Abstract
Introduction
Raynaud’s phenomenon is episodic vasospasm of the peripheral vessels. It presents as episodic colour changes of the digits (sometimes accompanied by pain and paraesthesia), usually in response to cold exposure or stress. The classic triphasic colour change is white (ischaemia), then blue (de-oxygenation), then red (reperfusion). Raynaud’s phenomenon can be primary (idiopathic) or secondary to several different conditions and causes. When secondary (e.g., to systemic sclerosis), it can progress to ulceration of the fingers and toes. This review deals with secondary Raynaud’s phenomenon.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of surgical interventions in complicated secondary Raynaud’s phenomenon? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found two studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: botulinum toxin, simple debridement/surgical toilet of ulcers, peripheral sympathectomy (digital, digital plus sympathectomy of the ulnar and/or radial artery, ligation of the ulnar artery), cervical/thoracic sympathectomy, arterial reconstruction (venous graft, arterial graft, balloon angioplasty), and amputation
Key Points
Raynaud’s phenomenon is episodic vasospasm of the peripheral vessels.
It presents as episodic colour changes of the digits (sometimes accompanied by pain and paraesthesia), usually in response to cold exposure or stress. The classic change is white (ischaemia), then blue (de-oxygenation), then red (reperfusion).
Raynaud’s phenomenon can be primary (idiopathic) or secondary to several different conditions and causes. When secondary (e.g., to systemic sclerosis), it can progress to ulceration of the fingers and toes. This review deals with secondary Raynaud’s phenomenon.
Most trials we found were in people with Raynaud's phenomenon secondary to systemic sclerosis.
We found no RCT evidence on the effectiveness of botulinum toxin, simple debridement/surgical toilet of ulcers, peripheral sympathectomy (digital, digital plus ulnar and/or radial artery, ligation of the ulnar artery), cervical/thoracic sympathectomy, arterial reconstruction (venous graft, arterial graft, balloon angioplasty), or amputation at improving outcomes for people with complicated secondary Raynaud’s phenomenon.
The use of botulinum toxin in people with complicated secondary Raynaud’s phenomenon is currently an off-license application that needs further research.
Clinical experience suggests surgical debridement improves symptoms in people with systemic sclerosis-related secondary Raynaud’s phenomenon and painful digital ulcers.
Peripheral digital sympathectomy may have a role in the treatment of people with complicated secondary Raynaud’s phenomenon. However, more research is required, especially for longer-term outcomes and the duration of any early effect.
The evidence is no more certain for more radical sympathectomy than for local surgery.
Amputation may be helpful in cases of refractory infection and provide pain relief in people with secondary Raynaud’s phenomenon complicated by digital ulceration and/or critical ischaemia when other treatment options have failed.
About this condition
Definition
Raynaud's phenomenon is episodic vasospasm of the peripheral vessels. It presents as episodic colour changes of the digits (sometimes accompanied by pain and paraesthesia), usually in response to cold exposure or stress. The classic triphasic colour change is white (ischaemia), then blue (de-oxygenation), then red (reperfusion). Raynaud's phenomenon can be primary (idiopathic) or secondary to several different conditions or causes, including connective tissue diseases such as systemic sclerosis, extrinsic vascular obstruction (e.g., in thoracic outlet syndrome), certain drugs/chemicals (e.g., ergotamine, vinyl chloride), vibration exposure (hand-arm vibration syndrome), and hyperviscosity states. When secondary, Raynaud's phenomenon can progress to ulceration of the fingers and toes and, less commonly, critical digital ischaemia. This review excludes primary (idiopathic) Raynaud's phenomenon, and concerns the management of complicated secondary Raynaud’s phenomenon. Most of the evidence we found on complicated secondary Raynaud's phenomenon was in people with systemic sclerosis.
Incidence/ Prevalence
See Raynaud's phenomenon (primary). The prevalence of secondary Raynaud's depends on the associated disease or condition. For example, the prevalence of Raynaud's phenomenon in people with systemic sclerosis is almost 100%.
Aetiology/ Risk factors
Many different conditions can be associated with secondary Raynaud’s phenomenon, and the pathogenesis and pathophysiology of Raynaud’s phenomenon vary depending upon these underlying conditions. Abnormalities of the blood vessel wall, of the neural control of vascular tone, and intravascular factors may all have a role. Other factors have also been implicated, including smoking (in people with systemic sclerosis, smoking is associated with severity of digital ischaemia), hormonal factors (Raynaud's is more common in women than in men), and genetic factors.
Prognosis
Secondary Raynaud’s phenomenon can be severe, and may progress to ulceration, scarring, and sometimes gangrene necessitating amputation. Therefore, prognosis depends, at least to some extent, on the underlying cause of Raynaud’s phenomenon. Prognosis has been studied most successfully in people with systemic sclerosis who developed underlying structural vascular abnormalities affecting both the microcirculation and the digital arteries. One study found that, of 1168 people with systemic sclerosis, 203 people (17.4%) over an 18-month period had severe digital vasculopathy (Raynaud's phenomenon complicated by digital ulceration, critical digital ischaemia, gangrene, or requiring digital sympathectomy).
Aims of intervention
To relieve or reduce the frequency and severity of Raynaud′s attacks, prevent tissue damage, preserve hand function, and improve quality of life, with minimal adverse effects of treatment.
Outcomes
Resolution of digital ulceration; pain management; improvement in hand function; Raynaud's condition score; adverse effects (surgical complications, infections, amputations, persistence of ulcers).
Methods
Clinical Evidence search and appraisal March 2014. The following databases were used to identify studies for this systematic review: Medline 1987 to March 2014, Embase 1987 to March 2014, and The Cochrane Database of Systematic Reviews, issue 3, 2014 (1966 to date of issue). Additional searches were carried out in the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) database. We also searched for retractions of studies included in the review. An information specialist identified titles and abstracts in an initial search, which an evidence scanner then assessed against predefined criteria. An evidence analyst then assessed full texts for potentially relevant studies against redefined criteria. An expert contributor was consulted on studies selected for inclusion. An evidence analyst then extracted all data relevant to the review. Study design criteria for evaluation in this review were: published RCTs and systematic reviews of RCTs in the English language that were at least single-blinded. There was no minimum sample size, length of follow up, or maximum loss to follow up. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. We included RCTs and systematic reviews of RCTs where harms of an included intervention were assessed, applying the same study design criteria for inclusion as we did for benefits. In addition, we used a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review. The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Raynaud's phenomenon (primary)
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Ariane Herrick, Centre for Musculoskeletal Research, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Lindsay Muir, Salford Royal NHS Foundation Trust, Salford, UK.
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