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Endothelial dysfunction, microvascular damage and ischemic peripheral vasculopathy in systemic sclerosis.

Ivone Silva1, Andreia Teixeira2, José Oliveira3

  • 1Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Multidisciplinar Unit of Biomedical Investigation, Porto, Portugal.

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Summary

Endothelial dysfunction and microvascular damage predict digital ulcers (DU) in systemic sclerosis (SSc) patients. Biomarkers like flow-mediated dilatation (FMD) and endothelin-1 (ET-1) identify high-risk individuals for DU development.

Keywords:
ADMAAllen testET-1Systemic sclerosisand microangiopathy evolution scorecapillaroscopydigital ulcersflow-mediated dilatation

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Area of Science:

  • Rheumatology
  • Vascular Biology
  • Dermatology

Background:

  • Systemic sclerosis (SSc) is associated with secondary Raynaud Phenomenon (SRP).
  • Digital ulcers (DU) are a common and debilitating complication in SSc patients.
  • Predicting DU development is crucial for timely intervention and improved patient outcomes.

Purpose of the Study:

  • To evaluate endothelial dysfunction and microvascular damage as predictors of ischemic fingertip digital ulcers (DU) in SRP and SSc-associated patients.
  • To assess the 3-year clinical follow-up for the occurrence of new DU.
  • To identify specific biomarkers and clinical factors associated with DU development.

Main Methods:

  • A 3-year observational cohort study involving 77 SRP patients with systemic sclerosis.
  • Analysis of flow-mediated dilatation (FMD), nailfold videocapillaroscopy (NVC), endothelin-1 (ET-1), and asymmetric dimethylarginine (ADMA).
  • Primary outcome measured was the occurrence of a new DU.

Main Results:

  • Risk factors for DU at baseline included low FMD%, specific NVC patterns, high microangiopathy evolution score (MES), increased ET-1, and increased ADMA.
  • Predictors for DU recurrence in follow-up included prior DU history, anti-SCL-70 autoantibody, late NVC pattern, high MES, low FMD%, and increased ET-1.
  • For first DU events in naive patients, late NVC pattern and MES score were independent predictors.

Conclusions:

  • Endothelial dysfunction biomarkers, specifically FMD and ET-1, are strong predictors of new DU in SSc patients.
  • Severe microvascular damage, as assessed by NVC, is also a significant predictor of DU development.
  • These findings highlight the importance of vascular assessment in managing SSc patients at risk for digital ulcers.