Relation between body mass index and radiological progression in patients with rheumatoid arthritis

OBJECTIVE: To determine if there is an influence of body mass index (BMI) on the radiological progression in early and longer duration rheumatoid arthritis (RA). METHODS: Fifty-four patients with RA were observed in a progressive 2 year followup for radiological progression of joint damage. At the beginning of study, 27 (50%) patients had a duration of complaints less than 6 months, grouped as early RA. BMI at the beginning and end of the study were monitored, together with HLA-DRB1 alleles, initial joint erosions, duration of disease, age, sex, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Outcome was defined as radiographic damage according to yearly increase of Larsen score. RESULTS: Increased radiographic joint damage of patients was significantly correlated with lower BMI at the beginning of the study (r = 0.363, p < 0.05), the presence of initial joint erosions (r = 0.341, p < 0.01), ESR (r = 0.315, p < 0.05), and CRP at study entry (r = 0.427, p < 0.01). Patients with an increase of Larsen score > or = 5.8/year were found to have a lower weight at the beginning of their complaints (BMI 24.8 +/- 4.7 vs 27.8 +/- 3.8; p < 0.05) as well as after the time of observation (BMI 24.6 +/- 3.7 vs 27.6 +/- 4.9; p < 0.05). Stepwise logistic regression analysis revealed a BMI < 27 at the beginning of disease (beta = 2.04, p = 0.003, odds ratio = 7.69), the presence of HLA-DR4 shared epitope (beta = 1.76, p = 0.015, OR 5.82), and joint erosions at study entry (beta = 1.56, p = 0.044, OR 4.78) as significant predictors for rapid joint damage. CONCLUSION: Together with the presence of HLA-DR4 shared epitope and erosive disease at study entry, a low BMI at the beginning of RA was found in association with higher radiographic progression in RA. Accordingly, BMI could be of interest as a sensitive and inflammation-independent predictor for radiological outcome of RA.     

HLA-DRB1 genes and disease severity in rheumatoid arthritis in Turkey

OBJECTIVE: Association with human leukocyte antigen (HLA)-DRB alleles, implicated in the aetiopathogenesis of rheumatoid arthritis (RA), is found to be different in various ethnic groups. This study aimed to investigate DRB1 alleles in RA patients in Turkey, and to examine the effect of these alleles on disease severity. METHODS: We performed PCR-based DRBI genotyping of 104 RA patients recruited from clinical settings and 110 healthy controls. HLA DRB1 alleles frequencies in RA patients and healthy controls were determined. Phenotype frequencies of patients and controls were compared. Disease severity was assessed by radiological erosion, presence of extra-articular involvement, and functional index. RESULTS: Significant differences were in the frequencies of DRB1*04 (46.2% versus 20.9%, p < 0.001), DRB1*0401 (10.6% versus 0%, p < 0.001), DRB1*0405 (8.7% versus 0%, p = 0.001), DRB1* 0404 (15.4% versus 3.6%, p < 0.01), DRB1*01 (21.2% versus 10.9%, p < 0.05) and DRB1*0101 (16.3% versus 5.5%, p = 0.01) between RA patients and controls. HLA-DRB1 alleles did not show any association with seropositivity, extra-articular involvement, radiological erosion, or functional index. CONCLUSION: Our results suggest that the HLA-DRB1 alleles, particularly HLA-DRB1*04 and subtypes, were associated with RA.     

Influence of HLA-DR alleles on rheumatoid arthritis: susceptibility and severity in Argentine patients

OBJECTIVE: To determine the frequency of shared epitopes in our population of patients with rheumatoid arthritis (RA) and to investigate whether the presence of these alleles is associated with a more aggressive form of disease. METHODS: Demographic and clinical data were obtained from 140 patients with RA, 123 female, mean age 49.9+/-11.7 years and mean disease duration 9.4+/-6.3 years. Radiographs of both hands were taken and scored by Larsen's method. HLA-DR alleles were determined by PCR-SSP. The control group comprised 202 healthy ethnic-matched subjects. RESULTS: DR4 was significantly more frequent in patients with RA than controls, and was observed in 70/140 patients (50%) versus 47/202 controls (23.27%) (odds ratio 3.25, CI 1.99-5.35, Pcorr 5 x 10(-5)). Within DR4 subtypes *0404 and *0401 were the most commonly found (37.7 and 29%, respectively). DR3 and DR11 exerted a protective effect with significantly higher frequency in controls than in patients with RA. When patients were divided into 2 groups according to disease severity (radiographic score) the frequency of alleles with QKRAA and QRRAA sequences was similar in both groups. Although with lower frequency, subtype *1001 alone was significantly more frequent in the severe-condition group [7 (13.5%) vs 3 (3.4%), p = 0.03]. CONCLUSION: These results are in accordance with findings observed in Caucasians and differ from other Latin American populations. However shared epitope alleles failed to correlate with more severe disease with the exception of subtype *1001 which, although infrequent, was significantly more frequent in patients with relevant radiological damage.     

