Insecticide allergyT78.81

Mostly IgE-mediated, possibly life-threatening immediate type reactions to allergens (especially phopholipases) transmitted by insect bites.

The most common are bee venom allergies or wasp venom allergies. A bee transmits about 50ug and a wasp about 3-5ug of venomous proteins during the sting.

Double positivity is found in about 50% of patients with insect venom allergies.

Less common are hornet sting allergies or bumblebee sting allergies, only exceptionally ant venom allergies.

Of the insects of the order Hymenoptera (hymenoptera), the stings of the state-forming families of wrinkled wasps (Vespidae s.u. wasp sting), bees (Apidae s.u. bee sting) and ants (Formicidae), more rarely of bumble bees (s. bumble bee sting) are responsible for general allergic reactions.

The family of wrinkled wasps comprises the subfamilies of the true wasps and field wasps. Genuine wasps include the short-headed wasp, the long-headed wasp and the hornet. In Europe, the short-headed wasps (Vespula germanica, Vespula vulgaris) are responsible for most allergic incidents. Unlike other wasp species, they are carrion and carnivores (interactions with humans, e.g. when eating outdoors). Stings of hornets and long-headed wasps, on the other hand, occur almost exclusively near the nest. In Europe, field wasps (Polistes spp.) are found mainly in the Mediterranean region. Small colonies are found everywhere except in England.

New in Europe is the appearance of the Asian hornet, which spreads from southern France.

Stings from ants often cause general allergic reactions in the southern states of the USA and in South and Central America. The fire ants (Solenopsis spp.) are mainly responsible. Anaphylactic reactions to ant species are rare.

In Australia the ant species "Myrmecia pilosula" (-jack jumper ant-, jumps up to 10 cm) plays a role for humans. A sting with the sting on the back of the body is comparable in its reaction to that of a bee or wasp. About 3% (!) of people in Australia react with allergic symptoms to the poison.

In contrast, the native forest and path ants only have a rudimentary stinging apparatus. Allergic general reactions caused by their stings are extremely rare.

After a hymenopteran sting (bee, wasp, hornet) systemic hypersensitivity reactions occur in about 0.8-5% of the population.

Influencing risk factors:

• Tryptase(mastocytosis): In several studies, an elevated serum tryptase level has been shown to increase the risk. An elevated tryptase level > 10ug/l indicates an increased risk of both severe reactions to insect bites and SIT ( specific immunotherapy) injections.
• Age: Older people tend to have stronger system reactions than younger people.
• Beta-blockers, ACE inhibitors: Ongoing treatment with beta-blockers or ACE inhibitors may increase the severity of systemic reactions.
• Atopy: Atopic people do not have a higher risk than non-atopic people.

Identified single allergens of clinically relevant insect species according to IUIS Allergen Nomenclature Sub-Committee.

Wasp Venom Allergens

• Dolichovespula arenaria (Wasp species/Yellow hornet)
  • Dol a 5 Antigen 5
• Dolichovespula maculata (Wasp species North America/White face hornet)
  • Dol m 1 Phospholipase A1B
  • Dol m 2 Hyaluronidase
  • Dol m 5 Antigen 5
• Polistes annularis (paper wasp/wasp)
  • Pole a 1 Phospholipase A1B
  • Pole a 2 Hyaluronidase
  • Pole a 5 Antigen 5
• Polistes dominula (Gallic field wasp/Mediterranean paper wasp)
  • Pole d 1 Phospholipase A1
  • Pole d 4 Serine protease
  • Pole d 5 Antigen 5
• Polistes exclamans (paper wasp/wasp)
  • Pol e 1 Phospholipase A1
  • Pol e 4 Serine protease
  • Pole e 5 Antigen 5
• Polistes fuscatus (field weeps/wasps)
  • Pole f 5 Antigen 5
• Polistes gallicus (Gallic field wasp)
  • Pole g 1 Phospholipase A1
  • Pole g 5 Antigen 5
• Polistes metricus (field weeps/wasps)
  • Pole m 5 Antigen 5
• Polybia paulista (Wasp)
  • Poly p 1 Phospholipase A1
• Polybia scutellaris (Wasp)
  • Poly s 5
• Vespa crabro (European hornet)
  • Vesp c 1 Phospholipase A1B
  • Vesp c 5 Antigen 5
• Vespa magnifica (Hornet/Hornet)
  • Vesp ma 2 Hyaluronidase 35 kDa No 2011-07-19 2011-07-22
  • Vesp ma 5 Antigen 5, member of PR-1 family
• Vespa mandarinia (Hornet/Giant asian hornet)
  • Vesp m 1 Phospholipase A1B
  • Vesp m 5 Antigen 5
• Vespula flavopilosa (Wasp/Yellow jacket)
  • Ves f 5 Antigen 5
• Vespula germanica (German Wepse/Yellow jacket)
  • Ves g 5 Antigen 5
• Vespula maculifrons (Wasp/Yellow jacket)
  • Ves m 1 Phospholipase A1B29
  • Ves m 2 Hyaluronidase
  • Ves m 5 Antigen 5
• Vespula pensylvanica (Pennsylvanian wasp/Yellow jacket)
  • Ves p 5 Antigen 5
• Vespula squamosa (Wasp/Yellow jacket)
  • Ves s 1 Phospholipase A1B
  • Ves s 5 Antigen 5
• Vespula vidua (Wasp/Wasp)
  • Ves vi 5 Antigen 5
• Vespula vulgaris (common wasp/yellow jacket)
  • Ves v 1 Phospholipase A1B
  • Ves v 2 Hyaluronidase
  • Ves v 3 Dipeptidylpeptidase IV
  • Ves v 5 Antigen 5
  • Ves v 6 Vitellogenin

