SNOWMASS, COLO. - Abnormal findings on nailfold capillary microscopy and the presence of scleroderma-specific autoantibodies in patients presenting with new-onset Raynaud’s phenomenon without overt connective tissue disease are powerful independent predictors of progression to definite scleroderma.

Dr. Fredrick M. Wigley

A landmark Canadian prospective study in 586 consecutive patients presenting with isolated Raynaud’s phenomenon showed that 13% of them developed scleroderma during 3,197 person-years of follow-up. Another 1% developed other connective tissue diseases. Fewer than 2% of those with normal nailfold capillaries and no scleroderma-specific antibodies went on to develop definite scleroderma during 15-20 years, and the majority who did progress to scleroderma did so within the first year or two, noted Dr. Fredrick M. Wigley at a symposium sponsored by the American College of Rheumatology.

In contrast, 80% of patients with baseline evidence of microvascular damage on nailfold microscopy together with one or more scleroderma-specific autoantibodies developed scleroderma. Two-thirds of patients with these baseline findings in the University of Montreal study (Arthritis Rheum. 2008;58:3902-12) progressed to definite scleroderma within the first 5 years of follow-up, added Dr. Wigley, professor of medicine and director of the scleroderma center at Johns Hopkins University, Baltimore.

Raynaud’s patients with one or more scleroderma-specific autoantibodies but no nailfold capillary abnormalities had a 35% rate of progression to scleroderma, with 60% of cases being diagnosed within the first 5 years. Patients with nailfold capillary abnormalities but no scleroderma-specific autoantibodies had a 26% long-term rate of progression to scleroderma, with roughly 90% of cases occurring within 5 years.

Nailfold microscopy is a simple matter. It can be carried out using a drop of immersion oil and an ophthalmoscope set at diopter 40. The microvascular damage that portends subsequent definite scleroderma follows a characteristic chronologic sequence consisting of enlarged capillary loops, followed by capillary loss, and capillary telangiectasias, Dr. Wigley explained.

The scleroderma-specific autoantibodies that proved predictive in the large Canadian study were anticentromere (anti-CENP-B) anti-TH/To, anti-topoisomerase I, and anti-RNA polymerase III.

The findings in the Canadian study, which was the first large prospective study of predictors of scleroderma in patients with Raynaud’s phenomenon, were remarkably consistent with those obtained earlier through a literature search by investigators at Dartmouth-Hitchcock Medical Center, Lebanon, N.H. They analyzed 10 published articles including 639 patients with primary Raynaud’s phenomenon, and determined that 12.6% of them developed a connective tissue disease during 2,531 person-years of follow-up, compared with 13.6% of patients in the Montreal study. Scleroderma accounted for the great majority of the cases of connective tissue disease in the Dartmouth-Hitchcock analysis, Dr. Wigley noted.

The mean rate of transition from isolated Raynaud's to scleroderma or another connective tissue disease in this series was 3.2 cases per 100 person-years. The best predictors were abnormal nailfold capillaries and the presence of antinuclear antibodies (Arch. Intern. Med. 1998;158:595-600).

Dr. Wigley declared that he receives consulting fees and/or research grants from Actelion, Amira, KineMed, MedImmune, Novartis, Orion, Pfizer, and United Therapeutics.

02/14/11  

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EXPERT ANALYSIS FROM A SYMPOSIUM SPONSORED BY THE AMERICAN COLLEGE OF RHEUMATOLOGY

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