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      Biologics in Dermatology: Off-Label Indications

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          Abstract

          Skin and subcutaneous diseases affect millions of people worldwide, causing significant morbidity. Biologics are becoming increasingly useful for the treatment of many skin diseases, particularly as alternatives for patients who have failed to tolerate or respond to conventional systemic therapies. Biological therapies provide a targeted approach to treatment through interaction with specific components of the underlying immune and inflammatory disease processes. Advances in the understanding of disease pathophysiology for inflammatory skin diseases and in drug development have ushered in biologic therapies in dermatology. Biologic therapies are molecules that target specific proteins implicated in immune-mediated disease. This review article highlights the increasing evidence base for biologics in dermatology for off-label use.

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          Most cited references 104

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          Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation.

          Tumor necrosis factor alpha (TNF alpha) is a potent immunomodulator and proinflammatory cytokine that has been implicated in the pathogenesis of autoimmune and infectious diseases. For example, plasma levels of TNF alpha are positively correlated with severity and mortality in malaria and leishmaniasis. We have previously described a polymorphism at -308 in the TNF alpha promoter and shown that the rare allele, TNF2, lies on the extended haplotype HLA-A1-B8-DR3-DQ2, which is associated with autoimmunity and high TNF alpha production. Homozygosity for TNF2 carries a sevenfold increased risk of death from cerebral malaria. Here we demonstrate, with reporter genes under the control of the two allelic TNF promoters, that TNF2 is a much stronger transcriptional activator than the common allele (TNF1) in a human B cell line. Footprint analysis using DNase I and B cell nuclear extract showed the generation of a hypersensitive site at -308 and an adjacent area of protection. There was no difference in affinity of the DNA-binding protein(s) between the two alleles. These results show that this polymorphism has direct effects on TNF alpha gene regulation and may be responsible for the association of TNF2 with high TNF alpha phenotype and more severe disease in infections such as malaria and leishmaniasis.
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            Sarcoidosis.

            Sarcoidosis is a systemic disease of unknown cause that is characterised by the formation of immune granulomas in various organs, mainly the lungs and the lymphatic system. Studies show that sarcoidosis might be the result of an exaggerated granulomatous reaction after exposure to unidentified antigens in individuals who are genetically susceptible. Several new insights have been made, particularly with regards to the diagnosis and care of some important manifestations of sarcoidosis. The indications for endobronchial ultrasound in diagnosis and for PET in the assessment of inflammatory activity are now better specified. Recognition of unexplained persistent disabling symptoms, fatigue, small-fibre neurological impairment, cognitive failure, and changes to health state and quality of life, has improved. Mortality in patients with sarcoidosis is higher than that of the general population, mainly due to pulmonary fibrosis. Predicted advances for the future are finding the cause of sarcoidosis, and the elucidation of relevant biomarkers, reliable endpoints, and new efficient treatments, particularly in patients with refractory sarcoidosis, lung fibrosis, and those with persistent disabling symptoms. Copyright © 2014 Elsevier Ltd. All rights reserved.
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              2018 update of the EULAR recommendations for the management of Behçet’s syndrome

              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.
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                Author and article information

                Journal
                Indian Dermatol Online J
                Indian Dermatol Online J
                IDOJ
                Indian Dermatology Online Journal
                Wolters Kluwer - Medknow (India )
                2229-5178
                2249-5673
                May-Jun 2020
                10 May 2020
                : 11
                : 3
                : 319-327
                Affiliations
                Department of Dermatology, Base Hospital Delhi Cantt, New Delhi, India
                [1 ] Department of Pediatrics, Base Hospital Delhi Cantt, New Delhi, India
                [2 ] Department of Dermatology, Jorhat Medical College and Hospital, Jorhat, Assam, India
                Author notes
                Address for correspondence: Dr. Ajay Chopra, Department of Dermatology, Base Hospital Delhi Cantt, New Delhi - 110 010, India. E-mail: debdeep7@ 123456gmail.com
                Article
                IDOJ-11-319
                10.4103/idoj.IDOJ_407_18
                7367577
                Copyright: © 2020 Indian Dermatology Online Journal

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                Categories
                Review Article

                Dermatology

                biologics, rituximab, secukinumab, tnf-α

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