Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content + Print Section ++ For further information, see CMDT Part 36-03: Histoplasmosis + Key Features Print Section ++ ++ 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 + Clinical Findings Print Section ++ ++ 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) + Diagnosis Print Section ++ ++ 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 + Treatment Print Section ++ ++ 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) + Outcome Print Section ++ ++ 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 + References Print Section ++ + +Azar MM et al. Clinical perspectives in the diagnosis and management of histoplasmosis. Clin Chest Med. 2017 Sep; 38(3):403–15. [PubMed: 28797485] + +Azar MM et al. Laboratory diagnostics for histoplasmosis. J Clin Microbiol. 2017 Jun;55(6):1612–20. [PubMed: 28275076] + +Deepe GS Jr. Outbreaks of histoplasmosis: the spores sail. PLoS Pathog. 2018 Sep 13;14(9):e1007213. [PubMed: 30212569] + +Wheat J et al. Central nervous system histoplasmosis: multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment. Medicine. 2018 Mar;97(13):e0245. [PubMed: 29595679] + +Wheat LJ et al. Histoplasmosis. Infect Dis Clin North Am. 2016 Mar;30(1):207–27. [PubMed: 26897068]