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]]
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]
ie bee/wasp. A common cause of anaphylaxis, and interestingly, not related to atopy. Reactions can be immunological (IgE or non IgE), or non-immunological (toxic).
Severe reactions related to allergy but also number of stings, insect type, cardiovascular/respiratory disease and also mastocytosis.
Whether it is bee or wasp or other is sort of important, from the point of view of cross reactivity and risk. Several major allergens eg hyaluronidase, phospholipase A2. Apid (bee) hyaluronidase is 50% identical to vespid, so good chance of being allergic just to one and not the other. Vespids subdivides into Vespa=hornets (found in UK, biggest, 35mm, reddish brown head); Vespula=wasps; and Dolichovespula (“short headed wasps” – harder to distinguish, “shorter distance between eyes and upper jaws”!). These 3 vespid types cross react strongly, so likely to be allergic to all. “Yellowjacket” is American name for wasps.
Bumblebee PLA2 is 53% identical to honeybee PLA2, so not necessarily cross reactive!
Polistes=”paper wasps”, distinct from other vespids, Southern Europe only (so far) – large, long legs, not esp colourful. Limited cross reactivity to wasps/hornets, thankfully.
Ants are also hymenoptera!
Clinical
“Normal” local
“large” local = >10cm swelling, plus >24hrs. Blisters sometimes present). Mech prob toxic, but sometimes evidence of IgE mediated mechanism,
systemic toxic (haemolysis, nephropathy, coagulopathy – rare, usually from multiple stings)
systemic +/- anaphylaxis [usually igE, rarely short term IgG, or complement activation by IgG-venom complexes]
(plus “unusual”).
Wasps and hornets not as fuzzy as bees. Was a barb left behind? Bees, not wasps. Multiple stings at the same location? Wasp, not bee.
Systemic reactions should be assessed by allergy specialist, including skin prick tests, total IgE and baseline tryptase tests.
Hypotension is the dominant feature and may occur alone.
Risk factors for outcome of anaphylactic reaction:
age,
CVS disease/drugs,
insect type,
time interval between stings (short interval increases risk of systemic reaction to second sting),
number of stings,
severity of previous reaction,
elevated mast cell tryptase, else known mastocytosis.
Bee allergic at higher risk of systemic reaction than vespid allergic. Hornets risk seems to be esp high.
Frequent stings can induce tolerance (but probably needs more than 200 per year!).
Venom IgE >1 had 12x risk of anaphylaxis (beekeepers, regardless of previous history). Pos skin test (adults without history of anaphylaxis) had 17% risk, cf 0% of neg skin test [so negative test v reassuring, but risk still low even if you are pos, which would be unusual in most kids]
Majority of fatalities have significant cardioresp co-morbidity. 40-85% of fatal reactions had no documented history of previous anaphylactic reactions.
Mild systemic reaction previously gives 18% risk of subsequent systemic reaction (kids). Compare after large local – 5-15%, so sl higher but not much. Children tend to have mild systemic reactions, cf most adults get resp or CVS symptoms.
Several case reports of severe reactions in mastocytosis; even without mastocytosis, high basal tryptase seems to increase risk of anaphylaxis.
Testing
Even when SPT pos, 25-84% of subjects do not react to subsequent sting!
Similarly, up to 22% of those with neg tests will have systemic reaction in future. [Allergy 2005: 60: 1339–1349]
Test all with systemic reaction, not recommended otherwise. If not witnessed? Only really useful to distinguish bees vs wasps (says the Anaphylaxis Campaign)!? Unless you’re a bee keeper, wasps are the one you are most likely to be stung by.
Skin prick testing more sensitive/specific. Probably sensible to leave a month or two between the event and testing else false negative due to “refractory period”. This period can sometimes be longer so consider repeating if good history. If negative, try IgE; then intradermal ( with 0.001-1mcg/mL solution -seems to have higher sensitivity).
Stepwise skin testing with 0.01-100mcg/ml solutions incrementally recommended.
Some people will be persistently negative on testing, probably due to being allergic to an unusual protein. Consider systemic mastocytosis as a differential.
Family history of venom anaphylaxis is a common cause of concern. Unfortunately, there is no point testing other family members – you are unlikely to test positive if you have never been stung.
Specific IgE levels (if you do test positive) only vaguely correlate with anaphylaxis risk (not statistically significant) [Allergy 62(8): 884-889, August 2007]. However, having low total IgE (<50kU/l) predicts anaphylaxis (not v sensitive, only explains 25%), whereas high total IgE (>250) protects (very specific)!
Serum IgE appears within a few days of sting, begins to decline at a variable time – wait long enough, and no IgE may be detectable. Double positivity to bee/vespid could be genuine cross sensitivity but might be cross reactivity of IgE to epitopes of unknown clinical significance.
Baseline serum tryptase over 11 has high positive predictive value for anaphylaxis but is not very sensitive. Good for picking up mastocytosis though!
