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Anaesthetic allergy

Allergy, General paediatrics, Immunology

Reactions to local anaesthetics are often reported, but given how often they are used, most turn out not to be allergic but rather toxic (eg to parabens or sulphite preservative) or autonomic. Where allergy is confirmed, it is often of a delayed hypersensitivity type eg 24-72 hours after exposure. Beware latex allergy and C1 esterase inhibitor deficiency too. Local anaesthetics come in 2 main groups, the esters (procaine, benzocaine) and the amides (lidocaine, bupivocaine). Cross-reactivity is common among the esters but not among the amides or between the 2 groups. Neomycin sensitivity may contribute to a reaction.

Asthma prevention

Common, General paediatrics, Respiratory

Atopy is not a single phenotype, the idea of an “atopic march” from infantile eczema through food allergy to asthma and rhinitis is way too simplistic. Early interventions have been disappointing. Curiously, food allergies and eczema often improve through childhood – this seems less common with asthma.

There are different risk groups.  Environmental exposure to allergens and microbes in early life is one factor.  Farm environment protects (exposures and/or dietary).

Most studies show dog ownership protective. Weaker evidence for cats. House dust mite sensitisation in early life predicts asthma in school age.  Primary prevention of HDM sensitisation has conflicting evidence – Isle of Wight study showed mite avoidance prevented sensitisation and asthma; Canada study showed effectiveness but Dutch study did not.  Manchester study reduced early wheezing but had higher rates of sensitisation. Australian study no effect overall but depended on age.

Reduced bacterial diversity is a risk factor for asthma and atopic wheeze – certain bacteria esp bacteroides and firmacutes seem to be protective.

Viruses also play a role.  RSV is associated with later asthma regardless of existing atopy or not, although perhaps not with asthma persisting into adulthood; rhinovirus wheezing in first 3yrs is similarly associated with persistent wheeze, especially in atopic persons. So impact of more RSV and other vaccines could be fascinating.

Heritability of asthma accounts for less than 50% of patients so gene-environment interactions are at least as important.  A gene has been found that is associated with early childhood asthma with severe exacerbations (CDHR3). TSLP gene on chromosome 5q22 encodes for a master regulator for TH2 processes. But another well recognised gene region on chromosome 17q12-21 (including ORMDL3 and GSDMB) seems to be involved in airway dysregulation after virus infection, rather than allergy.

Increasing evidence that respiratory health is influenced by parental exposures that occur long before conception. The strongest evidence relates adolescent tobacco smoking and overweight in future fathers to increased asthma and lower lung function in their offspring, supported by evidence on parental preconception occupational exposures and air pollution.  Antenatal and postnatal (passive) smoking important. Role of breast feeding vs formula still controversial.

No evidence for asthma preventer treatment as an early intervention – cf JIA and other inflammatory conditions.

Grass immunotherapy for rhinitis in children reduces the incidence of later asthma and need for asthma medication. Presumably house dust mite immunotherapy would help too? HDM antigens have allergenic but also endotoxin and enzymatic effects! Jurgen’s study of HDM SLIT in infancy found reduced sensitisation (to anything, but def HDM – but only 11% difference and active group had more pets…); at 3 yrs, no difference in clinical outcomes, unfortunately – in fact, more wheeze…

Spanish RCT of oral bacterial extracts (6 different ones for 6 months) significantly reduced number of wheeze episodes (40%) for up to 1 year. Animal experiments have already shown that oral administration of bacterial extracts prevents bronchial hyperreactivity.

We should therefore encourage less Caesarean sections, more breast feeding, less antibiotic use, more green spaces, more “natural” food preparation and distribution (ie less plastic!).

[PAI 2023]

Toxic shock syndrome

General paediatrics, Infectious disease

Criteria for Staphylococcal Toxic Shock Syndrome (TSS)

Necrotizing fasciitis

General paediatrics, Infectious disease

Life threatening infective necrosis of superficial tissue fascia, often more extensive than would be suspected by appearance of overlying skin.  Can start in previously normal skin, with an insignificant entry site!

