Pathogenesis and clinical features 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 was first described by a United States Army physician in Panama in 1906 and subsequently has become recognized as a common and usually asymptomatic infection [1,2]. Histoplasmosis is the most prevalent endemic mycosis in the United States . While most infections are asymptomatic or self-limited, some individuals develop acute pulmonary infections or severe and progressive disseminated infection .
The pathogenesis and clinical features of the various pulmonary syndromes that may result from Histoplasma capsulatum infection will be reviewed here. The diagnosis and treatment of pulmonary histoplasmosis, as well as the pathogenesis, clinical manifestations, diagnosis, and treatment of disseminated histoplasmosis are discussed separately. (See "Diagnosis and treatment of pulmonary histoplasmosis" and "Pathogenesis and clinical manifestations of disseminated histoplasmosis" and "Diagnosis and treatment of disseminated histoplasmosis in HIV-uninfected patients".)
H. capsulatum proliferates best in soil contaminated with bird or bat droppings, which are believed to alter the soil characteristics favoring sporulation of the organism. Sites commonly associated with exposure to H. capsulatum include chicken coops or farm buildings with large accumulations of chicken droppings, abandoned buildings, bird roost sites, caves, and wood lots . Activities that have been associated with exposure include excavation, construction, demolition, remodeling, wood cutting and gathering, exploring caves, and visiting campsites that are visibly contaminated with bat guano [6-12].
Heavy exposure usually occurs with activities disturbing a large accumulation of droppings in an enclosed area, such as a cave or an attic. However, in many cases, patients recall no such exposure.
Histoplasmosis and its causative agent, H. capsulatum, are found worldwide [4,13,14]. It is estimated that up to 500,000 new infections occur each year in the United States . Among the endemic mycoses, histoplasmosis is the most common cause for hospitalization. H. capsulatum is most prevalent in the midwestern and central states along the Ohio and Mississippi River valleys, but also occurs in microfoci in several states along the East Coast . In addition, H. capsulatum causes disease in Canada, Mexico, Central and South America, as well as in parts of eastern and southern Europe, Africa, eastern Asia, and Australia [16,17].
- Darling ST. A protozoan general infection producing pseudotubercles in the lungs and focal necrosis in the liver, spleen and lymph nodes. JAMA 1906; 46:1283.
- Riley WA, Watson CJ. Histoplasmosis of Darling with report of a case originating in Minnesota. Am J Trop Med 1926; 6:271.
- Chu JH, Feudtner C, Heydon K, et al. Hospitalizations for endemic mycoses: a population-based national study. Clin Infect Dis 2006; 42:822.
- Kauffman CA. Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev 2007; 20:115.
- Benedict K, Mody RK. Epidemiology of Histoplasmosis Outbreaks, United States, 1938-2013. Emerg Infect Dis 2016; 22:370.
- Wheat LJ, Conces D, Allen SD, et al. Pulmonary histoplasmosis syndromes: recognition, diagnosis, and management. Semin Respir Crit Care Med 2004; 25:129.
- Gustafson TL, Kaufman L, Weeks R, et al. Outbreak of acute pulmonary histoplasmosis in members of a wagon train. Am J Med 1981; 71:759.
- Ward JI, Weeks M, Allen D, et al. Acute histoplasmosis: clinical, epidemiologic and serologic findings of an outbreak associated with exposure to a fallen tree. Am J Med 1979; 66:587.
- Centers for Disease Control and Prevention (CDC). Outbreak of histoplasmosis among industrial plant workers--Nebraska, 2004. MMWR Morb Mortal Wkly Rep 2004; 53:1020.
- Luby JP, Southern PM Jr, Haley CE, et al. Recurrent exposure to Histoplasma capsulatum in modern air-conditioned buildings. Clin Infect Dis 2005; 41:170.
- Centers for Disease Control and Prevention (CDC). Histoplasmosis outbreak among day camp attendees--Nebraska, June 2012. MMWR Morb Mortal Wkly Rep 2012; 61:747.
- Centers for Disease Control and Prevention (CDC). Histoplasmosis outbreak associated with the renovation of an old house - Quebec, Canada, 2013. MMWR Morb Mortal Wkly Rep 2014; 62:1041.
- Bahr NC, Antinori S, Wheat LJ, Sarosi GA. Histoplasmosis infections worldwide: thinking outside of the Ohio River valley. Curr Trop Med Rep 2015; 2:70.
- Colombo AL, Tobón A, Restrepo A, et al. Epidemiology of endemic systemic fungal infections in Latin America. Med Mycol 2011; 49:785.
- Hammerman KJ, Powell KE, Tosh FE. The incidence of hospitalized cases of systemic mycotic infections. Sabouraudia 1974; 12:33.
- Panackal AA, Hajjeh RA, Cetron MS, Warnock DW. Fungal infections among returning travelers. Clin Infect Dis 2002; 35:1088.
- Cano MV, Hajjeh RA. The epidemiology of histoplasmosis: a review. Semin Respir Infect 2001; 16:109.
