Category Archives: Allergy

Cow’s milk protein/allergy intolerance

Allergy, General paediatrics, Immunology, Nutrition

A common issue for babies and infants.  But not that common – in EAT study, symptoms (vomiting, colic, eczema) related to milk reported by 13% of parents, but only found in 0.7%!

“Intolerance” suggests that cow’s milk causes adverse effects (generally gastrointestinal) but without committing to an underlying mechanism. 

If there is reason to think the adverse effects are immune mediated (because there are signs/symptoms outside the GI tract, for example) then it is preferable to use “cow’s milk allergy” (which then divides into type 1, non type 1, or mixed). 

Can even affect exclusively breast fed infants if sufficient milk proteins transmitted in breast milk, but probably over diagnosed (as challenge after 2-4 weeks not done).

Not the same as lactose intolerance – lactose is a sugar, intolerance to it is due to malabsorption and effects of undigested sugar in colon eg bloating, diarrhoea.  NOT rash, vomiting.  Usually post-gastroenteritis, transient.  No useful test other than lactose restriction for 2 weeks then rechallenge.

Some parents feel milk leads to more respiratory problems – there is some evidence that milk allergy is associated with more respiratory/GI infections and that an elimination diet (although supplemented by pre/probiotics) lead to reduced infections and less antibiotic use.

Cow’s milk allergy

Can be IgE mediated (immediate, histamine release, potentially anaphylaxis), else non-IgE mediated (typically more chronic, delayed symptoms, predominantly gastrointestinal, possibly a threshold level below which a patient is asymptomatic) but can be both. Non-IgE mediated symptoms include:

  • Eczema
  • Colic
  • Gastro-oesophageal reflux
  • Constipation [NOT green or mucuous stools]
  • Eosinophilic oesophagitis
  • Allergic Proctocolitis (FPIAP – see below)
  • Growth failure
  • Enterocolitis (FPIES)
  • Enteropathy – no blood, and longer recovery time (weeks)

Note that the first 4 problems are very common and cow’s milk protein intolerance may only be a factor in a small proportion of such patients. Best predictor of whether symptoms are due to milk allergy appears to be the background of the health care professional, not the history, age or family history of atopy! See Imperial College review of evidence (Munblit and Perkins 2020).

ESPGHAN 2023 guidance does detail trial of exclusion for reflux. For colic, very strict – only when Rome IV research criteria satisfied (3hrs per day, without obvious cause, cannot be prevented or resolved by care givers, 3 days a week, confirmed with prospective diary) AND suspected on basis of additional symptoms.

In patients with eczema, a mixture of IgE mediated and non-IgE mediated reactions can be seen (and immediate reactions may be seen on re-introduction even when only delayed reactions seen initially).

Food protein induced allergic proctocolitis

Well baby with blood +/- mucus in stool, usually in first few weeks of life. Associated with eczema and family history of food allergies. Mixed feeding appears to protect. Benign – in exclusively breast fed infants, ESPGHAN says no dietary intervention for first month. Even for formula fed babies controversial, as large study in Boston found elimination increased risk of later type 1 milk allergy by factor of 5!

DRACMA 2022 guidelines from WAO quote small Brazilian study showing 80% tolerant by 6 months so earlier reintroduction presumably possible if you do exclude. Calls for more research.

So depends on severity/frequency – and if you eliminate, definitely challenge early.

Diagnosis

Prescriptions for specialist formulas increased massively in early part of century – 10-12x higher than expected in England, for example. Estimated prevalence is 1% in the UK, less than 0.3% in Germany and Greece.

With delayed reactions, diagnosis depends on history, and then dietary exclusion followed by re-challenge after 2-4 weeks. In the case of FPIES, re-challenge may need to be done in hospital. Sometimes the diagnosis is only made at endoscopy.

Dietary exclusion has been shown to affect long term taste preferences. Also significantly restricts diet, with potential impact on calcium intake (and also riboflavin, niacin, zinc).

For immediate reactions, skin prick testing (SPT) more specific than IgE blood testing. 3mm SPT wheal considered positive in infants, but low specificity; when doing IgE/SPT tests, also check egg allergy (high cross-reactivity) and soy (for formula substitution). If IgE/SPT negative, needs challenge (ideally double blind).