Group A streptococcus mostly, but can be polymicrobial especially in immunocompromised.

The top three early presenting clinical features are swelling, pain and erythema but these are entirely non-specific, so initial misdiagnosis common (almost three-quarters of patients in 1 review). More specific features are:

  • pain out of proportion to the physical findings;
  • failure to improve despite broad-spectrum antibiotics;
  • presence of bullae in the skin; and gas in the soft tissue on plain X-ray.

Other possible characteristics described:

  • tense oedema extending beyond margin of erythema
  • loss of sensation
  • LRINEC score in adults based on lab criteria (high glucose, high creatinine, high CRP, high WCC, low sodium, low Hb) has 76% sensitivity, NPV 88.1%.

Early surgical exploration is the best approach in the uncertain case; and early surgical debridement is key to control. IVIG may be of benefit.

Notifiable in Scotland.

Group A Streptococcus

General paediatrics, Infectious disease

Various haemolytic groups, GAS is beta haemolytic.  Other groups of beta haemolytic identified by Rebecca Lancefield.

  • Beta haemolytic Group B is seen in the genitourinary tract of women and is an important pathogen in neonates.
  • Groups C and G both cause invasive disease, both have M proteins, more common throat carriage in developing countries. Maybe also responsible for acute rheumatic fever.
  • Alpha-haemolytic (strep viridans) are associated with line infections and endocarditis.
  • Gamma-haemolytic include enterococci, of which faecium is usually resistant to amoxicillin but faecalis is usually sensitive. Of note, some enterococci are now resistant to vancomycin (VRE).

Exercise induced anaphylaxis

Allergy, General paediatrics, Immunology

Rare but well recognized allergic condition, about half related to a food trigger.

Anaphylaxis can occur with any degree of exercise, does not need to be extreme, but typically follows submaximal exercise pretty quickly.  Deaths are fortunately rare.

Possible mechanisms:

  • Exercise induced increase in gastric permeability
  • increased tissue transglutaminase activity in gut
  • Exercise induced blood flow redistribution
  • Mast cell heterogeneity
  • Basophil trigger by increased plasma osmolality
  • Mast cell trigger by acidosis

All sound plausible but little evidence!

Co-factors play a role in many cases eg alcohol (but unpredictable), NSAIDs (85% will have reduced threshold, and severity increases too), infection, heat/cold – some evidence too for menstruation, anti-acids, stress, sleep deprivation (as in anaphylaxis).  Co-factors also multiply risk of reaction.

Food triggers

Mostly wheat, including hidden sources eg soap, shampoo, cream.

Diagnosis

SPT useful, also IgE omega-5-gliadin.  But gold standard is provocation test (and still only 70% sensitive).  No uniform protocol – use same as for exercise induced bronchoconstriction? Do 1 hour after meal with suspected trigger.

Management

Prescribe adrenaline auto-injector.  Avoid exercise 4-6 hours after food intake.  Discuss unplanned exercise!

Turners syndrome

General paediatrics, Genetics

45XO but mosaics occur.

  • Short stature
  • facial naevi, sphinx like bright eyes
  • Webbed neck
  • Puffy hands and feet as baby
  • Cystic hygroma ie soft tissue mass in neck or intra-thoracic
  • Streak ovaries ie infertile
  • middle ear probs
  • learning difficulties – not really, but maths can be a problem

Acute otitis media

Common, General paediatrics, Infectious disease

Probably 60% of infections are mixed viral/bacterial! Pneumococcus, Haemophilus (non capsulated), Moraxella catarrhalis. Group A Strep is characterized by older age, higher local aggressiveness (ie tympanic perforation and mastoiditis) but lower rates of fever and respiratory symptoms.

AOM is associated with dummy use, adenoids/tonsillitis.

