Histoplasmosis disseminated

Cytomegalovirus retinitis (with loss of vision) Encephalopathy, HIV-related Herpes simplex chronic ulcer(s) (duration >1 month) or bronchitis, pneumonitis, or esophagitis Histoplasmosis, disseminated or extrapulmonary Isosporiasis, chronic intestinal (duration >1 month) Kaposi s sarcoma... 

In patients exposed to a large inoculum and in immunocompromised hosts, progressive illness, disseminated histoplasmosis, occurs. The clinical severity of the diverse forms of disseminated histoplasmosis (Table 38-1) generally parallels the degree of macrophage parasitization observed. 

Acute (infantile) disseminated histoplasmosis is seen in infants and young children and (rarely) in adults with Hodgkin s disease or other lympho-... 

Disseminated histoplasmosis Acute (Infantile) Subacute Progressive histoplasmosis (immunocompetent patients and immunosuppressed patients without AIDS) 0.02-0.05 Disseminated histoplasmosis Untreated mortality 83% to 93% relapse 5% to 23% in non-AIDS patients therapy is recommended tor all patients Nonimmunosuppressedpatients Ketoconazole 400 mj day orally x 6-12 months or amphotericin B 35 mg/kg IV Immunosuppressed patients (non-AIDS) or endocarditis or CNS disease Amphotericin B >35 mg/kg x 3 months followed by fluconazole or itraconazole 200 mg orally twice daily x 12 months Life-threatening disease Amphotericin B 0.7-1 mg/kg/day IV for a total dosage of 35 mj kg over 2-4 months once the patient is afebrile, able to take oral medications, and no longer requires blood pressure or ventilatory support therapy can be changed to itraconazole 200 mg orally twice daily for 6-18 months Non-life-threatening disease Itraconazole 200-400 mg orally daily for 6-18 months fluconazole therapy 400-800 mg daily should be reserved for patients intolerant to itraconazole, and the development of resistance can lead to relapses... 

Most adults with disseminated histoplasmosis demonstrate a mild, chronic form of the disease. Untreated patients are often ill for 10 to 20 years, with long asymptomatic periods interrupted by relapses characterized by weight loss, weakness, and fatigue. 

In the AIDS patient with progressive disseminated histoplasmosis, the diagnosis is best established by bone marrow biopsy and culture, which yield positive cultures in 90% of patients. 

Patients with mild, self-limited disease, chronic disseminated disease, or chronic pulmonary histoplasmosis who have no underlying immunosuppression can usually be treated with either oral ketoconazole or IV amphotericin B. 

Histoplasmosis (capsules and injection) Treatment of histoplasmosis, including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis in nonimmunocompromised or immunocompromised patients. 

Amphotericin-B, an amphoteric polyene macrolide remains the most effective for severe systemic mycoses. It is indicated for systemic mycoses such as disseminated candidiasis, cryptococcosis, aspergillosis, mucormycosis, coccidioidomycosis, histoplasmosis, extracutaneous sporotrichosis and blastomycosis. It is a fungicidal antibiotic without antibacterial activity. It binds to ergosterol in the... 

Patients with HIV infection are at risk of developing disseminated histoplasmosis and coccidioidomycosis. In otherwise healthy people such infections are usually subclinical, or self-limiting within the lungs. 

Itraconazole is most useful in the long-term suppressive treatment of disseminated histoplasmosis in AIDS and in the oral treatment of nonmeningeal, non-life-threatening blastomycosis. It appears to be the drug of choice for all forms of sporotrichosis except meningitis and may have a lower relapse rate in the treatment of disseminated coccidioidomycosis than does fluconazole. 

Cryptococcosis blastomycosis systemic candidiasis disseminated forms of moniliasis, coccidioidomycosis, and histoplasmosis zygomycosis sporotrichosis and aspergillosis (Fungizone) IV Infusion Dosage based on patient tolerance, severity of infection. Initially, 1-mg test dose is given over 20-30 min. If test dose is tolerated, 5-mg dose may be given the same day. Subsequently, increases of 5 mg/dose are made q 12-24h until desired daily dose is reached. Alternatively, if test dose is tolerated, a dose of 0.25 mg/kg is given same day increased to 0.5 mg/kg the second day. Dose increased until desired daily dose reached. Total daily dose 1 mg/kg/day up to 1.5 mg/kg every other day. Do not exceed maximum total daily dose of 1.5 mg/kg. 

Unlabeled Uses Suppression of histoplasmosis treatment of disseminated sporotrichosis, fungal pneumonia and septicemia, or ringworm of the hand... 

Liposomal amphotericin (3 mg/kg/day) has been compared with conventional amphotericin (0.7 mg/kg/day) for induction therapy of moderate to severe disseminated histoplasmosis in a randomized, double-blind, multicenter trial in 81 patients with AIDS (119). The duration of induction was 2 weeks, to be followed by 10 weeks of itraconazole in the case of a response. Clinical success was achieved in 14 of 22 patients treated with conventional amphotericin compared with 45 of 51 patients who received liposomal amphotericin (difference, 24% 95% Cl = 1%, 52%). Culture conversion rates were similar. Three patients treated with conventional amphotericin and one treated with liposomal amphotericin died during induction. Infusion-related adverse effects were more common with conventional amphotericin (63%) than with liposomal amphotericin (25%). Nephrotoxicity occurred in 37% of patients treated with conventional amphotericin and 9% of patients treated with liposomal amphotericin. The results of this study suggest that liposomal amphotericin is less toxic than conventional amphotericin and is associated with improved survival. 

Histoplasmosis is caused by Histoplasma capsulatum and is endemic in parts of the central United States along the Ohio and Mississippi River valleys. Although most patients experience asymptomatic infection, some may experience chronic, disseminated disease. 

Adult patients with AIDS demonstrate an acute form of disseminated disease that resembles the syndrome seen in infants and children. Progressive disseminated histoplasmosis (PDH) can occur as the direct result of initial infection or because of the reactivation of dormant foci. In endemic areas, 50% of AIDS patients demonstrate PDH as the first manifestation of their disease. Progressive disseminated histoplasmosis is characterized by fever (75% of patients), weight loss, chills, night sweats, enlargement of the spleen, liver, or lymph nodes, and anemia. Pulmonary symptoms occur in only one-third of patients and do not always correlate with the presence of infiltrates on chest roentgenogram. A clinical syndrome resembling septicemia is seen in approximately 25% to 50% of patients. 

Crommentuyn KML, Mulder JW, Sparidans RW, Huitema ADR, Schellens JHM, Beijnen JH. Drug-drug interaction between itraconazole and the antirettoviral drug lopinavir/ritonavir in an HIV-l-infected patient with disseminated histoplasmosis. Clin Infect Dis (2004) 38, e73-e75. 

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