Raynaud’s phenomenon (and Raynaud's disease)

Raynaud’s phenomenon is a disorder that causes vasospasm of cutaneous arterioles, temporarily limiting blood flow, occuring in response to cold exposure or stress. The most common symptoms are episodes of coldness, numbness, and tingling in the fingers or toes. Affected digits develop pallor, and sometimes have sequential skin colour change from white, to blue, to red. Primary Raynaud's phenomenon (syn. Raynaud's disease) is idiopathic, secondary Raynaud's phenomenon occurs as a result of an underlying disorder.

This chapter is set out as follows:

Primary Raynaud's phenomenon

Occurs more frequently in women than in men by a ratio of 9 to 1 ratio. The cause in unknown; however, risk factors include:

• Female
• Colder climate
• Lower body weight
• Smoking
  
• A history of atherosclerosis
• A history of migraines
• Having a psychological impairment
• Working in a manual occupation
  
• Taking oestrogens 
• A family history of Raynaud’s 

Secondary Raynaud's phenomenon

There are many causes including:

• Vibration injury
• Following the frequent use of vibrating tools

• Connective tissue disorders and vasculitis
• The most common association is with systemic sclerosis and mixed connective-tissue disease
• Systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome can also cause Raynaud's
• Raynaud's may be one of the first presenting features of connective tissue disorders, and identifying Raynaud's phenomenon in these patients presents a significant opportunity for early intervention in the course of these disorders

• Haematological disorders
• Cryoglobulinaemia and Waldenström's macroglobulinaemia

• Arterial disease
• Peripheral vascular disease
• Thromboangiitis obliterans (Buerger's disease) - very rare

• Neurological disorders
• Carpal Tunnel syndrome and the Thoracic Outlet syndrome (eg from a cervical rib)

• Drugs / other chemicals
• Non-selective beta-blockers, sumatriptan and ergotamine, oral contraceptives, clonidine, and ciclosporin
• Polyvinyl chloride exposure

• Various
  • Hypothyroidism, anorexia nervosa, chronic renal failure, paraneoplastic syndromes  

• Episodes of Raynaud's are very painful
  
• Primary Raynaud's phenomenon usually occurs in the second or third decade of life. Secondary Raynaud's phenomenon begins in accordance with the underlying disorder
  

Clinical features

• Distribution
• The hands and feet, especially the digits, are the main sites affected, although the nose and ears can also be involved
• In primary Raynaud's the clinical features are usually symmetrical with several digits involved
• In secondary Raynaud's one to a few digits are affected, sometimes asymmetrically. The thumb is more likely to be involved compared to primary Raynaud's

• Morphology
• Raynaud's is classically describer as triphasic, having three sequential phases:
  • White (vasoconstriction)
  • Blue (cyanosis)
  • Red (rapid blood reflow)
• Raynaud's can also be biphasic, without the cyanotic phase, or monophasic with only the pallor
• A clear line of demarcation exists between the ischaemic and unaffected areas
• Tissue necrosis is very uncommon in primary Raynaud's, but not uncommon in some cases of secondary Raynaud's, such as cryoglobulinaemia, and can lead to loss of digits

Red flags for secondary Raynaud 's phenomenon

• Males 
• Patients presenting aged over 40 
• Worsening symptoms
• Systemic symptoms
• Relevant cutaneous signs, including features of systemic sclerosis, which include:
  • Atrophy begins first in the nail pulps causing small painful ulcers that leave pitted scars. With time the nails become much smaller and the whole distal finger becomes atrophic
  • Sclerodactyly - fingers become swollen, and the skin feels tight and has a shiny appearance. The fingers become less mobile
  • Nailfold changes include enlargement of capillary loops, disorganisation of the normal distribution of capillaries, budding capillaries, extravasates, and loss of capillaries
  • Telangiectases
  • Calcinosis (calcium deposits) develops in the skin, particularly the fingers, hands and other bony areas. These can breakdown and discharge chalky material
  • Ulceration and gangrene may occur with minor trauma, or at the tips of the fingers, as a result of poor circulation
• Abnormal investigations including a significantly positive ANA titre

• Investigations are only needed for suspected cases of secondary Raynaud's phenomenon - refer to the chapter Investigations for more information

Step 1: general measures

• Reduce exposure to cold and other triggers
• Stop smoking, if appropriate
• Wear warm gloves / mittens, and warm socks - hand warmers or heated gloves can be particularly useful 
  
• Swinging arms around during an attack may help to restore a normal circulation to the fingers

Step 2: medical treatments

• First-line treatment - are the calcium-channel blockers (CCBs) such as nifedipine (30-180 mg daily) or amlodipine (5-20 mg daily). Treatment is usually started at the lowest dose and titrated upwards. Typically slow-release or long-acting formulations are used. Verapamil appears ineffective

• Phosphodiesterase (PDE) inhibitors - if CCBs fail to improve symptoms, then a PDE inhibitor may be used either in conjunction with the CCB if there is a partial response or as monotherapy. The recommended sildenafil dose is 20 mg daily, which may be titrated over 4 to 6 weeks to a maximum dose of 20 mg 3 times daily. This is an off-license use

• Due to the vasoactive properties of vasodilating medications that lead to adverse effects, including headaches and presyncope, drug intolerance may be a barrier to pharmacologic treatment

• Other treatments that have also been tried include 2 % nitroglycerin ointment applied to the affected areas, losartan, fluoxetine, and prazosin. The recommended losartan dose is 25-100 mg once daily. The recommended fluoxetine dose is 20 mg once daily. The recommended prazosin dose is 500 micrograms twice daily to 2 mg twice daily. The evidence base for these therapies is weaker than the evidence based for CCB and PDE inhibitor pharmacologic management

Step 3: more severe symptoms

• Very severe disease that results in ulceration or resorption of the fingertips may be treated by an intravenous infusion of prostaglandins