Emerging Novel Treatment Strategies for Raynaud Phenomenon

If conservative treatment with medications such as dihydropyridine, calcium channel blockers, alpha-adrenergic blockers, and phosphodiesterase-5 inhibitors is unsuccessful, clinicians can consider chemical sympathectomy, botulinum neurotoxin injection, and fat pad grafting.

Rheumatologists may be able to provide better overall care for those with Raynaud phenomenon (RP) by establishing new partnerships and approaching the disease in a proactive manner.1 Joshua Beckman, MD, MS, Professor of Medicine and Director of the Section of Vascular Medicine at Vanderbilt University Medical Center in Nashville, Tennessee, said those with RP may achieve better results if partnerships are established among the surgical and medical teams. Being collaborative earlier in the course of the disease may have advantages over referring only when the patient fails first-line therapies.

“I [have been a] strong advocate for the team approach to complicated disease states,“ Dr Beckman told Rheumatology Advisor. “In my experience, rheumatologists are very facile with immune-modulating therapies, but [are] less comfortable with the vascular manifestations. For those whose comfort level may be low, I would suggest partnering with a vascular clinician or a surgical or medical associate who can work with the rheumatologist to help manage the vascular component of the disease,” said Dr Beckman.

He said several key components of managing RP are commonly overlooked by clinicians. He emphasized maintaining total body warmth because, commonly, the pathologic vasospasm has some response to the body’s perceived warmth. Dr Beckman also noted that it is important to be protective of the fingers and hands.

“In a state of blood flow barely adequate for the maintenance of baseline metabolism, small injuries may lead to wounds. Dosing the vasodilators takes some practice. In my experience, patients rarely feel lightheaded until the vasospasm begins to be relieved,” Dr Beckman told Rheumatology Advisor. “I commonly use doxazosin, a peripherally acting alpha blocker, instead of centrally acting agents to avoid the tolerance and rebound that centrally acting agents are more likely to cause.”

RP is marked by excessively reduced blood flow in response to cold or emotional stress and results in hyperactivation of the sympathetic nervous system, causing extreme vasoconstriction of the peripheral blood vessels. Primary RP, or Raynaud disease, is a distinct clinical entity from secondary RP, which is usually associated with autoimmune disease.

A host of pharmacologic and invasive therapies have been studied to treat symptoms of RP. In recent years, phosphodiesterase-5 inhibitors have shown considerable promise in patients with RP. However, there currently are no established therapeutic guidelines, and clinicians often use medications off-label.

Gregory Landry, MD, Professor of Surgery at Oregon Health & Science University Knight Cardiovascular Institute in Portland, Oregon, said most of the current medical treatment options for RP, such as calcium channel blockers, angiotensin receptor blockers, and alpha-receptor antagonists, seem to work best in patients with primary RP.

“The group of patients with secondary [RP] due to scleroderma are particularly difficult to treat,” said Dr Landry. “However, most of the research that has been done evaluating the phosphodiesterase-5 inhibitors, such as sildenafil and tadalafil, has been done in patients with secondary [RP] from rheumatologic diseases, and this group of patients does seem to respond well to these medications. I personally have treated several patients with scleroderma and finger ulcers who have gone on to heal finger ulcers that previously did not seem to be healing.”

If conservative treatment with oral medications such as dihydropyridine, calcium channel blockers, alpha-adrenergic blockers, and phosphodiesterase-5 inhibitors is unsuccessful, many clinicians refer patients for chemical sympathectomy. However, there are no randomized, controlled trials to support its use.

“I am not a big enthusiast for sympathectomy. My impression is that you can trick the sympathetic nervous system for a while but not permanently, and there is a high recurrence rate for upper extremity sympathectomy. This seems to be true whether it is a cervical, thoracic, or digital sympathectomy,” Dr Landry told Rheumatology Advisor.

“I would reserve sympathectomy for patients in which a short-term goal was the objective, such as trying to heal a refractory ulceration. It also seems to be of benefit in patients with concomitant hyperhidrosis. But as a long-term strategy for most people with [RP], I think the results have been disappointing.”