Diagnosis and treatment of pulmonary histoplasmosis
- Joseph Wheat, MD
Joseph Wheat, MD
- Owner and Director
- MiraVista Diagnostics
- Carol A Kauffman, MD
Carol A Kauffman, MD
- Section Editor — Fungal Infections
- Professor of Internal Medicine
- University of Michigan Medical School
- Veterans Affairs Ann Arbor Healthcare System
Histoplasmosis is a common endemic mycosis that is usually asymptomatic but occasionally results in severe illness. Histoplasmosis and its causative agent, Histoplasma capsulatum, are found worldwide but particularly in North and Central America. Within the United States, infection is most common in the midwestern states located in the Ohio and Mississippi River valleys. Among the endemic mycoses, it is the most common cause for hospitalization .
The diagnosis and treatment of the various histoplasmosis pulmonary syndromes will be reviewed here. The pathogenesis and clinical features of these syndromes and issues regarding histoplasmosis in HIV-infected patients are discussed separately. (See "Pathogenesis and clinical features of pulmonary histoplasmosis" and "Diagnosis and treatment of histoplasmosis in HIV-infected patients".)
WHEN TO SUSPECT HISTOPLASMOSIS
Pulmonary histoplasmosis should be considered in patients with the following clinical presentations, particularly in the appropriate epidemiologic setting:
●Pneumonia with mediastinal or hilar lymphadenopathy
●Mediastinal or hilar masses
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- Wheat LJ, Conces D, Allen SD, et al. Pulmonary histoplasmosis syndromes: recognition, diagnosis, and management. Semin Respir Crit Care Med 2004; 25:129.
- Gulati M, Saint S, Tierney LM Jr. Clinical problem-solving. Impatient inpatient care. N Engl J Med 2000; 342:37.
- Hage CA, Ribes JA, Wengenack NL, et al. A multicenter evaluation of tests for diagnosis of histoplasmosis. Clin Infect Dis 2011; 53:448.
- Hage CA, Davis TE, Fuller D, et al. Diagnosis of histoplasmosis by antigen detection in BAL fluid. Chest 2010; 137:623.
- Wheat LJ, Wass J, Norton J, et al. Cavitary histoplasmosis occurring during two large urban outbreaks. Analysis of clinical, epidemiologic, roentgenographic, and laboratory features. Medicine (Baltimore) 1984; 63:201.
- Wheat LJ. Approach to the diagnosis of the endemic mycoses. Clin Chest Med 2009; 30:379.
- Wheat LJ. Improvements in diagnosis of histoplasmosis. Expert Opin Biol Ther 2006; 6:1207.
- Swartzentruber S, Rhodes L, Kurkjian K, et al. Diagnosis of acute pulmonary histoplasmosis by antigen detection. Clin Infect Dis 2009; 49:1878.
- Lindsley MD, Holland HL, Bragg SL, et al. Production and evaluation of reagents for detection of Histoplasma capsulatum antigenuria by enzyme immunoassay. Clin Vaccine Immunol 2007; 14:700.
- Scheel CM, Samayoa B, Herrera A, et al. Development and evaluation of an enzyme-linked immunosorbent assay to detect Histoplasma capsulatum antigenuria in immunocompromised patients. Clin Vaccine Immunol 2009; 16:852.
- Cloud JL, Bauman SK, Neary BP, et al. Performance characteristics of a polyclonal enzyme immunoassay for the quantitation of Histoplasma antigen in human urine samples. Am J Clin Pathol 2007; 128:18.
- Theel ES, Harring JA, Dababneh AS, et al. Reevaluation of commercial reagents for detection of Histoplasma capsulatum antigen in urine. J Clin Microbiol 2015; 53:1198.
- Theel ES, Jespersen DJ, Harring J, et al. Evaluation of an enzyme immunoassay for detection of Histoplasma capsulatum antigen from urine specimens. J Clin Microbiol 2013; 51:3555.
- Wheat J, Wheat H, Connolly P, et al. Cross-reactivity in Histoplasma capsulatum variety capsulatum antigen assays of urine samples from patients with endemic mycoses. Clin Infect Dis 1997; 24:1169.
- Wheat J, French ML, Kohler RB, et al. The diagnostic laboratory tests for histoplasmosis: analysis of experience in a large urban outbreak. Ann Intern Med 1982; 97:680.
- Wheat LJ, French ML, Wass JL. Sarcoidlike manifestations of histoplasmosis. Arch Intern Med 1989; 149:2421.
- Picardi JL, Kauffman CA, Schwarz J, Phair JP. Detection of precipitating antibodies to Histoplasma capsulatum by counterimmunoelectrophoresis. Am Rev Respir Dis 1976; 114:171.
- Babady NE, Buckwalter SP, Hall L, et al. Detection of Blastomyces dermatitidis and Histoplasma capsulatum from culture isolates and clinical specimens by use of real-time PCR. J Clin Microbiol 2011; 49:3204.
- Bialek R, Cirera AC, Herrmann T, et al. Nested PCR assays for detection of Blastomyces dermatitidis DNA in paraffin-embedded canine tissue. J Clin Microbiol 2003; 41:205.
