What causes Raynaud's disease?

Causes of Raynaud's Phenomenon

Raynaud's phenomenon is primarily caused by excessive vasoconstriction of digital arteries in response to cold exposure or emotional stress, and can be classified as primary (idiopathic) or secondary to underlying conditions, with systemic sclerosis being the most common associated disease. 1

Primary vs. Secondary Raynaud's

• Primary Raynaud's (Raynaud's disease) occurs as an isolated condition without an underlying disease and affects up to 20% of the general population 2
• Secondary Raynaud's is associated with underlying conditions and typically presents with more severe symptoms and complications 1

Pathophysiological Mechanisms

• The classic triphasic color changes (white-blue-red) represent:

  • White phase: excessive vasoconstriction and cessation of blood flow
  • Blue phase: cyanosis from residual desaturated blood
  • Red phase: hyperemia as blood flow is restored 3

• Key mechanisms in primary Raynaud's include:

  • Increased activation of sympathetic nerves in response to cold or emotion 3
  • Local vascular dysfunction with increased sensitivity of alpha-2 adrenergic receptors to cold 4
  • Possible imbalance between vasoconstrictors and vasodilators 3

Common Causes of Secondary Raynaud's

Autoimmune and Connective Tissue Diseases

• Systemic sclerosis (scleroderma) - most common association 1
• Systemic lupus erythematosus 1
• Rheumatoid arthritis 1

Vascular Disorders

• Thromboangiitis obliterans (Buerger's disease) - particularly in young tobacco smokers 1
• Atherosclerosis with peripheral arterial disease 1
• Thromboembolic disease (both macroembolic and microembolic) 1

Hematologic and Prothrombotic Conditions

• Clotting system abnormalities (protein C, protein S, or antithrombin III deficiencies) 1
• Factor V Leiden or prothrombin mutations 1
• Hyperhomocysteinemia 1
• Presence of lupus anticoagulant or anticardiolipin antibody 1

Occupational and Environmental Factors

• Chronic cold exposure 1
• Radiation-associated arteritis 1
• Vibration injury 1

Drug-Induced Causes

• Ergot alkaloids 1
• Bleomycin 1
• Clonidine 1
• Beta-blockers 1

Other Conditions

• Primary biliary cirrhosis 1
• Malignancies (paraneoplastic phenomenon) 1

Distinguishing Features Between Primary and Secondary Raynaud's

• Primary Raynaud's typically:

  • Presents at a younger age (teens to 30s) 5
  • Has symmetric involvement 5
  • Rarely leads to tissue damage or ulceration 2

• Secondary Raynaud's typically:

  • Presents at an older age (>30 years) 5
  • May involve the entire hand rather than just individual digits 6
  • Has more severe manifestations with potential for digital ulcers, gangrene, or osteomyelitis 7
  • Features both vasospasm and fixed blood vessel defects 8

Red Flags for Secondary Raynaud's

• Onset after age 30 5
• Severe, painful episodes 1
• Digital ulceration or tissue necrosis 1
• Asymmetric involvement 5
• Associated systemic symptoms (e.g., joint pain, skin changes, dysphagia) 1

Complications

• Digital ulcers occur in 22.5% of patients with systemic sclerosis-associated Raynaud's 7
• Gangrene occurs in 11% of patients with systemic sclerosis-associated Raynaud's 7
• Osteomyelitis may develop in severe cases 7
• In extreme cases, amputation might be required 7

Understanding the underlying cause of Raynaud's phenomenon is crucial for determining appropriate treatment strategies and preventing serious complications, particularly in secondary forms of the condition.