S6278 Hemophagocytic Lymphohistiocytosis With Gastric and Duodenal Ulcers as the First Manifestation of Diffuse Large B-Cell Lymphoma

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome that causes pancytopenia and multiorgan damage. We present a young man with HLH who presented with gastrointestinal (GI) bleeding and was subsequently diagnosed with diffuse large B-cell lymphoma (DLBCL). Case Description/Methods: A 27-year-old man with a history of biopsy-proven HLH on dexamethasone and etoposide (last dose 2 weeks ago), presented to an outside hospital with 2 weeks of nausea, vomiting, and a 10-pound weight loss. He was tachycardic to 120 bpm but otherwise vitals were stable. Blood work revealed a white blood cell count of 2.94 × 10⁹/L, hemoglobin 8.1 g/dL, platelet 89 × 10⁹/L, and a cholestatic liver enzyme pattern with direct hyperbilirubinemia. He developed a massive upper GI bleed from gastric and duodenal ulcers, requiring embolization of the left gastric and gastroduodenal arteries, and a fever to 38.8°C without clear infection, prompting restart of HLH therapy with dexamethasone, anakinra, and ruxolitinib. After requiring 42 units of packed red blood cells over 10 days, he was transferred to our center. Ruxolitinib was discontinued due to worsening pancytopenia, while dexamethasone and anakinra continued. He developed hemorrhagic shock from recurrent bleeding ulcers located in the gastric cardia, body, fundus, and third part of duodenum. These lesions proved refractory to endoscopic clips, hemospray, and epinephrine injections. His gastrin level was 13 pg/mL, ferritin was 40,000 ng/mL, and soluble IL-2 receptor was 4000 pg/mL. In the context of ongoing cytopenia and hepatosplenomegaly, he fulfilled HLH-2024 criteria. A pectoral lymph node biopsy confirmed DLBCL, and he was started on R-CHOP chemotherapy. Bleeding resolved, and follow-up upper endoscopy at 2 weeks showed non-bleeding ulcers, with near-complete healing at 4 months. Discussion: HLH is driven by dysregulated immune activation, often secondary to malignancy in adults, with lymphoma accounting for up to 76% of cases. Peptic ulcers are an uncommon manifestation, but the cytokine storm in HLH may lead to mucosal injury and ischemia. Although previously described with Epstein Barr virus-associated HLH, to our knowledge, this is the first case of DLBCL-associated HLH with ulcers in atypical locations. Recognition of HLH in such presentations is critical, as prompt treatment of the underlying malignancy led to ulcer resolution. This case underscores the importance of considering HLH in refractory or atypical ulcer disease.