What are the recommended treatment options for Raynaud's phenomenon, including first‑line and second‑line therapies?

Treatment Options for Raynaud's Phenomenon

Extended-release nifedipine is the recommended first-line pharmacological therapy for both primary and secondary Raynaud's phenomenon, reducing attack frequency and severity in approximately two-thirds of patients with acceptable tolerability and low cost. 1

Non-Pharmacological Management (Essential Foundation for All Patients)

Before initiating or alongside any medication, implement these mandatory lifestyle modifications:

• Cold avoidance: Use insulated mittens (not gloves), footwear, hats, coats, and hand/foot warmers to minimize exposure. 1
• Smoking cessation: Tobacco directly aggravates vasospasm and reduces treatment efficacy—this is non-negotiable. 1
• Medication review: Discontinue vasospasm-triggering drugs including beta-blockers, ergot alkaloids, bleomycin, and clonidine when clinically feasible. 1
• Stress reduction: Implement techniques to minimize emotionally triggered attacks. 1
• Occupational modifications: Avoid vibration injury and repetitive hand trauma, particularly in work settings. 1
• Physical therapy: Structured exercises that stimulate peripheral blood flow and generate heat provide benefit. 1

Pharmacological Treatment Algorithm

First-Line: Calcium Channel Blockers

• Nifedipine (extended-release) is the gold standard initial agent, supported by multiple meta-analyses demonstrating reduction in both attack frequency and severity. 1
• If nifedipine is not tolerated due to headache, peripheral edema, or hypotension, switch to alternative dihydropyridines (felodipine, isradipine) or diltiazem, though efficacy may be modestly lower. 1

Second-Line: Phosphodiesterase-5 Inhibitors

• When calcium channel blockers provide inadequate response, add or switch to sildenafil or tadalafil. 1
• These agents effectively lower attack frequency, duration, and severity. 1
• Particularly valuable when digital ulcers are present, as they promote both ulcer healing and prevention. 1
• Cost considerations and off-label status may limit accessibility but should not prevent use when clinically indicated. 1

Third-Line: Intravenous Prostacyclin Analogue

• For severe Raynaud's refractory to oral therapies, intravenous iloprost is the next step. 1
• Demonstrated efficacy in reducing attack frequency and severity, with particular effectiveness for healing existing digital ulcers. 1
• This requires hospitalization or infusion center administration. 1

Severity-Based Treatment Pathway

Mild disease (infrequent attacks, no tissue damage):

• Non-pharmacological measures alone. 1
• Add nifedipine only if quality of life is impaired. 1

Moderate to severe disease or inadequate response to calcium channel blockers:

• Introduce or switch to phosphodiesterase-5 inhibitor (sildenafil or tadalafil). 1

Severe refractory disease (frequent attacks despite above therapies):

• Consider intravenous iloprost. 1

Presence of digital ulcers:

• For prevention: Bosentan is the most effective agent, especially in systemic sclerosis patients with ≥4 baseline ulcers. 1
• For healing: Use either intravenous iloprost or phosphodiesterase-5 inhibitors. 1

Digital Ulcer Management

Prevention

• Bosentan (endothelin receptor antagonist) is the most effective preventive agent for new digital ulcers in systemic sclerosis patients with multiple baseline ulcers. 1
• Phosphodiesterase-5 inhibitors also contribute to prevention, though study results are mixed. 1

Healing

• Both intravenous iloprost and phosphodiesterase-5 inhibitors have proven benefit for promoting healing of established ulcers. 1
• Specialized wound-care teams should manage ulcer care, reserving antibiotics strictly for suspected infection and providing adequate analgesia. 1

Additional Treatment Options

• Topical nitroglycerin may provide ancillary relief for acute painful episodes. 1
• Fluoxetine (selective serotonin reuptake inhibitor) can be considered in refractory cases, though supporting evidence is limited to small studies. 1
• Antiplatelet therapy with low-dose aspirin is recommended for all patients with secondary Raynaud's due to structural vessel damage. 2

Interventional Approaches for Refractory Disease

• Digital sympathectomy may be employed for persistent ulcer-related problems unresponsive to maximal medical therapy. 1
• Emerging therapies including botulinum toxin injections or autologous fat grafting show promise for ulcer healing and prevention. 1

Critical Red Flags Requiring Urgent Assessment

• Severe painful episodes with digital ulceration or tissue necrosis. 1
• Systemic symptoms including joint pain, skin changes, dysphagia, weight loss, or fever. 1
• Involvement of the entire hand rather than isolated digits. 1
• New onset after age 60, suggesting possible atherosclerotic disease. 1
• Systemic sclerosis must always be screened for, as Raynaud's is present in nearly all systemic sclerosis patients and often represents the initial manifestation. 1

Diagnostic Workup for Suspected Secondary Raynaud's

When red flags are present, obtain:

• Complete blood count with differential. 1
• Erythrocyte sedimentation rate. 1
• Antinuclear antibody panel. 1
• Rheumatoid factor. 1
• Anticentromere and anti-Scl-70 antibodies. 1
• Anticardiolipin antibodies and lupus anticoagulant testing. 1

Common Pitfalls to Avoid

• Continuing vasoconstrictive medications (beta-blockers, ergot derivatives) will undermine all treatment efforts—these must be discontinued. 1
• Delaying escalation in secondary Raynaud's leads to digital ulcers and poor outcomes; secondary disease requires more aggressive therapy than primary. 1
• Failing to screen for systemic sclerosis results in delayed diagnosis and increased morbidity from digital ulcers. 1
• Treating digital ulcers with antibiotics without infection is inappropriate; reserve antibiotics only for suspected infection. 1