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Raynaud's phenomenon

Reversible vasospasm of the digital arteries which may result in ischemia of the digits. Etiology: 1) primary (idiopathic) Raynaud's disease (70%) 2) Raynaud's phenomenon is secondary to other conditions a) connective tissue disease - systemic sclerosis (90%) - mixed connective tissue disease (85%) - systemic lupus erythematosus (10-44%) - Sjogren's syndrome (20%) - rheumatoid arthritis (5%) - dermatomyositis/polymyositis (20%) b) pharmacologic agents - chemotherapeutic agents: - bleomycin, vincristine, vinblastine, cisplatin - heavy metals - caffeine - others: - beta blockers, ergotamine, narcotics, birth control pills, sympathomimetics, imipramine, bromocryptine, alpha-interferon, methysergide, cyclosporine, interferon, nicotine, clonidine c) trauma/occupational - 90% of loggers - vibration white finger - carpal tunnel syndrome - polyvinyl chloride - jackhammer use - electric shock - cold injury - piano playing d) arterial occlusive disease - vasculitis: thromboangiitis obliterans (associated with smoking) - peripheral arterial disease - thoracic outlet syndrome e) hyperviscosity diseases - polycythemia - cryoglobulinemia - paraproteinemia, especially Waldenstrom's - cryofibrinogenemia - cold agglutinins - thrombocytosis f) arterial disease - atherosclerosis - thromboangiitis obliterans (associated with smoking) - tobaccoism (aggravated by cigarette smoking) g) neurologic disorders - intervertebral disk disease - syringomyelia - spinal cord tumors - stroke - poliomyelitis - carpal tunnel syndrome h) migraine syndrome (10%) i) primary pulmonary hypertension Epidemiology: 1) primary a) common b) most patients 15-20 years c) predominance of females d) affects 3-5% of male population, 4-9% of female population e) < 50% of affected individuals seek medical attention 2) secondary a) most individuals > 35 years b) no sex preference c) suspect if patient is male, >35 or <15 years of age 3) 8% of men, 11% of women (mean age 54 years) [8] Pathology: 1) vasospasm [5] 2) increased sympathetic tone or increased density or sensitivity of alpha 2-adrenergic receptors 3) endothelial damage 4) reduced release of nitric oxide & venodilation secondary to endothelial damage 5) intimal proliferation 6) fixed vascular obstruction 7) inflammation & release of vasospastic mediators a) endothelin-1 b) thromboxane A2 8) three phases a) pallor: vasospasm halts blood flow b) cyanosis: blood moving slowly through capillaries becomes deoxygenated c) redness: previously constricted arterioles dilate during hyperemic phase Clinical manifestations: 1) primary Raynaud's phenomenon - painful digits exacerbated by exposure to cold temperature or emotional stress - pallor often followed by cyanosis, then redness - affects fingers more often than toes, may spare thumb - may also affect earlobes, lips or tip of nose - symptoms last 15-30 minutes after rewarming - paresthesias may occur during rewarming 2) secondary Raynaud's phenomenon - symptoms similar to primary Raynaud's phenomenon, but may be more severe with rapid progression - symptoms may be unilateral - manifestations of precipitating etiology may be present - digital pitting scar or gangrene may occur 3) most cases without underlying connective tissue disease are mild [8] Criteria for diagnosis of primary Raynaud's phenomenon 1) episodic attacks with acral pallor or cyanosis 2) strong & symmetric peripheral pulses 3) no pitting edema, gangrene or ulcerations 4) normal finger & toenail capillaries 5) antinuclear antibody (ANA) titer < 1:100 (i.e. 1:10) 6) ESR < 20 mm/hr Laboratory: - serology for connective tissue disease not routinely indicated for patients with primary Raynaud's phenomenon [5] - yield is low & not cost effective, unless - severe & prolonged vasospasms - asymmetric involvement of digits - digital pitting Special laboratory: - capillaroscopy for differentiation of primary from secondary Raynaud's phenomenon [13] Differential diagnosis: 1) blue toe syndrome 2) erythromelagia Complications: < 10% of patients with isolated Raynaud's phenomenon will develop systemic connective tissue disease within 10 years Management: 1) general measures - avoid exposure to the cold - protect hands & feet from cold & trauma - cessation of smoking (smoking exacerbates Raynaud's phenomenon) - avoid over the counter sympathomimetics 2) pharmacologic agents a) dihydropyridine calcium channel blockers prior to precipitating event [11] - amlodipine - nifedipine (Procardia) b) anti-platelet agent c) topical nitroglycerin applied to fingers or toes d) prazosin e) reserpine f) guanethidine g) bosentan may be effective in preventing recurrences of digital ulcers in severe Raynaud's disease [5] h) vasodilator - prostacyclin analogs - intravenous epoprostenol for acutely ischemic digit(s) [5] - iloprost (not available in US) - improved symptoms of 47% of patients who failed nefedipine - ACE inhibitors (controversial) - sildenafil (Viagra) 50 mg BID [9]; tadalafil [14] - controversial - individualized effect taken before or during an episode [16] d) pentoxifylline (controversial) i) serotonin receptor antagonists - ketanserin (not available in US) - phenoxybenzamine - affects vasoconstriction & platelet aggregation 3) chronic pain or digital ulceration failing conservative management - sympathetic ganglion blockade - Botox 100 units injected into the hand effective (84%) [15] 3) prognosis - primary Raynaud's phenomenon carries low risk of progression [5] - 36% of cases without underlying connective tissue disease persist for 7 years [8]