So you may be able to find the occasional person who seems to be at particular risk (high tryptase, low total IgE), or relatively protected (high total IgE) but you will still miss most cases of anaphylaxis.
Immunoblotting, basophil activation tests etc sometimes used if others tests negative. But sens/spec generally not known.
High basal tryptase may increase risk of reactions with VIT but still indicated.
Give allergy plan and prescribe Adrenaline if severe systemic reaction, consider if moderate.
If successful VIT, still get adrenaline if further symptoms, continued exposure, high tryptase.
Reported, in most cases appears to be due to pollens contained in the honey, or at least allergens highly cross reacting with pollens. But in a minority, does appear to be due to bee derived components. Type of honey will determine what pollens are contained in it; commercial honey often contains v low amounts due to production techniques.
Prevention
Risk of sting related to zone, climate, temperature, outdoor activities etc. Some repellents marketed as effective against wasp/bee (IR3535 (Ethyl butylacetylaminopropionate) eg Jungle Formula “outdoor & camping”) but most creams/sprays (DEET, Citronella oils etc) are for biting insects (midges, mosquitoes etc), not stinging. Bees/wasps generally not interested on landing on your skin anyway! Sting because they are threatened!
Differential of eye allergy includes tear film dysfunction, infection, autoimmune/inflammatory conditions, blepharitis, dry eye.
Severe -2 of vision disturbance, impairment of daily activities (leisure, sport, school, work); troublesome symptoms.
Perennial conjunctivitis usually related to house dust mite (HDM), animal dander, moulds else multiple. Itch characteristic, as per seasonal conjunctivitis, findings non-specific eg tearing, redness, eyelid swelling, small papillary hypertrophy of tarsal conjunctiva. Neither has corneal involvement.
Beware pain, photophobia, visual disturbance, grittiness or foreign body sensation. These can indicated Vernal keratoconjunctivitis, which does affect the cornea (warm climates eg Mediterranean/Africa): typically boys aged 4-12yrs, T cell and IgE combined, improves after puberty. Severe itching, exacerbated by nonspecific stimuli eg wind, dust, sun. Cobblestone appearance of tarsal plate (ie inside upper eyelid) else limbic thickened and opacified +/- white/yellow gelatinous deposits (more typical of tropical form). Can get corneal ulcers.
Atopic keratoconjunctivits is also rare, the eye can be the only affected area cf atopic dermatitis. Hall mark is fissured eyelid. Staph colonization contributes. Limbus and cornea can be affected.
Giant papillary – associated with contact lenses.
Contact blepharoconjunctivitis is eyelid itching, oedema, eczema with less in the way of conj redness.
Conjunctival provocationtest can be done with standardized allergens – defer if on local or systemic antihistamines or anti-inflammatories, contra-indicated if uncontrolled asthma. Ideally when asymptomatic and eye not inflamed! Dilute extract to obtain several lower concentration solutions (last up to 6 hours at room temp). Administer 20microl dose at 30 min intervals at infero-external quadrant of right eye. Left eye is control! Have local antihistamine and steroids available, in addition to usual systemic medicines. Only 1 reported case of anaphylaxis!
Patch test for non-IgE. Else Conjunctival cytodiagnosis eg eosinophil infiltrates.
Treatment and prevention –
Avoid allergens, protect eye with sunglasses.
Lubricants and cold compresses are good.
Topical antihistamines eg azelastine, olapatadine but also Lodoxamide, ketotifen.
Mast cell stabilizer (ie cromoglycate) needs 2/52 preloading and multiple doses per day, plus stings! So poor compliance.
Systemic antihistamines if other symptoms else may be excessively drying.
Topical steroids should be avoided except where cornea involved, ie VKC, AKC, and then only in short pulses. Twice daily steroids for a month or more raises concern about glaucoma, cataracts.
Ciclosporin drops oily, supply probs – veterinary products used! Tacrolimus not available in drops; cream burns a little but gets better.
Nasal steroids work well for eye symptoms and appear to be safe.
For blepharitis, eyelid hygiene, emollients, 1% hydrocortisone.
Rome III classification (now Rome IV?) of functional GI disorders – has child section. Colic, rumination, cyclical vomiting, diarrhoea, dyspepsia, abdo migraine, IBS, abdominal pain, constipation.
Functional abdominal pain (FAP) must include all of the following:
Episodic or continuous abdominal pain
Insufficient criteria for other functional GI disorders
No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains the subject’s symptoms
Criteria fulfilled at least once per week for at least 2 months before diagnosis
Childhood Functional Abdominal Pain Syndrome
Must include childhood functional abdominal pain, and at least 25% of the time have 1 or more of the following:
Some loss of daily functioning
Additional somatic symptoms such as headache, limb pain, or difficulty sleeping
Criteria fulfilled at least once per week for at least 2 months before diagnosis
That loss of daily function is an optional criterion is because it would exclude motivated children who continued activity despite the pain and children whose parents insisted that they continue activities. However, it is recognized that there is a subgroup of children in whom loss of daily functioning and/or accompanying somatic symptoms form an important component of their symptom complex. This group is now referred to as having FAPS.
