BOSTON — Raynaud's phenomenon secondary to scleroderma can quickly progress to catastrophic ischemic events resulting in the loss of fingers, toes, and even limbs; at the same time, the efficacy of therapies varies widely.
Determining the root causes of a Raynaud's crisis can be difficult during an emergency. Local vasospasm and/or more complicated and widespread vascular disease can trigger the event. Initial therapies should target vasospasm; if the patient does not respond, treatment should shift to addressing small vessel disease and occlusions, according to Fredrick Wigley, M.D.
Dr. Wigley, of Johns Hopkins University in Baltimore, reviewed the therapies for treating a Raynaud's crisis at a recent meeting on rheumatology sponsored by Harvard Medical School.
In patients with primary Raynaud's disease that is not complicated by scleroderma, the loss of blood flow to the extremities and the subsequent pain or discomfort is typically caused by vasoconstriction, not vasculopathy.
Warmer temperatures or stress reduction may relieve the symptoms in these patients, he said. If lifestyle changes are not sufficient, he recommends trying a calcium channel blocker (for example, amlodipine).
In patients with scleroderma, the clinical picture is considerably more complex. “We see major vascular disease,” said Dr. Wigley. There's occlusion, structural disease, and thrombotic events. Treatment should address vascular disease as well as the vasospasm, he said.
Not all scleroderma patients are equally susceptible to catastrophic Raynaud's episodes, said Dr. Wigley. In his experience, those most prone to a crisis are scleroderma patients who have coexisting macrovascular disease, typically accompanied by recurrent digital ulcers and amputation.
These patients tend to have limited skin disease, are anticentromere positive, and demonstrate granzyme B cleavable autoantigens.
The macrovascular disease is often observed as palmar arch and ulnar artery disease. Symptoms during a crisis are markedly more severe than during a typical episode of primary Raynaud's. “Persistent widespread ischemic pain heralds tissue infarction and gangrene,” he said.
“If a patient comes to your office and says, 'I'm having a Raynaud's attack and my finger will not get warm. And not only that, the palm of my hand is hurting,' and the patient is holding the hand in a downward position, that patient is having a heart attack of the hand,” said Dr. Wigley, adding that it needs to be treated as a medical emergency.
Angiograms of scleroderma patients' hands reveal that not just tiny vessels but also medium-sized arteries “just disappear. … Only collateral flow is keeping the finger alive.”
Dr. Wigley offered the following observations about various treatment options:
▸ Prostaglandin infusions. For those patients already taking a calcium channel blocker, Dr. Wigley administers repeated infusions of a prostaglandin (epoprostenol in the United States and Canada; iloprost in Europe).
“It's effective and quite dramatic,” he observed. And for short periods of continuous infusion, the drugs are relatively inexpensive.
In randomized trials, Dr. Wigley and his colleagues have shown prostaglandin infusions to be beneficial (Ann. Intern. Med. 1994;120:199–206). However, oral therapy is ineffective (Arthritis Rheum. 1998; 41:670–7).
In one recent case series, five women who had suffered seven catastrophic Raynaud's crises received epoprostenol infusions over 5 days at a dose of 8 ng/kg per minute. The crises were completely resolved in two of the five patients, and improved in the remaining three, according to a paper presented at the 2004 annual meeting of the American College of Rheumatology (Arthritis Rheum. 2004; 50[suppl. 9]:S638).
Dr. Wigley recommends starting epoprostenol at a dose of 2 ng/kg per minute. “It's a very low dose and is well tolerated,” he said. He warns against infusing patients who have pulmonary artery hypertension, as these patients require very close attention.
▸ Chemical sympathectomy. In a crisis, Dr. Wigley said he performs a rapid chemical sympathectomy at the bedside or in the office, using lidocaine for a digital block. “It's short acting, but it decreases pain immediately. You can get a dramatic flush to skin and reverse the event if it's vasospastic.”
If the crisis is thrombotic, however, sympathectomy will be ineffective, he said.
▸ Antiplatelet therapy. “Aspirin works,” said Dr. Wigley.
Calcium channel blockers and prostaglandins are also potent vasodilators. “When you give these agents, you affect platelet function.”
Less is known about other agents, such as ticlopidine, clopidogrel, cilostazol, and pentoxifylline, he said.
▸ Anticoagulation. In patients who do not respond rapidly to prostaglandin infusion, sympathectomy, and/or antiplatelet therapy, the crisis is almost surely caused by thrombosis, said Dr. Wigley. In his experience, anticoagulation can help in the acute phase, and he advises treatment for 24 hours, although he acknowledged that there are no controlled trials to support this practice.