Thank you for your inquiry.
An excellent summary of the systemic reaction rate related to immunotherapy is contained in our "guidelines" (parameters) on immunotherapy (Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter, third update. The Journal of Allergy and Clinical Immunology, January 2011; Volume 127 (1), Supplement, page S1-S55).
I have copied the pertinent section summarizing the studies looking at the incidence of systemic reactions below:
Summary Statement 31: Although there is a low risk of severe systemic reactions with appropriately administered allergen immunotherapy, life-threatening and fatal reactions do occur.
A review of the subcutaneous immunotherapy (SCIT) systemic reaction rates reported in studies published within the past 15 years found that the percentage of systemic reactions per injection with conventional schedules is approximately 0.2%.230
In a 2006 survey of allergen immunotherapy-induced fatal reactions and non fatal( NFRs) sent to physician members of the AAAAI, 273 of 646 respondents reported NFRs during the period of 1990 to 2001.185 The incidence of unconfirmed NFRs was 23 per year (5.4 events per million injections). Administration during the height of the pollen season (46% of respondents) and immunotherapy dosing errors (25% of respondents) were cited as the 2 most important contributing factors in the NFRs. The most severe NFR was respiratory failure (10% of NFRs). One patient with an NFR was receiving a β-blocker, and none were taking concomitant ACE inhibitors. Ninety-three percent of the NFRs occurred in clinics staffed by allergists, and none occurred in medically unsupervised settings.
In a retrospective analysis of the incidence and characteristics of nonfatal SCIT-induced systemic reactions in 435,854 injections administered to 4,000 patients over a 20-year period (1981-2000), there were 115 systemic reactions (5.2% of patients and 0.06% of injections) in the first 10 years and 26 systemic reactions (1.08% of patients and 0.01% of injections) in the second 10 years.231, 232 There were significantly less asthma and urticaria reactions in the second period.232
In a prospective multicenter study there were 53 systemic reactions in 17,526 doses administered to 423 patients (0.3% per injection and 3.7% of patients).233 All systemic reactions were mild to moderate and responded well to treatment. Five patients experienced more than 3 systemic reactions (total of 36 reactions), and the authors noted that 40% of the systemic reactions would have been avoided if patients experiencing the third systemic reaction had been withdrawn.
In the previously mentioned AAAAI physician members' survey of fatal reactions and NFRs from immunotherapy injections, there were 41 fatalities identified in the initial brief survey.143 The estimated fatality rate was 1 per 2.5 million injections (average of 3.4 deaths per year), which is similar to 2 previous surveys of AAAAI physician members.183, 184 In a subsequent 3-year AAAAI/ACAAI Immunotherapy Safety Surveillance study, data were provided by 806 practices representing 1922 SCIT prescribers (>50% response rate).234 There were no fatalities reported in 2008 for the approximately 8.1 million injections administered, although respondents voluntarily reported 6 SCIT fatalities from 2001 to 2007 that occurred in other practices.
Therefore although severe systemic reactions to allergen immunotherapy are uncommon, serious systemic reactions (some fatal) can occur.
Thank you again for your inquiry and we hope this response is helpful to you.
Phil Lieberman, M.D.