It is still debatable whether H pylori can cause symptoms in the absence of peptic ulcer disease. Young children may of course not give a typical ulcer history, but clues would be epigastric, pain before meals or helped by eating or antacids. Not helpful when functional abdominal pain or reflux disease.
A meta-analysis of 45 studies concluded that H pylori infection is not associated with abdominal pain. In a German study of 1221 children social and familial factors (single-parent household, family history of PUD, or functional pain) were significantly associated with abdominal pain, but not with the H pylori status of the child, as assessed by the 13C-Urea Breath Test.
In a study of 695 schoolchildren between 10 and 12 years old there was no association between H pylori and recurrent abdominal pain, in fact there was an inverse relationship after adjustment for selected possible confounders!
Although there have been studies that seem to show that symptoms improve with treatment, these have been of poor quality and the natural course of illness is to improve anyway.
Now that a link has been established between helicobacter and cancer (esp stomach, via chronic gastritis, also non-Hodgkins lymphoma) in adults, benefits and risks of treatment when it has been discovered should be discussed.
Refractory iron-deficiency anaemia is not considered a good reason for testing anymore.
Gold standard is Gastric biopsies (antrum and corpus) for histopathology during endoscopy. Initial diagnosis of H. pylori infection can be based on either positive histopathology + positive rapid urease test, or a positive culture.
Stool antigen test is pretty reliable. Could simply indicate asymptomatic carriage though. Once you know about it, of course, you need to consider eradication given cancer risk.
You should wait at least 2 weeks after stopping proton pump inhibitor (PPI) therapy and 4 weeks after stopping antibiotics before doing any of these tests.
Detection of antibodies against H. pylori (whether in blood, urine, saliva) are not reliable for use in the clinical setting.
Who needs one? Anyone at risk of anaphylaxis, is the simple answer. But there are no reliable ways of identifying who is at risk of anaphylaxis!
There is also a big problem with them not being used even when they are available.
Who needs one?
EAACI position paper – see Anaphylaxis management. Only a couple of absolute indications, otherwise a risk assessment.
Prescribing a pen is only part of the overall management: nothing worse than prescribing a pen and not properly discussing avoidance, or having a pen that does not get used when it should be, because it’s left at home or because no-one remembers how to use it or they are too scared to use it.
In various studies, prescribed AAIs were only used in a third of recurrent episodes, despite being available and in date in two-thirds of episodes. The reason(s) for non-use requires further study: parental questionnaires indicate that parents have a poor recall of anaphylactic symptoms and how to use the AAI despite training.
2021 Expert working group – MHRA set up after further coroner’s inquests into anaphylaxis deaths, following European safety review in 2015. Recommendations are:
Early adrenaline. Which means teaching families/children recognition of signs.
Need for 2 pens emphasized.
Brand specific training
Key messages on packaging eg “don’t delay”, “use second pen if necessary”
Posture detailed – “lie down with legs up”, “sit up if breathing difficult but don’t change position suddenly”, “stay lying down [regardless of whether you feel better or what people tell you to do]”
Wider availability of AAIs in public places likely to be beneficial but this would require legislative amendment as well as public training, and concerns about storage conditions and supply would need to be addressed.
Dosing errors in hospital common, but given pressure on AAI supply may not be great solution. Other solutions would be labelled kits, pre-filled syringes, different system of labelling adrenaline (!).
Reporting of device related adverse events, and anaphylaxis events (including re-establishment of fatal anaphylaxis registry).
Technique
Patient should lie down (but if respiratory symptoms then may be more comfortable sitting). Video available at Epipen and Jext websites. 3 minute training video with more explanation on Youtube. Or scan this:
Remove safety cap (Blue for Epipen, Yellow for Jext).
Jab orange (Epipen) or black (Jext) tip firmly into upper outer thigh, through clothing if necessary but avoid seams and pocket contents eg coins, mobiles – clicks as it activates.
Hold for 3 secs (Epipen), 10 secs (Jext).
Previous advice was to rub area (probably now white) vigorously for 10 seconds. Adrenaline causes vasoconstriction in skin, but vasodilatation in muscle so should be absorbed as long as IM. Not specified now.
Phone 999.
Dispose of device safely (device is self sheathing). Note that some drug left behind, which is normal, and that pen cannot be reused!).
Repeat after 5 minutes if necessary. Use a different leg!
Training checklist (from GOS):
When to use it
How to use it
When to carry it ie at all times!
