Allergen Immunotherapy JENNIFER L. HUGGINS, M.D., and R. JOHN LOONEY, M.D. University of Rochester School of Medicine and Dentistry, Rochester, New York Allergen immunotherapy (also called allergy vaccine therapy) involves the administration of gradually increasing quantities of specific aller- gens to patients with IgE-mediated conditions until a dose is reached that is effective in reducing disease severity from natural exposure. The major objectives of allergen immunotherapy are to reduce responses to allergic triggers that precipitate symptoms in the short term and to decrease inflammatory response and prevent develop- ment of persistent disease in the long term. Allergen immunotherapy is safe and has been shown to be effective in the treatment of stinging- insect hypersensitivity, allergic rhinitis or conjunctivitis, and allergic asthma. Allergen immunotherapy is not effective in the treatment of atopic dermatitis, urticaria, or headaches and is potentially dangerous if used for food or antibiotic allergies. Safe administration of allergen immunotherapy requires the immediate availability of a health care professional capable of recognizing and treating anaphylaxis. An observation period of 20 to 30 minutes after injection is mandatory. Patients should not be taking beta-adrenergic blocking agents when receiving immunotherapy because these drugs may mask early signs and symptoms of anaphylaxis and make the treatment of anaphylaxis more difficult. Unlike antiallergic medication, allergen immunother- apy has the potential of altering the allergic disease course after three to five years of therapy. (Am Fam Physician 2004;70:689-96,703-4. Copyright© 2004 American Academy of Family Physicians.) � Patient information: llergen immunotherapy involves England whose allergic symptoms coincided A handout on allergy subcutaneous injections of gradu- with the pollination of grass.2 Since then, shots, written by the authors of this article, is ally increasing quantities of spe- controlled studies have shown that allergen provided on page 703. cific allergens to an allergic patient immunotherapy is effective in patients with Auntil a dose is reached that will raise the allergic rhinitis, allergic conjunctivitis, aller- See page 633 for definitions of strength-of- patient’s tolerance to the allergen over time, gic asthma, and allergic reactions to Hymen- recommendation labels. thereby minimizing symptomatic expression optera venom.3-6 Patients with one or more of the disease. Because the proteins and gly- of these diagnoses are considered for immu- coproteins used in allergen immunotherapy notherapy if they have well-defined, clini- are extracted from materials such as pollens, cally relevant allergic triggers that markedly molds, pelt, and insect venoms, they were affect their quality of life or daily function, originally called allergen extracts. In 1998, and if they do not attain adequate symptom the World Health Organization (WHO) pro- relief with avoidance measures and phar- posed the term “allergen vaccine” to replace macotherapy. Despite proven efficacy, the “allergen extract,” because allergen immu- exact mechanism of allergen immunotherapy notherapy is an immune modifier just as remains unknown. vaccines are.1 The efficacy of allergen immunotherapy has Selection of Patients been known since 1911, when Noon injected To make a definitive diagnosis of allergy, IgE- an extract of grass pollen into a person in mediated, type I, immediate-hypersensitivity Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2004 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2004 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. skin testing typically is performed by scratch- ing diluted allergen into the skin surface or TABLE 1 by injecting it intradermally. A positive skin Best Indications for Immunotherapy test reaction reflects the presence of specific IgE antibodies to the tested allergen, and a Allergic rhinitis, conjunctivitis, or allergic correlation of the specific IgE asthma History of a systemic reaction to Hymenoptera Type 1 immediate-hyper- antibodies with the patient’s symptoms, suspected triggers, and specific IgE antibodies to Hymenoptera sensitivity skin testing with venom and allergen exposure is defini- clinical correlation is used Patient wishes to avoid the long-term use or tive. In vitro, allergen-specific to diagnose a specific IgE- potential adverse effects of medications immunoassays to detect serum mediated allergy. Symptoms are not adequately controlled by IgE