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Autoinflammatory Syndrome (autoinflammatory + syndrome)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Response to IL-1-Receptor Antagonist in a Child with Familial Cold Autoinflammatory Syndrome

PEDIATRIC DERMATOLOGY, Issue 1 2007
Susan 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 perspective

THE JOURNAL OF DERMATOLOGY, Issue 9 2007
Nobuo 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]

Cryopyrin-associated periodic syndromes and autoinflammation

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2008
K. Shinkai
Summary Autoinflammatory syndromes are a distinct class of inherited diseases of cytokine dysregulation with important cutaneous features. Several disorders, including familial cold autoinflammatory syndrome (FCAS), Muckle,Wells syndrome and neonatal onset multisystem inflammatory disorder (NOMID), are associated with mutations in a common gene, CIAS-1. These disorders are now believed to represent related conditions along a spectrum of disease severity, in which FCAS is the mildest and NOMID is the most severe phenotype. Patients typically present with lifelong atypical urticaria with systemic symptoms, with potential for developing end-organ damage due to chronic inflammation. Advances in the understanding of the genetic basis of these syndromes have also revealed cytokine signalling molecules that are critical to normal regulation of inflammatory pathways. The dramatic response of these syndromes to anakinra, an interleukin (IL)-1 antagonist, highlights the important role of IL-1 cytokine signalling in the pathogenesis of this rare but fascinating class of diseases. [source]

The Schnitzler syndrome: Chronic urticaria and monoclonal gammopathy , an autoinflammatory syndrome?

JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 8 2008
Elisabeth Eiling
Summary Schnitzler syndrome describes the simultaneous occurrence of monoclonal gammopathy and chronic urticaria with at least two additional minor symptoms (arthralgia, bone pain, fever of uncertain origin, hepato- or splenomegaly, lymphadenopathy, increased erythrocyte sedimentation rate, leukocytosis/thrombocytosis or increased bone density). Schnitzler syndrome is not wellknown and very likely under-recognized. Comprehensive diagnostic examinations are necessary to rule out other diseases, especially those of hematologic origin. Close interdisciplinary collaboration is mandatory. The etiology of Schnitzler syndrome is unclear, but the rapid response to the interleukin-1 receptor inhibitor anakinra underlines the pivotal role which the proinflammatory cytokine interleukin-1 may play in the pathophysiology of this potentially autoinflammatory disorder. [source]

Autoinflammatory syndromes with a dermatological perspective

S100A12 is a novel molecular marker differentiating systemic-onset juvenile idiopathic arthritis from other causes of fever of unknown origin

ARTHRITIS & RHEUMATISM, Issue 12 2008
Helmut Wittkowski
Objective Fever of unknown origin (FUO) in children presents a diagnostic challenge. The differential diagnosis includes systemic-onset juvenile idiopathic arthritis (JIA), an autoinflammatory syndrome associated with activation of phagocytic cells that, at presentation, is difficult to differentiate from severe systemic infections. The aim of this study was to investigate whether serum concentrations of the phagocytic proinflammatory protein S100A12 may help in deciding whether to treat patients with FUO with antibiotics or immunosuppressive agents. Methods Serum samples were obtained from 45 healthy control subjects and from 240 patients (60 with systemic-onset JIA, 17 with familial Mediterranean fever [FMF], 18 with neonatal-onset multisystem inflammatory disease [NOMID], 17 with Muckle-Wells syndrome [MWS], 40 with acute lymphoblastic leukemia [ALL], 5 with acute myeloblastic leukemia [AML], and 83 with systemic infections). All samples were collected at the time of presentation, before the initiation of any treatment, and concentrations of S100A12 were determined by enzyme-linked immunosorbent assay. Results The mean ± 95% confidence interval serum levels of S100A12 were as follows: in patients with JIA, 7,190 ± 2,690 ng/ml; in patients with FMF, 6,720 ± 4,960 ng/ml; in patients with NOMID, 720 ± 450 ng/ml; in patients with MWS, 150 ± 60 ng/ml; in patients with infections, 470 ± 160 ng/ml; in patients with ALL, 130 ± 80 ng/ml; in patients with AML, 45 ± 60 ng/ml; in healthy control subjects, 50 ± 10 ng/ml. The sensitivity and specificity of S100A12 to distinguish between systemic-onset JIA and infections were 66% and 94%, respectively. Conclusion S100A12, a marker of granulocyte activation, is highly overexpressed in patients with systemic-onset JIA or FMF, which may point to as-yet unknown common inflammatory mechanisms in these diseases. The measurement of S100A12 serum levels may provide a valuable diagnostic tool in the evaluation of FUO. [source]

