Emerg Medicine 2019]

Removal of the battery alone may be insufficient action to prevent further damage, with further symptoms manifesting later; patients need expert input, and careful monitoring and follow-up. One further incident described the death of a child from late complications after they had been treated and sent home.

US Poisons centre recommends use of honey or sucralfate if ingestion within the last 12 hours.

Parenting and constipation

Common, General paediatrics, OPD, Psychology

Parental child-rearing attitudes (as assessed by the Amsterdam version of the Parental Attitude Research Instrument, A-PARI), are associated with constipation in children in Dutch study.

More specifically, both higher and lower scores on the autonomy attitude scale were associated with decreased defecation frequency and increased faecal incontinence. High scores on the overprotection and self-pity attitude scales were associated with increased faecal incontinence.

“Autonomy” reflects emphasis on encouraging independence.  “Overprotection” refers to concern about child with respect to prevention of disappointment and problems for the child, and need to know what’s going on inside child.  “Self pity” refers to irritability and frustration with respect to upbringing, which implies rejection.

More and stronger associations were found for children aged ≥6 years than for younger children.

Authors recommend addressing parenting issues during treatment and even referral to mental health services when parenting difficulties hinder treatment or when the parent–child relationship is at risk.  [Arch Dis Child 2015;100:329-333 doi:10.1136/archdischild-2014-305941]]

 

Marfans syndrome

Cardiology, General paediatrics, Genetics,

Chromosome 15, fibrillin 1 gene (FBN1) locus but lots of different mutations.  Variable penetrance, about a quarter de ovo.

Fibrillin is part of connective tissue, different from collagen, despite clinical overlap with Ehlers-Danlos etc.

Neonatal cases can occur, always severe, with cardiac abnormalities and contractures.

Clinical diagnosis – Beighton (he of benign hypermobility score fame) published Berlin criteria, later came Ghent criteria –

  • family history important, else
  • involvement of the skeleton, plus
  • at least 2 other systems, with a minimum of 1 major manifestation (ectopia lentis, aortic dilatation/dissection, or dural ectasia). 

Skeletal – Tall, disproportionate arm span (>1.05x height – 8cm wider than tall at 160cm) and digits, anterior chest deformity, hypermobility (joint laxity), scoliosis/lordosis, high arched palate and crowded teeth.

Eyes – Myopia, corneal flatness, subluxation of lens (ectopia lentis).

Cardiac – MVP, MR, AR and aortic root dilatation (chart of normal measurements available).  Cardiac examination is often normal despite abnormal echo findings! Aortic aneurysm and dissection can be life threatening.

Pulmonary blebs affect some people, recurrent pneumothorax.  Dural ectasia (widening of lumbosacral spinal canal) on CT is very common, hence why a major manifestation, although symptoms unusual.

Life expectancy is reduced, particularly in males. [Omim]

Hymenoptera venom allergy

Allergy, General paediatrics, Immunology

ie bee/wasp. A common cause of anaphylaxis, and interestingly, not related to atopy.  Reactions can be immunological (IgE or non IgE), or non-immunological (toxic). 

Severe reactions related to allergy but also number of stings, insect type, cardiovascular/respiratory disease and also mastocytosis.

Whether it is bee or wasp or other is sort of important, from the point of view of cross reactivity and risk. Several major allergens eg hyaluronidase, phospholipase A2. Apid (bee) hyaluronidase is 50% identical to vespid, so good chance of being allergic just to one and not the other.  Vespids subdivides into Vespa=hornets (found in UK, biggest, 35mm, reddish brown head); Vespula=wasps; and Dolichovespula (“short headed wasps” – harder to distinguish, “shorter distance between eyes and upper jaws”!). These 3 vespid types cross react strongly, so likely to be allergic to all.   “Yellowjacket” is American name for wasps.

Bumblebee PLA2 is 53% identical to honeybee PLA2, so not necessarily cross reactive!

Polistes=”paper wasps”, distinct from other vespids, Southern Europe only (so far) – large, long legs, not esp colourful. Limited cross reactivity to wasps/hornets, thankfully. 

Ants are also hymenoptera!

Clinical

  • “Normal” local
  • “large” local = >10cm swelling, plus >24hrs. Blisters sometimes present). Mech prob toxic, but sometimes evidence of IgE mediated mechanism,
  • systemic toxic (haemolysis, nephropathy, coagulopathy – rare, usually from multiple stings)
  • systemic +/- anaphylaxis [usually igE, rarely short term IgG, or complement activation by IgG-venom complexes]
  • (plus “unusual”).

Wasps and hornets not as fuzzy as bees. Was a barb left behind? Bees, not wasps. Multiple stings at the same location? Wasp, not bee.

Systemic reactions should be assessed by allergy specialist, including skin prick tests, total IgE and baseline tryptase tests.

  • rapid onset generalized urticaria and/or angio-oedema,
  • bronchospasm
  • laryngeal oedema
  • hypotension (collapse, loss of consciousness).

Hypotension is the dominant feature and may occur alone.

