What is the recommended treatment for a patient presenting with Raynaud's phenomenon?

Treatment of Raynaud's Phenomenon

All patients with Raynaud's phenomenon must implement non-pharmacological measures first, with nifedipine as first-line pharmacotherapy when medication is needed, escalating to phosphodiesterase-5 inhibitors for inadequate response, and reserving intravenous iloprost for severe refractory cases. 1

Non-Pharmacological Management (Mandatory First-Line for All Patients)

Every patient with Raynaud's must implement trigger avoidance and lifestyle modifications before or alongside any pharmacotherapy. 1 This is not optional—these measures form the foundation of treatment regardless of disease severity.

Essential Lifestyle Modifications

• Cold avoidance is critical: wear proper warm clothing including mittens (not gloves), insulated footwear, coat, and hat; use hand and foot warmers as needed 1, 2
• Smoking cessation is mandatory and non-negotiable—smoking directly worsens vasospasm and will undermine all other treatment efforts 1, 2
• Discontinue all triggering medications including beta-blockers, ergot alkaloids, bleomycin, and clonidine 1, 2
• Implement stress management techniques as emotional stress triggers attacks 1
• Avoid vibration injury and repetitive hand trauma, particularly in occupational settings 1
• Physical therapy with exercises to generate heat and stimulate blood flow can provide additional benefit 3, 1

Pharmacological Treatment Algorithm

First-Line Pharmacotherapy: Calcium Channel Blockers

Nifedipine (dihydropyridine-type calcium channel blocker) is the first-line pharmacological treatment for both primary and secondary Raynaud's. 1, 2 This recommendation is based on robust evidence showing it reduces both frequency and severity of attacks in approximately two-thirds of patients, with acceptable adverse effects and low cost. 1, 4

• Other dihydropyridine calcium channel blockers can be substituted if nifedipine is not tolerated 2
• Common adverse effects include hypotension, peripheral edema, and headaches 5

Second-Line Therapy: Phosphodiesterase-5 Inhibitors

When calcium channel blockers provide inadequate response, add or switch to phosphodiesterase-5 inhibitors (sildenafil or tadalafil). 1, 2 These agents effectively reduce frequency, duration, and severity of Raynaud's attacks. 1, 6

• PDE5 inhibitors are particularly valuable when digital ulcers are present, as they both heal existing ulcers and prevent new ones 1, 2
• Cost and off-label use may limit utilization 2

Third-Line Therapy: Intravenous Prostacyclin Analogues

For severe Raynaud's unresponsive to oral therapies, use intravenous iloprost. 1, 2 Iloprost is the most promising drug for secondary Raynaud's disease and has proven efficacy for healing digital ulcers. 1, 7

• Administer as continuous infusion over 6 hours daily for 5 consecutive days 8
• Initiate at 0.5 ng/kg/minute and titrate in 0.5 ng/kg/minute increments every 30 minutes according to tolerability, up to maximum 2 ng/kg/minute 8
• Monitor vital signs continuously—iloprost causes systemic vasodilation and may cause symptomatic hypotension 8
• Common adverse effects include headache, flushing, palpitations/tachycardia, nausea, vomiting, and dizziness 8

Management of Digital Ulcers

Digital ulcers represent a serious complication requiring aggressive treatment—they occur in 22.5% of systemic sclerosis patients with Raynaud's. 9

Prevention of New Digital Ulcers

Bosentan (endothelin receptor antagonist) is the most effective agent for preventing new digital ulcers, particularly in patients with multiple existing ulcers (≥4 ulcers at baseline). 1, 2, 5

• Bosentan prevents new ulcers but does not improve healing of existing ulcers 5, 10
• PDE5 inhibitors also prevent new digital ulcers and are effective alternatives 1, 2

Healing of Existing Digital Ulcers

For healing existing digital ulcers, use intravenous iloprost or phosphodiesterase-5 inhibitors. 1, 2

• Iloprost has proven efficacy for healing digital ulcers 1, 8
• PDE5 inhibitors improve healing rates 2
• Provide adequate wound care, pain control, and antibiotics only when infection is suspected 2

Treatment Algorithm Based on Severity

Mild Raynaud's (Primary or Secondary)

• Non-pharmacological measures alone 1
• Add nifedipine if symptoms significantly affect quality of life 2

Moderate Raynaud's or Inadequate Response to CCBs

• Continue non-pharmacological measures 1
• Add or switch to PDE5 inhibitors (sildenafil or tadalafil) 1, 2

Severe Raynaud's with Frequent Attacks Despite Above Treatments

• Continue non-pharmacological measures 1
• Intravenous iloprost for 5-day courses 1, 2, 8

Raynaud's with Digital Ulcers

• Prevention: Bosentan (first choice) or PDE5 inhibitors 1, 2
• Healing: Intravenous iloprost or PDE5 inhibitors 1, 2

Critical Pitfalls to Avoid

Always evaluate for systemic sclerosis and other connective tissue diseases in any patient with Raynaud's—delayed diagnosis leads to digital ulcers and poor outcomes. 1 Look for skin thickening, telangiectasias, digital pitting scars, abnormal nailfold capillaries, and positive autoantibodies (ANA, anticentromere, anti-Scl-70). 9, 10

Never continue triggering medications such as beta-blockers—this will undermine all treatment efforts. 1

Do not delay escalation in secondary Raynaud's—more aggressive therapy is required to prevent digital ulcers and tissue loss. 1 Secondary Raynaud's involves not only vasospasm but also fixed blood vessel defects, making ischemia more severe. 5, 6

Distinguish primary from secondary Raynaud's early: Primary Raynaud's typically affects younger women, is bilateral and symmetric, has no digital ulcers or tissue necrosis, and has normal physical examination between attacks. 9, 5 Secondary Raynaud's may involve the entire hand rather than isolated digits, presents with digital ulcers (22.5% of systemic sclerosis patients), and shows signs of underlying connective tissue disease. 9

Special Populations

Hepatic Impairment (Child-Pugh Class B or C)

• When using iloprost, initiate at 0.25 ng/kg/minute for 30 minutes, then titrate in 0.5 ng/kg/minute increments to maximum 2 ng/kg/minute 8

Renal Impairment (eGFR <30 mL/min)

• Initiate iloprost at standard dose (0.5 ng/kg/minute) or lower to 0.25 ng/kg/minute if not tolerated 8
• For patients on intermittent hemodialysis, administer iloprost after dialysis or start dialysis at least one hour after iloprost infusion ends 8