Interstitial Lung Disease Linked to More Severe Complications in SSc

SSc-ILD patients more likely to have diffuse disease, cardiovascular problems

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Systemic sclerosis (SSc) patients with interstitial lung disease (ILD) were more likely to have a diffuse cutaneous (dcSSc) disease type and certain cardiovascular complications than patients without ILD, according to a recent study in China.

Those with the lung condition were also significantly more likely have elevated levels of inflammatory and lung damage markers in the blood, as well as the presence of anti-scleroderma-70 (anti-Scl-70) antibodies.

“Several important differences in clinical and laboratory characteristics have been demonstrated between SSc patients with or without ILD,” the researchers wrote, noting that the findings could facilitate “early diagnosis, accurate stratification, pre-emptive therapy, and thus improve patient performance.”

The study, “Comparing clinical characteristics of systemic sclerosis with or without interstitial lung disease: A cross-sectional study from a single center of the Chinese Rheumatism Data Center,” was published in the journal Frontiers in Medicine.

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ILD refers to a group of disorders marked by inflammation and scar tissue buildup in the lungs. It is a common and serious complication of SSc — observed in 25%–90% of patients — and a significant contributor to patients’ disease burden.

Often, treatment for ILD is initiated once it has progressed enough for symptoms to become apparent. Identifying those who may be at risk for the lung disease before symptom onset could help to initiate earlier treatment and improve management of ILD, thereby preventing more severe consequences later on.

While studies have identified potential risk factors for SSc-ILD, these studies have focused mostly on white and Western populations, and the potential risk factors in Chinese patients aren’t well-established, according to the researchers.

To address that knowledge gap, the scientists investigated the clinical characteristics associated with ILD among SSc patients diagnosed at Second Affiliated Hospital of Nanchang University, in China, from 2013 to 2022.

A total of 227 SSc patients (82.8% women) were included in the analysis, 121 of whom had ILD (53.3%). Patients’ median age at disease onset was 48.2, with an age at diagnosis of 52.6.

A number of clinical differences were observed between patients with ILD and those without.

In particular, a significantly higher percentage of SSc-ILD patients had the diffuse cutaneous form of the disease marked by a greater risk of developing internal organ damage compared with limited cutaneous SSc, which is milder and largely affects the skin. A total of 44.6% of those with SSc-ILD had dcSSc, compared with 22.6% of the non-ILD group.

Moreover, loss of the fatty padding on the fingertips, sclerodactyly — a type of skin tightening common in SSc —  and muscle involvement were more common symptoms in the SSc-ILD group. These patients also had greater skin thickness, as measured by the Modified Rodnan Skin Score.

Cardiovascular complications, including left ventricular diastolic dysfunction (LVDD) — when the heart’s muscle doesn’t relax properly in between heartbeats — and pulmonary arterial hypertension (PAH), an elevated blood pressure in the arteries supplying blood to the lungs, were seen more often among patients with ILD.

Overall, 14% of ILD patients had PAH and 61.2% had LVDD, compared with rates of 2.8% and 43.4% in the non-ILD group.

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Pulmonary arterial hypertension was most strongly linked to ILD

Laboratory parameters also diverged between those with ILD and those without it. Particularly, more patients with ILD showed elevations in the blood of Krebs von den Lungen-6 (KL-6), a protein known to correlate with the progression of ILD.

That group also had significantly higher median neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, and were more likely to have elevated levels of ferritin, all of which are used to indicate inflammatory status.

SSc-associated antibodies differed between the groups, with ILD patients having higher rates of positivity for antinuclear antibody, and anti-Scl-70 antibodies, while those without ILD were more often anti-centromere antibody positive.

Unlike in reports from the U.S., Japan, Australia, and Europe, the proportion of anti-Scl-70 antibodies was higher than that of anti-centromere antibodies in this study of Chinese patients, the team noted.

Final statistical analyses revealed that muscle involvement, LVDD, PAH, and having dcSSc were each associated with increased odds of ILD. Likewise, PLR, elevated KL-6, and the presence of anti-Scl-70 antibodies were associated with a higher risk of ILD.

The strongest relationship observed was with PAH, which was associated with a nearly nine times increased odds of having ILD.

To learn more about these relationships, “future longitudinal cohort studies, including larger populations and longer-term follow-ups, to evaluate cause-effect relationships, are desirable,” the team concluded.