Raynaud Phenomenon

A vasospastic disorder in which the digits go white, then blue, then red, with pain, tingling and numbness. Necrosis is possible in severe cases. Raynaud phenomenon is categorised as either primary or secondary, and primary (benign) is by far the more common.

Attacks occur more frequently in women, about 20% to 30%, particularly in the teens to twenties, with a female-to-male ratio of about 9 to 1. Prevalence is higher in colder climates.

In primary Raynaud phenomenon an increase in alpha-2 adrenergic sensitivity in the digital and cutaneous vessels produces the vasoconstrictive response to cold. In secondary disease the underlying illness disrupts normal vessel reactivity, and endothelin-1 released by endothelial cells drives the vasoconstriction.

Secondary causes

• Connective tissue disease — most commonly scleroderma, SLE, Sjogren syndrome and antiphospholipid syndrome
• Occupational vibration exposure — hand-arm vibration syndrome, mostly in males; also polyvinyl chloride exposure and cold injury at work
• Drugs — non-selective beta blockers, sympathomimetics, ergotamine and antimigraine agents, interferon alpha and beta, ciclosporin
• Obstructive vascular disease — a frequent cause over age 60: thromboangiitis obliterans, microemboli, diabetic angiopathy, atherosclerosis
• Haematological — polycythaemia, cold agglutinin disease, leukaemia
• Infection — parvovirus B19, CMV, hepatitis B and C
• Other — fibromyalgia, arteriovenous fistula, malignancy

History

Fingers whiten, then turn blue, then red, painfully — triggered by cold, wet weather, emotional upset or smoking; attacks last minutes to hours.

Ask about age of onset, which areas are affected, whether it is symmetrical, whether there are digital ulcers, and how severe the attacks are. Elicit systemic symptoms to rule out a secondary cause.

Primary Raynaud’s usually starts in the teens or early 20s as an exaggerated cold response. Onset after age 30, or in a male, suggests an underlying connective tissue disease — also suspect a secondary cause with ulceration, year-round symptoms or more severe pain.

Examination

Colour change is usually symmetrical on both hands, and the thumb is typically spared; thumb involvement suggests secondary disease. Vasospasm can also affect the face, ears, knees or nipples.

Attacks are generally less severe in primary than in secondary Raynaud phenomenon. In severe attacks, usually secondary, digital ulceration of the fingertips and toes may occur from prolonged vasoconstriction and tissue ischaemia, and gangrene or loss of digits can follow.

Livedo reticularis — purplish mottling of the skin — may be seen during an attack. It reverses with rewarming in primary disease but is irreversible with secondary causes such as antiphospholipid syndrome, vasculitis, cold agglutinin disease or peripheral vascular disease.

Investigations

Nailfold capillary microscopy is used to differentiate primary from secondary Raynaud phenomenon.

Screen for connective tissue disease if secondary Raynaud’s is suspected: ANA, rheumatoid factor, ESR, FBC, TFTs.

Management

Most primary Raynaud’s responds to conservative measures: avoid cold exposure, stay warm, avoid stimulants, manage anxiety and emotional stress, and stop smoking. Warm the affected hand slowly during an attack.

If conservative therapy fails, add a vasodilator. Dihydropyridine calcium channel blockers are the first-line pharmacological treatment — amlodipine or nifedipine, started at the lowest dose and titrated every 4 weeks according to response, with blood pressure monitoring. Topical nitrates are an alternative.

For secondary Raynaud’s with recurrent digital ulceration in connective tissue disease such as systemic sclerosis, bosentan blocks the vasoconstrictive effect of endothelin-1. Low-dose aspirin is used where there is a history of ischaemic ulceration, with clopidogrel or dipyridamole if aspirin is not tolerated — check eTG or AMH for doses. Sympathectomy is reserved for severe refractory cases.

Refer to rheumatology for secondary Raynaud phenomenon; primary Raynaud phenomenon can be managed in general practice.

Prognosis

Spontaneous remission may occur in primary Raynaud phenomenon, but is not seen in secondary disease. Prognosis in young people with primary disease is good, with little morbidity or mortality — but if lifestyle does not change, or the patient continues smoking, ischaemia can affect the fingertips and lead to necrosis.