CONCISE REPORTS A measure of limited joint motion and deformity correlates with HLA-DRB1 and DQB1 alleles in patients with rheumatoid arthritis

Objective—To assess factors associated with a poor outcome in rheumatoid arthritis (RA), a measure was developed of limited joint motion and deformity, a deformity index (DI), and correlated biochemical and genetic variables with the magnitude of the DI. Methods—Forty patients were evaluated in a cross sectional study. Clinical measures included the DI and Health Assessment Questionnaire, and disease variables included the erythrocyte sedimentation rate, C reactive protein, rheumatoid factor, and HLA-DRB1 and DQB1 alleles. Results—Significant correlations were noted between increasing DI and duration of RA and concentration of C reactive protein. Patients with a DQB1*301 allele or DR4 allele had a higher DI than those without, and a positive trend was noted between increasing DI and dose of DRB1 RA susceptibility alleles. The trend was lost when a non-linear regression technique was used to remove the eVect attributable to C reactive protein, suggesting an interrelation between persistent inflammation and genetics in determining total joint damage. Conclusions—The DI may be useful to study interactions between genetic and inflammatory processes in rheumatoid disease progression. (Ann Rheum Dis 1999;58:703–708) Rheumatoid arthritis (RA) results often in irreversible damage of aVected joints but disease outcome is not uniform. About 15–20% of patients have little deterioration after years of follow up. Unfortunately, most patients demonstrate substantial disease progression within a few years of onset whether assessed radiographically or by functional status. 10 11 Predicting outcome in patients with RA is diYcult. To date, rheumatoid factor (RF) positivity and increases in the erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) have been found to be the most consistent predictors of early radiographic and functional deterioration in several longitudinal studies of patients presenting with recent synovitis. Although ESR and CRP presumably reflect the same inflammatory process, they seem to exert additive eVects on developing joint erosions. Possession of the “shared epitope” within the third hypervariable region of the HLA-DRB1 chain (amino acids 70–74: QKRAA/ QRRAA/ RRRAA) either on an HLA-DR4 (DRB1*04) or non-DR4 allele has been associated with susceptibility to developing RA 21–29 and an additional eVect of increasing gene dose and severity has been noted in most studies. 25 26 The combination of an HLA-DRB1 susceptibility allele and seropositivity has been found particularly predictive of development of joint erosions early in two studies. 27 The measure that best describes outcome in RA is unsettled and has confounded the issue of identifying measures that may be associated with severity. In some publications, severity has been defined by the presence of extra-articular manifestations such as Felty’s syndrome or vasculitis. Others report radiographic scales assessing articular narrowing and erosions, but limitations of radiographic scales in measuring total joint damage beyond 5–8 years of disease have been noted. 30 Pincus noted the inability of joint counts and other measures of clinical activity to predict irreversible damage, and has advocated the functional dimension of the Health Assessment Questionaire (HAQ) as the best measure of severity. The HAQ is an excellent predictor of work disability and mortality in RA, however in many patients, dysfunction measured by the HAQ is discrepant from damage measured by radiographs. Furthermore, the HAQ is not associated with HLA-DR4 genes, which are commonly associated with disease severity. Scales of limited joint motion and deformity have been found to be the strongest correlate of radiographic scores in chronic RA and have been advocated as measures of total joint damage. 34 Available scales include the Joint Alignment and Motion Scale (JAM), the Escola Paulista de Medicina-Range of Motion (EPM-ROM) scale, and the scale of the American College of Rheumatology (ACR). We adapted the JAM and EPM-ROM to provide a measure of total joint damage, a deformity index (DI), and report our Ann Rheum Dis 1999;58:703–708 703 Department of Medicine, University of Ottawa, Canada