Raynaud’s Disease 360°: Comprehensive 2025 Evidence-Based Guide to Primary & Secondary Raynaud’s

5–10% prevalence—90% primary. Amlodipine → 70% ↓ attacks. This 2025 EULAR-aligned guide covers primary vs secondary Raynaud’s, triphasic color change, capillaroscopy (SD pattern), ANA+, CCB (amlodipine 5–10 mg), sildenafil 25–50 mg, iloprost IV, bosentan 62.5 mg, AI thermography (98% sensitivity), and 10-yr SSc progression risk. Includes home warming protocol, trigger log, and prevention.

Epidemiology and Burden

• Prevalence: 3–20% (higher in cold climates, women)
• F:M Ratio: 9:1 (primary), 1:1 (secondary)
• Age Onset: 15–30 (primary), >35 (secondary)
• QoL Impact: 60% report daily interference

Classification: Primary vs Secondary

Feature	Primary	Secondary
Prevalence	90%	10%
Age	<30< /td>	>35
Symmetry	Yes	Asymmetric possible
Capillaroscopy	Normal	Abnormal (SD, late pattern)
ANA	Negative	Positive (80% SSc)
Ulcers	Rare	Common (SSc)

Pathophysiology: Vascular Dysregulation

1. Vasospasm: α2-adrenergic hyperactivity → arteriole constriction
2. Endothelial Dysfunction: ↓ NO, ↑ ET-1
3. Neuropathy: C-fiber dysfunction (cold sensitivity)
4. Fibrosis (Secondary): Intimal hyperplasia → ischemia

Common Triggers

• Cold: <15°C (most common)
• Stress: Sympathetic activation
• Smoking: Nicotine → vasoconstriction
• Vibration: Hand-arm vibration syndrome
• Medications: Beta-blockers, ergotamine, amphetamines

Clinical Features: Triphasic Attack

Phase	Color	Duration	Symptom
Pallor	White	5–15 min	Numbness
Cyanosis	Blue	Variable	Cold, pain
Erythema	Red	10–20 min	Tingling, throbbing

Red Flags: Asymmetric, ulcers, fixed cyanosis, age >35 → secondary

Diagnostic Workup

Step 1: History & Exam

• Triphasic? Symmetric? Ulcers?
• Autoimmune symptoms (dry eyes, arthritis)

Step 2: Nailfold Capillaroscopy

• Normal: Hairpin loops
• SD Pattern: Giant capillaries, hemorrhages → SSc risk
• Late Pattern: Avascular areas → severe

Step 3: Autoantibody Panel

• ANA (IF pattern), ENA (Scl-70, CENP-B, RNA Pol III)
• Positive in 95% limited SSc, 80% diffuse

Step 4: Thermography

• Cold challenge (10°C water 1 min) → rewarming time
• Delayed >10 min → abnormal

Non-Pharmacologic Management

Pharmacologic: Mild to Moderate

First-Line: Calcium Channel Blockers

• Amlodipine: 5–10 mg daily → 70% ↓ frequency
• Nifedipine XL: 30–60 mg (alternative)
• Side effects: edema, headache

Second-Line: PDE5 Inhibitors

• Sildenafil: 25–50 mg TID → 60% improvement
• Tadalafil: 10 mg daily (off-label)

Third-Line: Topical

• Nitroglycerin 2% ointment (fingers) → local vasodilation
• Compounded nifedipine gel

Severe/Secondary: Digital Ulcers

• Iloprost IV: 0.5–2 ng/kg/min ×5 days → 80% ulcer healing
• Bosentan: 62.5 mg BID → 50% ↓ new ulcers (RAPIDS-2)
• Sildenafil IV: Hospitalized crisis
• Botulinum Toxin: 50–100 U/palm → 3–6 mo relief

Surgical Options (Refractory)

• Digital Sympathectomy: Adventitial stripping → 70% success
• Arterial Bypass: Ulnar artery thrombosis
• Amputation: Gangrene (last resort)

Monitoring & Progression Risk

10-Year Risk of SSc (Secondary)

Annual Screening

• Capillaroscopy, ANA, PFT, echo (PAH risk)

2025 Digital Tools

• AI Thermography: Smartphone FLIR → 98% sensitivity
• Wearable Gloves: Temp monitoring + auto-heat
• Attack Tracker App: Trigger logging, weather API

Conclusion

Raynaud’s is manageable and predictable. Warmth + CCB + lifestyle → 90% control. With capillaroscopy, AI, and early bosentan, 80% prevent ulcers. One glove, one pill, one warmer life.