Patterns and predictors of joint damage as assessed by the rheumatoid arthritis articular damage (RAAD) score in South Africans with established rheumatoid arthritis

This study aimed to determine the pattern and predictors of joint damage measured by the rheumatoid arthritis articular damage (RAAD) score and to describe its relationship to functional disability in patients with established rheumatoid arthritis (RA). One hundred Black patients with RA of disease duration ≥5 years were studied cross-sectionally. Data collected included socio-demographics, disease duration, smoking, body mass index (BMI), extraarticular features, rheumatoid factor (RF), haemoglobin (Hb), disease activity (DAS28), delay in disease-modifying antirheumatic drug initiation (DMARD lag) and treatment history. As outcome measures, the RAAD score and modified Health Assessment Questionnaire (mHAQ-DI) were used to assess joint damage and disability, respectively. Data were analysed by univariate and multivariate analyses. The mean RAAD score was 28.2?±?12.8 for a mean disease duration of 17.5?±?8.5 years. The majority of patients still had active disease (mean DAS28 4.4) and severe disability (mean mHAQ-DI 1.9), reflected in part by a long mean DMARD lag (9 years). Wrist and ankle joints were commonly involved. Multivariate analysis revealed that longer disease duration, higher RF titres and lower BMI were significant independent predictors of a higher RAAD score. The mHAQ-DI was significantly associated with DAS28, RAAD, education and Hb. Our results provide support for aspects of validity of the RAAD score and for its use in under-resourced settings. Further longitudinal studies are needed to evaluate its sensitivity to change in monitoring joint damage. Patterns of joint involvement and the inverse relationship between BMI and joint damage also merit further investigation in Black RA patients.     

Articular damage in late rheumatoid arthritis

This study aims to examine the long-term articular damage in rheumatoid arthritis (RA) patients according to rheumatoid arthritis articular damage (RAAD) score and to evaluate the parameters correlated with this score. The RAAD score was assessed in 85 RA patients who had the disease for more than 10 years. Patients were divided into three groups according to duration of the disease: group 1, 10–14 years; group 2, 15–19 years; and group 3, more than 20 years. Patients were also divided into three groups according to the time of initiation of treatment with disease-modifying antirheumatic drugs: group A, within the first 2 years, group B, between 2 and 5 years; and group C, after 5 years. We investigated the RAAD score relationship between groups 1, 2, 3; groups A, B, C; sex; drug compliance; age of onset of the disease; and Health Assessment Questionnaire (HAQ). We observed significant differences in RAAD scores according to groups 1, 2, 3 (p<0.01), but not to groups A, B, C; sex; or drug compliance (p>0.05). While the RAAD score correlated well with the HAQ (r=0.560, p<0.001), it did not correlate with the age at onset of the disease (p>0.05). As RA is not a benign disease and articular damage progresses over time, the goal of RA therapy must be to maintain a response before the onset of irreversible damage and loss of function.     

Reliability of the rheumatoid arthritis articular damage score in Tunisian patients

The clinical rheumatoid arthritis articular damage (RAAD) score is easy to perform and showed good intraobserver reliability. It correlates well with the Larsen score and disease duration and can be recommended for rheumatoid arthritis patients follow-up in developing countries.     

Radiographic damage of large joints in long-term rheumatoid arthritis and its relation to function

OBJECTIVE: To describe the extent of radiographic damage of large joints in long-term rheumatoid arthritis (RA) and its relationship to small joint involvement and physical function. METHODS: After 12 yr of follow-up, radiographs of all large joints (Larsen large joint score 0-60) of 105 recent RA patients were assessed. Correlations were evaluated between the Larsen large joint score and radiographic damage of the hands and feet as measured by the van der Heijde modification of the Sharp score (SHS) and the health assessment questionnaire (HAQ). We determined the relative contributions of radiographic damage of small and large joints, disease activity and psychological function to the HAQ. RESULTS: The median Larsen large joint score was 3. In 54% of the patients at least one large joint was erosive. The correlation of the Larsen score with the SHS and HAQ scores was 0.76 and 0.60, respectively. Disease activity and radiographic damage of the large joints were the major determinants of the HAQ score. CONCLUSION: Large joint involvement after 12 yr of follow-up is extensive and is associated with functional disability. Large joint involvement is closely associated with small joint involvement.     

