Botulinum Toxin in the Long-Term Treatment of Refractory Raynaud’s Phenomenon

September 2019 | Volume 18 | Issue 9 | Case Reports | 943 | Copyright © September 2019

Usman Asad BS, Brett Austin MD, Michelle Tarbox MD, Brent Paulger MD

Texas Tech University Health Sciences Center, Lubbock, TX

Abstract

Raynaud’s phenomenon is an exaggerated physiological response of blood vessels in the distal extremities to emotional stress and cold. It can be idiopathic or secondary to a connective tissue disorder, such as scleroderma or systemic lupus erythematosus. Treatment for Raynaud’s phenomenon consists primarily of lifestyle modifications; if unsuccessful, pharmacotherapy with dihydropyridine calcium channel blockers can be added. Botulinum toxin (BTX-A) is a neurotoxic protein produced by Clostridium botulinum spores. While most widely known for its cosmetic use, BTX-A has many therapeutic utilities due to its ability to inhibit multiple neurotransmitters. In this report, we present a patient with Raynaud’s phenomenon refractory to standard therapies whose symptoms resolved after treatment with BTX-A. Follow-up with the patient after one and five years showed no relapse or recurrence of symptoms. 

J Drugs Dermatol. 2019;18(9):943-945. 

INTRODUCTION

Raynaud’s phenomenon is an exaggerated physio-logical response of blood vessels in the distal extremities, mainly in the digits, to emotional stress and cold. Raynaud’s phenomenon can be primary idiopathic or secondary to a connective tissue disorder, such as scleroderma or systemic lupus erythematosus. It can also occur secondary to a constant vibratory stimulus, notably in string musicians, construction workers, and similar occupations requiring manual dexterity and exposure to constant vibration.1 First-line treatment generally involves lifestyle modifications such as avoiding cold, minimizing stress, and smoking cessation.2,3 If unsuccessful, first-line pharmacotherapy is dihydropyridine calcium channel blockers (CCBs). Alternative therapies include phosphodiesterase-5-inhibitors, topical glyceryl trinitrate, prostacyclin analogues (iloprost), and endothelin receptor antagonists.4,5

Botulinum toxin-A (BTX-A) is a neurotoxic protein produced by Clostridium botulinum spores. While most widely known for its cosmetic applications, BTX-A also has utility in treatment of migraines, torticollis, detrusor hyperactivity, spasticity, strabismus, and blepharospasm.6 In this report, we present a patient with Raynaud’s phenomenon refractory to standard therapies whose symptoms resolved after treatment with BTX-A.

CASE REPORT

A 19-year-old-female presented to our clinic with a 2-month history of severe pain and ulceration of her fingers. She described the onset of her pain as erratic and triggered by exposure to the cold. Upon exposure, the skin on her fingers would change from pink to purple, white, or blue. Her left index finger was severely affected and remained purple in the absence of cold temperatures. Wearing gloves failed to alleviate her symptoms. Her past medical history was significant for hypothyroidism and a recent diagnosis of systemic lupus erythematosus. Her daily medications included thyroid supplementation and prednisone, which she had taken for one month without improvement. At the time, she was a music major in college and spent many hours playing the violin, thereby exposing her fingers to substantial vibratory stimulus. On physical examination, her fingertips were cold to touch and dusky with a blue-black discoloration bilaterally. Her left index fingertip was ulcerated and necrotic; her palms and proximal fingers were pink and warm (Figure 1). A diagnosis of Raynaud’s phenomenon with chronic debilitating digital ulcers was made. Multiple remedies were attempted including prednisone, hydroxychloroquine, tadalafil, aspirin, stellate ganglion nerve block, and nitroglycerin cream; however, they all failed to control the ischemia. On subsequent visits, we recommended botulinum toxin as an alternative therapy; however, there was a delay in initiation because the patient’s rheumatologist did not want to start BTX-A immediately. The patient soon developed fingertip necrosis that required intervention from an orthopedic hand surgeon. Once it became apparent that she needed quick, aggressive intervention to prevent further severe, debilitating necrosis of her digits, BTX-A treatment was immediately started.

A vial of BTX-A (100MU) was diluted in preservative-free normal saline for a final concentration of 2U/0.1mL. A cumulative total