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.

Nocardiosis in 30 patients with advanced human immunodeficiency virus infection: clinical features and outcome.

A total of 30 patients (aged 6-56 years) with nocardiosis and infection due to human immunodeficiency virus type 1 (HIV-1) were identified in our institution between January 1985 and June 1989. Eighteen patients had an AIDS-defining illness before or concurrently with nocardiosis. The mean CD4 lymphocyte count was 109/mm3. Pulmonary nocardiosis in 21 patients, extra-pulmonary nocardiosis in 8, and pulmonary and extrapulmonary nocardiosis in 1 patient was diagnosed. Chest radiographs showed alveolar patterns of infiltrates in 14 patients, reticulonodular patterns in 2, mixed alveolar and reticulonodular patterns in 6, cavitation in 4, and pleural effusion in 3. Of 27 patients treated, the conditions of 22 improved, but the extensive disease in 5 progressed. For 14 patients, recurrence was rapid after their treatment was discontinued. Nocardiosis caused or contributed to the death of 19 patients; in six patients, there was no evidence of nocardial infection at death. Nocardiosis can be a fatal complication of advanced HIV-1 disease. Delayed diagnosis, extensive disease, and early discontinuation of treatment were associated with poor outcome.

Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. Members of the ACTG 077p/ANRS 009 Study Team.

BACKGROUND: In patients with the acquired immunodeficiency syndrome (AIDS), toxoplasmic encephalitis is usually a presumptive diagnosis based on the clinical manifestations, a positive antitoxoplasma-antibody titer, and characteristic neuroradiologic abnormalities. A response to specific therapy helps to confirm the diagnosis, but it is unclear how rapid the response should be. We studied the course of patients treated for acute toxoplasmic encephalitis and evaluated objective clinical criteria for this empirical diagnosis. METHODS: A quantifiable neurologic assessment was used prospectively to evaluate the clinical outcome of patients with AIDS and toxoplasmic encephalitis who were treated with oral clindamycin (600 mg four times a day) and pyrimethamine (75 mg every day) for six weeks. RESULTS: Thirty-five of 49 patients (71 percent) responded to therapy, and 30 of these (86 percent) had improvement by day 7. Thirty-two of those with a response (91 percent) improved with respect to at least half of their base-line abnormalities by day 14. Improvement in neurologic abnormalities within 7 to 14 days after the start of therapy was strongly associated with the neurologic response at 6 weeks. The four patients in whom treatment failed and the two patients with lymphoma had progressing neurologic abnormalities or new abnormalities during the first 12 days of therapy. Nonlocalizing abnormalities (headache and seizure) improved regardless of the clinical outcome. CONCLUSIONS: Oral clindamycin and pyrimethamine are an effective treatment for toxoplasmic encephalitis. Patients who have early neurologic deterioration despite treatment or who do not improve neurologically after 10 to 14 days of appropriate antitoxoplasma therapy should be considered candidates for brain biopsy.

Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex.

