Purpose: There is a lack of a valid, definition for skin ulcers in SSc to be used in clinical trials. Our aim was to develop a consensus definition for SSc-skin ulcers based on the results of a systematic literature review (SLR) for skin ulcer definitions and expert opinion; and to evaluate its face validity, reliability and feasibility. Methods: SLR for skin ulcer definitions was conducted using PubMed, Web of Science, and Cochrane library for articles published from inception to January 1st, 2016. SSc experts were to discuss the definitions’ categories and vote for the relevant terms. Reliability of the definition were tested in a second expert meeting, seven SSc experts evaluated 7 SSc pts with skin lesions twice. Face validity and feasibility evaluated by sending out case report forms(CRFs) to 4 SSc experts, they were asked to use the definition in 5 pts each. Results: A total of 3464 abstracts and titles were screened, and 446 articles were fully evaluated. Of these, 66 met eligibility criteria and skin ulcer definitions were extracted. SSc experts discussed, refined and voted on the consensus definition using nominal process. Kappa for inter-, intra-rater rater agreement was 0.51, 0.90 respectively. The mean time to decide if the lesion is an ulcer was 7.4 sec. All investigators endorsed the face validity of the new definition in the CRFs. Conclusion: Using a SLR and a nominal technique, we developed a preliminary consensus-based definition of SSc-skin ulcers. Face validity, feasibility and reliability were demonstrated for the developed definition.

BACKGROUND: Digital ulcers (DU) affect 50% of systemic sclerosis (SSc) patients, representing a challenging clinical problem. Despite a high negative predictive value, capillaroscopic scores proposed to select patients at risk for DU show an inadequate positive predictive value, especially in patients without previous DU. AIM OF THIS STUDY: To increase the predictive value for DU development of capillaroscopy, through a predictive risk chart taking into account capillaroscopic, demographic, and clinico-serological parameters. PATIENTS AND METHODS: Two hundred and nineteen unselected SSc patients from 8 Italian Rheumatology Centers were consecutively enrolled during a 6-month period. Demographic, clinical, serological and instrumental data and capillaroscopy skin ulcers risk index (CSURI) were collected. A. Manfredi et al. / Prediction risk chart for scleroderma digital ulcers RESULTS:A multivariate logistic regression analysis showed a significant positive association between DU appearance and male gender, DU history, altered CSURI, and ESR. A prediction risk chart of the development of DU within 6 months were built on the basis of the above parameters. According to the risk level, four risk classes were identified: low (≤19.3%); medium (>19.3%, ≤58.6%); high (>58.6%, ≤89.2%), and very high risk (>89.2%). CONCLUSIONS: The systematic evaluation of the above parameters can be helpful to identify patients at risk to develop DU optimizing preventive vasoactive therapy.

Our study strengthens the specificity of DM and SSc microangiopathy and points out the need for large prospective studies to confirm our results and possibly to revise current terminology by distinguishing between "scleroderma" and "dermatomyositis" patterns.

BackgroundCSURI is a capillaroscopic index, able to identify scleroderma (SSc) patients at high risk for new or non-healing digital ulcers (DU) in the next three months. CSURI has been validated, only in patients not treated with bosentan, in a large multicenter study in 2011.ObjectivesTo evaluate the predictive value of CSURI in SSc patients assuming bosentan for the prevention of DU.MethodsSeventy-six consecutive SSc patients treated with bosentan were enrolled in a multicenter study (F/M 4.4/1; mean age 56.4±13.6 years; diffuse/limited cutaneous subset 30/44). All patients undergone to NVC and CSURI was calculated according to published studies.At baseline all patients had a history of at least one DU in the last year, and 26 patients (30.3%) showed a current DU. At the time of the study 76.3% of patients were also treated with intravenous prostanoids, while no patients was assuming bosentan for pulmonary arterial hypertension.ResultsAfter 3 months from NVC 18/26 patients showed non healing ulcers and 18/76 patients developed new DU. Receiver operator characteristic curve, performed to analyze the prognostic accuracy of CSURI in regard to DU development, is reported in the figure.The area under the curve (AUC) was 0.69 (95% CI 0.57-0.79, p=0.0019) and the higher sensitivity and specificity were observed for a CSURI value of 2.5 (sensitivity 94.4; specificity 57.5; positive and negative likehood ratio 2.22 and 0.097, respectively).At the validated cut-off value of 2.96 sensitivity was 86.1%, specificity 60.0%, positive and negative likehood ratio 2.15 and 0.23, respectively, showing a lower negative predictive value.ConclusionsIn patients treated with bosentan, CSURI shows a lower positive predictive value if compared with SSc population observed in our previous validation study, while the negative predictive value can be considered acceptable.The cause of this different result is not evaluable by our study. SSc peripheral microangiopathy is sustained by a multifactorial process, only partially known, involving a complex cytokines and cells network. In this picture, bosentan could reduce the incidence of new DU, without significantly interfere with the parameters included in CSURI calculation.Some Authors observed a general improvement of NVC parameters in SSc patients treated with bosentan. These data are not in contrast with our study since CSURI calculation is obtained by considering the “worst” capillaroscopic image. Moreover, a longer period of observation as in the other studies should more significantly influence changes in NVC parameters.In our previous studies, CSURI showed a higher predictive value than history of DU in detecting SSc patients at risk for new lesions. Anyway in this study this role of primary prevention cannot be applicable. Moreover, a special attention could be pointed on patients with recurrent DU, regardless specific treatments.A combined approach based on clinical picture and CSURI could probably help in managing therapy of SSc patients with DU, but only prospective clinical trial ...