Histoplasmosis Treatment & Management

Updated: Sep 15, 2020
  • Author: Jazeela Fayyaz, DO; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Medical Care

Most infections in individuals who are immunocompetent are self-limiting and do not require therapy. In cases of prolonged infection, cases of systemic infection, or those involving individuals who are immunocompromised, medical treatment is recommended. [27]

Acute pulmonary histoplasmosis

No treatment is required for individuals who are asymptomatic.

Monitor mild symptoms (without treatment).

In patients with prolonged symptoms (>4 wk) or those with overwhelming pulmonary involvement, initiate medical therapy with itraconazole for 6-12 weeks. Response to therapy should be monitored via chest imaging. Patients should be monitored for several years after treatment for possible relapse. [27]

Patients with severe infection should be treated with amphotericin B for 1-2 weeks; once the patient is stable, amphotericin B may be changed to itraconazole and should be continued for 1 year. [28] Patients with acute respiratory distress symptoms may require methylprednisone for 1-2 weeks. [27]

Chronic pulmonary histoplasmosis

This often is fatal if not treated; the mortality rate may be as high as 50% without treatment, compared with a mortality rate of 28% with treatment. [11]

Patients may have a progressive loss of pulmonary function.

Patients with cavitary lesions must be treated, in most patients itraconazole is sufficient and should be given for one year. Relapse may occur in up to 15% of patients.

Persistent cavitations despite multiple courses of medical treatment warrant surgical consideration.

Progressive disseminated histoplasmosis and meningitis

Initiate medical therapy for all patients with progressive disseminated histoplasmosis and meningitis.

Hemodynamic and respiratory compromise from pericardial and pleural involvement warrants immediate procedural intervention. Perform thoracentesis or pericardiocentesis in patients with severe pleural effusions and pericardial tamponade, respectively.

Cutaneous and rheumatologic histoplasmosis

Lesions are self-limiting. Therapy is indicated only for prolonged episodes or in individuals who are immunosuppressed.


Antifungal therapy does not play a role. Bronchoscopic or surgical removal may be required. [27]

Ocular histoplasmosis

Treat extensive maculopathy in presumed ocular histoplasmosis with steroids.

Mediastinal histoplasmosis

Treatment for mediastinal granuloma is not recommended in asymptomatic patients; for symptomatic patients, itraconazole may be used for 6-12 weeks, although clinical trials to support this are lacking. [28]

Antifungal therapy is not effective for fibrosing mediastinitis; corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) also are ineffective. Surgery is not recommended. Intravascular stents may be placed to open major vessels compromised by mediastinal fibrosis.

Antifungals are not recommended for pericarditis because it is an inflammatory reaction.


Surgical Care

Use surgical procedures for diagnostic purposes when other modalities are unrevealing. Intervention is also required when medical therapy is insufficient to alleviate the effects of progressive fibrosis, calcification, and scarring.

Thoracic surgery

In rare cases when serologic and procedural modalities cannot indicate a definitive diagnosis, consider obtaining sufficient tissue samples using thoracoscopy or by performing an open lung biopsy.

Surgical resection of pulmonary cavitary lesions is required when repeated relapses or progressive disease occurs despite repeated intensive medical therapy.

Progressive fibrosis of the mediastinum can produce traction or invade into adjacent structures and cause a distorted anatomy. Surgery with spiral vein grafts or vascular stents may be necessary to treat SVC syndrome associated with fibrosing mediastinitis. Surgery may also be required to alleviate scarring, to retain structural integrity, and to alleviate symptoms. The possibility of extensive adhesion and distortion associates surgery with high mortality rates.

Mechanical compression by mediastinal and hilar granulomatosis may require surgical excision. However, surgery is risky because of the possibility of spilling necrotic material into the mediastinum and initiating further fibrotic reaction. Patients may develop extensive symptoms from compression of pulmonary, vascular, and rarely, esophageal structures.

Cardiac surgery

Pericardial window placement may be needed when pericardiocentesis is insufficient to alleviate pericardial tamponade.

Endovascular histoplasmosis may result in infected valves and aneurysm formation, which requires surgical excision of infected valves and aneurysm repair. Treating endovascular histoplasmosis with medical therapy alone is rarely curative.

Ophthalmologic treatment

Laser photocoagulation treatment may be needed in patients with active neovascular membrane formation due to choroiditis.

Overgrowth may result in progressive vision loss.


Inpatient Care

Acute pulmonary histoplasmosis

In rare cases of overwhelming infection, extensive pulmonary involvement may cause severe hypoxemia and acute respiratory distress syndrome. In these instances, initiate antifungal therapy and arrange inpatient supportive respiratory care. [12]

Chronic pulmonary histoplasmosis

Most thin-walled cavities resolve spontaneously. [12] Superinfection of cavitations may occasionally require inpatient treatment with appropriate antimicrobials.

