The first-line therapy for mild to moderate disease refractory to conservative management includes monotherapy with dihydropyridine calcium channel blockers. For severe disease, combination therapy involves addition of other classes of medications including phosphodiesterase 5 inhibitors, topical nitrates, angiotensin receptor blockers, or selective serotonin reuptake inhibitors. Intravenous prostacyclin, endothelin receptor blockers, and onabotulinumtoxinA injections may be added as third-line therapy. Finally, surgical management including sympathectomy with continued pharmacologic therapy may be needed for disease recalcitrant to the aforementioned options.2
OnabotulinumtoxinA is a neurotoxin produced by the bacterium Clostridium botulinum. The toxin’s mechanism of action involves inhibition of the release of presynaptic acetylcholine-containing vesicles at the neuromuscular junction through cleavage of sensory nerve action potential receptor proteins. In addition, it inhibits smooth muscle vasoconstriction and pain by blocking α2-adrenergic receptors on blood vessels and chronic pain-transmitting C fibers in nerves, respectively.3,5
Only recently has onabotulinumtoxinA been used for treatment of RP. Botulinum toxin is approved for the treatment of spastic and dystonic diseases such as blepharospasm, headaches in patients with chronic migraines, upper limb spasticity, cervical dystonia, torticollis, ocular strabismus, and hyperhidrosis.3 However, the versatility of its therapeutic effects is evident in its broad off-label clinical applications, including achalasia; carpal tunnel syndrome; and spasticity relating to stroke, paraplegia, and cerebral palsy, among many others.5
Few studies have analyzed the use of onabotulinumtoxinA for the treatment of RP.3,6 There is no consensus yet regarding dose, dilution, or injection sites. One vial of onabotulinumtoxinA contains 100 U and is reconstituted in 20 mL of normal saline to produce 5 U/mL. The simplest technique involves the injection of 5 U into the medial and lateral aspects of each finger at its base, at the level of or just proximal to the A1 pulley, for a total of 50 U per hand.7 In the foot, injection can be made at the base of each toe near the proximal phalanges. A regimen of 50 to 100 U per hand was used by Neumeister et al5 on 19 patients, who subsequently standardized it to 10 U on each neurovascular bundle in a follow-up study,7 giving a total volume of 2 mL per injection. Associated pain or a burning sensation initially may be experienced, which may be mitigated by a lidocaine hydrochloride wrist block prior to injection.7 This technique produced immediate and lasting pain relief, increased tissue perfusion, and resolved digital ulcers in 28 of 33 patients. Most patients reported immediate relief, and a few noted gradual reduction in pain and resolution of chronic ulcers within 2 months. Of the 33 patients, 7 (21.2%) required repeat injections for recurrent pain, but the majority were pain free up to 6 years later with a single injection schedule.7
Injection into the palmar region, wrists, and/or fingers also may be performed. Effects of using different injection sites (eg, neurovascular bundle, distal palm, proximal hand) have been explored and were not notably different between these locations.8 Lastly, the frequency of injections may be attenuated according to the spectrum and severity of the patient’s symptoms. In a report of 11 patients who received a total of 100 U of onabotulinumtoxinA per hand, 5 required repeat injections within 3 to 8 months.9