Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
Allergen immunotherapy was introduced by Leonard Noon 100 years ago and is the only disease-modifying treatment for allergic individuals (Allergy, 2012).
Mechanisms of allergen-specific immunotherapy (click to enlarge the image).
Allergen (venom) vaccine is the recommended term for the therapeutic agent used in allergen immunotherapy. "Vaccine" is used when the therapeutic use of the preparation is
clear. "Extract" is used when the non-therapeutic aspects of the allergen preparation are discussed.
Extracts of honeybee, yellow jacket, white-faced hornet, yellow hornet, and wasp venom are available for skin testing and VIT.
There is no venom extract for fire ant hypersensitivity but a whole-body extract is available.
Skin prick tests with a concentration in the range of 1.0 to 100 mcg/mL may be performed before intracutaneous (intradermal) tests but are not used by all allergists.
Intracutaneous tests start with a concentration in the range of 0.001 to 0.01 mcg/mL. If
intracutaneous test results at this concentration are negative, the concentration is increased by 10-fold increments until a positive skin test response occurs or a maximum concentration of 1.0 mcg/ mL is reached.
A positive intradermal skin test to insect venom at a concentration of 1.0
mcg/mL or lower is indicative of specific IgE antibodies.
Skin testing with fire ant whole-body extract is indicative of specific IgE antibodies if a positive response occurs at a concentration of 1:100 wt/vol or less by prick method, or 1:1000 wt/vol or less by intradermal method.
If the skin test is negative despite a convincing history of anaphylaxis after
an insect sting, in vitro testing for IgE antibodies or repeat skin testing is recommended.
Venon immunotherapy (VIT)
30-60% of patients with a history of anaphylaxis from an insect sting who have venom-specific IgE antibodies (skin or in vitro testing) will experience a systemic reaction when stung again.
VIT is not necessary in children 16 years of age and younger who have experienced isolated
cutaneous systemic reactions without other systemic manifestations. They only have a 10% chance of having a systemic reaction if stung again, and if one occurs, it is unlikely to be worse
than the initial isolated cutaneous reaction.
VIT in adults who have experienced only cutaneous systemic reaction is controversial but usually recommended.
VIT is extremely effective in reducing the risk of systemic reaction to less than 5%, and sting reactions that occur during VIT are usually milder.
VIT is generally not necessary for patients who have had only a large local reaction because the risk of a systemic reaction is low.
The vast majority of patients who have had a large local reaction do not need to be tested for specific IgE.
How do you define a large local reaction to insect sting?
- increase in size for 24 to 48 hours,
- swelling to more than 10 cm in diameter
- 5 to 10 days to resolve
Patients who have experienced large local reactions often have large local
reactions to subsequent stings, and up to 10% might eventually have a systemic reaction.
What is the difference between a large local reaction and a systemic cutaneous reaction?
Systemic reactions can include a spectrum of manifestations ranging from mild to life-threatening:
- cutaneous reactions (eg, urticaria and angioedema),
- large airway obstruction (tongue or throat swelling, laryngeal edema)
- hypotension and shock.
The key feature that distinguishes a systemic cutaneous reaction from a large local reaction is the involvement of parts of the body not contiguous with the site of the sting.
What is the dose of VIT?
VIT injections start weekly, beginning with doses no greater than 0.1 to 1.0 mcg, and increasing to a maintenance dose of 100 mcg of each venom (e.g., 1 mL of a vaccine containing 100 mcg/mL of venom).
The dosage schedule for fire ant immunotherapy is less well defined. A maintenance dose
is 0.5 mL of a 1:100 wt/vol concentration.
The interval between maintenance dose injections can be increased to 4-week intervals during the first year of VIT and to every 6 to 8 weeks during subsequent years.
How long to continue VIT?
VIT should be continued for at least 3 to 5 years. Despite the persistence of a positive skin test response, 80-90% of patients will not have a systemic reaction to an insect sting if VIT is stopped after 3 to 5 years.
Some patients with a history of severe anaphylaxis with shock or loss of consciousness still might be at continued risk for a systemic reaction if VIT is stopped, even after
5 years of immunotherapy.
Patients who have experienced a systemic reaction carry injectable epinephrine (eg, EpiPenTM or TwinJectTM devices) at all times.
Patients who take beta-blocker are at greater risk for anaphylaxis to VIT or a sting. Patients who have stinging insect hypersensitivity should not be prescribed beta-blockers unless absolutely necessary.
Stinging Insect Hypersensitivity: A Practice parameter Update. Joint Council of Allergy, Asthma, and Immunology.
Hymenoptera Venom Immunotherapy. Medscape review, 2011.
Stinging Insect Guidelines - 2001 Update by AAAAI and ACAAI. Medscape, 2011.