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Histoplasmosis

  • Author: Jazeela Fayyaz, DO; Chief Editor: Ryland P Byrd, Jr, MD  more...
 
Updated: Dec 18, 2014
 

Background

Histoplasma capsulatum is a dimorphic fungus that remains in a mycelial form at ambient temperatures and grows as yeast at body temperature in mammals. Infection causes histoplasmosis. Although the fungus that causes histoplasmosis can be found in temperate climates throughout the world, it is endemic to the Ohio, Missouri, and Mississippi River valleys in the United States. Internationally, the fungus is predominantly found in river valleys in North and Central America, eastern and southern Europe, and parts of Africa, eastern Asia, and Australia.

The soil in areas endemic for histoplasmosis provides an acidic damp environment with high organic content that is good for mycelial growth. Highly infectious soil is found near areas inhabited by bats and birds, such as caves and chicken coops. Decaying trees and riverbanks also make good habitats for incubations.[1] Birds cannot be infected by the fungus and do not transmit the disease; however, bird excretions contaminate the soil, thereby enriching the growth medium for the mycelium. In contrast, bats can become infected and they transmit histoplasmosis through droppings. Contaminated soil can be potentially infectious for years. Outbreaks of histoplasmosis have been associated with construction and renovation activities that disrupt contaminated soil. In addition, travelers to endemic areas are at risk for histoplasmosis because airborne spores can travel hundreds of feet.[2]

Most individuals with histoplasmosis are asymptomatic. Those who develop clinical manifestations are usually immunocompromised or are exposed to a high quantity of inoculum. Histoplasma species may remain latent in healed granulomas and recur, resulting in cell-mediated immunity impairment.

Clinical presentations include asymptomatic pulmonary histoplasmosis, symptomatic pulmonary histoplasmosis, acute diffuse pulmonary histoplasmosis, chronic pulmonary histoplasmosis, acute respiratory distress syndrome, disseminated histoplasmosis, broncholithiasis, mediastinal granuloma, fibrosing mediastinitis, endobronchial histoplasmosis, and lung nodules.

Combined urine and serum antigen testing have a sensitivity of 90%. Bronchoalveolar lavage antigen testing is more sensitive than urine antigen testing. Fibrosing mediastinitis from histoplasmosis does not require treatment, and hepatosplenic calcifications may be observed. Acute histoplasmosis may not need treatment or may need three months of treatment if symptomatic (itraconazole 200 mg twice daily for 3 months, as compared to 12 months with blastomycosis). Histoplasmosis may mimic lung cancer and sarcoidosis. One of the fastest ways to diagnose histoplasmosis is with a bone marrow biopsy.

A summary of the features of histoplasmosis follows[3] :

  • Location: Midwestern United States, Southeastern United States, Central America, Eastern Canada
  • History: Large exposure includes construction sites, birds, caves; low exposure includes living in an endemic area
  • Sex/race/ethnicity: No predisposition
  • Clinical course: Usually asymptomatic (if symptoms occur they are nonspecific); symptoms < 1 month indicate acute disease; symptoms 1-3 months indicate subacute disease; symptoms >3 months indicate chronic disease
  • Acute syndromes: Pneumonia, disseminated disease in immunocompromised persons
  • Chronic syndromes: Cavitary pulmonary lung disease, calcified lymph nodes, mediastinal fibrosis
  • Physical examination: Uncommon findings include erythema nodosum and erythema multiforme
  • CBC count: Thrombocytopenia in disseminated disease
  • Serology: Useful in testing immunocompetent individuals with acute or subacute disease.
  • Antigen testing: Useful in testing infiltrative or chronic disease in immunosuppressed; urine antigen has ~60% sensitivity; serum antigen has ~60% sensitivity; both combined have >80% sensitivity
  • Acute/subacute presentation: Lung infiltrate, lobar pneumonia, micronodular pattern
  • Chronic presentation: Cavitary lung lesions
  • Immunosuppressed presentation: Diffuse disease.
  • Adenopathy: Common, granulomatous mediastinal involvement, can be profound, can calcify
  • Extrapulmonary findings: Liver and spleen calcifications, adrenals, oral ulcers, bone marrow
  • Differentials: Sarcoidosis and tuberculosis
  • Usual treatment: Itraconazole; amphotericin for severe or diffuse disease
  • Prognosis: Excellent
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Pathophysiology

H capsulatum in the saprobic state grows in the mycelial form. Macroconidia and microconidia are produced on the hyphae of mycelium and are converted to the yeast form under temperature-controlled regulation. The aerosolization of conidia and mycelial fragments from contaminated soil results in alveolar deposition via inhalation.

