Giovanni Brambilla

Corticosteroids for Recurrent Pericarditis High Versus Low Doses: A Nonrandomized Observation

Background— Corticosteroid use is widespread in recurrent pericarditis, even if rarely indicated, and high doses (eg, prednisone 1.0 to 1.5 mg · kg−1 · d−1) are generally recommended, although only weak evidence supports their use with possible severe side effects. The aim of this work was to compare side effects, recurrences and other complications, and hospitalizations of a low- versus high-dose regimen of prednisone for recurrent pericarditis. Methods and Results— A retrospective review of all cases of recurrent pericarditis treated with corticosteroids according to different regimens from January 1996 to June 2004 was performed in 2 Italian referral centers. One hundred patients with recurrent pericarditis (mean age, 50.1±15.8 years; 57 females) were included in the study; 49 patients (mean age, 47.5±16.0; 25 females) were treated with low doses of prednisone (0.2 to 0.5 mg · kg−1 · d−1), and 51 patients (mean age, 52.6±15.3; 32 females) were treated with prednisone 1.0 mg · kg−1 · d−1. Baseline demographic and clinical characteristics were well balanced across the groups. Each initial dose was maintained for 4 weeks and then slowly tapered. After adjustment for potential confounders (age, female gender, nonidiopathic origin), only high doses of prednisone were associated with severe side effects, recurrences, and hospitalizations (hazard ratio, 3.61; 95% confidence interval, 1.96 to 6.63; P<0.001). Conclusions— Use of higher doses of prednisone (1.0 mg · kg−1 · d−1) for recurrent pericarditis is associated with more side effects, recurrences, and hospitalizations. Lower doses of prednisone should be considered when corticosteroids are needed to treat pericarditis.

Anti-heart and anti-intercalated disk autoantibodies: evidence for autoimmunity in idiopathic recurrent acute pericarditis

Background Idiopathic recurrent acute pericarditis (IRAP) is a rare disease of suspected, yet unproved, immune-mediated origin. The finding of serum heart-specific autoantibodies in IRAP would strengthen the autoimmune hypothesis and provide aetiology-specific non-invasive biomarkers. Objective To assess frequency of serum anti-heart (AHA), anti-intercalated-disk (AIDA) and non-cardiac-specific autoantibodies and their clinical and instrumental correlates in patients with IRAP. Patients 40 consecutive patients with IRAP, 25 male, aged 37±16u2005years, representing a large single-centre cohort collected at a referral centre over a long time period (median 5u2005years, range 1–22u2005years). Control groups included patients with non-inflammatory cardiac disease (NICD) (n=160), ischaemic heart failure (n=141) and normal subjects (n=270). Methods AHA (organ-specific, cross-reactive 1 and 2 types) and AIDA were detected in serum samples from patients, at last follow-up, and control subjects by indirect immunofluorescence (IIF) on human myocardium and skeletal muscle. Non-cardiac-specific autoantibodies were detected by IIF, and anti-Ro/SSA, anti-La/SSB by ELISA. Results The frequencies of cross-reactive 1 AHA and of AIDA were higher (50%; 25%) in IRAP than in NICD (4%; 4%), ischaemic (1%; 2%) or normal subjects (3%; 0%) (p=0.0001). AHA and/or AIDA were found in 67.5% patients with IRAP. Of the non-cardiac-specific antibodies, only antinuclear autoantibodies at titre ≥1/160 were more common in IRAP (5%) versus normal (0.5%, p<0.04). AIDA in IRAP were associated with a higher number of recurrences (p=0.01) and hospitalisations (p=0.0001), high titre (1/80 or higher) AHA with a higher number of recurrences (p=0.02). Conclusions The detection of AHA and of AIDA supports the involvement of autoimmunity in the majority of patients with IRAP.

Clues to detect tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among patients with idiopathic recurrent acute pericarditis: results of a multicentre study

BackgroundThe potential clinical expression of tumor necrosis factor receptor-associated periodic syndrome (TRAPS), in the form of idiopathic recurrent acute pericarditis (IRAP) has not been explored in the medical literature. The aim of this study was to evaluate the incidence of TRAPS mutations in patients with recurrent pericarditis and identify possible clues to TRAPS diagnosis.MethodsTherefore, 131 consecutive Caucasian IRAP patients were investigated for mutations of the TRAPS gene and prospectively evaluated.ResultsOut of 131 patients, 8 (6.1%) carried a mutation in the TNFRSF1A gene. Compared with those without genetic mutations, patients with TRAPS mutations had more frequently a positive family history for pericarditis and periodic fever syndromes (pxa0<xa00.001), a higher mean number of recurrences after the first year (pxa0<xa00.001), on colchicine treatment (pxa0<xa00.001), and a higher need of immunosuppressive therapies (pxa0<xa00.001).ConclusionTRAPS is a cause of recurrent pericarditis in 6% of unselected cases with recurrent pericarditis. A positive family history for pericarditis or periodic fever syndromes, a poor response to colchicine, recurrences after the first year from the index attack or on colchicine treatment, as well as the need of immunosuppressive agents are clues of the possible presence of TNFRSF1A gene mutations in patients with recurrent pericarditis.

