Androgen and prolactin (Prl) levels in systemic sclerosis (SSc): relationship to disease severity.
ABSTRACT Testosterone (T), sex hormone-binding globulin, (SHBG), dehydroepiandrosterone sulfate (DHEAS), and prolactin (Prl) serum levels were measured by electrochemiluminescense immunoassay (ECLIA) in 39 patients with systemic sclerosis (SSc) and compared with serum hormonal levels in control subjects matched for sex and reproductive status. A possible relationship with disease duration and disease severity was examined. Our data show an altered androgen and prolactin (Prl) status in SSc patients, in most cases related to disease duration and disease severity score. We can hypothesize that hormonal dysregulation is a consequence of the chronicity of the disease. The altered hormonal status could result in relative immunological hyperactivity contributing to enhance tissue damage and disease severity.
SourceAvailable from: Cecilia Chighizola[Show abstract] [Hide abstract]
ABSTRACT: We assessed the profile and frequency of malignancy subtypes in a large single centre UK cohort for patients with scleroderma (systemic sclerosis; SSc). We evaluated the cancer risk among SSc patients with different antibody reactivities and explored the temporal association of cancer with the duration between onset of SSc and cancer diagnosis. A retrospective study of a well-characterised cohort of SSc cases attending a large tertiary referral centre was undertaken with clinical data collected through our clinical database and review of patient records. We evaluated development of all cancers in this cohort and comparison was assessed with the SSc cohort without cancer. The effect of demographics and clinical details including antibody reactivities were explored to find associations for development of cancer in SSc. Among 2177 patients with SSc, 7.1% of patients had a history of cancer. 26% were positive for anti-centromere antibodies (ACA), 18.2% were positive for anti-Scl70 antibodies and 26.6% were positive for anti-RNA polymerase III antibody (RNAP). The major malignancy subtypes were breast cancer (42.2%), haematological (12.3%), gastrointestinal (11.0%) and gynaecological cancers (11.0%). The frequency of cancers among patients with RNAP (14.2%) was significantly increased than those with anti-Scl70 (6.3%) and ACA (6.8%) (p < 0.0001 and p < 0.001 respectively). Among the patients, who were diagnosed with cancer within 36 months of the clinical onset of SSc, there were more patients with RNAP (55.3%) than other autoantibody specificities (ACA 23.5%; p < 0.008 and anti-Scl70 antibodies 13.6%, p < 0.002 respectively). Breast cancers were temporally associated with onset of SSc among patients with anti-RNAP and SSc patients with anti-RNAP had two-fold increased hazard ratio for cancers compared to patients with ACA (p < 0.0001). Our study confirmed independently, in the largest population examined to date, that there is an association with cancer among SSc patients with anti-RNAP antibodies in close temporal relationship to onset of SSc, which supports the paraneoplastic phenomenon in this subset of SSc cases. An index of suspicion should be cautiously maintained in these cases and investigations for underlying malignancy should be considered where clinically appropriate.Arthritis research & therapy 02/2014; 16(1):R53. DOI:10.1186/ar4486 · 4.12 Impact Factor
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ABSTRACT: Systemic sclerosis is a multifactorial and heterogeneous disease. Genetic and environmental factors are known to interplay in the onset and progression of systemic sclerosis. Sex plays an important and determinant role in the development of such a disorder. Systemic sclerosis shows a significant female preponderance. However, the reason for this female preponderance is incompletely understood. Hormonal status, genetic and epigenetic differences, and lifestyle have been considered in order to explain female preponderance in systemic sclerosis. Sex chromosomes play a determinant role in contributing to systemic sclerosis onset and progression, as well as in its sex-biased prevalence. It is known, in fact, that X chromosome contains many sex- and immuno-related genes, thus contributing to immuno tolerance and sex hormone status. This review focuses mainly on the recent progress on epigenetic mechanisms-exclusively linked to the X chromosome-which would contribute to the development of systemic sclerosis. Furthermore, we report also some hypotheses (dealing with skewed X chromosome inactivation, X gene reactivation, acquired monosomy) that have been proposed in order to justify the female preponderance in autoimmune diseases. However, despite the intensive efforts in elucidating the mechanisms involved in the pathogenesis of systemic sclerosis, many questions remain still unanswered.Clinical Reviews in Allergy & Immunology 10/2013; DOI:10.1007/s12016-013-8392-9 · 4.73 Impact Factor
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ABSTRACT: Previous research has shown inconsistent effect of systemic sclerosis (SSc) on bone mineral density (BMD). The objective of this study was to perform a meta-analysis of previous articles to investigate the differences in BMD (g/cm(2) ) between SSc and non-SSc populations and to discuss potential underlying mechanisms. Twelve full-text articles (including an outlier study and two studies with identical data) with 662 SSc patients and 886 controls were identified by searching Medline prior to 10 September, 2013 using search terms 'Systemic sclerosis' OR 'scleroderma' and 'osteoporosis' OR 'bone density' OR 'bone mass'. BMD (mean and standard deviation), T-scores and Z-scores at lumbar spine, femoral neck and total hip measured by dual-energy X-ray absorptiometry were extracted. Meta-analysis showed that a lower level of BMD was found in SSc patients, with weighted mean difference of -0.343 (95% CI: -0.500 to -0.186) at femoral neck, -0.084 (95% CI: -0.110 to -0.057) at total hip and -0.104 (95% CI: -0.135 to -0.073) at the lumbar spine. We conclude that patients with SSc may have a lower BMD level than healthy controls.International Journal of Rheumatic Diseases 06/2014; DOI:10.1111/1756-185X.12395 · 1.77 Impact Factor