Category Archives: General paediatrics

Enterovirus

Common, General paediatrics, Infectious disease

Mild: fever +/- rash, hand/foot/mouth, herpangina, pleurodynia, pharyngitis, conjunctivitis, croup.

Serious: meningitis, encephalitis, acute paralysis, neonatal sepsis, myo/pericarditis, hepatitis, chronic infection (immunocompromised).

Meningo-encephalitis in neonates usually associated with other organ involvement. In adolescents headache can be severe and symptoms last several weeks! Early CSF can show around 1000 neutrophils! Prognosis good, although some subtypes with encephalitis highly aggressive eg EV-71 outbreak in Taiwan in assoc with hand/foot/mouth (78 deaths).

Acute flaccid paralysis can occur cf polio. Particularly Enterovirus EV-D68 (also associated with respiratory disease), some clusters.  Increased incidence across Europe including Wales since April 2016.

Neonatal disease can be severe, mimicking bacterial sepsis or HSV. Maternal history is often elusive.

Virus is shed in throat and stool (rectal swab quicker than stool!), can also be detected in CSF, blood and urine.

Role of IVIG is unproven but antibody plays an important role in immune response to EV. Pleconaril in enteroviral meningitis RCT, 38% to 50% improvement in symptoms in the drug-treated group with improvement noted as early as 24 hours after initiation of therapy – no longer available.

[Current Opinion in Pediatrics. 13(1):65-9, 2001]

Human Parechovirus has been described in Japan, Canada and now the Netherlands, causing neonatal sepsis or encephalitis in about 10% of cases where culture suggests enterovirus but PCR is negative. [Clin Infect Dis. 2006 Jan 15;42(2):204-10]

Multiple sclerosis

Genetics, Neurology

Only 3-5% of cases of MS have symptoms before the age of 16. Most have a relapsing-remitting course, particularly in the beginning, typically with one to two relapses per year. The frequency of attacks does seem to predict disease severity and earlier evolution to secondary progressive phase.

Although it takes longer in kids to develop persistent disability, they still develop it at a relatively young age, for example the third or fourth decade of life. That is of course going to have significant effects on life course, including work and family life.

Even at onset, cognitive function is often reduced, which will also affect education and socialisation. So clearly there is interest in disease modifying treatments.

Presentation in younger children often follows an infectious illness. Cognitive impairment is more common relative to older kids.

Investigations

MRI of brain and spine, looking for demyelinating lesions.

Monoclonal bands in CSF.

Treatment

Steroids 10-30mg/kg for 3-5 days effective. No good evidence for IVIG. Where acute life threatening symptoms, plasmapheresis may be effective where steroids fail.

In adults good evidence for interferon Beta in relapsing-remitting disease, IM or SC depending on product, reduces relapse rate and probably slows progression of disability. Glatiramer is a synthetic product with similar effects.

Second line treatments in adults include Natalizumab, mitoxantrone and cyclophosphamide.

Differential diagnosis

  • lysosomal storage disorders,
  • various mitochondrial diseases,
  • other neurometabolic disorders,
  • Krabbe, Metachromatic leukodystrophy, X-linked adrenoleukodystrophy, Fabry, Niemann-Pick C, Chidak-Higashi.  [Clue is in the name, leukodystrophy]

Since these are genetic conditions, essential for management and genetic counselling.

J Weisfeld-Adams http://brain.oxfordjournals.org/content/138/3/517

Mitochondrial inheritance

Genetics

A mother with a mitochondrial DNA gene mutation will pass this abnormal gene to all of her children. The children will all be affected, but with different degrees of severity.

As it is not possible to predict how the children will be affected, this is immensely difficult for planning a family.

Leigh disease

General paediatrics, Genetics, Neurology

Infantile subacute necrotizing encephalopathy.

Clinically heterogenous, lots of different genes.  Can be X-linked, mitochondrial or recessive!!!  Main genetic problem is mitochondrial complex defect, but same disease can be caused by pyruvate dehydrogenase defect (actually a complex of enzymes).

Baby’s initial development may appear normal, although there may be failure to thrive.  Lactate can be raised in serum.  Progressive, often rapid, neurological deterioration including hypotonia, dystonia, seizures.

Lesions (necrotic, gliosis, spongiosis) seen in basal ganglia, brainstem, cerebellum, spinal chord.  CSF lactate and pyruvate may be raised, even if serum normal.

