Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome.

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.

Diagnostic challenges of old diseases in the COVID-19 era: a report of two cases of carbamazepine-induced DRESS syndrome.

INTRODUCTION: A new MIS-C that develops after the acute stage of COVID-19 infection has recently been reported worldwide. Drug reaction with eosinophilia and systemic symptoms syndrome is a rare but potentially severe adverse drug-induced reaction most commonly associated with anticonvulsants. Due to variability in clinical presentation involving cutaneous and multiorgan systems, broad differential diagnosis, and lack of definitive diagnostic tests, diagnosis may be delayed. CASE REPORTS: The authors report 2 cases of pediatric patients who presented with fever, diffuse rash, and exposure to COVID-19 infection with suspected MIS-C. Both patients' medical histories revealed carbamazepine treatment for approximately 2 months. The diagnosis of DRESS syndrome was associated with the use of carbamazepine. CONCLUSIONS: Distinguishing between MIS-C and DRESS syndrome may be difficult due to similar clinical and laboratory features and the lack of definitive diagnostic tests for either condition. When encountering cases like the current report, it is important to consider DRESS syndrome for early diagnosis and medical intervention.

Generalized pustular figurate erythema: A newly delineated severe cutaneous drug reaction linked with hydroxychloroquine.

A severe cutaneous drug reaction resembling acute generalized exanthematous pustulosis resulting from ingestion of hydroxychloroquine has been documented. It is distinguishable by its longer incubation period, more varied morphology with initially urticarial and later targetoid and arcuate plaques, recalcitrance to therapy and longer duration. Given the anticipated surge in the use of hydroxychloroquine due to its reported benefits in those with coronavirus disease 2019, specific recognition of this entity is pivotal. We delineate it as generalized pustular figurate erythema.