Lack of agreement between rheumatologists in defining digital ulceration in systemic sclerosis

Abstract

Objective. To test the intra-and interobserver variability, among clinicians with an interest in systemic sclerosis (SSc), in defining digital ulcers.Methods. Thirty-five images of finger lesions, incorporating a wide range of abnormalities at different sites, were duplicated, yielding a data set of 70 images. Physicians with an interest in SSc were invited to take part in the Web-based study, which involved looking through the images in a random sequence. The sequence differed for individual participants and prevented crosschecking with previous images. Participants were asked to grade each image as depicting "ulcer" or "no ulcer," and if "ulcer," then either "inactive" or "active." Images of a range of exemplar lesions were available for reference purposes while participants viewed the test images. Intrarater reliability was assessed using a weighted kappa coefficient with quadratic weights. Interrater reliability was estimated using a multirater weighted kappa coefficient.Results. Conclusion.The poor interrater reliability suggests that if digital ulceration is to be used as an end point in multicenter clinical trials of SSc, then strict definitions must be developed. The present investigation also demonstrates the feasibility of Web-based studies, for which large numbers of participants can be recruited over a short time frame.Digital ulcers, which are common in patients with systemic sclerosis (SSc) (1,2), are painful and disabling. These types of ulcers are often used as a primary end point in clinical trials of SSc-related digital ischemia and vasculopathy, as was the case in 2 recent multicenter placebo-controlled trials (3,4). Patient-assessed digital ulcer "activity" was among a core set of measures proposed for use in trials of SSc-related Raynaud's phenomenon (5). However, digital ulcers are difficult to define, which raises concerns about their reliability as an outcome measure. Problems include 1) making the distinction between "healed" and "nonhealed" ulcers, which can be difficult with lesions situated on the fingertips and the extensor surfaces, since an ulcer crater can persist for months after an acute episode, and 2) determining which sites to use. The study by Korn et al (3) included only those ulcers at or distal to the proximal interphalangeal joints, and yet, more proximal ulcers (e.g., those over the metacarpophalangeal joints) can be very painful, and healing can be difficult.

Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis: A Multicenter, Prospective Cohort Study

“…Limitations of this study include the fact that the diagnosis of DUs and critical digital ischemia is not always unequivocal , although definitions were provided in the protocol and/or the case report form. Investigators were not blinded to the NVC and other clinical characteristics assessed at enrollment and may therefore have been biased in favor of a diagnosis of a new DU.…”

Validation of the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria for systemic sclerosis in patients from a capillaroscopy clinic

“…In their study, sensitivity was maintained although puffy fingers were removed from the criteria, but became much lower when sclerodactily or both were removed (from 97% to 79% and to 62%) (11). Something similar may happen with digital tip ulcers and fingertip pitting scars (15), which are well delineated in the 2013 ACR/EULAR criteria, but can be difficult to differentiate in clinical practice.…”

Registry Evaluation of Digital Ulcers in Systemic Sclerosis

“…This evidence suggests to the community the urgent need to design a common strategy on DU mainly based on scientific evidence. Moreover, the DU classification still remains an unmet need that indeed may be helpful in identifying those lesions to be included or excluded from clinical trials [25]. The discrepancy of results in efficacy of some drugs seen in the trials published until today, may be probably due to the multifactorial pathogenesis of DU.…”