Tag Archives: hymenoptera

Hymenoptera venom allergy

Allergy, General paediatrics, Immunology

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. Bumblebee PLA2 is 53% identical to honeybee PLA2, so not necessarily cross reactive. Similarly, Apid (bee) hyaluronidase is 50% identical to vespid.  Vespids subdivides into Vespa=hornets (found in UK, biggest, 35mm, reddish brown head). Wasps and hornets not as fuzzy as bees.  Vespula=wasps, Dolichovespula (“short headed wasps”) are harder to distinguish (shorter distance between eyes and upper jaws!). These 3 vespid types cross react strongly, so likely to be allergic to all.

Polistes=”paper wasps”, distinct from other vespids, Southern Europe only (so far) – 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 (usually from multiple stings – haemolysis, nephropathy, coagulopathy – rare)
  • systemic +/- anaphylaxis [usually igE, rarely short term IgG, or complement activation by IgG-venom complexes]
  • (plus “unusual”).

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.

  • rapid onset generalized urticaria and/or angio-oedema,
  • bronchospasm
  • laryngeal oedema
  • hypotension (collapse, loss of consciousness).

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.

[BSACI guidelines – Clinical & Experimental Allergy. Volume 41, Issue 9, September 2011, Pages: 1201–1220 doi/10.1111/j.1365-2222.2011.03788.x]

Immunotherapy

See Venom immunotherapy.

Honey allergy

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!  

Avoid opening windows, avoid rubbish bins, tidy away food/drink (esp sugary) .  Calmly walk away!

Keep skin covered. Keep surfaces, mouth/face/hands clean of food residues after eating!!!

Raid-type killer sprays for environment.

Patient Support

Anaphylaxis campaign have insect venom leaflet.

Immunotherapy

Allergy, General paediatrics, Immunology, , ,

First described in the literature in 1908! For egg. Noon and Freeman described grass immunotherapy in 1911. First double-blind trial was by William Frankland in 1954 for subcutaneous grass immunotherapy for seasonal asthma.

Should always be done with extreme caution, if at all, if asthma.  Available for wasp/bee stings, grass and tree pollen.  See also current situation with peanut immunotherapy.  Some evidence that immunotherapy for rhinitis also prevents asthma, which fits with “one airway” hypothesis.

Immunotherapy should be initiated and monitored in a specialist centre experienced in immunotherapy.

Text message reminders doubles adherence – even non-personalised.

Immunomodulation with omalizumab appears to improve success rates of immunotherapy. Treatment with dupilumab (anti-IL4/13) reduces specific IgE levels in people with atopic dermatitis (clinical effect unknown just now).

Grass/pollen allergy

EAACI indications for rhinoconjunctivitis immunotherapy includes:

  • mild rhinitis for reasons of asthma control.
  • Moderate-severe symptoms.

Bad asthma and poor compliance are contraindications. Bad asthma was an exclusion criterium for most of the studies, so no evidence of safety.  Poor evidence for under 5yrs (for HDM).

Polysensitization common, US tend to to treat all, Europe tends to pick 1 or 2 most useful, at intervals. 17 fatalities to date with immunotherapy. 1 per million injections (risk with sublingual much less, even though used for higher risk patients). Large local reactions common but don’t predict further reactions. Risk of systemic reaction only increased if recurrent. Consider predosing with antihistamine, else reduce dose.

Sublingual immunotherapy (SLIT) in children aged 4 to 12  years with grass pollen-allergic rhinitis/rhinoconjunctivitis significantly  reduced symptoms and medication use, well tolerated, and no serious treatment-related  events were reported. [Journal of Allergy & Clinical Immunology.  130(4):886-93.e5, 2012 Oct.]

In metanalysis by Dhami S et al, overall standardized mean difference (SMD) of -0.53 (95% CI -0.63, -0.42) in symptoms scores, roughly equal numbers of SCIT and SLIT studies, roughly equivalent scores.  When looking just at children, benefit seems less (SMD -0.25 (95% CI -0.46, -0.05)).  Continuous treatment probably slightly better than pre/co-season treatment.  Manufacturers suggest “disease modifying effect” of treatment beyond first year, which has theoretical rationale.  Four studies of long term outcome, demonstrates continuing benefit if treatment continued beyond first year [Allergy 2017]. 

Grazax (grass) can be safely administered by general practitioners (£80 per month, licensed from 5yrs up): tablet needs to be kept under tongue for at least 1 minute, first dose should be monitored by doctor for 20 minutes.  Don’t eat or drink for 5 minutes.

Give antihistamines for local effects. Oral blistering occurs!  Isolated cases of eosinophilic oesophagitis but impossible to link of course.

Contains fish gelatine but no reported problems in those with fish allergy.  Severe asthma contraindication (in children, defined as <80% predicted FEV1 on treatment).

Aim to start 4 months before season starts, although still some benefit if started 2-3 months before.  If no benefit in first season, no point continuing (according to Grazax own SPC).

Symptom relief begins only in the second season of therapy?  BNFc says continue only for 3 yrs.  Not approved by SMC for Scotland, because no great evidence for benefit after first year – would need individual patient treatment request.  Rosie says children wouldn’t tolerate daily doses for months and years.

Pollinex subcut, given into middle third of upperarm.  2 versions: Trees, and 13 grasses incl rye. 3 injections at 7-14 day intervals each year (£450 each), before season starts.  Maintenance kit of 4 vials also available, presumably if additional benefit thought possible.  Manufacturer recommends using for 3 successive years. Asthma and beta blocker treatment are relative contraindications.  Age 6+, not in SMC at all. [Metanalysis, Chest 2008; 133:589, Journal of Allergy & Clinical Immunology. 115(4):676-84, 2005 Apr.]

Some evidence for short course – in multicentre study of adults (not UK) with grass mix SPT positive rhinitis, 8 subcutaneous injections of placebo or Lolium perenne (LPP) were administered in 4 visits (2 jabs each visit, 30 mins apart, different arms) over 3 weeks between January and April. Combined symptom and medication score (CSMS) measured over the peak pollen season was reduced 15.5% (P = .041) during the peak period and −17.9% (P = .029) over the entire pollen season. Also lower rhinoconjunctivitis QOL global score (P = .005) compared with placebo group.

Asthma

Dhami metanalysis immunotherapy for asthma in kids – symptoms improved, less medication, esp HDM, grass, cat/dog. Not just severe asthma! But no prolonged benefit.

1 study of adults with poor control, HDM. Reduces time to first exacerbation.

Mite allergy prevention study n=111 HDM treatment effective. 2002 PAT study reduced asthma at 10yr follow up after grass/pollen treatment.

[Gillian Vance, Newcastle]

Eczema

House dust mite immunotherapy with SLIT (3 doses per week) shown to have some benefit in RCT from Brazil (66 children and adults) using SCORAD eczema severity questionnaire. Placebo group showed 35% improvement over 18 months, SLIT group showed 55%. No difference in Dermatology Life Quality index, pruritus score or any of the various other measures used!