Substitute Formulas

  • Breast feeding mothers may need to exclude dairy in their own diet.  Daily requirement of calcium (1250mg) and Vitamin D (10mcg), so supplement and fortified alternative dairy products needed.
  • Because of theoretical risk from phyto-oestrogens in soya, use extensively hydrolysed formula (EHF) instead of soya formula if under 6 months. Soya cross reactivity is reported in up to 25% of young infants with non IgE allergy but this varies widely. Soya milk usage is also associated with increased risk of subsequent peanut allergy (RR=2.6)!
  • ESPGHAN says you can also use hydrolysed rice formula – available in UK? Reported arsenic values are within WHO limits.
  • About 10% of infants will not tolerate even extensively hydrolysed formula (eHF) and may require an amino acid based formula; anaphylaxis has been described even with hydrolysed formula.  AA formula should be used first line if:
    • anaphylaxis,
    • severe non IgE (eg PR bleeding leading to haematological disturbance, severe skin disease, FPIES),
    • faltering growth (says ESPGHAN but controversial).
  • eHF potentially better than other types of formula, and potentially added benefit from probiotics – in trial of N=260 (42% IgE mediated, non-randomised) tolerance after 12 months 79% for EHF & Lactobacillus rhamnosus GG (LGG), cf 43% for EHF. 23% soya, 18% AA. Associated with IgE mechanism (negatively, OR 0.12), and EHF (4.41) or EHF & LGG (29) [Canani, European lab for food induced diseases, Naples. PMID 23582142].

Challenge

Cow’s milk must be tried again to prove it is the causal agent, unless type 1 symptoms, or severe non-type 1 (FPIES).  If symptoms return then continue elimination diet for at least 6 months, else 1yr of age, then re-introduce gradually. ESPGHAN says do IgE for milk first if type 1! Highlights that boiling more likely to hydrolyse proteins than baking, but ignores matrix idea. No evidence for further challenges but suggests every 6 months.

Prognosis

Exposure does encourage tolerance. In studies, after 6 months of oral desensitization, 11% had had positive food challenges cf 40% for abstainers. And in the abstainers, the threshold of sensitivity tended to be lower, and symptoms more severe [Eur Ann Allergy Clin Immunol. 2007 39:12-9. PMID 17375736].

Almost all non IgE milk allergy and most type 1 resolves by 1yr after diagnosis.

Reintroduction is typically done according to a “ladder” of 4 or more steps – baked milk, then boiled milk, then yogurt, then fresh raw milk. Baked milk is less allergenic due to the matrix of wheat – if wheat allergic, then gluten free cheese oatcakes (Nairns) or shortbread (Walkers/Asda).

IgE disease less likely to resolve if asthma, rhinitis, severe reactions or strongly positive results.  Median age of tolerance 5yrs.  According to Thermofisher, positive IgE Casein (Bos d 8) means less likely to tolerate baked milk or outgrow, as protein (casein) more heat stable (no consensus on component testing in ESPGHAN 2023).

You could argue for early introduction of weaning foods but this is only briefly mentioned in ESPGHAN 2023 and not yet recommended.

Final adult height has been shown to be reduced in milk allergy – this could be related to co-morbidities (asthma, eczema, steroid use, sleep disruption etc) or feeding difficulties (associated with elimination diets).

Prevention

EAACI task force recommends against use of milk formula top ups in first week of life in breast fed babies. Low certainty, though. Also recommends avoidance of allergens (including milk but not limited to) in pregnancy and during breast feeding!

ESPGHAN discusses too. In a multivariate model, independent factors associated with milk allergy were family history of allergy (OR = 2.83), avoidance of dairy products during pregnancy or breastfeeding (OR = 5.62), and formula given at the maternity hospital (OR = 1.81). In an RCT of daily 10ml formula supplementation (n=504 breast fed) cf only soya formula if required, performed between 1 and 2 months of age, daily formula ingestion prevented nearly 90% of later milk allergy confirmed by OFC at 6 months (RR: 0.12). EAACI neutral on this – and regular top ups would never be supported by breast friendly clinicians. Overall however, ESPGHAN group decided there was insufficient evidence for any of these things.

See also EAT study, and GINI study.

Treatment

66% of kids grow out cow’s milk allergy, even if they completely avoid it. But rate rises to nearly 90% if baked milk introduced. And less restrictive diet good for everyone, of course.

Salmivesi RCT from Finland 2012 – n=28, age 6-14. 81% using daily milk 6400mg protein at 12 months. First dose milk 0.06mg – 8 further observed doses (0.12mg day 8; 0.24mg day 15; 2.0mg day 36 [big jump!]; 4.0mg day 38 [2 days later!?]; 8.0mg day 42; 40mg [big jump again!] day 57; 80mg day 64; and 160mg on day 78) with other dose increases done at home. Monitored for 2hr in clinic. Final dose of 6400mg (=200ml) was given at home (!) on day 162.

Oral immunotherapy (OIT) for severe milk allergy (IgE >85 or low eliciting dose):  at 1yr 36% tolerated 150ml, 54% 5-150ml (good enough for accidental exposure). 10% could not complete protocol. [reference?]

DRACMA update on milk immunotherapy (2021) mostly fresh milk used in research. Randomized trials looked at kids aged 2-14, mean 8. Non randomized had wider range. 67% tolerated 150ml (cf 2.2% of controls), 78% tolerated 5-150ml (=swig protection) (cf 3.3% of controls). Anaphylaxis rate of 5.5 per person-years (although not always defined, and not always usual definition). 63% used IM adrenaline!?

6.9% developed EOE but rarely biopsy confirmed. No deaths.

2–8 weeks after discontinuation of successful OIT, tolerance of cow’s milk persisted in only 36% (20%–91%). So you have to persevere life long, probably.

Quality of life badly reported – only 5 studies. 1 study found parents reported better QOL in 37%, worse in 26%, and unchanged in 38%! 2 conference abstracts reported improved QOL or at least reduced anxiety in general and reduced fear of unexpected reaction. Some studies found worse QOL! Certainty of evidence overall v low…

Only 1 trial and 2 non randomized studies of baked milk OIT! In the 1 RCT of baked milk, 73% achieved tolerance at 12 months (cf none of control group) – other studies did not find evidence of effectiveness however (meta-analysis of Anagnostou. Tolerance to heated or baked milk may be temporary and diminish within a few years. Dantzer. 20% required adrenaline! Only some children assessed for QOL, with evidence of benefit – of the parents studied, no improvement in QOL! [Dantzer and Dunlop 2021]. Low desensitization rate for unheated milk means persisting concern about exposure in real life despite less frequent adverse reactions (8%–33%).

Other studies did not find this relationship, which is consistent with the meta-analysis results of Anagnostou et al. (41). Tolerance to heated or baked milk may be temporary and diminish within a few years. Dantzer et al. found that a protocol involving gradually increasing doses of baked milk was effective in promoting desensitization (73% achieved end dose of 4000mg cf 0% of controls).  Mean age 11. “This suggests that the initial dose [and then building] may influence the efficacy of desensitization.” 

[Yan Wang, China – Front. Immunol., 04 June 2025]

4% rate of biopsy proven EOE – note EoE typically emerges approximately 2.8 years after initiating the maintenance phase so many studies will miss…

Longer duration better. None of the studies reported on sustained unresponsiveness.

Only Dantzer study reported quality of life! 

Highlights “a dire need for a standardization in outcome assessment and reporting,” and that successful completion of OFC needs to be validated as a predictor of “real world” success. [Natasha trial will hopefully clarify further…]

Separate article on OIT recommendations – apart from balancing risks and benefits, recommends using omalizumab (monoclonal anti-IgE) in advance and in initial stages of oral immunotherapy with unheated cow’s milk. Inferring from limited evidence (use in other food allergies, mostly) that risk of anaphylaxis reduced (RR0.34 but not significant!). Not really any downside? (But costs at least £256 per dose, maybe double? Lasts a month?). Plus, does not recommend baked milk OIT as very low certainty of benefit. More evidence on effect, risks, QOL benefit obviously required.  

Sublingual/epicutaneous immunotherapy (SLIT) for milk? Not much evidence – low rate of success and high rate of relapse.

[EGPHAN 2023, Frontiers in Pediatrics 2019; BMJ cmpa article sept 2013]

Rush study from Japan used microwaved milk – microwaved for 100s at 550W (!). Dosing was 2–4 times a day in hospital for several days (frequent adverse events) aiming for 200 mL dose (total daily, I assume). If not achieved, dose increases changed to 1ml per day. At 200ml, dosing changed to once a day. After 2 months of maintenance, length of time in the microwave gradually reduced.

