Disseminated miliary tuberculosis of the skin in patients with AIDS: report of four cases.

We present clinical, bacteriologic, and pathological findings for four patients with AIDS and cutaneous miliary tuberculosis. All patients had generalized tuberculosis with hematogenous dissemination to multiple organs including the skin. Microscopic examination of the skin lesions revealed ill-formed or no granulomata, extensive necrosis, and numerous acid-fast bacilli. Mycobacterium tuberculosis was detected in the skin lesions by cultures for three patients and by polymerase chain reaction for one. Three of the isolates were resistant to at least isoniazid and rifampin, and one was susceptible to these drugs. The outcome was rapidly fatal for the three patients with multidrug-resistant tuberculosis. This report draws attention to the reappearance of a once-rare manifestation of disseminated tuberculosis which, in the setting of advanced human immunodeficiency virus disease, may offer the first indication of infection with multidrug-resistant M. tuberculosis and a poor prognosis.

CNS Nocardia in AIDS patients: CT and MRI with pathologic correlation.

OBJECTIVE: Since CNS nocardiosis is an often fatal yet potentially treatable infection in HIV patients, we sought to identify and characterize imaging features that may suggest the diagnosis in the appropriate clinical setting. MATERIALS AND METHODS: The CT scan (six), MR scans (one), or both (two) were evaluated in nine HIV patients with pathologically proven CNS Nocardia asteroides. Chest X-ray films were available in seven patients. Findings were correlated with pathologic examination. RESULTS: All nine patients had brain abscesses, and in seven that received intravenous contrast agent, all lesions demonstrated ring enhancement. Five of nine patients had hydrocephalus and four of these had clinical evidence of meningitis. Small subependymal nodules were seen in five of nine patients and four of these also had meningitis. Pathologic examination in three of nine cases demonstrated a dense inflammatory infiltrate lining the ventricles that extended through the ependymal lining, producing small subependymal abscesses. Six of seven available chest X-ray films demonstrated infiltrates due to Nocardia. CONCLUSION: Our radiologic-pathologic correlation indicates that in an HIV-positive patient with enhancing parenchymal lesions, the additional findings of subependymal nodules and/or meningitis may suggest the diagnosis of nocardiosis. An associated pulmonary infiltrate can provide a clue to the diagnosis and serve as more accessible site for biopsy or culture.

Clinical presentation and outcome of patients with HIV infection and tuberculosis caused by multiple-drug-resistant bacilli.

OBJECTIVE: To determine the clinical manifestations of patients with human immunodeficiency virus (HIV) infection and tuberculosis caused by multiple-drug-resistant bacilli compared with those with single-drug-resistant or susceptible bacilli. DESIGN: Descriptive, case-control, and cohort studies. SETTING: A large urban teaching hospital. PATIENTS: Sixty-two patients with tuberculosis caused by multiple-drug-resistant bacilli (cases) and 55 patients with tuberculosis caused by single-drug-resistant or susceptible bacilli (controls). MEASUREMENTS: Characteristics of clinical presentation, radiographs, pathologic abnormalities, antituberculosis treatment, and clinical course. RESULTS: Twenty cases (32%) had concomitant pulmonary and extrapulmonary disease at presentation compared with 9 controls (16%; odds ratio, 2.4; 95% CI, 1.0 to 5.9). More cases had alveolar infiltrates (76%; odds ratio, 3.6; CI, 1.2 to 11.4), interstitial infiltrates with a reticular pattern (67%; odds ratio, 7.8; CI, 1.0 to 83.5), and cavitations (18%; odds ratio, 6.6; CI, 0.8 to 315.3) on initial chest radiographs compared with controls (49%, 19%, and 3%, respectively). Pathologic specimens from cases showed extensive necrosis, poor granuloma formation, marked inflammatory changes with a predominance of neutrophils, and abundant acid-fast bacilli. Twenty-five cases received two or more effective antituberculosis drugs for more than 2 months. Only 2 cases had three consecutive negative cultures for Mycobacterium tuberculosis; one patient died within 1 day of the last negative culture, and the other had positive cultures 496 days later. The remaining 23 cases had persistently or intermittently positive cultures despite therapy. The clinical course of these cases suggested overwhelming miliary tuberculosis with involvement of the lungs (77%), pleura (15%), stool (34%), meninges (13%), bone marrow (16%), blood (10%), lymph nodes (10%), and skin (8%). The median survival time was 2.1 months for cases compared with 14.6 months for controls (P = 0.001, log-rank test). CONCLUSIONS: Tuberculosis caused by multiple-drug-resistant bacilli in patients with HIV infection is associated with widely disseminated disease, poor treatment response with an inability to eradicate the organism, and substantial mortality.

A phase I study of recombinant human interferon-alpha 2a or human lymphoblastoid interferon-alpha n1 and concomitant zidovudine in patients with AIDS-related Kaposi's sarcoma.

To determine the safety, maximum tolerated dose, and preliminary efficacy of concomitant interferon-alpha and zidovudine therapy in AIDS-related Kaposi's sarcoma (KS), 56 patients with biopsy-proven KS and documented human immunodeficiency virus type 1 (HIV) infection were enrolled into a phase I study. Interferon-alpha was given intramuscularly at a dose of 9, 18, or 27 mu once a day and zidovudine was administered as 100 or 200 mg every 4 h for 8 weeks followed by a 48-week maintenance period. The major toxicities were anemia, neutropenia, and hepatotoxicity. Neutropenia was dose limiting with 1,200 mg of zidovudine/day and the lowest dose of interferon-alpha (9 mu/day). Hepatotoxicity was dose limiting with 27 mu of interferon and 600 mg of zidovudine/day. Cumulative dose-related anemia or neutropenia was not seen during long-term follow-up. The maximum tolerated doses for the combination were defined as 18 mu daily for interferon-alpha and 600 mg daily for zidovudine. Variable changes in CD4 lymphocytes occurred during the first 8 weeks of therapy. At higher doses of the combination, sustained increases in median CD4 lymphocyte numbers were noted (p less than 0.001). In HIV antigenemic patients, progressive antigen suppression was seen with increasing doses of the combination (p less than 0.005). The overall antitumor response rate was 47%. Tumor regression was associated with better survival benefits (p less than 0.001) and a pretreatment CD4 cell count greater than or equal to 200 cells/mm3 (p = 0.01). In conclusion, intermediate doses of interferon-alpha and lower doses of zidovudine appear to be relatively well tolerated and associated with disease improvement, including survival benefits.