PYPAF1 nonsense mutation in a patient with an unusual autoinflammatory syndrome: Role of PYPAF1 in inflammation

ARTHRITIS & RHEUMATISM, Issue 2 2006
I. Jéru
Objective To gain insight into the pathophysiology of an unusual autoinflammatory syndrome, in a patient of Armenian origin, that mimicked familial Mediterranean fever (FMF) but with episodes triggered by generalized exposure to cold, and to further elucidate the controversial function of the protein encoded by PYPAF1, whose mutations (exclusively missense to date) have been identified in 3 hereditary recurrent fever syndromes. Methods The patient's DNA was screened for mutations in both MEFV, the gene responsible for FMF, and PYPAF1. The ability of different recombinant PYPAF1 isoforms, expressed in HEK 293 cells, to regulate NF-,B signaling was subsequently assessed. Results No disease-causing mutation was found in MEFV. However, a nonsense mutation (p.Arg554X) was identified in PYPAF1; this defect resulted in a truncated protein lacking all leucine-rich repeats. Study of the wild-type and mutant PYPAF1 recombinant proteins revealed that PYPAF1 inhibited NF-,B proinflammatory pathways, and that the identified nonsense mutation impaired this property. Conclusion These molecular and clinical findings, together with the clinical manifestations in the patient, which call into question the current nosology of the hereditary recurrent fever syndromes, are consistent with the hypothesis that PYPAF1 acts as an inhibitor of NF-,B signaling. They also provide a clear elucidation of the functional consequences of this nonsense PYPAF1 mutation not previously described in the literature, which result in a partial loss of function and may thereby explain the pathophysiology of the autoinflammatory syndrome observed in this patient. [source]

Monocytic fasciitis: A newly recognized clinical feature of tumor necrosis factor receptor dysfunction

ARTHRITIS & RHEUMATISM, Issue 8 2002
Keith M. Hull
Tumor necrosis factor receptor,associated periodic syndrome (TRAPS) is a dominantly inherited autoinflammatory syndrome that results from mutations in TNFRSF1A, the gene that encodes the 55-kd tumor necrosis factor receptor. Clinically, patients present with recurrent episodes of fever in conjunction with localized inflammation at various sites. Myalgia is one of the most characteristic features of this syndrome and is frequently associated with an overlying erythematous, macular rash that, together with the myalgia, displays centrifugal migration. This has previously been believed to occur as a result of myositis. We describe herein the case of a 60-year-old man with TRAPS, in whom magnetic resonance imaging of the left thigh demonstrated edematous changes in the muscle compartments and surrounding soft tissues. A full-thickness wedge biopsy was performed, and hematoxylin and eosin staining and immunohistochemistry analysis of the specimen demonstrated normal myofibrils but a severely destructive monocytic fasciitis. These results suggest that the myalgia experienced by individuals with TRAPS is due to a monocytic fasciitis and not to myositis. [source]

A novel mutation in the third extracellular domain of the tumor necrosis factor receptor 1 in a Finnish family with autosomal-dominant recurrent fever