Storage/disposal – should be protected from heat and light
Expiry date – reminder service available from support website (link above)
They come in two different doses – standard strength is 0.3 mg, there is a 0.15 mg strength prescribed for younger children (15-30kg). Emerade (not currently available) gcomes in a 0.5mg strength for adults and children over 12, which is a more appropriate dose for bigger people viz over 60kg.
If patient is under 15kg, CYANS guidance is that over 7.5kg, the potential benefit outweighs the risk. For those under 7.5kg, need to balance risk of anaphylaxis with risk of drug error from drawing up adrenaline from vial with syringe and needle.
Epipen has 18 month shelf life, self sheaths, and has a window to show ready to use. Blue safety cap, orange needle end. JEXT pen similarly self sheathing, coloured window to show whether it is live or not, 24 months shelf life. Yellow safety cap, black needle end. Same needle length.
Anapen has been discontinued. Had a shorter needle, different technique – remove caps from both ends, hold against leg, put your thumb over the end and press red button.
Emerade pen has safety cap over needle end – this is different from the other types but is logically simpler. Needle is 25mm long cf 15mm Epipen/Jext. Currently off market due to reliability of activation concerns.
Number of Pens
2018 MHRA review recommends 2 pens available at all times, and made the recommendation directly to families so they can demand them from their doctor! BSACI (2016) suggested children should in most cases just get 2 pens, 1 for home and 1 for school, but this was contradicted by later European Medicines Agency (EMA) and previous NICE guidance. Still not clear why they should ever by prescribed in single rather than twin packs…
due to uncertainties about the site of drug delivery and the speed of adrenaline action within the body, it is recommended that healthcare professionals prescribe 2 auto-injectors, which patients should carry at all times
the needle length of the device is now stated in the product information because this may be an important factor for the prescriber to consider when choosing a suitable auto-injector
the training of patients and their carers in the correct use of the product is important and manufacturers were required to update their educational materials
manufacturers should carry out studies in humans to more fully understand when and how much adrenaline reaches the blood stream, and how quickly and effectively it acts on body tissues when given through an auto-injector
EAACI guideline says number of pens should be guided by individual assessment, and BSACI also allow that 2 pens may be more appropriate in some cases, eg obesity, previous need for 2 doses, remoteness etc. There has been good evidence published indicating that one-third of children with anaphylaxis require a second dose of epinephrine (Kornblat P, et al Allergy Asthma Proc. 1999; 20: 383–6), and deaths have occurred despite a single injection, but most of these reports describe subcutaneous adrenaline use, rather than intramuscular use. Dose is more likely to be an issue with big teenagers (eg over 45kg).
If you carry your pen, know how and when to use it, then you are doing to do significantly better if you have a bad reaction than most other people, so don’t get too hung up on how many pens!
Spare pens in school
New legislation (2017) allows schools to obtain without prescription spare pens. These can be used if the pupil’s own pen is not immediately available or already given. Note that children with food allergies are not always prescribed adrenaline auto injectors but may still be at risk of anaphylaxis. The spare pen can be used in such children if:
The child’s care plan confirms child is at risk of anaphylaxis
A health care professional has authorised use of the spare pen in an emergency
The child’s parent/guardian has provided consent for a spare pen to be administered
Note that advice on using pens can be given over the phone by emergency services, if it is made clear pens are available.
Further information about spare adrenaline pens, and advice on reducing the risk of reaction sin school, treating reactions in school, staff training etc can be found at https://www.sparepensinschools.uk/
Needle length
Doing ultrasounds of thighs shows that in a significant proportion of people, including children under 5 with high BMI, the distance to muscle is more than 15mm (and not including any clothing). 82% of the obese children studied had skin surface to muscle depth greater than needle length. This was only true for 25% of the non-obese children. 3/4 the way down the thigh, only 17% of obese children and 2% of those not obese. Arkwright, Royal Manchester Children’s Hospital – 2013 Annual AAAAI meeting.
Some suggestion from injection models that “jet” of adrenaline penetrates significantly deeper than needle alone, that the angle, force used, whether the device is spring loaded or not, all potentially affect depth. So concerning, especially given the cases where multiple injections have failed to prevent death (eg Natasha Ednan-Laperouse).
Emerade had longer needle (25mm) but not currently available. So inject in lower lateral thigh?
2015 European medicine agency review discussed above concluded that training remains the paramount issue, although further research into needle length should be done.
2021 Review found that blood adrenaline levels actually higher after Epipen and Jext cf
Failure to use
In a prospective UK study of children prescribed AAI for at least a year, the most common reasons given by patients for not using their AAI (245 episodes of anaphylaxis, AAI used in only 16.7%) were ‘thought adrenaline unnecessary’ (54.4%) and ‘unsure adrenaline necessary’ (19.1%). Device not being available only mentioned in 5%.
