Case Report

Cerebral Histoplasmosis in the Azole Era: Report of Four Cases and Review

Authors: Michael Saccente, MD, Richard W. McDonnell, MD, Larry M. Baddour, MD, M. Jane Mathis, MD, Robert W. Bradsher, MD

Abstract

We report four cases of cerebral histoplasmosis and discuss features of six additional cases reported in the medical literature in the past 10 years, when azoles have been available for therapy. Most patients with this disease are immunocompromised or have a history that suggests heavy exposure to Histoplasma capsulatum. Fever and other clinical findings of systemic toxicity caused by disseminated histoplasmosis may be absent; 5 of 10 patients did not manifest these findings. Although the mainstay of treatment for central nervous system histoplasmosis remains amphotericin B, 9 of the 10 patients received itraconazole or fluconazole either as initial therapy or after a course of treatment with amphotericin B.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

  1. Bradsher RW. Histoplasmosis and blastomycosis. Clin Infect Dis 1996; 22: S102–S111.
  2. Medoff G, Kobayashi GS, Painter A. Morphogenesis and pathogenicity of Histoplasma capsulatum. Infect Immun 1987; 55: 1355–1358.
  3. Wheat LJ, Slama TG, Zeckel ML. Histoplasmosis in the acquired immunodeficiency syndrome. Am J Med 1985; 78: 203–210.
  4. Huang CT, McGarry T, Cooper S. Disseminated histoplasmosis in the acquired immunodeficiency syndrome: Report of five cases from a nonendemic area. Arch Intern Med 1987; 147: 1181–1184.
  5. Wheat LJ, Connolly-Stringfield PA, Baker RL, Curfman MF, Eads ME, Israel KS, 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. 6. Wheat LJ, Batteiger BE, Sathapatavongs B. Histoplasma capsulatum infections of the central nervous system: A clinical review. Medicine (Baltimore) 1990; 69: 244–260.
  6. Anaissie E, Fainstein V, Samo T, Bodey GP, Sarosi GA. Central nervous system histoplasmosis: An unappreciated complication of the acquired immunodeficiency syndrome. Am J Med 1988; 84: 215–217.
  7. Como J, Dismukes W. Oral azole drugs as systemic antifungal therapy. N Engl J Med 1994; 330: 263–272.
  8. Wheat J, Hafner R, Korzun AH, Limjoco MT, Spencer P, Larsen RA, et al. Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome: AIDS Clinical Trial Group. Am J Med 1995; 98: 336–342.
  9. McKinsey DS, Kauffman CA, Pappas PG, Cloud GA, Girard WM, Sharkey PK, et al. Fluconazole therapy for histoplasmosis: The National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis 1996; 23: 996–1001.
  10. Wheat J, MaWhinney S, Hafner R, McKinsey D, Chen D, Korzun A, 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.
  11. Dismukes WE, Bradsher RW Jr, Cloud GC, Kauffman CA, Chapman SW, George RB, et al. Itraconazole therapy for blastomycosis and histoplasmosis. NIAID Mycoses Study Group. Am J Med 1992; 93: 489–497.
  12. Livas IC, Nechay PS, Nauseff WM. Clinical evidence of spinal cord and cerebral histoplasmosis twenty years after renal transplantation. Clin Infect Dis 1995; 20: 692–695.
  13. Vullo V, Mastroianni CM, Ferone U, Trinchieri V, Folgori F, Lichtner M, et al. Central nervous system involvement as a relapse of disseminated histoplasmosis in an Italian AIDS patient. J Infect 1997; 35: 83–84.
  14. Knapp S, Turnherr M, Dekan G, Willinger B, Stingl G, Rieger A. A case of HIV-associated cerebral histoplasmosis successfully treated with fluconazole. Eur J Clin Microbiol Infect Dis 1999; 18: 658–661.
  15. Klein CJ, Dinapoli RP, Temesgen Z, Meyer FB. Central nervous system histoplasmosis mimicking a brain tumor: Difficulties in diagnosis and treatment. Mayo Clin Proc 1999; 74: 803–807.
  16. Bamberger DM. Successful treatment of multiple cerebral histoplasmomas with itraconazole. Clin Infect Dis 1999; 28: 915–916.
  17. Mawhorter SD, Curley GV, Kursh ED, Farver CE. Prostatic and central nervous system histoplasmosis in an immunocompetent host: Case report and review of the prostatic histoplasmosis literature. Clin Infect Dis 2000; 30: 595–598.
  18. Tabbal SD, Harik SI. Images in clinical medicine: Cerebral histoplasmosis. N Engl J Med 1999; 340: 1176.
  19. Wheat J. Histoplasmosis: Experience during outbreaks in Indianapolis and review of the literature. Medicine (Baltimore) 1997; 76: 339–354.
  20. Wheat J, Sarosi G, McKinsey D, Hamill R, Bradsher R, Johnson P, et al. Practice guidelines for the management of patients with histoplasmosis: Infectious Diseases Society of America. Clin Infect Dis 2000; 30: 688–695.
  21. Wheat J, Hafner R, Wulfsohn M, Spencer P, Squires K, Powderly W, et al. Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome: The National Institute of Allergy and Infectious Diseases Clinical Trials and Mycoses Study Group Collaborators. Ann Intern Med 1993; 118: 610–616.
  22. Wheat J, Marichal P, Vanden Bossche H, Le Monte A, Connolly P. Hypothesis on the mechanism of resistance to fluconazole in Histoplasma capsulatum. Antimicrob Agents Chemother 1997; 41: 410–414.
  23. Goodpasture HC, Hershberger RE, Barnett AM, Peterie JD. Treatment of central nervous system fungal infection with ketoconazole. Arch Intern Med 1985; 145: 879–880.
  24. Galgiani JN, Catanzaro A, Cloud GA, Higgs J, Friedman BA, Larsen RA, et al. Fluconazole therapy for coccidioidal meningitis: The NIAID-Mycoses Study Group. Ann Intern Med 1993; 119: 28–35.
  25. Saag MS, Cloud GA, Graybill JR, Sobel JD, Tuazon CU, Johnson PC, et al. A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis: National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis 1999; 28: 291–296.
  26. van der Horst CM, Saag MS, Cloud GA, Hamill RJ, Graybill JR, Sobel JD, et al. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome: National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group. N Engl J Med 1997; 337: 15–21.
  27. Thaler F, Bernard B, Tod M, Jedynak CP, Petitjean O, Derome P, et al. Fluconazole penetration in cerebral parenchyma in humans at steady state. Antimicrob Agents Chemother 1995; 39: 1154–1156.
  28. Miyama T, Takanaga H, Matsuo H, Yamano K, Yamamoto K, Iga T, et al. P-glycoprotein-mediated transport of itraconazole across the blood-brain barrier. Antimicrob Agents Chemother 1998; 42: 1738–1744.