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      Comparative study of ophthalmological and serological manifestations and the therapeutic response of patients with isolated scleritis and scleritis associated with systemic diseases Translated title: Estudo comparativo entre as manifestações oftalmológicas, sorológicas e resposta terapêutica de pacientes com esclerite isolada e esclerite associada a doenças sistêmicas

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          Abstract

          INTRODUCTION: Scleritis is a rare, progressive and serious disease, the signs of which are inflammation and edema of episcleral and scleral tissues and is greatly associated with systemic rheumatoid diseases. PURPOSE: To perform a prospective and comparative study between ophthalmologic manifestations, serologic findings and therapeutic response of patients with isolated scleritis and scleritis associated with systemic rheumatoid disease. METHODS: Thirty-two outpatients with non-infectious scleritis were studied, from March 2006 to March 2008. The treatment was corticoid eye drops associated with anti-inflammatory agents, followed by systemic corticoids and immunosuppressive drugs if necessary, was considered successful after six months without scleritis recurrence. RESULTS: Fourteen of 32 patients had scleritis associated with systemic rheumatoid disease, of which nine had rheumatoid arthritis, two systemic lupus erythematosus, one Crohn's disease, one Behçet's disease and one gout. There were no difference in relation to involvement and ocular complications, there was predominance of nodular anterior scleritis and scleral thinning was the most frequent complication. The scleritis associated with systemic rheumatoid disease group had 64.3% of autoantibodies, versus 27.8% among those with isolated scleritis and this difference was statistically significant. In the isolated scleritis group 16.7% used anti-inflammatory, 33.3% corticosteroids, 27.8% corticosteroids with one immunosuppressive drug, 5.5% two immunosuppressive drugs, 16.7% corticosteroids with two immunosuppressive drugs and 33.3% pulse of immunosuppressive drugs, there was remission in 88.9%. In the scleritis associated with systemic rheumatoid disease group 7.1% used anti-inflammatory, 7.1% corticosteroids, 50% corticosteroids with one immunosuppressive drug, 7.1% two immunosuppressive drugs and 22.2% pulse of immunosuppressive drugs, 100% had treatment success. CONCLUSION: Prevalence of unilateral nodular scleritis was noted in both groups and higher rates of all the parameters tested were noted in the scleritis associated with systemic rheumatoid disease group. There were no differences between the groups with respect to the use of immunosuppressive drugs and therapeutic response, which was fully satisfactory in the scleritis associated with systemic rheumatoid disease group and satisfactory in the isolated scleritis group.

          Translated abstract

          INTRODUÇÃO: Esclerite é uma doença grave, rara e progressiva, que envolve inflamação e edema dos tecidos episcleral superficial, profundo e escleral e está associada com doenças sistêmicas reumatológicas em muitos casos. OBJETIVOS: Realizar um estudo prospectivo comparativo entre as manifestações oftalmológicas, achados sorológicos e resposta terapêutica de pacientes com esclerite isolada e com esclerite associada a doenças sistêmicas reumatológicas. MÉTODOS: Trinta e dois pacientes com esclerite não infecciosa participaram do estudo, de março de 2006 a março de 2008. O tratamento realizado baseou-se no uso de colírios de corticoides associados aos anti-inflamatórios não-hormonais, seguidos de corticoides sistêmicos e imunossupressores, se necessário. O sucesso do tratamento foi considerado como seis meses sem crises de esclerite. RESULTADOS: Quatorze dos 32 pacientes apresentaram esclerite associada à doença sistêmica, dos quais nove com artrite reumatóide, dois com lúpus eritematoso sistêmico, um com doença de Crohn, um com doença de Behçet e um com gota. Não houve diferenças em relação ao envolvimento ocular e suas complicações, predominando a esclerite anterior nodular e o afinamento escleral, respectivamente. O grupo com esclerite associada a doenças sistêmicas apresentou 64,3% de positividade de autoanticorpos contra 27,8% no grupo com esclerite isolada, sendo tal diferença estatisticamente significante. No grupo com esclerite isolada, 16,7% fez uso de apenas anti-inflamatórios, 33,3% de corticoide sistêmico, 27,8% de corticoide com um imunossupressor, 5,5% dois imunossupressores, 16,7% corticoide com dois imunossupressores e 33,3% pulsoterapia com imunossupressor; sendo que houve sucesso do tratamento em 88,9%. No grupo com esclerite associada à doença sistêmica, 7,1% fez uso de anti-inflamatórios, 7,1% corticoide sistêmico, 50% corticoide com um imunossupressor, 7,1% dois imunossupressores e 22,2% pulsoterapia com imunossupressor; com 100% de sucesso no tratamento nesse grupo. CONCLUSÃO: Em ambos os grupos houve predomínio da esclerite nodular unilateral e o grupo com esclerite associada a doença sistêmica apresentou taxas maiores de todos os autoanticorpos testados. Não houve diferença entre os grupos em relação ao uso de imunossupressores e à resposta terapêutica, a qual foi totalmente satisfatória no grupo com esclerite associada à doença sistêmica e satisfatória no grupo com esclerite isolada.

