Role of Autoimmunity and Autoinflammation in the Pathogenesis of Idiopathic Recurrent Pericarditis.

Idiopathic recurrent pericarditis is the most common and troublesome complication of acute pericarditis affecting about one third of such patients. The pericardium may be involved in different systemic autoimmune diseases (i.e., systemic lupus erythematosus, rheumatoid arthritis, progressive systemic sclerosis, mixed connective tissue disease, Sjogren's Syndrome, polyarteritis, giant cell arteritis, other systemic vasculitides) either in a symptomatic form (usually during the active phase of the disease) or as asymptomatic pericardial effusion. Moreover, idiopathic recurrent pericarditis mimicks hereditary periodic fever syndromes (HPFSs). HPFSs are a group of disorders characterized by primary dysfunction of the innate immune system mostly caused by mutations of genes involved in the regulation or activation of the inflammatory response, without any apparent involvement of antigen-specific T cells or significant production of autoantibodies. These disorders usually manifest in the pediatric population, with onset ranging from the first hours to the first decade of life, however a limited number of patients experience disease onset during adulthoo

Typical and severe tumor necrosis factor receptor-associated periodic syndrome in the absence of mutations in the TNFRSF1A gene: a case series.

Tumor necrosis factor receptor-1-associated periodic syndrome (TRAPS) is the most common autosomal dominant autoinflammatory disorder and is caused by mutations in the TNFRSF1A gene encoding the 55-kDa receptor for tumor necrosis factor (TNF)-alpha. TRAPS is characterized by recurrent attacks of fever, typically lasting from 1 to 3 weeks. In addition to fever, common clinical features include periorbital edema, a migratory erythematous plaque simulating erysipela with underlying myalgia, and arthralgia or arthritis. Serosal membrane inflammation is also a common feature, usually in the form of polyserositis. To date, at least 40 different TNFRSF1A mutations have been identified, but few patients with symptoms highly suggestive of TRAPS with no mutations in the TNFRSF1A gene have recently been described, thus suggesting that not all mutations are yet known or that alternative mechanisms might be involved in the pathogenesis of the disease. We report on three such patients here

Tumour necrosis factor receptor-associated periodic syndrome(TRAPS): State of the art and future perspectives.

Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory disorder characterized by periodic fever episodes, arthralgia, myalgia, abdominal pain, serositis, and skin rash. TRAPS is caused by mutations in the gene encoding the TNF Receptor Super Family 1A (TNFRSF1A) on chromosome 12p13. The identification of TNFRSF1A mutations as the genetic cause of TRAPS coincided with the wider use of biological agents in medicine and raised the possibility that blocking TNF could potentially represent the primary therapeutic goal in TRAPS, thus disclosing new treatment choices for this complex disease. Anti-TNF therapy in TRAPS has been based on etanercept, a recombinant human TNFR (p75)-Fc fusion protein comprising two receptors linked by an IgG(1) Fc fragment. However a decrease in responsiveness to etanercept over time has been described, and it may be due to a non-specific action of etanercept in TRAPS; its efficacy may reflect 'generic' anti-inflammatory properties. Long-term adherence to etanercept is poor and a significant number of patients need to switch to anti-interleukin (IL)-1β therapy. In fact, the IL-1 receptor antagonist anakinra has recently been shown to prevent disease relapses both in the short- and in the long-term, and to induce a prompt and stable disease remission

Bridging the gap between the clinician and the patient with cryopyrin-associated periodic syndromes

Cryopyrin-associated periodic syndromes are categorized as a spectrum of three autoinflammatory diseases, namely familial cold auto-inflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurological cutaneous articular syndrome. All are caused by mutations in the NLRP3 gene coding for cryopyrin and result in active interleukin-1 release: their rarity and shared clinical indicators involving skin, joints, central nervous system and eyes often mean that correct diagnosis is delayed. Onset occurs early in childhood, and life-long therapy with interleukin-1 blocking agents usually leads to tangible clinical remission and inflammatory marker normalization in a large number of patients, justifying the need to facilitate early diagnosis and thus avoid irreversible negative consequences for tissues and organs

The laboratory approach in the diagnosis of systemic autoinflammatory diseases

Autoinflammatory diseases are a relatively new category of diseases that also result from increased inflammation unrelated to autoreactive cells or autoantibodies. This overview contains general information about the diagnostic identification of the more common hereditary monogenic autoinflammatory diseases