- Centers for Disease Control and Prevention. Histoplasmosis in a state where it is not known to be endemic--Montana, 2012-2013. MMWR Morb Mortal Wkly Rep 2013; 62:834.
- Morgan J, Cano MV, Feikin DR, et al. A large outbreak of histoplasmosis among American travelers associated with a hotel in Acapulco, Mexico, spring 2001. Am J Trop Med Hyg 2003; 69:663.
- Centers for Disease Control and Prevention (CDC). Outbreak of histoplasmosis among travelers returning from El Salvador--Pennsylvania and Virginia, 2008. MMWR Morb Mortal Wkly Rep 2008; 57:1349.
- Goodwin RA, Loyd JE, Des Prez RM. Histoplasmosis in normal hosts. Medicine (Baltimore) 1981; 60:231.
- Limaye AP, Connolly PA, Sagar M, et al. Transmission of Histoplasma capsulatum by organ transplantation. N Engl J Med 2000; 343:1163.
- PROCKNOW JJ, PAGE MI, LOOSLI CG. Early pathogenesis of experimental histoplasmosis. Arch Pathol 1960; 69:413.
- Kataria YP, Campbell PB, Burlingham BT. Acute pulmonary histoplasmosis presenting as adult respiratory distress syndrome: effect of therapy on clinical and laboratory features. South Med J 1981; 74:534.
- Wynne JW, Olsen GN. Acute histoplasmosis presenting as the adult respiratory distress syndrome. Chest 1974; 66:158.
- Horwath MC, Fecher RA, Deepe GS Jr. Histoplasma capsulatum, lung infection and immunity. Future Microbiol 2015; 10:967.
- Garfoot AL, Zemska O, Rappleye CA. Histoplasma capsulatum depends on de novo vitamin biosynthesis for intraphagosomal proliferation. Infect Immun 2014; 82:393.
- Fojtasek MF, Sherman MR, Garringer T, et al. Local immunity in lung-associated lymph nodes in a murine model of pulmonary histoplasmosis. Infect Immun 1993; 61:4607.
- Paya CV, Roberts GD, Cockerill FR 3rd. Transient fungemia in acute pulmonary histoplasmosis: detection by new blood-culturing techniques. J Infect Dis 1987; 156:313.
- SCHWARZ J, SILVERMAN FN, ADRIANO SM, et al. The relation of splenic calcification to histoplasmosis. N Engl J Med 1955; 252:887.
- Wheat LJ, Slama TG, Norton JA, et al. Risk factors for disseminated or fatal histoplasmosis. Analysis of a large urban outbreak. Ann Intern Med 1982; 96:159.
- Allendoerfer R, Biovin GP, Deepe GS Jr. Modulation of immune responses in murine pulmonary histoplasmosis. J Infect Dis 1997; 175:905.
- Wu-Hsieh B, Howard DH. Histoplasmosis. In: Fungal Infections and Immune Responses, Murphy JW, Friedman H, Bendinelli M (Eds), Plenum Publishing, New York 1993. p.213.
- Deepe GS Jr. Modulation of infection with Histoplasma capsulatum by inhibition of tumor necrosis factor-alpha activity. Clin Infect Dis 2005; 41 Suppl 3:S204.
- Wallis RS, Broder M, Wong J, et al. Reactivation of latent granulomatous infections by infliximab. Clin Infect Dis 2005; 41 Suppl 3:S194.
- Hage CA, Bowyer S, Tarvin SE, et al. Recognition, diagnosis, and treatment of histoplasmosis complicating tumor necrosis factor blocker therapy. Clin Infect Dis 2010; 50:85.
- Goodwin RA Jr, Des Prez RM. State of the art: histoplasmosis. Am Rev Respir Dis 1978; 117:929.
- Goodwin RA Jr, Owens FT, Snell JD, et al. Chronic pulmonary histoplasmosis. Medicine (Baltimore) 1976; 55:413.
- 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.
- Goodwin RA, Nickell JA, Des Prez RM. Mediastinal fibrosis complicating healed primary histoplasmosis and tuberculosis. Medicine (Baltimore) 1972; 51:227.
- Wheat LJ, French ML, Wass JL. Sarcoidlike manifestations of histoplasmosis. Arch Intern Med 1989; 149:2421.
- Wheat LJ. Diagnosis and management of histoplasmosis. Eur J Clin Microbiol Infect Dis 1989; 8:480.
- Hage CA, Knox KS, Wheat LJ. Endemic mycoses: overlooked causes of community acquired pneumonia. Respir Med 2012; 106:769.
- Brodsky AL, Gregg MB, Loewenstein MS, et al. Outbreak of histoplasmosis associated with the 1970 Earth Day activities. Am J Med 1973; 54:333.
- Wheat LJ, Slama TG, Eitzen HE, et al. A large urban outbreak of histoplasmosis: clinical features. Ann Intern Med 1981; 94:331.
- Chick EW, Bauman DS. Editorial: Acute cavitary histoplasmosis--fact or fiction? Chest 1974; 65:497.
