Clinical characteristics, visceral involvement, and mortality in at-risk or early diffuse systemic sclerosis: a longitudinal analysis of an observational prospective multicenter US cohort

Abstract

Background Early diffuse cutaneous systemic sclerosis (dcSSc) has the highest case fatality among rheumatic diseases. We report baseline characteristics, current immunosuppressive therapies, progression of skin and internal organ involvement, and mortality in a multicenter prospective cohort from the United States (US) of America. Methods We performed a longitudinal analysis of participants from 12 US centers, from April 2012 to July 2020. All participants had early dcSSc or were at-risk for dcSSc, with ≤2 years since the first non-Raynaud’s phenomenon (RP) symptom. Results Three hundred one patients were included with a baseline median disease duration of 1.2 years since RP and a mean modified skin score of 21.1 units. At baseline, 263 (87.3%) had definite dcSSc and 38 (12.7%) were classified as at-risk; 112 (49.6%) patients were positive for anti-RNA polymerase III antibodies. The median follow-up duration was 24.5 months (IQR = 10.3–40.7 months). One hundred ninety (63.1%) participants were treated with an immunosuppressive therapy, of which mycophenolate mofetil was most used at baseline and follow-up. Of 38 who were classified as at-risk at baseline, 27 (71%) went on to develop dcSSc; these patients were characterized by higher baseline mean HAQ-DI (0.8 versus 0.4, p = 0.05) and higher baseline mRSS (8.8 versus 4.4, p < 0.01) in comparison with those who remained as limited cutaneous SSc. In the overall cohort, 48 participants (21.1%) had clinically significant worsening of skin fibrosis, mainly occurring in the first year of follow-up; 41 (23.3%) had an absolute forced vital capacity decline of ≥10%. Twenty participants (6.6%) died, of which 18 died in the first 3 years of follow-up. Cardiac involvement (33.3%), gastrointestinal dysmotility (22.2%), and progressive interstitial lung disease (ILD) (16.7%) were the main causes of death. Conclusion This US cohort highlights the management of early SSc in the current era, demonstrating progression of skin and lung involvement despite immunosuppressive therapy and high mortality due to cardiac involvement.

Management of Endothelial Dysfunction in Systemic Sclerosis: Current and Developing Strategies

“…Primary and secondary cardiac involvements are described as frequent and probably underestimated in SSc (81)(82)(83), and from 5 to 15% of SSc patients develop pulmonary hypertension (79,81). Less explored, but still frequent vascular manifestations of SSc are erectile dysfunction, vascular malformations of the gastro-intestinal mucosa (gastric antral vascular ectasia -GAVE) and, to some extent, myopathy (66,(84)(85)(86). Routine assessments for vascular involvement include clinical inspections, evaluation of organ function and, when required, right-heart catheterism.…”

Peripheral blood gene expression profiling shows predictive significance for response to mycophenolate in systemic sclerosis-related interstitial lung disease

“…Moreover, the recently completed Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial provided supportive data on the efficacy of background therapy with MMF as monotherapy or in combination with nintedanib in SSc-ILD 5. MMF is the most commonly used treatment for this disease manifestation in the clinical setting 6. However, response to immunosuppression is highly variable in SSc-ILD, with approximately one-third of patients experiencing lung volume decline despite treatment in SLS I and SLS II studies 3 4.…”

“…5 MMF is the most commonly used treatment for this disease manifestation in the clinical setting. 6 However, response to immunosuppression is highly variable in SSc-ILD, with approximately one-third of patients experiencing lung volume decline despite treatment in SLS I and SLS II studies. 3 4 Moreover, CYC and MMF can be associated with serious side effects, emphasising the need for identification of likely responders.…”

Skin involvement in early diffuse cutaneous systemic sclerosis: an unmet clinical need

“…dcSSc is the subtype of greater concern, because it is characterized by rapid progression and a high prevalence of early internal-organ involvement (including lung, heart and kidney), which can be life-threatening. dcSSc is therefore associated with high mortality 2 – 4 , with a 5-year survival rate of around 70%, and clinicians understandably tend to focus their attention on early identification and treatment of internal-organ disease. However, on a day-to-day basis, in patients with early dcSSc (those within the first 3–5 years of the onset of symptoms), it is skin thickening that has the greatest impact on quality of life, causing pain, intractable itching and functional limitation.…”