60% of placebo treated children were pain free within 24 hours of presentation [Cochrane 2004, PMID 14973951]. Antibiotics do not increase this proportion. At 2-7 days after presentation, antibiotics reduce by a third the number of children who still have pain (only 14% of the original number), giving a NNT of 15. Too few cases of complications eg mastoiditis to be able to comment on whether antibiotics are useful for preventing such complications.NICE clinical knowledge summary gives NNT of 4000 to prevent 1 case of mastoiditis!

Management is therefore primarily good analgesia. No role for decongestants/antihistamines (Cochrane/NICE).

SIGN guideline 66 on AOM in primary care does not recommend routine antibiotics (but if used, Amoxicillin or co-amox for 5 days recommended). SIGN warns that evidence is poor in infants or in severe disease.

NICE clinical knowledge summary states that at initial presentation, pain and fever should be treated with paracetamol or ibuprofen, at maximum doses if necessary.  No benefit from using both (though poor quality evidence).  For most children antibiotics can be delayed until day 4 of illness (mean duration of illness is 4 days).

Eardrops containing analgesia and anaesthetic (phenazone and lidocaine = “Otigo”) work within 10 minutes – they also significantly reduce the number of people who go on to have antibiotics. Not to be used instead, however, and not to be used where perforation/discharge.

Antibiotics should be offered however at presentation to people who are systemically unwell. Depending on severity, antibiotics should be considered where child is under 2yrs with bilateral otitis media, or if there is perforation and/or discharge in the ear canal.  This advice is also reflected in the British National Formulary for children.

Delaying antibiotics certainly reduces prescriptions, metanalysis of 4 studies in Cochrane did not find any significant difference in pain at 3-7 days, although all but 1 reported some benefit in the immediate treatment group.

A study comparing delayed antibiotics with vs without a prescription (ER based) found high and comparable parental satisfaction rates with both approaches [Chao Peds 2008 PMID 18450878]. In the Cochrane review of delayed antibiotics for URTI, which looked at both adults and children, immediate antibiotics were felt to be more likely to confer modest benefits than delayed antibiotics, with no differences in complication rates between immediate vs delayed antibiotics. Immediate antibiotics had slightly higher levels of patient satisfaction than delayed antibiotics but of marginal clinical significance (92% versus 87%). Concluded that as no evidence for benefit of delayed vs no prescription, best to offer nothing (likely to result in the least antibiotic use). [Cochrane 2011 Delayed antibiotics in URTI, PMID 17636757]

BNFc does suggest antibiotics if:

  • no improvement after 72 hours,
  • clinical deterioration,
  • systemically unwell,
  • at high risk of serious complications (eg in immunosuppression, cystic fibrosis),
  • mastoiditis is present,
  • under 2 years of age with bilateral otitis media.

BNFc also suggests that perforation of the tympanic membrane usually heals spontaneously without treatment; but treat if there is no improvement (eg pain or discharge persists).

Lancet 2006 [pmid 17055944] meta-analysis supports the idea of treating under 2s with bilateral signs (NNT=4), but unlike the BNFc supports treating otorrhoea (NNT=3), as does Cochrane!

Exponential increase in drug resistance and multiresistance. Given how effective placebo is, an effective drug has to do considerably better! Amoxicillin no longer useful (but still recommended by NICE), cefaclor and TMP-SMX not good for borderline resistant pneumococci, azithromycin does not achieve MIC for Hib/Pneumo in ear (although cure rates may not be all that bad…). Co-amox in double dose ie 90 mg/kg/d in 2 divided doses is effective, but increasing resistance.

