Gluten Gambit: A Case of Hemophagocytic Lymphohistiocytic Syndrome and Enteropathy-Associated T-cell Lymphoma in a Patient with Refractory Celiac Disease

Abstract

Purpose: Hemophagocytic lymphohistiocytic syndrome (HLH) is an uncommon syndrome characterized by overactive histocytes induced by disorders such as T-cell lymphoma. We describe a rare case of HLH in enteropathy-associated T-cell lymphoma (EATL) and refractory celiac disease (RCD). Methods: A 70-year-old woman with a 4-year history of celiac disease was transferred to our tertiary care hospital from a community hospital for RCD unresponsive to strict gluten-free diet and one-month of prednisone therapy. She initially presented with a 4-month history of 25 lbs weight loss and diarrhea. Abdominal CT demonstrated only small bowel inflammation. Multiple esophagogastroduodenoscopies and colonoscopies were optically normal. She was diagnosed with RCD type II based on duodenal and jejunal biopsies, showing severe villous blunting and intraepithelial lymphoplasmacytic infiltration. Upon arrival to our institution, the patient was tachycardiac, hypotensive, with ongoing melena and hematochezia. She had intermittent gastrointestinal (GI) bleeding prior to her transfer without an obvious source identified. She also experienced intermittent fevers and was treated empirically with broad-spectrum antibiotics. She was diagnosed with HLH after developing pancytopenia, low fibrinogen, elevated ferritin and hemophagocytosis on her bone marrow biopsy. She had no response to HLH treatment with dexamethasone, cyclosporin, anakinra, etoposide or intravenous immunoglobulin. Given her clinical picture suggested EATL, her previous biopsies were reviewed by a lymphoma pathologist. He revised the final diagnosis to type I EATL based on the high proportion of large T cells, infiltrating the lamina propria, and the abnormal T cell marker profile (positive CD3, 7, 30; negative CD5, 56). Unfortunately, the patient subsequently died from a massive small bowel GI bleed. Conclusion: To our knowledge, this is the first known case of HLH associated with localized EATL and RCD. Only 7 cases of HLH with EATL have been reported but none previously had documented RCD. We aim to highlight HLH as a rare but important condition that gastroenterologists must be aware of in their patients with RCD and EATL. Although, in all previous reported cases, HLH presented in the context of advanced EATL with metastasis, this case illustrates the importance of prompt referral as it is the first HLH case that presented with non-advanced EATL and facilitated early HLH therapy. Lastly, this case serves as a reminder that when suspicion is high and EATL is not seen on imaging, the clinician must remember that EATL is a histological diagnosis, requiring tissue and experienced pathology opinion.