Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities.

Objectives: To develop evidence-based European League Against Rheumatism (EULAR) recommendations for the management of Behçet disease (BD) supplemented where necessary by expert opinion. Methods: The multidisciplinary expert committee, a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), consisted of nine rheumatologists (one who was also a clinical epidemiologist and one also a Rehabilitation Medicine doctor), three ophthalmologists, one internist, one dermatologist and one neurologist, representing six European countries plus Tunisia and Korea. A patient representative was also present. Problem areas and related keywords for systematic literature research were identified. Systematic literature research was performed using Medline and the Cochrane Library databases from 1966 through to December 2006. A total of 40 initial statements were generated based on the systematic literature research. These yielded the final recommendations developed from two blind Delphi rounds of voting. Results: Nine recommendations were developed for the management of different aspects of BD. The strength of each recommendation was determined by the level of evidence and the experts' opinions. The level of agreement for each recommendation was determined using a visual analogue scale for the whole committee and for each individual aspect by the subgroups, who consider themselves experts in that field of BD. There was excellent concordance between the level of agreement of the whole group and the ''experts in the field''. Conclusion: Recommendations related to the eye, skinmucosa disease and arthritis are mainly evidence based, but recommendations on vascular disease, neurological and gastrointestinal involvement are based largely on expert opinion and uncontrolled evidence from open trials and observational studies. The need for further properly designed controlled clinical trials is apparent.The aim of treatment in Behçet disease (BD) is to prevent irreversible damage that mostly occurs early in the course of disease, especially in the highrisk group, young men, 1 2 and to prevent exacerbations of mucocutaneous and joint involvement, usually not causing damage but affecting quality of life. The multisystem involvement mandates collaboration between different specialties.Our aim was to develop recommendations for the management of BD, in line with the European Leage Against Rheumatism (EULAR)'s standardised operating procedures, 3 combining current evidence from clinical trials with expert opinion. The recommendations target all doctors and surgeons who are involved in the treatment of BD. METHODS The expert committeeThe committee consisted of nine rheumatologists (one who was also a clinical epidemiologist and one also a rehabilitationist), three ophthalmologists, one internist, one dermatologist and one neurologist, representing six European countries plus Tunisia and Korea. A patient representative was also present. Development of recommendationsThe experts were invited to propose problem areas and r...

Human cytomegalovirus (HCMV), a betaherpesvirus, has developed several ways to evade the immune system, notably downregulation of cell surface expression of major histocompatibility complex class I heavy chains. Here we report that HCMV has devised another means to compromise immune surveillance mechanisms. Extracellular accumulation of both constitutively produced monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor–superinduced RANTES (regulated on activation, normal T cell expressed and secreted) was downregulated in HCMV-infected fibroblasts in the absence of transcriptional repression or the expression of polyadenylated RNA for the cellular chemokine receptors CCR-1, CCR-3, and CCR-5. Competitive binding experiments demonstrated that HCMV-infected cells bind RANTES, MCP-1, macrophage inflammatory protein (MIP)-1β, and MCP-3, but not MCP-2, to the same receptor as does MIP-1α, which is not expressed in uninfected cells. HCMV encodes three proteins with homology to CC chemokine receptors: US27, US28, and UL33. Cells infected with HCMV mutants deleted of US28, or both US27 and US28 genes, failed to downregulate extracellular accumulation of either RANTES or MCP-1. In contrast, cells infected with a mutant deleted of US27 continues to bind and downregulate those chemokines. Depletion of chemokines from the culture medium was at least partially due to continuous internalization of extracellular chemokine, since exogenously added, biotinylated RANTES accumulated in HCMV-infected cells. Thus, HCMV can modify the chemokine environment of infected cells through intense sequestering of CC chemokines, mediated principally by expression of the US28-encoded chemokine receptor.

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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.

Diagnosis of PIOL is often made months or years after the initial onset of ocular symptoms. Cytology remains the gold standard for diagnosis. However, measurement of IL-10 in the AH is a good screening test to reduce diagnostic delays.

The prognosis of the disease remains poor. However, the new diagnostic tools and therapeutic strategies may improve the diagnostic delay and the survival outcome.