Idiopathic recurrent pericarditis refractory to colchicine treatment can reveal tumor necrosis factor receptor-associated periodic syndrome.
Recurrences develop in up to 20-50% of patients with acute pericarditis. Although different causes of recurrent pericarditis have been identified, the etiology remains obscure in most cases which are therefore labelled as idiopathic. Autoinflammatory syndromes include familial Mediterranean fever (FMF), due to mutations in the MEFV gene, and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), due to mutations in the TNFRSF1A gene. Recurrent pericarditis is a common feature of both conditions, but it rarely occurs alone. Colchicine is the standard treatment for FMF, while patients with TRAPS do not respond to colchicine therapy, but are responsive to corticosteroids. Based on the proven efficacy of colchicine in preventing polyserositis in FMF, colchicine has been proposed for the treatment of recurrent pericarditis and is able to decrease the recurrence rate. Our aim was to investigate the possible involvement of TNFRSF1A mutations in a group of patients with idiopathic recurrent pericarditis who were refractory to colchicine treatment. Thirty consecutive patients (17 males, 13 females) diagnosed with idiopathic recurrent pericarditis, who were characterized by a poor response to colchicine treatment, were enrolled in the study. Mutations of the TNFRSF1A gene were searched for by amplifying, using polymerase chain reaction (PCR), genomic DNA, and direct sequencing. TNFRSF1A mutations were found in 4 of the 30 patients. None of these 4 patients had a family history of recurrent inflammatory syndromes or history of pericarditis. One of the 4 patients had a novel heterozygous deletion (DeltaY103-R104) and three patients carried a heterozygous low-penetrance R92Q mutation. Our data suggest that TRAPS should be kept in mind in the differential diagnosis of recurrent pericarditis, and mutation analysis of the TNFRSF1A gene should be considered, in addition to MEFV analysis, in patients of Mediterranean origin. A poor response to colchicine treatment and/or a steroid-dependence may be the clue to investigate TNFRSF1A mutations in patients with idiopathic recurrent pericarditis.
Cantarini
L
L
Interdepartmental Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Unit of Rheumatology, Policlinico Le Scotte, University of Siena, Siena, Italy. cantariniluca@hotmail.com
Lucherini
O M
OM
Cimaz
R
R
Baldari
C T
CT
Bellisai
F
F
Rossi Paccani
S
S
Laghi Pasini
F
F
Capecchi
P L
PL
Sebastiani
G D
GD
Galeazzi
M
M
D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D003078:Colchicine / Q000627:therapeutic use*; D003598:Cytoskeletal Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D010505:Familial Mediterranean Fever / Q000150:complications / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010493:Pericarditis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D000071198:Pyrin; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D012008:Recurrence; D012307:Risk Factors; D013577:Syndrome; D017211:Treatment Failure; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; D047888:Receptors, Tumor Necrosis Factor, Type I; C506235:TNFRSF1A protein, human; D003078:Colchicine