Advancements in Managing Intractable Raynaud Phenomenon: The Role of Integrated Neurectomy and Sympathectomy

Abstract

Raynaud's phenomenon (RP) is characterized by digit discoloration including pallor, cyanosis, and rubor. While some experience only mild numbness or tingling during RP attacks, many progress to severe conditions, including intractable pain, nonhealing digital ulcers, and even self-amputation. Although mild symptoms can often be managed conservatively through lifestyle modifications, such as avoiding triggering factors, or with pharmacological interventions, surgical treatments are often required for those with persistent pain and ulcers. Advances in microsurgical techniques have introduced peripheral sympathectomy, peripheral neurectomy, and distal artery bypass as promising options for managing refractory and severe cases of RP. This review explores the epidemiology, pathophysiology, and particularly the evolution of microsurgical interventions for the treatment of RP.

Keywords

Raynaud's phenomenon - connective tissue disease - microsurgical intervention - sympathectomy - arterial bypass

Publication History

Article published online:
13 June 2025

• References

• 1 Raynaud M. De l'asphyxie locale et de la gangrène symétrique des extrémités [On local asphyxia and symmetrical gangrene of the extremities]. Rignoux; 1862
• 2 Curtiss P, Svigos K, Schwager Z, Lo Sicco K, Franks Jr AG. Part I: Epidemiology, pathophysiology, and clinical considerations of primary and secondary Raynaud's phenomenon. J Am Acad Dermatol 2024; 90 (02) 223-234
• 3 Garner R, Kumari R, Lanyon P, Doherty M, Zhang W. Prevalence, risk factors and associations of primary Raynaud's phenomenon: systematic review and meta-analysis of observational studies. BMJ Open 2015; 5 (03) e006389
• 4 Suter LG, Murabito JM, Felson DT, Fraenkel L. The incidence and natural history of Raynaud's phenomenon in the community. Arthritis Rheum 2005; 52 (04) 1259-1263
• 5 Ingegnoli F, Ughi N, Mihai C. Update on the epidemiology, risk factors, and disease outcomes of systemic sclerosis. Best Pract Res Clin Rheumatol 2018; 32 (02) 223-240
• 6 Meier FM, Frommer KW, Dinser R. et al.; EUSTAR Co-authors. Update on the profile of the EUSTAR cohort: an analysis of the EULAR Scleroderma Trials and Research group database. Ann Rheum Dis 2012; 71 (08) 1355-1360
• 7 Wigley FM, Flavahan NA. Raynaud's phenomenon. N Engl J Med 2016; 375 (06) 556-565
• 8 LeRoy EC, Medsger Jr TA. Raynaud's phenomenon: a proposal for classification. Clin Exp Rheumatol 1992; 10 (05) 485-488
• 9 Spencer-Green G. Outcomes in primary Raynaud phenomenon: A meta-analysis of the frequency, rates, and predictors of transition to secondary diseases. Arch Intern Med 1998; 158 (06) 595-600
• 10 Watson HR, Robb R, Belcher G, Belch JJ. Seasonal variation of Raynaud's phenomenon secondary to systemic sclerosis. J Rheumatol 1999; 26 (08) 1734-1737
• 11 Hummers LK, Dugowson CE, Dechow FJ. et al. A multi-centre, blinded, randomised, placebo-controlled, laboratory-based study of MQX-503, a novel topical gel formulation of nitroglycerine, in patients with Raynaud phenomenon. Ann Rheum Dis 2013; 72 (12) 1962-1967
• 12 Rirash F, Tingey PC, Harding SE. et al. Calcium channel blockers for primary and secondary Raynaud's phenomenon. Cochrane Database Syst Rev 2017; 12 (12) CD000467
• 13 Roustit M, Blaise S, Allanore Y, Carpentier PH, Caglayan E, Cracowski JL. Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud's phenomenon: systematic review and meta-analysis of randomised trials. Ann Rheum Dis 2013; 72 (10) 1696-1699
• 14 Lawson O, Sisti A, Konofaos P. The use of botulinum toxin in raynaud phenomenon: A comprehensive literature review. Ann Plast Surg 2023; 91 (01) 159-186
• 15 Hughes M, Snapir A, Wilkinson J, Snapir D, Wigley FM, Herrick AL. Prediction and impact of attacks of Raynaud's phenomenon, as judged by patient perception. Rheumatology (Oxford) 2015; 54 (08) 1443-1447
• 16 Karapolat S, Turkyilmaz A, Tekinbas C. Effects of endoscopic thoracic sympathectomy on Raynaud's disease. J Laparoendosc Adv Surg Tech A 2018; 28 (06) 726-729
• 17 Merritt WH. Role and rationale for extended periarterial sympathectomy in the management of severe Raynaud syndrome: Techniques and results. Hand Clin 2015; 31 (01) 101-120
• 18 Thoresen M, Walløe L. Skin blood flow in humans as a function of environmental temperature measured by ultrasound. Acta Physiol Scand 1980; 109 (03) 333-341
• 19 Flavahan NA. A vascular mechanistic approach to understanding Raynaud phenomenon. Nat Rev Rheumatol 2015; 11 (03) 146-158