In 2002 Australian retrospective study of patients with previous anaphylaxis, shortness of breath usually recognised as anaphylaxis symptom but less commonly upper airway or cardiovascular symptoms/signs. Half forgot the need to remove safety cap and hold for 10 seconds in scenario. 71% of anaphylactic reactions were not treated with AAI, even though AAI was available in most cases. About half of those needed adrenaline treatment in hospital (which was rare in AAI treated cases).
In a 3 year Canadian study of 1500 ED episodes, almost 50% of adults were not treated with epinephrine in or outside of the hospital. Slightly better for kids, 28.7%. Almost all of these children had been prescribed auto-injectors. The need for multiple doses in ED was less in those who received epinephrine outside ED. [Allergy, Asthma & Clinical Immunology 2014, 10(Suppl 2):A3]
In a Canadian email survey of 1885 anaphylaxis survivors (adults and kids, food and insect etc), 73% did not give epipen. Most common reason for not giving, was that an antihistamine had been given first. Only 28% gave reason as being that they did not have epipen! 13% judged reaction as mild. 41% of epipens were given by someone other than patient, mostly family of children. 53% of epipen users had previously used one before. [simons, clark, camargo – JACI 2009:124;301 doi:10.1016/j.jaci.2009.03.050]
Failure to prescribe
In an online survey presenting 10 paediatric allergy case histories to paediatricians (all were severe, although only 1 case specifically mentioned anaphylaxis). There was significant variability in prescribing practices. Although all allergists and generalists prescribed an autoinjector (94.4% and 92.6%, respectively) or would offer the patient a choice about autoinjectors (5.6% and 7.4%, respectively) in the case specifically mentioning anaphylaxis, many cases had almost no consensus on prescription of adrenaline autoinjector. The prescribing patterns of allergists and generalists showed no significant differences for 9 of the cases. For the remaining case, which described a child with oral allergy syndrome, all specialists (n=54, 100%) reported that they would not prescribe an autoinjector (in line with guidelines) compared with only 20 (74.1%) of generalists (p<0.001). [Johnson MJ, Foote KD, Moyses HE et al. (2012) Practices in the prescription of adrenaline autoinjectors. Pediatric Allergy and Immunology 23: 124-7]
In a survey of all GPs in Scotland, 90% of the 613 respondents had prescribed adrenaline autoinjectors. However, only 49% of prescribers were confident in use of these devices, and only 17% had access to a trainer pen for demonstration to patients. If called upon in an anaphylactic emergency (experienced by 36% of respondents), only 50% of respondents would use the appropriate dose and 14% would use an inappropriate route of administration (subcutaneous or intravenous). [Lowe G, Kirkwood E, Harkness S (2010) Survey of anaphylaxis management by general practitioners in Scotland. Scottish Medical Journal 55:11-4]
Failure to Use – Doctors
When scenarios presented to junior doctors (same questions posed 10 years earlier) – all recognized need for adrenaline in anaphylaxis scenario but dose often wrong and 25% gave adrenaline IV. For non-anaphylactic scenarios, adrenaline frequently recommended eg inhaled peanut. Not much improvement over decade. [Postgrad Med J 2015;91:3-7 doi:10.1136/postgradmedj-2013-132181 ]
Editorial discusses how doctors know that adrenaline is required in anaphylaxis, but that this knowledge is often not translated into practice. Many of these doctors had had ALS training; most had not worked in an emergency department. Simulation? Australian experience. Booster sessions?
Management of anaphylaxis involves treating the acute emergency, in the community first (see adrenaline autoinjectors), then in hospital, and then arranging appropriate follow up. See also anaphylaxis definition.
Hospital
APLS guidelines (updated 2021) on management of acute anaphylaxis from the United Kingdom Resuscitation Council.
No distinction between anaphylactic and anaphylactoid reactions – confusing and may lead to inadequate treatment. Patients taking beta blockers may have a more severe reaction and respond less well to adrenaline.
Adrenaline is the only evidence based treatment specified in the guidelines. It is therefore the treatment of choice. You could argue that anaphylaxis is the one condition in which the ABC approach is not appropriate – as soon as anaphylaxis is suspected, you should give intramuscular adrenaline, and then proceed to airway, breathing etc.
Adrenaline is underused. 34% of cases of anaphylaxis in Patel’s metanalysis did not receive adrenaline (my calculation from table III); 10% needed more than 1 dose [Patel JACI 2021]. In scenario based studies, adrenaline is often not given.
Adrenaline by the intramuscular route is safe. If in doubt, just give it! Dose is 0.15mg for under 6yrs, 0.3mg for 6-12yrs, 0.5mg for over 12. This is slightly different from the adrenaline autoinjector dose the child may have been prescribed for home use.
Repeat within five minutes if there is no improvement or if the patient’s condition deteriorates – not based on any evidence!
New guideline does not mention steroids or antihistamines at all! But does include IV bolus with second dose IM adrenaline after 5 minutes .
