Background Hypothyroidism is usually, in iodine-repleted areas, of autoimmune nature and leads to chronic thyroxin substitution. It shares some risk factors with anti-citrullinated-peptide antibodies (ACPA) positive rheumatoid arthritis (RA). 1,2
Objectives We asked whether thyroxin substitution associated with risk of ACPA-positive or ACPA-negative RA, and whether interactions with established risk factors were present.
Methods Data from a population-based case-control study with incident RA cases was analysed (1998 adult cases, 2252 controls). Individuals reporting thyroxin substitution were compared with those without thyroxin, by calculating odds ratios (OR) with 95% confidence interval (CI), excluding participants reporting non-autoimmune causes for thyroxin substitution (thyroid cancer, iodine-containing drugs). Interaction was evaluated by attributable proportion (AP) with 95% CI.
Results Thyroxin substitution was associated with a twofold risk of both ACPA-positive (OR=1.9, 95% CI 1.4-2.6) and ACPA-negative RA (OR=2.1, 95% CI 1.5-3.1). For ACPA-positive RA, the risk associated with the combination thyroxin+ HLA-DRB1 shared epitope alleles (SE) was much higher (OR=11.8, 95% CI 6.9-20.0) than for thyroxin (OR=1.4, 95% CI 0.7-3.0) or SE (OR=5.7, 95% CI 4.6-6.9) alone, indicating a strong interaction (AP=0.5, 95% CI 0.2-0.8). Thyroxin substitution interacted non-significantly with smoking (AP=0.4, 95% CI 0.0-0.7; OR thyroxin+smoking=3.6, thyroxin.5, smoking.8). Thyroxin did not interact with the PTPN22*R620W allele.
Conclusions Thyroxin users had a doubled risk of both ACPA-positive and ACPA-negative RA. The risk of ACPA-positive RA was manifold if they smoked or carried the SE. Furthermore, although joint symptoms can be a manifestation of hypothyroidism, physicians might consider whether it could be an early RA.
Tomer Y, Huber A: The etiology of autoimmune thyroid disease: a story of genes and environment. Journal of autoimmunity 2009;32:231-239.
Klareskog L, Catrina AI, Paget S: Rheumatoid arthritis. Lancet 2009;373:659-672.
Acknowledgements We express our sincere gratitude to Prof. Lars Alfredsson and Prof. Lars Klareskog, the principal investigators and founders of the EIRA study. We thank all participating controls and patients with RA, and the EIRA study group who recruited patients for EIRA along with their collaborating clinicians and nurses.
Disclosure of Interest None Declared
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