- Tang YW, Li H, Durkin MM, et al. Urine polymerase chain reaction is not as sensitive as urine antigen for the diagnosis of disseminated histoplasmosis. Diagn Microbiol Infect Dis 2006; 54:283.
- Goodwin RA Jr, Owens FT, Snell JD, et al. Chronic pulmonary histoplasmosis. Medicine (Baltimore) 1976; 55:413.
- Loyd JE, Tillman BF, Atkinson JB, Des Prez RM. Mediastinal fibrosis complicating histoplasmosis. Medicine (Baltimore) 1988; 67:295.
- Peikert T, Colby TV, Midthun DE, et al. Fibrosing mediastinitis: clinical presentation, therapeutic outcomes, and adaptive immune response. Medicine (Baltimore) 2011; 90:412.
- Davis AM, Pierson RN, Loyd JE. Mediastinal fibrosis. Semin Respir Infect 2001; 16:119.
- 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.
- 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.
- Dismukes WE, Bradsher RW Jr, Cloud GC, et al. Itraconazole therapy for blastomycosis and histoplasmosis. NIAID Mycoses Study Group. Am J Med 1992; 93:489.
- McKinsey DS, Kauffman CA, Pappas PG, et al. Fluconazole therapy for histoplasmosis. The National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis 1996; 23:996.
- Wheat LJ, Connolly P, Smedema M, et al. Emergence of resistance to fluconazole as a cause of failure during treatment of histoplasmosis in patients with acquired immunodeficiency disease syndrome. Clin Infect Dis 2001; 33:1910.
- Restrepo A, Tobón A, Clark B, et al. Salvage treatment of histoplasmosis with posaconazole. J Infect 2007; 54:319.
- Freifeld AG, Iwen PC, Lesiak BL, et al. Histoplasmosis in solid organ transplant recipients at a large Midwestern university transplant center. Transpl Infect Dis 2005; 7:109.
- Freifeld A, Proia L, Andes D, et al. Voriconazole use for endemic fungal infections. Antimicrob Agents Chemother 2009; 53:1648.
- Putnam, LR, Sutliff, WD, Larkin, JC, et al. Histoplasmosis cooperative study: Chronic pulmonary histoplasmosis treated with amphotericin B alone and with amphotericin B and triple sulfonamide. Am Rev Respir Dis 1968; 97:96.
- Hammoud ZT, Rose AS, Hage CA, et al. Surgical management of pulmonary and mediastinal sequelae of histoplasmosis: a challenging spectrum. Ann Thorac Surg 2009; 88:399.
- Goodwin RA, Nickell JA, Des Prez RM. Mediastinal fibrosis complicating healed primary histoplasmosis and tuberculosis. Medicine (Baltimore) 1972; 51:227.
- Doyle TP, Loyd JE, Robbins IM. Percutaneous pulmonary artery and vein stenting: a novel treatment for mediastinal fibrosis. Am J Respir Crit Care Med 2001; 164:657.
- Albers EL, Pugh ME, Hill KD, et al. Percutaneous vascular stent implantation as treatment for central vascular obstruction due to fibrosing mediastinitis. Circulation 2011; 123:1391.
- Goodwin RA Jr, Snell JD Jr. The enlarging histoplasmoma. Concept of a tumor-like phenomenon encompassing the tuberculoma and coccidioidoma. Am Rev Respir Dis 1969; 100:1.
- Wheat LJ, Stein L, Corya BC, et al. Pericarditis as a manifestation of histoplasmosis during two large urban outbreaks. Medicine (Baltimore) 1983; 62:110.
- Picardi JL, Kauffman CA, Schwarz J, et al. Pericarditis caused by Histoplasma capsulatum. Am J Cardiol 1976; 37:82.
- Rosenthal J, Brandt KD, Wheat LJ, Slama TG. Rheumatologic manifestations of histoplasmosis in the recent Indianapolis epidemic. Arthritis Rheum 1983; 26:1065.
- WHEN TO SUSPECT HISTOPLASMOSIS
- Histopathology and cytology
- Fungal cultures
- Antigen detection
- - Comparison of serologic methods
- Polymerase chain reaction
- Distinction from sarcoidosis
- SELECTION OF DIAGNOSTIC TESTS FOR DIFFERENT PULMONARY SYNDROMES
- Acute diffuse pulmonary disease
- Acute localized pulmonary disease
- Chronic cavitary pulmonary histoplasmosis
- Mediastinal syndromes, broncholithiasis, and lung nodules
- ANTIFUNGAL THERAPY
- General approach
- Amphotericin B
- THERAPY FOR PULMONARY HISTOPLASMOSIS
- Acute diffuse pulmonary histoplasmosis
- Acute localized pulmonary disease
- Chronic cavitary pulmonary histoplasmosis
- Granulomatous mediastinitis
- Fibrosing mediastinitis
- Pulmonary nodules (histoplasmomas)
- EXTRAPULMONARY MANIFESTATIONS
- Pericarditis or rheumatologic syndromes
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS