eMedicine Specialties > Pulmonology > Infectious Lung Diseases

Histoplasmosis: Follow-up

Author: Jazeela Fayyaz, DO, Senior Fellow, Department of Pulmonology, Lenox Hill Hospital
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
Contributor Information and Disclosures

Updated: Aug 14, 2009

Follow-up

Further 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.⁴
• Chronic pulmonary histoplasmosis
  • Most thin-walled cavities resolve spontaneously.⁴
  • 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.

Further Outpatient Care

• 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.⁶
• 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%.¹³ Routine examination is important to monitor for relapses, whether or not maintenance therapy is initiated.⁶
• Presumed ocular histoplasmosis
  • Monitor the progression of maculopathy with routine ophthalmologic evaluations.
  • Consider laser or prednisone treatment for progressive disease.

Inpatient & Outpatient Medications

• Antifungals
  • The current Infectious Diseases Society of America guidelines recommend itraconazole for mild-to-moderate infection and amphotericin B for severe infection.¹² Itraconazole levels should be monitored starting 2 weeks after the start of treatment. The treatment success rate with itraconazole is 80-100%.⁶
  • Fluconazole is recommended as a second-line agent. Treatment success is approximately 63% with fluconazole; relapse rates may also be higher.³ Resistance to fluconazole may be seen in AIDS patients with histoplasmosis.
  • Voriconazole and posaconazole are also second-line agents; currently, no clinical trials demonstrate benefit with voriconazole and posaconazole.
  • Ketoconazole is no longer recommended because of its toxicity.
  • Echinocandins are not active against histoplasmosis and should not be used.¹²
  • Patients with chronic cavitary pulmonary histoplasmosis should be treated for 1 year.⁴
  • Amphotericin B is the drug of choice for treating overwhelming acute pulmonary histoplasmosis, chronic pulmonary histoplasmosis, and all forms of progressive disseminated pulmonary histoplasmosis. If using amphotericin B for maintenance therapy for acute progressive disseminated histoplasmosis, continue weekly intravenous treatment in an outpatient setting.
  • Treatment is recommended for at least 1 year; immunosuppressed patients may need a longer duration of treatment.⁶
  • Patients with relapse of infection (10-15% of patients) after completion of therapy may require lifelong therapy.⁶
  • Also see the guideline summary, Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America.¹²
• Anti-inflammatory drugs
  • Use NSAIDs when pericarditis is present.
  • Use steroids to decrease the severe hypersensitivity inflammatory response to histoplasmal antigens. Carefully monitor patients with systemic infections or sepsis and those who are immunosuppressed. Assess for signs of superinfection and worsening sepsis.

Transfer

• 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.

Deterrence/Prevention

• 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.
• 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.¹²  
• 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.

Complications

• Mediastinal and hilar lymphadenopathies usually resolve. Granulomatous inflammation causes extensive enlargement with caseating necrosis that may fibrose with progressive healing. Occasionally, the lymph nodes may remain enlarged, compressing surrounding structures and distorting anatomic architecture. Postobstructive pneumonia, bronchiectasis, persistent cough, hemoptysis, and/or dysphagia (rarely) are consequences of continued compression. Broncholiths may appear with erosion into a bronchus. Histoplasmal-induced mediastinal fibrosis is the most benign nonmalignant cause of SVC syndrome.
• Cavitary lesions develop predominantly in chronic pulmonary histoplasmosis.  When persistent or progressive, the cavities are excised surgically. With continued infection, fibrosis and pulmonary scarring continue, causing a progressive deterioration in lung function.
• Pulmonary lesions heal to become a residual nodule, usually 1-4 cm in diameter. Occasionally, the histoplasmoma may enlarge as an immunologic response to the yeast antigens present within the core. Histoplasmomas are common sites of reactivation.
• Adrenal insufficiency develops in 5-10% of patients with subacute pulmonary disseminated histoplasmosis, regardless of treatment.⁶
• Overwhelming sepsis with disseminated intravascular coagulation and gastrointestinal bleeding is common with acute progressive disseminated histoplasmosis.
• Pleural effusions are rare. If present, the effusion is a lymphocytic-predominant exudate. Although not necessary, a pleural biopsy usually reveals noncaseating granulomas. The effusion normally resolves spontaneously over several weeks. No treatment is necessary unless the effusion persists for more than 3-4 weeks or if it occurs in an immunocompromised individual.

Prognosis

• Acute pulmonary histoplasmosis is associated with a good outcome.
• Chronic progressive disseminated histoplasmosis has a long-term protracted course, lasting up to years, with long asymptomatic periods.
• If untreated, subacute progressive disseminated histoplasmosis results in death within 2-24 months.
• A relapse rate of 50% is associated with acute progressive disseminated histoplasmosis, if treated. The rate decreases to 10-20% with life-long antifungal maintenance. Death is imminent without treatment.⁶
• Cure rates in histoplasmal meningitis with therapy are 50%, with a high rate of relapse.
• In histoplasmal endocarditis, medical therapy alone rarely is curative.

Patient Education

• For excellent patient education resources, visit eMedicine's Procedures Center. Additionally, see eMedicine's patient education article Bronchoscopy.

Miscellaneous

Medicolegal Pitfalls

• Histoplasmosis has varied presentations. A thorough evaluation is essential to exclude other etiologies.

Special Concerns

• Inform travelers to endemic areas how to minimize exposure.
• Geriatric and pediatric populations without full immunity are at higher risk of infection.
• Individuals who are immunocompromised from underlying disease, especially AIDS and lymphoma, or from chronic immunosuppression are at higher risk of infection.

The authors and editors of eMedicine 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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