Hand disability and related variables in patients with rheumatoid arthritis

Objective: To carry out a cross-sectional study of patients with rheumatoid arthritis (RA) for hand disability, articular damage and to define their relation with demographic, laboratory and clinical parameters. Methods: The study included 105 RA patients with a mean age of 49.4 years. Demographic parameters of the patients were recorded. Clinical parameters including disease duration, duration of morning stiffness, pain assessed by visual analog scale, Ritchie Articular Index, grip strength, lateral, tip and three-fingered pinch, and laboratory parameters comprising C-reactive protein, erythrocyte sedimentation rate and rheumatoid factor were evaluated in all patients. The Rheumatoid Arthritis Articular Damage (RAAD) score was used to assess the irreversible articular damage and deformities of the hand. Hand disability was assessed by the special hand disability index of Standford Health Assessment Questionnaire (HAQ). Results: Hand disabilities of various levels were detected in 81% of the patients. Disease duration, grip strength, pinch measurements, clinical and laboratory activity parameters were strongly correlated with hand disability (p<0.01). Hand disability was more related to disease activity parameters than articular damage (p<0.01 and p<0.05, respectively). Grip strength and pinch measurements were the most related parameters with hand disability. The disability scores were significantly higher in female patients (p<0.01). The RAAD score was correlated with disease duration and grip strength (p<0.01). The clinical and laboratory parameters and seropositivity were not correlated with articular damage assessed by RAAD score (p>0.05). Conclusion: Our data suggest that grip strength and pinch measurements seem to be the most related variables with hand disability and articular damage. Therefore, grip strength and pinch measurement should be included in the evaluation and follow-up of the patients with RA in hand rehabilitation units.     

Radiographic joint destruction in postmenopausal rheumatoid arthritis is strongly associated with generalised osteoporosis

OBJECTIVES: To investigate determinants of joint destruction and reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) not treated with bisphosphonates or hormone replacement therapy and to evaluate if there are common markers of erosive disease and bone loss. METHODS: BMD was measured using dual x ray absorptiometry and joint damage was examined by x ray examination according to the Larsen method in 88 patients with RA. Associations between BMD and Larsen score, and between demographic and disease related variables, including proinflammatory cytokines, HLA-DR4 epitopes, and markers of bone and cartilage turnover, were examined bivariately by simple and multiple linear regression analyses. RESULTS: 49/88 (56%) patients had osteoporosis in at least one site. Reduced BMD and increased joint destruction were associated with: at the forearm and femoral neck, high Larsen score, low weight, and old age (R(2)=0.381, p<0.001; R(2)=0.372, p<0.001, respectively); at the total hip, low weight, high Larsen score, and dose of injected glucocorticosteroids (R(2)=0.435, p<0.001); at the lumbar spine, low weight, reduced cartilage oligomeric matrix protein, and increased carboxyterminal propeptide of type I procollagen (R(2)=0.248, p<0.001). Larsen score was associated with long disease duration and increased C reactive protein (CRP) (R(2)=0.545, p<0.001). CONCLUSIONS: Osteoporosis is common in postmenopausal patients with RA. Low weight and high Larsen score were strongly associated with BMD reduction. Increased CRP and long disease duration were determinants of erosive disease in postmenopausal women with RA. These findings indicate common mechanisms of local and generalised bone loss in RA.     

Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis

OBJECTIVE: Calprotectin is a major leucocyte protein, shown to correlate well with laboratory and clinical assessments in several inflammatory rheumatic diseases, and large concentrations of calprotectin have been found in synovial fluid from patients with rheumatoid arthritis (RA). The objective of the present study was to examine correlations between calprotectin and joint damage. METHODS: 145 patients with RA were analysed cross sectionally with laboratory (calprotectin, C reactive protein (CRP), and erythrocyte sedimentation rate (ESR)), clinical (28 joint counts (tender, swollen), physician global VAS, DAS28 and RA Articular Damage score (RAAD)), and radiographic (plain hand radiographs; modified Sharp's method) measurements, on the same day. RESULTS: Calprotectin showed a highly significant correlation with measures of joint damage; modified Sharp score r = 0.43 (p<0.001) and RAAD r = 0.40 (p<0.001). The association with modified Sharp score and RAAD score was maintained after adjustment for CRP, ESR, rheumatoid factor, DAS28, sex, and age in a multiple regression analysis (p = 0.018 and p = 0.04, respectively), while neither CRP nor ESR showed any independent associations. Highly significant correlations (p<0.001) were also found between calprotectin and both laboratory and clinical markers of inflammation. CONCLUSION: Calprotectin was found to significantly and independently explain the variation in the radiological and clinical assessments of joint damage. Longitudinal studies are required to examine whether calprotectin may predict the progression of joint damage in RA.     

The number of deformed joints as a surrogate measure of damage in rheumatoid arthritis

OBJECTIVE: To evaluate the reliability and validity of the number of deformed joints (NDJ) as a surrogate measure of joint damage in rheumatoid arthritis (RA). METHODS: We tested interrater reliability and validity in determining the NDJ as a surrogate for joint damage in consecutive patients with RA. We rated each of 48 joints as normal or abnormal in terms of alignment and range of motion, and expressed the results as the total number of deformed joints. We compared the NDJ with the severity of damage on a plain radiograph of the hands, scored using Sharp's technique, as the gold standard measure of joint damage. We also compared the correlation between the NDJ and radiographic joint damage, on the one hand, and disease duration, performance-based measures of physical function, and the self-reported level of disability. RESULTS: The interrater reliability of the NDJ was excellent, with an intraclass correlation among four examiners of 0.94. To assess validity of the NDJ, we studied 273 RA patients from 5 clinical settings. Their average NDJ was 14 (range 0-43), and their average Sharp's score for joint space narrowing and erosions combined was 106 (range 4-309). The NDJ and the total Sharp's score were highly correlated (r = 0.83). Both measures were correlated to a similar degree with disease duration (r = 0.51 for each measure), grip strength (r = -0.49 for NDJ, and r = -0.51 for Sharp's score), walking velocity (r = -0.44 for NDJ, and r = -0.45 for Sharp's score), the timed button test (r = -0.62 for NDJ, and r = -0.57 for Sharp's score), and the Modified Health Assessment Questionnaire (r = 0.38 for NDJ, and r = 0.38 for Sharp's score). Both the Sharp's score and the NDJ worsened significantly in 38 patients for whom 1-2 year followup data were available. CONCLUSION: The NDJ is reliable and is strongly associated with the standard measure of joint damage in RA. Because it is easily performed in a clinical setting, it could be used as an economical surrogate of joint damage in studies of the long-term outcome of RA.     

Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis

OBJECTIVE: Expression and activation of matrix metalloproteinases such as MMP-3 (stromelysin-1) and MMP-1 (collagenase-1) are increased in patients with rheumatoid arthritis (RA). Previous negative reports of their value as predictors of joint damage may be due to the lack of a large longitudinal study of early RA patients. This study evaluated their use in assessing early untreated patients with RA and predicting subsequent joint damage. METHODS: Ninety-eight patients with early untreated RA of less than 12 months duration and 20 normal controls had baseline serum samples tested with a double-antibody enzyme-linked immunosorbent assay for each of MMP-1 and MMP-3. The subsequent changes in Larsen score (DeltaLarsen) and Health Assessment Questionnaire (DeltaHAQ) over the first 12 months were recorded. RESULTS: Baseline serum levels of MMP-3 and MMP-1 correlated significantly with baseline C-reactive protein (CRP) (r=0.42 and 0.49, P<0.001), DeltaHAQ (r=0.32 and 0.30, P<0.01) and DeltaLarsen (r=0.23 and 0.32, P<0.05) respectively. Analysis of the group of patients with a normal CRP at presentation (n=21) showed correlation of the baseline MMP-3 and MMP-1 with the presence of erosive disease during the first 12 months (r=0.52 and 0.65 respectively, P<0.05). Logistic regression analysis, in the patients who were non-erosive at presentation, showed that the strongest correlation with progression in Larsen score was the baseline MMP-3 level (r=0.30, P=0.01). CONCLUSIONS: Baseline serum MMP-1 and MMP-3 levels correlate with disease activity and predict functional and radiographic outcome in early untreated RA. They may have a particular value in predicting the progression of erosive disease in patients who are not erosive at presentation.     

