D2.440 - From Steroid Dependence to Remission: Anti–IL-5 Therapy in Gastrointestinal Hypereosinophilic Syndrome

Hypereosinophilic syndrome (HES) with gastrointestinal involvement is a rare and frequently underdiagnosed condition that requires extensive etiological evaluation and exclusion of secondary causes. Corticosteroid dependence is common and contributes substantially to morbidity and treatment-related adverse effects. Mepolizumab, an anti–IL-5 monoclonal antibody approved for selected HES subgroups, has emerged as an effective therapeutic option, enabling disease control and corticosteroid withdrawal.

We report a 35-year-old female patient that was living in Germany since she was 25 years-old. She was hospitalized due to diarrhea, nausea and vomiting during last year. Clinical and laboratory work-up revealed marked blood eosinophilia and, parasitic infections, inflammatory bowel disease, systemic mastocytosis and malignancy were excluded.

Due to suspected eosinophilic enteropathy, she began an elimination diet of the six foods most frequently implicated: milk, egg, wheat, soya, nuts and seafood, with no improvement. At age 30, already in Portugal treated with prednisolone 1 mg/kg/day by Gastroenterology department, was referred to Immunoallergology department. Extensive food skin testing was performed and was negative.

Due to corticosteroid dependence, immunosuppressive drugs, azathioprine 100 mg and subsequently infliximab 10 mg/kg every 6 weeks, were introduced. However, in multiple attempts to reduce corticosteroid therapy, the symptoms recurred, requiring hospitalization.

Further diagnostic workup included upper gastrointestinal endoscopy showing erythematous antral gastropathy, bulbitis, and delayed gastric emptying; colonoscopy was unremarkable, and entero-MRI demonstrated minimal ascites. Persistent hypereosinophilia was documented over several years, with eosinophil counts ranging from 1,400 to 3,300 cells/µL. The FIP1L1–PDGFRA fusion gene was negative. A diagnosis of hypereosinophilic syndrome with gastrointestinal involvement was established.

In June 2025, treatment with mepolizumab 300 mg subcutaneously every four weeks was initiated, resulting in rapid clinical remission and successful gradual tapering, with complete discontinuation of corticosteroids by August 2025. The patient remained asymptomatic, with normalization of eosinophil counts (100 cells/µL) and no abnormalities on follow-up MRI.

We present a case of severe gastrointestinal HES, dependent on corticosteroid and refractory to previous immunosuppressive therapy. The use of mepolizumab demonstrated marked clinical efficacy, allowing sustained control until complete discontinuation of corticosteroids.