Another Japanese study looked at using heated milk powder (3 mins at 125degC) vs unheated milk. Rush protocol (5 days in hospital) up to maintenance of just 3ml daily. At 1 year, 35% and 18% in the HM group and 50% and 31% in UM group passed the 3 and 25 mL OFCs, respectively, so not great efficacy. Rates of moderate or severe symptoms significantly lower (halved) in the heated milk group however.

Natasha Trial is looking at Peanut or cow’s milk OIT in UK – groups are Peanut age 6-23yrs, Peanut age 2-3yrs, Cow’s milk age 3-23yrs. Using everyday food products. Final results expected 2027.

LEAP-On study

Allergy, General paediatrics, Immunology

Follow-up from LEAP study, after both groups (eating and avoiding) told to avoid peanuts for 12 months. The rate of adherence to avoidance in the follow-up study was high (90.4% in the peanut-avoidance group and 69.3% in the peanut-consumption group). Peanut allergy at 72 months was significantly more prevalent among participants in the peanut-avoidance group than among those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270].

[George du Toit, Gideon Lack in London, DOI: 10.1056/NEJMoa1514209]

Legume/pulse allergy

Allergy, General paediatrics

Legumes, pulses, beans…  Some terminology first: legumes are plants in family Fabaceae (or Leguminosae).  Pulses are (strictly) those cultivated for DRY seed, as opposed to green beans, broad beans etc that are eaten fresh.  Lentil simply describes shape (“like lens”).  So other examples of legumes are peanut, lupin, tamarind, carob, alfalfa!

Very common cause of food allergy, even excluding peanut! And varies across different cultures, depending on typical pulses used.  Fifth most common cause of food allergy in Spain.  In India, often a trigger of asthma/rhinitis when being boiled.  Cross sensitivity is seen, but not automatic, and hard to predict.

Soya allergy is sometimes seen in highly atopic babies, but otherwise actually pretty rare (except in Japan) – lucky, cause gets into lots of different things eg many breads.  Soya lecithin is a common additive, used to make texture more smooth, but usually only in very small amounts. Fermentation eg soy sauce appears to significantly reduce allergenicity, soya flour also seems less allergenic than soya milk, even though most of the allergens are cupins eg 2s albumin and would therefore be considered heat stable.

Lupin is used in some continental baked goods, for example packaged waffles.  A good proportion of peanut allergic children will be allergic to it too, but as lupin is not found very commonly most will never know or have a problem with it. A few restaurants (in UK and abroad) have lupin in their allergy menus.

A couple of lentil allergens have been identified including a vicilin and a lipid transfer protein.  In my experience pappadoms can often be tolerated – there is certainly evidence that autoclaving for 30 mins can affect binding, but these are only deep fried for a few seconds.

Both the known pea allergens are vicilins, hence cross reactivity with lentil.  Chickpea allergens however are not (one a prolamin, the other a cupin) – still, cross reactivity fairly common.

French beans have an LTP so potentially severe, and potentially fruit allergies too.  Green (mung bean) and red gram are cupins, black gram appears to be something else.

[Clin Rev Allergy Immunol. 45(1):30-46, 2013 Aug]

Angioedema

Allergy, Clinical, Common, General paediatrics, Immunology

Swelling, usually acute, non-pitting.  May be erythema too.  Typically affects face, especially lips, tongue, eyes, but can be limbs, even internal!

Usually related to urticaria (wheals). As with urticaria, can be allergy – clue is consistent trigger, pattern of recurrent episodes – but can have other causes.

Angioedema without urticaria – consider hereditary or drugs, especially NSAIDs and ACE inhibitors.

Testing for antibiotic allergy

Allergy, General paediatrics

See also Penicillin allergy.

Systematic review – just 0.21% of unselected general paediatric outpatients exhibit positive antibiotic allergy tests, and only 6.8% of those with suspected allergy test positive.

No evidence to support using skin prick testing.  Intradermal testing has high false positive rate (64-67% for penicillin and clarithromycin). Caubet did oral provocation test (OPT) regardless of intradermal result to beta lactam, NNT=11 to avoid one OPT! [Ped All Immun 2015 ]. OPT reactions tend to be cutaneous and mild, usually more than 1hr post administration.

Where reaction is severe but non-immediate, eg Stevens Johnson syndrome, Toxic Epidermal Necrolysis (TEN), Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), care needs to be taken with investigation, but studies have reported intradermal and OPT without unsafe adverse effects.  If reaction is anaphylaxis with first dose, then OPT contraindicated.

