Immunotherapy venom

Berger J, Ring J Efficacy of antihistamine pretreat- 15 ment in the prevention of adverse reactions to Hymenoptera venom immunotherapy a prospective randomized placebo-controlled trial. J Allergy 16 Clin Immunol 1997 100 458-463. 

Jutel M, Pichler WJ, Skrbic D, Urwyler A, Dahinden C, Muller UR Bee venom immunotherapy results in decrease of lL-4 and lL-5 and increase of IFN-y secretion in specific allergen-stimulated T cell cultures. J Immunol 1995 154 4187-4194. 

Fatal anaphylaxis after ayellow jacket sting, despite 41 venom immunotherapy, in two patients with mastocytosis. J Allergy Clin Immunol 1997 99 153-154. 

Rueff F, Wenderoth A, Przybilla B Patients still reacting to a sting challenge while receiving conventional Hymenoptera venom immunotherapy are protected by increased venom doses. J Allergy Clin Immunol 2001 108 1027-1032. 

The natural history of Hymenoptera venom anaphylaxis, that is the risk to develop anaphylaxis again when re-stung, has been analyzed in several prospective studies (table 3) [35-37], and in placebo or whole-body extract treated controls of prospective studies on venom immunotherapy [38-40]. It is higher in patients with a history of severe as compared to mild systemic anaphylactic reactions, and in honey bee than in vespid venom-allergic patients - most likely because of the smaller and less constant amoimt of venom applied by vespids [10,41]. A short interval between two stings increases the risk of anaphylaxis [25], but severe anaphylaxis may occur again even after intervals of 10-20 years or more. 

Sting provocation tests are often considered to be the gold standard, although they are less reliable in vespids than in honey bees [35-37, 41, 43]. They are commonly used to assure the efficacy of venom immunotherapy, but are generally considered as unethical in untreated patients with a history of venom anaphylaxis. 

Table 4. Efficacy of venom immunotherapy controlled prospective studies... 

Table 5. Efficacy of venom Immunotherapy Result of sting challenge on maintenance Immunotherapy [1,41,44] ...

The indication for venom immunotherapy is based on a history of systemic allergic reactions to Hymenoptera stings and positive diagnostic tests, skin tests and/or venom-specific serum IgE antibodies [45, 49]. In the presence of only mild systemic allergic reactions, limited to the skin, immunotherapy is not generally recommended in the USA not for children, in Europe not for children and adults, unless they are heavily exposed and had repeated such reactions. 

Contraindications are the same as for immunotherapy for inhalant allergy, but are relative in nature because of the life-saving potential of venom immunotherapy. Elderly patients, especially with preexisting cardiovascular disease, are at a high risk to develop severe or even fatal anaphylaxis [26]. Therefore, venom immunotherapy is often recommended in patients over 50-60 years of age. Since (3-blocker treatment is associated with a significantly increased survival rate in patients with coronary heart... 

Brown SG, Wiese M, Blackman K, Heddle R Ant 47 venom immunotherapy a double blind, placebo-controlled crossover trial. Lancet 2003 361 1101-1106. 

Muller UR, Jutel M, Reimers A, Zumkehr J, Huber C, Kriegel C, Steiner U, Haeberli G, Akdis M, Helbling A, Schnyder B, Blaser K, Akdis C Clinical and immunologic effects of H1 antihistamine preventive medication during honey bee venom immunotherapy. J Allergy Clin Immunol 2008 122 1001-1007. 

Jutel M, Zak-Nejmark T, Wrzyyszcz M, Malolepszy J Histamine receptor expression on peripheral blood CD4 + lymphocytes is influenced by ultrarush bee venom immunotherapy. Allergy 1997 52(suppl37) 88. 

Are regulatory T cells the target of venom immunotherapy Curr Opin Allergy Clin Immunol 2005 5 365-369. Strachan DP Hay fever, hygiene, and household size. BMJ 1989 299 ... 

Philadelphia, Saunders, 1992, pp 13-37. Jutel M, Muller UM, Pricker M, Rihs S, Pichler W, Dahinden C Influence of bee venom immunotherapy on degranulation and leukotriene generation in human blood basophils. Clin Exp Allergy 1996 26 112-118. 

Akdis CA, Akdis M, Blesken T, Wymann D, Alkan SS, Muller U, et al Epitope specific T-cell tolerance to phospholipase A2 in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro. J Clin Invest 1996 98 1676-1683. 

