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.

Raynaud's phenomenon (RP) was first described by Maurice Raynaud in 1862. ¹ A typical presentation is characterized by a triphasic color sequence at the digits induced by stress or cold exposure: pallor, caused by vasospasm; cyanosis, from prolonged ischemia; and rubor, caused by hyperemia, as the vasospasm resolves. RP is generally categorized into primary RP (PRP) and secondary RP (SRP). PRP is idiopathic, while SRP is associated with underlying conditions, most commonly connective tissue diseases (CTDs), such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and inflammatory myopathies. ² PRP has a reported pooled prevalence of approximately 5% of the general population, ³ and a higher baseline prevalence was observed in females. ⁴ The prevalence of SRP varies depending on the associated CTDs, with SSc notably linked to SRP. Although SSc is relatively rare, affecting 100 to 300 individuals per million, ⁵ a registry study ⁶ reported that over 96% of patients with SSc also experience RP.

Symptoms of PRP are generally mild, often manifesting as subtle tingling or numbness without progression. These symptoms can typically be managed conservatively by avoiding exposure to cold or stressful conditions. ⁷ In contrast, severe RP, commonly associated with SRP, may progress from mild symptoms to intractable pain, digital ulcers, gangrene, or even self-amputation. ² Early differentiation of CTD-related SRP from other causes is critical, as SRP can follow a progressively destructive course. Delayed diagnosis and treatment exacerbate patient discomfort and increase the risk of tissue loss. Accurate differentiation of SRP from PRP using well-defined exclusion criteria is essential for timely and appropriate intervention. LeRoy and Medsger ⁸ proposed that PRP should be diagnosed only when patients exhibit normal findings in nailfold capillaroscopy, antinuclear antibody tests, and erythrocyte sedimentation rate, along with the absence of peripheral vascular disease, digital necrosis, and previous vasospasm episodes. Despite these clear diagnostic criteria, studies have reported that approximately 13% of patients initially diagnosed with PRP transition to SRP over a follow-up period of 2,500 patient-years. ⁹

In addition to lifestyle modifications designed to minimize exposure to triggering factors such as cold and stress, ¹⁰ various pharmacologic treatments have been proposed for managing RP. These include topical nitrates, ¹¹ calcium channel blockers, ¹² phosphodiesterase-5 inhibitors, ¹³ and botulinum toxin injections. ¹⁴ Despite these options, only 16% of patients report significant medication effectiveness. ¹⁵ Consequently, surgical interventions such as endoscopic thoracic sympathectomy ¹⁶ and periarterial sympathectomy ¹⁷ have been explored as alternative treatment options. Therefore, this study aimed to review the current research on the pathophysiology and microsurgical interventions of this disorder.

Pathophysiology

Primary Raynaud's Phenomenon

A network of arteriovenous anastomoses and nutritional capillaries primarily governs cutaneous circulation. ¹⁸ In healthy individuals, sympathetic activation of α ₂ adrenoceptors within these anastomoses induces vessel constriction during cold exposure. In contrast, adequate vessel patency is maintained to facilitate flow-mediated dilation driven by endothelial shear stress. ¹⁹ Conversely, in patients with PRP, heightened expression and activity of α ₂ adrenoceptors lead to excessive vasoconstriction. This abnormal response impairs flow-mediated dilation, resulting in transient digital ischemia and visible skin color changes. ²⁰ Notably, despite these episodes, vascular patency in PRP spontaneously normalizes under physiological conditions without progressing to endovascular injury, stenosis, or fibrosis. ²

Secondary Raynaud's Phenomenon

SRP typically arises from the interplay between direct vasospasm and vasculitic mechanisms associated with CTDs, both factors of which contribute to ischemic tissue injury. ^{21 22} Recurrent reperfusion injuries caused by vasospastic episodes result in intimal remodeling, which subsequently promotes abnormal peptide production. ²³ This includes elevated levels of endothelin-1 and angiotensin II alongside reduced nitric oxide, collectively intensifying vasospasm. ^{24 25} Furthermore, increased levels of thromboxane and von Willebrand factor in CTDs, such as SSc, fulfill Virchow's triad and further contribute to thrombus formation. ^{26 27} Beyond endothelial dysregulation, myofibroblasts activated by tumor growth factor-β invade vessel walls, causing vascular narrowing through extravascular fibrosis and smooth muscle contraction. ²⁸ Although the body attempts to compensate for this vasculopathy by increasing vascular endothelial growth factor to promote angiogenesis, ²⁹ studies indicate that this response is ineffective, leading to a disorganized capillary structure visible on nailfold capillaroscopy. ^{30 31}

