Raynaud's phenomenon

Introduction

Reversible vasospasm of the digital arteries which may result in ischemia of the digits.

Etiology

• primary (idiopathic) Raynaud's disease (70%)
• Raynaud's phenomenon is secondary to other conditions
  • connective tissue disease
    • systemic sclerosis (90%)
    • mixed connective tissue disease (85%)
    • systemic lupus erythematosus (10-44%)
    • Sjogren's syndrome (20%)
    • rheumatoid arthritis (5%)
    • dermatomyositis/polymyositis (20%)
  • pharmacologic agents
    • chemotherapeutic agents:
      • bleomycin, vincristine, vinblastine, cisplatin
    • heavy metals
    • caffeine
    • others:
      • beta blockers, ergotamine, narcotics, birth control pills, sympathomimetics, imipramine, bromocryptine, alpha-interferon, methysergide, cyclosporine, interferon, nicotine, clonidine
  • trauma/occupational
    • 90% of loggers - vibration white finger
    • carpal tunnel syndrome
    • polyvinyl chloride
    • jackhammer use
    • electric shock
    • cold injury
    • piano playing
  • arterial occlusive disease
    • vasculitis: thromboangiitis obliterans (associated with smoking)
    • peripheral arterial disease
    • thoracic outlet syndrome
  • hyperviscosity diseases
    • polycythemia
    • cryoglobulinemia
    • paraproteinemia, especially Waldenstrom's
    • cryofibrinogenemia
    • cold agglutinins
    • thrombocytosis
  • arterial disease
    • atherosclerosis
    • thromboangiitis obliterans (associated with smoking)
    • tobaccoism (aggravated by cigarette smoking)
  • neurologic disorders
    • intervertebral disk disease
    • syringomyelia
    • spinal cord tumors
    • stroke
    • poliomyelitis
    • carpal tunnel syndrome
  • migraine syndrome (10%)
  • primary pulmonary hypertension

Epidemiology

• primary
  • common
  • most patients 15-20 years
  • predominance of females
  • affects 3-5% of male population, 4-9% of female population
  • < 50% of affected individuals seek medical attention
• secondary
  • most individuals > 35 years
  • no sex preference
  • suspect if patient is male, >35 or <15 years of age
• 8% of men, 11% of women (mean age 54 years)

Pathology

• vasospasm
• increased sympathetic tone or increased density or sensitivity of alpha 2-adrenergic receptors
• endothelial damage
• reduced release of nitric oxide & venodilation secondary to endothelial damage
• intimal proliferation
• fixed vascular obstruction
• inflammation & release of vasospastic mediators
  • endothelin-1
  • thromboxane A2
• three phases
  • pallor: vasospasm halts blood flow
  • cyanosis: blood moving slowly through capillaries becomes deoxygenated
  • redness: previously constricted arterioles dilate during hyperemic phase

Clinical manifestations

• primary Raynaud's phenomenon
  • painful digits exacerbated by exposure to cold temperature or emotional stress
  • pallor often followed by cyanosis, then redness
  • affects fingers more often than toes, may spare thumb
  • may also affect earlobes, lips or tip of nose
  • symptoms last 15-30 minutes after rewarming
  • paresthesias may occur during rewarming
• secondary Raynaud's phenomenon
  • symptoms similar to primary Raynaud's phenomenon, but may be more severe with rapid progression
  • symptoms may be unilateral
  • manifestations of precipitating etiology may be present
  • digital pitting scar or gangrene may occur
  • digital pitting & ulceration of the fingertips typically reflect ischemic injury
    • occurs rarely in primary (idiopathic) Raynaud disease but commonly in patients with secondary Raynaud phenomenon
• most cases without underlying connective tissue disease are mild

Criteria for diagnosis of primary Raynaud's phenomenon

• episodic attacks with acral pallor or cyanosis
• strong & symmetric peripheral pulses
• no pitting edema, gangrene or ulcerations
• normal finger & toenail capillaries
• antinuclear antibody (ANA) titer < 1:100 (i.e. 1:10)
• ESR < 20 mm/hr

Laboratory

• serology for connective tissue disease not routinely indicated for patients with primary Raynaud's phenomenon
  • yield is low & not cost effective, unless
    • severe & prolonged vasospasms
    • asymmetric involvement of digits
    • digital pitting

Diagnostic procedures

• capillaroscopy for differentiation of primary from secondary Raynaud's phenomenon

Complications

< 10% of patients with isolated Raynaud's phenomenon will develop systemic connective tissue disease within 10 years

Differential diagnosis

• blue toe syndrome
• erythromelagia

Management

• general measures
  • avoid exposure to the cold
  • protect hands & feet from cold & trauma
  • cessation of smoking (smoking exacerbates Raynaud's phenomenon)
  • avoid over the counter sympathomimetics
• pharmacologic agents
  • dihydropyridine calcium channel blockers prior to precipitating event
    • amlodipine
    • nifedipine (Procardia)
  • anti-platelet agent
  • topical nitroglycerin applied to fingers or toes
  • prazosin
  • reserpine
  • guanethidine
  • bosentan may be effective in preventing recurrences of digital ulcers in severe Raynaud's disease
  • vasodilator
    • prostacyclin analogs
      • intravenous epoprostenol for acutely ischemic digit(s)
      • iloprost (not available in US)
        • improved symptoms of 47% of patients who failed nefedipine
    • ACE inhibitors (controversial)
    • sildenafil (Viagra) 50 mg BID; tadalafil
      • controversial
      • individualized effect taken before or during an episode
  • pentoxifylline (controversial)
  • serotonin receptor antagonists
    • ketanserin (not available in US)
    • phenoxybenzamine
    • affects vasoconstriction & platelet aggregation
• chronic pain or digital ulceration failing conservative management
  • sympathetic ganglion blockade
  • Botox 100 units injected into the hand effective (84%)
• prognosis
  • primary Raynaud's phenomenon carries low risk of progression
  • 36% of cases without underlying connective tissue disease persist for 7 years

More general terms

• peripheral vascular disease (PVD)
• sign/symptom
• syndrome

Additional terms

• blue toe syndrome
• erythromelalgia (erythermalgia)

Patient information

Raynaud's disease patient information