Pregnancy and oral contraceptive use do not significantly influence outcome in long term rheumatoid arthritis

BACKGROUND: Oral contraceptives (OC) and pregnancy are known to have an influence on the risk of onset of rheumatoid arthritis (RA). Pregnancy itself has beneficial effects on the activity of the disease, with relapses post partum. It is not known, however, whether OC and pregnancies influence the ultimate outcome of RA. Objectives: To explore whether OC use and pregnancies influence the 12 year outcome in RA as measured by radiological damage and disability. METHODS: In a prospective inception cohort of 132 female patients with recent RA according to the 1987 American College of Rheumatology criteria-a cohort initially gathered to study the association between hormonal factors and the onset of RA-outcome was assessed in a follow up after 12 years. The outcome was evaluated in 112 (85%) women by the radiological damage of hands and feet as measured with the Sharp score modification van der Heijde (SHS), the damage of the large joints measured with the Larsen score (LS) of large joints (0-60), and the disability measured with the Health Assessment Questionnaire (HAQ). The median values of each outcome variable were calculated for several subgroups of patients stratified for OC use and pregnancies before and after onset of the disease and the tertiles of the total number of months of OC use and of pregnancies. The association of OC use and pregnancies before and after onset of the disease with the outcome variables was calculated using Spearman's rank correlation (r(s)). The combined influence of OC use and pregnancies on the SHS, LS, and HAQ at 12 years was estimated using ordinal polytomous logistic regression. RESULTS: The median values of the SHS, LS, and HAQ showed a trend towards less radiological joint damage and less disability in women with long term OC use and multiple pregnancies. This difference, however, was not significant, except for the HAQ score in women with three or more pregnancies in life. There was no association between pregnancies, however defined, and any parameter of RA outcome after 12 years (maximum r(s)=-0.10). The only significant correlation was found between OC use before symptom onset and the LS (r(s)=-0.22, p<0.05). The combination of hormonal variables explained no more than a maximum of 3% of the variance of the 12 year outcome as measured by the SHS. CONCLUSION: OC use and pregnancy do not significantly influence outcome in long term RA. There is, however, a trend for patients with multiple pregnancies and long term OC use to have less radiographic joint damage and a better functional level.     

Assessment of long-term articular damage and function in rheumatoid arthritis patients

Aim of the work

This study aimed to assess long-term articular damage and function in rheumatoid arthritis (RA) patients in relation to the type of treatment. Early disease modifying anti-rheumatic drug (DMARD) therapy has not been evaluated in this study.

Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritis

OBJECTIVE: To investigate development of radiographic damage in hands and feet of patients with early rheumatoid arthritis (RA) monitored prospectively for 10 years, and to search for prognostic factors. PATIENTS AND METHODS: 181 patients with early RA (mean disease duration one year) were assessed annually with radiographs of hands and feet during years 0-5 and at year 10. Radiographs were evaluated according to Larsen (range 0-200). Predictive factors for progressive disease for years 0-5 and 5-10 were evaluated by logistic regression analyses. RESULTS: 82/168 (49%) patients had erosions at inclusion and almost all became erosive with time (90% after two years and 96% after 10 years). Radiographic progression was most rapid during the first two years and 75% of all damage occurred during the first five years. The median Larsen score increased from 6 at inclusion to 41 after five years and 54 after 10 years. Only 5.3% of all evaluated joints became maximally eroded, the second metacarpophalangeal joint being the most commonly affected. Mean ESR during the first three months and rheumatoid factor status were significant predictors for radiographic progressive disease, it was not possible to predict non-progressive disease. CONCLUSIONS: Joint damage in hands and feet developed early and progression was most rapid during the first years of disease. The different rates of progression at different stages should be considered in the design of trials of drugs aimed at retarding joint damage. Disease activity at study start influenced the degree of joint damage during the entire 10 years.     

