title: Causes, clinical symptoms, and outcomes of infectious diseases associated with hemophagocytic lymphohistiocytosis in Taiwanese adults.
abstract: BACKGROUND
  Hemophagocytic lymphohistiocytosis (HLH) is an uncommon but a potentially life-threatening condition. Few systematic reviews have been published on the clinical manifestations, causes, and indicators for prognosis of HLH caused by infections.
  
  
  METHODS
  We retrospectively reviewed the medical records of patients diagnosed with HLH documented by bone marrow study at a teaching hospital between 2000 and 2007. HLH was defined according to the HLH-2004 diagnostic guidelines, which include fever; splenomegaly; cytopenia; hypertriglyceridemia; hypofibrinogenemia; and hemophagocytosis evident on pathological examination of bone marrow, spleen, or lymph node tissue; low or absent natural killer cell activity; hyperferritinemia; and high serum levels of soluble CD25. The demographic characteristics, clinical presentations, laboratory results, and final outcomes were recorded. The cause of HLH was diagnosed by microbiological, pathological, serological, and molecular biological methods.
  
  
  RESULTS
  Among the studied patients, 66 had HLH because of noninfectious causes and 30 because of infections. Compared with patients with HLH related to noninfectious causes, those with HLH related to infections had lower mortality (70% vs. 47%, p=0.03). The most common causative pathogens causing HLH were virus (41%), mycobacteria (23%), bacteria (23%), and fungi (13%), in that order of frequency. Clinical presentations of HLH were variable and included fever (90%), tachypnea (83%), tachycardia (80%), hepatosplenomegaly (40%), lymphadenopathy (27%), and altered consciousness (23%). Laboratory findings revealed thrombocytopenia in 93%, hyperferritinemia in 90%, elevated serum lactate dehydrogenase levels in 80%, anemia in 67%, and leukopenia in 60% of the patients. Fourteen patients (47%) died. In multivariate analysis, age more than 50 years (p=0.05; odds ratio [OR], 3.46; 95% confidence interval [CI], 1.00-15.73), fever not subsiding within 3 days of diagnosing HLH (p=0.003; OR, 2.38; 95% CI, 1.21-11.25), and occurrence of disseminated intravascular coagulation as a complication (p=0.009; OR, 3.22; 95% CI, 1.68-10.01) were found to be statistically significant indicators of mortality in patients with HLH.
  
  
  CONCLUSIONS
  The infectious diseases associated with HLH were diverse and resulted in a high mortality rate. Cases in which the patients were aged more than 50 years, developed DIC, and had persistent fever even after 3 days of being diagnosed with HLH showed poor prognosis.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Tseng
authors.forename: Wang-Huei
authors.initials: WH
authors.lastname: Sheng
authors.forename: Bo-Han
authors.initials: BH
authors.lastname: Lin
authors.forename: Chung-Wu
authors.initials: CW
authors.lastname: Lin
authors.forename: Jann-Tay
authors.initials: JT
authors.lastname: Wang
authors.forename: Yee-Chun
authors.initials: YC
authors.lastname: Chen
authors.forename: Shan-Chwen
authors.initials: SC
authors.lastname: Chang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow; D003141:Communicable Diseases / Q000175:diagnosis* / Q000209:etiology; D003710:Demography; D005260:Female; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications* / Q000175:diagnosis / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D013624:Taiwan; D014777:Virus Diseases / Q000175:diagnosis* / Q000209:etiology