Damage to heart, other organs possible with SSc sine scleroderma
Study finds risks with skin symptoms like telangiectasias rather than fibrosis
Skin symptoms not due to fibrosis or scarring among people with systemic sclerosis (SSc) sine scleroderma can associate with damage to internal organs, particularly the heart, according to a large data study.
Among these symptoms, skin telangiectasias — marked by small blood vessels that widen near the skin’s surface, appearing as pink or red spots or lines — most often linked with cardiac damage.
People with systemic sclerosis sine scleroderma had a better survival rate at 15 years that those with other types of SSc, findings showed. Still, about half of the SSc sine scleroderma patients studied had interstitial lung disease (ILD, a group of conditions that cause lung scarring) and around 3% had scleroderma-related kidney (renal) crisis.
“Even in patients without skin fibrosis, the assessment of other dermatological features, such as skin telangiectasias, is of utmost importance, as such nonfibrotic manifestations were also associated with [internal organ] manifestations,” the researchers wrote.
The study, “Cutaneous Manifestations, Clinical Characteristics, and Prognosis of Patients With Systemic Sclerosis Sine Scleroderma,” was published in the journal JAMA Dermatology.
Systemic sclerosis sine scleroderma often is seen as a limited disease form
SSc sine scleroderma, considered a rare subtype of SSc, is defined by SSc-associated internal organ damage and the absence of scar tissue on the skin. With other disease types, including limited cutaneous SSc and diffuse SSc, skin fibrosis is evident.
Although many studies make no distinction between SSc sine sclerosis and limited SSc, differentiating disease subtypes could aid in the treatment given to patients.
People with systemic sclerosis may experience early skin manifestations, such as Raynaud’s phenomenon (changes to the fingers and toes due to cold or stress), digital ulcers (sores), puffy fingers, and telangiectasias.
However, “to date, little is known on the natural history of skin involvement and on skin manifestations” in people with SSc sine scleroderma, the researchers wrote.
To characterize its main symptoms compared with other SSc types, researchers analyzed data covering 4,263 patients included in the international EUSTAR (European Scleroderma Trials and Research) database.
Among them, 376 (8.8%) were classified as having systemic sclerosis sine scleroderma, with an absence of skin fibrosis at all study visits. They had a mean age of 55.3 and most were female (91.8%).
Almost 5 times higher risk of heart value problems with skin telangiectasias
At their first visit, almost half of the patients (47.8%) had telangiectasias, 40.3% had puffy fingers, and 11.5% had pitting scars. Digital ulcers had occurred in 19% of them and were currently present in 4.7% of this group.
The presence of telangiectasias was associated with an 4.8 times higher risk of diastolic dysfunction — when the heart’s ventricles are stiff and do not relax properly — for people with SSc sine scleroderma.
Most patients (57%) showed damage to the esophagus — the tube connecting the throat with the stomach — and 39.4% had ILD.
Regarding typical SSc-associated autoantibodies (self-reactive antibodies), 61% SSc sine scleroderma patients had anti-centromere antibodies and 15.1% had anti-topoisomerase antibodies. The presence of anti-topoisomerase antibodies was associated with an approximately three times higher risk of skin fibrosis.
According to the researchers, this finding strengthens “the relevance of antibody subtypes to predict the trajectory of skin involvement in patients with SSc.”
In comparison, skin fibrosis at an initial study visit was evident in 184 people (4.3%) with other SSc forms — 13 with diffuse SSc, 171 with limited SSc. Such scarring was present at follow-up visits.
There also was a lower prevalence of previous or current digital ulcers at last follow-up in SSc sine scleroderma patients relative to those with other forms and a similar disease duration (28.2% vs. 53.1% in limited and 68.3% in diffuse SSc). Likewise, there was a lower prevalence for puffy fingers (63.8% SSc sine scleroderma vs. 82.4% in limited and 87.6% in diffuse SSc), and telangiectasias (65.8% vs. 74.7% in limited and 79.7% in diffuse SSc).
ILD prevalence, however, was similar between SSc sine scleroderma patients (49.8%) and those with limited SSc (57.1%). Its prevalence was higher among people with diffuse SSc (75%).
There were no significant differences among the three groups regarding the prevalence of kidney crisis, which affected around 3% of the SSc sine scleroderma group.
Study findings call into question SSc sine scleroderma as “rare” subtype
Immunomodulatory therapies were used by almost half of the SSc sine scleroderma patients (49.4%), compared with their use in 64.2% of limited SSc and 75% of diffuse SSc patients. Therapies for digital ulcers were also less common in the SSc sine scleroderma group.
In line with findings of a 2021 published study, SSc sine scleroderma patients had a higher survival rate (92.4%) through up to 15 years of follow-up, compared with 69.4% of the limited SSc group and 55.5% of those with diffuse SSc.
“This cohort study … provides unique insight on this specific SSc subtype and the associated skin manifestations,” the researchers wrote, and “to our knowledge” is “the first international multicenter study specifically exploring patients with ssSSc.”
Study results also “suggest that [systemic sclerosis sine scleroderma] is not a rare subset, as it accounted for almost 10% of patients with SSc in the EUSTAR registry,” they added.
As such, “systemic sclerosis sine scleroderma should not be neglected, considering the high prevalence of ILD (>40%) and of scleroderma renal crisis (almost 3%),” and the risk of diastolic dysfunction in patients with nonfibrotic skin manifestations like telangiectasias, the scientists concluded.
“Acknowledging the specific prognosis and [presentation] of [SSc sine scleroderma] is among the necessary steps toward precision medicine and updated classification for SSc,” they added.
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