Younger Age at Scleroderma Onset, Being Male Linked to Digital Ulcers, Study Reports

Scleroderma patients who develop digital ulcers are more likely to be younger at disease onset, male, and have the diffuse type of the disease, a study has found.

Digital ulcers — sores on the fingers and toes — are estimated to affect half of people with scleroderma. The ulcers are prone to infection and slow to heal, and are associated with lower quality of life and higher healthcare costs. Yet there has been little research on which patients are at risk of developing the ulcers and the impact on healthcare resources.

The study, “Digital ulcers in systemic sclerosis: their epidemiology, clinical characteristics, and associated clinical and economic burden,” was published in the journal Arthritis Research & Therapy.

Researchers in Australia analyzed clinical and demographic data of people with scleroderma who were treated at one of four centers between 2008 and 2015.

Of the 1,085 patients, 527 (48.6%) experienced digital ulcers over a mean follow-up time of just more than five years.

Compared with patients who had never had digital ulcers, the group with the sores had a greater proportion of males (18%, compared with 11.5%) and of individuals with the diffuse subtype of the disease (34.9%, compared with 18.2%). They were also significantly younger at onset of scleroderma (age 43.6 vs. 48.8) and had a longer disease duration (12.2 years vs. 10.1 years).

People with a history of digital ulcers were also more likely to be positive for autoantibodies — self-targeting antibodies that drive scleroderma. Some 18.9% of those with the ulcers tested positive for antitopoisomerase-1, compared with 9.3% of those without the ulcers. For anti-RNA polymerase III, the rate was 16.9%, compared with 11.8%. Both these autoantibodies target the cell nucleus.

Those with digital ulcers also had significantly higher rates of clinical manifestations including gastrointestinal involvement, pulmonary arterial hypertension, and interstitial lung disease (ILD).

Increasing severity of digital ulcers (as determined by the number of newly appearing ulcers) was also associated with being male, having diffuse scleroderma, and the presence of anti-Scl-70 autoantibodies. Clinical signs such as ILD were also significantly linked to greater digital ulcer severity.

In contrast, the presence of anti-centromere autoantibodies — which are also specific to scleroderma — was associated with less digital ulcer severity.

Health-related quality of life (HRQoL), as assessed by the physical component of the Medical Outcome Short Form-36, was significantly lower for those with a history of digital ulcers, compared with those not affected. Those with ulcers scored 36.1 on the measure, compared with 39.2 for those without ulcers.

Those with digital ulcers also used significantly more healthcare resources. This was primarily driven by hospitalizations, but also included emergency room visits and ambulatory care services. Excluding medication costs, scleroderma patients with digital ulcers cost AU$12,474 (about US$8,500) a year more than those without them.

On average, these patients had more hospital visits per year (2.1 visits vs. 1.5) and stayed longer (2.3 days vs. 1.8). Likewise, more people with digital ulcers had gone to an emergency room at some point in the study period (71.2%, compared with 63.8%).

“DUs [digital ulcers] place a large burden on the patient and healthcare system through reduced HRQoL and increased healthcare resource utilization and associated cost,” the researchers said. “To reduce the clinical burden of DUs, additional research is needed to determine effective interventions and management plans.”