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Articular Syndrome (articular + syndrome)
Selected AbstractsResponse to IL-1-Receptor Antagonist in a Child with Familial Cold Autoinflammatory SyndromePEDIATRIC DERMATOLOGY, Issue 1 2007Susan M. O'Connell M.R.C.P.I. They appear to represent a continuum of one disease characterized by IL-1-mediated inflammation. Until recently, these conditions have been difficult to treat; however, with the advent of IL-1-receptor antagonist therapy, many reports of successful treatment of patients with these autoinflammatory diseases have emerged in the past 2 years. We describe an 8-year-old girl, diagnosed with Familial cold auto-inflammatory syndrome, confirmed by presence of a novel CIAS1 mutation, who was refractory to symptomatic treatment. As frequent attacks of urticaria and associated arthralgia had a debilitating effect on the child's lifestyle, a trial of IL-1-receptor antagonist (anakinra) was instituted. Dramatic sustained clinical improvement was evident within days and serum amyloid and C-reactive protein levels normalized within a month. Although several authors have reported successful use of this agent in children with chronic infantile neurologic, cutaneous, articular syndrome, we believe ours is the first report of successful treatment with anakinra in a young child with familial cold auto-inflammatory syndrome. [source] Autoinflammatory syndromes with a dermatological perspectiveTHE JOURNAL OF DERMATOLOGY, Issue 9 2007Nobuo KANAZAWA ABSTRACT The term autoinflammatory syndromes describes a distinct group of systemic inflammatory diseases apparently different from infectious, autoimmune, allergic and immunodeficient ones. Originally, it was almost synonymous with clinically defined hereditary periodic fever syndromes, including familial Mediterranean fever, hyper immunoglobulin D syndrome with periodic fever and tumor necrosis factor receptor-associated periodic syndrome. Similar but distinct periodic fever syndromes accompanied by urticarial rash, familial cold autoinflammatory syndrome, Muckle,Wells syndrome and chronic infantile neurological cutaneous articular syndrome, have all been reportedly associated with CIAS1 mutations and are collectively called cryopyrin-associated periodic syndromes. Consequently, the concept of autoinflammatory syndromes has been spread to contain other systemic inflammatory diseases: rare hereditary diseases with or without periodic fevers, such as pyogenic sterile arthritis, pyoderma gangrenosum and acne syndrome, Blau syndrome and chronic recurrent multifocal osteomyelitis, and the more common collagen disease-like diseases, such as Behcet's disease, Crohn's disease, sarcoidosis and psoriatic arthritis. These diseases are all caused by or associated with mutations of genes regulating innate immunity and have common clinical features accompanied with activation of neutrophils and/or monocytes/macrophages. In this review, major autoinflammatory syndromes are summarized and the pathophysiology of related skin disorders is discussed in association with dysregulated innate immune signaling. [source] A somatic NLRP3 mutation as a cause of a sporadic case of chronic infantile neurologic, cutaneous, articular syndrome/neonatal-onset multisystem inflammatory disease: Novel evidence of the role of low-level mosaicism as the pathophysiologic mechanism underlying mendelian inherited diseasesARTHRITIS & RHEUMATISM, Issue 4 2010Juan I. Aróstegui Objective Chronic infantile neurologic, cutaneous, articular syndrome (CINCA), also known as neonatal-onset multisystem inflammatory disease (NOMID), is a severe, early-onset autoinflammatory disease characterized by an urticaria-like rash, arthritis/arthropathy, variable neurologic involvement, and dysmorphic features, which usually respond to interleukin-1 blockade. CINCA/NOMID has been associated with dominant Mendelian inherited NLRP3 mutations. However, conventional sequencing analyses detect true disease-causing mutations in only ,55,60% of patients, which suggests the presence of genetic heterogeneity. We undertook the current study to assess the presence of somatic, nongermline NLRP3 mutations in a sporadic case of CINCA/NOMID. Methods Clinical data, laboratory results, and information on treatment outcomes were gathered through direct interviews. Exhaustive genetic studies, including Sanger method sequencing, subcloning, restriction fragment length polymorphism assay, and pyrosequencing, were performed. Results