Risk factors for outcome of anaphylactic reaction:

  • age,
  • CVS disease/drugs,
  • insect type,
  • time interval between stings (short interval increases risk of systemic reaction to second sting),
  • number of stings,
  • severity of previous reaction,
  • elevated mast cell tryptase, else known mastocytosis.

Bee allergic at higher risk of systemic reaction than vespid allergic. Hornets risk seems to be esp high.

Frequent stings can induce tolerance (but probably needs more than 200 per year!). 

Venom IgE >1 had 12x risk of anaphylaxis (beekeepers, regardless of previous history). Pos skin test (adults without history of anaphylaxis) had 17% risk, cf 0% of neg skin test [so negative test v reassuring, but risk still low even if you are pos, which would be unusual in most kids]

Majority of fatalities have significant cardioresp co-morbidity. 40-85% of fatal reactions had no documented history of previous anaphylactic reactions.

Mild systemic reaction previously gives 18% risk of subsequent systemic reaction (kids). Compare after large local – 5-15%, so sl higher but not much. Children tend to have mild systemic reactions, cf most adults get resp or CVS symptoms.

Several case reports of severe reactions in mastocytosis; even without mastocytosis, high basal tryptase seems to increase risk of anaphylaxis.

Testing

Even when SPT pos, 25-84% of subjects do not react to subsequent sting!
 
Similarly, up to 22% of those with neg tests will have systemic reaction in future. [Allergy 2005: 60: 1339–1349]

Test all with systemic reaction, not recommended otherwise. If not witnessed? Only really useful to distinguish bees vs wasps (says the Anaphylaxis Campaign)!? Unless you’re a bee keeper, wasps are the one you are most likely to be stung by.

Skin prick testing more sensitive/specific. Probably sensible to leave a month or two between the event and testing else false negative due to “refractory period”. This period can sometimes be longer so consider repeating if good history.  If negative, try IgE; then intradermal ( with 0.001-1mcg/mL solution  -seems to have higher sensitivity).

Stepwise skin testing with 0.01-100mcg/ml solutions incrementally recommended. 

Some people will be persistently negative on testing, probably due to being allergic to an unusual protein. Consider systemic mastocytosis as a differential. 

Family history of venom anaphylaxis is a common cause of concern.  Unfortunately, there is no point testing other family members – you are unlikely to test positive if you have never been stung.

Specific IgE levels (if you do test positive) only vaguely correlate with anaphylaxis risk (not statistically significant) [Allergy 62(8): 884-889, August 2007]. However, having low total IgE (<50kU/l) predicts anaphylaxis (not v sensitive, only explains 25%), whereas high total IgE (>250) protects (very specific)!

Serum IgE appears within a few days of sting, begins to decline at a variable time – wait long enough, and no IgE may be detectable. Double positivity to bee/vespid could be genuine cross sensitivity but might be cross reactivity of IgE to epitopes of unknown clinical significance.

Baseline serum tryptase over 11 has high positive predictive value for anaphylaxis but is not very sensitive. Good for picking up mastocytosis though!

So you may be able to find the occasional person who seems to be at particular risk (high tryptase, low total IgE), or relatively protected (high total IgE) but you will still miss most cases of anaphylaxis.

Immunoblotting, basophil activation tests etc sometimes used if others tests negative. But sens/spec generally not known.  

High basal tryptase may increase risk of reactions with VIT but still indicated.

Give allergy plan and prescribe Adrenaline if severe systemic reaction, consider if moderate. 

If successful VIT, still get adrenaline if further symptoms, continued exposure, high tryptase.

[BSACI guidelines – Clinical & Experimental Allergy. Volume 41, Issue 9, September 2011, Pages: 1201–1220 doi/10.1111/j.1365-2222.2011.03788.x]

Immunotherapy

See Venom immunotherapy.

Honey allergy

Reported, in most cases appears to be due to pollens contained in the honey, or at least allergens highly cross reacting with pollens. But in a minority, does appear to be due to bee derived components. Type of honey will determine what pollens are contained in it; commercial honey often contains v low amounts due to production techniques.

Prevention

Risk of sting related to zone, climate, temperature, outdoor activities etc. Some repellents marketed as effective against wasp/bee (IR3535 (Ethyl butylacetylaminopropionate) eg Jungle Formula “outdoor & camping”) but most creams/sprays (DEET, Citronella oils etc) are for biting insects (midges, mosquitoes etc), not stinging. Bees/wasps generally not interested on landing on your skin anyway!  Sting because they are threatened!  

Avoid opening windows, avoid rubbish bins, tidy away food/drink (esp sugary) .  Calmly walk away!

Keep skin covered. Keep surfaces, mouth/face/hands clean of food residues after eating!!!

Raid-type killer sprays for environment.

Patient Support

Anaphylaxis campaign have insect venom leaflet.

Ocular allergy

Allergy, General paediatrics, Immunology

Differential of eye allergy includes tear film dysfunction, infection, autoimmune/inflammatory conditions, blepharitis, dry eye.

Severe -2 of vision disturbance, impairment of daily activities (leisure, sport, school, work); troublesome symptoms.

