Contemporary Management of Raynaud's Phenomenon and Digital Ischaemic Complications

Ariane L. Herrick

Disclosures

Curr Opin Rheumatol. 2011;23(6):555-561. 

In This Article

Abstract and Introduction

Abstract

Purpose of review: The present review gives an update of the current management of Raynaud's phenomenon and its ischaemic complications (digital ulceration and critical ischaemia) and discusses possible further developments in the next 5–10 years. New approaches to therapy are being driven by increased understanding of pathophysiology and by increased international networking of clinicians and scientists, facilitating clinical trials.
Recent findings: Key points include phosphodiesterase inhibitors most likely confer benefit, although clinical trials have given somewhat conflicting results, and have been short-term; a new topical, easy-to-use glyceryl trinitrate preparation has been shown to improve Raynaud's Condition Score; the endothelin-1 receptor antagonist bosentan has now been shown to reduce the number of new systemic sclerosis (SSc)-related digital ulcers in two multinational clinical trials; and although statin therapy is likely to confer benefit in SSc-related Raynaud's phenomenon, further research is required to confirm this.
Summary: New therapeutic approaches in patients who do not respond to more traditionally used vasodilators include phosphodiesterase inhibitors and (for those with recurrent SSc-related digital ulcers) endothelin-1 receptor antagonism. Several other potential new therapies are being researched. Optimal management of digital ulceration is multidisciplinary including tissue viability and (sometimes) surgical input.

Introduction

The management of Raynaud's phenomenon and of its ischaemic complications (digital ulceration and critical ischaemia) continues to evolve. This is because increased understanding of pathogenesis is informing new treatment approaches which are being put to the text in multicentre clinical trials, facilitated by increased international networking of clinicians. In the 3–4 years since this topic was last reviewed in Current Opinion in Rheumatology,[1] a number of clinical trials have been published, including those examining safety and efficacy of phosphodiesterase inhibitors, topical glyceryl trinitrate (GTN), and endothelin-1 (ET-1) receptor antagonism. Oral prostanoid therapy is currently in clinical trial, and other drugs are in development.

Although the pathogenesis of Raynaud's phenomenon is complex and not fully understood, several key mediators are recognized to play a role in maintaining the normal balance between vasoconstriction and vasodilation, which, in Raynaud's phenomenon, is upset in favour of vasoconstriction. This means that there are multiple possible targets for therapy. In the patient with a systemic sclerosis (SSc)-spectrum disorder, Raynaud's phenomenon is associated with structural as well as functional vascular problems (unlike the situation in primary Raynaud's phenomenon, which is believed to be an entirely reversible 'benign' vasospasm) and can progress to critical digital ischaemia and/or digital ulceration (Fig. 1). Therefore, in patients with SSc, other factors enter into the treatment equation and ideally we should also aim to prevent/reduce vascular injury, and to inhibit the increased platelet aggregation/procoagulant tendency, which is part of the SSc disease process. Several drugs currently used to treat SSc-related digital ischaemia have multiple potentially beneficial types of effect: for example, calcium channel blockers are thought not only to be vasodilators but to have antiplatelet[2] and possibly antioxidant[3] effects.

Figure 1.

Fingertip ulceration and critical digital ischaemia

Therefore, current and future treatment of Raynaud's phenomenon differs between patients, depending on severity and whether there is an underlying secondary cause, of which SSc-spectrum disorders are most relevant to the rheumatologist. On the one hand, mild primary Raynaud's phenomenon may respond to general/'nondrug' measures (including avoiding cold exposure, wearing warm clothes, smoking cessation), whereas on the other hand, the patients shown in Fig. 1a and b will require aggressive drug therapy and possibly surgery. This review will outline current principles of management, highlight recent advances and then discuss possible future treatment options.

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