405 Alarcon, et al: Cumulative joint damage patterns in RA Personal non-commercial use only. The Journal of Rheumatology Copyright © 2015. All rights reserved. Characterization of Cumulative Joint Damage Patterns in Patients with Rheumatoid Arthritis: A Clinical, Serological, and Gene Polymorphism Perspective Renata Trigueirinho Alarcon, Artur da Rocha Corrêa Fernandes, Ieda Maria Laurindo, Manoel Barros Bértolo, Geraldo Castelar Pinheiro, and Luís Eduardo Andrade ABSTRACT. Objective. To characterize cumulative joint damage (CJD) patterns in rheumatoid arthritis (RA) and determine their associations with demographic/clinical features and HLA-DRB1 gene polymorphism. Methods. Hand and foot radiographs were obtained from 404 patients with RA. CJD patterns were determined by 3 derivations from Sharp/van der Heijde scores, obtained by the mathematical division of scores for hands/feet (Sharp-h/f score), fingers/wrists (Sharp-f/w score), and erosion/space narrowing (Sharp-e/sn score), respectively. DNA and serum were obtained for deter- mination of HLA-DRB1 polymorphism, rheumatoid factor (RF), and anticitrullinated protein antibodies (ACPA). Results. Patients with wrist-dominant CJD pattern were more likely to have severe RA than those with finger-dominant pattern (68.4% vs 46.0%; p = 0.036) as were those with foot-dominant vs hand-dominant CJD pattern (76.5% vs 56.4%; p = 0.044). HLA-DRB1 shared epitope (SE) alleles were associated with erosion-dominant CJD pattern (p = 0.021). Patients with erosion-dominant CJD pattern had higher levels of RF and ACPA than those with space-narrowing–dominant CJD pattern (median RF 71.35 U/ml vs 22.05 U/ml, respectively; p = 0.003; median ACPA 187.9 U/ml vs 143.2 U/ml, respectively; p < 0.001). The majority of triple-positive patients (SE+, RF+, ACPA+) had erosion-dominant CJD pattern (62.3%) while the majority of triple-negative patients (SE–, FR–, ACPA–) had space narrowing–dominant CJD pattern (75%; p = 0.017). ACPA was associated with HLA-DRB1 SE alleles (p < 0.05). Patients with foot-dominant CJD pattern were taller than those with hand-dominant CJD pattern (p = 0.002); those with erosion-dominant CJD pattern had higher weight and body mass index than those with space narrowing–dominant CJD pattern (p = 0.014, p = 0.001). Conclusion. CJD patterns were associated with disease severity, HLA-DRB1 SE status, presence and titer of ACPA and RF, and morphometric features. (First Release Feb 1 2015; J Rheumatol 2015;42:405–12; doi:10.3899/jrheum.131177) Key Indexing Terms: RHEUMATOID ARTHRITIS DIAGNOSTIC IMAGING JOINT EROSIONS RHEUMATOID FACTOR ANTICITRULLINATED PROTEIN ANTIBODIES From the Rheumatology Division, Universidade Federal de São Paulo (UNIFESP), São Paulo; Rheumatology Division, Universidade Estadual do Rio de Janeiro (UERJ), Rio de Janeiro; Rheumatology Division, Universidade de São Paulo (USP); Rheumatology Division, Universidade Estadual de Campinas (UNICAMP), São Paulo, Brazil. Dr. Alarcon received an academic grant from CAPES (Brazilian Agency for Scientific Development) and Dr. Andrade receives a research grant from CNPq (Brazilian Agency for Research Development). Partially supported by grant # 07/50523-9 from the São Paulo Research Foundation. R.T. Alarcon, PhD, Research Fellow, Biol.; A.R.C. Fernandes, MD, PhD, Associate Professor, UNIFESP; I.M. Laurindo, MD, PhD, Associate Researcher, USP; M.B. Bértolo, MD, PhD, Associate Professor, UNICAMP; G.C. Pinheiro, MD, PhD, Associate Professor, UERJ; L.E. Andrade, MD, PhD, Associate Professor, UNIFESP. Address correspondence to Dr. L.E. Andrade, Rheumatology Division, Universidade Federal de São Paulo, Rua Botucatu 740, São Paulo, 04023-062, Brazil. E-mail: luis.andrade@unifesp.br Accepted for publication November 14, 2014. Rheumatoid arthritis (RA) is a heterogeneous disease in terms of joint damage. Some patients present mild joint involvement and others develop progressive joint destruction and severe functional impairment 1 . Despite recent progress, the available therapeutic options are not entirely satisfactory for all patients. Pathophysiological definition and therapeutic management of RA might be improved if it were possible to identify more homogeneous disease subphenotypes. One possible way to identify RA subphenotypes is the definition of distinct patterns of cumulative joint damage (CJD). Radiographic analysis allows the identification of distinct patterns of joint involvement regarding the topography of joint damage (hands vs feet and fingers vs wrists) and the type of lesion (erosion vs space narrowing; Figure 1). Total joint damage www.jrheum.org Downloaded on April 25, 2022 from