ABSTRACT
Historical Perspective Since inception (1), specific immunotherapy has generally been administered via subcutaneous injections [also known as subcutaneous immonutherapy (SCIT)], but other modalities of administration were proposed and investigated during the 20th century. In some approaches, the rationale was to specifically desensitize the target organs (nose or bronchi) by giving the allergen as a nasal spray (local nasal immunotherapy) or inhaled aerosol (bronchial immunotherapy). Alternatively, a systemic desensitization was targeted by administering the allergen orally or sublingually. Among these “local” or “noninjection” routes of administration, intranasal immunotherapy was extensively investigated with favorable clinical results (2). In contrast, the oral (allergen immediately swallowed) and the local bronchial routes were abandoned in the 1970s because of lack of efficacy or unacceptable side effects (3). In 1986, the British Committee for the Safety of Medicines (4) reported several deaths associated with SCIT and raised serious concerns about the safety and the risk/benefit ratio of immunotherapy. Although some cases of life-threatening events were due to avoidable human errors (wrong dose, improper prescription, incorrect administration) (5), most cases of anaphylaxis are unexplained and unpredictable (6).
