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Adjuvant corticosteroids for tuberculous pericarditis: promising, but not proven.

BACKGROUND: There is controversy regarding the effectiveness of corticosteroids in tuberculous pericarditis, particularly in patients who are immunocompromised by HIV. AIM: To determine the effectiveness of adjuvant corticosteroids in tuberculous pericarditis. DESIGN: Systematic review of randomized controlled trials. METHODS: We searched the Cochrane Infectious Diseases Group trials register (June 2002), the Cochrane Controlled Trials Register (Issue 2, 2002), MEDLINE (January 1966 to March 2003), EMBASE (1980 to May 2002), and the reference lists of existing reviews, for randomized and quasi-randomized controlled trials of adjuvant corticosteroids in the treatment of suspected tuberculous pericarditis. We also contacted organizations and individuals working in the field. Two reviewers independently assessed trial quality and extracted data. We used meta-analysis with a fixed effects model to calculate the summary statistics, provided there was no statistically significant heterogeneity, and expressed results as relative risk. RESULTS: Four trials with a total of 469 participants met our criteria. Three (total n = 411) tested adjuvant steroids in participants with suspected tuberculous pericarditis in the pre-HIV era. Fewer participants died in the intervention group, but the potentially large reduction in mortality was not statistically significant (relative risk RR 0.65, 95%CI 0.36-1.16, n = 350; p = 0.14). One trial with 58 patients that enrolled HIV-positive individuals also showed a promising but non-significant trend on mortality (RR 0.50, 95%CI 0.19-1.28; p = 0.15). There was no significant beneficial effect of steroids on re-accumulation of pericardial effusion or progression to constrictive pericarditis. Patients with pericardial effusion were significantly more likely to be alive with no functional impairment at 2 years following treatment. However, the effect was not sustained in a sensitivity analysis that included patients who were lost to follow-up. DISCUSSION: Steroids could have large beneficial effects on mortality and morbidity in tuberculous pericarditis, but published trials are too small to be conclusive. Large placebo-controlled trials are required, and should include sufficient numbers of HIV-positive and HIV-negative participants, and an adequate adjuvant steroid dose.

Adrenal Cortex Hormones↗

Tuberculous pericarditis: long-term outcome in patients who received medical therapy alone.

A conservative approach to operative intervention in the treatment of active tuberculous pericarditis was adopted and only 4 of 16 consecutive patients underwent pericardiectomy, all within 2 months of diagnosis. One patient died of constrictive pericarditis despite pericardiectomy, and one died of acute bronchopneumonia after 8 months of otherwise successful medical management. All 14 long-term survivors were reevaluated to exclude chronic constrictive pericarditis and other potential sequelae of tuberculous pericarditis. Reevaluation included physical examination, chest radiograph, electrocardiogram, M-mode and two-dimensional echocardiogram, computed tomography (CT) scan, and in patients less than or equal to 75 years of age, incremental cycle exercise to maximum oxygen consumption. None were found to have chronic constrictive pericarditis or convincing evidence of other recognized complications of tuberculous pericarditis. Our results suggest that when pericardiectomy is not required for the relief of cardiac compression during the acute phase of tuberculous pericarditis and patients are treated with medical therapy alone, an excellent long-term outcome may be anticipated.

Adrenal Cortex Hormones↗

Tuberculous pericarditis: importance of adenosine deaminase activity in pericardial fluid.

We present a case of tuberculous pericarditis that was diagnosed early by a high titer of adenosine deaminase activity in the pericardial fluid and by a strongly positive tuberculin test. Within 2 weeks of initiation of treatment, pericardial effusion gradually decreased while clinical symptoms improved markedly. Culture from sputum, gastric juice, urine, and pericardial fluid were negative for tubercle bacillus. Measurement of adenosine deaminase activity in the pericardial fluid is a supplementary diagnostic test which is as important as for tuberculous pericarditis as it is for tuberculous pleuritis, because negative Ziehl Neelsen staining and culture for tubercle bacillus are common in tuberculous pericarditis.

Adenosine Deaminase↗

Tuberculous pericarditis in Birmingham.