OBJECTIVE: To determine whether alternating regimens consisting of zidovudine and 2',3'-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone. DESIGN: An unblinded, randomized (phase II) clinical trial in which seven treatment regimens were compared. SETTING: Outpatient clinics of 12 AIDS Clinical Trials Units. PATIENTS: One hundred thirty-one patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and serum p24 antigenemia (> or = 70 pg/mL). INTERVENTION: Treatments included weekly or monthly alternating zidovudine (200 mg every 4 hours) and ddC (0.01 or 0.03 mg/kg body weight every 4 hours); weekly intermittent zidovudine, 200 mg every 4 hours, or ddC, 0.03 mg/kg every 4 hours; and continuous zidovudine. MEASUREMENTS: Toxicity, CD4 cell counts, serum p24 antigen levels, and clinical end points. Data were analyzed for the first 48 weeks of therapy (median follow-up, 40 weeks). RESULTS: Hematologic toxicity was significantly less frequent in patients who received zidovudine therapy every other week (11% to 15%) or every other month (11% to 14%) than in those who received continuous zidovudine therapy (33%) (P < 0.02). Weekly alternating therapy with zidovudine and ddC, 0.03 mg/kg, or intermittent therapy with ddC, 0.03 mg/kg, produced high rates of peripheral neuropathy (41% and 50%, respectively). Neuropathy occurred in 10% to 21% of patients in the other three alternating-therapy limbs and in 17% of patients receiving zidovudine alone (intermittently or continuously). Initial increases in CD4 cell counts were sustained in three alternating-therapy limbs, but counts returned to baseline by week 28 in the remaining limbs. The median weight gain at week 48 was significantly greater in patients treated with alternating regimens (0.9 to 3.8 kg) compared with those treated with continuous zidovudine therapy (-0.7 kg) (P = 0.008). Patients treated with alternating regimens and those treated with continuous zidovudine had similarly sustained decreases in p24 antigen levels. CONCLUSIONS: These findings suggest that alternating therapy with zidovudine and ddC reduces the toxicity associated with each drug alone while maintaining strong antiretroviral activity.

An outbreak of tuberculosis caused by multiple-drug-resistant tubercle bacilli among patients with HIV infection.

OBJECTIVE: To evaluate a nosocomial outbreak of tuberculosis caused by multiple-drug-resistant bacilli among patients with tuberculosis and HIV infection. DESIGN: A case-control study. PATIENTS: Patients with HIV infection and culture-proven tuberculosis. MEASUREMENTS: Patient characteristics, date of diagnoses of HIV infection and disease, date of diagnosis of tuberculosis, Mycobacterium tuberculosis susceptibility results, and medical center contact. RESULTS: Sixty-two patients who had tuberculosis caused by multiple-drug-resistant bacilli (cases) and 55 patients who had tuberculosis caused by susceptible or single-drug-resistant bacilli (controls) were identified. Controls were more likely to be black (odds ratio, 0.4; 95% CI, 0.2 to 0.9) or Haitian (odds ratio, 0.2; CI, 0.1 to 0.6) compared with cases, who were more likely to be homosexual men (odds ratio, 2.9; CI, 1.3 to 6.4). Forty-four cases (71%) had previous contact with an HIV clinic compared with 15 controls (27%) (P less than 0.0001). Cases were more likely to have had AIDS (odds ratio, 7.7; CI, 1.5 to 53.7), to have been hospitalized on an HIV ward (odds ratio, 8.3; CI, 2.3 to 29.7), to have been seen in an HIV clinic (odds ratio, 7.8; CI, 3.4 to 18.1), to have received intravenous therapy in an HIV clinic (odds ratio, 13.0; CI, 4.6 to 37.0), or to have received inhalation pentamidine in an HIV clinic before a diagnosis of tuberculosis was made. Multiple logistic regression analysis showed that a diagnosis of AIDS (odds ratio, 11.2; CI, 3.1 to 40.6) and HIV clinic visits (odds ratio, 13.0; CI, 2.7 to 63.7) before a diagnosis of tuberculosis were significantly associated with tuberculosis caused by multiple-drug-resistant bacilli. Using susceptibility patterns and appointment dates, we found that 22 cases had previous contact with a person who had tuberculosis caused by multiple-drug-resistant bacilli in the HIV clinic. CONCLUSIONS: Nosocomial transmission of M. tuberculosis from other HIV-infected patients with tuberculosis caused by multiple-drug-resistant bacilli can occur. These findings have serious public health implications and demand strict adherence to acid-fast bacilli isolation precautions.

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.

Value of needle biopsy in directing management of parotid lesions in HIV-positive patients.

