Histoplasmosis

July 2006

Chapter Contents

Background

Subjective

Objective

Assessment

Plan

Patient Education

References

Table 1. Common Clinical Manifestations of Histoplasmosis

Background

Histoplasmosis is caused by Histoplasma capsulatum , a fungus that thrives in soil contaminated by certain bird and bat droppings. In the United States, H capsulatum is found most often along the Ohio and Mississippi river valleys, and in the central, mid-Atlantic and south-central states, from Alabama to southwest Texas. In highly prevalent areas, such as Indianapolis and Kansas City, more than 80% of the population has been exposed to Histoplasma through inhalation of airborne infectious elements. Histoplasmosis is also found in the Canadian provinces of Quebec and Ontario, Mexico, Central and South America, Africa, East Asia, and Australia.

The initial infection usually causes either no symptoms or only a mild flulike illness. However, immunosuppressed individuals may develop disseminated disease. Progressive disseminated histoplasmosis often represents a reactivation of latent infection, occurs late in the course of HIV disease (the CD4 count usually is <150 cells/µL), and is an AIDS-defining illness. Pulmonary histoplasmosis (without dissemination) may occur in people with higher CD4 counts. Within endemic areas, histoplasmosis accounts for 5% of opportunistic infections among AIDS patients. In hyperendemic areas, the prevalence of histoplasmosis may reach 25% among patients with AIDS. The incidence of histoplasmosis in the United States has declined with the use of effective antiretroviral therapy (ART).

Table 1 describes common clinical features that may be associated with histoplasmosis.

S: Subjective

Histoplasmosis may be difficult to diagnose because the symptoms are nonspecific. In addition, clinicians may not suspect this diagnosis in low-prevalence areas.

The patient complains of fever, weight loss, fatigue, cough, and shortness of breath. He or she may also note skin lesions, adenopathy, central nervous system (CNS) changes, oropharyngeal ulcers, nausea, diarrhea, or abdominal pain. Symptoms usually begin several weeks before presentation. On occasion, histoplasmosis presents abruptly as a sepsis-like syndrome.

The following activities are associated with significant risk of exposure (note that absence of reported exposures does not rule out histoplasmosis):

• Residence or travel in endemic areas (or coastal AIDS centers of New York, Los Angeles, San Francisco, and Miami)
• Occupational history of farming or construction/remodeling
• Hobbies that involve contact with caves, bird roosts or nests, or farm areas
• Contact with soil with a high organic content and undisturbed bird droppings, such as around old chicken coops and bird roosts

O: Objective

Measure vital signs and document fever. Perform a complete physical examination, with special attention to the lymph nodes, lungs, abdomen, skin, and neurologic system. Common findings include enlargement of the liver, spleen, and lymph nodes. Skin lesions and oropharyngeal ulcers may be seen.

A: Assessment

A partial differential diagnosis includes:

• Other deep-seated fungal infections, such as cryptococcosis and coccidioidomycosis
• Mycobacterial disease ( Mycobacterium tuberculosis or Mycobacterium avium complex)
• Pneumocystic pneumonia
• Lymphoma

P: Plan

Diagnostic Evaluation

• The H capsulatum polysaccharide antigen test is sensitive and specific. The test is most sensitive for urine samples, but can be used on serum, bronchial fluids, or cerebrospinal fluid specimens. Results may be obtained in a few days. Urine antigen levels can be used to monitor the response to therapy. The antigen test is available from a private laboratory, MiraVista Diagnostics ( http://www.miravistalabs.com ).
• Cultures of blood, bone marrow, and specimens from other sources have reasonable sensitivity but may take several weeks. Wright stain of buffy coat of blood may reveal intracellular organisms.
• Biopsies of lymph nodes, liver, cutaneous lesions, and lungs may be diagnostic in up to 50% of cases; bone marrow can be stained with methenamine silver to show the organism within macrophages.
• Lactate dehydrogenase (LDH) and ferritin, although not specific, may be markedly elevated in disseminated disease.
• Complete blood count and chemistry panels may show pancytopenia, elevated creatinine, or abnormal liver function tests.

