Venom immunotherapy for insect allergy

Indications for venom immunotherapy

Venom immunotherapy is requires careful selection of patients: only those with a history of systemic allergic reaction to a sting and evidence of venom-specific IgE antibodies with a positive venom skin test or elevated specific IgE level.

Large local reactions are not usually a predictor of systemic reactions. The risk of anaphylaxis in patients with large local reactions is 5–10%, and venom immunotherapy is not typically recommended. Adults with cutaneous systemic reactions are still advised to undergo venom immunotherapy. There is no test for either large local or cutaneous reactors that predicts which patients will progress to anaphylaxis.

It is important to check serum tryptase in all patients undergoing workup for venom allergy to rule out indolent mastocytosis.


A yellow jacket wasp with a typical narrow waist (left) and a honey bee with a fat hairy "fuzzy" body (right). Image source: Wikipedia 1, 2, GNU Free Documentation License.

Safety of venom immunotherapy

Adverse reactions to venom immunotherapy are no more common than reactions during inhalant allergen immunotherapy (SCIT). Systemic symptoms occur in 5–15% of patients during the initial weeks of treatment, regardless of the regimen used.

Fewer than 5% of patients receiving venom immunotherapy ever require epinephrine treatment for a reaction to an injection.

Large local reactions to venom injections occur in up to 50% of patients, especially with the dose 20–50 mcg.

Efficacy of venom immunotherapy

Venom immunotherapy is 75–98% effective in preventing sting anaphylaxis (95–100% for the 300 mcg dose of mixed vespid venoms). Most patients can discontinue treatment after 5 years.

Studies of immunotherapy with a 100 mcg dose of individual venoms (honeybee, yellow jacket or wasp) have been associated with 75–95% efficacy.

Insect species and immunotherapy dose

The selection of venom extracts dependens on the positive venom skin test reaction, or venom-specific IgE antibody levels. The immunotherapy prescription should include all that are positive.

The standard recommended dose of 100 mcg of each venom. This is considered equivalent to the venom protein content of 2-4 insect stings. The amount of venom protein injected by a honeybee sting is 50 mcg. However, the amount of venom injected by the vespids is much lower, in the range of 2–20 mcg per sting.

Schedule for venom immunotherapy

The schedule for venom immunotherapy depends on the recommendations of the source laboratory which prepared the allergen extract.

Some of the products available in the USA include:

- "modified rush" regimen (ALK-Abello Labs, Round Rock, TX) achieves maintenance dose in 8 weekly injections

- "traditional" regimen (Hollister-Stier Labs, Spokane, WA) achieves maintenance dose in 4–6 months

In one study, both regimens were equally effective. The frequency of systemic reactions was also similar.

When the full maintenance dose is achieved, it is repeated in:

- 1 week
- 2 weeks (after the 1st dose of maintenance injection)
- 3 weeks (after the 2nd dose of maintenance injection)

"Traditional" regimen schedule based on the package insert for Hollister-Stier venom extracts (Spokane, WA) (always verify with the manufacturer)

Week 1, concentration 1 mcg/ml, volume 0.05 ml
Week 2, concentration 1 mcg/ml, volume 0.1 ml
Week 3, concentration 1 mcg/ml, volume 0.2 ml
Week 4, concentration 1 mcg/ml, volume 0.4 ml
Week 5, concentration 10 mcg/ml, volume 0.05 ml
Week 6, concentration 10 mcg/ml, volume 0.1 ml
Week 7, concentration 10 mcg/ml, volume 0.2 ml
Week 8, concentration 10 mcg/ml, volume 0.4 ml
Week 9, concentration 100 mcg/ml, volume 0.05 ml
Week 10, concentration 100 mcg/ml, volume 0.1 ml
Week 11, concentration 100 mcg/ml, volume 0.2 ml
Week 12, concentration 100 mcg/ml, volume 0.4 ml
Week 13, concentration 100 mcg/ml, volume 0.6 ml
Week 14, concentration 100 mcg/ml, volume 0.8 ml
Week 15, concentration 100 mcg/ml, volume 1 ml
Week 16, concentration 100 mcg/ml, volume 1 ml
Week 18, concentration 100 mcg/ml, volume 1 ml (2 weeks later after the 1st dose of maintenance injection, 1 ml)
Week 21, concentration 100 mcg/ml, volume 1 ml (3 weeks later after the 2nd dose of maintenance injection, 1 ml)
Monthly injection, concentration 100 mcg/ml, volume 1 ml, for 3 years



Only 70% of patients with stinging insect allergy fill their epinephrine prescriptions (Rudders, Annals 2013).

References

Chapter 57 – Insect Allergy, David B.K. Golden, Adkinson: Middleton's Allergy: Principles and Practice, 7th ed., 2008.
3-Day Rush Venom Immunotherapy in Bee Allergy: Safe, Inexpensive and Instantaneously Effective (http://goo.gl/afeso)
Stinging Insect Guidelines - 2001 Update by AAAAI and ACAAI. Medscape, 2011.
Bee Aware Allergy - Insect allergy educational website by Hollister-Stier Laboratories.

Related reading

Honeybee immunotherapy is less safe and less effective than for other flying Hymenoptera http://goo.gl/RgAjj

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