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      Gender Differences in Axial Spondyloarthritis: Women Are Not So Lucky

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          Abstract

          Purpose of Review

          Ankylosing spondylitis (AS) was historically seen as a predominantly male disease. However, more recent data showed a more homogenous sex prevalence. Unfortunately, in many studies in axial spondyloarthritis (axSpA), the number of women included is low and the analyses are often not stratified for gender distribution. The purpose of this review is to aggregate the existing data on gender differences in axSpA in order to increase the awareness that female axSpA patients are still under-recognized.

          Recent Findings

          Several studies considering gender differences revealed that female axSpA patients had different disease manifestations due to different immunological, hormonal, and genetic responses. For instance, allelic frequencies of the AHNK-gene and tissue non-specific alkaline phosphatase (TNAP) haplotypes differed between men and women with ankylosing spondylitis (AS). In addition, different levels of tumor necrosis factor (TNF), interleukins IL-6, IL-17, and IL-18, were found between the two sexes. Furthermore, female patients show a higher diagnostic delay compared to males. Several studies indicate a higher frequency of extra-articular manifestations (EAM) in female axSpA patients, such as enthesitis, psoriasis, and inflammatory bowel disease (IBD), whereas acute anterior uveitis is more prevalent in male patients. Male AS patients more frequently show a higher Bath Ankylosing Spondylitis Radiology Index (BASRI) scores and modified Stoke Ankylosing Spondylitis Spine Scores (mSASSS) than females, which indicates that males have higher radiological damage and radiographic progression. However, disease activity (BASDAI) and quality of life (AsQol) scores are significantly higher in women, and more importantly, they have significantly lower response rates to treatment with TNF inhibitors (TNFi) and a significantly lower drug adherence.

          Summary

          Despite the fact that men with axial SpA have a worse radiologic prognosis, women have a high disease burden, in part because they have a longer delay in diagnosis, higher disease activity, and significantly less responsiveness to treatment with TNFi.

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          Most cited references63

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          The X-files in immunity: sex-based differences predispose immune responses

          Sex-based differences in immune responses can influence the susceptibility to autoimmune and infectious diseases and the efficacy of therapeutic drugs. In this Perspective, Eleanor Fish discusses factors, such as X-linked genes, hormones and societal context, that underlie disparate immune responses in men and women.
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            Prevalence of peripheral and extra-articular disease in ankylosing spondylitis versus non-radiographic axial spondyloarthritis: a meta-analysis

            Background Peripheral disease (arthritis, enthesitis and dactylitis) and extra-articular disease (uveitis, psoriasis and inflammatory bowel disease) is common in ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). So far, however, summary data on the prevalence are lacking. The objective of this meta-analysis was to assess the prevalence of peripheral and extra-articular manifestations in ankylosing spondylitis (AS) and nr-axSpA. Methods We performed a systematic literature search to identify publications describing the prevalence of peripheral and extra-articular disease manifestations in patients with AS and nr-axSpA. We assessed the risk of bias and between-study heterogeneity, and extracted data. Pooled prevalence and prevalence differences were calculated. Results Eight studies comprising 2236 patients with AS and 1242 with nr-axSpA were included: 7 of the studies were longitudinal cohort studies. There was male predominance in AS (70.4 %, 95 % CI 64.4, 76.0 %) but not in nr-axSpA (46.8 %, 95 % CI 41.7, 51.9), which was independent of the prevalence of human leukocyte antigen (HLA)-B27. The prevalence of HLA-B27 was similar in AS (78.0 % (95 % CI 73.9, 81.9 %) and nr-axSpA (77.4 %, 95 % CI 68.9, 84.9 %)). The pooled prevalence of arthritis (29.7 % (95 % CI 22.4, 37.4 %) versus 27.9 % (95 % CI 16.0, 41.6 %)), enthesitis (28.8 % (95 % CI 2.6, 64.8) versus 35.4 % (95 % CI 6.1, 71.2)). dactylitis (6.0 % (95 % CI 4.7, 7.5 %) versus 6.0 % (95 % CI 1.9, 12.0 %)), psoriasis (10.2 % (95 % CI 7.5, 13.2 %) versus 10.9 % (95 % CI 9.1, 13.0 %)) and inflammatory bowel disease (4.1 % (95 % CI 2.3, 6.5 %) versus 6.4 % (95 % CI 3.6, 9.7 %)) were similar in AS and nr-axSpA. The pooled prevalence of uveitis was higher in AS (23.0 % (95 % CI 19.2, 27.1 %)) than in nr-axSpA (15.9 % (95 % CI 11.8, 20.4 %)). Conclusion Peripheral and extra-articular manifestations are equally prevalent in AS and nr-axSpA, except for uveitis, which is slightly more prevalent in AS. These data provide evidence for the largely equal nature of disease manifestations in nr-axSpA and AS. Electronic supplementary material The online version of this article (doi:10.1186/s13075-016-1093-z) contains supplementary material, which is available to authorized users.
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              Prevalence and characteristics of uveitis in the spondyloarthropathies: a systematic literature review.

              Uveitis is reported to be the most common extra-articular manifestation in spondyloarthritis (SpA); however, its prevalence and characteristics are not well established. To perform a systematic literature review in order to examine these topics. A systematic literature analysis was conducted in the Medline database up to October 2006 and in the abstracts of rheumatology scientific meetings for the years 2004, 2005 and 2006. A hand search of references was also performed. Articles were analysed if they reported the prevalence or characteristics of uveitis in SpA. Data abstraction was standardised. Statistical analysis was mainly descriptive. Among the 957 articles selected by the search, 126 articles (29,877 patients) allowed a calculation of the prevalence of uveitis in SpA; 36 articles (1989 patients) described its characteristics. The mean (SD) prevalence of uveitis was 32.7 (0.5)%; it varied with the type of SpA--for example, 33.2 (0.8)% for ankylosing spondylitis versus 25.1 (2.3)% for psoriatic arthritis. This prevalence increased with mean disease duration and was higher in HLA-B27-positive patients with an odds ratio of 4.2. Uveitis was acute in 88.7 (2.5)%, anterior in 90.5 (2.0)%, unilateral in 87.3 (2.8)%. Recurrence occurred in 50.6 (2.6)% and a reduction of visual acuity was observed in 8.3 (3.8)%. The prevalence of uveitis varies with disease duration and according to the type of SpA. Reduction of visual acuity is not exceptional. Because of recent promising data about the effects of anti-tumour necrosis factor therapy on uveitis flares in SpA, it was important to determine this baseline prevalence.
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                Author and article information

                Contributors
                +31204443432 , ie.vanderhorst@vumc.nl
                Journal
                Curr Rheumatol Rep
                Curr Rheumatol Rep
                Current Rheumatology Reports
                Springer US (New York )
                1523-3774
                1534-6307
                12 May 2018
                12 May 2018
                2018
                : 20
                : 6
                : 35
                Affiliations
                Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands
                Article
                744
                10.1007/s11926-018-0744-2
                5949138
                29754330
                b742b7ee-a645-4009-8e23-08893f0d0165
                © The Author(s) 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Funding
                Funded by: VU University Medical Center (VUmc)
                Categories
                Spondyloarthritis (M Khan, Section Editor)
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2018

                Rheumatology
                axial spondyloarthritis,gender,sex,disease manifestation,tnf inhibitors,radiological progression

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