Histoplasmosis

For further information, see CMDT Part 36-03: Histoplasmosis

Essentials of Diagnosis

• Exposure to bird and bat droppings; common along river valleys (especially the Ohio River and the Mississippi River valleys)

• Most patients are asymptomatic; respiratory illness is the most common clinical problem

• Disseminated disease is common in AIDS or other immunosuppressed states; poor prognosis

• Blood and bone marrow cultures and urine polysaccharide antigen are useful in diagnosis of disseminated disease

General Considerations

• Acute histoplasmosis frequently occurs in epidemics, often when soil containing infected bird or bat droppings is disturbed

• Infection presumably occurs by inhalation of conidia

• These convert into small budding cells that are engulfed by phagocytes in the lungs

• The organism then proliferates and undergoes lymphohematogenous spread to other organs

• Progressive disseminated histoplasmosis is commonly seen in patients with underlying HIV infection (with CD4 cell counts usually < 100 cells/mcL) or other conditions of impaired cellular immunity

Demographics

• Endemic areas

  • Central and eastern United States (especially Ohio River and Mississippi River valleys)

  • Eastern Canada

  • Mexico

  • Central America

  • South America

  • Africa

  • Southeast Asia

• Cases are increasingly being recognized outside of endemic areas

• Chronic progressive pulmonary histoplasmosis occurs in older patients with chronic obstructive pulmonary disease

Symptoms and Signs

• Most cases are asymptomatic with no pulmonary symptoms or signs even in those who later have calcifications on chest radiograph

• Mild symptomatic illness: influenza-like illness, often lasting 1–4 days

• More severe illness: presents as atypical pneumonia, with fever, cough, and mild central chest pain for 5–15 days

• Physical examination is usually normal

• Acute pulmonary histoplasmosis: clinical manifestations can vary from a mild influenza-like illness to life-threatening pneumonia

• Progressive histoplasmosis

  • Fever, weight loss, prostration

  • Dyspnea, cough

  • Ulcers of the mucous membranes of the oropharynx

  • Liver and spleen are nearly always enlarged

  • All organs of the body are involved, particularly the adrenal glands, though this infrequently results in adrenal insufficiency

  • Gastrointestinal involvement may mimic inflammatory bowel disease

  • Central nervous system (CNS) invasion occurs in 5–10% of individuals with disseminated disease

• Disseminated histoplasmosis occurs mainly in immunocompromised patients

  • Fever and multiple organ system involvement

  • Presentation may be fulminant, simulating septic shock

Differential Diagnosis

• Influenza

• Atypical pneumonia

• Tuberculosis

• Coccidioidomycosis

• Sarcoidosis

• Blastomycosis

• Pneumoconiosis

• Pneumocystis jirovecii pneumonia

• Lymphoma (including lymphocytic interstitial pneumonia)

Laboratory Tests

• Elevations of serum lactate dehydrogenase (marked) and ferritin are common

• Serum aspartate aminotransferase levels are mildly elevated

• Anemia of chronic disease occurs in chronic pulmonary histoplasmosis

• Sputum culture is rarely positive except in chronic pulmonary histoplasmosis

• Antigen testing of bronchoalveolar lavage fluid may be helpful in acute disease

• Blood or bone marrow cultures are positive in > 80% of disseminated disease in immunocompromised individuals

• Bone marrow involvement with pancytopenia may be prominent in disseminated forms

• Urine antigen test

  • Sensitivity > 90% for disseminated disease in immunocompromised patients

  • Declining titer is useful to follow as a marker of response to therapy

• Combination of a first morning urine and serum polysaccharide antigen assays has an 83% sensitivity for the diagnosis of acute pulmonary histoplasmosis

• Diagnosis of CNS disease requires antigen and antibody testing of the cerebrospinal fluid (CSF) and serum as well as urine antigen testing

Imaging Studies

• Lung and splenic calcifications on radiographs may reflect past infection

• Radiographic findings during acute illness are variable and nonspecific

• In profoundly immunocompromised individuals with disseminated disease: chest radiograph may show a miliary pattern

Medications

• Itraconazole is treatment of choice for progressive localized disease and for mild to moderately severe nonmeningeal disseminated disease in both immunocompromised and immunocompetent patients

  • Oral itraconazole, 200–400 mg/day divided into two doses

  • Oral solution is better absorbed than capsule formulation

  • Duration of therapy ranges from weeks to several months depending on the severity of illness

  • Response rates of ∼80% can be expected

• Intravenous liposomal amphotericin B, 3 mg/kg/day is used in patients with more severe illness, such as meningitis

• Recent guidelines favor use of amphotericin B liposomal or lipid complex formulations at a dose of 3 mg/kg/day over amphotericin B deoxycholate

• Once the patient is stable and afebrile (which usually occurs in 3–7 days), oral itraconazole can replace amphotericin

• Patients with AIDS-related histoplasmosis

  • Require lifelong suppressive therapy with itraconazole, 200 mg/day orally

  • May discontinue secondary prophylaxis if immune reconstitution occurs in response to antiretroviral therapy

• Adding rituximab may be beneficial (begin only after testing for prior hepatitis B infection requiring medication prophylaxis)

Complications

• Granulomatous mediastinitis

Prognosis

• Acute histoplasmosis: lasts from 1 week to 6 months but is almost never fatal

• Progressive disseminated histoplasmosis: death ensues rapidly without treatment