非EB病毒病原体所致感染相关噬血细胞综合征的临床特征及预后

OBJECTIVE: To explore the clinical characteristics and outcomes of patients with non-Epstein-Barr virus (EBV) infection-associated hemophagocytic lymphohistiocytosis (IAHLH). METHODS: Clinical data of 48 patients diagnosed with non-EBV IAHLH in Beijing Friendship Hospital from January 2015 to March 2021 were collected, and the clinical characteristics, treatment, curative effect and prognosis of the patients were analyzed retrospectively. RESULTS: This study included 48 patients, 28 males and 20 females, with a median（range）age of 34.5（2–74）years. Pathogens that cause IAHLH were as follows: virus（16 cases, 33.3％）, bacteria（17 cases, 35.4％）, parasitic agents（13 cases, 27.1％）, and fungi（2 cases, 4.2％）. The median time from onset to diagnosis of hemophagocytic syndrome（HLH）was 40（10–160）days. The median（range）time duration from prodrome to the definite diagnosis of IAHLH was 67（23–270）days. The clinical characteristics were fever（48 cases, 100％）, splenomegaly（34 cases, 70.8％）, cytopenia（38 cases, 79.1％）, elevated ferritin（45 cases, 93.8％）, elevated fasting triglyceride levels（7 cases, 14.6％）, hypofibrinogenemia（17 cases, 35.4％）, decrease natural killer cell activity（26 in 44 cases, 59.1％）, and elevated sCD25（35 cases, 74.5％）. Twenty-five patients（52.1％）had adenopathy. Once a certain pathogen was identified as the causative factor of hemophagocytic lymphohistiocytosis（HLH）, cytotoxic agents and glucocorticoids were withdrawn, and specific pathogen-directed treatment was initiated. After treatment, 36 cases（75.0％）achieved complete response, and 14 of 15 patients（93.3％）with parasitic and fungal HLH got a response; however, the response rate of patient with bacterial and viral HLH was only 66.7％（22 of 33 patients）. The estimated 5-year overall survival rate was 72.3％（95％ CI 50.3％–69.8％）. The adverse prognostic factors were total bilirubin over the upper limit of normal（OR＝20.0, 95％ CI 1.1–378.3, P＝0.046）and pathogenic infection not fully controlled（OR＝19.9, 95％ CI 2.9–134.5, P＝0.002）. CONCLUSION: Non-EBV IAHLH has a good prognosis. When diagnosed, cytotoxic agents and glucocorticoids should be tapered off, and pathogen-targeted therapy should be critically administered to clear the triggering infection.