Microsurgical Intervention in Raynaud's Phenomenon

Surgical interventions are typically reserved for refractory cases with progressive ischemic tissue that does not respond to medical treatments. ⁷ Studies have reported that patients experience symptoms for an average of 10 years before undergoing surgical treatment. ³² Advances in microsurgical techniques have made periarterial sympathectomy and arterial bypass promising options, offering both immediate symptom relief and long-term improvement for patients with intractable RP. ¹⁷ Periarterial sympathectomy relieves fibrosis surrounding damaged arteries and decreases segmental sympathetic innervation by removing sympathetic fibers in the tunica adventitia. ³³ In contrast, arterial bypass provides a more effective approach for managing arterial stenosis or occlusion, improving distal perfusion, and promoting the healing of ulcers caused by occluded segments, particularly when medications with sympatholytic or vasodilatory properties prove insufficient. ³⁴

Periarterial Sympathectomy

Periarterial sympathectomy, first described by Flatt ³⁵ in 1980, involves a 3- to 5-mm stripping segment at the bifurcation of the common digital arteries to the proper digital arteries. Over time, larger stripping segments were developed to address symptom recurrence and arterial occlusion. ^{17 36 37} Jones et al. ³⁶ were the first to describe adventitiectomy extending to the entire superficial palmar arch, while el-Gammal and Blair ³⁷ proposed including the ulnar and radial arteries to minimize disease recurrence. Merritt ¹⁷ later advanced this approach by introducing an extended sympathectomy that became widely adopted. The technique included the ulnar artery in the distal one-third of the forearm, the superficial palmar arch, the common and proper digital arteries, the dorsal radial artery, and a neurectomy of the nerve of Henle, the only named peripheral sympathetic nerve supplying the distal ulnar artery, which contributes to vasoconstriction. ³⁸ Studies using this extended surgical technique have reported favorable outcomes. ^{27 32 39 40} For instance, Ruch et al. examined 22 patients (29 hands) with SRP and observed that, after a mean follow-up of 31 months, 82% reported subjective improvement in ulcer healing and reduced ulcer occurrences, while 76% demonstrated statistically significant objective improvements in vascular perfusion as measured by laser Doppler flowmetry. ²⁷ Hartzell et al. ³⁹ revealed that 15 of 20 patients (75%) with SRP diagnosed with various autoimmune diseases experienced either complete ulcer healing or decreased ulcer numbers following sympathectomy. However, the digital amputation rate in this cohort was 26% during an average follow-up of 90 months. Hartzell et al. ³⁹ also found that patients with ischemic episodes related to atherosclerotic diseases derived limited benefit from the procedure; only 12.5% of patients had ulcer improvement, while 59% required digital amputation. Momeni et al. ³² investigated 17 patients with SRP due to SSc. Their findings indicated that over 90% of the patients experienced total pain resolution or significant pain improvements after extended sympathectomy, with only 7.7% requiring additional surgical intervention for recurrent ulcers. ³² Pace and Merritt ⁴⁰ also reported favorable surgical outcomes in 46 patients, with an average follow-up of 4 years. In their study, 78% achieved complete ulcer healing, and 95% reported sustained relief from ischemic pain. ⁴⁰ Despite the promising results, previous studies lack comprehensive subjective and objective assessments, and the long-term rate of symptom recurrence remains unclear. In our study, ⁴¹ we prospectively followed 19 patients with 20 affected hands for 3 years after undergoing periarterial sympathectomy and resection of the nerve of Henle. Figs. 1 and 2 depict our preoperative planning and the process of sympathectomy in our cohort. Figs. 3 and 4 demonstrate the artery before and after adventitiectomy in one of our patients, respectively. Perioperative indocyanine green (ICG) angiography served as an objective measure, while the Michigan Hand Outcomes Questionnaire and the 36-Item Short Form Health Survey assessed physical and psychosocial outcomes, respectively. Our cohort demonstrated immediate improvement in postoperative ICG signals and sustained enhancements in questionnaire scores throughout the 3-year follow-up period. ⁴¹

Fig. 1.