Forty-one patients with acute tuberculous pericarditis were studied retrospectively. Anti-tuberculosis chemotherapy alone was effective in thirty. Five patients died, two from unrelated causes, two due to delayed diagnosis, and one after pericardiectomy. Constrictive pericarditis developed in seven patients, six of whom had successful pericardiectomy. Corticosteroids could not be shown to have reduced the risk of developing constriction. When constriction occurred it did so within the first six months of illness in all cases in contrast to a separate series of 15 patients who presented with constrictive pericarditis. These had had no previous history of tuberculosis, and in 10 cases where pericardiectomy was done, no histological evidence of tuberculosis was found. They were European with an average age of 49 years whereas in the group with acute tuberculous pericarditis 33 were Asian and the average age was 36 years.

Acute Disease↗

Comparison of PCR, culture, and histopathology for diagnosis of tuberculous pericarditis.

Nucleic acid amplification techniques for the diagnosis of tuberculosis (TB) are rapidly being developed. Scant work, however, has focused on pericardial TB. Using cryopreserved specimens from a prior study of pericarditis, we compared PCR to culture and histopathology for the diagnosis of tuberculous pericarditis in 36 specimens of pericardial fluid and 19 specimens of pericardial tissue from 20 patients. Fluid and tissue were cultured on Lowenstein-Jensen and Middlebrook solid media and in BACTEC radiometric broth. Tissue specimens were stained with hematoxylin-eosin, Ziehl-Neelsen, auramine O, and Kinyoun stains and were examined for granuloma formation and acid-fast bacilli. PCR was performed with both fluid and tissue with IS6110-based primers specific for the Mycobacterium tuberculosis complex by published methods. Sixteen of the 20 patients had tuberculous pericarditis and 4 patients had other diagnoses. TB was correctly diagnosed by culture in 15 (93%) patients, by PCR in 13 (81%) patients, and by histology in 13 of 15 (87%) patients. PCR gave one false-positive result for a patient with Staphylococcus aureus pericarditis. Considering the individual specimens as the unit of analysis, M. tuberculosis was identified by culture in 30 of 43 specimens (70%) from patients with tuberculous pericarditis and by PCR in 14 of 28 specimens (50%) from patients with tuberculous pericarditis (P > 0.15). The sensitivity of PCR was higher with tissue specimens (12 of 15; 80%) than with fluid specimens (2 of 13; 15%; P = 0.002). In conclusion, the overall accuracy of PCR approached the results of conventional methods, although PCR was much faster. Therefore, PCR merits further development in this regard. The sensitivity of PCR with pericardial fluid was poor, and false-positive results with PCR remain a concern.

Adolescent↗

Relevance of adenosine deaminase and lysozyme measurements in the diagnosis of tuberculous pericarditis.

OBJECTIVE: To assess the value of pericardial fluid adenosine deaminase (ADA) and pericardial lysozyme (Lys) as tools in diagnosing tuberculous pericarditis. METHODS: Forty-one patients (age range 17--77 years) with significant pericardial effusion were included in the study. Diagnostic pericardiocentesis and pericardial biopsy were performed while serum and pericardial fluid ADA and Lys were measured in all patients. Grouping of patients resulted as follows: group I = 7 patients with tuberculous pericarditis; group II = patients with neoplastic pericarditis; group III = 30 patients with idiopathic pericarditis. RESULTS: Pairwise multiple comparison procedures revealed a significant difference of ADA in group I versus group III (p < 0.05) but not versus group II. Furthermore, pericardial Lys in group I was higher than in groups II and III (p < 0.05). A strong correlation between pericardial ADA and Lys was found (r = 0.733, p = 0.01) for all the patients. Receiver operating curves showed a value of 72 U/l as cutoff point of pericardium ADA, with a sensitivity of 100% and a specificity of 94% in the diagnosis of tuberculous pericarditis. Similarly for pericardial Lys, a value of 6.5 microg/dl had a sensitivity and specificity of 100 and 91.17%, respectively. CONCLUSIONS: Both measurements of pericardial ADA and Lys need to be taken into account when attempting the early diagnosis of tuberculous pericarditis.

