What are the causes of Raynaud's phenomenon?

Causes of Raynaud's Phenomenon

Primary vs. Secondary Classification

Raynaud's phenomenon is caused by excessive vasoconstriction of digital arteries in response to cold exposure or emotional stress, and is classified as either primary (idiopathic) or secondary to underlying conditions. 1

• Primary Raynaud's phenomenon occurs as an isolated condition without any underlying disease, representing a functional vasospastic disorder 1, 2
• Secondary Raynaud's phenomenon is associated with identifiable underlying pathology and typically presents with more severe manifestations including potential for digital ulcers, gangrene, or osteomyelitis 1

Causes of Secondary Raynaud's Phenomenon

Autoimmune and Connective Tissue Diseases

Systemic sclerosis (scleroderma) is the most common condition associated with secondary Raynaud's phenomenon. 1, 2

• Systemic lupus erythematosus 1, 2
• Rheumatoid arthritis 1, 2
• Mixed connective tissue disease/overlap syndromes 3

The pathophysiological mechanisms in connective tissue diseases remain incompletely understood but may involve a "pulmonary Raynaud's phenomenon" (pulmonary vasospasm), and immunological mechanisms are suggested by the presence of antinuclear antibodies, rheumatoid factor, immunoglobulin-G, and complement deposits in pulmonary vessel walls 3

Vascular and Thrombotic Disorders

• Thromboangiitis obliterans (Buerger's disease), particularly in young tobacco smokers 1, 2
• Atherosclerosis with peripheral arterial disease 1, 2
• Thromboembolic disease (both macroembolic and microembolic) 1, 2

Hematologic and Prothrombotic Conditions

• Clotting system abnormalities: protein C, protein S, or antithrombin III deficiencies 1, 2
• Factor V Leiden or prothrombin mutations 1, 2
• Hyperhomocysteinemia 1, 2
• Lupus anticoagulant or anticardiolipin antibody 1, 2
• Prothrombotic states associated with malignancies 2
• Inflammatory bowel disease-related prothrombotic states 2

Occupational and Environmental Exposures

• Chronic cold exposure 1, 2
• Vibration injury 1, 2
• Radiation-associated arteritis 1, 2

Drug-Induced Causes

• Ergot alkaloids 1, 2
• Bleomycin 1, 2
• Clonidine 1, 2
• Beta-blockers 1, 2

Other Associated Conditions

• Primary biliary cirrhosis 1, 2
• Malignancies (paraneoplastic phenomenon) 1, 2
• HIV-related conditions (though this represents pulmonary arterial hypertension rather than typical Raynaud's) 3

Key Distinguishing Features

Secondary Raynaud's differs from primary in several critical ways:

• May involve the entire hand rather than just individual digits 1, 4
• More severe manifestations with risk of digital ulcers (22.5% in systemic sclerosis), gangrene (11% in systemic sclerosis), or osteomyelitis 1
• Severe, painful episodes are a red flag for secondary disease 1, 2
• Associated systemic symptoms such as joint pain, skin changes, or dysphagia suggest underlying connective tissue disease 1

Pathophysiological Mechanisms

The underlying mechanisms vary by cause but include:

• Local abnormalities in digital arteries, possibly involving increased sensitivity of alpha-2 adrenergic receptors to cold 5
• Fixed blood vessel defects in secondary forms, not just vasospasm 6
• Deficiency or increased degradation of nitric oxide, possibly due to oxidative stress 5
• Involvement of vasoconstrictors including endothelin, serotonin, and thromboxane 5