Treatment

Treatment consists of 2 phases: induction and chronic maintenance.

Induction therapy

Mild to moderate disseminated histoplasmosis without CNS involvement

Administer itraconazole 200 mg orally 3 times daily or 300 mg orally twice daily for 3 days, followed by itraconazole 200 mg twice daily for 12 weeks. (See " Treatment note " below regarding itraconazole.) Induction therapy must be followed by maintenance therapy (see below).

Severe disseminated histoplasmosis

Severe infection requires intravenous induction therapy with amphotericin B 0.7-1.0 mg/kg/d (or a lipid formulation 3-5 mg/kg/d). After 3-10 days of therapy and stabilization of the patient's clinical status, therapy may be switched to itraconazole 200 mg twice daily to complete 12 weeks of therapy. If itraconazole is not available or is not tolerated, fluconazole 800 mg orally once daily can be used as an alternative. (See "Treatment note" below regarding itraconazole and fluconazole.) CNS infection must be treated with a full course of amphotericin B, because of poor penetration of itraconazole into the CNS. Induction therapy must be followed by maintenance therapy (see below).

Maintenance/suppressive therapy

Lifelong maintenance therapy must be given to prevent relapse after the 12-week course of induction therapy and typically includes itraconazole 200 mg orally once daily or twice daily. Amphotericin B 50 mg once weekly or fluconazole 400-800 mg daily are alternatives for those who cannot tolerate or cannot obtain itraconazole. (See "Treatment note" below regarding itraconazole and fluconazole.)

It is not known whether maintenance therapy can be discontinued safely in patients who achieve immune reconstitution during antiretroviral therapy.

Treatment note

Itraconazole and fluconazole may cause fetal abnormalities if taken during the first trimester of pregnancy. Check pregnancy status in women of childbearing potential before starting these medications, and ensure that women are using appropriate birth control. Note the possibility of drug interactions involving itraconazole, especially with rifamycins.

Patient Education

• Histoplasmosis is not transmitted from person to person, so isolation is not necessary.
• Patients should take all of their medications exactly as prescribed by their health care providers.
• Even with maintenance therapy, relapses can occur. Patients should call their providers immediately if symptoms worsen.
• Itraconazole and fluconazole may cause birth defects. Women who are taking either of these medicines should avoid pregnancy. In addition, itraconazole interacts with some other medications; patients should tell their providers if they begin any other new medicines while taking itraconazole.

References

• U.S. Public Health Service, Infectious Diseases Society of America. Guidelines for preventing opportunistic infections among HIV-infected persons--2002 . MMWR Recomm Rep. 2002 Jun 14;51(RR08);1-46. Available online at aidsinfo.nih.gov/Guidelines/. Accessed May 19, 2006.
• Centers for Disease Control and Prevention, National Institutes of Health, HIV Medicine Association/Infectious Diseases Society of America. Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents . MMWR Recomm Rep. 2004 Dec 17; 53(RR15);1-112. Available online at aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=14. Accessed May 19, 2006.
• Deepe GS Jr. Histoplasma Capsulatum . In: Mandell G, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 6th ed . Philadelphia: Elsevier; 2005:3012-26.
• Goldman M, Zackin R, Fichtenbaum CJ, et al. Safety of discontinuation of maintenance therapy for disseminated histoplasmosis after immunologic response to antiretroviral therapy . Clin Infect Dis. 2004 May 15;38(10):1485-9.
• Wheat J. Histoplasmosis . In: Dolin R, Masur H, Saag M, eds. AIDS Therapy, 2nd ed . Philadelphia: Churchill Livingstone; 2003:511-521.
• Wheat J, Sarosi G, McKinsey D, et al. Practice guidelines for the management of patients with histoplasmosis. Infectious Diseases Society of America . Clin Infect Dis. 2000 Apr;30(4):688-95.