Contemporary Management of Raynaud's Phenomenon and Digital Ischaemic Complications

Ariane L. Herrick


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

In This Article

Possible Future Treatment Options, and Questions Still to be Answered

What advances are likely to be made in the next 3–4 years, and what are the important questions which clinicians often ask but which remain unanswered?

Statin Therapy

There is currently considerable interest in the use of statins in SSc,[35–37] including in SSc-related digital ischaemia. Statins could confer benefit in SSc via a number of different mechanisms.[38] Abou-Raya et al.[39] reported improvements in both clinical and laboratory measurements (including number of new digital ulcers and visual analogue score for severity of Raynaud's) in patients with SSc treated with atorvastatin 40 mg/day for 4 months, indicating that statins deserve further research. However, at present, there is insufficient evidence to recommend statins as standard therapy for either primary or SSc-related Raynaud's phenomenon.

Antioxidant Therapy

Despite increasing evidence to support the hypothesis that oxidant stress contributes to the pathogenesis of the vascular injury of SSc,[40] there have been relatively few studies examining efficacy of antioxidants. Acetylcysteine was recently reported to be beneficial in SSc-related digital ulceration, but this was a small open study[41] and further trials are required.

Topical Treatment of Digital Ulcers

A recent open study[42] suggested that vitamin E gel improved digital ulcer healing rate in patients with SSc. It is hoped that this study will stimulate researchers to undertake further much-needed trials to establish an evidence base for tissue viability input to the care of patients with SSc-related digital ulcers.

Botulinum Toxin

Although botulinum toxin has been reported, in case series, to confer benefit in patients with digital ischaemia, including those with SSc,[43,44] this form of therapy requires further evaluation before it can be recommended.

Should Aspirin or Other Antiplatelet Agents Be Prescribed for Patients With Raynaud's Phenomenon?

Although there is a good theoretical rationale for antiplatelet therapy, at least in SSc-related Raynaud's phenomenon [patients with SSc demonstrate increased platelet activation and aggregation (reviewed in[45])], the only clinical trials which have been performed have been small and have not shown any definite benefit.[46] However, it is unlikely that adequately powered studies of antiplatelet agents will be performed in the foreseeable future. At present, it seems reasonable to prescribe antiplatelet therapy in patients with severe SSc-related Raynaud's phenomenon, especially in those with critical ischaemia (remembering that many patients with SSc have upper gastrointestinal involvement and an alternative to aspirin may be preferable).

What Other Therapies Are Currently Being Researched?

This is an exciting time for clinicians and scientists with an interest in Raynaud's phenomenon because a number of different drugs are currently being researched. These include treprostinil (an oral prostanoid), different phosphodiesterase inhibitors, ET-1 receptor antagonists, and RhoA/Rho kinase inhibitors.[47] The next 5 years should see publication of trials of these novel therapies.

Are There Any 'Disease-modifying' Drugs That Could Prevent Progression to Systemic Sclerosis-related Digital Ulceration and Critical Ischaemia?

This is the key question. The ideal is to prevent tissue injury and the problems exemplified in Fig. 1. At present, there is no drug known to remodel the digital vasculature, although some drugs currently prescribed for their vasodilatory actions – including prostanoids,[48] ACE inhibitors,[49] and ET-1 receptor antagonists[50] – are thought to have effects on vascular remodelling. What are required are long-term studies to address this issue, although one of the major challenges is to develop robust endpoints of SSc-related digital vasculopathy to facilitate such trials.


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