Wide variety in regimens.  Suggests 1-5 incremental doses of amoxicillin for mild reactions (timing not specified), giving cumulative dose appropriate to child, then continuing for 3 days.  Skin testing may be appropriate for severe reactions according to risk:benefit balance.  Check asthma well controlled, no antihistamines.  Warn that low risk of false negative result (absent co-factors) and low risk of re-sensitization.

Intravenous provocation only where PICU!

[Marrs, ArchDisChild 2015]

Macy article says any rash can have OPT! 5mm pos SPT for penicilloyl-polylysine has good negative predictive value for anaphylaxis with OPT. Recommends 5 days amoxicillin.

[Ann Allergy Asthma Immunol 121(2018):523−529]

Mirakian article suggests SPT for all immediate reactions! Split dose challenges, with a week between first and second doses!

For non immediate reactions (1-72hrs), OPT confirmed in 59%, ID less than 40%.

6 studies showing that benign reactions (ie witnessed macpap or urticarial, no pain/burning, <50% skin surface etc) do not need skin testing.  Geneva have done more than 800 straight to OPT.  New EAACI guidelines in press.

If delay in reaction is unclear, assume immediate.  SPT vs amoxicillin, PPL, MDM.  IgE vs BPL.  0.04ml ID volume.  Note different reference ranges!  See Brockour, Allergy 13

Recent letter claimed OPT after skin test was “unnecessary, dangerous, unethical”!  But 30-100% false negatives!

Clavulanate allergy described.

Test sensitivity falls more than 4/12 after episode, ideally do within 4-6/52????

Basophil activation test using flow cytometry looking promising for IgE mediated drug reactions.  EAACI interest group working on Drug Allergy Passport.

Prednisolone allergy

Allergy, General paediatrics, Immunology

Both type I and type IV allergic reactions associated with corticosteroids have been reported in the literature.  Due to drug itself, the excipients making up the drug, or both?

Corticosteroids have been classified into 5 different categories based on their structural and chemical properties:

Group Agents
A Hydrocortisone

Methylprednisolone

Prednisolone
B Budesonide

Triamcinolone
C Betamethasone

Dexamethasone
D1 Mometasone furoate

Fluticasone propionate

Cross-reactivity outside of these groups has only really been seen with group D2, which includes only lesser known steroids eg hyrdocortisone 17 butyrate, and group A.  Budesonide has also been described to exhibit some cross-reactivity with group D2, due to a stereoisomer, rather than its group conformation.  There is also some cross-reactivity with sex hormones, although the clinical significance is unclear – there is a type of cyclical dermatitis which is thought to be related to endogenous progesterone sensitivity.

[Allergy. 2009 Jul;64(7):978-94. doi: 10.1111/j.1398-9995.2009.02038.x]

Oral allergy syndrome

Allergy, General paediatrics, Immunology

Used interchangeably with Pollen food syndrome, although PFS is probably a better name because it is more specific and more closely represents what is going on. Only described in 1942!

Pollen Food Syndrome (PFS) refers to fruit and/or nut allergy, associated with birch pollen allergy (ie hayfever).  The food allergy part of the deal however is usually mild, eg itching/tingling/scratching/numbness, of lips/tongue/throat (sometimes ears) only, which distinguishes it from primary peanut or tree nut allergy. Peri-oral rash, nausea, abdo pain are sometimes reported. Mild angioedema of tongue and lips can occur, as can cough – you would be more nervous about assuming PFS in this situation, of course.

Peeling root vegetables is a trigger in those who have vegetable types of PFS! Another reason why PFS is a better name.

Extremely common – probably 40% of children with birch pollen related hay fever (and more than 70% of adults)! Getting more common too – climate change related hay fever season, and more allergenic pollen (thought to be related to ozone levels, hence cities can be worse)…

Due to cross reactions between birch pollen and similar proteins (most commonly PR-10 group – also oak, beech, alder) found in fruit, particularly those fruit with pips inside and a peel eg apple, pear, peach – this group of fruit is known as Rosaceae and includes nectarine, cherry, apricot, plum.

Other fruits involved include Kiwi, Mango, Melon, Tomato, Raspberry, Strawberry. Kiwi and banana still quite common primary allergies. Can be both, of course!

Peanut, Hazelnut and almond most common nuts involved in PFS in UK. 

Sometimes vegetables (Carrot, Celery, Potato, Asparagus, Pepper). Poppy seed, herbs and spices (Aniseed, Camomile, Coriander, Cumin, Fennel, Parsley).

Profilin group (Bet v2) about 20% of PFS in UK, more common in Southern Europe. Birch and oak too, but also olive tree, London plane, grasses (Phl p12), ragweed. Watermelon profilin cross reacts with melon, kiwi, peach.

There are other similar allergy syndromes including celery-spice-mugwort syndrome and latex allergy. 

You may find that you can eat the fruit if peeled, tinned, cooked or processed (eg jam). The ripeness, even the specific species, can matter too. Cold storage may increase the risk of reactions. Freezing doesn’t seem to make any difference.

Some affected individuals even put up with the itching because they prefer not to miss out on their favourite fruit!

Often emerges in later childhood or early adulthood, and only after hay fever develops. Seen in up to 25% of kids, but they don’t always recognise it themselves! Big variations geographically, obviously related to distribution of birch.

The main impetus for making the diagnosis is to select patients with a lower risk of anaphylaxis, even if nut allergic.  However, not always possible, and certainly not 100% reliable.  Thought that about 3% of PFS patients have systemic rather than just oral symptoms, and 1-2% will have anaphylaxis.  Potential confusion too because people who have primary IgE mediated peanut or nut allergy may of course also report isolated oral symptoms if low dose exposure.  In the original description of oral allergy syndrome, 50% progressed to systemic reactions!

So, important to differentiate –

  • primary IgE peanut or tree nut allergy who have only had oral symptoms so far (but are are risk of severe reactions, due to sensitisation to storage proteins, typically found in seed/kernel)
  • benign PFS, where allergic to Bet v 1, its homologues (eg Ara h 8, Cor a 1 – see peanut allergy) or other PR-10 or Profilin.  These proteins are usually in the pulp of the fruit. Soya (Gly m 4) is an exception where soya milk can cause severe reactions.
  • PFS with potential for systemic reactions where allergic to LTP (typically found in the peel)

BSACI peanut and tree nut allergy guidance is to go with typical history and only test if:

  • Atypical/severe reactions
  • reactions to processed rather than raw plants (including roast nuts)
  • Soya products other than soya milk
  • Tree nuts other than hazelnut, almond, walnut
  • Legumes other than peanut

BSACI guideline says beware younger children (under 8) with kiwi, melon or banana allergy, even if otherwise typical history – PFS unlikely.

Testing could be Prick to prick tests (important to get skin and pulp!), or else consider:

  • Pru p 3 for LTP allergy– if reacts to cooked food or other atypical features (even if not peach specifically!)
  • Gly m 4 if soya milk negative (PR-10 but can be severe reactions).  Gly m 5/6/8 if atypical
  • For hazelnut and almond, best to do prick to prick, for raw AND roast; if positive, do Cor a 1 (PR-10, so PFS) with 9 and 14 (which would suggest primary)
  • Ara h 2 if any standard tests for peanut positive (should be negative in PFS) – if negative, Ara h 1/3/6
  • Jug r 1 if walnut tests positive, Ber e 1 for brazil nut.

Oral challenges only possibly needed if avoiding multiple foods.

Pollen subcut immunotherapy does not seem to help PFS, unfortunately.  Insufficient evidence about pollen sublingual immunotherapy.  Some work around oral immunotherapy with fresh food or with isolated proteins.

The risk of anaphylaxis in PFS is quoted as 10%, but this is perhaps misleading as it usually relates to very high doses such as smoothies, tofu, soya milk. Other possible risk factors include:

  • severe seasonal asthma
  • Acid suppression therapy!
  • Jackfruit!

Adrenaline autoinjectors are rarely justified.

But there are reports of anaphylaxis to peanut despite being exclusively Ara h 8 sensitised and passing an oral challenge – but had big dose on empty stomach! [https://doi.org/10.1111/cea.12425]

Golden Delicious, Granny Smith and Cox’s the worst of the fruit, with the most Mal d 1 (Bet v 1 homologue).

BSACI does not mention whether prick to prick with frozen is effective, only that you can still react to frozen fruit/veg.

More severe reactions described with jackfruit! Beware smoothies, protein shakes, edamame beans!

