Raynaud phenomenon

Raynaud phenomenon refers to skin colour changes that occur in the fingers and toes from vasospasm.

Raynaud phenomenon is an exaggerated response to cold temperatures or emotional stress. It is due to abnormal vasoconstriction of digital and cutaneous arterioles often referred to as ‘vasospasm’. Vasospasm refers to the sudden constriction of blood vessels.

Raynaud phenomenon presents with classic skin changes that occur suddenly. These may be divided into three stages:

1. White: development of white fingers with sharp demarcation of colour change due to vasoconstriction.
2. Blue: vasoconstriction leads to tissue hypoxia and development of cyanosis.
3. Red: as vasoconstriction improves, there is an increase in blood flow leading to reperfusion and subsequent erythema

Raynaud phenomenon is common, often occurring in young women.

The true prevalence of Raynaud phenomenon is difficult to quantify due to variability in its definition. It is estimated that 3-20% of women and 3-14% of men may have the condition.

Raynaud phenomenon is more common in young women and often seen within families suggesting a genetic element. Primary Raynaud’s (discussed in aetiology) is more commonly seen in the second and third decade of life, whereas secondary Raynaud’s occurs in relation to the onset of the underlying disorder.

Regulation of skin blood vessels is complex, involving the nervous system, chemical mediators and non-neuronal pathways.

Vasoconstriction is a normal physiological response to cold temperature to maintain core body temperature. This is regulated by several pathways including the sympathetic nervous system, local chemical mediators (e.g. nitric oxide), sensory nerves and non-neuronal pathways.

Thermoregulation of the skin is primarily controlled by reflex activation of the sympathetic nervous system due to the direct effect of cold temperature on cutaneous vessels. Cold weather leads to activation of vasoconstriction through increasing the responsiveness of vascular smooth muscle to noradrenaline. Those with Raynaud phenomenon have a more exaggerated response leading to vasospasm and a dramatic fall in blood flow to the fingers and/or toes.

Other mechanisms involved in regulation of skin blood vessels may be affected in patients with secondary Raynaud phenomenon that is linked to an underlying disorder (see aetiology). These can include disrupted endothelial function, altered microvasculature and altered expression of chemical mediators.

Raynaud phenomenon may be primary or secondary.

Raynaud phenomenon may be divided into primary or secondary:

• Primary: Raynaud phenomenon without an underlying disorder (i.e. idiopathic Raynaud disease).
• Secondary: Raynaud phenomenon in association with an underlying disorder (e.g. systemic sclerosis).

Primary

Primary Raynaud phenomenon is thought to be an exaggerated response to cold temperatures. There is no underlying disorder and it usually presents between 15-30 years of age and is more common in women.

Secondary

Multiple conditions can be associated with Raynaud phenomenon. Due to the complex regulation of digital blood flow, the mechanism leading to Raynaud’s varies depending on the underlying aetiology.

Causes include:

• Connective tissue disease (i.e. rheumatological): systemic sclerosis, systemic lupus erythematosus, Sjögren’s syndrome and dermatomyositis/polymyositis.
• Medications: amphetamines, certain chemotherapy drugs.
• Haematological: cryoglobulinemia, cold agglutinin disease (type of haemolytic anaemia), paraprotein disorders.
• Occupational: frostbite, use of vibrating tools, trauma.

The hallmark of Raynaud phenomenon is a change in colour of fingers/toes from white, to blue to red.

Raynaud phenomenon is characterised by a sudden onset of cold fingers that are associated with three classic colour changes

• White: Sharp demarcated colour change to white due to vasoconstriction
• Blue: Development of tissue hypoxia due to vasoconstriction leads to cyanosis appearance
• Red: reperfusion following a period of iscahemia results in erythema.

The ischaemic phase usually last 15-20 minutes before evidence of reperfusion on rewarming. Episodes usually start with a single finger before spreading to involve more fingers of both hands in a symmetrical distribution. The thumb is usually spared.

Most commonly affected fingers:

• Index
• Middle
• Ring

NOTE: less common sites may include the nose, face, knees, nipples and ears.

Other features

• Paraesthesia
• Clumsiness
• Aching
• Ulceration (usually seen in severe secondary Raynaud’s due to critical iscahemia)
• Abnormal nail fold capillaries (suggest underlying rheumatic disease)

Diagnosis of Raynaud phenomenon can be made clinically by the classic colour changes.

