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      Certolizumab-Induced Uveitis: A Case Report and Review of the Literature


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          We report the case of a 64-year-old woman with rheumatoid arthritis and bilateral visual deterioration. The patient had been treated with certolizumab, a new tumor necrosis factor alpha (TNFα) antagonist, and her findings were consistent with bilateral uveitis, suggestive of sarcoidosis. Here, we review the literature on TNFα antagonist-induced sarcoidosis and report the first case of uveitis induced by certolizumab. Awareness of the possibility of this unique complication is important for both rheumatologists and ophthalmologists who treat patients with this new agent.

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          Most cited references14

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          International criteria for the diagnosis of ocular sarcoidosis: results of the first International Workshop On Ocular Sarcoidosis (IWOS).

          To report criteria for the diagnosis of intraocular sarcoidosis, taking into account suggestive clinical signs and appropriate laboratory investigations and biopsy results. Concensus workshop of an international committee on nomenclature. An international group of uveitis specialists from Asia, Africa, Europe, and America met in a concensus conference in Shinagawa, Tokyo on October 28-29, 2006. Based on questionnaires that had been sent out prior to the conference, the participants discussed potential intraocular clinical signs eligible for a diagnosis of ocular sarcoidosis. A refined definition of clinical signs, which received two-thirds majority of votes, was included in the list of signs consistent with ocular sarcoidosis. Laboratory investigations were similarly discussed and those tests reaching a two-thirds majority were retained for the diagnosis of ocular sarcoidosis. Finally diagnostic criteria were proposed based on ocular signs, laboratory investigations, and biopsy results. The concensus conference identified seven signs in the diagnosis of intraocular sarcoidosis: (1) mutton-fat keratic precipitates (KPs)/small granulomatous KPs and/or iris nodules (Koeppe/Busacca), (2) trabecular meshwork (TM) nodules and/or tent-shaped peripheral anterior synechiae (PAS), (3) vitreous opacities displaying snowballs/strings of pearls, (4) multiple chorioretinal peripheral lesions (active and/or atrophic), (5) nodular and/or segmental peri-phlebitis (+/- candlewax drippings) and/or retinal macroaneurism in an inflamed eye, 6) optic disc nodule(s)/granuloma(s) and/or solitary choroidal nodule, and (7) bilaterality. The laboratory investigations or investigational procedures that were judged to provide value in the diagnosis of ocular sarcoidosis in patients having the above intraocular signs included (1) negative tuberculin skin test in a BCG-vaccinated patient or in a patient having had a positive tuberculin skin test previously, (2) elevated serum angiotensin converting enzyme (ACE) levels and/or elevated serum lysozyme, (3) chest x-ray revealing bilateral hilar lymphadenopathy (BHL), (4) abnormal liver enzyme tests, and (5) chest CT scan in patients with a negative chest x-ray result. Four levels of certainty for the diagnosis of ocular sarcoidosis (diagnostic criteria) were recommended in patients in whom other possible causes of uveitis had been excluded: (1) biopsy-supported diagnosis with a compatible uveitis was labeled as definite ocular sarcoidosis; (2) if biopsy was not done but chest x-ray was positive showing BHL associated with a compatible uveitis, the condition was labeled as presumed ocular sarcoidosis; (3) if biopsy was not done and the chest x-ray did not show BHL but there were 3 of the above intraocular signs and 2 positive laboratory tests, the condition was labeled as probable ocular sarcoidosis; and (4) if lung biopsy was done and the result was negative but at least 4 of the above signs and 2 positive laboratory investigations were present, the condition was labeled as possible ocular sarcoidosis. Various clinical signs, laboratory investigations, and biopsy results provided four diagnostic categories of sarcoid uveitis. The categorization allows prospective multinational clinical trials to be conducted using a standardized nomenclature, which serves as a platform for comparison of visual outcomes with various therapeutic modalities.
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            Autoimmune diseases induced by TNF-targeted therapies.

            Anti-TNF agents are increasingly being used for a rapidly expanding number of rheumatic and systemic autoimmune diseases. As a result of this use, and of the longer follow-up periods of treatment, there are a growing number of reports of the development of autoimmune processes related to anti-TNF agents. The clinical characteristics, outcomes, and patterns of association with the different anti-TNF agents used in all reports of autoimmune diseases developing after TNF-targeted therapy, were analyzed through a baseline Medline search of articles published between January 1990 and May 2008 (www.biogeas.org). A total of 379 cases of autoimmune diseases secondary to TNF-targeted therapies were identified. The anti-TNF agents were administered for rheumatoid arthritis in more than 80% of cases. The use of anti-TNF agents has been associated with an increasing number of cases of autoimmune diseases, principally cutaneous vasculitis, lupus-like syndrome, systemic lupus erythematosus and interstitial lung disease. Other autoimmune diseases associated with TNF-targeted therapies have been recently described, e.g. sarcoidosis, antiphospholipid syndrome-related features, and autoimmune hepatitis or uveitis. Large, prospective, postmarketing studies are required to evaluate the risk of developing autoimmune diseases in patients receiving TNF-targeted therapies.
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              Tumor necrosis factor-alpha antagonist-induced sarcoidosis.

              Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Tumor necrosis factor (TNF)-alpha is an important player in granuloma formation, and recent clinical trials have investigated the efficacy of TNF-alpha inhibitors in sarcoidosis. Paradoxically, there are several case reports in the medical literature describing the development of sarcoidosis in patients treated with TNF-alpha inhibitors. We describe 3 cases of TNF-alpha antagonist-induced sarcoidosis: 1 case of pulmonary, ocular and cutaneous sarcoidosis developing in a patient receiving infliximab for erosive rheumatoid arthritis, 1 case of etanercept-induced sarcoidosis in a patient with seronegative rheumatoid arthritis, and 1 case of sarcoidosis developing in a patient receiving etanercept for erosive rheumatoid arthritis. We also provide a brief discussion on the role of TNF alpha in granuloma formation and implications in the use of TNF-alpha antagonists in autoimmune disease.

                Author and article information

                Case Reports in Ophthalmology
                S. Karger AG
                January – April 2014
                12 February 2014
                : 5
                : 1
                : 54-59
                Department of Ophthalmology, Tel Aviv Medical Center, affiliated to the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
                Author notes
                *Elad Moisseiev, MD, Department of Ophthalmology, Tel Aviv Medical Center, Weitzman 6 St., Tel Aviv 64239 (Israel), E-Mail elad_moi@netvision.net.il
                358324 PMC3975203 Case Rep Ophthalmol 2014;5:54-59
                © 2014 S. Karger AG, Basel

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 2, Pages: 6
                Published: February 2014

                Vision sciences,Ophthalmology & Optometry,Pathology
                Ocular sarcoidosis,Certolizumab,Uveitis,Tumor necrosis factor alpha,Sarcoidosis


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