Prognostic value of baseline nailfold videocapillaroscopy in predicting pulmonary decline and disease progression in Systemic Sclerosis

Abstract

Objectives: Systemic sclerosis (SSc) is a complex connective tissue disease frequently complicated by interstitial lung disease (ILD), which remains the leading cause of mortality. Nailfold videocapillaroscopy (NVC) is a widely used non-invasive technique for assessing microvascular damage in SSc, but its role in predicting ILD progression remains underexplored. Additionally, Krebs von den Lungen-6 (KL-6) has emerged as a potential biomarker for ILD severity, yet its relationship with NVC patterns and pulmonary function decline requires further investigation. To determine whether baseline NVC abnormalities predict pulmonary function decline, ILD progression, and longitudinal changes in serum biomarkers (KL-6, IL-18, IL-18BP), inflammatory markers, and disease activity indices (EUSTAR 2017, SCTC-DI) over a two-year follow-up in patients with SSc.

Methods: In this prospective longitudinal study, patients diagnosed with SSc according to the 2013 ACR/EULAR criteria were stratified based on the presence of ILD. Baseline assessments included NVC, high-resolution computed tomography (HRCT), pulmonary function tests (PFTs), and serum biomarker measurements using quantitative ELISA. ILD progression was assessed by changes in forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO), and HRCT findings. Correlations between baseline NVC abnormalities and longitudinal changes in pulmonary function, biomarkers, and disease indices were analyzed using multivariate regression modeling.

Results: 74 patients (27% male, mean age 57.5 ± 15 years) were included, with a mean disease duration of 7.67 ± 8 years. At baseline, 38% had ILD, which increased to 51% after two years, while the proportion with ≥20% lung involvement on HRCT rose from 32% to 43%. Disorganization of capillary architecture at baseline predicted greater declines in %FVC (β = -0.75, p = 0.03) and %DLCO (β = -0.24, p = 0.03), as well as worsening modified Rodnan skin score (mRSS) (β = 0.23, p = 0.03) over two years. A late NVC pattern was associated with worsened mRSS (β = 0.47, p = 0.004), larger increases in KL-6 (β = 0.18, p = 0.04), and more pronounced declines in %DLCO (β = -0.38, p = 0.04). Additionally, a higher baseline SCTC-DI score was predictive of progressive semiquantitative fibrosis on HRCT (β = -0.32, p = 0.003) and elevated CRP levels (β = 0.38, p = 0.003) at two years.

Conclusions: Baseline NVC abnormalities-particularly capillary disorganization and late pattern morphology-are independent predictors of ILD progression and worsening pulmonary function in SSc over two years in SSc. Elevated KL-6 levels further correlate with NVC abnormalities and pulmonary decline. These findings highlight the potential role of NVC as a non-invasive tool for ILD risk stratification, complementing traditional imaging and biomarker assessments. Early identification of patients at higher risk for ILD progression could enable more intensive monitoring and timely therapeutic interventions, improving long-term outcomes in SSc-ILD.

Keywords: NFC; systemic sclerosis: ILD.