Articular damage in adults with juvenile idiopathic arthritis

The goal of this study was to assess the long-term articular damage in adults with juvenile idiopathic arthritis (JIA) using the Rheumatoid Arthritis Articular Damage (RAAD) score and to determine any associations between the disease-related parameters and RAAD score. Thirty-eight adults identified with JIA at 18 years of age or older with disease duration of at least 5 years were assessed by means of the RAAD score. Patients were divided into three groups according to disease duration as 5-10 years (group 1), 11-15 years (group 2) and more than 16 years (group 3), and into three groups according to JIA subtypes as seropositive polyarticular (group A), seronegative polyarticular (group B), and oligoarticular (group C). Functional disability, functional status, disease activity and depression were measured by Health Assessment Questionnaire (HAQ), Steinbrocker classification, Disease Activity Score 28 (DAS 28), and Beck Depression Inventory, respectively. We investigated any possible associations between the RAAD score and groups, sex, age at onset of the disease, HAQ, Steinbrocker classification, DAS 28, and Beck Depression Inventory. We observed significant differences in RAAD scores according to groups A, B, C (p < 0.01), but not according to groups 1, 2, 3 or sex (p > 0.05). While the RAAD score correlated well with HAQ (p < 0.001), Steinbrocker classification (p < 0.001) and DAS 28 (p < 0.01), it did not correlate with age at onset of the disease (p > 0.05) or Beck Depression Inventory (p > 0.05). Seropositive polyarticular patients demonstrate the worst articular damage scores. Even though articular damage does not progress over time and JIA frequently has a benign course, care should be given to establishing regular follow-up periods and well-arranged treatments, especially for seropositive polyarticular groups, to maintain satisfactory long-term disease outcome throughout the lives of JIA patients.     

Effect of a high-intensity weight-bearing exercise program on radiologic damage progression of the large joints in subgroups of patients with rheumatoid arthritis

OBJECTIVE: To investigate whether a high-intensity exercise program accelerates the rate of radiologic damage of the large joints in predefined subgroups of patients with rheumatoid arthritis. METHODS: The data of 277 participants in a 2-year randomized controlled trial, comparing the effects of high-intensity exercises with usual care, were used. Linear regression analysis was used to test which predefined variables at baseline (age, disease duration, disease activity, physical capacity, functional ability, joint damage) modified the effect of high-intensity exercise on the progression of radiologic damage of the large joints over 24 months. RESULTS: Baseline radiologic joint damage was the only variable associated with the effect of high-intensity exercise on joint damage progression in large joints. In a subgroup of 218 patients with no or little joint damage (defined as Larsen score < or = 5; 80% of our study population) the proportions of patients with an increase in joint damage were similar for the exercise and usual-care group (35% versus 36%, risk ratio [RR] 1.0 [0.7-1.4]; P = not significant), whereas, in a subgroup of 59 patients who already had extensive damage of large joints (defined as Larsen score >5) the proportion was significantly higher in the exercise group (85% versus 48%, RR 1.8 [1.2-2.6]; P < 0.05). CONCLUSION: High-intensity weight-bearing exercises appear to accelerate joint damage progression in patients with preexisting extensive damage. Patients with extensive large joint damage should, therefore, be advised to refrain from activities excessively loading the damaged joints.     