Bean sprouts, mange tout and sugar snap mentioned specifically as usually only lightly cooked, or just raw.

[Isabel Skypala, BSACI PFS guidance, Clin Exp Allergy 2022]

Macrolide allergy

Allergy

The majority of cases reported are non immediate reactions eg maculopapular rash, urticaria. The incidence of anaphylactic reactions is extremely low.

Less than 15% of those suspected of having macrolide allergy are finally confirmed as allergic, mainly by direct provocation testing.

Cross-reactivity between the different macrolides is variable and little information is available.

Current Opinion in Allergy and Clinical Immunology 14(4), August 2014, p 278–285. DOI: 10.1097/ACI.0000000000000069

Penicillin allergy

Allergy

Children with pneumonia with a label of penicillin allergy were found to have:

  • higher risk of hospitalization (RR 1.15)
  • acute respiratory failure (RR 1.27)
  • and need for intensive care (RR 1.46; 95% CI, 1.15-1.84)
  • increased cutaneous drug reactions (RR 2.43)

[US Journal of Allergy & Clinical Immunology in Practice.  11(6):1899-1906.e2, 2023 Jun.]

Cephalosporins

Atanaskovic-Markovic et al found that cross-reactivity between cephalosporins and penicillins varied between 0.3 and 23.9%, being higher among penicillins and between first-generation and second-generation cephalosporins.

However, it has recently been shown that all penicillin allergic children can tolerate cefuroxime, presumably as it has a different side chain.

Cross-reactivity appears to be higher in immediate reactions, and when penicillins and cephalosporins are identical or similar in the R1 side chain, as happens with the first and second-generation cephalosporins.

Currently BNFc says to avoid cefalosporins if history of immediate penicillin hypersensitivity, but if use of cefalosporin is “essential” then can be used (but not cefalexin!).

Canadian study did oral challenges for non-blistering rashes – safe – but mostly cefprozil allergy (and linked to food allergies).

De-labelling

In hypothetical case of de-labelled patient, 47% of anaesthetists would not prescribe penicillin to patient anyway (n=5000)!

Primary care don’t always remove label even after de-labelling! (patient held records would help…)

Needs culture change in primary care and paeds of documenting reactions!

Make sure note is added to patient record when de-labelled. Electronic labels don’t necessarily help – not always possible to remove an allergy label from drug prescription system, depending on the system, may only allow subsequent note to be added.  Free text systems do not encourage accurate description!

Alabama trial from NIHR to report on RCT of de-labelling in primary care; SPACE study in secondary care (nurse/pharmacist delivered).

See Testing for antibiotic allergy.

NSAID hypersensitivity

Allergy, General paediatrics, Immunology

Ibuprofen etc are a common cause of reactions, but mostly non immune mediated, via COX -1 inhibition. Previously called pseudo-allergy or intolerance, best called hypersensitivity, then subdivided into allergic or non-allergic. Often occurs in patients with underlying problem eg asthma, chronic urticaria, rhinosinusitis – exacerbates underlying condition. Hypersensitivity can be to a single drug, or cross-reactive, ie to unrelated drugs from different families (salicylates ie aspirin, propionic derivatives eg ibuprofen, acetic acid derivatives eg diclofenac, etc). Cross reactivity suggests a non-immune mechanism. Without history to support single drug (or family) hypersensitivity, you would have to advise the patient to avoid all NSAIDs.

Testing

  • Skin testing with culprit drug is appropriate if you have an acute urticarial or angioedema reaction in a single drug/family.
  • Oral challenge is appropriate to confirm all types of hypersensitivity, esp in equivocal histories. At the same time, challenge with aspirin to check cross-reactivity, and with next best alternative NSAID. Start 1/10 dose, increase every 2 hours.
  • For nasal/bronchial symptoms, inhaled lysine aspirin is safer and faster, but only 77-90% sensitive cf 90% for oral. Intranasal is equivalent if inhaled/oral not possible.
  • If patient is on long term steroids, or else has been well controlled for a long time, sensitivity seems less!
  • Consider proceeding to challenge with COX2 (coxib) if challenge positive.

Aspirin desensitization works for NSAID exacerbated respiratory disease, and NSAID induced (cross reactive) skin disease, controversial for chronic urticaria and no data for single drug skin disease or anaphylaxis. But needs maintenance dosing so only really useful for chronic conditions eg needing antiplatelet therapy.

Allergy 2013:68;1219