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Listeria

Congenital, General paediatrics, Infectious disease, Neonatology

An intracellular gram positive rod – not many of those, apart from in probiotic drinks!  Resistant to cold and salt, so particularly a problem in ready to eat foods eg deli meats, hot dogs (unless steaming hot), cheese esp soft (incl blue veined, but excl mozzarella), raw and cooked poultry, ice cream, raw vegetables, raw and smoked fish (unless in shelf stable form). Melons and hummus have been sources in US.  In adults, tends to affect those with underlying health problems.

Infection in pregnancy often undiagnosed. May cause preterm labour or intrauterine death. Infection at birth may be severe, with classic fine papular rash, widespread microabscesses and granulomas, and bacteria visible on gram stain of the meconium. Or infection may be late in onset eg 1-2 weeks, with meningitis (note low counts cf other causes), else endocarditis, osteomyelitis etc.

Preterm meconium staining of the amniotic fluid (MSAF) is a “classic” feature – was observed in 4.3% of infants below 33/40. No maternal or infant listeriosis was identified in any of the 1000 cases. MSAF was associated with prolonged rupture of the membranes and severe (grade 3/4) intraventricular haemorrhage (OR 2), not sepsis or mortality. (Simpsons, Arch Dis Child Fet 2004)

Surveillance study of bacterial meningitis in infants aged <90 days in the UK 2010-11 showed that then usual three bacteria (GBS, E. Coli and Listeria) remained dominant, their frequency varied significantly by month of life. In the first 30 days of life. L. monocytogenes was the third most common bacteria, responsible for 6% of cases. The median age of meningitis due to L. monocytogenes was 13 days (IQR 3–18 days) with the oldest infant being 29 days; Listeria meningitis was therefore not seen beyond the 1st month of life. Of the 11 cases of Listeria meningitis, a good number (although a minority) were preterm and most first became unwell when at home. 2 cases had serious complications but no deaths.

Public Health England have published 24 years data on listeria septicaemia and meningitis. 97% of all cases presented in the first 30 days of life. Bacteraemia is more common but tends to be early onset (<7 days of age) whereas most meningitis were late onset.

It is also prudent to consider the possibility of Listeria infection in older infants (and therefore add amoxicillin) if:

  • Gram-positive rods are seen in the cerebrospinal fluid,
  • if the infant is immunocompromised
  • or if the clinical response to empirical therapy is suboptimal

Treat with high dose amoxicillin/ampicillin. Gentamicin is synergistic but does not penetrate intracellular compartment (or CSF) – can be stopped after a week assuming good clinical improvement. For allergic, TMP-SMX (Septrin) is best alternative! Cephalosporins are useless! Treat for 2 weeks if no meningitis, at least 3 weeks if meningitis, longer if abscesses or heart involvement.

[Okike, Arch Dis Child 2015;100:426-431]

Hepatitis B

Gastro, General paediatrics, Infectious disease

Highly infectious blood borne virus. A single contaminated needle stick injury carries a significant risk of transmission. In endemic areas, significant rates of postnatal infection in children, presumably from minor trauma.

Acute infection develops over 1-6 weeks and can be fulminant. Symptoms are non-specific fever, lethargy, abdo pain.  15% have serum sickness type  symptoms in pre-icteric phase viz fever, arthralgia, urticaria. Jaundice then develops.   Various antigens, which may or may not clear as antibodies produced, used to diagnose, judge stage of infection, and infectivity.

  • HBsAg – shows Acute or chronic hepatitis B infection. Can be negative in acute fulminant disease.
  • Anti HBs (or Anti HBs) – Immunity to hepatitis B, postinfective (only 6% of patients) or with active or passive immunization
  • Anti HBc IgM – first antibody to appear, even before HBsAg.  High titer: acute hepatitis; Low titer: chronic infection
  • Anti HBc IgG – Past exposure to hepatitis B, or maternal antibody crossing placenta in young infants
  • HBeAg – highly infectious.  Without treatment, 85% of children clear HBe.
  • anti HBe – not immune, but low infectivity. Do not develop chronic hepatitis; but low risk of hepatocellular carcinoma persists.

NB there may be an interval following the disappearance of a hep B antigen before its antibody becomes detectable.

For acute hepatitis, no specific treatment is required, just supportive. If fulminant, some people use antivirals, but basically the issue is whether you need to transplant – see below.

Carrier rate (ie chronic infection, = HBsAg pos for 6/12, and hence potential for serious sequelae) is higher in males and greatest in those infected in first 3 years of life.  Also higher in those with mild symptoms viz anicteric with minimal elevation of transaminases.

Some carriers will be inactive with anti-HBe, low levels of DNA (<100 000 copies on PCR) and normal transaminases. Liver disease progresses very slowly if at all, although hepatocellular carcinoma risk is still higher than normal (but much less than in HbeAg positive). Monitor LFTs every 6-12 months.

In active chronic infection, DNA levels are high indicating active replication, transaminases are 2x the upper limit of normal or higher, and biopsy will show stage 4 histological activity or more. HBeAg is usually positive although some mutants will be negative. Adults with chronic hep B have 20% cirrhosis rate after 10 years and 37% after 15 years. Alcohol intake is an independent factor. Hepatocellular Ca rate is about half that.

When to biopsy is tricky, partly because the clinical course is unpredictable but also because treatment is ineffective. Transaminases can be raised transiently, so repeat after 1-3 months. Histological cirrhosis has a poor prognosis. With treatment, 32% of patients with chronic disease clear HBeAg cf 11% of untreated (metanalysis). There is no benefit in patients with normal LFTs.

Do USS and alpha fetoprotein every 2 years as screening for hepatocellular Ca for both inactive carriers and chronically infected.

Other management points –

  • immunisation of household contacts
  • vaccination against hepatitis A (in low prevalence areas)
  • avoiding alcohol
  • safe sexual practices
  • weight reduction
  • Careers advice
  • Immunosuppressive drugs may activate hepatitis B infection. Equally, immunosuppressed children may have hepatitis B infection without serological evidence – so do PCR.

Treatment

For acute, no specific treatment, just supportive. If fulminant, look for co-infections that may have precipitated episode. Main issue is whether transplant required, although American Association for study of liver diseases recommends using antivirals in adults: no great evidence but seem reasonably safe, and reduces risk of re-infection of grafted liver after transplant (pretty inevitable – HBIg post transplant also delays infection but resistant mutants come through). Lamivudine or telbivudine suggested when the anticipated duration of treatment is short; otherwise, entecavir is preferred. Treat until HBsAg cleared or indefinitely in transplants. Interferon is contraindiated.

For chronic infection:

  • Pegylated IFN alpha (5 million units a day or 10 MU thrice SC for 48 weeks) both antiviral and immunomodulatory activity.

Other issues:

  • Co-infection with HCV has a poorer prognosis even though DNA levels may be less; treatment should be considered at 1000+ copies.
  • In decompensated cirrhosis, transplantation is the only definitely effective option. Lamivudine may help (historical controls). IFN increases complications.

Hepatitis A

Gastro, General paediatrics, Infectious disease

Faeco-oral transmission.  Global distribution.

Incubation 4/52, can be asymptomatic in young children. Non-specific fever, malaise, possibly RUQ pain before jaundice appears, usually with rapid relief in symptoms.  Up to 1% however have fulminant disease with hepatic failure.

Post exposure prophylaxis for hepatitis A with hepatitis A vaccine reduces secondary infection rate from 13% to 2.8% (NNT=18).

See also viral hepatitis.

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]