Raynaud’s phenomenon is a common medical condition that represents an exaggerated vasoconstrictor response to normal stimuli such as cold or emotional stress.
In a minority of patients it is a manifestation of a more serious underlying disease.
The decision to reassure patients, treat with drug therapy or refer for specialist investigation can be difficult. The differential diagnosis of Raynaud’s phenomenon includes a number of severe and complex disorders but these are rare (see table bottom).
There are complex but important mechanisms that regulate blood flow through key thermoregulatory vascular beds including the hands, feet, face and other extremities.
This is an adaptive mechanism for regulation of normal body temperature and to ensure appropriate distribution of blood flow. When the central temperature falls or at times of increased stress the blood flow to these territories is reduced by vasoconstriction of small arteries and arterioles.
While this can be a normal response, when vasoconstriction is disproportionate signs and symptoms of Raynaud’s phenomenon may develop.
The aetiology and pathogenesis of Raynaud’s phenomenon are poorly understood. Whether an increase in sensitivity to vasoconstrictor stimuli or an attenuated response to vasodilator signals is more important is unclear.
There is an ongoing debate about whether a local defect in the microcirculation or larger arterial blood vessels may underlie Raynaud’s phenomenon, or whether a defect in central control of the circulation is more significant. Both mechanisms may operate.
It has been shown that there is an excess of vasoconstrictor adrenergic receptors in the small blood vessels of patients with Raynaud’s phenomenon secondary to connective tissue disease. The variable response of patients to pharmacological therapy is consistent with varied pathogenic mechanisms in different individuals.
The first feature is blanching of the skin, which causes pallor.
This is followed by stagnation of blood within the cutaneous circulation, leading to cyanosis.
Finally, as the vasospasm reverses there is increased blood flow to the affected sites, leading to redness or suffusion.
All of these phases may cause additional symptoms such as pain, paraesthesiae or numbness. There is often impairment of fine finger movement due to the sensory disturbance during an attack.
Raynaud’s phenomenon is classified as primary when there is no underlying or associated medical condition or secondary when it occurs in the context of another condition.
Distinguishing these groups is central to management and since the first medical assessment is very likely to be in general practice it is relevant to consider the main features of each group of patients.
Primary Raynaud’s phenomenon was previously termed Raynaud’s disease, but this term is not favoured as it may lead to confusion.
Up to 10 per cent of young adult females describe some symptoms of cold-induced vasospasm of the extremities without other health problems.
Onset of symptoms in the teenage years and having other members of the family with the disease are clinical hallmarks of primary Raynaud’s phenomenon.
Secondary Raynaud’s is often associated with an underlying connective tissue disease (CTD). One condition that is almost always accompanied by Raynaud’s phenomenon is systemic sclerosis (SSc). More than 95 per cent of SSc cases report significant Raynaud's phenomenon.
Polymyositis, dermatomyositis, systemic lupus erythematosus and overlap CTD are also accompanied by Raynaud's phenomenon but less frequently.
An important group of patient have some underlying features of CTD, for example arthralgia or photosensitivity, but do not fulfil classification criteria for a defined disorder. These are termed undifferentiated connective tissue disease.
Finally, there are cases that have isolated Raynaud’s phenomenon but in whom investigations such as antinuclear antibody (ANA) testing or nailfold capillaroscopy are abnormal. Positive ANA and Raynaud’s phenomenon is designated autoimmune Raynaud’s phenomenon.
Identification of these cases is important because a proportion of cases of isolated Raynaud’s phenomenon with positive ANA and abnormal nailfold capillaries may develop a defined CTD during follow-up. These tests have a very strong negative predictive value and cases that are ANA negative and have normal capillaroscopy and do not have clinical evidence of CTD are extremely unlikely to progress.
All patients in whom secondary Raynaud’s is suspected should be further evaluated.
There are a few dedicated Raynaud’s clinics but most patients are likely to be referred to rheumatologists.
Treatment of Raynaud’s phenomenon should initially focus on trying to avoid triggers.
All patients with a history of Raynaud’s should be strongly advised to avoid smoking. Some patients find an antioxidant supplement helpful.
Prescription vasodilators can be beneficial and calcium channel blockers are widely used. Side effects including postural hypotension, headache, dizziness, ankle swelling and gastroesophageal reflux should be explained.
Other oral agents reported to be helpful include angiotensin receptor blockers, SSRIs and topical nitrate preparations. These are not currently licensed for treatment.
Complications of severe Raynaud’s phenomenon generally occur in the presence of associated structural vascular disease, such as vasculitis or in SSc. All of these should involve hospital-based management. In such cases ischaemic digital ulceration, critical ischaemia or gangrene may occur.
Ulcers should be managed with local treatment of infection, protection from local trauma and optimising Raynaud’s therapy. Healing and prevention of digital ulcers can be helped with IV therapy with prostacyclin analogues.
Some of the therapies that are effective in other vascular complications of CTD, for example pulmonary arterial hypertension, have been used for ischaemic digital ulceration in SSc.
Published reports suggest that there is potential benefit from using PDE5 inhibitors in severe Raynaud’s, digital ulceration or critical digital ischaemia.
The endothelin antagonist bosentan has been shown to be effective in reducing new digital ulcer formation if SSc in clinical trials.
The majority of patients who have primary Raynaud’s can be reassured that they are unlikely to develop any more serious related medical condition and may be managed in primary care.
Professor Denton is professor of experimental rheumatology, University College London and honorary consultant rheumatologist, Royal Free Hospital, London
Raynaud's awareness month runs from 1–28 February 2007