Fourteen human immunodeficiency virus (HIV)-positive patients with parotid enlargement were reviewed retrospectively in order to elucidate the natural history of this clinical entity. The efficacy of fine-needle aspiration (FNA) in predicting benign nonsurgical disease was evaluated. The most common findings on FNA were proteinaceous fluid and/or epithelial cells consistent with cyst contents in 71% of the patients, followed by reactive lymphadenitis (50%), and chronic or granulomatous inflammation (21%). No evidence of malignancy was seen in any patient. These results correlated well with the histopathologic diagnosis in all operated patients. Surgery did not affect the ultimate clinical outcome. This study suggests that HIV-positive patients with isolated asymptomatic parotid swelling in the absence of other clinical features suggestive of malignancy can be followed conservatively with FNA, avoiding the risks of surgery.

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.

The radiographic appearance of pulmonary nocardiosis associated with AIDS.

Pulmonary nocardiosis is a well-described infection in immunocompromised patients; however, it is less well documented in patients with AIDS. The pulmonary manifestation in 21 HIV-positive patients who developed pulmonary infection with Nocardia asteroides is described. The radiographic picture included lobar or multilobar consolidation (52 percent [11/21]), solitary masses (24 percent [5/21]), reticulonodular infiltrates (33 percent [7/21]), and pleural effusion (33 percent [7/21]). Cavitation was common (62 percent [13/21]), and upper lobes were more commonly involved (71 percent [15/21]). Although the radiographic picture is variable, nocardiosis should be suspected in an HIV-positive patient who has subacute pulmonary disease with an unexplained lung mass or cavitary lesions.

Eosinophilic pleural effusion in cutaneous myiasis.

We have reported the case of a 54-year-old man with recurrent painful migratory subcutaneous nodules associated with marked blood eosinophilia and an eosinophilic pleural effusion. The entire syndrome was subsequently determined to be due to cutaneous myiasis caused by the larvae of Hypoderma lineatum, the cattle botfly. Infestation by this or other dipterous fly larvae should be among the parasitic diseases considered in the differential diagnosis of any patient with similar symptoms.

Circulating p24 antigen levels and responses to dideoxycytidine in human immunodeficiency virus (HIV) infections. A phase I and II study.

STUDY OBJECTIVE: To determine the safety and efficacy of dideoxycytidine in patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex. DESIGN: A partially randomized phase I and II outpatient, dose-ranging study. SETTING: Four university medical centers involving government-supported referral AIDS Clinical Trial Units. PATIENTS: Sixty-one patients with AIDS or advanced AIDS-related complex and 100 pg/mL or more serum p24 antigen titers. INTERVENTIONS: Dideoxycytidine was administered orally at 0.06, 0.03, 0.01, or 0.005 mg/kg body weight every 4 hours for 3 to 6 months depending on tolerance and benefit. MEASUREMENTS AND MAIN RESULTS: In patients receiving 0.06 and 0.03 mg/kg, diffuse erythematous rash, fever, and aphthous stomatitis occurred in the first weeks of therapy, but resolved later. Hematopoietic suppression was rare. Peripheral sensory neuropathy occurred in patients receiving 0.06 mg/kg and 0.03 mg/kg and improved after discontinuation of therapy. Serum p24 antigen fell significantly (P less than 0.01) from baseline entry values in most of these patients. The CD4 lymphocytes rose transiently at the 0.03 mg/kg dosage. At the 0.005 mg/kg dosage, skin rash, fever, and aphthous stomatitis were mild or absent. Peripheral neuropathy, which occurred in all patients receiving 0.01 mg/kg was less severe than at higher dosages. At the 0.005 mg/kg dosage, peripheral neuropathy was occasionally seen. Significant suppression of serum p24 antigen was seen in most patients with AIDS-related complex receiving 0.01 mg/kg and less frequently in patients receiving 0.005 mg/kg. CONCLUSIONS: Less toxic regimens of dideoxycytidine merit clinical assessment for advanced anti-human immunodeficiency virus-1 (HIV) infection. Several studies alternating dideoxycytidine and zidovudine are in progress.