The influence of sex on the phenotype of rheumatoid arthritis.

OBJECTIVE To explore whether there are different disease patterns of rheumatoid arthritis (RA) in women and men. METHODS We studied 55 male case patients and 110 female control patients who developed RA between 1970 and 1985 and who resided and received medical care in Olmsted County, Minnesota, for at least 10 years after the diagnosis of RA. Case and control patients were matched for the date of first diagnosis. The pattern and extent of joint involvement, the frequency of joint surgeries, and the presence and type of extraarticular manifestations were determined by retrospective chart review. RESULTS Incidence rates in women were variable and age dependent, whereas the risk in men older than 36 years was constant over their lifetime. Erosive disease was more frequent in men than in women (72% versus 55%, respectively; P < 0.05) and tended to occur earlier (47% versus 31% for erosive disease within the first 4 years of RA). Although male sex was correlated with a higher risk of bony erosions and an accelerated course of RA, structural consequences of joint destruction were more pronounced in women. Joint surgery was performed more frequently in women (50%) than in men (27%) (P = 0.01). In particular, the frequencies of arthroplasties and arthrodeses of hand and foot joints were different (34 procedures in women versus 1 procedure in men; P < 0.001). Sex influenced the risk as well as the pattern of organ involvement in RA. Nodules and rheumatoid lung disease were typical manifestations in men (P = 0.001 and P < 0.001, respectively), whereas women typically developed sicca syndrome (P = 0.05). Despite differences in disease aggressiveness and disease pattern, there was little difference in the medical therapy in the men compared with the women. CONCLUSION RA is a heterogeneous disease with variations in phenotype. Sex-associated factors influence disease severity as well as disease pattern. Because sex-related effects influence treatment goals, treatment responses, and side effects, they should be considered in clinical study design and analysis as well as in the treatment decisions for individual patients with RA.