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The autoinflammatory side of recurrent pericarditis: Enlightening the pathogenesis for a more rational treatment.
Trends Cardiovasc Med. 2020 May 03 [Online ahead of print]TC

Abstract

Recurrent pericarditis (RP) is a troublesome and debilitating complication of acute pericarditis. Although the etiopathogenesis of this condition remains unknown, an intricate overlap of autoimmune and autoinflammatory pathways has been hypothesized to explain its beginning and recurrence over time. The majority of cases are defined as "idiopathic", reflecting our awkwardness to unravel the intimate mechanisms of RP. Given the possible occurrence of anti-nuclear, anti-heart and anti-intercalated disk antibodies as well as the association with peculiar human leukocyte antigen haplotypes, an autoimmune contribution has been claimed to specify the nature of RP. However, the most innovative pathogenic scenario of RP has been conferred to the innate immune system, mainly involving neutrophils and macrophages that produce a large amount of interleukin (IL)-1 via inflammasome activation. The clinical resemblance of RP with autoinflammatory diseases that may be marked by symptomatic serositis, high fevers and strikingly increased inflammatory parameters further suggests a similar inflammasome-mediated pathogenesis. Aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of therapy in RP, whereas colchicine is recommended on top of standard anti-inflammatory therapy, due to its role in inhibiting the IL-1 converting enzyme (caspase 1) within the inflammasome as well as the release of additional pro-inflammatory mediators and reactive oxygen species. With regard to treatment of RP refractory to NSAIDs and colchicine, blockade of IL-1 is the most relevant advance achieved in the last decade: the outstanding effect of the short-acting IL-1 receptor antagonist anakinra has been first recognized in the pediatric population, giving a proof of its practical feasibility. Over a more recent time, a growing experience with anakinra deriving from both large and small studies has further confirmed that RP might be regarded as an IL-1-mediated disease. This review aims to provide a contemporary insight into the mechanisms leading to RP as well as into the most recent literature data showing the beneficial approach originating from IL-1 blockade in this intriguing disorder.

Authors+Show Affiliations

Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Piazza G. Cesare 11, Bari 70124, Italy. Electronic address: glopalco@hotmail.it.Department of Life Sciences and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy; Università Cattolica Sacro Cuore, Rome, Italy.Research Centre of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Centre, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.Cardiovascular and Thoracic Department, University Cardiology, Turin, Italy; AOU Città della Salute e della Scienza of Turin, University of Turin, Turin, Italy.Department of Pharmacy - Drug Sciences, University of Bari, Bari, Italy.Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Piazza G. Cesare 11, Bari 70124, Italy.Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Piazza G. Cesare 11, Bari 70124, Italy.Research Centre of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Centre, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.Department of Medicine, Azienda Socio Sanitaria Territoriale (ASST) Fatebenefratelli-Sacco and Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milan, Italy.Department of Medicine, Azienda Socio Sanitaria Territoriale (ASST) Fatebenefratelli-Sacco and Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milan, Italy.Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Piazza G. Cesare 11, Bari 70124, Italy.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32376492

Citation

Lopalco, Giuseppe, et al. "The Autoinflammatory Side of Recurrent Pericarditis: Enlightening the Pathogenesis for a More Rational Treatment." Trends in Cardiovascular Medicine, 2020.
Lopalco G, Rigante D, Cantarini L, et al. The autoinflammatory side of recurrent pericarditis: Enlightening the pathogenesis for a more rational treatment. Trends Cardiovasc Med. 2020.
Lopalco, G., Rigante, D., Cantarini, L., Imazio, M., Lopalco, A., Emmi, G., Venerito, V., Fornaro, M., Frediani, B., Nivuori, M., Brucato, A., & Iannone, F. (2020). The autoinflammatory side of recurrent pericarditis: Enlightening the pathogenesis for a more rational treatment. Trends in Cardiovascular Medicine. https://doi.org/10.1016/j.tcm.2020.04.006
Lopalco G, et al. The Autoinflammatory Side of Recurrent Pericarditis: Enlightening the Pathogenesis for a More Rational Treatment. Trends Cardiovasc Med. 2020 May 3; PubMed PMID: 32376492.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The autoinflammatory side of recurrent pericarditis: Enlightening the pathogenesis for a more rational treatment. AU - Lopalco,Giuseppe, AU - Rigante,Donato, AU - Cantarini,Luca, AU - Imazio,Massimo, AU - Lopalco,Antonio, AU - Emmi,Giacomo, AU - Venerito,Vincenzo, AU - Fornaro,Marco, AU - Frediani,Bruno, AU - Nivuori,Mariangela, AU - Brucato,Antonio, AU - Iannone,Florenzo, Y1 - 2020/05/03/ PY - 2020/03/09/received PY - 2020/04/09/revised PY - 2020/04/10/accepted PY - 2020/5/8/pubmed PY - 2020/5/8/medline PY - 2020/5/8/entrez KW - Anakinra KW - Autoinflammation KW - Autoinflammatory disease KW - Innovative biotechnologies KW - Interleukin-1 KW - Pericardial disease KW - Pericardium KW - Personalized medicine KW - Recurrent pericarditis JF - Trends in cardiovascular medicine JO - Trends Cardiovasc. Med. N2 - Recurrent pericarditis (RP) is a troublesome and debilitating complication of acute pericarditis. Although the etiopathogenesis of this condition remains unknown, an intricate overlap of autoimmune and autoinflammatory pathways has been hypothesized to explain its beginning and recurrence over time. The majority of cases are defined as "idiopathic", reflecting our awkwardness to unravel the intimate mechanisms of RP. Given the possible occurrence of anti-nuclear, anti-heart and anti-intercalated disk antibodies as well as the association with peculiar human leukocyte antigen haplotypes, an autoimmune contribution has been claimed to specify the nature of RP. However, the most innovative pathogenic scenario of RP has been conferred to the innate immune system, mainly involving neutrophils and macrophages that produce a large amount of interleukin (IL)-1 via inflammasome activation. The clinical resemblance of RP with autoinflammatory diseases that may be marked by symptomatic serositis, high fevers and strikingly increased inflammatory parameters further suggests a similar inflammasome-mediated pathogenesis. Aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of therapy in RP, whereas colchicine is recommended on top of standard anti-inflammatory therapy, due to its role in inhibiting the IL-1 converting enzyme (caspase 1) within the inflammasome as well as the release of additional pro-inflammatory mediators and reactive oxygen species. With regard to treatment of RP refractory to NSAIDs and colchicine, blockade of IL-1 is the most relevant advance achieved in the last decade: the outstanding effect of the short-acting IL-1 receptor antagonist anakinra has been first recognized in the pediatric population, giving a proof of its practical feasibility. Over a more recent time, a growing experience with anakinra deriving from both large and small studies has further confirmed that RP might be regarded as an IL-1-mediated disease. This review aims to provide a contemporary insight into the mechanisms leading to RP as well as into the most recent literature data showing the beneficial approach originating from IL-1 blockade in this intriguing disorder. SN - 1873-2615 UR - https://www.unboundmedicine.com/medline/citation/32376492/The_autoinflammatory_side_of_recurrent_pericarditis:_Enlightening_the_pathogenesis_for_a_more_rational_treatment L2 - https://linkinghub.elsevier.com/retrieve/pii/S1050-1738(20)30060-8 DB - PRIME DP - Unbound Medicine ER -
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