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Raynaud Phenomenon
Herbert L. Muncie Jr., MD
Kelsey E. Phelps, MD
image BASICS
DESCRIPTION
  • Idiopathic intermittent episodes of vasoconstriction of digital arteries, precapillary arterioles, and cutaneous arteriovenous shunts in response to cold, emotional stress, or blunt trauma
    • A triphasic color change of the fingers (occasionally the toes, rarely nipples) is the principal physical manifestation.
      • The initial color is white from extreme pallor, then blue from cyanosis, and finally with warming and vasodilatation the skin appears red.
      • Thumbs are rarely involved.
    • Swelling, throbbing, and paresthesias are associated symptoms.
    • Primary
      • 80% of patients have primary disease.
      • Episodes are bilateral and nonprogressive.
      • Diagnosis confirmed if after 2 years of symptoms, no underlying connective tissue disease develops.
    • Secondary
      • Progressive and asymmetric
      • Vascular spasm is more frequent and more severe over time. Ulceration is rare; gangrene does not develop; 13% progress to digital fat pad atrophy and ischemic changes of the fingertips.
      • Typically associated with an underlying connective tissue disorder
  • System(s) affected: hematologic, lymphatic, immunologic, musculoskeletal, dermatologic, exocrine
Pregnancy Considerations
  • Raynaud phenomenon can appear as breast pain in lactating women (1).
  • Positive breast milk bacterial culture distinguishes mastitis from Raynaud phenomenon.
Geriatric Considerations
Initial appearance of Raynaud phenomenon after age 40 years often indicates underlying connective tissue disease.
Pediatric Considerations
Associated with systemic lupus erythematosus (SLE) and scleroderma
EPIDEMIOLOGY
Incidence
  • Primary
    • Predominant age: 14 years; ˜1/4 begin >40 years
    • Predominant sex: female > male (4:1)
  • Secondary
    • Predominant age: >40 years
    • Predominant sex: no gender predilection
Prevalence
  • Primary: 3-12.5% of men; 6-20% of women (based on clinical history)
  • Secondary: ˜1% of population
ETIOLOGY AND PATHOPHYSIOLOGY
Unknown. Dysregulation of vascular control mechanisms leads to imbalance between vasodilation and vasoconstriction. There is a reduced endothelin-dependent vasodilation activity and an increased vasoconstriction in peripheral vessels by overproduction of endothelin-1. 5-HT2 serotonin receptors may be involved in secondary Raynaud phenomenon. Platelet and blood viscosity abnormalities in secondary contribute to ischemic pathology.
Genetics
Some studies suggest dominant inheritance pattern. ˜1/4 of primary patients have a first-degree relative with Raynaud phenomenon.
RISK FACTORS
  • Existing autoimmune or connective tissue disorder
  • End-stage renal disease with hemodialysis may increase risk if a steal phenomenon associated with the arterial-venous shunt develops.
  • Primary and secondary disease associated with elevated homocysteine levels.
  • Smoking is not associated with increased risk of Raynaud phenomenon but may worsen symptoms.
GENERAL PREVENTION
  • Avoid cold exposure.
  • Tobacco cessation
  • No relationship has been established between Raynaud phenomenon and vibratory tool use.
COMMONLY ASSOCIATED CONDITIONS
Secondary Raynaud
  • Scleroderma; SLE; polymyositis
  • Sjögren syndrome; occlusive vascular disease
  • Cryoglobulinemia
image DIAGNOSIS
PHYSICAL EXAM
Pallor (whiteness) of fingertips with cold exposure, then cyanosis (blue), then redness and pain with warming
  • Ischemic attacks evidenced by demarcated or cyanotic skin limited to digits; usually starts on one digit and spreads symmetrically to remaining fingers of both hands. The thumb is typically spared.
  • May rarely involve other peripheral tissues (e.g., tongue) (2).
  • Beau lines: transverse linear depressions in nail plate on most or all fingernails that occurs after exposure to cold or any insult that disrupts normal nail growth.
  • Livedo reticularis: mottling of the skin of the arms and legs; benign and reverses with warming
  • Primary
    • Normal physical exam
    • Nail bed capillaries have normal appearance: Place 1 drop of grade B immersion oil on skin at base of fingernail and view capillaries with hand-held ophthalmoscope at 10 to 40 diopters.