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.     

Intensifying treatment of rheumatoid arthritis with combinations of traditional disease-modifying anti-rheumatic drugs among patients with persistent disease did not reduce the need for large joint surgery

OBJECTIVE: To analyse how treatment of patients with rheumatoid arthritis (RA) influenced the duration of the disease before the first large joint surgery, arthrodesis or arthroplasty, in two patient cohorts 10 years apart. METHODS: Data on patients with RA having an arthrodesis or arthroplasty of a large joint from 1990 to 1992 and from 2000 to 2002 and the type of medication used among all patients with RA in 1988-2002 were extracted from the data set of Kuopio University Hospital. RESULTS: The median duration of the disease before the decision of arthrodesis was 6.0 (range 1-25) years in 1990-92 and 9.0 (1-31) years (p = 0.307) in 2000-02, and of arthroplasty 10.5 (0-27) and 12.5 (0-59) years (p = 0.820), respectively. A significant shift from only symptomatic treatment or one disease-modifying anti-rheumatic drug (DMARD) to the more common use of immunosuppressants and/or combinations of at least two DMARDs occurred between 1992 and 2002. CONCLUSIONS: Treatment of RA at diagnosis and during the first years after diagnosis was traditional. Intensifying treatment later in the disease course did not reduce the need for large joint surgery as it occurred in the same time range in both cohorts.     

Differences between female and male patients with familial rheumatoid arthritis

OBJECTIVE: To determine whether there are genetic differences between female and male patients with familial rheumatoid arthritis (RA). METHODS: 45 men and 119 women from 78 families with RA who all had at least one first degree relative with RA were compared. HLA-DRB1 alleles were analysed, including DRB1*04 subtypes and associations of DRB1*04 haplotypes with DQB1*0301 or DQB1*0302 alleles, the age of the patients at disease onset, the presence of rheumatoid factor (RF), joint erosions, and rheumatoid nodules. RESULTS: HLA-DRB1*13 allele (the subtype allele of DR6, reported to be protective against the development of RA) was found in 14/119 (12%) of female but in none of the male patients (p=0.036). The HLA-DR4 allele was found slightly more often in men than women patients with familial RA (31/45 (69%) v 75/119 (63%), NS). Men were also more often RF positive than women (44/45 (98%) v 98/117 (84%); p=0.031). On the other hand, the mean age at onset of RA was significantly lower in the female group (40.4 years) than in men (46.6 years, p=0.0044). CONCLUSION: The results indicate that there is stronger genetic background in familial male than female patients with RA in the genetic susceptibility defined by the studied HLA antigens. However, the earlier age of onset of the disease in female group and the increased proportion of women with RA indicate that there are additional sex related predisposing factors enhanced in familial cases.     

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.     

Patients with rheumatoid arthritis are more tender than those with psoriatic arthritis.

Articular and nonarticular tenderness was examined in 51 patients with rheumatoid arthritis (RA) and 50 patients with psoriatic arthritis (PsA) by scored palpation and dolorimeter readings. Fifty-seven percent of patients with RA had 10 or more tender fibrositic points vs 24% of patients with PsA (p = 0.0008). Thresholds of tenderness measured by dolorimetry of 6 fibrositic point sites were 3.97 (1.99) [mean (SD)] for RA vs 5.95 (2.28) for PsA (p less than 0.0001). Thresholds over actively inflamed joints were 4.19 (1.53) for RA vs 6.78 (2.55) for PsA (p less than 0.0001). In both RA and PsA, fibrositic sites were more tender than actively inflamed joints (p less than 0.0001). Nonarticular control sites were also more tender in subjects with RA with dolorimeter thresholds at 5.99 (1.96) in RA vs 7.58 (1.60) in PsA (p less than 0.0001). These data demonstrate that actively inflamed joints, fibrositic and control nonarticular sites were all more tender in patients with RA than PsA. Both groups were similar in their disease duration and clinical assessments of joint inflammation and damage. We suggest that there may be a disease specific diffuse increase in tenderness in patients with RA, which is not related to joint inflammation. Similarly, the severity of articular inflammation may be underestimated in subjects with PsA.     