The patient's CINCA/NOMID was diagnosed based on clinical features (early onset of the disease, urticaria-like rash, knee arthropathy, and dysmorphic features). The patient has exhibited a successful response to anakinra within the last 28 months. Analysis of NLRP3 identified a novel heterozygous variant (p.D303H) that was detected in ,30,38% of circulating leukocytes. The absence of this variant in healthy controls and in the patient's parents suggested a de novo true disease-causing mutation. Additional analyses showed that this novel mutation was present in both leukocyte subpopulations and epithelial cells. Conclusion Our findings identify the novel p.D303H NLRP3 variant in a Spanish patient with CINCA/NOMID as a new disease-causing mutation, which was detected as a somatic, nongermline mutation in hematopoietic and nonhematopoietic cell lineages. Our data provide new insight into the role of low-level mosaicism in NLRP3 as the pathophysiologic mechanism underlying cryopyrin-associated periodic syndrome. [source] Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndromeARTHRITIS & RHEUMATISM, Issue 1 2010Bénédicte Neven Objective Cryopyrin-associated periodic syndromes (CAPS) are a group of rare autoinflammatory diseases. Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic, cutaneous, articular syndrome (CINCA syndrome) is the most severe phenotype, with fever, rash, articular manifestations, and neurologic and neurosensory involvement. CAPS are caused by mutations in CIAS1, the gene encoding NLRP3, which plays a critical role in interleukin-1 (IL-1) processing. Anakinra, an IL-1 receptor antagonist, has been shown to be an effective treatment; however, data on long-term efficacy and safety have been sparse. This study was undertaken to assess the long-term efficacy and safety of anakinra treatment in patients with NOMID/CINCA syndrome. Methods We retrospectively analyzed the medical records of NOMID/CINCA syndrome patients referred to 2 centers, who had started anakinra treatment before June 2007. Results There were 10 patients with NOMID/CINCA syndrome who had been treated with anakinra. The patients' ages at the time anakinra treatment was initiated ranged from 3 months to 20 years. They had been followed up for 26,42 months. Sustained efficacy in the treatment of systemic inflammation and, in some cases, neurologic involvement and growth parameters, was achieved. The dosage of anakinra required for efficacy ranged from 1 to 3 mg/kg/day in the 8 oldest patients and from 6 to 10 mg/kg/day in the 2 youngest. Residual central nervous system inflammation and deafness persisted in some patients, especially if there had been a delay in diagnosis and treatment. Secondary amyloidosis persisted in cases in which it was present at treatment initiation, but no new lesions developed. No effect on overgrowth arthropathy was observed. Adverse events consisted of mild injection-site reactions. Conclusion The present results indicate that anakinra treatment is effective over the long term in NOMID/CINCA syndrome. However, treatment has to be initiated before irreversible lesions develop, and, particularly in very young patients, dosage adjustment is required. [source] 4252: An introduction to autoinflammatory syndromesACTA OPHTHALMOLOGICA, Issue 2010B BODAGHI To define the spectrum and pathophysiology of autoinflammatory syndromes. This term has been proposed to describe a new group of diseases characterized by attacks of seemingly unprovoked inflammation in the absence of pathogens, without significant levels of autoantibodies and autoreactive T cells. Hereditary periodic fever syndrome, Crohn's disease, Blau syndrome, Chronic infantile neurologic cutaneous and articular syndrome and Muckle-Wells syndrome are examples of autoinflammatory conditions characterized by recurrent attacks of inflammation without any association with auto-antigens. The study of autoinflammatory diseases has progressed from genetics to definition of the functional defects. Although a direct association between defective innate immune responses to bacterial components and these diseases has not been established yet, this hypothesis remains highly plausible. Mutations in genes encoding the tumour necrosis factor (TNF) receptor and pyrin superfamilies of molecules may induce persistence of leukocytes that would ordinarily undergo apoptosis with further amplification of inflammatory stimuli. The use of biologics may control some of these conditions. [source] | ||||||||||