antibodies are less sensitive avoidance measures or medications than skin testing but may be Cost of immunotherapy will be less than cost used in patients with skin diseases that would of long-term medications obscure skin testing results or in those who cannot stop taking medications that suppress the skin test response. The circumstances in received three to four years of immuno- which allergen immunotherapy is particu- therapy. They were able to demonstrate a larly useful are summarized in Table 1. The marked reduction in allergy symptom scores allergens for which immunotherapy is known and antiallergic medication usage, as well to be effective are Hymenoptera venom,5 pol- as an alteration in the natural course of lens,5,6 cat dander,7 dust mites,8 cockroaches,9 allergic disease. Preliminary reports suggest and fungi.10 Allergy immunotherapy is not that immunotherapy for allergic rhinitis efficacious for atopic dermatitis, urticaria, may reduce the risk for later development or headaches, and cannot be used for food of asthma in children.12,13 In addition, early allergies because the risk of anaphylaxis is treatment with allergen immunotherapy in too great. children who were sensitive only to house dust mites reduced development of sen- Benefits sitivity to other allergens.14 In contrast to Durham and colleagues11 conducted a ran- the use of antiallergic medication, allergen domized, double-blind, placebo-controlled immunotherapy has the potential to alter trial to look at effects in patients who had the natural course of allergic disease and prevent progression or development of mul- tiple allergies. Consequently, many allergists The Authors have suggested its use earlier in the course of JENNIFER L. HUGGINS, M.D., is a fellow in allergy/immunology and rheumatol- allergic disease. ogy at the University of Rochester School of Medicine and Dentistry, Rochester, In 2000, the Immunotherapy Commit- N.Y. She received her medical degree from the University of Kansas School tee of the American Academy of Allergy, of Medicine, Kansas City, Kan. Dr. Huggins completed postdoctoral training Asthma, and Immunology (AAAAI) pro- in pediatrics at Baylor University in Houston, and in internal medicine at the University of Rochester School of Medicine and Dentistry. She is board-certified vided a five-year cost comparison of medi- in internal medicine and pediatrics. cation usage and single-injection allergen immunotherapy for allergic rhinitis. The R. JOHN LOONEY, M.D., is associate professor of medicine and director of the cost of medications is much greater than that Allergy and Immunology training program at the University of Rochester School of single-injection immunotherapy. Long- of Medicine and Dentistry, where he also received his medical degree and completed postdoctoral training in internal medicine, infectious diseases, and term costs deriving from the morbidity and immunology. He is board certified in infectious diseases, allergy and immunol- complications of allergic diseases are not ogy, and rheumatology. established, but allergies usually begin early in life and persist if not treated with allergen Address correspondence to Jennifer L. Huggins, M.D., University of Rochester, Allergy/Immunology/Rheumatology Fellow, 601 Elmwood Ave., Box #695, immunotherapy. A reasonable assumption is Rochester, NY 14642 (e-mail: [email protected]) Reprints that allergen immunotherapy dramatically are not available from the authors. lowers the cost of treating allergic diseases. 690 American Family Physician www.aafp.org/afp Volume 70, Number 4 � August 15, 2004 Allergen Immunotherapy Standardization, Storage, and contains an antimicrobial agent. A volume Mixing of Allergen Vaccines effect can occur as a result of adherence of Ideally, vaccines should be standardized the allergen to the vial surface; the larger with a defined potency and labeled with the surface area of the vial, the more allergen a common unit.15 Such standardization is lost. Glycerol and human serum albu- would eliminate the variability in vaccines min (0.03 percent) are used to and allow for safer and more effective dos- mitigate the volume effect. Glyc- The maintenance con- ing. The Bioequivalent Allergy Unit (BAU), erol has the added advantage of centrate is the dose of which is assigned by the U.S. Food and Drug being an antimicrobial agent. At vaccine considered to be Administration based on quantitative skin a concentration of 50 percent, therapeutically effective testing performed on a reference population glycerol inhibits