HLA-DRB1 alleles and shared amino acid sequences in disease susceptibility and severity in patients from eastern France with rheumatoid arthritis.

OBJECTIVE: To examine the effects of HLA-DRB1 alleles and amino acid sequences that carry the shared epitope (SE) upon rheumatoid arthritis (RA) susceptibility and disease severity in patients from Eastern France. METHODS: HLA-DRB1 alleles were determined in 120 patients and 104 healthy controls by polymerase chain reaction/sequence specific oligonucleotide probes. Subtyping of DRB1*01 and *04 were performed using sequence specific primers. Patients were retrospectively evaluated for disease duration, age at disease onset, presence of rheumatoid factors, subcutaneous nodules, vasculitis and other extraarticular diseases, for the need for arthroplasty and immunosuppressive/immunoregulatory agents, and for radiographic damage. RESULTS: The prevalence of HLA-DRB1*04 was significantly higher in patients (46.6%) than in controls (17.3%) (Pcorr = 0.000003). HLA-DRB1*0101 and *0401 were the most prominently associated subtypes in patients with RA (33.3%, Pcorr = 0.011, and 28.3%, Pcorr = 0.00008, respectively). A significant fraction of patients (72.5%) expressed one or 2 copies of the SE (p < 0.0000001; OR 4.77, CI 2.61-8.78). The presence of double SE was associated with a higher risk of developing RA (OR 4.83, CI 1.91-12.71; p = 0.0001). No significant differences in the clinical records among patients expressing no RA linked alleles, one and 2 copies of the SE, were observed. However, analyzing the specific effect of each amino acid sequence, we observed a significant association of the QKRAA motif with vasculitis (p = 0.03) and history of joint replacement surgery (p = 0.05), suggesting a role for lysine in position 71 of the shared sequence. CONCLUSION: These findings differ from those of previous HLA-DRB1 allele studies in patients with RA from other regions of France. Thus, the heterogeneity in both the expression of DRB1 alleles and the association of these alleles with disease severity could be relevant within a country such as France.     

Expression of QK/QR/RRRAA or DERAA motifs at the third hypervariable region of HLA-DRB1 and disease severity in rheumatoid arthritis

OBJECTIVE: To examine the relationship between disease severity in patients with confirmed rheumatoid arthritis (RA) and the carriage of alleles expressing the high risk epitope (HRE) QK/QR/RRRAA or the low risk epitope (LRE) DERAA at positions 70-74 of the third hypervariable region of HLA-DRB1. METHODS: A case-control design to compare allele carriage rates in 204 Caucasian subjects with severe RA and mild RA and healthy controls. Patients had a mean disease duration of 12-18 years and severity of RA was defined using clinical and therapeutic criteria. Molecular typing at the HLA-DRB1 locus was performed using a polymerase chain reaction method. RESULTS: Eighty-seven percent of patients (52/60) with severe RA had one or more of the alleles bearing the QK/QR/RRRAA motif or HRE, compared with 54% (21/39) with mild RA (OR 5.57, p = 0.0007) and 39% (41/105) of controls (OR 10.15, p < 0.0001). Twenty-five percent of patients (15/60) with severe disease expressed 2 disease associated HRE DRB1 alleles, compared with 13% of patients (5/39) with mild disease (OR 2.3, p = NS) and 5% (5/105) of controls (OR 6.67, p = 0.0003). In contrast, only 5% of patients (3/60) with severe RA expressed one of the LRE alleles that carry the DERAA motif at positions 70-74, compared with 31% of patients (12/39) with mild RA (OR 0.12, p = 0.0013) and 22% of controls (23/105) (OR 0.19, p = 0.0082). No patient or control was homozygous for LRE alleles. Eighty-three percent (50/60) of patients with severe RA expressed the HRE without the LRE, compared with 44% (17/39) of those with mild disease (OR 6.47, p < 0.0001) and 35% (37/105) of controls (OR 9.19, p < 0.0001). In contrast, only one patient (2%) with severe disease expressed the LRE without the HRE, compared with 20% (8/39) of those with mild disease (OR 0.07, p = 0.0047) and 16% (17/105) of controls (OR 0.09, p = 0.009). There was no significant difference between the 3 groups in the frequency of patients who expressed both or neither epitope. Logistic regression showed that age at disease onset (p = 0.0009), duration of disease (p = 0.007), positive rheumatoid factor status (p = 0.003), and presence of the HRE or LRE (p = 0.00005) were significantly associated with the presence of severe disease. CONCLUSION: HLA-DRB1 alleles appear to confer an important bidirectional influence on the risk of disease severity in RA, with 20-fold difference in OR between those associated with the highest (HLA-DRB1*0401) and lowest (HLA-DRB1*1301/02) risk. The HRE and LRE exhibit diametrically opposed effects, which may be mutually antagonistic. These data support a multistep pathogenesis in which MHC class II genes are one component of a coordinate genetic and environmental interaction leading to immunological injury and joint destruction.     

