What is the differential diagnosis (Ddx) for cold hands?

Differential Diagnosis for Cold Hands

The differential diagnosis for cold hands requires systematic evaluation of vascular, autoimmune, environmental, and arterial occlusive causes, with Raynaud's phenomenon (primary or secondary) being the most common etiology, followed by peripheral arterial disease, connective tissue disorders, and environmental exposure. 1

Primary Vascular Disorders

Raynaud's Phenomenon is the leading cause to consider:

• Primary Raynaud's disease affects 5-20% of the European population, occurring four times more often in women than men, typically manifesting around age 40 1
• Presents as isolated episodic vasospasm affecting individual digits (not entire hand) with characteristic white-blue-red color changes triggered by cold or stress 1, 2
• Episodes last an average of 23 minutes but can persist for hours 1
• Digital blood pressure measurements are typically normal in primary Raynaud's (decreased pressure in only 5 of 123 fingers with cold sensitivity) 3

Secondary Raynaud's phenomenon has distinct features:

• Involves entire hands rather than just individual digits 1, 2
• Associated with severe, painful episodes that can progress to digital ulcers, gangrene, or osteomyelitis 1, 2
• Digital blood pressure is significantly low in 90 of 91 fingers with cold sensitivity in arterial occlusion cases 1, 3

Arterial Occlusive Disease

Peripheral arterial disease must be differentiated from vasospastic disorders:

• Digital blood pressure measurement is essential—significantly low pressures indicate arterial occlusion rather than vasospasm 1, 3
• Particularly suspect in patients with diabetes, hypertension, or history of peripheral vascular disease 4, 1
• Unilateral cold hand strongly suggests arterial occlusion or steal syndrome rather than Raynaud's 1
• Thromboangiitis obliterans (Buerger's disease) should be considered, especially in young tobacco smokers 5

Connective Tissue and Autoimmune Diseases

Systemic sclerosis (scleroderma) is the most common underlying disease associated with secondary Raynaud's:

• Look for skin thickening, digital pitting scars, and calcinosis 1
• A relative digital systolic pressure <70% at low local finger cooling temperatures (15°C and 10°C) has 97.1% sensitivity in differentiating scleroderma-spectrum RP from primary RP 6
• Thermography shows differences between mean temperatures of metacarpus and digits ≥3°C suggest RP 7

Other autoimmune conditions to consider:

• Systemic lupus erythematosus—check for malar rash, photosensitivity, and joint symptoms 1, 5
• Rheumatoid arthritis—mainly targets MCPJs, PIPJs, and wrists (not DIPJs like osteoarthritis) 4, 5
• Inflammatory myopathies—look for mechanic's hands, fever, myositis, and arthritis 4

Hand Osteoarthritis

While primarily causing joint symptoms, HOA enters the differential:

• Psoriatic arthritis may target DIPJs or affect just one ray 4
• Gout may superimpose on pre-existing HOA 4
• Haemochromatosis mainly targets MCPJs and wrists 4
• Diagnosis depends on composite features: age, female gender, joint distribution, bone swelling (not soft tissue), and radiographic changes 4

Environmental and Occupational Causes

Frostbite presents distinctly:

• Numbness with complete inability to sense touch 4
• Progression from pale to hardened and dark skin 4
• Fingers are particularly susceptible extremities 4
• Tissue should be rewarmed at 37-40°C (98.6-104°F) if refreezing risk is negligible 4

Cold sensitivity without vasospasm:

• Lower baseline skin perfusion and temperature but normal reagibility to reflex contractile stimulus 8
• Thermal asymmetry >0.5°C between hands or >1°C between metacarpus and digits suggests pathology 7

Critical Red Flags Requiring Urgent Evaluation

Immediate vascular surgery referral is required for:

• Digital ulcers, tissue necrosis, or gangrene 1, 2
• Unilateral presentation suggesting arterial occlusion 1
• Monomelic ischemic neuropathy (acute neuropathy with global muscle pain, weakness, and warm hand with palpable pulses) 4

Essential Diagnostic Workup

Initial assessment:

• Digital blood pressure measurement to differentiate arterial occlusion from vasospastic disorders 1, 3
• Pulse oximetry (noting that readings may be unreliable with cold hands, especially in severe Raynaud's with collagen vascular diseases) 4
• Antinuclear antibody (ANA) testing for connective tissue disease 1
• Complete blood count and inflammatory markers 1

Advanced testing when indicated:

• Anti-Sjögren syndrome A antibody if dry eyes or mouth present 2
• Prothrombotic workup (protein C, protein S, antithrombin III, Factor V Leiden, prothrombin mutations, lupus anticoagulant, anticardiolipin antibody) if vascular thrombosis suspected 2, 5
• Viral serology (HBV, HCV, HIV) if systemic disease suspected 2
• Plain radiographs if joint involvement suggests HOA or inflammatory arthropathy 4

Common Pitfalls to Avoid

• Missing secondary causes like systemic sclerosis can lead to delayed treatment and poor outcomes 2
• Assuming all cold hands are benign primary Raynaud's without checking digital blood pressures 3
• Using beta-blockers, ergot alkaloids, bleomycin, or clonidine can induce or worsen Raynaud's 2, 5
• Failing to remove constricting items (jewelry, tight clothing) in frostbite cases 4
• Delaying vascular surgery referral when digital necrosis is present 1