Related

blue toe syndrome erythromelalgia (erythermalgia)

General

peripheral vascular disease (PVD) sign/symptom syndrome

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 525-26
  2. Guide to Physical Examination & History Taking, 4th edition, Bates B, JB Lippincott, Philadelphia, 1987
  3. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 288-90
  4. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 874-75
  5. Medical Knowledge Self Assessment Program (MKSAP) 11,14,16,17. American College of Physicians, Philadelphia 1998,2006,2012,2014
  6. Principles of Ambulatory Medicine, 4th edition, Barker et al (eds), Williams & Wilkins, Baltimore, 1995, pg 893
  7. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1139
  8. Journal Watch 25(11):91, 2005 Suter LG, Murabito JM, Felson DT, Fraenkel L. The incidence and natural history of Raynaud's phenomenon in the community. Arthritis Rheum. 2005 Apr;52(4):1259-63. PMID: 15818710
  9. Prescriber's Letter 13(1): 2006 Viagra and Raynaud's phenomenon Detail-Document#: 220111 (subscription needed) http://www.prescribersletter.com
  10. Hirschl M et al, Transition from primary Raynaud's phenomenon to secondary Phenomenon identified by diagnosis of an associated disease: Results of ten years prospective surveillance. Arthritis Rheum 2006; 54:1974 PMID: 16732585
  11. Prescriber's Letter 15(12): 2008 Drugs that Aggravate or Improve Raynaud's Phenomenon Detail-Document#: 241207 (subscription needed) http://www.prescribersletter.com
  12. Neumeister MW et al. Botox therapy for ischemic digits. Plast Reconstr Surg 2009 Jul; 124:191. PMID: 19568080
  13. Lambova SN, Muller-Ladner U. The role of capillaroscopy in differentiation of primary and secondary Raynaud's phenomenon in rheumatic diseases: a review of the literature and two case reports. Rheumatol Int. 2009 Sep;29(11):1263-71. PMID: 19547979
  14. Shenoy PD, Kumar S, Jha LK et al Efficacy of tadalafil in secondary Raynaud's phenomenon resistant to vasodilator therapy: a double-blind randomized cross-over trial. Rheumatology (Oxford). 2010 Dec;49(12):2420-8 PMID: 20837499
  15. Wigley FM, Flavahan NA Raynaud's Phenomenon N Engl J Med 2016; 375:556-565. August 11, 2016 PMID: 27509103 http://www.nejm.org/doi/full/10.1056/NEJMra1507638
  16. Roustit M, Giai J, Gaget O et al On-Demand Sildenafil as a Treatment for Raynaud Phenomenon: A Series of n-of-1 Trials. Ann Intern Med. 2018. Oct 30. PMID: 30383134 http://annals.org/aim/article-abstract/2709822/demand-sildenafil-treatment-raynaud-phenomenon-series-n-1-trials
  17. RNational Institute of Arthritis and Muscluloskeletal and Skin Diseases (NIAMS) Raynaud's Phenomenon https://www.niams.nih.gov/health-topics/raynauds-phenomenon