Disclosure(s): No financial relationships with ineligible companies to disclose
Background/Purpose: Interstitial lung disease (ILD) is traditionally associated with the diffuse subset of systemic sclerosis (dcSSc) but may be observed in limited SSc (lcSSc), with features not clearly defined, but antiScl-70. This study aims to characterize risk factors and prognosis of lcSSc-ILD within the EUSTAR cohort. Methods: We performed the CP175 retrospective study including patients in EUSTAR up to February 2025 and arrayed according to skin subset and presence/absence of ILD at chest HRCT at enrollment (baseline). Disease features were analyzed for risk factors and survival of lcSSc patients with: (i) ILD at baseline (multivariable logistic regression), (ii) incident ILD during follow-up (Cox proportional hazards models), and (iii) progressive ILD (Hoffmann-Vold, 2021). Results: Baseline HRCT was available in 5953/8153 (73%) lcSSc cases (vs 3248/3974 [81%] dcSSc; p < 0.001), more frequently with coexisting anti-Scl70 (OR 1.5, CI 1.3–1.8), lower FVC and DLCO (OR 0.99 both), but less frequently with serum ACA (OR 0.7, CI 0.6–0.8).
At baseline (Fig 1A), 36% (2127/5953) lcSSc patients had ILD, in association with older age (OR 1.03, CI 1.02–1.03), digital ulcers (OR 1.18, CI 1.00–1.38), skin thickening proximal to metacarpophalangeal (MCP) joints (OR 1.14, CI 1.01–1.29), esophageal involvement (OR 1.18, CI 1.04–1.34), anti-Scl70 (OR 1.98, CI 1.7–2.3), lower FVC (OR 0.99, CI 0.98–0.99) and lower DLCO (OR 0.98, CI 0.97–0.98). Serum ACA were protective (OR 0.28, CI 0.24–0.32), also in anti-Scl70+ or anti-RNAPOL+ lcSSc (OR 0.3, CI 0.2–0.4). Among ACA+ lcSSc cases, skin fibrosis proximal to MCP (OR 1.3, CI 1.03–1.6) and concurrent anti-Scl70 (OR 2.4, CI 1.7–3.4) were risk factors for ILD. Among anti-Scl70+ lcSSc patients, digital ulcers increased ILD risk (OR 1.5, CI 1.1–2.0). In lcSSc, ILD extension >20% (19% vs 31%) and honeycombing (14% vs 22%) were less frequent with ACA, honeycombing more with anti-Scl70 (23% vs 16%) (Fig 1B).
Among 3826 lcSSc cases without ILD at baseline, 443 developed it during follow-up (incidence rate 6% person-years) and the incidence was highest with anti-Scl70 (14% person-years) and lowest with ACA (4% person-years). Incident ILD was independently associated with age (HR 1.03, CI 1.02–1.04), male sex (HR 1.4, CI 1.1–1.9), anti-Scl70 (HR 1.7, CI 1.3–2.1), lower FVC and DLCO (HR 0.99 for both); telangiectasias (HR 0.6, CI 0.5–0.8) and ACA (HR 0.4, CI 0.4–0.6) were protective (Fig 2).
Of 472 ILD patients with available follow-up data, 64 (14%) met the criteria for ILD progression within the first year. ILD significantly reduced survival in lcSSc, though to a lesser extent than in dcSSc. Patients with progressive ILD had significantly worse survival compared to non-progressors (Fig 3). Conclusion: ILD is found in 36% of lcSSc patients, with a 6% person-years subsequent incidence rate. ILD in lcSSc carries a poor prognosis and may progress over time. Peculiar risk factors can aid stratify patient risk, and early identification is crucial for establishing proper treatment. This study supports the inclusion of patients with lcSSc-ILD in therapeutic trials and underscores the need for risk-adapted ILD monitoring protocols and multidisciplinary care in this subgroup.
