Contemporary use of adjunctive corticosteroids in tuberculous pericarditis

There is controversy concerning the effectiveness of adjunctive corticosteroids in reducing mortality in tuberculous pericarditis. To assess the impact of this controversy on contemporary clinical practice, we studied the use of adjunctive corticosteroid in 185 consecutive patients with suspected pericardial tuberculosis from 15 hospitals in Cameroon, Nigeria, and South Africa. 109 (58.9%) patients received steroids with significant variation in corticosteroid use ranging from 0% to 93.5% per centre (P<0.0001). The presence of clinical features of HIV infection was the independent predictor of the non-use of adjunctive corticosteroids (OR 0.39, 95% CI 0.20-0.75, P=0.005). We have demonstrated marked variation in the use of corticosteroids by practitioners, with nearly half of all patients not receiving this intervention. Taken together with the statistical uncertainty regarding the effectiveness of adjunctive steroids in tuberculous pericarditis, these observations probably reflect a state of genuine uncertainty or clinical equipoise among practitioners who care for patients with tuberculous pericarditis in sub-Saharan Africa. These data provide a justification for the establishment of adequately powered randomised clinical trials to assess the effectiveness of adjunctive corticosteroids in patients with tuberculous pericarditis.     

Effusive-constrictive pericarditis

Effusive-constrictive pericarditis (ECP) is an increasingly recognized clinical syndrome. It has been best characterized in patients with tamponade who continue to have elevated intracardiac pressure after the removal of pericardial fluid. The disorder is due to pericardial inflammation causing constriction in conjunction with the presence of pericardial fluid under pressure. The etiology is diverse with similar causes to constrictive pericarditis and the condition is more prevalent with certain etiologies such as tuberculous pericarditis. The diagnosis is most accurately made using simultaneous intrapericardial and right atrial pressure measurements with pericardiocentesis, although non-invasive Doppler hemodynamic assessment can assess residual hemodynamic findings of constriction following pericardiocentesis. The clinical presentation has considerable overlap with other pericardial syndromes and as yet there are no biomarkers or non-invasive findings that can accurately predict the condition. Identifying patients with ECP therefore requires a certain index of clinical suspicion at the outset, and in practice, a proportion of patients may be identified once there is objective evidence for persistent atrial pressure elevation after pericardiocentesis. Although a significant number of patients will require pericardiectomy, a proportion of patients have a predominantly inflammatory and reversible pericardial reaction and may improve with the treatment of the underlying cause and the use of anti-inflammatory medications. Patients should therefore be observed for the improvement on these treatments for a period, whenever possible, before advocating pericardiectomy. Imaging modalities identifying ongoing pericardial inflammation such as contrast-enhanced magnetic resonance imaging or nuclear imaging may identify those subsets more likely to respond to medical therapies. Pericardiectomy, if necessary, requires removal of the visceral pericardium.     

Mortality in patients treated for tuberculous pericarditis in sub-Saharan Africa

OBJECTIVE: To determine the mortality rate and its predictors in patients with a presumptive diagnosis of tuberculous pericarditis in sub-Saharan Africa. DESIGN: Between 1 March 2004 and 31 October 2004, we enrolled 185 consecutive patients with presumed tuberculous pericarditis from 15 referral hospitals in Cameroon, Nigeria and South Africa, and observed them during the 6-month course of antituberculosis treatment for the major outcome of mortality. This was an observational study, with the diagnosis and management of each patient left at the discretion of the attending physician. Using Cox regression, we have assessed the effect of clinical and therapeutic characteristics (recorded at baseline) on mortality during follow-up. RESULTS: We obtained the vital status of 174 (94%) patients (median age 33; range 14 - 87 years). The overall mortality rate was 26%. Mortality was higher in patients who had clinical features of HIV infection than in those who did not (40% v. 17%, p=0.001). Independent predictors of death during followup were: (i) a proven non-tuberculosis final diagnosis (hazard ratio (HR) 5.35, 95% confidence interval (CI) 1.76 - 16.25), (ii) the presence of clinical signs of HIV infection (HR 2.28, CI 1.14 - 4.56), (iii) coexistent pulmonary tuberculosis (HR 2.33, CI 1.20 - 4.54), and (iv) older age (HR 1.02, CI 1.01 - 1.05). There was also a trend towards an increase in death rate in patients with haemodynamic instability (HR 1.80, CI 0.90 - 3.58) and a decrease in those who underwent pericardiocentesis (HR 0.34, CI 0.10 - 1.19). CONCLUSION: A presumptive diagnosis of tuberculous pericarditis is associated with a high mortality in sub-Saharan Africa. Attention to rapid aetiological diagnosis of pericardial effusion and treatment of concomitant HIV infection may reduce the high mortality associated with the disease.     

Established and novel pathophysiological mechanisms of pericardial injury and constrictive pericarditis

This review article aims to:(1) discern from the literature the immune and inflammatory processes occurring in the pericardium following injury; and(2) to delve into the molecular mechanisms which may play a role in the progression to constrictive pericarditis. Pericarditis arises as a result of a wide spectrum of pathologies of both infectious and non-infectious aetiology, which lead to various degrees of fibrogenesis. Current understanding of the sequence of molecular events leading to pathological manifestations of constrictive pericarditis is poor. The identification of key mechanisms and pathways common to most fibrotic events in the pericardium can aid in the design and development of novel interventions for the prevention and management of constriction. We have identified through this review various cellular events and signalling cascades which are likely to contribute to the pathological fibrotic phenotype. An initial classical pattern of inflammation arises as a result of insult to the pericardium and can exacerbate into an exaggerated or prolonged inflammatory state. Whilst the implication of major drivers of inflammation and fibrosis such as tumour necrosis factor and transforming growth factor β were foreseeable, the identification of pericardial deregulation of other mediators(basic fibroblast growth factor, galectin-3 and the tetrapeptide Ac-SDKP) provides important avenues for further research.     

HIV-1 infection alters CD4+ memory T-cell phenotype at the site of disease in extrapulmonary tuberculosis

HIV-1-infected people have an increased risk of developing extrapulmonary tuberculosis (TB), the immunopathogenesis of which is poorly understood. Here, we conducted a detailed immunological analysis of human pericardial TB, to determine the effect of HIV-1 co-infection on the phenotype of Mycobacterium tuberculosis (MTB)-specific memory T cells and the role of polyfunctional T cells at the disease site, using cells from pericardial fluid and blood of 74 patients with (n = 50) and without (n = 24) HIV-1 co-infection. The MTB antigen-induced IFN-γ response was elevated at the disease site, irrespective of HIV-1 status or antigenic stimulant. However, the IFN-γ ELISpot showed no clear evidence of increased numbers of antigen-specific cells at the disease site except for ESAT-6 in HIV-1 uninfected individuals (p = 0.009). Flow cytometric analysis showed that CD4+ memory T cells in the pericardial fluid of HIV-1-infected patients were of a less differentiated phenotype, with the presence of polyfunctional CD4+ T cells expressing TNF, IL-2 and IFN-γ. These results indicate that HIV-1 infection results in altered phenotype and function of MTB-specific CD4+ T cells at the disease site, which may contribute to the increased risk of developing TB at all stages of HIV-1 infection.