Extracorporeal Shock Wave Therapy for Digital Ulcers of Systemic Sclerosis: A Phase 2 Pilot Study

Saito, Shinichiro; Ishii, Tomonori; Kamogawa, Yukiko; Watanabe, Ryu; Shirai, Toshikazu; Fujita, Yöko; Shirota, Yuko; Fujii, Hiroshi; Ito, Kei; Shimokawa, Hiroaki; Yamaguchi, Takuhiro; Kawaguchi, Yasushi; Harigae, Hideo

doi:10.1620/tjem.238.39

Cited by 19 publications

(12 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In SSc, these tend to be confined to patients who have progressed to digital Extracorporeal shock wave therapy was reported to confirm some benefit in a study of 9 patients with SSc and 49 ulcers [64].…”

Section: Raynaud's Phenomenon (Which Has Not Progressed To Digital Ulmentioning

confidence: 93%

Recent advances in the pathogenesis and management of Raynaud's phenomenon and digital ulcers

Herrick

2016

Current Opinion in Rheumatology

View full text Add to dashboard Cite

Purpose of review: Systemic sclerosis (SSc)-related digital vasculopathy can progress from severe Raynaud's phenomenon (RP) to digital ulceration, is a major cause of pain and disability, and impacts negatively on quality of life. Current treatments are often ineffective and poorly tolerated. This review summarises some of the progress which has been made in the last 12 to 18 months in terms of our understanding of disease process, measurement and treatment. Recent findings:The most important findings include that we can now better predict which patients with SSc are most likely to develop digital ulcers. In terms of treatment, a multicentre trial showed that the phosphodiesterase inhibitor sildenafil confers some benefit in SSc-related digital ulceration.Topical therapies are being explored: iontophoresis of vasodilators increases local blood flow, and in an avian model, VEGF 121 fibrin applied in a gel matrix improved wound healing. A number of challenges confront clinicians and scientists with an interest in SSc-related digital vasculopathy, specific questions being:1. What mechanisms drive the digital vasculopathy and lead to structural as well as functional change? 2. Can we predict which patients progress to digital ulceration? 3. Can we measure disease process reliably (in terms of both RP and digital ulcers), to provide outcome measures to facilitate clinical trials?4. Are we making progress in developing safe and effective treatments, for both severe RP and SScrelated digital ulceration?In this review I shall outline developments over the last 12-18 months in answering these four questions, under the headings of pathophysiology, predictors of digital ulceration, measurement of disease process, and management. Under each heading I shall consider firstly RP and secondly digital ulceration, although this is a false distinction because both are part of the spectum of SSc-digital vasculopathy. PATHOPHYSIOLOGY Raynaud's phenomenonThe pathophysiology of RP is complex and most likely involves an interplay between vascular factors, neural control mechanisms and intravascular factors [6]. Flavahan, in a recent review [7**], describes thermoregulatory mechanisms as central to an understanding of RP, highlighting the role of arteriovenous anastomoses, and how local cooling leads to increased activity of alpha 2 -adrenoceptors, resulting in reduced blood flow. In patients with SSc, structural microvascular changes mean that upstream vasoconstriction can irretrievably compromise nutritional blood flow and lead to tissue injury [7**,8]. The review also gives a framework for targetted therapeutic interventions [7**]. Digital ulcerationA commonly held view is that fingertip ulceration is ischaemic, whereas ulceration over the extensor surfaces of fingers is 'traumatic'. To date there has been very little direct evidence to support this theory. However, a study by Ruaro et al [9*] of 20 patients with SSc and fingertip ulcers demonstrated that blood flow is reduced at the site of fingertip ulcers (and improves wit...

show abstract

Section: Raynaud's Phenomenon (Which Has Not Progressed To Digital Ulmentioning

confidence: 93%

Recent advances in the pathogenesis and management of Raynaud's phenomenon and digital ulcers

Herrick

2016

Current Opinion in Rheumatology

View full text Add to dashboard Cite

show abstract

“…Iontophoresis studies of non-invasive transdermal drug delivery based on the transfer of charged molecules using a low-intensity electric current is complex and a potential ancillary modality for SSc-related DU management, but safety may be an issue (52). Another interesting modality is extracorporeal shockwave therapy, which was shown to significantly reduce the number of DUs over 9 weeks from 5.4 to 1.1 in a Japanese Phase 2 study consisting of 9 SSc patients studied for this indication (53).…”