Long term high intensity exercise and damage of small joints in rheumatoid arthritis

OBJECTIVE: To investigate the effect of long term high intensity weightbearing exercises on radiological damage of the joints of the hands and feet in patients with rheumatoid arthritis (RA). METHODS: Data of the 281 completers of a 2 year randomised controlled trial comparing the effects of usual care physical therapy (UC) with high intensity weightbearing exercises were analysed for the rate of radiological joint damage (Larsen score) of the hands and feet. Potential determinants of outcome were defined: disease activity, use of drugs, change in physical capacity and in bone mineral density, and attendance rate at exercise sessions. RESULTS: After 2 years, the 136 participants in high intensity weightbearing exercises developed significantly less radiological damage than the 145 participants in UC. The mean (SD) increase in damage was 3.5 (7.9) in the exercise group and 5.7 (10.2) in the UC group, p = 0.045. Separate analysis of the damage to the hands and feet suggests that this difference in rate of increase of damage is more pronounced in the joints of the feet than in the hands. The rate of damage was independently associated with less disease activity, less frequent use of glucocorticoids, and with an improvement in aerobic fitness. CONCLUSION: The progression of radiological joint damage of the hands and feet in patients with RA is not increased by long term high intensity weightbearing exercises. These exercises may have a protective effect on the joints of the feet.     

HLA-DRB1 alleles associated with rheumatoid arthritis in Northern Italy: correlation with disease severity

The aim of the study was to evaluate the relationship between the presence of the 'rheumatoid epitope', defined by a sequence motif in the HLA-DRB1 alleles, rheumatoid factor and disease severity in Northern Italian patients with rheumatoid arthritis (RA). Twenty-nine DR4-positive and 57 DR4-negative RA patients were studied. Each DR4- positive patient was matched with two DR4-negative controls of similar disease duration and sex. HLA-DRB1 alleles were determined in the 86 patients and 351 controls from the same geographical area. The patients were retrospectively evaluated for extra-articular features (EAF) and radiographic damage. The rheumatoid epitope was expressed in 45% of patients. No significant differences in the presence of rheumatoid factor, EAF and articular damage were observed between patients with no, one or two doses of epitope. However, the patients encoding the epitope by an HLA-DR4 allele had a higher number of eroded joints and a higher Larsen score compared to those without the epitope. No differences were present between patients expressing HLA-DRB1*01 alleles and those lacking the rheumatoid epitope. Even in the absence of expression of the rheumatoid epitope, seropositive patients had more EAF and more erosive disease compared to those who were seronegative. Even if most Northern Italian RA patients do not express the rheumatoid epitope, the radiological severity of disease is associated with HLA- DRB1*04 alleles.      

Leukocyte protein calprotectin and outcome in rheumatoid arthritis. A longitudinal study

OBJECTIVE: To determine if calprotectin is predictive for outcome in patients with rheumatoid arthritis (RA). METHODS: Fifty six RA in-patients with variable disease duration were prospectively followed for five years. Clinical and laboratory data were collected to assess disease activity. Health Assessment Questionnaire (HAQ) and radiographic scores (of hands and wrists) as described by Larsen were used as outcome measures. Plasma calprotectin levels were determined with ELISA technique. RESULTS: Significant correlations (r) were found cross-sectionally at follow-up between calprotectin concentration and other known parameters of disease activity and severity: CRP (r = 0.67). investigator's global assessment of disease activity (r = 0.57). Waaler titre (r = 0.50). HAQ score (r = 0.48) and number of swollen joints (r = 0.48). Calprotectin at baseline was not identified as an independent predictor for HAQ or radiographic progression in the multivariate analysis. CONCLUSION: The results confirm calprotectin as a good measure of disease activity and joint inflammation in RA. However, the level of calprotectin at baseline was not predictive for radiographic damage or functional impairment five years later.     

Comparison of disability and quality of life in rheumatoid and psoriatic arthritis

