Histoplasmosis Clinical Presentation

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


A thorough social and occupational history is essential in the initial evaluation of histoplasmosis. Travel or residence in an endemic area or activities involving bats or birds, whether recent or remote, should aid in the differential. Determine if the patient has a drug history or comorbid condition that is contributing to an immunocompromised state. The diagnosis of histoplasmosis should be considered in anyone with an acute febrile respiratory illness who has traveled to an area where histoplasmosis is endemic.[2] Major extrapulmonary manifestations include pericarditis, rheumatologic symptoms, and ocular involvement.

Acute and subacute pulmonary histoplasmosis

Approximately 90% of patients are asymptomatic. If symptoms develop, onset occurs 3-14 days after exposure.[8] Acute is defined as less than 1 month of symptoms, whereas subacute refers to more than 1 month of symptoms but less than 3 months.[1] Fever, headache, malaise, myalgia, abdominal pain, and chills are common symptoms; usually, histoplasmosis is self-limited. Individuals exposed to a large inoculum may develop severe dyspnea resulting from diffuse pulmonary involvement. Joint pain and skin lesions occur in 5-6% of patients, mostly in females.[5] Enlarged hilar and mediastinal lymph nodes are present in 5-10% of patients. Broncholithiasis can occur if these nodes calcify and erode into the airways, resulting in possible hemoptysis, obstructive pneumonia, and stone expectoration.[1]

Cough, hemoptysis, dyspnea, and/or chest pain may be present and are related to the degree of compression on the pulmonary airway and circulation. Paratracheal involvement may cause cough or dyspnea because of compression on the trachea or bronchi. Rarely, compression of the esophagus occurs, which causes dysphagia.

Chronic pulmonary histoplasmosis

This form occurs mostly in older patients with underlying pulmonary disease and is associated with cough, weight loss, fevers, and malaise of more than 3 months' duration.[1] Generally, infection involves the apical segments and occurs near emphysematous bullae. Pleural thickening is often seen.[5] If cavitations are present, hemoptysis, sputum production, and increasing dyspnea are common symptoms. On imaging, upper lobe infiltrates and thick-walled cavities may be seen. Fibrosis and scarring may also be seen.

Progressive disseminated histoplasmosis

This form occurs mostly in hosts who are immunocompromised. Major risk factors include exposure to the fungus as an infant, AIDS with CD4 count of less than 150 cells/µL, use of corticosteroids, hematologic malignancy, and solid organ transplantation. Patients requiring tumor necrosis factor antagonists (eg, etanercept, infliximab) are also an increased risk for disseminated histoplasmosis.[6]

After initial exposure, H capsulatum may remain dormant, and reactivation may occur years after initial exposure. The organism may even be transmitted with donated organs.[6]

Symptoms vary depending on duration of illness. The acute form may produce fever, worsening cough, weight loss, malaise, and dyspnea. Approximately 5-20% of patients have CNS involvement. The subacute form is associated with a wide spectrum of symptoms that may occur as a result of dissemination and subacute expression in the affected organs. Aside from constitutional symptoms, gastrointestinal involvement may produce diarrhea and abdominal pain. Cardiac involvement resulting in valvular disease, cardiac insufficiency, or vegetations may produce dyspnea, peripheral edema, angina, and fever. CNS involvement may produce headache, visual and gait disturbances, confusion, seizures, altered consciousness, and neck stiffness or pain. The chronic form is associated with constitutional symptoms. Mucous membrane lesions are common in disseminated histoplasmosis.[5]

Presumed ocular histoplasmosis syndrome

Approximately 1-10% of individuals living in endemic areas have ocular involvement that is usually asymptomatic.[8] Macula involvement may result in blindness.