ARTHRITIS & RHEUMATISM, Issue 4 2002
Hanna Nevala
Objective To investigate the presence of TRAPS (tumor necrosis factor receptor,associated periodic syndrome), which is a recently defined, dominantly inherited autoinflammatory syndrome caused by mutations in the tumor necrosis factor receptor superfamily 1A gene (TNFRSF1A, CD120a), in a Finnish family with recurrent fever. Methods The TNFRSF1A gene was sequenced in both affected and unaffected family members. Flow cytometry and enzyme-linked immunosorbent assay analyses were used to assess membrane expression and serum levels of the TNFRSF1A protein, respectively. Results A missense mutation in exon 4, located in the third extracellular domain of TNFRSF1A and resulting in an amino acid substitution (F112I) close to a conserved cysteine, was found in all 4 affected family members and in 1 asymptomatic individual. The mutation was clearly associated with low levels of soluble TNFRSF1A as well as with the clinical symptoms of recurrent fever and abdominal pain. Impaired shedding of TNFRSF1A after phorbol myristate acetate stimulation was detected in blood granulocytes and monocytes from the 3 adult family members with the mutation, but in the child bearing the mutation and showing clinical symptoms of recent onset, the shedding defect was less marked. Conclusion TRAPS should be suspected in any patient who presents with a history of intermittent fever accompanied by unexplained abdominal pain, arthritis, or skin rash, particularly in the presence of a family history of such symptoms. Screening for low serum levels of soluble TNFRSF1A identifies individuals who are likely to have TNFRSF1A mutations. [source]

Cryopyrin-associated periodic syndromes and autoinflammation

Genetics of inflammasome-associated disorders: A lesson in the guiding principals of inflammasome function

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2010
Ian Gaël Rodrigue-Gervais
Abstract Human genetics research has had a great impact on the genesis of the inflammasome field and the treatment of certain inflammasomopathies. The identification of mutations causing rare autoinflammatory syndromes, reproductive wastage disorders and of single nucleotide polymorphisms influencing susceptibility to complex diseases such as vitiligo, sepsis, and Crohn's disease has not only led to the characterization of novel proteins involved in NOD-like receptor-coupled inflammatory signaling pathways but also to greater insights into pathogenic mechanisms. [source]

Periodic fever syndromes: a diagnostic challenge for the allergist

ALLERGY, Issue 12 2007
M. Lierl
The objective was to present a case of periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA), summarize the medical literature on PFAPA, review the differential diagnosis and suggest a diagnostic approach to periodic fevers in children. A PubMed search was conducted for all case reports and series of patients with PFAPA. The references of these papers yielded further case reports. Review articles or large case series were used for sources of information regarding the other periodic fever and autoinflammatory syndromes. All cases reported as PFAPA were included in the review, even though a few of the cases may not have been accurately diagnosed. The periodic fever and autoinflammatory syndromes of childhood are a group of diseases that cause repeated febrile illnesses with various associated symptoms. Except for PFAPA, each of these diseases is caused by a known genetic mutation. Effective treatment options and long-term prognosis varies among these syndromes. Children with periodic fever or autoinflammatory syndromes sometimes present to an Allergy/Immunology clinic for immunologic evaluation. It is important for the Allergy/Immunology specialist to be familiar with the clinical presentation, diagnostic approach and treatment of these conditions. [source]

Autoinflammatory syndromes with a dermatological perspective

4251: General principles of autoinflammation and autoimmunity

ACTA OPHTHALMOLOGICA, Issue 2010
F WILLERMAIN
Purpose In this talk, the definition and the molecular mechanisms of autoinflammation and autoimmunity will be introduced. Methods Defense against invading microorganisms is one of the main challenges of life. Very early in the evolution, a series of germline-encoded protein capable to detect pathogen associated molecular patterns (PAMP) have evolved. PAMPs include toll-like receptors, NOD like receptors and C-type lectin. Their activation converges to the rapid stimulation of proinflammatory pathways. Results PAMPs are at the basis of the innate immune response which represent the first line of defense and will shape the nature of the adaptive immune system. The latter is mediated by clonal selection and expansion of antigen specific T and B lymphocytes. It is now well described that dysregulations of those two arms of the immune system are associated with distinct clinical diseases. Conclusion Various anomalies of the innate immune system have been found in a series of disease grouped under the name autoinflammatory syndromes. This term highlight the distinction between those diseases and classical autoimmune diseases, characterized by an abnormal adaptive immune response with the presence of autoantibodies and/or autoreactive T cells. [source]

4252: An introduction to autoinflammatory syndromes

ACTA OPHTHALMOLOGICA, Issue 2010
B 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]