International journal of rheumatic diseases
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Immunoglobulin G4-related disease (IgG4-RD) is a regional or systemic fibro-inflammatory disease of unknown etiology. It presents a distinctive histopathological appearance of dense lymphoplasmacytic infiltrates with abundant IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis with the appearance of inflammatory swelling or tumefactive lesions. ⋯ IgG4-RD was recognized internationally in 2011, and new evidence has accumulated regarding its pathogenesis, clinical features and treatment. In this review, we outline our present understanding of IgG4-RD.
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The purpose of this review is to establish whether there is a significantly increased incidence of serious infections during treatment for rheumatoid arthritis (RA) with etanercept, infliximab or adalimumab, to determine the background risk of serious infection in RA patients without treatment with any biological therapy and to ascertain which organisms are involved in serious infections in RA patients while being treated with etanercept, infliximab or adalimumab. Randomised controlled trials (RCTs), meta-analyses of RCTs, Cochrane reviews, national registry articles and case reports were identified using PubMed/MEDLINE, The Cochrane Library and Google Scholar. The medical subject heading "rheumatoid arthritis" was combined with "serious infection" or "infection" or "adverse drug events" with each of the three reference biological therapies separately: etanercept, infliximab and adalimumab. ⋯ The background risk of serious infection appears to be approximately two-fold more than non-RA patients before any treatment with biological therapy. The national registries, which may represent the typical RA patient more accurately than clinical trials, suggest a small but significantly increased incidence of serious infection ranging 1.2-2.78 times that of control (treatment with methotrexate). Mycobacteria spp., Staphyloccus aureus, Listeria monocytogenes, Varicella zoster virus and Leishmania species (spp.) repeatedly appear in the case report literature and should be in the mind of the clinician faced with a serious infection in a RA patient with an unknown pathogen who is being treated with either etanercept, infliximab or adalimumab.
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Significant progress has been made in the development of therapies for systemic lupus erythematosus (SLE). These include agents which target interferons, cytokines, T lymphocytes and co-stimulatory molecules, B-lymphocytes and B stimulatory molecules. The latter are of special interest having the most robust efficacy data to date, ranging from clinical experience to clinical trials, with belimumab as the first Food and Drug Administration-approved biologic for the treatment of SLE. Given the wide disease heterogeneity, certain issues like clinical trial design and pharmacogenomics will continue to challenge drug development in SLE, there will always be a growing and compelling need for more of these drugs in order to alleviate the burden of illness in lupus patients.
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Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by periods of flares and remission, resulting in organ damage over time caused by persistent disease activity and treatment-related complications. Conventional therapies are not ideal in terms of efficacy and safety. Novel biological therapies are being developed to enhance therapeutic efficacy, minimize disease exacerbation and reduce toxicities. ⋯ While the efficacy of this regimen has to be confirmed, future controlled trials should focus on the efficacy of rituximab in refractory lupus manifestations and its synergistic effect with other immunosuppressive agents such as cyclophosphamide. In short-term randomized controlled trials, a non-significant increase in serious adverse events was observed in SLE patients treated with rituximab. Long-term safety data of rituximab in SLE, in particular the incidence of hypogammaglobulinemia and serious/opportunistic infections, have to be continuously surveyed.
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The management of systemic lupus erythematosus (SLE) is complicated by heterogeneous clinical presentations, a lack of universally accepted tools for the measurement of disease activity and a lack of powerful, safe, specific targeted therapies. Current medical treatment of disease activity relies on glucocorticoids as well as agents including hydroxychloroquine (HCQ), mycophenolate mofetil (MMF) azathioprine (AZA), and less frequently cyclophosphamide. ⋯ Measurement of drug or metabolite concentrations has been shown in a number of studies to identify under- and over-dosing, predict efficacy and detect non-adherence to therapy, with positive associations between optimum drug or metabolite levels and improved outcomes. In this paper, we will review the literature regarding the measurement of HCQ, MMF, AZA and cyclophosphamide drug and metabolite levels in SLE and inflammatory disease, and make recommendations for future research that could facilitate improved outcomes for patients with SLE.