Recommendations related to ocular, mucosal and cutaneous involvement of Behçet's disease (BD) are mainly evidence-based, but in cases of vascular, neurological and gastrointestinal involvement there ...are no guidelines to define the best treatment strategy. We report three adult patients with BD, who received an interleukin-1β inhibitor by subcutaneous injections, canakinumab (at the dosage of 150 mg every 6 weeks), after failure shown by corticosteroids and different combinations of immunosuppressant agents. The prompt and sustained clinical efficacy demonstrated by canakinumab as a monotherapy supports the opportunity of using this specific anti-interleukin-1β agent as a valid therapeutic option for resistant or refractory BD. Open trials and observational studies should be performed to test canakinumab efficacy on a larger number of patients. The most appropriate dosage and intervals between administrations should be decided according to the individual patient, severity or recurrence of clinical manifestations and major organ involvement.
Abstract Relapsing polychondritis is a rare and potentially fatal autoimmune disease of unknown etiology, characterized by inflammation and destruction of different cartilaginous structures, ...including the ear, nose, larynx, trachea, bronchi, peripheral joints, eye, heart and skin, with high risk of misdiagnosis. The spectrum of clinical presentations is protean and may vary from intermittent episodes of painful and disfiguring auricular and nasal chondritis or polyarthritis to severe progressive multi-organ damage. A laryngotracheobronchial involvement appears in nearly half of patients and is complicated by local obstructions, which may be life-threatening. A highly medical specialized approach is required for diagnosis of relapsing polychondritis. This review comprehensively examines the literature related to the clinical sceneries of the disease and focuses on both diagnostic tools used in clinical studies and recent findings related to its etiopathogenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Treatment of monogenic autoinflammatory disorders, an expanding group of hereditary diseases characterized by apparently unprovoked recurrent episodes of inflammation, without high-titre ...autoantibodies or antigen-specific T cells, has been revolutionized by the discovery that several of these conditions are caused by mutations in proteins involved in the mechanisms of innate immune response, including components of the inflammasome, cytokine receptors, receptor antagonists, and oversecretion of a network of proinflammatory molecules. Aim of this review is to synthesize the current experience and the most recent evidences about the therapeutic approach with biologic drugs in pediatric and adult patients with monogenic autoinflammatory disorders.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
A host of clinical scenarios can be depicted in hereditary autoinflammatory diseases, and the cardiovascular system can also be involved especially in familial Mediterranean fever (FMF), ...caused by mutations in the MEFV gene, and tumour necrosis factor receptor-associated periodic syndrome (TRAPS), caused by mutations in the TNFRSF1A gene. Pericardial diseases are the most represented cardiovascular abnormalities, though the role of MEFV and TNFRSF1A in the initiation of heart involvement has not been demonstrated formally and will be discussed herein.
Abstract 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 IgG1 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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background
The 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.
Methods
Therefore, 131 consecutive Caucasian IRAP patients were investigated for mutations of the TRAPS gene and prospectively evaluated.
Results
Out 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 (
p
< 0.001), a higher mean number of recurrences after the first year (
p
< 0.001), on colchicine treatment (
p
< 0.001), and a higher need of immunosuppressive therapies (
p
< 0.001).
Conclusion
TRAPS 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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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 adulthood.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Systemic autoinflammatory diseases are a group of inherited disorders of the innate immune system characterized by seemingly unprovoked inflammation recurring at variable intervals and ...involving skin, serosal membranes, joints, and gastrointestinal apparatus, with reactive amyloidosis as a possible severe long-term complication. Recent advances in genetics and molecular biology have improved our understanding of the pathogenesis of these diseases, including familial Mediterranean fever, mevalonate kinase deficiency syndrome, tumor necrosis factor receptor-associated periodic syndrome, cryopyrin-associated periodic syndromes, and hereditary pyogenic and granulomatous disorders: the vast majority of these conditions are related to the activation of the interleukin-1 pathway, which results in (or from?) a common unifying pathogenetic mechanism. Their diagnostic identification derives from the combination of clinical data, evaluation of acute phase reactants, clinical efficacy in response to specific drugs, and recognition of specific mutations in the relevant genes, although genetic tests may be unconstructive in some cases. This review will discuss clinical and laboratory clues useful for a diagnostic approach to systemic autoinflammatory diseases.
Abstract Hereditary periodic fever syndromes (HPFSs) are a group of inherited disorders of the innate immune system caused by mutations of genes involved in the regulation or activation of the ...inflammatory response, which belong to the category of autoinflammatory disorders. Most HPFs typically have an onset in pediatric age, while a limited number of patients experience disease onset during adulthood. The relative rarity and lack of information on adult-onset autoinflammatory diseases make it likely that genetic testing is often inconclusive. Recently, we have identified a set of variables related to the probability of detecting gene mutations in MEFV , responsible for familial Mediterranean fever, and TNFRSF1A , responsible for tumor necrosis factor receptor-associated periodic syndrome. In addition, we have proposed a diagnostic score for identifying those patients at high risk of carrying mutations in these genes. However, before the score can be recommended for application, further evaluation by means of longitudinal studies on different ethnicities and different populations deriving from other geographical areas is needed in order to definitively verify both its sensitivity and its specificity. The present manuscript offers our suggestions on how to establish a differential diagnosis for adult-onset HPFs, as well as a review of the literature, and we also provide a score revision available online.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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