Hemophagocytic Lymphohistiocytosis in Patients with Inflammatory Bowel Diseases: A Systematic Review

Tingwei Lan¹Qinhuan Luo¹Xiaojuan Guo²Xuan Jiang^3*

• ¹School of Medicine, Tsinghua Medicine, Tsinghua University, Beijing, China
• ²Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, Beijing, China
• ³Department of Gastroenterology.Beijing Tsinghua Changgeng Hospital, Tsinghua University, Beijing, China

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening hyperinflammatory syndrome. Patients with inflammatory bowel diseases (IBD) appear to be at increased risk of developing HLH, potentially due to the use of immunosuppressive therapies. However, the epidemiology, clinical characteristics, management strategies, and outcomes of HLH in this population remain poorly understood. Here we performed a systematic review of the literature (PubMed, Web of Science and Embase). 97 secondary HLH (sHLH) and 18 HLH cases with genetic mutations were identified. Among IBD patients, sHLH predominantly occurred in males with Crohn's disease, with a median age of 33.5 years and a median disease duration of 4 years. The majority of these patients were receiving thiopurines for IBD management and were in clinical remission at the onset of sHLH. The most common trigger was infection, particularly CMV and EBV, followed by lymphoma. The overall survival rate for sHLH was 62.50%. Most patients successfully resumed IBD maintenance therapy within 5 months after the sHLH episode, with minimal complications and rare recurrence of IBD or HLH. We also identified older age, induced by lymphoma and currently not on biologics or thiopurines as potential factors associated with the sHLH mortality of IBD patients. Compared to those with sHLH, patients with primary HLH were younger, more often male, predominantly had CD, were less likely to be in remission despite biologic therapy, and had better prognosis with hematopoietic stem cell transplantation (HSCT). This study provides a comprehensive characterization of HLH in IBD patients, offering valuable insights to guide future research aimed at improving clinical outcomes in this unique population.