The figure shows preoperative planning of periarterial sympathectomy. The incision wound be made on the proximal ulnar forearm, both distal radial and ulnar forearm, and the palm.

Fig. 2.

The figure shows an intraoperative image of periarterial sympathectomy. The arteries identified during dissection were labeled with elastic bands.

Fig. 3.

The figure shows an artery before periarterial sympathectomy. The artery was encased with dense adventitia before periarterial sympathectomy.

Fig. 4.

The figure shows an artery after periarterial sympathectomy. Improvement in pulsation was observed after removing the encased dense adventitia.

Arterial Bypass for Thrombosis

While no studies have specifically examined the prevalence of arterial thrombosis in RP, previous research has reported ulnar artery thrombosis rates of 57 to 63% among patients with SSc, ^{42 43} with only 4% exhibiting radial artery thrombosis. The difference in thrombosis rate is hypothesized to stem from the anatomical position of the ulnar artery, ⁴⁴ surrounded by tighter structures such as the deep fascia, flexor carpi ulnaris, and palmar carpal ligament overlying Guyon's canal. This anatomical feature has been linked to diminished blood flow during wrist extension in some patients with SSc, as demonstrated by sonographic measurements of resistive index and peak systolic velocity. ⁴⁴ Although arterial bypass is an established treatment for thrombosis in the forearm and hand arteries, ³⁴ limited research exists regarding its outcomes, specifically in RP. Ruch et al. ⁴⁵ investigated the efficacy of radial artery bypass in 13 patients with RP or peripheral artery disease. Over an average follow-up of 22 months, all bypass grafts remained patent, as confirmed by sonography, with patients reporting significant pain relief. Additionally, Pace and Merritt ⁴⁰ reviewed their 35-year experience, including 31 patients with RP who underwent radial or ulnar artery vein grafts. Over a mean follow-up of 4 years, the patency rate of arterial bypass procedures was approximately 80%, as determined by magnetic resonance angiography or sonography. Similarly, favorable clinical outcomes were reported, with over 90% of patients experiencing pain relief and 80% achieving ulcer healing when periarterial sympathectomy was performed alongside arterial bypass. While most studies have focused on arterial bypasses from the distal ulnar or radial artery to the superficial or deep palmar arches, ^{40 45} digital artery bypass has recently been proposed as a management strategy for SRP. ⁴⁶ Park et al. utilized cutaneous veins to bypass occluded segments in proper digital arteries. Among 57 patients undergoing proper digital artery reconstruction, over 90% reported significant pain relief and ulcer healing. However, the 5-year recurrence-free rate was approximately 70%, with advanced age and smoking identified as significant risk factors for recurrence. ⁴⁶ Studies have indicated that arterial bypass should be performed promptly upon the detection of thrombosis, as delays may lead to extensive clot formation and the absence of a suitable distal target for reconstruction. ^{17 36} Fig. 5 shows a thrombus formation in one of our patients. Fig. 6 demonstrates an interposition vein graft after thrombus resection.

Fig. 5.

The figure shows an arterial thrombosis at radial artery. A dark purplish thrombus was identified in the distal radial artery under tourniquet control.

Fig. 6.

The figure shows an vein grafting for arterial thrombosis. An interposition vein graft was performed after thrombus resection.

Conclusion

Recent advancements in microsurgery have introduced effective and promising interventions, such as periarterial sympathectomy and arterial bypass, for managing severe cases of intractable RP. These procedures provide significant relief from symptoms, including cold intolerance, chronic pain, and nonhealing ulcers, severely hindering daily activities. In cases where medical treatments are insufficient to control the debilitating effects of intractable RP, these surgical approaches have consistently yielded satisfactory outcomes.

Funding Statement

Funding None.