The host defense includes the fungistatic properties of neutrophils and macrophages. T lymphocytes are crucial in limiting the extent of infection. Susceptibility to dissemination is increased markedly with impaired cellular host defenses.

Conversion from the mycelial to the pathogenic yeast form occurs intracellularly. After phagocytosis by macrophages, the yeast replicates in approximately 15-18 hours. Despite fusion with lysosomes, multiplication continues within the phagosomes. Proposed theories suggest that the yeasts may produce proteins that inhibit the activity of lysosomal proteases.

As the host immunity response develops, yeast growth ceases within 1-2 weeks after exposure. Cytokines systemically activate the fungistatic activity of macrophages against intracellular yeasts. With further maturation of the cell-mediated response, delayed-type hypersensitivity to histoplasmal antigens occurs (3-6 wk after exposure). Approximately 85-90% of individuals who are immunocompetent produce a positive response to skin antigen test for Histoplasma species.[4] Over weeks to months, the inflammatory response produces calcified fibrinous granulomas with areas of caseous necrosis.

Clinical manifestations of histoplasmosis appear with continued exposure to large inocula. The initial pulmonary infection may disseminate systemically, with hematogenous spread, and produce extrapulmonary manifestations. Hematogenous spread to regional lymph nodes may occur through the lymphatics or the liver and spleen. Progressive disseminated histoplasmosis is rare in adult hosts who are immunocompetent. Systemic spread usually occurs in patients with impaired cellular immunity and typically involves the CNS, liver, spleen, and rheumatologic, ocular, and hematologic systems.

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Epidemiology

Frequency

United States

Histoplasmosis is the most common endemic fungal infection seen in humans. The central river valleys in the midwestern and south central United States are endemic for histoplasmosis. Approximately 250,000 individuals are infected annually. Clinical manifestations of histoplasmosis occur in less than 5% of the population. Most infections are sporadic, although large outbreaks of histoplasmosis may occur.

Population studies have demonstrated that greater than 80% of young adults from endemic areas (Ohio Valley, Mississippi Valley) have been previously infected with H capsulatum.[5]

International

The fungus is predominantly found in river valleys between latitudes 45° north and 30° south in South and Central America.[6, 7]

Mortality/Morbidity

Morbidity and mortality are related to the duration and extent of systemic infection.

Approximately 90% of patients with acute pulmonary histoplasmosis are asymptomatic. Acute pericarditis can occur in as many as 5% of patients who are symptomatic.[2] The pericardial fluid is generally exudative.[6] Pleural effusions develop in 40-60% of patients with pericarditis.

Chronic pulmonary histoplasmosis occurs in patients with underlying lung disease. Patients develop cavities that may enlarge and result in necrosis. Untreated histoplasmosis may lead to progressive pulmonary fibrosis that results in respiratory and cardiac failure and recurrent infections.

Progressive disseminated histoplasmosis occurs in 1 case per 2000 cases in adults who are immunocompetent. Progressive disseminated histoplasmosis occurs in 4-27% of infected children, older individuals, persons who are immunosuppressed. In the subacute form, death occurs within 2-24 months in untreated cases. The acute form, if untreated, results in death within weeks.[5]

Sex

The rates of positive results on skin testing for sensitivity to antigens of H capsulatum are similar in males and females. Rheumatologic manifestations tend to occur predominantly in females.[8]

Age

Although histoplasmosis can affect individuals of any age, those in extreme age ranges are more prone to developing infection as a result of immature or deteriorated immune defenses.

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Contributor Information and Disclosures
Author

Jazeela Fayyaz, DO Pulmonologist, Department of Pulmonology, Unity Hospital

Jazeela Fayyaz, DO is a member of the following medical societies: American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Coauthor(s)

Klaus-Dieter Lessnau, MD, FCCP Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Ravikanth Vydyula, MD Fellow in Pulmonary and Critical Care Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Ravikanth Vydyula, MD is a member of the following medical societies: American College of Physicians, American Association of Physicians of Indian Origin

Disclosure: Nothing to disclose.

Maciej P Walczyszyn, MD Fellow in Pulmonary and Critical Care Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital; Hospitalist, Alliance Medical Group, Inc, Waterbury Hospital

Maciej P Walczyszyn, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Michael Peterson, MD Chief of Medicine, Vice-Chair of Medicine, University of California, San Francisco, School of Medicine; Endowed Professor of Medicine, University of California, San Francisco-Fresno, School of Medicine

Michael Peterson, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Ryan C. Chang, MD, and Irawan Susanto, MD, to the development and writing of this article.

References
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