  • Secondary
    • Skin changes, arthritis, and abnormal lung findings suggest connective tissue disease,
    • Ischemic skin lesions: ulceration of finger pads (autoamputation in severe, prolonged cases)
    • Nail bed capillary distortion including giant loops, avascular areas, and increased tortuosity
    • Abnormal Allen test: conducted by having the patient open and close his or her hand several times and then squeezing his or her hand tightly into a fist. The examiner sequentially occludes the ulnar and radial arteries while the patient opens his or her hand to reveal the return of color as a measure of circulation.
DIFFERENTIAL DIAGNOSIS
  • Thromboangiitis obliterans (Buerger disease): primarily affects men; smoking-related
  • Rheumatoid arthritis (RA)
  • Progressive systemic sclerosis (scleroderma): Raynaud phenomenon precedes other symptoms.
  • SLE
  • Carpal tunnel syndrome; thoracic outlet syndrome
  • Hypothyroidism
  • CREST syndrome (calcinosis cutis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias)
  • Cryoglobulinemia; Waldenström macroglobulinemia
  • Acrocyanosis
  • Polycythemia
  • Occupational (e.g., especially from vibrating tools, masonry work, exposure to polyvinyl chloride)
  • Drug-induced (e.g., clonidine, ergotamine, methysergide, amphetamines, bromocriptine, bleomycin, vinblastine, cisplatin, cyclosporine)
DIAGNOSTIC TESTS & INTERPRETATION
Provocative test (e.g., ice water immersion) unnecessary
  • Primary
    • Antinuclear antibody: negative
    • ESR: normal
  • Secondary
    • Tests for secondary causes (e.g., CBC, ESR)
    • Positive autoantibody has low positive predictive value for connective tissue disease (30%).
    • Antibodies to specific autoantigens (e.g., scleroderma with anticentromere or antitopoisomerase antibodies)
    • Videocapillaroscopy is gold standard (200 times magnification).
P.897

Follow-Up Tests & Special Considerations
Periodic assessments for a connective tissue disorder
Diagnostic Procedures/Other
Diagnosis is determined by history and physical exam.
image TREATMENT
Assess using a Raynaud Condition Score.
GENERAL MEASURES
  • Dress warmly, wear gloves, and avoid cold temperatures.
  • During attacks, rotate the arms in a windmill pattern or placing the hands under warm water or in a warm body fold to alleviate symptoms.
  • Tobacco cessation
  • Avoid &bgr;-blockers, amphetamines, ergot alkaloids, and sumatriptan.
  • Temperature-related biofeedback may help patients increase hand temperature. 1-year follow-up is no better than control.
  • Finger guards to protect ulcerated fingertips
MEDICATION
First Line
  • Calcium channel blockers (CCBs). Nifedipine is the best studied and most frequently used.
  • Nifedipine: 30 to 180 mg/day (sustained-release form); seasonal (winter) use is effective with up to 75% of patients experiencing improvement.
  • Is compatible with breastfeeding
  • Contraindications: allergy to drug, pregnancy, CHF
  • Precautions: may cause headache, dizziness, lightheadedness, edema, or hypotension
  • Significant possible interactions
    • Increases serum level of digoxin
Second Line
  • Amlodipine (5 to 10 mg/day) and nicardipine are effective and may have fewer adverse effects.
  • No data exist to support switching CCB if initial drug is ineffective.
  • Small studies support benefit from losartan and fluoxetine.
  • Phosphodiesterase type-5 inhibitors (sildenafil, vardenafil) may reduce symptoms without increasing blood flow.
  • Parenteral iloprost, a prostacyclin, in low doses (0.5 ng/kg/min over 6 hours), has improved ulcerations with severe Raynaud phenomenon when CCBs failed. Oral prostacyclin has not proven useful.
  • Nitroglycerin patches may be helpful, but use is limited by the incidence of severe headache. Nitroglycerin gel has shown promise as a topical therapy.
  • Prazosin (1 to 2 mg TID) is the only well-studied &agr;1-adrenergic receptor blocker with modest effect, but adverse effects may outweigh any benefit.
  • ACE inhibitors are no longer recommended.
ISSUES FOR REFERRAL
If an underlying disease is suspected, consider rheumatology consultation for evaluation and treatment.
ADDITIONAL THERAPIES
  • Botulinum toxin has shown some effect in reducing vasospastic episodes, frequency of attacks, rest pain, and helping to promote digital ulcer healing (3)[C].
