Botulinum toxin in the treatment of Raynaud's phenomenon: a pilot study (2004)

Sir, Raynaud's phenomenon (RP) is defined as an episodic digital asphyxia caused by arterial insufficiency. Although RP aetiology remains incompletely understood, abnormal central sympathetic control via vascular innervation has been discussed. This concept is supported by the clinical observation that emotional stress is a trigger in up to a third of vasospastic attacks in primary RP [1], and studies demonstrating the beneficial effects of sympatholytic drugs [2] and the use of sympathectomy [3]. The use of Botulinum toxin A (BTX-A) is an established treatment for focal dystonic and spastic syndromes. Additionally, clear beneficial effects of BTX-A have been shown in various types of focal hyperhidrosis [4]. In general, the effect of BTX-A is based on the anticholinergic effects at the neuromuscular endplate and the eccrine sweat glands. Recently, differential effects of BTX-A on vasoconstriction and vasodilation have been studied in vitro[5]. Botulinum toxin type A reduced the amplitude of arterial isometric contractions in response to repeated electrical stimulation of sympathetic axons by 70–80%. Furthermore, the presynaptic cholinergic inhibition of neurogenic relaxation was abolished by BTX-A. As a pilot to a randomized, double-blinded, placebo-controlled trial we treated primary and secondary RP patients with intradigital BTX-A injections. The clinical response was measured using a visual analogue scale (VAS range 0–10) for clinical symptoms (pain, stiffness, numbness, cold sensation), and the superficial skin blood flow was assessed with laser Doppler interferometry (LDI). A 19-year-old female patient with a 2-year history of MCTD refractory to any other treatment was randomly injected on fingers 2 and 5 of the right and on fingers 2 and 3 of the left hand at six injection sites per finger (1 MU per site of BOTOX®, Allergen Pharmaceuticals Ltd, Westport, Ireland). After 1 week the patient reported relief from pain (VAS pre: 8, post: 5), stiffness (VAS pre: 7, post: 4) and numbness (VAS pre: 6, post: 4). After 6 weeks the LDI scan showed a significant difference between the treated and untreated fingers (102·2 ± 12·1 aU vs. 718 ± 5·6 aU, P < 0·004, Fig. 1). After 9 weeks the patient also reported an improvement in the noninjected fingers. Laser Doppler interferometry scan of the left (a) and right hand (b) 6 weeks after local injections with Botulinum toxin type A. The white arrows mark the injected fingers. The second patient was a 65-year-old female who had suffered 7 years’ of primary RP resistant to conventional treatment strategies. Baseline LDI scans of both hands were obtained. Subsequently, all five fingers of the more affected left hand were injected at six sites per finger (10 MU per site of Dysport®, Ipsen Pharma, Ettlingen, Germany). Three days after the injections, the patient reported relief from stiffness (VAS pre: 5, post: 3), numbness (VAS pre: 8, post: 3) and cold sensation (VAS pre: 8·5, post: 4). Pain was not reported. After 6 weeks, the LDI scan revealed an increased superficial skin blood flow of both hands. However, the increase of blood flow in the treated hand was 58·1% and in the untreated hand 24·8% (Table 1). Our data suggest a beneficial effect of BTX-A in these two patients with primary and secondary RP based on clinical evaluation as well as objective LDI measurements. Furthermore, there is some suggestion of a mild systemic effect on noninjected fingers. This phenomenon has also been observed in patients with excessive axillary hyperhidrosis in two multicentre trials [6,7]. To evaluate the clinical relevance of BTX-A in RP, randomized, controlled clinical studies are warranted.