Adenosine Deaminase↗

Double blind randomised placebo controlled trial of adjunctive prednisolone in the treatment of effusive tuberculous pericarditis in HIV seropositive patients.

OBJECTIVE: To determine the effect of adjunctive prednisolone on morbidity, pericardial fluid resolution, and mortality in HIV seropositive patients with effusive tuberculous pericarditis. DESIGN: Double blind randomised placebo controlled trial. SETTING: Two medical school affiliated referral hospitals in Harare, Zimbabwe. PATIENTS: 58 HIV seropositive patients aged 18-55 years with tuberculous pericarditis. INTERVENTIONS: All patients received standard short course antituberculous chemotherapy and were randomly assigned to receive prednisolone or placebo for six weeks. MAIN OUTCOME MEASURES: Clinical improvement, echocardiographic and radiologic pericardial fluid resolution, and death. RESULTS: 29 patients were assigned to prednisolone and 29 to placebo. After 18 months of follow up there were five deaths in the prednisolone treated group and 10 deaths in the placebo group. Mortality was significantly lower in the prednisolone group (log rank chi(2) = 8. 19, df = 1, p = 0.004). Resolution of raised jugular venous pressure (p = 0.017), hepatomegaly (p = 0.007), and ascites (p = 0.015), and improvement in physical activity (p = 0.02), were significantly more rapid in the prednisolone treated patients. However, there was no difference in the rate of radiologic and echocardiographic resolution of pericardial effusion. CONCLUSIONS: Adjunctive prednisolone for effusive tuberculous pericarditis produced a pronounced reduction in mortality. It is suggested prednisolone should be added to standard short course chemotherapy to treat HIV related effusive tuberculous pericarditis.

AIDS-Related Opportunistic Infections↗

Clinical response of tuberculous pericarditis to medical treatment: a retrospective survey.

BACKGROUND: The prevalence of tuberculosis has declined with advanced antituberculous chemotherapy. However, the occurrence of subsequent constrictive pericarditis in tuberculosis has not reduced. Clinical progress of tuberculous pericarditis was investigated in patients receiving antituberculous chemotherapy. METHODS: Thirteen patients with tuberculous pericarditis (11 men and 2 women aged 14 to 86 years [mean 60.0 +/- 17.0]), treated initially with antituberculous medications were analyzed. All patients underwent pericardiocentesis on admission following echocardiography. RESULTS: Dyspnea was the most common clinical pictures. Bloody effusion fluids were noted in 10 patients. Moreover, the lymphocytic fluids were present in 78% of all patients. The neutrophilic fluids tended to have a bloody color, and there was progress to constrictive pericarditis even for those on anti-tuberculous chemotherapy. Five patients with subsequent constrictive pericarditis received pericardiectomy within 3.5 months of admission. Three of them received pericardiectomy later, despite pericardial window procedure. CONCLUSIONS: Follow-up by echocardiogram is necessary within three months after commencing medical treatment because of the high incidence of progression constrictive pericarditis despite aggressive medical treatment. Pericardiectomy seems to be the only solution to the catastrophic outcome of constrictive pericarditis.

Adolescent↗

Tuberculous pericarditis: optimal diagnosis and management.

Pericarditis is a rare manifestation of tuberculous disease. The appropriate diagnostic workup and optimal therapeutic management are not well defined. We present 10 new cases of tuberculous pericarditis and review the relevant literature. The specific topics addressed are (1) the importance of tissue for diagnosis, (2) the optimal surgical management, (3) the role of corticosteroids, and (4) the impact of human immunodeficiency virus (HIV) on the management of this disease. The cases and the literature suggest that the optimal management includes an open pericardial window with biopsy, both for diagnosis and to prevent reaccumulation of fluid. Corticosteroids probably offer some benefit in preventing fluid reaccumulation as well. The data are inconclusive regarding whether open drainage or corticosteroid use prevents progression to constrictive pericarditis. No studies have addressed these issues specifically in HIV-positive patients, but the 3 HIV-positive patients in our series had an excellent response to drainage and antituberculous therapy.

AIDS-Related Opportunistic Infections↗