See mitochondrial inheritance.

 

Legume/pulse allergy

Allergy, General paediatrics

Legumes, pulses, beans…  Some terminology first: legumes are plants in family Fabaceae (or Leguminosae).  Pulses are (strictly) those cultivated for DRY seed, as opposed to green beans, broad beans etc that are eaten fresh.  Lentil simply describes shape (“like lens”).  So other examples of legumes are peanut, lupin, tamarind, carob, alfalfa!

Very common cause of food allergy, even excluding peanut! And varies across different cultures, depending on typical pulses used.  Fifth most common cause of food allergy in Spain.  In India, often a trigger of asthma/rhinitis when being boiled.  Cross sensitivity is seen, but not automatic, and hard to predict.

Soya allergy is sometimes seen in highly atopic babies, but otherwise actually pretty rare (except in Japan) – lucky, cause gets into lots of different things eg many breads.  Soya lecithin is a common additive, used to make texture more smooth, but usually only in very small amounts. Fermentation eg soy sauce appears to significantly reduce allergenicity, soya flour also seems less allergenic than soya milk, even though most of the allergens are cupins eg 2s albumin and would therefore be considered heat stable.

Lupin is used in some continental baked goods, for example packaged waffles.  A good proportion of peanut allergic children will be allergic to it too, but as lupin is not found very commonly most will never know or have a problem with it. A few restaurants (in UK and abroad) have lupin in their allergy menus.

A couple of lentil allergens have been identified including a vicilin and a lipid transfer protein.  In my experience pappadoms can often be tolerated – there is certainly evidence that autoclaving for 30 mins can affect binding, but these are only deep fried for a few seconds.

Both the known pea allergens are vicilins, hence cross reactivity with lentil.  Chickpea allergens however are not (one a prolamin, the other a cupin) – still, cross reactivity fairly common.

French beans have an LTP so potentially severe, and potentially fruit allergies too.  Green (mung bean) and red gram are cupins, black gram appears to be something else.

[Clin Rev Allergy Immunol. 45(1):30-46, 2013 Aug]

Thyroid

Endocrinology, General paediatrics

Thyroid issues can be congenital, neonatal, autoimmune, or related to syndromes eg Downs, Digeorge.

Note that thyroid function tests can be affected by intercurrent illness, there is also viral thyroiditis where you might get transient (usually mild) abnormalities.  So borderline results (especially if asymptomatic or other medical issues) usually just need repeated.  If results confusing, do T3.  If normal then abnormal T4 likely to be transient.  If suspicion of evolving problem, do autoantibodies (TPO antibody, Thyroid Receptor Ab (TRab)).  If progressive decline then likely to be emerging autoimmune condition.

All kinds of unusual clinical presentations in thyroid disease, for example:

  • Effusions in hypothyroidism, including pericardial effusions – capillary dysfunction!? Impaired lymphatic drainage?
  • Body pain
  • Precocious puberty (although delayed more typical)

Congenital Hypothyroidism

Endocrinology, General paediatrics

Isolated TSH elevation >20 is usually treated.

True congenital hypothyroidism mostly dysgenesis, ie poorly formed gland, of which <2% have identified mutations (mostly thyroid peroxidise, thyroglobulin and TSH receptor proteins – EDTA sample, Dr Therese Bradley at SGH Genetics).  May be due to dyshormonogenesis (10%, autosomal dominant, gland looks normal on scan), TSH Receptor defect. Do a Family History.

Mostly found on newborn screening now.  Life long.

Placental thyroxine important, iodine too, on neonatal thyroid function.  In the first 14/7 of life, high TSH/T4/T3 seen.  Transient neonatal hypothyroidism seen, 25% of +ve guthrie tests!

Symptoms

If missed or untreated, classic signs are umbilical hernia, goitre, hoarse cry, coarse facies, Developmental Dysplasia of Hip!

Imaging

SPEG recommend that all families should be given the opportunity for imaging, subject to availability, because more informative than blood tests alone, will aid in genetic counselling, likelihood of lifelong treatment if proven permanent CH, provides a useful guide as to thyroxine dose.

