Twenty years ago, molecular biology transitioned from predominantly studying genes as isolated elements to viewing them as part of complex modules, giving rise to the field of systems biology. This transition was made possible by technological advances that allowed to simultaneously measure the expression levels of thousands of genes in a single experiment and drove a shift toward analyses identifying gene sets, modules, and pathways involved in a biological process of interest. Today we are excitingly facing a similar turning point in cell biology, where single‐cell technologies have enabled us to approach cells as cellular modules.
BackgroundThe 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.ObjectivesWe 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.MethodsHerein, 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.ResultsA 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.ConclusionCurrent 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.
Crystal deposit disease is a rare disorder with benign dense soft tissue calcium containing accumulations presenting as pseudogout or tumoral calcinosis. It rarely affects the head and neck region and even less to the petrous bone. We describe a case of para-articular tumoral calcinosis involving the external auditory canal wall in close proximity to the temporomandibular joint with extension towards the middle cranial fossa floor in a 73-year-old man presenting with otalgia and progressing mixed hearing loss. Subtotal petrosectomy with obliteration of the middle ear and mastoid was done with complete removal of the lesion. We discuss the course, treatment and final pathology with possible explanations for the pathophysiology in this particular case. Although tumoral calcinosis is uncommon, this entity should be considered in the differential diagnosis when an osteogenic temporal lesion is seen on computed tomography or magnetic resonance imaging. The treatment for this benign tumor includes complete excision of the lesion in symptomatic cases. Proper evaluation including anamnesis of the family history and previous trauma as well as serology should be done. The exact etiology and classification of crystal deposit diseases require further study.
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