Posture emphasised in new guidance – Lie down with legs raised, or allow sitting up in semi-recumbent position if that helps breathing. Beware sitting up, standing and walking even if feeling better – reported trigger for cardiac arrest – so caution when transferring.
Refractory Anaphylaxis
After that, if still not improving, there is a new Refractory anaphylaxis guideline.
Get expert help. Intravenous adrenaline should only be given by experienced practitioner.
Give repeated IM doses of adrenaline, or if experienced, start low dose IV adrenaline infusion:
1 mg (1 mL of 1 mg/mL [1:1000]) adrenaline in 100 mL of 0.9% sodium chloride, ie 1:100 000.
Beware BP cuffs and piggy back lines that will interfere and potentially cause extravasation.
Start at 0.5-1ml/kg/hr and titrate.
Use ECG monitoring.
Use nebulised adrenaline for stridor, neb salbutamol for wheeze or bronchospasm.
After that intubation, inhalational anaesthetics (good for bronchospasm), repeat fluid boluses.
Discharge
Before, advice was observe for 6-12 hours, or admit if child. Now this has been risk stratified, with 6-12 hour rule applying for most cases. Exceptions are:
2hr discharge if a) good response (5-10 minutes), to b) single dose adrenaline, c) given within 30 minsPLUS complete resolution PLUS already trained and with 2 unused AAIs PLUS adequate supervision
At least 12 hours after resolution if any of:
severe, needed more than 2 doses adrenaline
severe asthma, or had severe respiratory compromise
possibility of ongoing absorption eg slow release medication
late at night or potential to not respond to any deterioration
areas where emergency care difficult
or in context of supervised challenge
No reliable way to predict biphasic reaction so this should be discussed and decision made by senior clinician.
Basic principles are to not discharge too soon, in case of a biphasic attack, but just as importantly, to consider prevention of further episodes (which involves making a diagnosis), and giving the patient and their family the appropriate information and skills to deal with an unexpected further allergic reaction.
Liverpool study (adults and children, I presume) found IM adrenaline given in 91.7% of cases, recommended observation period (6–12 h) achieved in 91.7% of patients. Long-term management not great – adrenaline auto-injector prescriptions provided to 50% of patients, “structured patient education” documented in 17.9% of cases, and allergy clinic referrals in 42.9%.
Who needs an Adrenaline auto-injector?
EAACI position paper suggests:
Absolute indications:
Previous cardiovascular or respiratory reaction to a food, insect sting or latex.
Child with food allergy and co-existent persistent asthma.
Relative indications:
Any reaction to small amounts of a food (e.g. airborne food allergen or contact only via skin).
History of only a previous mild reaction to peanut or a tree nut.
Remoteness of home from medical facilities.
Food allergic reaction in a teenager.
Prescribing a pen is only part of the overall management: nothing worse than prescribing a pen and not properly discussing avoidance, or having a pen that does not get used when it should be, because it’s left at home or because no-one remembers how to use it or they are too scared to use it.
Referral to an allergist is highlighted. According to a Mayo Clinic study, 35% of those referred by emergency department (ED) had an alteration in the diagnosis or suspected trigger after allergy/immunology follow up. Either anaphylaxis was ruled out; or an unknown trigger was successfully identified; or the suspected trigger was ruled out. Allergists are also good at identifying new triggers, different from the one suspected (JACI In Practice 2014)
How well is anaphylaxis managed by emergency departments?
In 1 study from Arkansas, n=187 patients (all under 19), food (44%) and stings (22%) were the main triggers, whereas 29% had no identifiable allergen. Only 47% (n = 87) received adrenaline in the ED and only 31% of those via the preferred IM route (the rest were treated subcutaneously). 61% received autoinjectors at discharge. Only 45% received an allergy referral. [Ped Emergency Care 2016] Similar results from Birmingham, Alabama in 2010.
Most cases of anaphylaxis are coded as “allergic reaction” rather than anaphylaxis, which suggests hospital statistics are likely to represent only a minority of the cases coming to hospital. In the study above, before the 2006 NIAID anaphylaxis guidelines, only 20% of cases were accurately coded.
Anaphylaxis is usually defined as an acute systemic allergic reaction with compromise airways, breathing and/or circulation. Systemic here means that the reaction is not limited to just one body system (skin, GI, respiratory etc) but spreads to others. It is usually – but not exclusively – mediated by IgE-antibodies.
There are however 5 different international definitions – not all include systemic, and of course not all systemic are anaphylaxis (for example skin and gut, 2 systems, not usually called anaphylaxis – except 2016 NIAD/FAAD definition in US, which specifies “persistent gut symptoms”). Respiratory involvement alone sometimes not called anaphylaxis by experts, even when treated as such! 3 definitions use “life threatening” but that is somewhat subjective and poses the danger of delaying appropriate management until the reaction is already advanced.
Use of the word “anaphylactic” is discouraged in the Resus council guideline, unless talking about anaphylactic shock, as it is misused to describe patients at risk of anaphylaxis (they may describe themselves as such), whereas this is actually anyone with a type 1 allergy.
Anaphylactoid reactions are immediate systemic reactions that mimic anaphylaxis but for which an IgE-mediated immune mechanism can not be established – most people don’t bother trying to make a distinction now.
EAACI task force anaphylaxis criteria (2007, from Sampson): any one of –
acute onset (up to several hours) skin/mucosa reaction (eg generalized hives, pruritus or flushing, swollen lips/tongue/uvula) plus respiratory or cardiovascular compromise eg dyspnoea, bronchospasm, stridor, hypoxia, hypotension, collapse
acute onset after exposure to likely allergen of at least 2 of: skin/mucosa changes, resp, cardio compromise, persistent GI (eg crampy abdo pain, vomiting)
hypotension after exposure to known allergen for that individual
Note that this definition talks about “compromise”, and the examples given are mostly signs that only a medical professional could identify! This doesn’t help patients/parents. It also allows for anaphylaxis with just skin and persistent GI symptoms (where likely allergen exposure).
In Sampson’s original 2003 criteria, he grades anaphylaxis into 5 types. 1 and 2 would not be considered anaphylaxis these days at all!
WAO 2020 revised definition, based on input from 15 different allergy societies – “highly likely when any 1 of
acute onset skin/mucosa plus one of airway/breathing compromise, circulation, severe GI, or
acute hypotension, laryngeal involvement, bronchospasm [specifically] after likely exposure, even without skin symptoms.
BSACI’s allergy plan includes as severe symptoms hoarseness, dysphagia but also:
AAP also has cough, hoarse, PLUS severe vomiting and diarrhoea, “many hives”(!), agitation!
On logistic regression, confusion and incontinence were strongly associated with hypotension and hypoxia. Dizziness, vomiting, abdominal pain, dyspnea and chest/throat tightness had weaker, albeit significant, associations. Pre-existing lung disease was associated with an increased risk of hypoxia. [Journal of Allergy and Clinical Immunology Volume 114, 2004, 371-376]
In a survey of kids with anaphylaxis, the mean latent period was 15.4 (SD27.5) minutes, ie 95% will react within 90 minutes of exposure. The type of allergy does not predict the latency well; however, age is inversely related, with younger children having more gradual onset. GI and cardiovascular symptoms tended to come later than skin/respiratory. 60% of anaphylactic reactions occurred in the home, and 10% happened in health care environments. Males predominate, particularly with regards exercise induced and insect venom anaphylaxis [PEDIATRICS Vol. 101 No. 4 April 1998].
Biphasic anaphylaxis
About 20% to 30% of food-induced anaphylactic events have a biphasic or recurrent response, although only half of those severe. 90% of recurrent reactions within 12 hours. Delay in giving adrenaline increases risk of recurrence! Some anaphylactic reactions are persistent, going on for hours.
Recognition
Recognition of anaphylaxis can be poor by non-experts. It is sometimes assumed that anaphylaxis must be life threatening, and that it must be progressive to the point of shock/collapse. Well recognised that anaphylaxis can resolve without treatment in some cases. Some have called for anaphylaxis grading, such as Sampson’s, but this then undermines the basic distinction.
Equally, people will sometimes diagnosis anaphylaxis on the basis of severe facial swelling, or widespread rash, neither of which are criteria.
Part of the problem of course is that what parents report is not the medical terminology included under the definitions. Infants and toddlers are a particular problem, since they cannot describe what they feel, and hypotension/syncope are extremely late signs. In US study, 48% of caregivers recognized 1 or more less obvious symptoms of anaphylaxis only in retrospect [but that includes skin/tongue/GI symptoms: looking at table II, 15% recognised sudden behaviour change in retrospect, 11% cough/wheeze, 6% wobbly/lethargy, difficult to rouse – can’t add up though]– that lack of recognition may affect management by medical team.
US 2024 study (Handorf) proposes modified NIAID/FAAN criteria – swollen tongue/uvula/pharynx becomes respiratory, not mucocutaneous; adds cough, drooling, hoarse cry/voice to respiratory too; specifies gagging, spitting up, diarrhoea, back arching as GI; pallor, mottling, obtunded/lethargy, altered mental state as CVS. By these criteria, 52% of all ED visits in children under 5 then became “anaphylaxis” (includes those given that diagnosis by attendings plus some ambiguous cases determined by clinicians to be anaphylaxis). Attendings diagnosed anaphylaxis in 68% of cases, but falls to 59% in infants. Original NIAD/FAAN criteria have 85% sensitivity, but falls to 77% infants. Modified criteria 100% sensitive for infants; 96-98% of older children. Compared with NIAD/FAAN, modified criteria picked up 43% more CVS signs, and 32% respiratory. Only 5% increase in GI. No hypotension/syncope in infants/toddlers, as expected.