- Sathapatayavongs B, Batteiger BE, Wheat J, et al. Clinical and laboratory features of disseminated histoplasmosis during two large urban outbreaks. Medicine (Baltimore) 1983; 62:263.
- Connell JV, Muhm JR. Radiographic manifestations of pulmonary histoplasmosis: a 10-year review. Radiology 1976; 121:281.
- Quasney MW, Leggiadro RJ. Pleural effusion associated with histoplasmosis. Pediatr Infect Dis J 1993; 12:415.
- RUBIN H, FURCOLOW ML, YATES JL, BRASHER CA. The course and prognosis of histoplasmosis. Am J Med 1959; 27:278.
- Schiavo DN, Bauer PR, Iyer VN, Ryu JH. Fatal fulminant necrotizing pneumonia: a case report. J Med Case Rep 2014; 8:37.
- Conces DJ Jr, Tarver RD, Vix VA. Broncholithiasis: CT features in 15 patients. AJR Am J Roentgenol 1991; 157:249.
- Arrigoni MG, Bernatz PE, Donoghue FE. Broncholithiasis. J Thorac Cardiovasc Surg 1971; 62:231.
- Garrett HE Jr, Roper CL. Surgical intervention in histoplasmosis. Ann Thorac Surg 1986; 42:711.
- Coss KC, Wheat LJ, Conces DJ Jr, et al. Esophageal fistula complicating mediastinal histoplasmosis. Response to amphotericin B. Am J Med 1987; 83:343.
- Rabinowitz JG, Prater W, Silver J, et al. Mediastinal histoplasmosis. Mt Sinai J Med 1980; 47:356.
- Schowengerdt CG, Suyemoto R, Main FB. Granulomatous and fibrous mediastinitis. A review and analysis of 180 cases. J Thorac Cardiovasc Surg 1969; 57:365.
- Savides TJ, Gress FG, Wheat LJ, et al. Dysphagia due to mediastinal granulomas: diagnosis with endoscopic ultrasonography. Gastroenterology 1995; 109:366.
- Sakulsky SB, Harrison EG, Dines DE, et al. Mediastinal granuloma. J Thorac Cardiovasc Surg 1967; 54:280.
- KUNKEL WM Jr, CLAGETT OT, McDONALD JR. Mediastinal granulomas. J Thorac Surg 1954; 27:565.
- Landay MJ, Rollins NK. Mediastinal histoplasmosis granuloma: evaluation with CT. Radiology 1989; 172:657.
- Loyd JE, Tillman BF, Atkinson JB, Des Prez RM. Mediastinal fibrosis complicating histoplasmosis. Medicine (Baltimore) 1988; 67:295.
- 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.
- Medeiros AA, Marty SD, Tosh FE, Chin TD. Erythema nodosum and erythema multiforme as clinical manifestations of histoplasmosis in a community outbreak. N Engl J Med 1966; 274:415.
- Ozols II, Wheat LJ. Erythema nodosum in an epidemic of histoplasmosis in Indianapolis. Arch Dermatol 1981; 117:709.
- SELLERS TF Jr, PRICE WN Jr, NEWBERRY WM Jr. AN EPIDEMIC OF ERYTHEMA MULTIFORME AND ERYTHEMA NODOSUM CAUSED BY HISTOPLASMOSIS. Ann Intern Med 1965; 62:1244.
- Jones PG, Rolston K, Hopfer RL. Septic arthritis due to Histoplasma capsulatum in a leukaemic patient. Ann Rheum Dis 1985; 44:128.
- Ryder KW, Jay SJ, Kiblawi SO, Hull MT. Serum angiotensin converting enzyme activity in patients with histoplasmosis. JAMA 1983; 249:1888.
- Baughman RP, Lower EE. Fungal infections as a complication of therapy for sarcoidosis. QJM 2005; 98:451.
- Mathur P, Zurlo JJ, Crook TJ. The intricate relationship of histoplasmosis and sarcoidosis: a case report. J Med Case Rep 2014; 8:235.
- Bansal A, Drewek R. Sarcoidosis and Histoplasmosis: Is One a Consequence of the Other? A Case Report and Review of the Literature. Case Rep Rheumatol 2015; 2015:108459.
- Wheat LJ, Kauffman CA. Histoplasmosis. Infect Dis Clin North Am 2003; 17:1.
- Gulati M, Saint S, Tierney LM Jr. Clinical problem-solving. Impatient inpatient care. N Engl J Med 2000; 342:37.
- CLINICAL MANIFESTATIONS
- Symptomatic pulmonary histoplasmosis
- Acute diffuse pulmonary histoplasmosis
- Chronic pulmonary histoplasmosis
- Mediastinal granuloma
- Fibrosing mediastinitis
- Other manifestations
- - Pericarditis
- - Rheumatologic manifestations
- - Dermatologic manifestations
- ASSOCIATION WITH SARCOIDOSIS
- WHEN TO SUSPECT PULMONARY HISTOPLASMOSIS
- INFORMATION FOR PATIENTS