Treatment leads to higher numbers of resistant species in nasopharynx, esp dually resistant bugs. Azithromycin persists in body for several weeks so is excellent for inducing resistance. Despite overall trend towards reducing antibiotic usage in AOM, most reduction in amoxicillin, with increased prescribing of quinolones and azithromycin. So don’t treat at all unless added features (unless under a year). [Ron Dagan, Beersheva]

Lots of potential complications:

  • Acute mastoiditis = a type of osteomyelitis, with potential for intracranial spread and meningitis/cerebral abscess formation.  Classic signs are erythema, swelling and tenderness behind the ear, with deviation of the pinna.
  • Gradenigo syndrome = intratemporal extension of AOM, causing VI nerve palsy (via apex of petrous temporal bone).
  • Grisel’s syndrome = non-traumatic subluxation of the atlanto-axial joint caused by inflammation of the adjacent tissues.  Clue is trismus and torticollis.

HIV/AIDS

Immunology, Infectious disease

2015 37m worldwide living with HIV, vast majority in Sub-Saharan Africa. Growth is N Africa and Middle East.

20 years since introduction of ART. Still over 1 m deaths per year. Only about a third have access to ART. $250 per child per year.

West Africa seroprevalence only 1-2%, S Africa 25% of sexually active!!!

Treatment for pregnant women actually very good coverage in South and East Africa, much poorer elsewhere.

WHO now recommends treatment for everyone at diagnosis, regardless of CD4, symptoms etc!

In UK 5000 new cases per year, peaked in 2005 (8000), pretty stable now, still mostly migrant associated. Average age of HIV pos child is now 13.6!!! No neonatal cases in Scotland for years.

Majority of known patients have undetectable viral load!

Maternal transmission

Previous advice to breast feed exclusively for 6/12 then stop, now WHO say at least 10-12 months, with no recommendation on stopping. Mixed feeding is now considered acceptable. But this weighs benefits of breast feeding against low rate of transmission of under 2%.

In UK, completely discourage breast feeding, but “not a child protection issue”! Still controversial. Check with your local team!

Transition

Focus now on optimisation of health status through childhood rather than survival! Worry that significant numbers of deaths in survivors of childhood HIV.

Future

Treatment interruptions (not good outcomes in adults)?  Reduction in lab monitoring? Still new (delayed) toxicities eg portal hypertension with DDI. Depot injections!

Treatment

Kaletra + nevirapine first line. Commissioning in England influences treatment recommendations. PENTA 2016 now recommends ART for all children.

Dolutegravir has best results, side effect profile and low interactions (Integrase strand transfer inhibitors (INSTIs)).

Hydrolysed Formulas

Allergy, General paediatrics, Immunology, Nutrition

Alternatives and variations on cow’s milk based formulas:

  • Extensively hydrolysed – protein is broken down so good for cow’s milk protein allergy.  Not very nice tasting!  Can be whey-based eg Pepti (which includes lactose, so more palatable but no good for lactose intolerance), else casein-based eg Nutramigen (lactose free).
  • Partially hydrolysed – better tasting but symptoms may persist if true allergy
  • Anti-reflux “stay down”
  • Soya – good for cow’s milk protein allergy but cross reactivity can occur, plus theoretical phyto-oestrogen effect so avoid if under 6 months.  But the only one you can use if you are vegan or have galactosaemia.

Aptamil Pepti is made by Milupa (which is where GP’s will find it on electronic prescribing system). Not suitable for vegetarians and not Halal!

Some are lactose free, others not. Some have medium chain triglycerides as main fat source, eg Pepti Junior, Pregestimil, Peptisorb.

Nutramigen contains prebiotics – should therefore not be given to preterm babies (theoretical risk of gut translocation), and should be made up at room temperature (so not suitable for prep machines).

For those who require a vegetarian or halal diet, the only suitable extensively hydrolysed infant milk is SMA Althéra. Of the amino acid formulas, all are halal, and Neocate/Alfamino are vegetarian. None are vegan friendly.

SMA Alfamino does not have coconut oil, unlike some of the others.  No evidence that there is sufficient coconut protein in formula to cause an allergic reaction but it often gets accused of suspected reactions.