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.

An Analysis of Factors Predicting Post-Traumatic Stress Disorder and Grief Following Comrade Loss.

This study explored how "inhibiting factors" associated with military-bereavement impact combatants' psychological sequelae following comrade loss. One hundred six eligible Israeli combat male-soldiers completed the Texas-Revised-Inventory of Grief, the post-traumatic-stress-disorder symptoms scale (PSS), the Male Role Norms Scale, the Social Acknowledgment Questionnaire, and a scale assessing Military Encouragement to Grieve (MEG-8). Time since loss had no impact on soldiers' levels of PSS or prolonged grief. Regression analysis indicated that higher masculinity-perception and disapproval from the family predicated higher PSS, above and beyond grief. Conversely, lower disapproval from the family, and higher disapproval from the general community, predicted higher grief, above and beyond PSS. Also, military encouragement significantly mediated the positive relationship between masculinity and sense of social-recognition. The results show how inhibiting factors contribute differently to the perpetuation of PSS and grief. This interplay sheds light on soldiers' "external" and "internal" loss processes of traumatic bereavement. The practical implications to treatment are also discussed.