Digital Ulcers in Systemic Sclerosis – How to Manage in 2013?

Abstract

Digital ulcers (DUs) are among the most frequent and disabling vascular complications in patients with systemic sclerosis (SSc). The etiology and pathogenesis of DUs differs depending on the lesion localization. For this reason the underlying etiologic and pathogenetic factors will guide the therapeutic decision. The main pathogenic mechanism that contributes to the development of fingertip DUs is ischemia owing to SSc-related vasculopathy. DUs over bony prominences are mainly a result of skin fibrosis, epidermal thinning and mechanical friction. At the areas of subcutaneous calcinosis DUs can develop as a result of mechanical friction and inflammation. Thus, in cases of DUs over bony prominences and calcinosis, avoidance of trauma and skin care are main measures of primary prophylaxis. In pure ischemic DUs, a combination of vasodilators (calcium channel blockers (CCBs), intravenous prostanoid, phosphodiesterase inhibitors) and antiplatelet drugs should be applied. Despite the lack of controlled trials addressing the administration of antiplatelet agents and anticoagulants in DUs in the context of SSc, the current knowledge about the platelet and coagulation dysfunction leads to their frequent administration from the leading experts in the field of SSc. In our opinion, as more powerful agents, anticoagulants should be considered in severe cases of development of digital gangrenes. Analgetics and antibiotics may be indicated and local treatment is a mandatory care. Currently, the EUSTAR recommendations for the treatment of RP and DUs in SSc include CCBs, intravenous prostanoids and endothelin receptor antagonists. Although for the inclusion of other options in the official recommendations, their efficacy should be confirmed by controlled clinical trials, they are routinely used in the leading scleroderma-centers based on the current knowledge about the pathogenesis of development of DUs in SSc.

Successful Combination Therapeutic Strategy for Treatment of Digital Necrosis in Systemic Sclerosis

“…La Montagna et al (2002) have observed digital ulcers of the hands in 43% of cases vs 8% prevalence of the feet (p < 0.001) [11]. Similar are the results from an own study (Lambova et al, 2013), in which the prevalence of digital ulcers of the hands was 35% (21/60) vs 10% (6/60) -prevalence of the toes (p < 0.05) [10].…”

“…We have previously reported personal experience with administration of subcutaneous low-molecular heparin for one month with switching on low-dose aspirin after documented improvement in SSc patients with digital gangrene [10]. Official recommendations about the administration of antiplatelet drugs (e. g., low-dose aspirin, clopidogrel) and anticoagulants (heparin) in the therapeutic protocol of digital ulcers in SSc are absent and their use is based on experts' opinion [25,26].…”

“…Digital gangrene were rare finding (n = 7) that were more frequent in diffuse cutaneous form of SSc (0.9% vs 0.25% in cases with limited cutaneous involvement) [6]. In an own study (Lambova et al, 2013) that included 60 SSc patients, it has been also observed that prevalence of digital ulcers is higher among scleroderma patients with diffuse cutaneous involvement vs limited cutaneous form of SSc [10].…”

Long non-coding RNA HOTAIR drives EZH2-dependent myofibroblast activation in systemic sclerosis through miRNA 34a-dependent activation of NOTCH

“…Systemic sclerosis (SSc) is a prototypic fibrotic disease that causes tissue and vascular fibrosis in the skin and internal organs including heart, lungs, kidneys and gastrointestinal tract 1 2. Tissue fibrosis typically starts in the skin at the level of hands and feet3 and progresses through the arms and thighs to eventually involve the chest and abdomen in the most severe cases (diffuse cutaneous SSc) 1…”