title: Cryptococcal meningitis in HIV-negative patients with systemic connective tissue diseases.
abstract: BACKGROUND
  Cryptococcal meningitis (CM) is a rare condition in non-HIV patients. The clinical manifestations in patients with systemic lupus erythematosus (SLE) are often confused with immunological activity, resulting in delayed diagnosis.
  
  
  OBJECTIVE
  We describe the natural history and outcome of eight HIV-negative patients with SLE and confirmed CM.
  
  
  RESULTS
  Mean age at the time of infection was 30·2 years (20-42). Mean dose of prednisone was 38·3 ± 13 mg/day and of azathioprine was 95 ± 37 mg/day. The most common clinical manifestation was headache with nausea or vomit (75%), followed by altered sensorium (50%), fever (50%), cranial nerve deficits (37%), or seizures (25%). Mean time between symptoms onset and diagnosis was 19 days (6-56). All patients had low lymphocyte cell counts (504 ± 229 cells/μl) and low CD4+ cell counts (113·2 ± 59·2 cells/μl). Active SLE assessed by a systemic lupus erythematosus disease activity index (SLEDAI) score ≧4 was found in 83% patients at the time of the diagnosis and 87% had renal involvement. The positivity of cryptococcal antigen, India ink stain, and culture in the cerebrospinal fluid (CSF) was 90, 70, and 50%, respectively. Magnetic resonance was abnormal in 90% of the patients. Higher titers of cryptococcal antigen were suggestive of worse outcome and increased hospital stay. After a mean follow-up of 4·9 years, one patient had a relapse of the CM, associated with persistent low CD4+ cell counts.
  
  
  CONCLUSIONS
  Cryptococcal meningitis in patients with SLE was associated with severe delay in diagnosis and profound lymphopenia. Follow-up should include CD4+ cell counts, and maintenance treatment with fluconazole should be continued until lymphopenia resolution.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Gonzalez-Duarte
authors.forename: Maria Del Mar
authors.initials: Mdel M
authors.lastname: Saniger-Alba
authors.forename: Jesús
authors.initials: J
authors.lastname: Higuera-Calleja
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000175:diagnosis*; D008297:Male; D016919:Meningitis, Cryptococcal / Q000150:complications* / Q000175:diagnosis*; D012189:Retrospective Studies; D055815:Young Adult
keywords: Central nervous system infections,; Cryptococcal meningitis,; Cryptococcosis in HIV-negative patients,; Fungal infections; Systemic connective tissue diseases,; Systemic lupus erythematosus,