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For progressive localized disease and for mild to moderately severe nonmeningeal disseminated disease in immunocompetent or immunocompromised patients, itraconazole, 200 400 mg/d orally divided into two doses, is the treatment of choice with an overall response rate of approximately 80% The oral solution is better absorbed than the capsule formulation Duration of therapy ranges from weeks to several months depending on the severity of illness Amphotericin B is reserved for individuals who cannot take oral medications; for those who have not responded to itraconazole therapy; for those with meningitis; and for management of severe disseminated disease in an immunocompromised person Up to 25 g total may need to be given in the latter two situations, though this course of treatment can be abbreviated and oral itraconazole instituted once clinical stabilization has occurred (See Additional Reading at the end of the chapter) Liposomal amphotericin B in a dosage of 3 mg/kg/d intravenously may be more effective and safer than conventional amphotericin B in seriously ill individuals Patients with AIDS-related histoplasmosis require lifelong suppressive therapy with itraconazole, 200 400 mg/d orally, although secondary prophylaxis may be discontinued if immune reconstitution occurs in response to antiretroviral therapy

Wheat LJ Histoplasmosis: a review for physicians from non-endemic areas Mycoses 2006 Jul;49(4):274 82 [PMID: 16784440]

Influenza-like illness with malaise, fever, backache, headache, and cough Arthralgia and periarticular swelling of knees and ankles Erythema nodosum common Dissemination may result in meningitis, bony lesions, or skin and soft tissue abscesses Chest radiograph findings vary widely from pneumonitis to cavitation Serologic tests useful; spherules containing endospores demonstrable in sputum or tissues

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Most patients with progressive pulmonary disease show anemia of chronic disease Bone marrow involvement may be prominent in disseminated forms with occurrence of pancytopenia Alkaline phosphatase and marked lactate dehydrogenase (LDH) and ferritin elevations are also common In pulmonary disease, sputum culture is rarely positive except in chronic disease; antigen testing of bronchoalveolar lavage fluid may be helpful in acute disease Blood or bone marrow cultures from immunocompromised patients with acute disseminated disease are positive more than 80% of the time but may take several weeks A urine antigen assay has a sensitivity of greater than 90% for disseminated disease in AIDS patients and can be used to follow response to therapy The sensitivity of screening immunodiffusion is 70% in acute pulmonary histoplasmosis, and complement fixation titers are positive in about 80% of cases A combination of these two

Coccidioidomycosis should be considered in the diagnosis of any obscure illness in a patient who has lived in or visited an endemic area Infection results from the inhalation of arthroconidia of Coccidioides immitis or Coccidioides posadasii; both organisms are molds that grow in soil in certain arid regions of the

southwestern United States, in Mexico, and in Central and South America Less than 1% of immunocompetent persons show dissemination, but among these patients, the mortality rate is high In HIV-infected people in endemic areas, coccidioidomycosis is a common opportunistic infection In these patients, disease manifestations range from focal pulmonary infiltrates to widespread miliary disease with multiple organ involvement and meningitis

FIGURE 10-7

Symptoms of primary coccidioidomycosis occur in about 40% of infections Symptom onset (after an incubation period of 10 30 days) is usually that of a respiratory tract illness with fever and occasionally chills Pleuritic pain is common Nasopharyngitis may be followed by bronchitis accompanied by a dry or slightly productive cough Arthralgia accompanied by periarticular swelling, often of the knees and ankles, is common Erythema nodosum may appear 2 20 days after onset of symptoms Persistent pulmonary lesions, varying from cavities and abscesses to parenchymal nodular densities or bronchiectasis, occur in about 5% of diagnosed cases Disseminated disease occurs in about 01% of white and 1% of nonwhite patients Filipinos and blacks are especially susceptible, as are pregnant women of all races Any organ may be involved Pulmonary findings usually become more pronounced, with mediastinal lymph node enlargement, cough, and increased sputum production Lung abscesses may rupture into the pleural space, producing an empyema These may also extend to bones and skin, and pericardial and myocardial involvement has been occasionally observed Fungemia may occur and is characterized clinically by a diffuse miliary pattern on chest radiograph and by early death The course may be particularly rapid in immunosuppressed patients Bone lesions most often occur at bony prominences Meningitis occurs in 30 50% of cases of dissemination Subcutaneous abscesses and verrucous skin lesions are especially common in fulminating cases Lymphadenitis may occur and may progress to suppuration Mediastinal and retroperitoneal abscesses are not uncommon HIV-infected persons with disseminated disease have a higher incidence of miliary infiltrates, lymphadenopathy, and meningitis, but skin lesions are uncommon

HIV-related coccidioidomycosis, the false-negative rate may be as high as 30% Demonstrable complement-fixing antibodies in spinal fluid are diagnostic of coccidioidal meningitis These are found in over 90% of cases Spinal fluid findings include increased cell count with lymphocytosis and reduced glucose Spinal fluid culture is positive in approximately 30% of meningitis cases Spherules filled with endospores may be found in biopsy specimens; though they are not infectious, they convert to the highly contagious arthroconidia when grown in culture media Blood cultures are rarely positive

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