Nasal Adrenaline for Anaphylaxis

Allergy, General paediatrics

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) –

  • Patients who have previously required more than 1 dose of adrenaline with a reaction
  • Patients who had hypotension with a reaction

Rare Disease

General paediatrics, Genetics

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

Dare to think rare!

Common challenges –

  • Misdiagnosis
  • Inappropriate treatment
  • Passing between specialties
  • Having lived experience denied or not listened to
  • Then having to become advocates +/- carer
  • Diagnostic criteria can be unclear
  • Stigma – outward appearance or misconceptions
  • Cf invisible conditions – “doesn’t look disabled”
  • Poor coordination of care. Role of primary care unclear.
  • “Burden of explanation” and lack of knowledge in professionals
  • Transition
  • Guilt (where genetic)
  • Mental health (chronic illness or underlying disease)

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

No treatment is not no management

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.

Diagnosis

“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 –

  • Group of congenital anomalies – 1 is common, 2+ less so
  • Extreme/exceptional presentation of common condition – eg infection, or child presentation of something seen normally in adults
  • Neurodevelopmental delay/regression – “bad behaviour”?
  • Extreme/exceptional pathology
  • Surprising lab results

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

[Medics 4 Rare Diseases]

Discharge Summaries

Communication, Generic, Health Literacy, Patients

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 brief description of the episode of care
  • A record of investigations and procedures requested, results and plans
  • Any known allergies, intolerances or adverse reactions
  • Medications and medical equipment, with changes highlighted
  • Actions to be taken by the patient, secondary care clinician and primary care team.

A section of the discharge letter should be written to the patient:

  • The reason they came to hospital
  • What was done during the hospital stay
  • What they can do to help themselves
  • What they should watch for or monitor
  • What they should do if they have questions or concerns, with a hospital telephone number and email address (safety-netting)

Iron deficiency

Common, General paediatrics, Nutrition, OPD

Iron found in:

  • red meat (also poultry and fish, but less). Liver has high iron content…
  • pulses/legumes (eg lentils, pea, beans, kidney beans, chickpeas, edamame)
  • nuts
  • dried fruit eg raisins, dried apricots (but not great for teeth…)
  • fortified breakfast cereals (so not porridge?)
  • dark green vegetables (including broccoli) – but the iron is harder to absorb
  • Bread is generally fortified in the UK. Wholemeal is naturally high in iron but also contains phytates that inhibit absorption…). Not sure about flatbreads/wraps etc.

Vitamin C helps absorption.

See also anaemia.

Paracetamol toxicity

Emergency medicine, General paediatrics

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.

Neurofibromatosis

General paediatrics, Genetics, Neurology

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:

  • 6 or more cafe-au-lait spots (at least “pencil thickness” in diameter?)
  • axillary or groin freckling
  • 2 or more Lisch nodules – pigmented lesions in iris, may need slit lamp to see. No clinical consequence!
  • 2 or more neurofibromas,
  • optic pathway glioma (OPG),
  • bone dysplasia,
  • first-degree family relative with NF1 

Plexiform neurofibromas are larger ones with potential to cause visual, hearing, even cardiac problems.

Issues are:

  • High blood pressure
  • Epilepsy (lesions develop in brain)
  • Bone problems including scoliosis
  • Effects of neurofibromas in sensitive locations
  • Cosmetic appearance, self image
  • Cancer (malignant change in neurofibroma but also brain and breast)
  • Risk to own children

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.

Status Epilepticus

Emergency medicine, General paediatrics, Neurology

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]

Sleep-related hypermotor epilepsy

General paediatrics, Neurology

Onset around age 9.

Can be just waking up, possibly confused, but multiple times a night.

Easier to diagnose if more dramatic twisting, grimacing, thrusting movements, posturing. Can be wandering like parasomnia, can be vocalisations (screaming, moaning, crying).

Can be aware during seizure. Can be sensation of unable to catch breath.

Usually around 30 secs.

Often inherited (prev called autosomal dominant frontal lobe epilepsy). Not always frontal!

Probably needs video EEG.

See also Panayiotopoulos (occipital lobe) epilepsy.

Mast cell activation syndrome

General paediatrics, Immunology

Recurrent mast cell degranulation causing episodes of hives, diarrhoea, swelling, dizziness, even anaphylaxis.

Thought to be due to clonal expansion of abnormal mast cells, not requiring usual triggers.

Diagnosis is on basis of rise in tryptase levels during an episode from base line. If base line tryptase is abnormal, then likely mastocytosis.

Look for KIT D816V on flow cytometry? Urine mast cell products eg leukotriene, prostaglandin? Bone marrow aspiration?

Scoring systems available.

Treatment is predictably:

  • Antihistamines, preferably non sedating. Some people however benefit from the additional sedative effect of older antihistamines eg ketotifen, hydroxyzine.
  • Adrenaline autoinjectors for anaphylaxis self management
  • Montelukast/zafirlukast has systemic anti-inflammatory action
  • Famotidine has anti-histamine action
  • Steroids for short term use
  • Omalizumab

Citrus allergy

Allergy, General paediatrics

Orange, mandarin, tangerine all varieties of orange. Seeds probably rich in allergens but less likely to be eaten (chewing probably also required for reaction)!

Various allergens identified, including profilin (so oral allergy syndrome) and LTP (more in Mediterranean, cross reacts with Pru p3, not surprisingly).

One letter briefly touches on citrus cross reactivity – some tolerate lemon and/or tangerine, some had oral symptoms with tangerine, none had tried grapefruit. So varying and not well explored…