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Central nervous system histoplasmosis

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Opinion statement

Involvement of the central nervous system (CNS) is recognized clinically in 5% to 10% of patients with progressive disseminated histoplasmosis. The risk of developing CNS histoplasmosis is increased in individuals with impaired cellular immunity, but not all patients with this condition are immunocompromised. Clinical syndromes include chronic meningitis, focal parenchymal lesions of the brain or spinal cord, stroke due to infected emboli, and diffuse encephalitis. CNS histoplasmosis should be considered in any patient with one of these syndromes who has resided in an area endemic for histoplasmosis. A high index of suspicion is necessary when extraneural signs and symptoms are absent. Culture of the causative fungus, Histoplasma capsulatum, from cerebrospinal fluid, brain tissue, or other sites is the gold standard for diagnosis. In culture-negative cases, detection of H. capsulatum antigen in cerebrospinal fluid, urine, or blood is helpful diagnostically. Aggressive and prolonged antifungal therapy is indicated in all cases of CNS histoplasmosis. There are no data from prospective comparative trials upon which to base specific recommendations for treatment. Expert opinion favors an initial course of liposomal amphotericin B, followed by at least 1 year of itraconazole.

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References and Recommended Reading

  1. Bradsher RW: Histoplasmosis and blastomycosis. Clin Infect Dis 1996, 22(Suppl 2):S102–S111.

    PubMed  Google Scholar 

  2. Medoff G, Kobayashi GS, Painter A, Travis S: Morphogenesis and pathogenicity of Histoplasma capsulatum. Infect Immun 1987, 55:1355–1358.

    PubMed  CAS  Google Scholar 

  3. Wheat LJ, Connolly-Stringfield PA, Baker RL, et al.: Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature. Medicine (Baltimore) 1990, 69:361–374.

    CAS  Google Scholar 

  4. Anaissie E, Fainstein V, Samo T, et al.: Central nervous system histoplasmosis: an unappreciated complication of the acquired immunodeficiency syndrome. Am J Med 1988, 84:215–217.

    Article  PubMed  CAS  Google Scholar 

  5. Wheat LJ, Batteiger BE, Sathapatayavongs B: Histoplasma capsulatum infections of the central nervous system: a clinical review. Medicine (Baltimore) 1990, 69:244–260.

    Article  CAS  Google Scholar 

  6. Lee J-H, Slifman NR, Gershon SK, et al.: Life-threatening histoplasmosis complicating immunotherapy with tumor necrosis factor α antagonists infliximab and etanercept. Arthritis Rheum 2002, 46:2565–2570.

    Article  PubMed  CAS  Google Scholar 

  7. Wheat LJ: Histoplasmosis: experience during outbreaks in Indianapolis and review of the literature. Medicine (Baltimore) 1997, 76:339–354.

    Article  CAS  Google Scholar 

  8. Sarosi GA, Johnson PC: Disseminated histoplasmosis in patients with human immunodeficiency virus. Clin Infect Dis 1992, 14(Suppl 1):S60–S67.

    PubMed  Google Scholar 

  9. Wheat LJ, Slama TG, Zeckel ML: Histoplasmosis in the acquired immune deficiency syndrome. Am J Med 1985, 78:203–210.

    Article  PubMed  CAS  Google Scholar 

  10. Wheat LJ, Musial CE, Jenny-Avital E: Diagnosis and management of central nervous system histoplasmosis. Clin Infect Dis 2005, 40:844–852.

    Article  PubMed  CAS  Google Scholar 

  11. Wheat LJ, Kohler RB, Tewari RP. Diagnosis of disseminated histoplasmosis by detection of Histoplasma capsulatum antigen in serum and urine specimens. N Engl J Med 1986, 314:83–88.

    PubMed  CAS  Google Scholar 

  12. Wheat LJ, Freifeld AG, Kleiman MB, et al.: Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis 2007, 45:807–825.

    Article  PubMed  Google Scholar 

  13. Wheat J, Hafner R, Wulfsohn M, et al.: Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1993, 118:610–616.

    PubMed  CAS  Google Scholar 

  14. Goldman M, Zackin R, Fichtenbaum CJ, et al.: Safety of discontinuation of maintenance therapy for disseminated histoplasmosis after immunologic response to antiretroviral therapy. Clin Infect Dis 2004, 38:1485–1489.

    Article  PubMed  Google Scholar 

  15. Johnson PC, Wheat LJ, Cloud GA, et al.: Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS. Ann Intern Med 2002, 137:105–109.

    PubMed  CAS  Google Scholar 

  16. Groll AH, Giri N, Petraitis V, et al.: Comparative efficacy and distribution of lipid formulations of amphotericin B in experimental Candida albicans infection of the central nervous system. J Infect Dis 2000, 182:274–282.

    Article  PubMed  CAS  Google Scholar 

  17. Saccente M, McDonnell RW, Baddour LM, et al.: Cerebral histoplasmosis in the azole era: report of four cases and review. South Med J 2003, 96:410–416.

    Article  PubMed  Google Scholar 

  18. Dismukes WE: Introduction to antifungal drugs. Clin Infect Dis 2000, 30:653–657.

    Article  PubMed  CAS  Google Scholar 

  19. Ashley ESD, Lewis R, Lewis JS, et al.: Pharmacology of systemic antifungal agents. Clin Infect Dis 2006, 43:S28–S39.

    Article  Google Scholar 

  20. Branch RA: Prevention of amphotericin B-induced renal impairment: a review on the use of sodium supplementation. Arch Intern Med 1988, 148:2389–2394.

    Article  PubMed  CAS  Google Scholar 

  21. Goodwin SD, Cleary JD, Walawonder CA, et al.: Pretreatment regimens for adverse events related to infusion of amphotericin B. Clin Infect Dis 1995, 20:755–761.

    PubMed  CAS  Google Scholar 

  22. Wheat J, Hafner R, Korzun AH, et al.: Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome. Am J Med 1995, 98:336–342.

    Article  PubMed  CAS  Google Scholar 

  23. Wheat J, MaWhinney S, Hafner R, et al.: Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Acquired Immunodeficiency Syndrome Clinical Trials Group and Mycoses Study Group. Am J Med 1997, 103:223–232.

    Article  PubMed  CAS  Google Scholar 

  24. Haynes RR, Connolly PA, Durkin MM, et al.: Antifungal therapy for central nervous system histoplasmosis, using a newly developed intracranial model of infection. J Infect Dis 2002, 185:1830–1832.

    Article  PubMed  Google Scholar 

  25. Como JA, Dismukes WE: Oral azole drugs as systemic antifungal therapy. N Engl J Med 1994, 330:263–271.

    Article  PubMed  CAS  Google Scholar 

  26. Piscitelli SC, Gallicano KD: Interactions among drugs for HIV and opportunistic infections. N Engl J Med 2001, 344:984–996.

    Article  PubMed  CAS  Google Scholar 

  27. Odio CM, Navarrete M, Carrillo JM, et al.: Disseminated histoplasmosis in infants. Pediatr Infect Dis 1999, 18:1065–1068.

    Article  CAS  Google Scholar 

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Correspondence to Michael Saccente.

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Saccente, M. Central nervous system histoplasmosis. Curr Treat Options Neurol 10, 161–167 (2008). https://doi.org/10.1007/s11940-008-0017-x

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