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Hand swelling and other non-Raynaud's symptoms as the initial presentation of systemic sclerosis: prevalence and clinical associations in two U.S. cohorts.
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Hand swelling and other non-Raynaud's symptoms as the initial presentation of systemic sclerosis: prevalence and clinical associations in two U.S. cohorts. Arthritis & rheumatology (Hoboken, N.J.) Hanif, I., Assassi, S., Mayes, M. D., McMahan, Z. H., Zhang, M., Charles, J., VanBuren, J. M., Alvey, J. S., Ghaffari, K., Bernstein, E. J., Castelino, F. V., Chung, L., Evnin, L., Frech, T. M., Gordon, J. K., Hant, F. N., Hummers, L. K., Khanna, D., Lakin, K. S., Lebiedz-Odrobina, D., Luo, Y., Makol, A., Molitor, J. A., Moore, D. F., Richardson, C., Sandorfi, N., Shah, A. A., Shah, A., Shanmugam, V. K., Steen, V. D., Volkmann, E. R., Zahn, C., Skaug, B. 2025Abstract
Raynaud's phenomenon (RP) is often the initial clinical manifestation of systemic sclerosis (SSc), but some patients develop other manifestations first. To help elucidate the diversity of SSc presentation in its early stages, we describe the initial clinical manifestations and antinuclear antibody (ANA) profiles of patients in two early SSc cohorts.All patient data in the GENISOS and CONQUER cohorts were reviewed. Both studies enrolled patients within five years of the first non-RP symptom.194/439 (44.2%), and 292/938 (31.1%) patients in GENISOS and CONQUER, respectively, had a non-RP initial symptom, most commonly puffy fingers/hands. Black patients had a non-RP symptom prior to RP more commonly than other race and ethnicity categories. Non-RP first patients were more likely than RP first patients to have diffuse cutaneous involvement and joint contractures at enrollment and had a higher prevalence of RNA Polymerase III antibody positivity.In two large U.S. cohorts, >30% of patients began to manifest SSc with puffy fingers/hands or other symptoms, without the "warning sign" of RP as their initial symptom. These patients presented with more severe skin and musculoskeletal disease on average, highlighting the importance of early recognition. The most common autoantibody associated with this presentation was RNA Polymerase III. These results should be considered in efforts to recognize SSc in its earliest stages. Puffy fingers/hands, even in the absence of RP, should prompt consideration of early SSc and testing for ANA and SSc-associated autoantibodies including RNA Polymerase III.
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