Bee Venom Allergens

• Apis cerana (Eastern honey bee/Eastern hive bee)
  • Api c 1 phospholipase A2
• Apis dorsata (Giant honeybee)
  • Api d 1 Phospholipase A2
• Apis mellifera (honey bee)
  • Api m 1 phospholipase A2
  • Api m 2 Hyaluronidase
  • Api m 3 Acid phosphatase
  • Api m 4 Melittin
  • Api m 5 Dipeptidyl peptidase IV
  • Api m 6
  • Api m 7 CUB serine protease
  • Api m 8 Carboxylesterase
  • Api m 9 Serine carboxypeptidase
  • Api m 10 Icarapine variant 2, carbohydrate-rich protein
  • Api m 11 Major royal jelly protein
  • Api m 12 Vitellogenin

Bumblebee poison allergens

• Bombus pennsylvanicus (Bumble Bee)
  • Bom p 1 Phospholipase A2
  • Bom p 4 Protease
• Bombus terrestris (dark earth bumble bee)
  • Bom t 1 Phospholipase A2
  • Bom t 4 Protease

The clinical reactions range from an increased local reaction (> 10 cm; lasting > 24 h) to a potentially life-threatening general reaction (see anaphylaxis below) , which can occur particularly in the case of unfavourable localisation of the sting (e.g. in the region of the upper airways). The symptoms usually begin within minutes, intervals of more than 30 minutes are rather rare.

The sting reactions are classified as follows:

1. normal local reaction
2. severe local reaction
3. systemic-toxic sting reaction
4. systemic-allergic sting reaction
5. unusual sting reaction (rare, neither IgE-mediated nor toxic: lymphadenopathy, peripheral neuropathies, vasculitides)

Toxic reactions occur after multiple hymenopteran stings. Threatening toxic reactions occur in >10 stings in children, 50-100 stings in adults.1000 stings are rarely survived.

Systemic reactions are classified according to Ring & Messmer as follows:

• Stage I skin manifestation and or slight increase in temperature.
• Stage II detectable, but not life-threatening cardiovascular reactions (tachycardia, drop in blood pressure)
• Stage III Shock, life-threatening spasm of the smooth muscle class
• Stage IV Cardiovascular arrest

