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CHICAGO -- Although the pathophysiology of Raynaud's phenomenon really arises in the brain, the most effective treatments remain those targeting its vascular manifestations, a specialist told rheumatologists here.

Efforts thus far to interrupt the neurological dysfunction underlying Raynaud's have come up short and there aren't many others in the offing, said Frederick M. Wigley, MD, of Johns Hopkins University in Baltimore.

For now, therefore, vasodilators are the mainstays of treatment and the challenge for clinicians is which ones to use in which patients, Wigley said at the .

Raynaud's phenomenon is persistent and severe vasoconstriction in the fingers and/or toes resulting in extreme pallor. In the worst cases, the chronic ischemia leads to tissue damage, with patients prone to infection. Pain is not a common feature of Raynaud's and, when it does occur, it calls for a change in management, Wigley said.

Although the vasoconstriction appears to be a local phenomenon, it's ordered from the hypothalamus, where temperature signals are received and processed. In patients with Raynaud's, the hypothalamus overreacts to signals that the body is cold (which may be false) and triggers mechanisms to conserve body heat. That includes reducing blood flow to the extremities. (People exposed to cold weather are well aware of these mechanisms.)

Cold, of course, is the main trigger in Raynaud's phenomenon, although roughly one-third of patients experience it in response to stress and anxiety -- another indication that the condition is neurological and even psychological in origin. (Other risk factors include smoking and drugs with vasoconstricting effects -- some 30% of children treated with stimulants for ADHD will experience Raynaud's, Wigley said -- although caffeine does not appear to be linked with Raynaud's.)

The stress trigger might suggest psychological interventions would be effective, but that hasn't proved out, Wigley said. Controlled trials of "biofeedback" and other behavioral therapies have not shown a clear benefit. Nor have relaxation techniques or acupuncture.

What does work, he said, is avoidance of risk factors and vasodilator drug therapy.

For starters, that means patients should keep warm (a variety of hand-warmers are marketed expressly for Raynaud's patients) and quit smoking. Treatments for other disorders may also be adjusted to minimize vasoconstriction.

Drug therapy should be reserved for patients with relatively severe Raynaud's that affects quality of life. For such patients whose Raynaud's has not progressed to the point of developing skin ulcers, current thinking is to begin with a sustained-release calcium channel blocker. Initial dosing should be low, then gradually titrated upward until symptoms are brought under control. These agents are relatively easy to take and will help many patients, although Wigley pointed out that relief tends to be modest.

If response is not adequate, Wigley said anti-platelet therapy with low-dose aspirin or clopidogrel (Plavix) can be added.

A second vasodilator is appropriate for patients whose fingers are ulcerated, he said. This can be either a phosphodiesterase-5 inhibitor such as sildenafil (Viagra) or a topical nitrate. Wigley noted, though, that patients develop tolerance to nitrates over time.

Third-line treatment can include endothelin receptor antagonists such as bosentan (Tracleer), another type of vasodilator.

Patients in ischemic crisis stemming from Raynaud's can have vascular surgery or sympathectomy in the hand or forearm, but this "may not cure the problem" permanently, Wigley cautioned.

Another speaker (a dermatologist) at the symposium endorsed botulinum toxin (e.g., Botox) as a therapy for Raynaud's, but Wigley demurred. He helped lead a randomized trial published in 2017 that found no benefit for the injections in patients with Raynaud's secondary to systemic sclerosis. "I don't have a lot of enthusiasm for [Botox] because of this study," he said, adding that the injections cost around $1,000 per session.

One point he stressed during his talk was that "persistent pain is a medical emergency." Pain is rare in primary Raynaud's, he said, but is more common when the condition is secondary to another illness.

In any event, patients in pain need urgent treatment, Wigley said: local digital block to control the pain and immediate vasodilator therapy (such as short-acting calcium channel blocker) to relieve the acute ischemia. For patients whose blood flow remains severely impaired, he recommended intravenous prostaglandins.

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