Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology

Abstract

Objective There is still a great deal to learn about the influence of gender in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying gender differences in disease expressions, with a special focus on demographic, clinical and serological characteristics. Methods A multicenter SSc cohort of 2,281 patients, 247 men, was recruited in the Italian SPRING (Systemic Sclerosis PRogression INvestiGation) registry. Demographic data, disease manifestations, serological profile and internal organ involvement were compared. Results The overall female/male ratio was 8.2/1. Female/male ratios for limited SSc, diffuse SSc and sine SSc subsets were 8.7/1, 4.9/1, and 10.7/1 respectively. A shorter Raynaud's onset to SSc diagnosis, an increased prevalence of diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, while a significant higher percentage of sicca syndrome, serum ANA, anti-ENA, anti-La/SSB, and anti-CENP-1 was detected in the female group. Males exhibited lower left ventricular ejection fraction, higher prevalence of conduction blocks, arrhythmias, ground glass and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. Conclusion Our study further supports the presence of several gender-related differences in SSc patients. These differences were pronounced as regards the severity of cutaneous, peripheral vascular and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterize the female gender.

Systemic sclerosis sine scleroderma: clinical and serological features and relationship with other cutaneous subsets in a large series of patients from the national registry ‘SPRING’ of the Italian Society for Rheumatology

“…In 2014, the Italian Society for Rheumatology promoted the development of the national SPRING (Systemic sclerosis PRogression INvestiGation) registry, which includes the clinical conditions preceding the onset of definite SSc and the main disease subsets 15. The overall baseline data have already been published15 16 while the assessment of more than 2400 consecutive patients is still in progress. The aim of the present work was to analyse the main demographic, clinical and laboratory features of patients with ssSSc in comparison with lcSSc and dcSSc subsets within the SPRING registry.…”

Peripheral Microangiopathy Changes in Pulmonary Arterial Hypertension Related to Systemic Sclerosis: Data From a Multicenter Observational Study

“…Another valuable observation of the study was the female prevalence in our PAH patients' cohort, confirming the registries worldwide PAH data showing a female predominance of pulmonary hypertension. Dysregulation of estrogen synthesis and metabolism seems to play a major role in these sex-related differences ( 28 , 35 ), so further analyses on larger sample size are needed to better understand the penetrance of PAH in SSc women in order to translate to a better prognosis and/or a better quality of life. Finally, if the association between PAH and ILD is expected in SSc ( 17 , 18 ), even together with NVC alterations ( 36 ), the lack of association with DU's is conflicting and needs of further investigation ( 37 ).…”

“…Hearth is frequently affected, and the burden of cardiac complications leads to a reduction in life expectancy of these patients (12)(13)(14)(15). In particular PAH is characterized by increased resistance of pulmonary vessels because of remodeling and obstruction of pulmonary arterioles with subsequent increase of the mean pulmonary artery pressure and is usually diagnosed 10 to 15 years after the onset of the disease, so the majority of the SSc patients are usually presented with serious manifestations, severe hemodynamic impairment and associated with poor prognosis and increased mortality especially in male subjects (18,28,30). Early screening through systematic evaluation of asymptomatic SSc patients could diagnose PAH at an early stage with a consequent better prognosis of the disease (17).…”

“…The patients' demographic and clinical findings were carefully considered. Data collected at registration included: age, disease duration, type of skin subset (limited/diffuse), presence of Raynaud's phenomenon (RP), modified Rodnan skin score, other skin involvement (subcutaneous calcinosis, telangiectasia), digital ulcers-DUs, lung involvement, gastro-intestinal symptoms (dysphagia, reflux), cardiopulmonary signs and symptoms (heart failure, pericardial effusion, dilated cardiomyopathy), sicca syndrome (xerostomia/xeropthalmia), and joint involvement (tenosynovitis, arthritis, tendon friction rubs), as previously described ( 20 , 21 , 28 ). Laboratory and instrumental evaluations included antinuclear antibodies (ANA), anti-extractable nuclear antigens (anti-ENA), SSc-related antibodies (mainly anti-centromere/CENP-B and anti-topoisomerase I/Scl-70), diffusion capacity for carbon monoxide (DLCo) and high-resolution computed tomography-HRCT were reported ( 17 , 18 , 20 , 21 , 28 ).…”

Can home rehabilitation impact impulse oscillometry and lung ultrasound findings in patients with scleroderma-associated interstitial lung disease? A pilot study

“…Second, we only evaluated women in our sample. However, most scleroderma patients are women, with a ratio of approximately 8:1 [ 29 ], and sex accounts for 30% of the variation in lung function, thus supporting sex-differentiated interpretive strategies [ 30 , 31 ]. Third, we did not assess exercise tolerance and quality of life, although exercise has previously been demonstrated to be beneficial for these measures in people with scleroderma [ 32 , 33 ].…”