Perennial conjunctivitis usually related to house dust mite (HDM), animal dander, moulds else multiple. Itch characteristic, as per seasonal conjunctivitis, findings non-specific eg tearing, redness, eyelid swelling, small papillary hypertrophy of tarsal conjunctiva. Neither has corneal involvement.

Beware pain, photophobia, visual disturbance, grittiness or foreign body sensation.  These can indicated Vernal keratoconjunctivitis, which does affect the cornea (warm climates eg Mediterranean/Africa): typically boys aged 4-12yrs, T cell and IgE combined, improves after puberty. Severe itching, exacerbated by nonspecific stimuli eg wind, dust, sun. Cobblestone appearance of tarsal plate (ie inside upper eyelid) else limbic thickened and opacified +/- white/yellow gelatinous deposits (more typical of tropical form).  Can get corneal ulcers.

Atopic keratoconjunctivits is also rare, the eye can be the only affected area cf atopic dermatitis. Hall mark is fissured eyelid. Staph colonization contributes. Limbus and cornea can be affected.

Giant papillary – associated with contact lenses.

Contact blepharoconjunctivitis is eyelid itching, oedema, eczema with less in the way of conj redness.

Investigations for ocular allergy

Skin prick testing incl moulds. Consider latex. Else IgE.

Conjunctival provocation test can be done with standardized allergens – defer if on local or systemic antihistamines or anti-inflammatories, contra-indicated if uncontrolled asthma.  Ideally when asymptomatic and eye not inflamed! Dilute extract to obtain several lower concentration solutions (last up to 6 hours at room temp).  Administer 20microl dose at 30 min intervals at infero-external quadrant of right eye.  Left eye is control!  Have local antihistamine and steroids available, in addition to usual systemic medicines.  Only 1 reported case of anaphylaxis!

Patch test for non-IgE. Else Conjunctival cytodiagnosis eg eosinophil infiltrates.

Treatment and prevention –

  • Avoid allergens, protect eye with sunglasses.
  • Lubricants and cold compresses are good.
  • Topical antihistamines eg azelastine, olapatadine but also Lodoxamide, ketotifen.
  • Mast cell stabilizer (ie cromoglycate) needs 2/52 preloading and multiple doses per day, plus stings! So poor compliance.
  • Systemic antihistamines if other symptoms else may be excessively drying.
  • Topical steroids should be avoided except where cornea involved, ie VKC, AKC, and then only in short pulses.  Twice daily steroids for a month or more raises concern about glaucoma, cataracts.
  • Ciclosporin drops oily, supply probs – veterinary products used! Tacrolimus not available in drops; cream burns a little but gets better.

Nasal steroids work well for eye symptoms and appear to be safe.

For blepharitis, eyelid hygiene, emollients, 1% hydrocortisone.

[Leonardi, Allergy 67 (2012):1327]

Functional abdominal pain

Common, Gastro, General paediatrics

Rome III classification (now Rome IV?) of functional GI disorders – has child section.  Colic, rumination, cyclical vomiting, diarrhoea, dyspepsia, abdo migraine, IBS, abdominal pain, constipation.

Functional abdominal pain (FAP) must include all of the following:

  • Episodic or continuous abdominal pain

  • Insufficient criteria for other functional GI disorders

  • No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains the subject’s symptoms

Criteria fulfilled at least once per week for at least 2 months before diagnosis

Childhood Functional Abdominal Pain Syndrome

Must include childhood functional abdominal pain, and at least 25% of the time have 1 or more of the following:

  • Some loss of daily functioning

  • Additional somatic symptoms such as headache, limb pain, or difficulty sleeping

Criteria fulfilled at least once per week for at least 2 months before diagnosis

That loss of daily function is an optional criterion is because it would exclude motivated children who continued activity despite the pain and children whose parents insisted that they continue activities. However, it is recognized that there is a subgroup of children in whom loss of daily functioning and/or accompanying somatic symptoms form an important component of their symptom complex. This group is now referred to as having FAPS.

Helicobacter

Gastro, General paediatrics

See testing.

It is still debatable whether H pylori can cause symptoms in the absence of peptic ulcer disease. Young children may of course not give a typical ulcer history, but clues would be epigastric, pain before meals or helped by eating or antacids. Not helpful when functional abdominal pain or reflux disease.

A meta-analysis of 45 studies concluded that H pylori infection is not associated with abdominal pain.  In a German study of 1221 children social and familial factors (single-parent household, family history of PUD, or functional pain) were significantly associated with abdominal pain, but not with the H pylori status of the child, as assessed by the 13C-Urea Breath Test.

In a study of 695 schoolchildren between 10 and 12 years old there was no association between H pylori and recurrent abdominal pain, in fact there was an inverse relationship after adjustment for selected possible confounders!

Although there have been studies that seem to show that symptoms improve with treatment, these have been of poor quality and the natural course of illness is to improve anyway.

Now that a link has been established between helicobacter and cancer (esp stomach, via chronic gastritis, also non-Hodgkins lymphoma) in adults, benefits and risks of treatment when it has been discovered should be discussed.