The association of race and ethnicity with disease expression in male US veterans with rheumatoid arthritis

OBJECTIVE: To examine the association of race/ethnicity with measures of disease activity and severity among male US veterans with rheumatoid arthritis (RA). METHODS: Measures of disease activity and severity were examined in a group of US veterans (n = 573) with RA, comparing measures in African American men (n = 79) with Caucasian men (n = 494). Dichotomous variables were compared using logistic regression while continuous variables were examined using linear regression, adjusting for the effects of age, disease duration, and smoking status. RESULTS: Compared to Caucasians, African Americans were slightly younger (65.0 vs 67.1 yrs; p = 0.09) at enrollment and had a similar age at disease onset (50.5 vs 50.6 years; p = 0.98). After adjusting for age, disease duration, and smoking status, there were no differences based on race/ethnicity in rheumatoid factor positivity, the presence of radiographic changes, physical functioning, swollen joint counts, Disease Activity Score (DAS28), or global well-being scores. In contrast, African Americans were about 50% less likely than Caucasians with RA to have subcutaneous nodules (adjusted OR 0.51, 95% CI 0.30-0.86) and had lower tender joint counts (p = 0.007), associations that were attenuated and not significant with further adjustment for collection site. CONCLUSION: With the possible exception of lower rates of rheumatoid nodules and lower tender joint counts in African Americans, there is little evidence to support the existence of important racial/ethnic differences in RA disease expression between African American and Caucasian men.     

Oral contraception, parity, breast feeding, and severity of rheumatoid arthritis.

OBJECTIVE: To investigate the influence of breast feeding, use of the oral contraceptive pill (OCP), and parity on rheumatoid arthritis (RA). METHODS: One hundred and seventy six women with RA were compared with 145 control subjects; all had at least one child. RA patients were classified as having severe (n = 82) or mild disease (n = 89) according to clinical joint evaluation, radiological score, biological inflammation, and the presence of HLA-DR1 or -DR4 alleles. RESULTS: The mean age of RA patients was 58 years, and the mean age at the time of diagnosis of RA was 46 years. The mean time between onset of RA and the first birth was 23.6 (SD 3.8) years. The OCP user rates were 33% in the RA group and 47.6% in the control group (p < 0.02). OCP use was related to the mother's year of birth. The relative risk for developing RA was 0.598 (95% confidence interval (CI) 0.33 to 1.1) in women who had used OCP for more than five years compared with those who had never used OCPs. In contrast, the age at which the first pregnancy occurred, the number of children breast fed, and the duration of breast feeding were comparable in RA patients and healthy subjects. Among the RA patients, parity, duration of breast feeding, and the number of breast fed children were significantly increased in those with severe disease. Having more than three children increased the risk of developing severe disease 4.8-fold when adjusted for age and OCP use. Forty six percent of women with severe RA had a history of breast feeding duration greater than six months before disease onset, compared with 26% of patients with mild disease (p < 0.008). Having more than three breast fed children increased the risk of poor disease prognosis 3.7-fold. In contrast, OCP use had a protective role in the course of RA (44% of RA patients with mild disease were OCP users, compared with 21.7% of those with severe RA; p < 0.001). Among those using OCP for more than five years, the relative risk of developing severe disease was 0.1 (95% CI 0.01 to 0.6), after adjustment for age, parity, and breast feeding. CONCLUSION: Our results suggest that parity, and to a lesser extent breast feeding, before RA onset worsened RA prognosis, whereas OCP use had a protective role. Prolactin and oestrogen may have a role in these effects.     

