Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome
Authors: Limor Rubin, Aviv Talmon, Yaarit Ribak, Asa Kessler, Yossi Martin, Tal Keidar Haran, Oded Shamriz, Irit Adini, Yuval Tal
Journal: Front Immunol (2023)
Keywords: il-5 antibody, biotherapeutic agent, drug reaction with eosinophilia and systemic symptoms (dress), interleukin (il), monoclonal antibodies (mabs)
MeSH terms: Drug Hypersensitivity Syndrome / diagnosis, Drug Hypersensitivity Syndrome / drug therapy, Drug Hypersensitivity Syndrome / etiology, Eosinophilia / complications, Eosinophilia / drug therapy, Interleukin-5 / metabolism, Review, Anti-Bacterial Agents / therapeutic use, COVID-19 / complications, Female, Humans, Male, Middle Aged, Prospective Studies, Anti-Bacterial Agents, Interleukin-5

Background:
The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe hypersensitivity reaction. Up-to-date treatment is based on withdrawal of medication, supportive care, and immunosuppression using high-dose corticosteroid (CS) therapy. However, evidence-based data are lacking regarding second-line therapy for steroid-resistant or steroid-dependent patients.
Objectives:
We hypothesize that the interleukin (IL)-5 axis plays a critical role in the pathophysiology of DRESS; hence, inhibition of this signaling pathway could offer a potential therapy for steroid-dependent and/or steroid-resistant cases, and it may offer an alternative to CS therapy in certain patients more prone to CS toxicity.
Methods:
Herein, we collected worldwide data on DRESS cases treated with biological agents targeting the IL-5 axis. We reviewed all cases indexed in PubMed up to October 2022 and performed a total analysis including our center experience with two additional novel cases.
Results:
A review of the literature yielded 14 patients with DRESS who were treated with biological agents targeting the IL-5 axis as well as our two new cases. Reported patients are characterized by a female-to-male ratio of 1:1 and a mean age of 51.8 (17-87) years. The DRESS-inducing drugs, as expected from the prospective RegiSCAR study, were mostly antibiotics (7/16), as follows: vancomycin, trimethoprim-sulfamethoxazole, ciprofloxacin, piperacillin-tazobactam, and cefepime. DRESS patients were treated with anti-IL-5 agents (mepolizumab and reslizumab) or anti-IL-5 receptor (IL-5R) biologics (benralizumab). All patients have clinically improved under anti-IL-5/IL-5R biologics. Multiple doses of mepolizumab were needed to achieve clinical resolution, whereas a single dose of benralizumab was often sufficient. Relapse was noted in one patient receiving benralizumab treatment. One patient receiving benralizumab had a fatal outcome, although mortality was probably related to massive bleeding and cardiac arrest due to coronavirus disease 2019 (COVID-19) infection.
Conclusion:
Current treatment guidelines for DRESS are based on case reports and expert opinion. Understanding the central role of eosinophils in DRESS pathogenicity emphasizes the need for future implementation of IL-5 axis blockade as steroid-sparing agents, potential therapy to steroid-resistant cases, and perhaps an alternative to CS treatment in certain DRESS patients more prone to CS toxicity.