Safety of allergen immunotherapy in North America from 2008-2017: Lessons learned from the ACAAI/AAAAI National Surveillance Study of adverse reactions to allergen immunotherapy.

In 2004, it was estimated that one fatal anaphylactic reaction (FR) occurred in every 2.4 million subcutaneous immunotherapy (SCIT) injection visits. Uncontrolled asthma was the most commonly cited factor that contributed to FRs. Results of the annual American College of Allergy, Asthma, and Immunology/American Academy of Allergy, Asthma and Immunology sponsored survey conducted among practicing allergists suggest that one nonfatal systemic reactions (SR) occurred in 0.15% of injection visits and in 0.7% of patients who were treated. Analysis of recent data indicated that FRs are 3.75-fold less frequent. Life-threatening grade 4 anaphylactic reactions are estimated to occur in 0.005% of patients who receive SCIT (or 1/160,000 injection visits). Analysis of data from annual surveys identified the following possible risk factors for SRs: a history of SRs to SCIT, the administration of injections in patients with uncontrolled asthma, use of accelerated buildup regimens, and never adjusting doses during the height of the allergy season. Delayed-onset SRs beginning >30 minutes after injections represented 15% of all SRs in clinics with 30-minute observation periods. The safety profile of sublingual immunotherapy is favorable, with no FRs yet identified for sublingual tablet or liquid formulations. Risk management should focus mainly on patients with uncontrolled asthma by withholding injections in such patients, with recent worsening in asthma symptoms and lung function (e.g., peak expiratory flow rate). Because nearly all FRs and SRs occur within 30 minutes of injections, a 30-minute observation period is recommended. Routinely prescribing epinephrine for all patients did not prevent severe SRs, likely due to poor adherence when SRs occurred. Also, no local or systemic infections were identified in 2.3 million patients attending 24.5 million injection visits, which allayed concerns over infections associated with compounding of allergen extracts by practicing allergists.