The most common clinical presentation in patients with HIV/ AIDS is disseminated disease. Constitutional symptoms are prominent and include fever, weight loss, fatigue, lymphadenopathy, and cough. Ten percent to 20% of patients will present with septic shock.11 Chest radiographs can show diffuse infiltrates, usually in a miliary reticulonodular pattern16; however, findings on chest radiographs also may be normal,17 so a high index of suspicion is needed for diagnosis.
In SOT recipients, fever, fatigue, and dry cough are the most common presenting symptoms. Other reported symptoms have included malaise, fatigue, and dyspnea for up to 30 days before presentation. An infiltrate seen in initial chest radiographs or CT scans commonly has a diffuse miliary pattern.13
Histoplasma antigen testing of urine samples is commonly used for diagnosis. Sensitivity is 90% in patients with disseminated disease and 75% in patients with acute pulmonary histoplasmosis.18 Specificity has been reported to be as high as 98%18; however, false-positive results can occur in patients who are infected with other endemic mycotic pathogens. 19 Positive serum antigen assays but negative urine antigen assays are uncommon and should raise suspicion for a false-positive serum assay.10,16
In tissue specimens, H capsulatum appears as a distinctive 2- to 4-mm, oval, narrow-based budding yeast. Routine H&E staining will not always result in visualization of the organisms; instead, a GMS stain should be used. Routine peripheral blood smears from patients with serious illness and disseminated disease will sometimes show yeast within neutrophils.10
Data from a prospective randomized controlled trial showed that antifungal prophylaxis with oral itraconazole(Drug information on itraconazole) 200 mg qd for patients with HIV-1 infection and CD4+ T-cell counts of less than 100/μL who are living in regions in which H capsulatum is highly endemic can reduce the frequency of disease; however, no survival benefit was observed in the patients who were receiving itraconazole therapy.20 Avoidance of activities associated with increased risk of histoplasmosis, such as remodeling or demolishing old buildings, cleaning chicken coops, exploring caves, disturbing areas contaminated with bird or bat droppings, and so on, has been recommended.4
Prophylaxis in patients who have hematological malignancies or who have undergone HSCT or SOT has not been studied, but the risk of histoplasmosis appears low. Prophylaxis may be appropriate in patients with a history of active histoplasmosis within 2 years of planned immunosuppressive therapy or transplant; however, the optimal duration of prophylaxis is unknown. Urine antigen testing should be obtained before the treatment or transplant and should be measured every 2 to 3 months during intensive immunosuppression. If there is an increase in the titer, further workup for active disease is indicated as well as prompt initiation of empirical antifungal therapy.8,21
The antifungal agents that have proved to be effective and are preferred for the treatment of histoplasmosis include amphotericin B(Drug information on amphotericin b), lipid formulations of amphotericin B, and itraconazole. Echinocandin therapy is not recommended.
Patients with severe disseminated disease should be treated with intravenous liposomal amphotericin B (3 mg/kg/d), intravenous amphotericin B lipid complex (5 mg/kg/d), or intravenous amphotericin B deoxycholate (0.7 to 1 mg/kg/d) for 1 to 2 weeks, followed by oral itraconazole 200 mg bid for at least 12 months.8 In a randomized doubleblind trial that compared conventional amphotericin B with liposomal amphotericin B for induction therapy in patients who have histoplasmosis and HIV/AIDS, liposomal amphotericin B was less toxic and was associated with improved survival.22 For patients with mild to moderate histoplasmosis, treatment with oral itraconazole 200 mg bid for at least 12 months is recommended. Longer treatment may be required in those patients who have persistent immunodeficiency.8