Drug Hypersensitivity and Anaphylaxis in Cancer and Chronic Inflammatory Diseases: The Role of Desensitizations

Abstract

Drug allergy is a rising problem in the twenty-first century which affects all populations and races, children, and adults, and for which the recognition, diagnosis, management, and treatment is still not well standardized. Classical and new chemotherapy drugs, monoclonal antibodies (MoAbs), and small molecules to treat cancer and chronic inflammatory diseases are aimed at improving quality of life and life expectancy of patients, but an increasing number of reactions including anaphylaxis precludes their use in targeted populations. Women are more affected by drug allergy and up to 27% of women with ovarian and breast cancer develop carboplatin allergy after multiple cycles of treatment. Carriers of BRCA genes develop drug allergy after fewer exposures and can present with severe reactions, including anaphylaxis. Atopic patients are at increased risk for chemotherapy and MoAbs drug allergy and the current patterns of treatment with recurrent and intermittent drug exposures may favor the development of drug allergies. To overcome drug allergy, desensitization has been developed, a novel approach which provides a unique opportunity to protect against anaphylaxis and to improve clinical outcomes. There is evidence that inhibitory mechanisms blocking IgE/antigen mast cell activation are active during desensitization, enhancing safety. Whether desensitization modulates drug allergic and anaphylactic responses facilitating tolerance is currently being investigated. This review provides insight into the current knowledge of drug allergy and anaphylaxis to cancer and chronic inflammatory diseases drugs, the mechanisms of drug desensitization and its applications to personalized medicine.

The soluble isoform of human FcɛRI is an endogenous inhibitor of IgE‐mediated mast cell responses

“…Therefore, we further investigated the signaling requirements for sFcεRI production with MCs from FcεRIα‐humanized mice. IgE‐mediated activation of MCs triggers a series of FcεRI signaling events starting with phosphorylation of ITAM domains by Src kinases, specifically Lyn and Syk, followed by receptor internalization and degradation by the endo/lysosomal compartment . Consequently, we tested the effects of the Src inhibitor PP2 and the endo/lysosomal acidification inhibitor chloroquine on the production of sFcεRI by MCs.…”

Desensitization therapy using ‘Mariana Castells’ protocol in a patient with multiple autoimmune disorders- does it work?

“…Hypersensitivity to drug therapy has remained a significant control factor in therapeutic approaches towards controlling various infectious diseases. Numerous papers have shown the effect of hypersensitivity on the quality of life for these patients [7]. However, despite the success of rapid desensitization, the cellular and molecular inhibitory mechanisms are incompletely understood [1].…”

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

“…Although the specific treatment of DHRs is avoiding the drug involved and those chemically related, desensitization is nowadays a frequent option . In that sense, rapid drug desensitization is a cost‐effective technique that activates inhibitory mechanisms and permits patients to receive the first‐choice medications to which they are allergic …”

“…Although the specific treatment of DHRs is avoiding the drug involved and those chemically related, desensitization is nowadays a frequent option . In that sense, rapid drug desensitization is a cost‐effective technique that activates inhibitory mechanisms and permits patients to receive the first‐choice medications to which they are allergic Research needs for DHRs The prevalence and incidence of DHRs Underlying mechanisms of DHRs The most adequate classification of DHRs Definition of endotypes and biomarker identification The most accurate diagnostic approach: i Skin test standardization, sensitivity, specificity, and predictive values for most drugs ii A standardized protocol for performing drug provocation test iii The role of in vitro tests for diagnosis The mechanism of inhibition in rapid drug desensitization procedure …”

“…148 Although the specific treatment of DHRs is avoiding the drug involved and those chemically related, desensitization is nowadays a frequent option. [149][150][151] In that sense, rapid drug desensitization is a cost-effective technique that activates inhibitory mechanisms and permits patients to receive the first-choice medications to which they are allergic. 149,150 Research needs for DHRs • Could nasal cytology be used in the study of chronic rhinitis, especially for the differential diagnosis of chronic rhinitis?…”