Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, 03766, USA.
Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, MI, USA.
Dig Dis Sci. 2021 Mar;66(3):843-854. doi: 10.1007/s10620-020-06252-z. Epub 2020 Apr 16.
Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive syndrome of excessive cytokine requiring prompt recognition and aggressive therapy.
We aimed to systematically characterize HLH in moderate-to-severe inflammatory bowel disease (IBD).
We performed a systematic review of the literature (PubMED; EMBASE) and FDA Adverse Event Reporting System in accordance with the PRISMA statement. Use of biologics was used as a surrogate definition for disease severity (consistent with usual and contemporary clinical management), to enable identification of rare HLH cases with the highest fidelity.
58 cases of HLH occurring in IBD patients are known (mean age: 26.0 years, 70% male, 83% with Crohn's disease, mean disease duration 7.0 years). 34.5% of patients were undergoing induction therapy at HLH diagnosis. All cases occurred on patients exposed to anti-TNF agents, but cases with anti-integrin or anti-IL-12/23 exposure were reported. 2/3 of cases did not report prior AZA/6MP exposure. Underlying opportunistic infection or lymphoma was found in > 80% of cases. Survival was 70% if promptly recognized and treated. Five patients restarted biologics after HLH resolved, and one patient developed recurrent HLH.
HLH is rare among IBD patients exposed to biologic therapy. Most cases had an identifiable infection or malignancy at the time of diagnosis as well as history of immunomodulator use. Risk factors may include younger age, male gender, presence of Crohn's disease, and induction phase of treatment. Our study is not intended to assess risk of HLH with specific IBD therapies.
噬血细胞性淋巴组织细胞增生症（HLH）是一种罕见且侵袭性的细胞因子过度分泌综合征，需要及时识别并进行积极治疗。
我们旨在系统性地描述中重度炎症性肠病（IBD）患者中的 HLH。
我们根据 PRISMA 声明对文献（PubMED；EMBASE）和 FDA 不良事件报告系统进行了系统性回顾。生物制剂的使用被用作疾病严重程度的替代定义（与常规和当代临床管理一致），以确保以最高的准确性识别出具有最高 HLH 风险的罕见病例。
已知有 58 例 IBD 患者发生 HLH（平均年龄：26.0 岁，男性占 70%，83%为克罗恩病，平均病程 7.0 年）。34.5%的患者在 HLH 诊断时正在接受诱导治疗。所有病例均发生在接受抗 TNF 治疗的患者中，但也有报告称抗整合素或抗 IL-12/23 暴露的病例。2/3的病例未报告先前使用 AZA/6MP。超过 80%的病例存在潜在的机会性感染或淋巴瘤。如果及时识别和治疗，存活率为 70%。5 例患者在 HLH 缓解后重新开始使用生物制剂，1 例患者出现复发性 HLH。
在接受生物治疗的 IBD 患者中，HLH 较为罕见。大多数病例在诊断时都有明确的感染或恶性肿瘤病史，以及免疫调节剂的使用史。危险因素可能包括年龄较小、男性、存在克罗恩病和治疗诱导期。我们的研究并非旨在评估特定 IBD 治疗方案的 HLH 风险。