Antinuclear antibodies in recurrent idiopathic pericarditis: Prevalence and clinical significance

BACKGROUNDnA positive result for antinuclear antibodies (ANA), often as a fortuitous observation, may be cause for concern in idiopathic recurrent pericarditis (IRP), nevertheless data are lacking on their prevalence and clinical significance. This study is sought to investigate the prevalence and clinical significance of ANA in IRP.nnnMETHODSnANA titres were assessed in consecutive patients with recurrent pericarditis, and matched healthy controls. Baseline and follow-up data were recorded and compared according to ANA results.nnnRESULTSnA total of 145 consecutive patients with recurrent pericarditis were studied: 122 patients with IRP, 23 patients with pericarditis due to known etiologies (rheumatologic diagnoses and postpericardiotomy syndrome), and 122 healthy controls. ANA were detected in 53 of 122 (43.4%) patients with IRP, and in only 12 of 122 (9.8%) controls (p<0.001). Low titres (1/40-1/80) were found in the majority of cases, while moderate positivity (1/160-1/320) was more common in patients with a known rheumatic disease (26.7% vs. 5.7%; p=0.020). High concentrations of ANA (> or =1/640) were not recorded. Women were at increased risk for ANA (OR 2.22 95%CI 1.07-4.60; p=0.033). During a mean follow-up of 32 months, complications and new diagnoses were similar in patients with or without ANA positivity.nnnCONCLUSIONSnLow-positive titres are more common in patients with IRP than in controls, suggesting a possible autoimmune pathogenesis. Nevertheless, they are often a clinically non-specific finding. Routine serologic testing for ANA suggests a source for recurrent pericarditis in less than 10% of cases, and in these cases other evidence typically suggests the underlying disease.

Recurrent pericarditis: infectious or autoimmune?

The etiology and pathogenesis of idiopathic recurrent acute pericarditis (IRAP) remain controversial standing like a bridge that crosses infectious, autoimmune and autoinflammatory pathways. Anything may cause acute pericarditis; Echo-virus, and Coxsackie are the most frequently involved viruses, Mycobacterium tuberculosis and Coxiella burnetii the most common bacteria, but in 85% of cases it remains idiopathic. Recurrences occur in up to 20-50% of patients. An immuno-mediated pathogenesis is suggested by the presence of pro-inflammatory cytokines in pericardial fluid, the presence of antinuclear autoantibodies (ANA) in sera of the patients, the occurrence of new autoimmune diagnoses and the good response to anti-inflammatory or immunosuppressive therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) must be used at recommended dosages, till the resolution of symptoms and normalization of C-reactive protein and erythrocyte sedimentation rate. Corticosteroids should be used rarely, at low doses, with an extremely low tapering and with osteoporosis prevention. Colchicine leads to a clinically important and statistically significant benefit, reducing recurrences by 50%. The long term outcome of IRAP is good, without evidence of constriction even after a very long follow-up.

The Efficacy of Colchicine in the Treatment of Recurrent Pericarditis Related to Postcardiac Injury (Postpericardiotomy and Postinfarcted) Syndrome: A Multicenter Analysis

Background: Pericarditis related to the postcardiac injury syndrome (PCIS) following myocardial infarction or cardiac surgery is a troublesome and often recurrent clinical entity resistant to therapeutic interventions. The usefulness of colchicine in the prevention of recurrent PCIS has not been evaluated. Objective: We performed a cumulative analysis of available multicenter data with the aim of evaluating the efficacy of colchicine in the treatment of recurrent PCIS. Methods and Results: The study was designed as a multicenter all-cases analysis. Researchers who had published studies and case reports on colchicine treatment in recurrent pericarditis related to PCIS during the last 15 years were approached and asked to contribute all available cases to the database. There were 28 patients, 18 male (64%) and 10 female (36%), ranging in age from 21 to 82 years (mean 53 ± 15 years). PCIS pericarditis was secondary to pericardiotomy in 19 patients and infarction in 9. In 21 patients (75%), colchicine therapy was discontinued during follow-up and renewed only in the case of relapse. In these patients, the total period of treatment was summed up for analysis. 7 patients (25%) were taking colchicine as a permanent treatment, and no colchicine-free follow-up was documented. In total, 130 recurrences (mean 4.64 ± 3.7 per patient, range 2–16) were noted before colchicine therapy was initiated. During colchicine treatment (mean duration of treatment 16.6 ± 13.5 months), a significant reduction in the number of recurrences was observed. Only 5 of 28 patients (18%) presented with new recurrences (mean 0.25 ± 0.59 vs. 4.64 ± 3.7 per patient in the precolchicine period, p < 0.001). The mean follow-up period after colchicine discontinuation (data were available for 21 patients) was 31.9 ± 28 months; during follow-up, 13 patients (62%) remained recurrence free and 8 of them (38%) experienced relapses (mean 0.43 ± 0.6 per patient, p < 0.001 vs. precolchicine). Conclusions: It seems that colchicine may be effective in preventing new relapses in patients with recurrent pericarditis related to postcardiac injury both during active therapy and after its discontinuation.