The Role of Botulinum Toxin A in the Treatment of Raynaud Phenomenon

Abstract

Raynaud phenomenon (RP) is a transient digital ischemia that occurs after exposure to cold temperature or emotional distress. It presents with a triphasic course: the initial white phase is followed by cyanotic discoloration and, subsequently, erythema. The attacks may be associated with pain, paresthesia, and complicate with nonhealing ulceration often leading to amputation. To date, there are no clear-cut therapeutic guidelines and many medications are used off-label. Encouraging results were reported with the use of botulinum neurotoxin-A (BoNT-A). However, there is still ongoing debate regarding indications, contraindications, best injection technique, and mechanism of action. The aim of this study was to address these issues by providing an up-to-date and detailed overview of the use of BoNT-A in RP.A PubMed database search was conducted. The available studies and techniques were evaluated and compared.The search yielded a total of 29 studies. Ten papers, published between 2004 and 2014, were considered relevant. A total of 128 patients underwent BoNT-A injections. Seventy-five percent to 100 % of the patients reported pain reduction after treatment. Healing of ulcers was reported in 75% to 100% of the affected patients. The most common complication was temporary hand weakness, with an average incidence of 14.1%. Injections targeting the neurovascular bundle at or slightly proximal to the A1 pulley were the most commonly performed.Botulinum neurotoxin-A injection proved to be a valid approach in both primary and secondary RP. The available evidence shows the achievement of both symptomatic and functional improvements in this debilitating condition. However, the patient should be adequately informed about the risk of transient hand weakness.

Injection Techniques for Common Chronic Pain Conditions of the Hand: A Comprehensive Review

“…Raynaud's phenomenon (RP) is an exaggerated thermoregulatory response triggered by cold temperature or emotional stress, resulting in local artery vasoconstriction secondary to sympathetic activation and local alpha receptors [46]. This ischemic disturbance in the fingers and toes manifests with characteristic color changes, significant pain or paresthesia, and complications such as disability and ulcers, which may require amputation [47,48].…”

“…No precise mechanism of action has been identified. Most commonly cited areas of injection include neurovascular bundles at the MCP joint or more proximally at areas including the wrist, distal palm, para-ulnar artery, para-radial artery, and the common palmar digital artery [47,48,52]. Successful injection techniques include USI and use of conservative doses of BTX-A.…”

The use of Botulinum Toxin in digital reconstruction of patients affected by Raynaud’s phenomenon: a case report

“…Raynaud's phenomenon may be "primary" (also referred to as Raynaud's disease), when it is an isolated symptom, or "secondary" (Raynaud's syndrome) if it associates with collagen diseases, medications, physical etiologies, paraneoplastic or endocrine syndromes [2]. The former was found to have a prevalence of 8.1% in men and 9.6% in women; the latter of 18.6% and 19.7% in men and women, respectively [7].…”

“…Specifically, BoNT-A may increase blood flow by mean of vasodilation. The increased vessels diameter results from chemical sympathectomy, due to the inhibition of norepinephrine release, the abolished cholinergic inhibition of neurogenic relaxation and the prevention of recruitment and activity of α2 adrenergic receptors [2,8]. Moreover, in RP patients, the lack of substance P, glutamate and calcitonin gene-related protein releases reduces nociception and, consequently, the sympathetic stimulation induced by pain [9,10].…”

“…Once internalized in the nerve terminal, the toxin cleaves the synaptosomal associated protein-25 (SNAP-25), thus blocking acetylcholine and other vesicles migration and release. Recently, several papers reported the offlabel use of BoNT-A in RP, achieving both symptomatic and functional improvements [2]. Moreover, experimental studies described a beneficial effect on flap vascularization and survival, although all limited to animal models [3,4].…”