Raynaud phenomenon

Raynaud phenomenon (RP) is an exaggerated vasoconstrictive response of the digital arteries and arterioles (e.g., in the fingers and/or toes) to cold or emotional stress. It is termed primary or secondary based on the underlying cause. The etiology of primary RP is poorly understood. Secondary RP, on the other hand, is caused by underlying systemic diseases (e.g., mixed connective tissue disease, vasculitides, hematologic abnormalities). Both types typically present with the sequential discoloration of fingers and/or toes from white (ischemia) to purplish-blue (hypoxia) to red (reactive hyperemia). Episodes of vasoconstriction usually end 15–20 minutes after the trigger is removed, and last no longer than an hour following adequate warming or stress reduction. Secondary RP may be accompanied by complications of underlying diseases and/or trophic disorders. Management involves the treatment of any underlying conditions, avoidance of situations that may trigger an attack, and calcium channel blockers (e.g., nifedipine, diltiazem). Rubefacients, or vasoactive agents, are indicated in severe cases.

Overview

• Vasospastic attack triggered by cold or emotional stress.
• More common in women.

Primary RP (also called Raynaud disease)

• Idiopathic (no identifiable vascular changes)
• Vasospasms of the digital arteries and arterioles
• Onset usually < 30 years of age

Secondary RP (also called Raynaud syndrome)

• Vasospasms due to arteriolar changes in the fingers (and/or toes), which may be precipitated by the following:
  • Drugs: beta-blockers, ergotamine, bleomycin
  • Smoking
  • Occupational trauma: from handling vibrating tools, typing
  • Hyperviscocity: polycythemia, paraproteinemias (plasmacytoma, Waldenstrom macroglobulinemia), cryoglobulinemia, cold agglutinin disease
  • Vasculitides: e.g., Buerger's disease
  • Connective tissue diseases: e.g., scleroderma (CREST syndrome), systemic lupus erythematosus, mixed connective tissue disease, Sjogren syndrome
  • Arterial disease: e.g., peripheral artery disease
  • Frostbite
  • Neurological disease: e.g., carpal tunnel syndrome, intervertebral disc disease
• Onset usually ≥ 30 years of age

References:^[1][2]

• Manifestation
  • Ischemic phase (white): exposure to trigger (e.g., cold) → vasoconstriction of digital arteries and arterioles → ischemia and pallor
    • Sometimes accompanied by pin-and-needles sensation, numbness, or pain
  • Hypoxic phase (blue): low oxygen supply → cyanosis
  • Hyperemic phase (red): rewarming or removal of stressor leads to recovery and reperfusion → erythema
  • Livedo reticularis might occur during attacks
• Location
  • Most commonly affects the fingers and toes
  • Rarely the nose, ears, nipples, and lips
• Duration: Spasms are usually reversible, typically lasting 15–20 minutes after removing the trigger, but may last for up to an hour.

An attack does not always involve all three phases; often, the hyperemic phase does not occur!Irreversible ischemia with tissue damage indicates secondary RP and requires further investigation to identify the underlying cause!

While primary RP is primarily a clinical diagnosis, additional testing is required to diagnose secondary RP. Differentiating between the two types enables the practitioner to identify and assess the severity of any possible underlying condition.

Patient history

• Assessment of patient history focuses on the onset of symptoms, triggers of attacks, time course, pattern of attacks, accompanying symptoms (pain, paresthesias), and impairment of everyday life.
• See “Etiology” and “Symptoms/Clinical findings” above.

Bedside test

• Allen test

Nailfold capillary microscopy

• Important means of distinguishing primary from secondary RP
  • Primary RP: normal capillaroscopic pattern
  • Secondary RP: abnormal capillaroscopic pattern.

Laboratory tests

• All values typically normal in primary RP
• In suspected secondary RP, analyses should focus on diagnosis of underlying diseases.
  • Abnormal CBC
  • Abnormal plasma viscosity
  • ↑ Infection parameters (CRP, ESR)
  • ↑ Antibody serology: e.g., antinuclear antibody (ANA)

Perniosis ^[3]

• Definition: a seasonal condition characterized by the inflammation of small blood vessels that is triggered by an abnormal reaction to cold and humid conditions
• Epidemiology: higher incidence in women (especially those with low body mass index) and individuals who smoke
• Etiology is unknown but associated conditions include:
  • Connective tissue diseases (especially systemic lupus erythematosus)
  • Anorexia nervosa
  • Dysproteinemias
  • Celiac disease
• Pathophysiology: not fully understood, but it is thought that exposure to cold conditions leads to persistent vasoconstriction and subsequent inflammation of small blood vessels
• Clinical features
  • Bluish-red bumps predominantly on the hands, fingers, toes, legs, and face that appear 12–24 hours after exposure to cold and last for 2–3 weeks
  • Lesions are accompanied by pain, itching, burning, and/or swelling.
  • In severe cases: blisters, ulcerations
• Diagnostics: Perniosis is a diagnosis of exclusion.
• Treatment
  • First-line: protection from cold conditions (e.g., multiple layers of warm clothing, gloves)
  • Second-line: calcium channel blockers (e.g., nifedipine)
  • Topical corticosteroids and intense pulsed light therapy may help to relieve symptoms of itching and erythema.

Other

• Acrocyanosis: cyanotic discoloration of the hands, knees, feet, and distal parts of the face without triphasic course or episodic onset, as in RP
• Erythromelalgia: episodic occlusion of blood vessels in the hands and feet followed by hyperemia and inflammation. Toes and fingers flare up episodically without a preceding ischemic phase.
• Peripheral artery disease (PAD)
• Acute arterial occlusion of an extremity

The differential diagnoses listed here are not exhaustive.

The general approaches to primary and secondary RP are similar. However, in cases of secondary RP, the underlying condition should also be treated.

General measures

• Avoid triggers: dampness, cold , emotional stress
• Stop smoking
• Adjust medication (discontinue drugs that may cause attacks: e.g., beta-blockers, ergotamine, oral contraceptives)

Medical therapy

• First‑line: : calcium channel blockers; the drug of choice is nifedipine administered orally
• Second‑line:
  • Topical agents to increase perfusion (e.g., topical nitroglycerin)
  • Off-label therapy with orally administered vasoactive agents: prostacyclin analog (e.g., iloprost), SSRIs (e.g., fluoxetine), PDE5 inhibitors (sildenafil, tadalafil, vardenafil), endothelin receptor antagonists (bosentan)

• Trophic disorders (rare in primary RP)
• Other systemic complications of underlying disease in secondary RP

References:^[4][5]

We list the most important complications. The selection is not exhaustive.