Hanif Iqtidar, Assassi Shervin, Mayes Maureen D, McMahan Zsuzsanna H, Zhang Meng, Charles Julio, VanBuren John M, Alvey Jessica S, Ghaffari Kimia, Bernstein Elana J, Castelino Flavia V, Chung Lorinda, Evnin Luke, Frech Tracy M, Gordon Jessica K, Hant Faye N, Hummers Laura K, Khanna Dinesh, Lakin Kimberly S, Lebiedz-Odrobina Dorota, Luo Yiming, Makol Ashima, Molitor Jerry A, Moore Duncan F, Richardson Carrie, Sandorfi Nora, Shah Ami A, Shah Ankoor, Shanmugam Victoria K, Steen Virginia D, Volkmann Elizabeth R, Zahn Carleigh, Skaug Brian
University of Texas Health Science Center at Houston.
University of Utah, Salt Lake City.
Arthritis Rheumatol. 2025 May 19. doi: 10.1002/art.43237.
Raynaud 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 Genetics vs Environment in Scleroderma Outcomes Study (GENISOS) and Collaborative National Quality and Efficacy Registry (CONQUER) cohorts were reviewed. Both studies enrolled patients within five years of the first non-RP symptom.
In GENISOS and CONQUER, respectively, 194 (44.2%) of 439 and 292 (31.1%) of 938 patients had a non-RP initial symptom, most commonly puffy fingers/hands. Black patients had a non-RP symptom before RP more commonly than patients in 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 US 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.
雷诺现象（RP）通常是系统性硬化症（SSc）的初始临床表现，但有些患者先出现其他表现。为了帮助阐明SSc早期表现的多样性，我们描述了两个早期SSc队列中患者的初始临床表现和抗核抗体（ANA）谱。
回顾了硬皮病结局研究（GENISOS）和全国协作质量与疗效登记处（CONQUER）队列中的所有患者数据。两项研究均纳入了出现首个非RP症状后五年内的患者。
在GENISOS和CONQUER队列中，分别有439例患者中的194例（44.2%）和938例患者中的292例（31.1%）有非RP初始症状，最常见的是手指/手部肿胀。黑人患者在出现RP之前出现非RP症状的情况比其他种族和族裔类别的患者更常见。非RP首发患者比RP首发患者在入组时更可能有弥漫性皮肤受累和关节挛缩，且RNA聚合酶III抗体阳性率更高。
在美国的两个大型队列中，超过30%的患者开始表现为SSc时出现手指/手部肿胀或其他症状，而没有RP这一“警示信号”作为初始症状。这些患者平均表现出更严重的皮肤和肌肉骨骼疾病，凸显了早期识别的重要性。与这种表现相关的最常见自身抗体是RNA聚合酶III。在努力尽早识别SSc时应考虑这些结果。即使没有RP，手指/手部肿胀也应促使考虑早期SSc并检测ANA和与SSc相关的自身抗体，包括RNA聚合酶III。