• 20 Sawasaki N, Iwase S, Mano T. Effect of skin sympathetic response to local or systemic cold exposure on thermoregulatory functions in humans. Auton Neurosci 2001; 87 (2-3): 274-281
• 21 Kao L, Weyand C. Vasculitis in systemic sclerosis. Int J Rheumatol 2010; 2010: 385938
• 22 Barile-Fabris L, Hernández-Cabrera MF, Barragan-Garfias JA. Vasculitis in systemic lupus erythematosus. Curr Rheumatol Rep 2014; 16 (09) 440
• 23 Kahaleh B, Matucci-Cerinic M. Raynaud's phenomenon and scleroderma. Dysregulated neuroendothelial control of vascular tone. Arthritis Rheum 1995; 38 (01) 1-4
• 24 Takagi K, Kawaguchi Y, Hara M, Sugiura T, Harigai M, Kamatani N. Serum nitric oxide (NO) levels in systemic sclerosis patients: Correlation between NO levels and clinical features. Clin Exp Immunol 2003; 134 (03) 538-544
• 25 Mostmans Y, Cutolo M, Giddelo C. et al. The role of endothelial cells in the vasculopathy of systemic sclerosis: A systematic review. Autoimmun Rev 2017; 16 (08) 774-786
• 26 Herrick AL, Illingworth K, Blann A, Hay CR, Hollis S, Jayson MI. Von Willebrand factor, thrombomodulin, thromboxane, beta-thromboglobulin and markers of fibrinolysis in primary Raynaud's phenomenon and systemic sclerosis. Ann Rheum Dis 1996; 55 (02) 122-127
• 27 Ruch DS, Holden M, Smith BP, Smith TL, Koman LA. Periarterial sympathectomy in scleroderma patients: Intermediate-term follow-up. J Hand Surg Am 2002; 27 (02) 258-264
• 28 Flavahan NA, Flavahan S, Mitra S, Chotani MA. The vasculopathy of Raynaud's phenomenon and scleroderma. Rheum Dis Clin North Am 2003; 29 (02) 275-291 , vi vi
• 29 Distler O, Del Rosso A, Giacomelli R. et al. Angiogenic and angiostatic factors in systemic sclerosis: increased levels of vascular endothelial growth factor are a feature of the earliest disease stages and are associated with the absence of fingertip ulcers. Arthritis Res 2002; 4 (06) R11
• 30 Mackiewicz Z, Sukura A, Povilenaité D. et al. Increased but imbalanced expression of VEGF and its receptors has no positive effect on angiogenesis in systemic sclerosis skin. Clin Exp Rheumatol 2002; 20 (05) 641-646
• 31 Maricq HR, Downey JA, LeRoy EC. Standstill of nailfold capillary blood flow during cooling in scleroderma and Raynaud's syndrome. Blood Vessels 1976; 13 (06) 338-349
• 32 Momeni A, Sorice SC, Valenzuela A, Fiorentino DF, Chung L, Chang J. Surgical treatment of systemic sclerosis–is it justified to offer peripheral sympathectomy earlier in the disease process?. Microsurgery 2015; 35 (06) 441-446
• 33 Morgan RF, Reisman NR, Wilgis EF. Anatomic localization of sympathetic nerves in the hand. J Hand Surg Am 1983; 8 (03) 283-288
• 34 Fox P, Chung L, Chang J. Management of the hand in systemic sclerosis. J Hand Surg Am 2013; 38 (05) 1012-1016 , quiz 1017
• 35 Flatt AE. Digital artery sympathectomy. J Hand Surg Am 1980; 5 (06) 550-556
• 36 Jones NF, Imbriglia JE, Steen VD, Medsger TA. Surgery for scleroderma of the hand. J Hand Surg Am 1987; 12 (03) 391-400
• 37 el-Gammal TA, Blair WF. Digital periarterial sympathectomy for ischaemic digital pain and ulcers. J Hand Surg (Br) 1991; 16 (04) 382-385
• 38 McCabe SJ, Kleinert JM. The nerve of Henlé. J Hand Surg Am 1990; 15 (05) 784-788
• 39 Hartzell TL, Makhni EC, Sampson C. Long-term results of periarterial sympathectomy. J Hand Surg Am 2009; 34 (08) 1454-1460
• 40 Pace CS, Merritt WH. Extended periarterial sympathectomy: Evaluation of long-term outcomes. Hand (N Y) 2018; 13 (04) 395-402
• 41 Chen SH, Lien PH, Lee CH. et al. Neurectomy of the nerve of Henle associated with periarterial sympathectomy for management of intractable Raynaud phenomenon. Plast Reconstr Surg 2024; 153 (06) 1333-1344
• 42 Park JH, Sung YK, Bae SC, Song SY, Seo HS, Jun JB. Ulnar artery vasculopathy in systemic sclerosis. Rheumatol Int 2009; 29 (09) 1081-1086
• 43 Leyden J, Burn MB, Wong V. et al. Upper extremity angiographic patterns in systemic sclerosis: Implications for surgical treatment. J Hand Surg Am 2019; 44 (11) 990.e1-990.e7
• 44 Titan AL, Chang J, Megerle K, Murray P, Hammert W. State of the art review: The management of chronic vascular disorders in the hand and upper limb. J Hand Surg Eur Vol 2023; 48 (04) 295-302
• 45 Ruch DS, Aldridge M, Holden M, Smith TL, Koman LA, Smith BP. Arterial reconstruction for radial artery occlusion. J Hand Surg Am 2000; 25 (02) 282-290
• 46 Park SO, Wang HW, Han Y, Ahn HC. Digital artery reconstruction with interposition vein graft: impact on secondary Raynaud's phenomenon. Rheumatology (Oxford) 2024; 63 (08) 2123-2127