# Refractory Digital Ulcers in Systemic Sclerosis Sine Scleroderma Associated With Antiphospholipid Syndrome: A Case-Based Review

## TL;DR

A rare case of systemic sclerosis sine scleroderma with antiphospholipid syndrome is reported, where anticoagulation successfully treated severe digital ulcers.

## Contribution

This is the first reported case of ssSSc with secondary APS presenting with recurrent digital ulcers and pulmonary embolism.

## Key findings

- Anticoagulation led to complete healing of digital ulcers within two months.
- The patient tested positive for lupus anticoagulant and anti-β2-glycoprotein I IgG, confirming secondary APS.
- This case highlights the importance of considering APS in SSc patients with refractory digital ulcers.

## Abstract

Digital ulcers (DUs) are a severe manifestation of the vasculopathy underlying systemic sclerosis (SSc). In cases refractory to treatment, the presence of other modifiable causes of vasculopathy, such as antiphospholipid syndrome (APS), should be considered, although its diagnosis in patients with systemic sclerosis sine scleroderma (ssSSc) is exceedingly rare. We report the case of a 20-year-old Caucasian female with ssSSc, who presented with Raynaud’s phenomenon (RP), recurrent DU, telangiectasias, inflammatory arthralgias, dyspepsia, and epigastric pain, in the absence of skin thickening. Laboratory investigation revealed a high-titre antinuclear antibody (ANA; 1:2560) with an anti-centromere pattern, and positivity for both anti-centromere antibodies (ACA) and anti-Ro-52 antibodies. Nailfold capillaroscopy showed an early scleroderma pattern. Despite optimized vasodilatory therapy, including calcium channel blockers, phosphodiesterase inhibitors, endothelin receptor antagonists, and regular iloprost infusions, the patient continued to experience recurrent DU. Following a pulmonary embolism with lingula infarction, anticoagulation was initiated, resulting in complete healing of the DU within two months and no subsequent thrombotic events. Repeat testing confirmed persistent positivity for lupus anticoagulant (LA) and anti-β2-glycoprotein I (anti-β2GPI) IgG more than 12 weeks apart, establishing the diagnosis of secondary APS. To our knowledge, this is the fourth reported case of ssSSc with secondary APS, and the first presenting with recurrent DU and pulmonary embolism, highlighting the rarity of this association and the importance of considering APS in SSc patients with refractory DU. The association between SSc and APS remains poorly understood, and further research is needed to clarify the underlying mechanisms and guide optimal management.