Granulomatous mediastinitis may result from enlargement of multiple nodes that undergo necrosis. Fibrosing mediastinitis is an uncommon complication associated with excessive fibrosis that invades the structures of the mediastinum. It is caused by Histoplasma antigen release. Most patients are young adults, and women are more commonly affected than men.[5] Associated complications of this condition include pulmonary hypertension, superior vena cava syndrome, airway constriction, and pericarditis with sterile pericardial effusions. Splenic and liver calcifications often help to identify Histoplasma as the causative agent.[1]



Findings on a physical examination are related to the extent and duration of infection. Histoplasmosis may mimic sarcoidosis, and it has been suggested that every patient diagnosed with sarcoidosis should have antigen testing to exclude histoplasmosis.

Acute pulmonary histoplasmosis

Findings are usually minimal. Approximately 5-6% of patients develop rheumatologic manifestations of erythema multiforme, arthritis, and erythema nodosum.[5] Auscultation may rarely reveal rales or wheezes. In cases with high inoculum, individuals may develop severe hypoxemia associated with rales that may mimic acute respiratory distress syndrome. Approximately 10% of patients have asymptomatic pleural effusions.[8] In 5% of patients, pericarditis may be present and can be associated with rubs.[9] Hepatosplenomegaly may occasionally be present.

Chronic pulmonary histoplasmosis

This form may manifest during pulmonary auscultation as nonspecific rales, wheezes, or findings consistent with the extent of underlying pneumonitis, consolidation, or cavitation.

Chronic progressive disseminated histoplasmosis

This condition may produce oropharyngeal ulcers involving the buccal mucosa, tongue, gingiva, and larynx. Lesions do not suggest dissemination. Rare cases of isolated lesions have been seen in individuals who are immunocompetent.

Subacute progressive disseminated histoplasmosis

Gastrointestinal dissemination may result in abdominal mass or intestinal ulcers and lesions. Surgical abdomen may result from intussusception, perforation, or obstruction.

CNS dissemination may produce findings associated with possible mass lesions or meningismus, including cranial nerve deficits, muscle weakness, ataxia, altered consciousness, or focal deficits.

Cardiac dissemination may result in signs and complications of endocarditis, including murmurs, peripheral edema, pulmonary rales or wheezes, petechia, or skin lesions.

Acute progressive disseminated histoplasmosis

CNS manifestations that include a mass lesion, encephalopathy, and meningitis (as observed in the subacute form) occur in 5-20% of patients.

Hepatosplenomegaly and lymphadenopathy may be present. Superior vena cava (SVC) syndrome may be present with lymphadenopathy severe enough to cause obstruction. The resulting increased venous pressure may manifest as dilatation of collaterals in the neck and thorax; edema of the face, neck, and upper torso; and conjunctiva.

Cutaneous lesions are present in 10% of patients. Erythematous maculopapular lesions, ulcerations, purpura, and/or manifestations of endocarditis may be present. Oropharyngeal lesions may also be present.[6]

Presumed ocular histoplasmosis syndrome

Atrophic scars containing foci of lymphocytic cell infiltration termed histo spots may be present and are located posterior to the equator of the eye. If the scars are located on the macula, retinal hemorrhage, detachment, or edema may be present.



The risk of infection is mostly related to environmental exposure and underlying immune status.

Living in endemic areas with contaminated soil increases the risk of exposure.

Inoculum size plays a role. Individuals who are immunocompetent and exposed to a low inoculum of histoplasmosis usually are asymptomatic. Inhalation of a large inoculum can cause diffuse pulmonary symptoms that may have a protracted course.

Immune status and comorbid factors affect causation. Reactivation, reinfection, or complications of infection usually occur in individuals who are immunocompromised or immunosuppressed. Cases of histoplasmosis have been reported in patients receiving infliximab. A high index of suspicion should be present in patients on tumor necrosis factor-alpha inhibitors.[10] Antifungal therapy in these patients is highly effective; however, the safety of restarting tumor necrosis factor inhibitors remains unclear.[11] Histoplasmosis is rare in solid organ transplant patients; most cases have been reported from the midwest, where it is endemic.[12, 13] Chronic pulmonary histoplasmosis is more prevalent in patients with underlying emphysema.

The risk factors include AIDS, primary immunodeficiencies, drug-induced immunosuppressive states, and the extremes of age.

Contributor Information and Disclosures

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.


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.


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.

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