Meeting Report Immune-Mediated Drug Hypersensitivity Reactions (IDHR) Workshop

Immune-mediated drug hypersensitivity reactions (IDHR) are relatively rare reactions to drugs that can be observed in a limited population of patients, yet these reactions can have significant impacts on public health, clinical practice, and drug development. Despite the potentially significant impact of IDHR, research into the causes and mechanisms of action of these reactions has been limited. In order to identify and enhance potential research opportunities in IDHR, the Health and Environmental Sciences Institute (HESI) hosted a two-day workshop involving stakeholders from government, academia, and industry. Discussions focused on ways to increase IDHR research opportunities within both presently existing collaborative structures and new networks. Based on these discussions, workshop participants concluded that a volunteer organization of interested stakeholders could be established to provide for ongoing advocacy and coordination of efforts related to IDHR research. The primary objectives of such an organization would be to increase public awareness of the impact of IDHR, encourage multidisciplinary IDHR research and training, encourage the development and funding of IDHR research network and seed grants, and to establish a framework for the further exchange and dissemination of IDHR information.     

Hypersensitivity Reactions to Corticosteroids

Hypersensitivity reactions to corticosteroids (CS) are rare in the general population, but they are not uncommon in high-risk groups such as patients who receive repeated doses of CS. Hypersensitivity reactions to steroids are broadly divided into two categories: immediate reactions, typically occurring within 1 h of drug administration, and non-immediate reactions, which manifest more than an hour after drug administration. The latter group is more common. We reviewed the literature using the search terms “hypersensitivity to steroids, adverse effects of steroids, steroid allergy, allergic contact dermatitis, corticosteroid side effects, and type I hypersensitivity” to identify studies or clinical reports of steroid hypersensitivity. We discuss the prevalence, mechanism, presentation, evaluation, and therapeutic options in corticosteroid hypersensitivity reactions. There is a paucity of literature on corticosteroid allergy, with most reports being case reports. Most reports involve non-systemic application of corticosteroids. Steroid hypersensitivity has been associated with type I IgE-mediated allergy including anaphylaxis. The overall prevalence of type I steroid hypersensitivity is estimated to be 0.3–0.5 %. Allergic contact dermatitis (ACD) is the most commonly reported non-immediate hypersensitivity reaction and usually follows topical CS application. Atopic dermatitis and stasis dermatitis of the lower extremities are risk factors for the development of ACD from topical CS. Patients can also develop hypersensitivity reactions to nasal, inhaled, oral, and parenteral CS. A close and detailed evaluation is required for the clinician to confirm the presence of a true hypersensitivity reaction to the suspected drug and choose the safest alternative. Choosing an alternative CS is not only paramount to the patient’s safety but also ameliorates the worry of developing an allergic, and potentially fatal, steroid hypersensitivity reaction. This evaluation becomes especially important in high-risk groups where steroids are a life-saving treatment. The assessment should be done when the patient’s underlying condition is in a quiescent state.     

Drug Desensitization in the Management of Hypersensitivity Reactions to Monoclonal Antibodies and Chemotherapy

Hypersensitivity reactions to monoclonal antibodies and chemotherapy, which may vary in severity from mild to life-threatening, can lead to their discontinuation and replacement by alternative agents that are often less effective, more toxic, and/or more expensive. Drug desensitization has emerged as the best treatment modality capable of allowing re-introduction of the hypersensitivity reaction-inducing medication in highly sensitized patients in need of first line therapies. In recent years, the availability of new anti-neoplastic drugs and therapeutic monoclonal antibodies has increased, as has the potential for hypersensitivity reactions. Development of desensitization protocols for these new medications requires a careful assessment of the potential risks and benefits. The purposes of this review are to provide an overview of the presentation of hypersensitivity reactions amenable to desensitization and to increase awareness of the indications for and outcomes of desensitization protocols. Rapid drug desensitization has proven to be a safe and effective way of administering first line therapy to patients with hypersensitivity reactions, providing an extremely powerful treatment modality for patients for whom alternative drugs are deemed unacceptable. Rapid drug desensitization protocols should be administered only by highly trained allergists and nurses who have experience in determining which reactions are amenable to desensitization, and can identify high risk patients and provide them with appropriate care. Efforts should be made to increase awareness of the remarkable safety and efficacy of rapid drug desensitization among non-allergists, especially in the fields of oncology and rheumatology, so as to favor its universal application. Development of desensitization units to provide state-of-the-art care is possible only through coordinated teamwork.     

Cyclic AMP in Hypersensitivity Reactions

Phytohemagglutinin (PHA) was capable of inducing non-cytotoxic histamine release from human leucocytes. In the presence of deuterium oxide (D2O), PHA caused significantly greater histamine release. Dibutyryl cyclic AMP (d-cAMP) could enhance the histamine release in the presence of D2O although it was an inhibitor of the release if used alone. However, a beta agonist, isoproterenol, which increases intracellular level of cAMP was inhibitory with or without D2O. These data ask the question about dual effect of cAMP and suggest the possibility of different polls of cAMP in the target cells.