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          Scleral structure, organisation and disease. A review.

          Although disease of the sclera is unusual, when it occurs it can rapidly destroy both the eye and vision. However, normally the sclera provides an opaque protective coat for the intraocular tissues and a stable support during variations in internal pressure and eye movements, which would otherwise perturb the visual process through distortion of the retina and the lens/iris diaphragm. This stability, which is vital for clear vision is made possible by the organisation and viscoelastic properties of scleral connective tissue. Microscopically, the sclera displays distinct concentric layers including, from outside, Tenon's capsule, episclera, the scleral stroma proper and lamina fusca, melding into underlying choroid. Two sites exhibit specialised structure and function: the perilimbal trabecular meshwork, through which aqueous filters into Schlemm's canal, and the lamina cribrosa, which permits axons of the optic nerve to exit the posterior sclera. Throughout, sclera is densely collagenous, the stroma consisting of fibrils with various diameters combining into either interlacing fibre bundles or defined lamellae in outer zones. Scleral fibrils are heterotypic structures made of collagen types I and III, with small amounts of types V and VI also present. Scleral elastic fibres are especially abundant in lamina fusca and trabecular meshwork. The interfibrillar matrix is occupied by small leucine-rich proteoglycans, decorin and biglycan, containing dermatan and dermatan/chondroitin sulphate glycosaminoglycans, together with the large proteoglycan, aggrecan, which also carries keratan sulphate sidechains. Decorin is closely associated with the collagen fibrils at specific binding sites situated close to the C-terminus of the collagen molecules. Proteoglycans influence hydration, solute diffusion and fluid movement through the sclera, both from the uvea and via the trabecular meshwork. As the sclera is avascular, nutrients come from the choroid and vascular plexi in Tenon's capsule and episclera, where there is an artery to artery anastomosis in which blood oscillates, rather than flows rapidly. This predisposes to the development of vasculitis causing a spectrum of inflammatory conditions of varying intensity which, in the most severe form, necrotising scleritis, may destroy all of the structural and cellular components of the sclera. Scleral cells become fibroblastic and the stroma is infiltrated with inflammatory cells dominated by macrophages and T-lymphocytes. This process resembles, and may be concurrent with, systemic disease affecting other connective tissues, particularly the synovial joints in rheumatoid arthritis. Current views support an autoimmune aetiology for scleritis. Whilst the role of immune complexes and the nature of initial pro-inflammatory antigen(s) remain unknown, the latter may reside in scleral tissue components which are released or modified by viral infection, injury or surgical trauma.
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            Episcleritis and scleritis: clinical features and treatment results.

            To evaluate the clinical experience with episcleritis and scleritis at a tertiary care eye center. Retrospective chart review. One hundred thirty-four patients with scleral inflammation were seen over a 12-year period. Thirty-seven patients had episcleritis, and 97 patients had scleritis. Ocular complications occurred in only 13.5% of patients with episcleritis but in 58.8% of patients with scleritis (P <.0001). No patient with episcleritis had a decrease in visual acuity, whereas 15.9% of patients with scleritis did. Only 16.7% of patients with episcleritis required more than topical corticosteroids for treatment, and these patients required oral nonsteroidal anti-inflammatory drugs. Conversely, 30.4% of patients with scleritis required nonsteroidal anti-inflammatory drugs, 31.9% oral prednisone, and 26.1% systemic immunosuppressive drugs (P <.0001). Necrotizing scleritis and posterior scleritis more often were associated with ocular complications, occurring in 91.7% and 85.7%, respectively, than were diffuse anterior scleritis and nodular anterior scleritis (P =.020). Patients with necrotizing scleritis and posterior scleritis were more likely to be treated with oral corticosteroids or immunosuppressive drugs (90% and 100%, respectively) than were patients with diffuse anterior scleritis and nodular anterior scleritis (56.4% and 21.4%, respectively, P =.002). Scleritis is a severe ocular inflammation, often associated with ocular complications, and nearly always treated with systemic medications. Nearly 60% of these patients will need oral corticosteroids or immunosuppressive drugs to control the disease.
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              Tumor necrosis factor alpha drugs in rheumatoid arthritis: systematic review and metaanalysis of efficacy and safety