Section: General Principles Of Wound Managementmentioning

confidence: 99%

Review of local wound management for scleroderma-associated digital ulcers

Lebedoff

Frech

Shanmugam

et al. 2017

Journal of Scleroderma and Related Disorders

View full text Add to dashboard Cite

REVIEW population is a potentially heterogeneous population and thus, standardizing wound care protocols is crucial. Furthermore, it is important to standardize DU outcome measures, for example, assessments of healing and development of new lesions, during the design phase of DU clinical trials. In general, there is a paucity of evidence on the wound care for managing SSc patients. The purpose of this manuscript is to review the current recommendations for local wound management in patients with ulcerations, which we believe to be applicable to digital ulcers. The overarching goal is to develop recommendations for local wound care for SSc-associated DUs that might be a useful starting point for future clinical trial design. Role of tissue perfusion in digital ulcer healing The importance of local wound perfusion in both SScrelated DU development and healing has been demonstrated by flow-mediated dilatation, laser Doppler imaging (LDI) and thermography (12-14). An increase in DU perfusion correlates with healing, and LDI has successfully been implemented as an outcome measure in a clinical trial (15). Similarly, a study investigating power Doppler ultrasonography found that ulnar artery occlusion was a predictor of new or recurrent DUs in patients with SSc (16). Thus, documentation of adequate perfusion by noninvasive measures of blood flow is an important initial step for DU evaluation and may be used both for assessment of severity of vasculopathy as well as likely responsiveness to vasoactive treatments (17).

show abstract

“…Accordingly, we performed two trials to obtain basic information on the efficacy and safety of ESWT. One was a proof of concept (POC) study (32), and the other was a control study used to observe the natural history of ulcers with conservative treatment. In the POC study, the mean number of ulcers showed a significant reduction in only 8 weeks after ESWT (32).…”

Section: Use Of Low-energy Eswt For Digital Ulcers Associated With Sscmentioning

confidence: 99%

“…One was a proof of concept (POC) study (32), and the other was a control study used to observe the natural history of ulcers with conservative treatment. In the POC study, the mean number of ulcers showed a significant reduction in only 8 weeks after ESWT (32). In spite of an essentially positive result in the POC trial, there were issues requiring further analysis.…”

Section: Use Of Low-energy Eswt For Digital Ulcers Associated With Sscmentioning

confidence: 99%

Extracorporeal shock wave therapy for digital ulcers associated with systemic sclerosis

Saito¹,

Ishii

Ito

et al. 2016

Journal of Scleroderma and Related Disorders

Self Cite

View full text Add to dashboard Cite

The medical cost to the government is also significant. Thus, a new treatment strategy is needed. Etiology and pathogenesis of DUs of scleroderma SSc is an autoimmune disease characterized by microvascular damage and heterogeneous fibrosis of skin and multiple organs; the vascular involvement can be life-threatening, with complications such as renal crisis (3). The disease onset is usually in the third to fifth decades, and women are affected five times as often as men. Increased fibrosis in the skin and other organs, such as the lungs, gastrointestinal tract, heart, and kidneys, sometimes results in organ dysfunction leading to death. The primary event in SSc is postulated to be endothelial cell injury in the blood vessels, from the small arteries to the capillaries. Therefore, nailfold capillaroscopy is used to monitor disease. It is one of the most important diagnostic tools, and is recognized as the most sensitive and specific technique to detect vascular abnormalities. Early diagnosis and prediction of disease onset are possible by using this tool (4). DUs are a severe complication of SSc caused by microvascular impairment and persistent vasospasm associated with Raynaud's phenomenon. Approximately 50% of patients in a study of 938 subjects with SSc experienced DUs; 10% required continuous therapy, whereas 1% exhibited severe symptoms such

show abstract

Extracorporeal Shock Wave Therapy for Digital Ulcers of Systemic Sclerosis: A Phase 2 Pilot Study

Cited by 19 publications

References 26 publications

Recent advances in the pathogenesis and management of Raynaud's phenomenon and digital ulcers

Recent advances in the pathogenesis and management of Raynaud's phenomenon and digital ulcers

Review of local wound management for scleroderma-associated digital ulcers

Extracorporeal shock wave therapy for digital ulcers associated with systemic sclerosis

Contact Info

Product

Resources

About