Table_1_Hemophagocytic Lymphohistiocytosis Secondary to Disseminated Histoplasmosis in HIV Seronegative Patients: A Case Report and Review of the Literature.xlsx

Hemophagocytic lymphohistiocytosis (HLH) secondary to Histoplasma capsulatum infection is a rare disorder with poor outcome. Although cases of patients with human immunodeficiency virus (HIV) infection have been well documented, little study has reported in the setting of HIV seronegative. In this study, we report a case of HLH secondary to histoplasmosis in an immunocompetent patient in China and review all cases on this situation. The objective was to summary their epidemiology, clinical characteristics, diagnostic approaches, and therapeutic response. A 46-year-old male cooker presented fever, fatigue, anorexia, and weight loss. Bone marrow examination suggest fungus organism and hemophagocytosis, and further, bone marrow culture confirmed Histoplasma capsulatum, as the etiology of HLH. The patient was successfully treated. We reviewed a total of the 13 cases (including our patient) of HLH with histoplasmosis in intact immunology patients. Twelve of the 13 patients are from endemic areas, and nine of the 12 cases are from emerging endemic areas, India and China. Three patients had sojourn history may related to the disease onset. Twelve of the 13 cases fulfilled HLH-2004 criteria. The diagnosis of Histoplasma capsulatum infection was established by histological examination (13 of 13), culture (4 of 13), molecular method (2 of 13), and antigen or serological assays (2 of 13). Amphotericin B, posaconazole, and itraconazole show favorable activity against the fungus, seven patients used specific treatment for HLH. For analysis of outcomes, two of the 13 patients died. Our present case report and literature review show that disseminated Histoplasma capsulatum infection with HLH in the immunocompetent population becomes increasingly common in emerging endemic areas and have high mortality. It is necessary for clinicians to improve the awareness of disease diagnosis due to the atypical population and disease presentation. Timely diagnosis and early use of antifungal agents will lead to favorable prognosis.

嗜血细胞淋巴组织细胞增生症（HLH）继发于球孢子菌感染是一种罕见病症，其预后不佳。尽管关于人类免疫缺陷病毒（HIV）感染者病例的记录已相当详尽，但在HIV血清阴性人群中的研究却鲜有报道。在本研究中，我们报告了一例中国免疫正常患者因球孢子菌感染引起的HLH病例，并对该情况下的所有病例进行了综述。研究旨在总结其流行病学、临床特征、诊断方法和治疗反应。一名46岁的男性厨师出现发热、疲劳、厌食和体重下降等症状。骨髓检查提示真菌病原体和噬血细胞现象，进一步骨髓培养确认球孢子菌为HLH的病因。患者得到了成功治疗。我们回顾了包括我们的患者在内的13例HLH伴球孢子菌感染的完整免疫学患者病例。其中12例来自流行区，9例来自新流行区，包括印度和中国。三名患者有短暂居留史，可能与疾病发作有关。13例中有12例符合HLH-2004标准。球孢子菌感染的诊断通过组织学检查（13/13）、培养（4/13）、分子方法（2/13）以及抗原或血清学检测（2/13）确立。两性霉素B、泊沙康唑和伊曲康唑对真菌具有良好活性，七名患者使用了针对HLH的特异性治疗。在分析结果时，13名患者中有两名死亡。我们的现例报告和文献综述表明，免疫正常人群中的播散性球孢子菌感染伴HLH在新流行区日益普遍，且死亡率高。鉴于不典型人群和疾病表现，临床医生有必要提高对疾病诊断的意识。及时诊断和早期使用抗真菌药物将有助于改善预后。