Drug Hypersensitivity and Desensitizations: Mechanisms and New Approaches

Abstract

Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS). DS induces a temporary hyporesponsive state by incremental escalation of sub-optimal doses of the offending drug. In vitro models have shown evidence that IgE desensitization is an antigen-specific process which blocks calcium flux, impacts antigen/IgE/FcεRI complex internalization and prevents the acute and late phase reactions as well as mast cell mediator release. Through a “bench to bedside” approach, in vitro desensitization models help elucidate the molecular pathways involved in DS, providing new insights to improved desensitization protocols for all patients. The aim of this review is to summarize up to date information on the drug HSRs, the IgE mediated mechanisms of desensitization, and their clinical applications.

Recent developments and highlights in drug hypersensitivity

“…Nowadays, desensitization is the only treatment for DHRs and is critical especially when patients need first‐line therapy . This procedure allows the safe reintroduction of the drugs independently of the mechanisms . New nondilution, or 1‐solution, desensitization protocols are safe and effective for platinum agents' re‐administration .…”

“…23,[174][175][176][177] This procedure allows the safe reintroduction of the drugs independently of the mechanisms. 178 New nondilution, or 1-solution, desensitization protocols are safe and effective for platinum agents' re-administration. 175,179,180 Besides, 12-and 16-step rapid desensitization protocols are effective and safe for biologicals and antineoplastic agents.…”

“…184 Moreover, long premedication protocols increase costs, side effects and length of hospital stay. 185 In general, desensitization has been shown to be useful to maintain the first election treatment in multiple groups of drugs, 67 including anticonvulsants, 13 antituberculosis medication, 186,187 antibiotics, [188][189][190] NSAIDs 96,183,191,192 and others, 193,194 in both IR 96,174,178,188,191,194 and NIR, 96,186,187,190,193 and even in paediatric population 86,188,192 and patients with multiple autoimmune disorders. 189…”

Hypersensitivity reaction to certolizumab pegol in a patient affected by psoriatic arthritis

“…HSRs can occur after the first exposure or multiple exposures (Tétu, Hamelin, Moguelet, Barbaud, & Soria, ). Underlying pathogenic mechanism is not fully understood (de Las Vecillas Sánchez, Alenazy, Garcia‐Neuer, & Castells, ; Tétu et al, ). Although the Gell and Coombs classification has been useful to provide mechanistic understanding of HSRs, the classification and diagnosis of reactions to mAbs have provided a challenge (Isabwe, Garcia Neuer, de Las Vecillas Sanchez, Lynch, & Castells, ).…”

“…Although the Gell and Coombs classification has been useful to provide mechanistic understanding of HSRs, the classification and diagnosis of reactions to mAbs have provided a challenge (Isabwe, Garcia Neuer, de Las Vecillas Sanchez, Lynch, & Castells, ). HSRs to mAbs include acute infusion reactions (AIR) induced by cytokine release, besides Type I, Type III, and Type IV reactions (de Las Vecillas Sánchez et al, ; Tétu et al, ). The clinical presentation of mAbs HSRs, especially if immediate such as Type I HSR and AIR, may overlap and diagnosis and management protocols have not been standardized (Isabwe et al, ).…”