What is the general treatment for Raynaud's disease?

Treatment of Raynaud's Phenomenon

All patients with Raynaud's phenomenon should begin with non-pharmacological measures and trigger avoidance, followed by oral nifedipine (a dihydropyridine calcium channel blocker) as first-line pharmacotherapy if symptoms impair quality of life, with escalation to phosphodiesterase-5 inhibitors for inadequate response, and intravenous iloprost reserved for severe, refractory disease. 1, 2

Non-Pharmacological Management (Foundation for All Patients)

Every patient must implement lifestyle modifications before or alongside any medication: 2

• Cold avoidance measures including wearing proper warm clothing (coat, mittens rather than gloves, hat, insulated footwear) and using hand/foot warmers to reduce attack frequency and severity 2, 3
• Mandatory smoking cessation as tobacco directly worsens vasospasm and undermines all treatment efforts 2, 3
• Discontinue triggering medications including beta-blockers, ergot alkaloids, bleomycin, and clonidine 2, 3
• Stress management techniques to reduce emotionally-triggered attacks 2
• Avoid vibration injury and repetitive hand trauma, particularly in occupational settings 2
• Physical therapy with exercises to generate heat and stimulate blood flow 2, 3

Pharmacological Treatment Algorithm

First-Line: Calcium Channel Blockers

Nifedipine (dihydropyridine-type calcium channel blocker) is the established first-line pharmacotherapy for both primary and secondary Raynaud's, reducing frequency and severity of attacks in approximately two-thirds of patients with acceptable adverse effects and low cost 1, 2, 3

• Other dihydropyridine calcium channel blockers can be substituted if nifedipine is poorly tolerated or ineffective 3
• Common adverse effects include hypotension, peripheral edema, and headaches 4

Second-Line: Phosphodiesterase-5 Inhibitors

Add or switch to PDE5 inhibitors (sildenafil or tadalafil) when calcium channel blockers provide inadequate response 1, 2, 3

• Meta-analysis of six RCTs demonstrated significant improvement in Raynaud's condition score (mean difference −0.46, p=0.002), daily frequency of attacks (mean difference −0.49, p<0.0001), and daily duration of attacks (−14.62 minutes, p<0.0001) 1
• PDE5 inhibitors are particularly valuable if digital ulcers are present, as they promote both healing and prevention 1, 2, 3
• Cost and off-label use may limit utilization in some healthcare systems 1

Third-Line: Intravenous Prostacyclin Analogues

Intravenous iloprost should be considered for severe Raynaud's unresponsive to oral therapies, particularly with critical digital ischemia or risk of tissue loss 1, 2, 3

• Iloprost is the only prostacyclin analogue with proven efficacy in systemic sclerosis-associated Raynaud's 1, 3
• Effective for reducing frequency and severity of attacks and healing digital ulcers 1, 2, 3
• Adverse effects include tachycardia, hypotension, jaw pain, gastrointestinal symptoms, and headache 1

Management of Digital Ulcers

Prevention of New Digital Ulcers

Bosentan (endothelin receptor antagonist) should be considered specifically for preventing new digital ulcers in patients with systemic sclerosis, particularly those with ≥4 existing ulcers at baseline 1, 2, 3

• Bosentan prevents new digital ulcers but does not improve healing of existing ulcers 1, 3
• Other endothelin receptor antagonists (macitentan) showed negative results in RCTs and are not recommended 1

Healing of Existing Digital Ulcers

For healing digital ulcers, use PDE5 inhibitors and/or intravenous iloprost: 1, 2, 3

• Intravenous iloprost has proven efficacy for digital ulcer healing 1, 2, 3
• PDE5 inhibitors effectively improve healing, though prevention data are mixed 1, 2, 3
• Specialized wound care, appropriate pain control, and antibiotics only when infection is suspected are essential 3

Critical Pitfalls to Avoid

Always evaluate for systemic sclerosis and other connective tissue diseases in secondary Raynaud's, as delayed diagnosis leads to digital ulcers and poor outcomes 2

Never continue triggering medications (beta-blockers, vasoconstrictors) as they will undermine all treatment efforts 2

Do not delay escalation in secondary Raynaud's, as more aggressive therapy is required to prevent digital ulcers and tissue loss 2

Recognize that secondary Raynaud's requires more aggressive pharmacological intervention compared to primary Raynaud's due to fixed vascular defects in addition to vasospasm 5, 4

Additional Considerations

• Topical nitrates (nitroglycerin or glyceryl trinitrate) may provide ancillary benefit for acute painful episodes, though headache can be limiting and combination with PDE5 inhibitors is contraindicated 1, 3
• Antiplatelet therapy with low-dose aspirin is recommended for all patients with secondary Raynaud's due to structural vessel damage 5
• Fluoxetine was deprioritized in the 2023 EULAR update and is not included in current recommendations 1
• Surgical interventions (digital sympathectomy, botulinum toxin injections, fat grafting) have limited evidence from small observational studies and should be reserved for refractory cases 1, 3