              Background To analyse available evidence on the efficacy and safety of anti-TNFα drugs (infliximab, etanercept and adalimumab) for treating rheumatoid arthritis (RA). Methods We searched systematically for randomised controlled clinical trials on treatment of RA with anti-TNFα drugs, followed by a systematic review with metaanalysis. Trials were searched from MEDLINE, EMBASE and Cochrane Library databases. The American College of Rheumatology (ACR) efficacy response criteria were used. Safety parameters provided by the trials were also assessed. Positive and undesired effects were estimated using combined relative risks (RR), number needed to treat (NNT) and number needed to harm (NNH). Heterogeneity was evaluated by Cochrane's Q and I2 statistics. Results Thirteen trials (7087 patients) met the inclusion criteria. The combined RR to achieve a therapeutic response to treatment with recommended doses of any anti-TNFα drug was 1.81 (95% CI 1.43–2.29) with a NNT of 5 (5–6) for ACR20. NNT for ACR50 [5 (5–6)] and ACR70 [7 (7–9)] were similar. Overall therapeutic effects were also similar regardless of the specific anti-TNFα drug used and when higher than recommended doses were administered. However, lower than recommended doses elicited low ACR70 responses (NNT 15). Comparison of anti-TNFα drugs plus methotrexate (MTX) with MTX alone in patients with insufficient prior responses to MTX showed NNT values of 3 for ACR20, 4 for ACR50 and 8 for ACR70. Comparison of anti-TNFα drugs with placebo showed a similar pattern. Comparisons of anti-TNFα drugs plus MTX with MTX alone in patients with no previous resistance to MTX showed somewhat lower effects. Etanercept and adalimumab administered as monotherapy showed effects similar to those of MTX. Side effects were more common among patients receiving anti-TNFα drugs than controls (overall combined NNH 27). Patients receiving infliximab were more likely to drop out because of side effects (NNH 24) and to suffer severe side effects (NNH 31), infections (NNH 10) and infusion reactions (NNH 9). Patients receiving adalimumab were also more likely to drop out because of side effects (NNH 47) and to suffer injection site reactions (NNH 22). Patients receiving etanercept were less likely to drop out because of side effects (NNH for control versus etanercept 26) but more likely to experience injection site reactions (NNH 5). Conclusion Anti-TNFα drugs are effective in RA patients, with apparently similar results irrespective of the drug administered. Doses other than those recommended are also beneficial. The main factor influencing therapeutic efficacy is the prior response to DMARD treatment. The effect of treatment with etanercept or adalimumab does not differ from that obtained with MTX. The published safety profile for etanercept is superior but the fact that no patients are treated with higher than recommended doses requires explanation.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                abo
                Arquivos Brasileiros de Oftalmologia
                Arq. Bras. Oftalmol.
                Conselho Brasileiro de Oftalmologia (São Paulo, SP, Brazil )
                0004-2749
                1678-2925
                December 2011
                : 74
                : 6
                : 405-409
                Affiliations
                [04] São Paulo SP orgnameUniversidade Federal de São Paulo orgdiv1Departamento de Oftalmologia orgdiv2Setor de Doenças Externas Oculares e Córnea Brazil
                [02] São Paulo SP orgnameUniversidade de Santo Amaro Brazil
                [01] São Paulo SP orgnameUniversidade Federal de São Paulo Brazil
                [03] São Paulo SP orgnameUniversidade Federal de São Paulo orgdiv1Departamento de Oftalmologia orgdiv2Setor de Doenças Externas Oculares e Córnea Brazil
                Article
                S0004-27492011000600004
                10.1590/S0004-27492011000600004
                22331111
                866b18c5-b943-4760-9e1c-3b1b7d3d6e4b

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 08 February 2011
                : 05 November 2011
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 41, Pages: 5
                Product

                SciELO Brazil


                Inflamação,Imunossupressores,Scleritis,Rheumatic diseases,Autoantibodies,Inflammation,Immunosuppressive agents,Esclerite,Doenças reumáticas,Autoanticorpos

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