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Khalid Al-Kofahi,1,* Peter Korsten,2,* Christian Ascoli,3 Shanti Virupannavar,4 Mehdi Mirsaeidi,5 Ian Chang,6 Naim Qaqish,7 Lesley A Saketkoo,8 Robert P Baughman,9 Nadera J Sweiss3,4 1Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA; 2Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany; 3Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, Chicago, IL, 4Division of Rheumatology, University of Illinois at Chicago, Chicago, IL, 5Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, Miami, FL, 6Department of Medicine, Michigan State University College of Osteopathic Medicine, East Lansing, MI, 7Department of Gastroenterology, Hepatology and Nutrition, University of Buffalo, Buffalo, NY, 8New Orleans Scleroderma and Sarcoidosis Patient Care and Research Center, Louisiana State University Health Sciences Center, New Orleans, LA, 9Department of Medicine, University Medical Center of Cincinnati, Cincinnati, OH, USA *These authors contributed equally to this work Background: Sarcoidosis is a chronic multisystem disease of unknown etiology characterized by noncaseating granulomas that most often involves the lungs, but frequently has extrapulmonary manifestations, which might be difficult to treat in individual patients. Objective: To review different disease manifestations, focusing on extrapulmonary organ systems, and to provide treatment options for refractory cases. Materials and methods: We performed a literature search using Medline and Google Scholar for individual or combined keywords of “sarcoidosis, extrapulmonary, treatment, kidney, neurosarcoidosis, cardiovascular, gastrointestinal, transplantation, musculoskeletal, rheumatology, arthritis, and skin”. Peer-reviewed articles, including review articles, clinical trials, observational trials, and case reports that were published in English were included. References from retrieved articles were also manually searched for relevant articles.Results and conclusion: Isolated involvement of a single organ or organ system is rare in sarcoidosis, and thus all patients must be thoroughly evaluated for additional disease manifestations. Cardiac sarcoidosis and neurosarcoidosis may be life-threatening. Clinicians need to assess patients comprehensively using clinical, laboratory, imaging, and histopathological data to recommend competently the best and least toxic treatment option for the individual patient. Keywords: sarcoidosis, immunosuppressive agents, chronic granulomatous diseases, diagnostic tests

Anjali Shetty,1 Rebekah Hanson,1 Peter Korsten,2 Munir Shawagfeh,3 Shiva Arami,1 Suncica Volkov,1 Olga Vila1 William Swedler,1 Abdel Naser Shunaigat,4 Sameer Smadi,4 Ray Sawaqed,5 David Perkins,1 Shiva Shahrara,1 Nadera J Sweiss11Department of Rheumatology, Pharmacy, Transplant, University of Illinois at Chicago, Chicago, IL, USA; 2Department of Nephrology and Rheumatology, University Medicine Göttingen, Göttingen, Germany; 3Anesthesia and Pain Management, King Hussein Cancer Center, Amman, Jordan; 4Liver Transplant, Kidney Transplant Royal Medical Services, Jordan; 5Cardiac Surgery Methodist Hospitals, Merrillville, IN, USAAbstract: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by joint pain, swelling, stiffness, and progressive destruction of the small joints of the hands and feet. Treatment of RA has improved over the past decade. With multiple cytokines well-known now to play a role in the pathogenesis of RA, including tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6, many targeted biological treatments against these cytokines have emerged, changing the treatment of this disease. Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs (DMARDs) or cannot tolerate other approved drug classes for RA. The aim of this review is to discuss the role of IL-6 in RA, and to provide an overview of the mode of action, pharmacokinetics, and safety of TCZ. Furthermore, efficacy studies of TCZ as both monotherapy and combination therapy will be evaluated. There have been several important clinical trials evaluating the efficacy and safety of TCZ in RA patients; this review summarizes this data from 14 key trials with emphasis on Phase III trials. Review of these trials provides strong evidence that its use, both as monotherapy and in combination with methotrexate or other DMARDs, is an effective treatment in reducing the signs and symptoms of RA. TCZ showed tolerable safety but care is required for its use since there are some important safety concerns including elevated liver enzymes, elevated low-density lipoprotein, infections, and gastrointestinal perforations. Additionally, given the efficacy of TCZ in the treatment of RA, this review discusses how TCZ may be beneficial in the treatment of other autoimmune diseases, spinal disease, cardiovascular disease, organ transplantation, and malignancies where elevated levels of IL-6 may play a role in the pathogenesis of these diseases.Keywords: tocilizumab, IL-6, rheumatoid arthritis, biologics