Bellinghausen I, Metz G, Enk AH, Christmann S, Knop J, Saloga J Insect venom immunotherapy induces interleukin-10 production and a Th2- to-Thl shift, and changes surface marker expression in venom-allergic subjects. Eur J Immunol 1997 27 1131-1139. 

Nasser SM, Ymg S, Meng 0, Kay AB, Ewan PW Interleukin-10 levels increase in cutaneous biopsies of patients undergoing wasp venom immunotherapy. Eur J Immunol 2001 31 3704-3713. 

Pierkes M, Bellinghausen I, Hultsch T, Metz G, Knop J, Saloga J Decreased release of histamine and sulfi-doleukotrienes by human peripheral blood leukocytes after wasp venom immunotherapy is partially due to induction of IL-10 and IFN- production of T cells. J Allergy Clin Immunol 1999 103 326-332. 

The efficacy of desensitization using subcutaneous maintenance venom immunotherapy is well established and is usually considered in patients with severe systemic allergic reactions to both yellow jacket and bee venom (grade III or IV according to Mueller). 

Wolf BL, Hamilton RG. Near-fatal anaphylaxis after Hymenoptera venom immunotherapy J Allergy Clin Immunol 1998 102(3) 527-8. 

Golden DB, Kwiterovich KA, Kagey-Sobotka A, Lichtenstein LM. Discontinuing venom immunotherapy extended observations. J Allergy Chn Immunol 1998 101(3) 298-305. 

Devey, M.E., Lee, S.R., Richards, D. and Kemeny, D.M. (1989). Serial studies on the functional afiinity and heterogeneity of antibodies of different IgG subclasses to phospholipase A-2 produced in response to bee-venom immunotherapy. J. Allergy Clin. Immunol. 84, 326-330. 

A report describes 2 cases of anaphylactoid reactions during wasp venom immunotherapy in patients taking enalapril. In one patient, generalised pruritus and severe hypotension occurred within a few minutes of the first venom injection. Desensitisation was achieved after the enalapril was stopped, and then the immunotherapy was maintained by diseontinuing the enalapril 24 hours before the monthly venom injection. However, on one oeeasion, when the enalapril had not been stopped, the patient expe-rieneed a severe anaphylactoid reaction 30 minutes after the venom injee-tion. In the other patient an anaphylactoid reaction occurred after the seeond dose of venom. The ACE inhibitor was replaced with nifedipine so that venom immunotherapy could be continued. ... 

In another report, a 43-year-old man who had been taking ACE inhibitors for 2 years (lisinopril 40 mg daily for the previous 5 months) had a hypotensive reaction to an insect sting. After skin testing, he received venom immunotherapy. About 4 months later, he had a severe anaphylactic reaction 5 minutes after being given a maintenance dose of wasp venom and mixed vespid venom. The ACE inhibitor was replaced with a calcium-channel blocker, and he subsequently tolerated full-strength venom immunotherapy injections. ... 

On the basis of these few reports, it cannot be said with certainty that an interaction occurs however, it is possible that ACE inhibitors could exacerbate the response to insect venom immunotherapy. Because of the potential severity of the reaction, extra caution should be taken in patients taking ACE inhibitors and undergoing desensitising treatment with Hy-menoptera (bee or wasp) venom. Some authors " and manufacturers advise temporarily withholding the ACE inhibitor before each desensitisation (24 hours was sufficient in one case), while others suggest temporary substitution of a different antihypertensive e.g. a calcium-channel blocker. Note that some evidence suggests that anaphylactic shock in patients taking beta blockers may be resistant to treatment with adrenaline (epinephrine), see Beta blockers + Inotropes and Vasopressors , p.848. Therefore beta bloekers are probably not a suitable alternative. 

Ober A, MacLean JA, Hannaway PJ. Life-frireatening anaphyl ds to venom immunotherapy in a patient taking an angiotensin-converting enz3fme inhibitor. J Allergy Clin Immunol (2003) 112, 1008-9. 

Lichtenstein, L.M., 1994, A reappraisal of sting challenges To whom should we offer venom immunotherapy. J. Allergy Clin. Immunol. 94 137-138. 

Bernstein, J.A., Kagen, S.L., Bernstein, D.L, Bernstein, I.L., 1994, Rapid venom immunotherapy is safe for routine use in the treatment of patients with Hymenoptera anaphylaxis. Ann. Allergy 73 423-428. 

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