OBJECTIVE: There is controversy about the severity of peripheral psoriatic arthritis (PsA) compared to rheumatoid arthritis (RA). Early reports found PsA to be a milder disorder, excepting the mutilans form. Recent reports suggest that PsA can be as severe as RA. We compared severity, disability, and quality of life in patients with PsA and RA matched primarily for disease duration. METHODS: Data relating to the extent and severity of disease were recorded in a hospital clinic setting. Recent radiographs of hands and feet were read blinded to diagnosis, and information on function and quality of life was collected with the Health Assessment Questionnaire (HAQ) and EuroQol-5D, respectively. RESULTS: Forty-seven patients were matched for disease duration (median PsA 5 yrs, RA 7 yrs). The male/female ratio was 24/23 for PsA, 16/31 for RA, and median ages were 45 and 51 years, respectively. Patients with RA had significantly more joint involvement of metacarpophalangeal joints and wrists, whereas distal interphalangeal joints, spine, sternoclavicular joints, and sacroiliac joints were significantly more involved in PsA. No difference was found regarding Ritchie Articular Index, inflammatory markers, HAQ score, or EuroQol-5D. Patients with RA had significantly more damage on radiographs of hands and feet: median (range) Larsen score hands PsA 8 (0-91), RA 38 (0-125); feet PsA 4 (0-34), RA 11(0-56). Patients with RA were taking significantly more disease modifying drugs. CONCLUSION: Peripheral joint damage is significantly greater in RA than in PsA after equivalent disease duration, but function and quality of life scores are the same for both groups. The additional burden of skin disease in PsA may account for this.     

HLA-DMA*0103 and HLA-DMB*0104 alleles as novel prognostic factors in rheumatoid arthritis

OBJECTIVE: To evaluate HLA-DM alleles as markers for disease severity in rheumatoid arthritis (RA). METHODS: Two distinct cohorts of patients with RA were oligotyped for HLA-DB1 and HLA-DM genes using PCR amplified genomic DNA with sequence specific oligonucleotide probes. Cohort 1 comprised 199 unselected patients with RA (mean (SD) age 45.5 (13.5) years; disease duration 11.9(8.8) years), whose disease severity was assessed using Larsen score on hand and foot radiographs. Cohort 2 comprised 95 patients with severe RA and 70 patients with benign RA according to the Larsen method. RESULTS: In cohort 1, after stratification according to DRB1 genotypes, patients positive for HLA-DMA*0103 and negative for HLA-DRB1*04 tended to have greater articular damage on hands and wrists (p = 0.07 by Mann-Whitney U test) and reached statistical significance for the Larsen score per year (p = 0.05). This association between HLA-DMA*0103 and articular damage was especially observed in patients with HLA-DRB1*01. Similarly, HLA-DMB*0104 positive patients had higher Larsen score on hands and wrists (p = 0.02). This association was even stronger in DRB1*04 positive patients (p = 0.005). In cohort 2, HLA-DMA*0103 was associated with severe RA in patients negative for HLA-DRB1*04 (OD = 5.4; p = 0.014). HLA-DMB*0104 allele frequency tended to be higher in patients with severe RA but without reaching significance. CONCLUSION: This is the first study evaluating the role of HLA-DM genes in the severity of RA. Our results suggest that HLA-DMA*0103 and HLA-DMB*0104 alleles may represent new genetic markers of RA severity. The HLA-DMA*0103 allele tends to be associated with patients with RA negative for DRB1*04 and could predict a more severe form of disease especially in HLA-DRB1*01 positive patients. The HLA-DMB*0104 allele could have an additive effect in HLA-DRB1*04 patients. Combined determination of HLA-DM and HLA-DRB1 alleles could facilitate identification of patients likely to have a poor disease course.     

Progressive joint damage during penicillamine therapy for rheumatoid arthritis

Summary Progressive joint damage characterises rheumatoid arthritis despite treatment with slowacting drugs such as penicillamine. We examined a cohort of 145 RA patients, treated with 250 or 500 mg penicillamine daily for 18 months to study progressive joint damage measured using Larsen's standard radiographs. Overall damage increased significantly over 18 months at both doses of penicillamine. Radiological changes between 6–18 months were studied in detail in 55 cases. They were divided into rapidly progressive (increases in Larsen score of more than 5) or slowly progressive (increases in Larsen score of 5 or less). Overall clinical response, visual analogue pain score, ESR, haemoglobin and platelet count were significantly lower in the slowly progressive patients; articular index and duration of morning stiffness were slightly lower; latex titre, RAHA titre, joint size and white cell count showed no differences between groups. There is an indirect relationship between progressive joint damage and some clinical and laboratory measures. The reasons underlying our failure to control progression in some cases need further definition.