The autoinflammatory side of recurrent pericarditis: Enlightening the pathogenesis for a more rational treatment

• Published in: Trends in cardiovascular medicine 2021-07, Vol.31 (5), p.265-274
• Main Authors: Lopalco, Giuseppe, Rigante, Donato, Cantarini, Luca, Imazio, Massimo, Lopalco, Antonio, Emmi, Giacomo, Venerito, Vincenzo, Fornaro, Marco, Frediani, Bruno, Nivuori, Mariangela, Brucato, Antonio, Iannone, Florenzo
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Anakinra; Antigens; Aspirin; Autoimmune diseases; Autoinflammation; Autoinflammatory disease; Caspase-1; Colchicine; Cytokines; Genotype & phenotype; Haplotypes; Histocompatibility antigen HLA; Hypotheses; Immune system; Immunosuppressive agents; Inflammasomes; Inflammation; Inflammatory diseases; Injuries; Innate immunity; Innovative biotechnologies; Interleukin 1; Interleukin 1 receptor antagonist; Kinases; Leukocytes (neutrophilic); Macrophages; Mitochondrial DNA; Nonsteroidal anti-inflammatory drugs; Pathogenesis; Pericardial disease; Pericarditis; Pericardium; Personalized medicine; Proteins; Reactive oxygen species; Recurrent pericarditis; Serositis; Tumor necrosis factor-TNF
• ISSN: 1050-1738; 1873-2615
• DOI: 10.1016/j.tcm.2020.04.006

•The pathogenesis of recurrent pericarditis is still obscure, standing at a crossroad between autoimmune and autoinflammatory pathways.•The presence of anti-nuclear, anti-heart and anti-intercalated disk antibodies suggests the existence of autoimmune mechanisms.•The clinical resemblance with autoinflammatory diseases, supports the involvement of innate immunity.•Neutrophils and monocytes produce a large amount of interleukin-1 via inflammasome activation in patients with recurrent pericarditis.•Anakinra is an effective therapeutic choice to manage refractory cases of recurrent pericarditis. 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