• Local reaction: cooling compresses, also potent glucocorticoid ointments(e.g. Emovate, Dermoxin) under moist saline compresses. In case of itching, topical antihistamines such as dimetindene (e.g. Fenistil) can be tried in between; in case of severe itching, internal antihistamines such as desloratadine (e.g. Aerius) 1-2 tbl./day are more effective.
• Generalized reaction: Stage-dependent treatment of anaphylactic shock.
• Avoidance of situations where insect bites may occur.
• Immunotherapy, specific: In bee and/or wasp sting allergies with systemic type I reaction, specific immunotherapies often show very good success, i.e. in 80-100% of patients, a sting is no longer followed by systemic reactions (in 95% of wasp venom allergic patients, in 80% of bee venom allergic patients).
• Indication: Systemic reaction associated with bee/wasp sting. Caution is indicated in children < 5 years of age, as they rarely have severe anaphylactic reactions after a sting, but are prone to adverse and generalized side effects during immunotherapy. In the elderly, on the other hand, specific immunotherapies are useful, as insect stings are often met with severe anaphylactic reactions. For details and technical procedure see Immunotherapy, specific.
• The choice of bee or wasp venom is made after anamnesis, skin test and RAST. If this does not allow a clear decision between bee and wasp venom, immunotherapy with both venoms is performed.
  • In case of hornet venom allergy: In these latitudes specific immunotherapy with wasp venom.
  • Bumblebee venom allergy: immunotherapy with bee venom.
  • In case of double sensitisation, immunotherapy is carried out consecutively with both venoms. According to the anamnesis, hazard/exposure, it is usually started with the venom to which there is a stronger sensitisation. After reaching the maintenance concentration, start with the second immunotherapy.
• Specific ultra-short-term therapy (rush regimen): The most common and generally most effective procedure is initiation as rush immunotherapy with aqueous preparations (e.g. with ALK-lyophilized SQ) in an inpatient setting; see below. Table 1. after 1-2 weeks continuation in outpatient setting with depot preparations (e.g. ALK depot SQ/Scherax); see Table 2. then continuation therapy; see Table 3.
• Conventional regimen: Specific immunotherapy for outpatient treatment. Start with 1/10 (or 1/100) of the concentration determined in the intradermal test (or prick test). Uniform initial concentration for immunotherapy: 0.01 μg. In case of bee venom allergy and extremely low threshold in the skin test, decrease the initial concentration! At doses < 1 μg allergic general reactions are rare, below a dose of 0.01 μg general reactions are observed only in 2-3% with ultra-short term therapy. There is a relationship between reactivity in the intradermal test and frequency of systemic reactions during ultra-short-term therapy.
• For continuation of specific immunotherapy

  ,

  see Table 3.

  Therapy target: 100 μg (1 ml) every 4 weeks for both adults and children!

• In case of particular risk of exposure (beekeeper) or very severe reactions in the anamnesis: 200 μg/4 weeks. Consideration of accidental bee stings in active beekeepers during immunotherapy. After tolerated sting provocation, beekeepers possibly stung by a bee every 1-2 weeks in summer, immunotherapy with injections in winter. In case of interval violations, see Table 4. In case of undesirable NW, dose reduction, see Table 5.
• Duration of specific immunotherapy: minimum therapy: 3 (up to 5) years, then six-monthly controls. Specifically, treatment may be terminated when the highest venom dose has been tolerated without systemic adverse effects, sting provocation or accidental sting have produced a normal or only enhanced local reaction, RAST class 0 or 1 are present, and the skin test becomes negative (1 μg/ml).
• Prolonged therapy duration is required in case of severe systemic reactions as therapy side effects, very severe sting reactions, strikingly high concentrations of specific IgE, strikingly low skin test thresholds after 3 years of therapy, very high risk of exposure. In this case, half-yearly follow-up controls (if necessary annually) with collection of the anamnesis (further stings? reactions?), control of the completeness of the emergency set and testing of the reactivity, are necessary. A lifelong therapy obligation is required for patients with cardiovascular or respiratory arrest after a sting (Fischer 2013).
• Sting provocation: sting by a clearly living insect 6-12 months after reaching maintenance dose under anaesthesiological emergency preparedness (i.v. access, medication at hand, possibility for intubation, continuous control of pulse, RR, respiratory rate).

  Notice.

  Sting provocation is the most reliable parameter for estimating the current reactivity to the insect venom in question, for confirming the success of the therapy or for detecting therapy failures!
  Sting provocation with wasp venom may be less reliable than with bee venom, due to the greater variability of the amount of venom delivered per sting.
• Procedure: Obtain written consent from the patient. The patient should be fasting and remain sober for one hour afterwards. Place insect on skin with forceps, apply slight pressure to induce sting and remove stinger after 1 min. Use only if there are clear local reactions. The test depends on the age of the insect, the duration of the sting, the actual amount of venom in the venom sac. Follow up until the next day. In systemically reacting patients: aim to increase maintenance dose of insect venom immunotherapy to 150/200 μg (or shorten injection intervals). Possibly boosting of sensitization, therefore control of sensitization after 2-4 weeks.

Introductory phase of a specific immunotherapy for bee or wasp sting allergies

Continuation therapy of the specific immunotherapy (e.g. ALK-depot SQ)

Procedure in case of interval violations during the continuation therapy (e.g. Reless, Venomil) of the specific immunotherapy

Dose reduction for undesirable side effects during specific immunotherapy

1. Varga R.et al (2011) Does the current specific immunotherapy (SIT) with wasp venom offer protection against systemic reactions to stings of Dolichovespula spp. Abstract CD 46th DDG meeting P02/14 -
2. Helbling A et al (2014) Update on Hymenopteran Poison Allergy with special aspects of diagnostics and therapy. Allergo J 22: 265-273