Combined isotope and ultrasound imaging (dual scanning) is preferred. Isotope scans should be performed by day 5 of start of treatment to ensure avoidance of false negatives due to TSH suppression (advisable to take thyroid function sample on day of scans to confirm reliability of results). Ultrasound may show an abnormal gland (dyshormonogenesis) or else agenesis (no gland).   But in agenesis may be remnants of embryonic structural elements which can be mistaken for a gland – can persist into teenage years but max 5mm x 5mm! Hence importance of supporting radio-isotope imaging.  Experience of ultrasonographer important.

Management

Some concern that thyroxine liquid not as consistent levels?  Automatic script request from pharmacy, patient then notified when ready.

Repeat TGTs at 10-12 weeks.  Aim to keep TSH in lower half of reference range (room to spare as child grows).

Follow up

  1. Scottish guideline suggests typical doses at different ages, up to age 3, to encourage dose changes with growth rather than waiting till dose insufficient and hypothyroidism emerges (see table).  Use TFTs to confirm compliance.
  2. Assess growth: weight, length until 2 years, then height, head circumference until 3 years
  3. Assess development – consider pre-school audiology (for subtle hearing impairment due to CH)
  4. Transition – patient education. Boys to GP (unless problems with control), girls – to adult endocrinology (for pre-pregnancy counselling).

Aim for fT4 > 15 pmol/l and TSH <5.0 mU/l

Age LT4 dose (ug daily) LT4 dose (ug/kg/day)
Female Male Female Male
3 months 41.3 43.3 7.2 6.9
6 months 45.8 50.0 6.1 6.2
9 months 47.9 53.1 5.6 5.7
12 months 55.0 53.1 5.8 5.2
18 months 62.5 61.1 5.8 5.3
24 months 70.3 58.3 5.9 4.6
36 months 75.0 62.5 5.3 4.25

Haemophilia

General paediatrics, Haem/Oncology

The clinical severity of a patient’s hemophilia is gauged by the baseline clotting factor level, a value that remains fairly constant throughout that person’s life, and is pretty consistent through a family. Around 5% of normal is moderate.

Intramuscular injections should be avoided if at all possible. If they must be given, factor replacement therapy should precede the injection. Parenteral agents should be given intravenously or subcutaneously. Immunizations are administered subcutaneously.

Aspirin is contraindicated due to antiplatelet effect. Avoid NSAIDs if possible, and contraindicated if actively bleeding or being treated for a recent bleeding problem.

Indications for Factor Replacement Therapy

  1. Suspected bleeding into a joint or muscle.
  2. Any significant injury to the head, neck, mouth or eyes or evidence of bleeding in those areas.
  3. Any new or unusual headache, particularly one following trauma.
  4. Severe pain or swelling at any site.
  5. All open wounds requiring surgical closure, wound adhesive, or steri-strips.
  6. History of an accident or trauma that might result in internal bleeding.
  7. Necessity of a surgical or invasive procedure.
  8. Heavy or persistent bleeding from any site.
  9. Gastrointestinal bleeding.
  10. Acute fractures, dislocations and sprains.

Treatment

Hemophilia A

The treatment of choice for individuals with factor VIII deficiency is recombinant factor VIII. There are different brands, with different combinations of additives which may or may not be antigenic. Cryoprecipate and fresh frozen plasma are used only if factor cannot be obtained.

  • When bleeding is severe, or for a head injury, the appropriate dose of factor VIII is 50 units/kg. This should result in a factor VIII level of 80-100%. Half life is 8-10 hrs so repeat if necessary.
  • Mild Hemophilia A (factor VIII greater than 5%) with Non-Life/ Limb Threatening Bleeding may respond to desmopressin (some don’t) – 0.3mcg/kg IV over 30 minutes, else as nasal spray (Stimate, 1 spray in one nostril for individuals <50 kg and 1 spray in each nostril for individuals >50 kg). Otherwise, treatment dose is 15-25u/kg.

Hemophilia B

For individuals with Christmas disease (factor IX deficiency), recombinant factor IX is the treatment of choice. Fresh frozen plasma is only used if factor is unavailable.

