Common viral skin infection of children – perfect, umbilicated papules, take a few months to disappear.
Not usually a problem but can be very widespread and can trigger a dermatitis.
Treatment is trickly – you can get Cryotherapy or curettage but might scar.
Antiseptics such as hydrogen peroxide cream or povidone iodine solution may help.
Podophyllotoxin cream? Wart treatments (salicylic acid)?
If actually inflamed, treat in the usual way with mild topical topical corticosteroids.
Chromosome 15q11 related. Results from deletion of paternal copy of imprinted gene (the rare genes where the copy from one parent is turned off by DNA methylation). See also Angelman syndrome (also chromosome 15).
Beware pregnancies with Trisomy 15 where subsequent testing looks like normal diploid…
Classically severe hypotonia at birth, often with mild growth restriction, causing significant feeding difficulties.
Facial appearance characteristic even at birth: high forehead, narrow bifrontal diameter, downturned corners of the mouth, micrognathia, and dysplastic ears. As they age, almond eyes become apparent, face is rather unexpressive of course. Hands are small.
After age 1, ironically, appetite then seems to surge, leading to obesity.
Scottish genomic test directory says test if:
=Avoidant restrictive food intake disorder.
Extreme fussy eating, low appetite, slow eating, rigid eating behaviours eg brand-specific or position of food on plate. Often related to sensory issues (texture, colour, temperature) but also anxiety about potential choking or vomiting (emetophobia). But often food/eating is the only issue.
BPSU study 2024 described 300 cases across the UK. Slightly more boys than girls, 71% white. Comorbidity (anxiety and autism spectrum disorder) common.
Case definition from BPSU was:
If known medical/mental disorder, the severity of eating disturbance should exceed that routinely associated with the particular condition/disorder.
In practice, consider where:
Neffy now available in the UK, under brand name EURNeffy, for emergency treatment of anaphylaxis outside of hospital.
2 strengths – 1mg (age 4yr+ and 15-30kg+), 2mg (age 4yr+ and 30kg+). Lower dose version not yet in BNFC.
£182 for 2 unit pack so £236 on private prescription, probably. EpiPens/Jext £120 for 2 so 50% more expensive for newer device (but probably longer shelf life too).
Licensed on basis of equivalent plasma adrenaline levels to intramuscular dosing – not on real world anaphylaxis use. But quite a few reports now, and mostly effective (as intramuscular is also mostly but not always effective).
BSACI statement says for 2 groups, should still have autoinjectors (although EURNeffy can be used first line) –
EU definition – less than 1 in 2000 people affected. But at least 7000 described. So prob 3.5 million in the UK, and lifetime risk 1 in 17?
Most present in childhood. And 30% will die before age 5…
9 rare diseases tested for at birth so drop in the ocean… Some US states test over 45…
Average delay in diagnosis in UK patients is 5.6 years, with average of 4 different primary care and 4 secondary care clinicians! https://globalgenes.org/wp-content/uploads/2013/04/ShireReport-1.pdf
Common challenges –
Diagnostic “odyssey” – unfathomable obstacles. Often labelled functional (or worse…), and parents as “anxious”, “demanding”.
Doctors tend to force a common diagnosis on to symptoms/signs that don’t quite fit.
Parents struggling with a sick child may delay having other children, may spend out on private treatment or move to different areas/countries to seek care, lose earnings/educational attainment, and family relationships suffer.
Once diagnosis is made, life begins with health issues being only 1 part of the whole picture rather than defining life. And provides access to experts and family support all over the world.
Become expert patients/families. Patient organisations offer support but also advocacy, research
Not knowing the condition doesn’t mean you can’t listen and try to understand, or that you can’t coordinate things (esp when multiple teams/professionals involved).
Some will be happy to disclose/discuss diagnosis – others may get bored and frustrated at times – and may be stigma
Primary care and emergency departments gain very little confidence. Hospital staff involved in ongoing care still only considered to be knowledgable by about 40%!
Health care teams need to monitor research landscape.
“Dare to think rare” – medical education tends to stifling curiosity. Proformas and pathways as a hindrance to rare conditions.
Eg crushing chest pain in 40yr old slim female – spontaneous coronay artery dissection!
GENES –
History – trying not to ignore anything. 3 generation family history. Pregnancy loss; disability.
“THINK AND” – many stories of diagnosis only being made when someone listens to whole story from beginning to end. Parental concerns AND multisystem problems AND family history AND disability… Example of Alstrom syndrome – visual impairment then obesity, then heart failure.
“THINK AGAIN” – beware diagnostic bias of having a diagnosis from the past or from another doctor. “Momentum bias” – diagnosis might start as tenuous but become entrenched. “Premature closure” – thinking stops when diagnosis accepted (even if not verified). New test available to confirm?
