Hand swelling and other non-Raynaud's symptoms as the initial presentation of systemic sclerosis: prevalence and clinical associations in two U.S. cohorts

Iqtidar Hanif, UTHealth Houston, Division of Rheumatology, Houston, TX.
Shervin Assassi, UTHealth Houston, Division of Rheumatology, Houston, TX.
Maureen D. Mayes, UTHealth Houston, Division of Rheumatology, Houston, TX.
Zsuzsanna H. McMahan, UTHealth Houston, Division of Rheumatology, Houston, TX.
Meng Zhang, UTHealth Houston, Division of Rheumatology, Houston, TX.
Julio Charles, UTHealth Houston, Division of Rheumatology, Houston, TX.
John M. VanBuren, Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, UT.
Jessica S. Alvey, Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, UT.
Kimia Ghaffari, Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, UT.
Elana J. Bernstein, Division of Rheumatology, Department of Medicine, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, New York, NY.
Flavia V. Castelino, Division of Rheumatology, Massachusetts General Hospital, Boston, MA.
Lorinda Chung, Division of Immunology and Rheumatology, Stanford University and Palo Alto VA Health Care System, Palo Alto, CA.
Luke Evnin, Scleroderma Research Foundation.
Tracy M. Frech, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, TN.
Jessica K. Gordon, Division of Rheumatology, Hospital for Special Surgery, New York City, NY.
Faye N. Hant, Division of Rheumatology, Medical University of South Carolina, Charleston, SC.
Laura K. Hummers, Division of Rheumatology, Johns Hopkins University, Baltimore, MD.
Dinesh Khanna, University of Michigan Scleroderma Program, Division of Rheumatology, University of Michigan, Ann Arbor, MI.
Kimberly S. Lakin, Division of Rheumatology, Hospital for Special Surgery, New York City, NY.
Dorota Lebiedz-Odrobina, Division of Rheumatology, Department of Internal Medicine, University of Utah, Salt Lake City, UT.
Yiming Luo, Division of Rheumatology, Department of Medicine, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, New York, NY.
Ashima Makol, Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN.
Jerry A. Molitor, Division of Rheumatic and Autoimmune Diseases, Department of Medicine, University of Minnesota, Minneapolis, MN.
Duncan F. Moore, Division of Rheumatology, Northwestern University, Chicago, IL.
Carrie Richardson, Division of Rheumatology, Northwestern University, Chicago, IL.
Nora Sandorfi, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA.
Ami A. Shah, Division of Rheumatology, Johns Hopkins University, Baltimore, MD.
Ankoor Shah, Division of Rheumatology and Immunology, Duke University, Durham, NC.
Victoria K. Shanmugam, The George Washington University School of Medicine and Health Sciences, Department of Anatomy, George Washington University, Washington, D.C.
Virginia D. Steen, Georgetown University Medical Center, Washington, DC.
Elizabeth R. Volkmann, Division of Rheumatology, Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine, CA.
Carleigh Zahn, University of Michigan Scleroderma Program, Division of Rheumatology, University of Michigan, Ann Arbor, MI.

Document Type

Journal Article

Publication Date

5-19-2025

Journal

Arthritis & rheumatology (Hoboken, N.J.)

DOI

10.1002/art.43237

Abstract

OBJECTIVE: 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. METHODS: All patient data in the GENISOS and CONQUER cohorts were reviewed. Both studies enrolled patients within five years of the first non-RP symptom. RESULTS: 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. CONCLUSION: 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.

Department

Anatomy and Regenerative Biology

Link to Full Text

Share

COinS