REVIEW - Treating Raynaud's crises can be tricky

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VascularWeb

Volume 1

Issue 2

2005

Treating Raynaud's Crises Can Be Tricky

By Colin

Elsevier Global Medical News

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., of s

Hopkins University in Baltimore.

Dr. Wigley 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, " Dr. Wigley said. There's

occlusion, structural disease, and thrombotic events. Treatment should

address vascular disease as well as the vasospasm.

Not all scleroderma patients are equally susceptible to catastrophic

Raynaud's episodes, Dr. Wigley said. 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, " Dr. Wigley said.

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 were

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.

PIChemical 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.

PIAntiplatelet therapy. " Aspirin works, " Dr. Wigley said.

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.

PIAnticoagulation. In patients who do not respond rapidly to prostaglandin

infusion, sympathectomy, and/or antiplatelet therapy, the crisis is almost

surely caused by thrombosis, Dr. Wigley said.

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.

Anticoagulation is unproven as chronic therapy for Raynaud's phenomenon

unless patients have a secondary hypercoagulation disorder, such as

antiphospholipid antibody syndrome.

PIThrombolytic therapy. There is little evidence to support the use of

thrombolytic therapy in patients with scleroderma who have catastrophic

Raynaud's events, and Dr. Wigley does not recommend it.

PISurgical sympathectomy. Surgical sympathectomy denervates the finger. ' " We

use a digital sympathectomy when medical therapy is not working, " he said.

However, there is conflicting evidence on the efficacy of this procedure.

In a recent retrospective review of 129 fingers in 38 patients with

scleroderma and chronic digital ischemia, 86% reported improved symptoms

with periarterial sympathectomy after a follow-up period of up to 41 months.

The study was presented at the 2003 annual meeting of the American College

of Rheumatology (Arthritis Rheum. 2003;48[suppl. 9]:S560).

However, a recent systematic review of 251 digits came to less optimistic

conclusions. It found that 14% of all patients required amputation and 18%

of patients had ulcer recurrence, after up to nearly 5 years of follow-up.

" Some type of postoperative complication was reported in 37% of patients

with systemic sclerosis, " according to the authors, who noted that the

literature is marred by a number of shortcomings (J. Rheumatol.

2003;30:1788-92).

" Sympathectomy can reverse an ischemic crisis, but may not cure the

problem, " Dr. Wigley said. It sometimes leads to finger contractures and

fibrosis, " so I don't use it lightly, " he added.

" Usually it gets the patient out of a crisis. A year later the Raynaud's is

back, but it tends not to be as severe. "

PIVascular surgery. A retrospective case series reported on the outcomes of

revascularization of occluded ulnar arteries in eight patients with

scleroderma and severe Raynaud's phenomenon with digital ulcers. The

patients had positive 's tests, had angiograms showing occlusive

disease, and had failed to improve with nonoperative treatment.

All eight patients " experienced dramatic improvement in Raynaud's phenomenon

and refractory digital ulcers, " according to the authors (J. Rheumatol.

2002;29:102-6).

In isolated cases, " you need to consider it, " Dr. Wigley said. However, he

advises caution. " You have to be dealing with an experienced vascular

surgeon and be very conservative about attacking these blood vessels. ...

Patients have lost not just their finger but parts of their hands. "

Dr. Wigley said it's rare to find a lesion that is an appropriate target for

microsurgical repair.

" Most of the time you have the combination of a large vessel, such as an

ulnar occlusion, and a microvascular disease, so there's nothing you can

connect to, to make a repair. "

For prevention of recurrent crises, " there's no drug more effective than

warm temperatures, " Dr. Wigley said.

When cold is unavoidable, he recommends using continued vasodilator therapy,

aspirin, and antioxidants. Statins " will play a bigger role as we learn more

about these agents. "

Other options for preventing recurrences include:

PIIloprost infusions. Recent trials from Europe suggest that prophylactic

infusions of iloprost may reduce the frequency and severity of Raynaud's

events among scleroderma patients (Med. Clin. [barc.] 2004;122:501-4; Clin.

Rheumatol. 2002;21:244-50).

PIBosentan. Findings from a recent trial demonstrated a reduction in digital

ulcers among scleroderma patients after treatment with the endothelin

receptor antagonist bosentan (Arthritis Rheum. 2004;50:3985-93).

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