Epidemiology
UK hospital admissions for food anaphylaxis have increased by 6.6% each year between 1998 and 2018 for under 15s (about 3x increase over whole period). For other ages much lower increase. Possibly due to 4hr waiting time rules for emergency departments? Or NICE recommendation on observation after suspected anaphylaxis? Case fatality rate has gradually fallen over time. At least 46% of all deaths triggered by peanuts or tree nuts. Cow’s milk responsible for 26% of deaths in school aged children (and rising), which shows how serious it can be when you don’t grow out of it in infancy. About a quarter trigger unknown (no comment – presumably no details in coding, rather than actually unknown), peanut and tree nuts together about a third. AAI prescriptions over the same period have increased by 336%.
Commentary by authors talks about effects on family of food allergy diagnosis but then goes straight into reasons for overdiagnosis, either through self reporting, commercial pressures, even campaigning by allergy charities. They say it is a “familiar pattern” with sharp increases in softer indicators of allergy, but no increase in markers of severe disease, and that this is the case in other countries such as the US and Australia. They conclude that we live in an era of increasing concern and awareness, but not a food allergy epidemic.
Whether the data are reliable, is a whole other question. Anaphylaxis is not well recognized, treated or documented, and only cases that were admitted were included, so these cases are probably just a fraction of what is actually coming to emergency departments. That doesn’t matter so much if that fraction stays the same and you’re only interested in trends. But even the interpretation of their own data seems curiously sceptical – if it is true that allergy is no more common than it was at any time in the last 30 years, are we saying families in the past just didn’t bother bringing their children to hospital when they had anaphylaxis? Or just more likely to admit (as NICE guidance from 2011 encourages observation for at least 6 hours, although the authors themselves say this probably only produced a minor increase in cases)?
Falling rates in peanut/nut, better awareness esp industry? Whereas milk awareness low? Although milk allergy common in young children, 5% of deaths in adults still due to milk (and prob harder to spot than nuts in food).
Higher rates of food anaphylaxis admissions in boys before puberty (male-to-female ratio 1.6:1), but reverses from age 15 years onwards. Highest rates of admission and death in teenagers, but in this study this risk continues through into mid adulthood, so supports the idea that it’s not specifically “teenage behaviour” that increases risk, rather biological vulnerability. In children under 5, deaths rare even though highest rate of admission.
Fatal anaphylaxis rate is about 1 in ¼ million. Risk of hospital admission with anaphylaxis 1 in 10 000. More likely to die on way to hospital appointment!? Doesn’t mean we avoid driving. Important to see that there can be an “acceptable risk” of living with food allergy.
Although there are a range of associations, most of these are very weak, which makes them unhelpful, or even misleading.
There is also a difference between sensitivity and severity. Some children during food challenges may only start reacting after a relatively high threshold dose – but their reactions tend to be worse, not unexpectedly.
Exercise is an important factor esp in teenagers, can even (rarely) be the sole identifiable trigger! See Exercise-Induced Anaphylaxis.
Statistically, females have worse reactions. In mice, the difference appears to be due to effect of oestradiol on increased tissue expression of eNOS (one of the NO synthases).
Medication – eg beta blockers, NSAIDS may increase risk.
Sleep deprivation reduced threshold in UK TRACE peanut study!
Most food anaphylaxis related to nuts (including peanut) and milk, but this is partly just how frequent these allergies are and how frequently the foods are encountered.
Deaths
Mostly in children over 5, despite the fact that food allergies are more common under 5 and usually lessen with time. Families often assume risk is higher in young children, which is incorrect. Nearly all are in children with asthma. Of the 8 deaths between 1990 and 2000, 4 were due to milk, 2 peanut, 1 egg and 1 mixed (but see below for bigger study). Both the peanut deaths were in children over 13yrs. Children are over 250x more likely to die in road traffic accident, although this is hardly a fair comparison.
Fatal Anaphylaxis Registry – set up in 1994 by Dr Richard Pumphrey based at Manchester University NHS Foundation Trust. This is now evolving into a European wide anaphylaxis registry.
In 80% of fatal anaphylaxis cases [mixed causes], adrenaline not given before arrest, which suggests delayed administration could be a factor. Same study shows that adrenaline does not prevent death even when given before arrest.
Most cases were in people with no previous history of anaphylaxis [but how many nut+asthma, where higher risk recognised?]
Survival better if adrenaline given within 30 mins [1992 Sampson article NEJM].
1 death at 6 hours, despite repeated adrenaline. 1 death after intentional consumption, despite immediate epipen administration.
So avoidance and asthma management are arguably more important than providing adrenaline autoinjectors! [Pumphrey]
Differential
If test unexpectedly negative, consider anergy if recent reaction. Test with raw food rather than commercial product, in case relevant protein under-represented.
