Abstract Introduction Severe eosinophilic asthma is a challenging phenotype marked by persistent eosinophilic inflammation, frequent exacerbations, and poor response to conventional therapy. Management becomes more complex when eosinophilic inflammation extends beyond the airways. We present a case of a young woman with refractory eosinophilic asthma, eosinophilic fasciitis, and traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) who demonstrated systemic improvement with mepolizumab (Nucala), underscoring its potential therapeutic value beyond the lungs. Case Report A 37-year-old non-smoking woman with a medical history notable for TUGSE, eosinophilic fasciitis, and asthma presented with poorly controlled asthma and persistent peripheral eosinophilia. Tuberculosis screening revealed a positive PPD but negative QuantiFERON test, without evidence of active infection. Her asthma, initially classified as moderate persistent, was reclassified as severe persistent due to frequent exacerbations, high symptom burden, and inadequate response to multiple therapies, including high-dose inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), long-acting muscarinic antagonist (LAMA), and prolonged courses of oral corticosteroids. Laboratory evaluation consistently demonstrated elevated eosinophil counts. Despite optimized inhaled and systemic therapy, she remained symptomatic and highly dependent on oral corticosteroids. The concurrence of refractory asthma, TUGSE, and eosinophilic fasciitis suggested a systemic eosinophilic disorder. Given multi-organ involvement and poor response to standard therapy, targeted biologic therapy against interleukin-5 (IL-5) with mepolizumab was initiated. Following treatment, the patient experienced marked improvement in asthma control, with resolution of nocturnal symptoms, reduced albuterol use, decreased prednisone requirement, and notable healing of oral ulcers associated with TUGSE. Discussion This case demonstrates the novel application of mepolizumab for systemic eosinophilic inflammation, specifically in TUGSE, and demonstrates that it may offer therapeutic benefits beyond the airways. By targeting IL-5 and limiting eosinophil activation and survival, mepolizumab can reduce inflammation in multiple tissues, including the skin, fascia, and oral mucosa. The resolution of TUGSE and improvement in eosinophilic fasciitis observed in this patient suggest that IL-5 inhibition may have broader applications in eosinophil-driven disorders. In addition to enhancing asthma control, mepolizumab allowed for reduced systemic corticosteroid use and alleviated extra-pulmonary manifestations. This case underscores the need to recognize eosinophilic disease as a systemic condition and highlights the value of a multidisciplinary, precision-medicine approach to optimize patient outcomes. This abstract is funded by: None
Umer et al. (Fri,) studied this question.