Open access tools – www.FindZebra.com, OMIM, Orphanet. Only Google after trying these! Start with 2 most specific (stand out) terms. [Phenomizer appears to be defunct]. Mendelian – AI tool in development.
NHS is at forefront of genomic medicine (whole genome analysis rather than panels of tests) – 100 000 genomes of people with rare disease and cancer analysed. Approx 1 in 4 rare disease patients have had useful (“actionable”) results.
Phenotypes are helpful but same pathway can be affected by different mutations and same phenotype can be seen in different conditions.
Microarray vs gene panel vs whole exome (coding only) vs whole genome…
Hope is for quicker diagnosis, less tests, less inappropriate treatment, support family planning decisions, enhance research.
National Genomic Test directory – https://www.england.nhs.uk/publication/national-genomic-test-directories/
Downside is variants of uncertain significance… https://vimeo.com/451887065
2026 advice from Academy of Royal Medical Colleges – part of “Please write to me” guidance, previously just about clinic letters:
A list of the patient’s problems or diagnoses
A section of the discharge letter should be written to the patient:
Iron found in:
Vitamin C helps absorption.
See also anaemia.
Common choice for intentional overdose – mostly young women but males and older adults tend to take bigger amounts…
Acetylcysteine almost universally effective when administered within 8-10 hours – but occasional acute liver failure, with high mortality and still one of the most common reasons for hyperacute liver transplant.
Usually no symptoms in first 24 hours after ingestion – by which time the stress that triggered the ingestion has usually passed… Then just nausea, vomiting- not at all clear that acute liver injury is progressing. Abdominal pain then develops (jaundice unusual).
With very large overdoses, can present early with altered mental status or metabolic acidosis.
With overdoses taken in staggered doses (over more than 1-2 hours) risk higher and nomogram unreliable. Paracetamol level x ALT predictive?
Acute kidney injury is seen with acute liver injury (hepatorenal syndrome) but sometimes is main issue (acute tubular necrosis caused by local CYP450 activation).
CYP450 enzymes produce toxic metabolites. Glutathione is natural antidote but once it is used up cell death starts to occur.
Scottish & Newcastle antiemetic protocol (SNAP) – higher initial acetylcysteine dosing (first bag over 2 hours, second bag over 10 hours – cf prev 21 hour regimen), less anaphylactoid reactions. Current HiSNAP trial looking at even higher doses.
Haemodialysis can be considered in severe metabolic acidosis and high paracetamol levels (>900mg/L) but also removes acetylcysteine so dose needs to be doubled.
Co-ingestion of opiates or anticholinergics may delay absorption, so repeat level?
Low body weight tend to get fluid overloaded. Use saline rather than dextrose
Nomograms vary internationally – UK more conservative than US/Australia.
Activated charcoal useful in acute ingestion (<4 hours) or massive overdose.
Anaphylactoid reactions caused by non-immune histamine release – urticaria, flushing, bronchospasm, but not upper airway compromise, angioedema or hypotension. Not a contraindication to repeat treatment.
INR >3 or ALT >1000 are high risk for liver failure, even before encephalopathy develops.
Autosomal dominant condition, so 50% risk of passing on to offspring and variable penetrance. May be spontaneous mutation.
Diagnosis still essentially clinical: 1988 Consensus is for any 2 of the following:
Plexiform neurofibromas are larger ones with potential to cause visual, hearing, even cardiac problems.
Issues are:
Ophthalmology review annually in children, every 2 yrs in adults, given risk of optic gliomas.
Family support at https://nervetumours.org.uk/
Clinical trial of selumetinib had beneficial effect on inoperable plexiform fibromas.
Resus council guideline 2021.
Definition (convulsive) – seizure lasting more than 5 minutes. Used to be 30 minutes! Unlikely to terminate spontaneously after 5 minutes. Evidence that the longer it lasts, the hard it is to treat.
Use existing seizure management plan, if there is one!
Buccal midazolam (0.3-0.5mg/kg depending on age) and IM/IO lorazepam 0.1mg/kg – max 2 doses of benzo’s, including any home/prehospital doses.
If no response to first dose after 5 minutes, go for IV lorazepam and prepare next step.
2nd line should then be within 15 minutes of start of seizure – Levetiracetam, phenytoin, phenobarb.
Phenytoin needs to go slowly (over 20 mins – risk of brady/asystole) cf levetiracetam (over 5 mins). Call anaesthetist.
After 5 mins, either try alternative or go for intubation and deep sedation: RSI with thiopental, or propofol +/- rocuronium. Ketamine and midaz given as alternatives as no evidence for 3rd line agent!
Meanwhile – check glucose, sodium, calcium/Mg (if sepsis). Temperature control.
Beware CNS haemorrhage (trauma?), raised intracranial pressure, meningitis, encephalitis.
[no rectal medicines mentioned but paraldehyde worked pretty well back in the day]