  • When bleeding is severe, or head injury, the appropriate dose of factor IX is 100-120 units/kg. This should result in a factor IX level of 80-100%, but in Hemophilia B the response is variable so check the level and adjust as necessary.
  • Mild – 25-35u/kg, check level

Ideally let patients/parents reconstitute and administer their own factor. Families should have an emergency dose of factor concentrate or DDAVP in their home and to take it with them when they travel, esp if they do not live close to a hospital. Factor replacement should be offered within 1 hour of the patient’s arrival: it should be readily available, the patient should not be left waiting, and treatment should not be deferred pending x-rays or other results. The most experienced IV therapist or phlebotomist available should perform venipuncture – misses and tourniquets may cause painful hematomas which then limit further IV access – use the smallest needle possible unless volume replacement is needed..

Factor replacement must be administered intravenously by IV push over 1-2 minutes. Round the dose up to the closest full vial ie don’t throw away any left overs (excess factor does not create a hypercoaguable state but will prolong the therapeutic half-life of the product administered).

For individuals with inhibitors (antibodies to factor VIII or IX), treatment decisions may be more complicated. The care of inhibitor patients should be urgently discussed with the patient’s hematologist. If an individual with an inhibitor presents in a life- or limb-threatening scenario, the safest immediate action is to prescribe recombinant factor VIIa (rFVIIa, Novoseven) at a dose of 90 mcg/kg or activated prothrombin complex concentrates (FEIBA, Autoplex) at 75-100 units/kg (contraindicated in factor IX patients with a history of inhibitors and anaphylaxis). Hopefully the patient/family can provide information on response to second line therapeutic agents.

[Medical and Scientific Advisory Council (MASAC) of the US National Hemophilia Foundation 2003]

Haematuria

Common, General paediatrics, OPD, Renal

In a study of 342 kids with asymptomatic microscopic haematuria, no cause was found in the large majority of patients. The most common cause discovered was hypercalciuria (16% of patients) followed by post–streptococcal glomerulonephritis (1%). No evidence for value of early detection of hypercalciuria (may be at long-term risk for nephrolithiasis and bone demineralization).  The children with asymptomatic post–streptococcal glomerulonephritis all improved spontaneously and without complication.  None had evidence of urinary tract infection! Clinically insignificant abnormalities in the upper urinary tracts of 5 children and grade 3 reflux in 1  [Arch Pediatr Adolesc Med. 2005;159(4):353-355. doi:10.1001/archpedi.159.4.353]

Asympt recurrent can be monitored for 5yr!

Beware:

  • frank blood,
  • protein,
  • hypertension,
  • other features (joints, rash, wt loss)

Haematuria defined as persistent dipstick positive on at least 3 occasions for at least 3 months. Else as >2rbc per HPF (not same as flow cytometry). Then consider:

  • Red cells or not?
    • myoglobinuria = haemolysis
    • beetroot!
    • Porphyrins, other unusual pigments
  • Proteinuria or not?

If spot urine abnormal, repeat on early morning urine and then proceed to 12-14hr collection. Urine calcium/creatinine has age specific normals, high at birth (up to 1.5 in toddlers) falling to adult max of 0.7 at age 7. High levels especially significant in the presence of a normal plasma calcium

Investigations – only do bloods if macroscopic or nephritis suspected:

  • Do urine culture and microscopy.
  • Do PCR if proteinuria.
  • If macroscopic, do FBC, U&Es, LFTs, Coag.
  • Renal USS
  • Screen family members with urinalysis
  • Spot urine calcium/creatinine
  • If acute nephritis, do C3/4, ASOT, immunoglobulins, ANCA, anti GBM as below.
  • If stones suspected, do 2 sets of spot urine Ca/creat, Oxalate/creat, Urate, amino & organic acids, pH, KUB.

Differential is:

  • Tumour – bladder (colour changes during voiding, dysuria with sterile culture) or kidney
  • IgA nephropathy – persistent, progressive in 30%, diagnosis on biopsy
  • Alports – usually X dominant, deafness in minority, cataracts in 10%
  • Sickle cell – 1% macroscopic, 16% microscopic. Papillary necrosis, usually painless, episodic. May progress to sickle nephropathy.
  • Venous thrombosis – esp neonates, nephrotics.
  • Vascular – AVM, Nutcracker syndrome (compression of the left renal vein between the abdominal aorta and SMA)
  • Nail-patella syndrome (BM disorder, like Alports)
  • Polycystic Kidney Disease

Biopsy if persistent high grade microscopic, or microscopic with proteinuria (>150 mg/24 hr)/hypertension/impaired renal function, or 2 episodes of gross haematuria. Cystoscopy for bladder problem.