The diagnosis of primary Raynaud phenomenon is usually suggestive by the clinical history, normal clinical examination and absence of features of an underlying cause. Assessment should include nailfold capillary microscopy.

Nailfold capillary microscopy

This involves using a specialised handheld dermatoscope to magnify the periungual area. This refers to the area around the nail and nail bed. Abnormal capillaries are suggestive of an underlying rheumatological condition.

Diagnosis of secondary Raynaud’s is suggestive by the classic appearance with features of an underlying disorder.

The history and clinical examination of a patient with Raynaud’s may be suggestive of a secondary cause. For example, there may be a history of working with vibrating tools or there may be features of an underlying rheumatological condition (e.g. sclerodactyly in systemic sclerosis). The presence of ulceration is suggestive of severe secondary Raynaud’s.

Features of secondary Raynaud’s

A number of features are suggestive of an underlying cause of Raynaud phenomenon.

• Older age of onset (>40 years)
• Known precipitant (e.g. vibrating tools)
• Male
• Digital ulceration
• Clinical features of an underlying condition (e.g. malar rash of SLE)
• Abnormal capillaries in the nail folds
• Asymmetrical episodes
• Abnormal laboratory findings (e.g. autoantibodies suggestive of secondary cause).

Further investigations

In patients with suspected secondary Raynaud phenomenon, further investigations are needed to look for an underlying cause. This usually includes blood tests, anti-nuclear antibodies and more specialist autoantibody screening.

• Full blood count
• Urea & electrolytes
• Bone profile
• C-reactive protein
• Complement
• Anti-nuclear antibody (ANA): see below
• Extractable nuclear antigens (ENA): see below
• Specific autoantibodies (e.g. anti-dsDNA seen in SLE)

ANA & ENA

Testing for ANA screens for the presence of antibodies that are reacting to nuclear antigens. Testing for ENA then looks for the specific nuclear antigen these antibodies are reacting to. ENA panels are usually added by the laboratory following a positive ANA. Certain staining patterns of ANA exist, which relates to the specific nuclear staining (e.g. speckled, diffuse, nucleolar). The staining pattern is suggestive of the underlying disorder.

Treatment of Raynaud phenomenon aims to reduce the intensity of attacks and prevent tissue loss.

The treatment of primary Raynaud phenomenon focuses on symptomatic treatment of episodes, reducing the intensity of attacks and improving quality of life. Tissue loss due to ischaemia and ulceration is less likely.

Treatment of secondary Raynaud phenomenon is more complicated as the disease can be more severe with risk of tissue loss. Treatment should be directed to the episodes as well as treating, or addressing, the underlying disorder.

Conservative

Conservative measures should be tried in the first instance in all patients. These include:

• Patient education
• Avoid cold exposure
• Wear warm gloves and socks
• Consider warming hands
• Aborting attacks: place hands in warm water, rotate arms in windmill pattern, rubbing hands together
• Avoid drugs that induce vasospasm: sumatriptan, phenylephrine (found in nasal decongestants), methylphenidate
• Smoking cessation

NOTE: non-selective beta-blocker are usually recommended to avoid in patients with severe Raynaud phenomenon.

Medical

Several medications can be used when conservative measure fail to reduce severity of episodes.

• Calcium-channel blockers (e.g. amlodipine or nifedipine)
• Phosphodiesterase type 5 inhibitors (e.g. sildenafil)
• Angiotensin II receptor antagonists (e.g. losartan)
• Topical nitrates: applied to a single, severely affected digit

Other options are available but efficacy is variable.

If patients develop severe, refractory digital ischaemia then referral to hospital may be required for further evaluation. It is important to exclude another cause of digital ischaemia and to consider other treatments including analgesia, calcium-channel blockers (if not already received) or intravenous prostaglandins. If refractory, local or regional anaesthesia may be required for pain control.

Surgical

Surgical techniques may be needed in patients with recurrent or severe symptoms despite exhausting medical therapies. A digital sympathectomy may be completed that involves dividing terminal sympathetic nerves. It is a highly specialised surgery and reversible causes of Raynaud’s should be excluded (e.g. treatable vasculitis).

Primary Raynaud phenomenon is a benign condition that disappears in up to one third of patients.

Primary Raynaud phenomenon is a benign disease, but some patients can be severely affected by recurrent episodes due to the impact on their quality of life. Secondary Raynaud phenomenon is more commonly associated with severe, progressive disease with risk of digital ischaemia, ulceration and necrosis.