Hemophagocytic Lymphohistiocytosis Triggered by HSV‑1 in a Patient with Refractory Crohn’s Disease After Long‑Term Sequential Immunosuppressive Therapy

Lingya Yao,1,2,* Hanxiao Tu,1,2,* Qian Cao1,21Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, People’s Republic of China; 2Inflammatory Bowel Disease Center, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian Cao, Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, People’s Republic of China, Email [email protected]: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of immune dysregulation. Here, we presented the case of a young male diagnosed with psoriasis and Crohn’s disease (CD), after multiple therapy failures, he started upadacitinib (UPA) in 2023. After induction and maintenance therapy, colonoscopy revealed suboptimal disease control. In November 2024, he was admitted to our hospital with fever and elevated liver enzymes, the final diagnosis was HSV-1-associated secondary HLH. After antiviral and hormonal treatment, the patient was discharged in stable condition. This case illustrates that HLH in such patients is rarely attributable to a single drug, rather, it results from the convergence of underlying CD, cumulative multi-agent immunosuppression, and an acute infectious trigger (HSV-1). Clinicians should maintain high vigilance for virus-associated HLH in heavily immunosuppressed IBD patients.Keywords: inflammatory bowel disease, hemophagocytic lymphohistiocytosis, herpes simplex virus, Jak kinase inhibitors