What are the treatment options for a patient diagnosed with Raynaud's disease?

Treatment of Raynaud's Phenomenon

All patients with Raynaud's should begin with non-pharmacological measures including cold avoidance and smoking cessation, followed by nifedipine as first-line pharmacotherapy if symptoms affect quality of life, with escalation to phosphodiesterase-5 inhibitors for inadequate response and intravenous iloprost for severe refractory disease. 1

Non-Pharmacological Management (Foundation for All Patients)

Every patient must implement lifestyle modifications before or alongside any medication: 1

• Cold avoidance using proper warm clothing, mittens (not gloves), hats, insulated footwear, and hand/foot warmers to reduce attack frequency and severity 1
• Mandatory smoking cessation as tobacco directly worsens vasospasm and undermines all treatment efforts 1
• Discontinue triggering medications including beta-blockers, ergot alkaloids, bleomycin, and clonidine 1
• Stress management techniques to reduce emotionally-triggered 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 1

Pharmacological Treatment Algorithm

First-Line: Calcium Channel Blockers

Nifedipine (dihydropyridine-type calcium channel blocker) is the gold standard first-line therapy recommended by the European League Against Rheumatism for both primary and secondary Raynaud's, reducing both frequency and severity of attacks with acceptable adverse effects and low cost. 1 Meta-analyses of randomized controlled trials confirm its efficacy. 1

• Other dihydropyridine calcium channel blockers can be substituted if nifedipine is poorly tolerated 1
• Common adverse effects include ankle swelling, headache, flushing, and hypotension 2, 3
• Long-acting or retard preparations may reduce adverse effects 4

Second-Line: Phosphodiesterase-5 Inhibitors

For inadequate response to calcium channel blockers, add or switch to sildenafil or tadalafil, which effectively reduce frequency and severity of attacks. 1 These agents also heal existing digital ulcers and may prevent new ones, though prevention results are mixed. 1

• Cost and off-label use may limit utilization 1
• This class represents a significant advance in treatment options 3

Third-Line: Intravenous Prostacyclin Analogues

Intravenous iloprost should be used for severe Raynaud's unresponsive to oral therapies, with proven efficacy for both reducing attack frequency/severity and healing digital ulcers. 1 This is the most promising drug for severe secondary Raynaud's disease. 5

• Disadvantaged by parenteral route of administration 4
• Reserved for the most severe forms, especially those with tissue loss 6

Management of Digital Ulcers (Secondary Raynaud's)

For patients with multiple existing digital ulcers, particularly in systemic sclerosis:

• Bosentan (endothelin receptor antagonist) prevents new digital ulcers but does not affect healing time 1, 3
• Phosphodiesterase-5 inhibitors both heal existing ulcers and may prevent new ones 1
• Intravenous iloprost is proven effective for healing existing digital ulcers 1

Critical Pitfalls to Avoid

Always evaluate for systemic sclerosis and other connective tissue diseases, as delayed diagnosis leads to digital ulcers and poor outcomes. 1 Look specifically for:

• Severe, painful episodes with digital ulceration (red flag for secondary Raynaud's) 7
• Associated systemic symptoms including joint pain, skin changes, dysphagia, weight loss, malaise, fatigue, fever, photosensitivity, dry eyes, or dry mouth 8
• Involvement of entire hand rather than individual digits 8

Never continue triggering medications such as beta-blockers and other vasoconstrictors, as they will undermine all treatment efforts. 1

Do not delay escalation in secondary Raynaud's, as more aggressive therapy is required to prevent digital ulcers and poor outcomes. 1 Secondary Raynaud's has more severe manifestations with potential for digital ulcers, gangrene (11% in systemic sclerosis), or osteomyelitis (22.5% develop digital ulcers in systemic sclerosis). 8

Treatment Algorithm Based on Severity

Mild Raynaud's (Primary):

• Non-pharmacological measures alone may suffice 1
• Add nifedipine if symptoms affect quality of life 1

Moderate to Severe Raynaud's or Inadequate Response:

• Add or switch to phosphodiesterase-5 inhibitors 1
• Consider combination therapy with vasodilators 4

Severe Refractory Raynaud's with Frequent Attacks:

• Escalate to intravenous prostacyclin analogues 1

Digital Ulcers Present:

• Use bosentan for prevention of new ulcers (especially if multiple existing ulcers) 1
• Use intravenous iloprost or phosphodiesterase-5 inhibitors for healing 1

Additional Considerations

Simple vasodilators like naftidrofuryl, inositol nicotinate, and pentoxifylline may be useful in mild disease with fewer adverse effects than calcium channel blockers. 4 However, these are not included in major guideline recommendations. 1

Topical nitrates can be considered but are limited by adverse effects including flushing, headache, and hypotension. 3 Fluoxetine has limited evidence from small studies. 1

In extreme cases with gangrene or osteomyelitis, amputation may be required. 7 Lumbar sympathectomy retains a role for lower limb involvement, though chemical or surgical sympathectomy for upper extremities is obsolete without long-term benefit. 5, 4