Being a current or prior smoker, having a history of gangrene or upper limb sympathectomy, and presence of ≥3 finger digital ulcers were identified as independent risk factors for gangrene development in systemic sclerosis (SSc).1 These results were recently reported in the Annals of the Rheumatic Diseases.

Much of the morbidity and pain associated with SSc is related to the development of digital vasculopathy, including Raynaud phenomenon, digital ulcers (DUs), digit ischemia, and digit gangrene. When complications related to severe vasculopathy do occur, hospitalization is often required to administer intravenous medication or initiate surgical intervention.2 Prevention of the serious adverse effects associated with vasculopathy is of paramount importance when treating SSc. 

Thus, researchers sought to clarify the rates and risk factors of gangrene formation in patients with SSc utilizing the Digital Ulcer Outcomes (DUO) Registry. 

Continue Reading

High Yield Data Summary

  • Being a current or prior smoker, history of gangrene, history of upper limb sympathectomy, and ≥3 finger digital ulcers were identified as independent risk factors for the development of gangrene in SSc

The DUO Registry is a prospective, multicenter, observational cohort of patients in Europe diagnosed with SSc who currently have, or have had, DUs at the time of assessment for registry enrollment.  All patients with SSC and a history of DU at the participating centers are included into the registry, regardless of treatment regimen.

Patients’ demographic and clinical variables including age, sex, SSc disease manifestations, organ involvement, smoking status, antibody serologies, comorbidities, complications, and interventions were recorded at time of inclusion into the registry.

Of the 4 944 patients enrolled in the DUO registry between April 2008 and November 2014, 3 787 were classified into the “never gangrene” group, 855 were classified into the “ever gangrene” group, and 258 were classified into the “current gangrene” group. 

Among these groups, baseline demographics were all similar except for the fact that the “ever gangrene” and “current gangrene” groups had more current smokers at time of registry enrollment than the “never gangrene” group.  As expected, the proportion of patients who had histories of DU-associated complications and hospitalizations were highest in the “ever gangrene” group.

Univariable logistic regression was used to identify potential risk factors for progression to gangrene in patients with ≥1 follow-up visit and no current gangrene at time of enrollment in the registry. Multivariable logistic regression using forward selection was then utilized with covariate information, using variables identified from the univariable logistic regression analysis with P<.15 and sample size >3 000.

Being a current or prior smoker, history of gangrene, upper limb sympathectomy, and having ≥3 finger digital ulcers were subsequently identified as independent risk factors for the development of gangrene.

Summary and Clinical Applicability

Gangrene is still occurring at relatively high rates despite modern medical management. This study identified risk factors that appear to be independently associated with gangrene formation in SSC DUs. 

“These results will help to risk-stratify patients with SSc–DUs and to evaluate preventive gangrene management strategies,” the authors stated.

Limitations and Disclosures

Medical centers who participated in the DUO registry were Ssc-DU specialty referral centers, and the possibility of inclusion of patients with more advanced SSc disease cannot be excluded. 

This DUO Registry is actively sponsored by Actelion Pharmaceuticals. Acetelion is involved in the collection, analysis, and interpretation of data related to the registry.

Related Articles


1. Allanore Y, Denton CP, Krieg T, et al.  Clinical characteristics and predictors of gangrene in patients with systemic sclerosis and digital ulcers in the Digital Ulcer Outcome Registry: a prospective, observational cohort. Ann Rheum Dis. 2016  Published online ahead of print June 27. 2016. doi:10.1136/annrheumdis-2016-209481

2. Hachulla E, Clerson P, Launay D, et al. Natural history of ischemic digital ulcers in systemic sclerosis: single-center retrospective longitudinal study. J Rheumatol 2007;34:2423–30.