Sine Sclerosis Linked to Better Survival Than Limited, Diffuse Types

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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People with sine sclerosis — a rare form of scleroderma without skin involvement — have better survival than those with limited and diffuse scleroderma, according to a retrospective study of up to 18 years of patient data.

In addition, male sex, poor lung function, heart involvement, and systemic inflammation were found to be independent risk factors of mortality in these patients, which was mainly associated with causes unrelated to scleroderma, also known as systemic sclerosis (SSc).

Non-SSc-related cardiovascular events were the main cause of death among these patients.

These findings shed light on survival differences between scleroderma subtypes and highlight the contribution of cardiovascular causes in non-SSc-related death, calling for effective management of heart complications in this patient population to improve survival, the researchers noted.

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The study, “Sine scleroderma, limited cutaneous, and diffused cutaneous systemic sclerosis survival and predictors of mortality,” was published in the journal Arthritis Research & Therapy.

Scleroderma is an autoimmune disease characterized by tissue scarring that most often affects the skin, but can also damage internal organs such as the lungs, heart, kidneys, and gastrointestinal tract.

Due to its high variability, the 10-year survival rate of scleroderma reported to date has varied greatly across studies, between 50% and 84%. While SSc-related interstitial lung disease (ILD) and pulmonary hypertension (PH) remain the main causes of death, those unrelated to scleroderma “are increasing, particularly cardiovascular diseases, and infections,” the researchers wrote.

In addition, few studies have reported survival outcomes and causes in people with sine sclerosis, a rare type of SSc that shows no skin involvement, making it harder to diagnose.

Now, a team of researchers in Toulouse, France, evaluated the mortality rate, as well as its causes and predictors, in 375 adults (292 women and 83 men) with scleroderma who were diagnosed at two Toulouse hospitals and followed for up to 18 years.

The team retrospectively and systematically analyzed the medical records of these patients, who had a disease onset between Jan. 1, 2000, and Jan. 1, 2018, and who were followed until May 31, 2018.

Most (76.7%) patients had limited SSc, while 63 (15.2%) had diffuse SSc and 33 (8.1%) were diagnosed with sine sclerosis.

Results showed that during the study period, 69 (18.4%) patients died and six patients (only women, five with diffuse SSc and one with sine scleroderma) were lost to follow-up.

Patients’ mean age at the time of death was 69.1, with men dying at a younger age relative to women (mean of 64.2 vs. 72).

The overall survival rates were 97.6% at one year, 93.4% at three years, 87.1% at five years, 77.9% at 10 years, and 61.3% at 15 years. Sine scleroderma patients had the best survival at all time points, with all of them being alive at one and three years, 88.9% at five years, and 81.9% at 10 and 15 years.

Consistent with a more extensive disease, diffuse scleroderma was associated with the worst survival rate: 95.1% at one year, 89.8% at three years, 85.5% at five years, 69.7% at 10 years, and 54.9% at 15 years.

These findings were also confirmed through an analysis of standardized mortality ratio (SMR), a ratio between the observed number of deaths in a study population and those expected based on age- and sex-specific rates in the general population. Values over 1 mean a higher number of deaths than expected.

Scleroderma patients had an age- and sex-adjusted SMR of 1.88, reflecting their increased mortality relative to the general healthy population. Consistently, patients with sine sclerosis showed the lowest SMR (1.03) while those with diffuse SSc had the highest SMR (3.31).

More than half (53.6%) of patients’ deaths were considered unrelated to SSc, with cardiovascular events (37.8%) and infections (35.1%) as the main causes. The most common scleroderma-related causes of death were ILD (34.4%), PH (31.2%), and digestive tract involvement (18.8%).

Further analysis showed that being a man, having a carbon monoxide diffusing capacity (DLCO) of less than 70% — indicative of reduced lung function — having heart involvement, and high levels of C-reactive protein (suggestive of systemic inflammation) were significant, independent predictors of mortality among these patients.

These risk factors were consistent with findings from previous studies and other known associations, such as the fact that lower-than-normal DLCO in SSc is often linked to ILD and/or PH, the two main causes of death.

These findings highlight that “mortality is still substantial in SSc despite constant therapeutic progress,” the researchers wrote, adding that this was “one of the first studies that ascertained sine scleroderma mortality rate versus diffuse and limited subtypes.”

The team added that “this serves as an important reference for future survival analysis and epidemiology surveys.”

Given that non-SSc-related cardiovascular diseases were the most frequent cause of death among these patients, “an early and systematic management of the large proportion of cardiac complications is in order, in hope of extending SSc outcome,” the researchers wrote.