  • Aspirin
  • Digital or wrist block with lidocaine or bupivacaine (without epinephrine) for pain control
  • Short-term anticoagulation with heparin if persistent critical ischemia, evidence of large-artery occlusive disease, or both
SURGERY/OTHER PROCEDURES
Surgical intervention is rarely indicated or used for Raynaud phenomenon. Effect of cervical sympathectomy is transient; symptoms return in 1 to 2 years. Digital fat grafting is a novel modality that has shown improved symptomatology and evidence of measurably increased perfusion in several cases; further study is needed (4)[C].
COMPLEMENTARY & ALTERNATIVE MEDICINE
  • Ginkgo biloba may reduce the frequency of attacks.
  • Well-designed studies have not been done yet (5)[B].
  • Fish oil supplements may increase digital systolic pressure and time to onset of symptoms after exposure to cold; not proven in controlled trials
  • Vitamin D supplementation led to improvement in self-reported symptoms in vitamin D-deficient patients with Raynaud phenomenon (6)[B].
  • Evening primrose oil reduced severity of attacks in one study.
  • Oral arginine is no better than placebo.
  • Biofeedback is not helpful.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Avoid exposure to cold; reassess for secondary causes.
Patient Monitoring
Manage fingertip ulcers and rapidly treat infection.
DIET
No special diet.
PATIENT EDUCATION
  • Tobacco cessation.
  • Avoid triggers (e.g., trauma, vibration, cold).
  • Dress warmly; wear gloves.
  • Warm hands when experiencing vasospasm.
PROGNOSIS
  • Attacks may last from several minutes to a few hours.
  • 2/3 of attacks resolve spontaneously.
  • ˜13% of Raynaud patients develop a secondary disorder, typically connective tissue diseases.
REFERENCES
1. Barrett ME, Heller MM, Stone HF, et al. Raynaud phenomenon of the nipple in breastfeeding mothers: an underdiagnosed cause of nipple pain. JAMA Dermatol. 2013;149(3):300-306.
2. Lioger B, Diot E. Raynaud’s phenomenon of the tongue: uncommon presentation of a classical sign. QJM. 2013;106(6):583-584.
3. Neumeister MW, Webb KN, Romanelli M. Minimally invasive treatment of Raynaud phenomenon: the role of botulinum type A. Hand Clin. 2014;30(1): 17-24.
4. Bank J, Fuller SM, Henry GI, et al. Fat grafting to the hand in patients with Raynaud phenomenon: a novel therapeutic modality. Plast Reconstr Surg. 2014;133(5):1109-1118.
5. Bredie SJ, Jong MC. No significant effect of Ginkgo biloba special extract EGb 761 in the treatment of primary Raynaud phenomenon: a randomized controlled trial. J Cardiovasc Pharmacol. 2012;59(3):215-221.
6. Hélou J, Moutran R, Maatouk I, et al. Raynaud’s phenomenon and vitamin D. Rheumatol Int. 2013;33(3):751-755.
Additional Reading
&NA;
  • Herrick AL. Contemporary management of Raynaud’s phenomenon and digital ischaemic complications. Curr Opin Rheumatol. 2011;23(6):555-561.
  • Huisstede BM, Hoogvliet P, Paulis WD, et al. Effectiveness of interventions for secondary Raynaud’s phenomenon: a systematic review. Arch Phys Med Rehabil. 2011;92(7):1166-1180.
  • Malenfant D, Catton M, Pope JE. The efficacy of complementary and alternative medicine in the treatment of Raynaud’s phenomenon: a literature review and meta-analysis. Rheumatology (Oxford). 2009;48(7):791-795.
  • Maverakis E, Patel F, Kronenberg DG, et al. International consensus criteria for the diagnosis of Raynaud’s phenomenon. J Autoimmun. 2014; 48-49:60-65.
See Also
&NA;
Algorithm: Raynaud Phenomenon
Codes
&NA;
ICD10
  • I73.00 Raynaud’s syndrome without gangrene
  • I73.01 Raynaud’s syndrome with gangrene
Clinical Pearls
&NA;
  • The diagnosis of Raynaud phenomenon is based on clinical symptoms.
  • Provocative testing is not recommended.
  • Initial presentation of Raynaud phenomenon after age 40 years suggests underlying (secondary) disease.
  • Raynaud phenomenon is a cause of breast pain in lactating women.
  • Primary Raynaud phenomenon is symmetric; secondary Raynaud phenomenon is asymmetric.
  • Primary Raynaud phenomenon is treated with handwarming and avoiding cold exposure.
  • Digital ulcers are not normal and always merit a workup for secondary disease.