Progressive disseminated histoplasmosis

Chronic infection has a long protracted course over months to years, with long asymptomatic periods. Inpatient care is required when transformation to subacute or acute infection occurs.

Subacute infection requires inpatient treatment.

Acute infection is life threatening and requires immediate inpatient care. Many of these patients are immunocompromised and have multiorgan involvement. Patients with AIDS usually have other opportunistic infections. Disseminated intravascular coagulation, overwhelming sepsis, and associated gastrointestinal bleeding require ICU monitoring.


Intensive care monitoring

Patients may require inpatient intensive care monitoring, especially those with progressive disseminated histoplasmosis and overwhelming acute progressive histoplasmosis. Respiratory and systemic support is needed for decompensation.

Procedural suite

If studies are not diagnostic, bronchoscopy may be needed for tissue and lavage samples. Secure facilities for pericardiocentesis in cases of pericardial tamponade.

Surgical suite

Surgical interventions are rarely needed on an emergency basis. Rarely, a patient with pericardial tamponade that is not amenable to a pericardiocentesis needs placement of a pericardial window. Elective procedures to excise a persistent cavitation, to decompress mediastinal fibrosis or granulomatosis, and to obtain tissue biopsy may be required.



Obtain the following consultations when complications of histoplasmal infection compromise organ systems; seek out a specialist to perform diagnostic procedures if other modalities do not provide adequate information to make a diagnosis:

  • Pulmonary specialist: Bronchoscopy may be needed for diagnostic purposes. Bronchial washings and aspirates are sent for culture and analysis. Transbronchial tissue biopsy provides specimens for histiologic examination.

  • Cardiology specialist: Pericardiocentesis is required to restore hemodynamic stability in patients with pericardial tamponade.

  • Cardiothoracic or ophthalmologic surgeon: Such surgery may be needed if complications arise or if further diagnostic options are required.



Most outbreaks are associated with activities that disrupt contaminated soil in endemic areas. Decontaminating infected soil with a 3% formalin solution, with the assistance of local and federal agencies, can prevent aerosolization of conidia and yeast.

Educate individuals residing or traveling in endemic areas about exposure risks, including both leisure and work activities. Advance preparation reduces exposure to contaminated soil, bat and bird dwellings, and inoculum.

Workers participating in high-risk activities should wear respirators. Water sprays should be used during demolition work to decrease dust. [12]

Itraconazole (200 mg/d) has been shown to be effective in the prevention of histoplasmosis in AIDS patients with CD4 counts of less than 150 cells/µL who are at high risk for infection. [28]

Although many exposed immunocompetent individuals from endemic areas do not develop extensive clinical manifestations, reactivation can occur. These individuals, when placed at risk for immunosuppression because of impaired immunity or prolonged drug suppression, may develop active infection from prior lesions. Knowing their history of prior exposures can help to detect and treat subsequent complications.

Prior infection does not prevent future reinfection. Individuals should take similar precautions when facing increased exposure risk.


Long-Term Monitoring

To assess resolution of the disease, periodically monitor all patients with histoplasmal infection in an outpatient setting.

Chronic pulmonary histoplasmosis

Periodically observe thin-walled cavities with chest radiography to monitor for resolution. If symptoms or cavitations persist over a 2- to 4-month period, initiate antimicrobial treatment.

All cavitations require close monitoring. The relapse rate for thick-walled cavities is approximately 20%. Patients with progressive disease and those with repeated relapses despite medical therapy need surgical resection. With ongoing infection, pulmonary function progressively declines. Monitor disease progression or resolution with pulmonary function tests.

Most relapses occur within 2 years. Chest radiography should be performed every 6 months for the first year and then annually for 4 years to monitor for relapse. [15]

Progressive disseminated histoplasmosis

In chronic and subacute infection, 90% of cases resolve with treatment. Routine examination for relapses is helpful. If relapse occurs, conduct a systemic evaluation for infection by evaluating cardiovascular, neurologic, adrenal, and gastrointestinal systems.

Acute infection is associated with a high relapse rate, up to 50% in patients with AIDS. With life-long antifungal maintenance therapy, the relapse rate drops to 10-20%. [29] Routine examination is important to monitor for relapses, whether or not maintenance therapy is initiated. [15]

Presumed ocular histoplasmosis

Monitor the progression of maculopathy with routine ophthalmologic evaluations. Consider laser or prednisone treatment for progressive disease.