The predictive value of the HLA shared epitope for severity of radiological joint damage in patients with rheumatoid arthritis. A 10 year observational prospective study

OBJECTIVE: To evaluate the clinical importance of the RA "shared epitope" (SE) as a prognostic marker of radiological severity and extension of the disease to large joints in patients with rheumatoid arthritis (RA). METHODS: Eighty-two patients who met the American College of Rheumatology criteria for RA with a disease duration < 2 years at presentation were included in the study. Radiographs of hands, wrists, feet, shoulders, elbows, hips, and knees were taken at study entry and 8-10 years later. HLA-DRB1 genotypes were determined by polymerase chain reaction-sequence-specific oligonucleotide probes. Radiological severity was assessed in small joints of hands, wrists, and feet. Extension of the disease to large joints was evaluated in radiographs of shoulders, elbows, hips, and knees. RESULTS: At the end of the study, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) titer, and percentage of maximum radiological score at baseline were significantly associated with RA severity (p < 0.01, p < 0.01, p < 0.05, respectively). Extension of RA to large joints was related to a higher ESR (p < 0.001) and a lower hemoglobin level (p < 0.01) at baseline. Neither at entry nor at the end of the study was the RA shared epitope predictive for radiologic severity or extension of disease to large joints (p = 0.8, p = 0.3, respectively). CONCLUSION: Presence of the SE in patients with RA is not a good prognostic marker of radiological severity after a mean followup period of 9 years.     

Functional disability in relation to radiological damage and disease activity in patients with rheumatoid arthritis in remission

OBJECTIVE: To investigate the relationship between functional disability, disease activity and radiological damage in patients with rheumatoid arthritis (RA) in remission. METHODS: One hundred and eighty-six patients with RA in remission or with low disease activity were studied. The following variables were assessed at one time point: joint count, visual analog scale for pain, functional disability, i.e., health assessment questionnaire (HAQ) score, radiological joint damage as assessed by radiographs of hands and feet and scored according the Sharp-van der Heijde method, and presence of comorbidity. Disease activity was expressed as the disease activity score (DAS). Correlations were calculated by Spearman's rho coefficient of correlation. In addition, variables associated with the score were analyzed by logistic regression. RESULTS: The median HAQ score was 0.25 [interquartile (IQR) range 0-0.75] and the median DAS was 1.0 (IQR 0.7-1.5). Of the 186 RA patients included, 82% were in remission according to the DAS. The median joint damage as assessed by the Sharp-van der Heijde score was 21 (IQR 9-74). Functional disability was significantly correlated with pain (rho 0.48, p < 0.001), disease activity (rho 0.42; p < 0.001), disease duration (rho 0.39; p < 0.001), radiographic joint damage (rho 0.37; p < 0.001), and age (rho 0.19; p = 0.01). In a logistic regression model functional disability was independently related to presence of pain, disease activity, radiographic joint damage and disease duration in decreasing order of strength, but not to age. sex and co-morbidity. CONCLUSION: Patients with RA who are in remission might experience minimal functional disability and radiographic joint damage. Functional disability in RA patients in remission is most strongly related to the presence of pain and in lesser extent to disease activity, radiographic joint damage, and disease duration.     

The temporal relationship of Raynaud's phenomenon and features of connective tissue disease in rheumatoid arthritis

OBJECTIVE: In a prospective cohort study we examined the relationship between Raynaud's phenomenon (RP) onset and other connective tissue disease (CTD) characteristics in rheumatoid arthritis (RA) to determine if RP is predictive of RA severity and associated with other CTD signs, and if late onset RP in RA has an effect on prognosis compared to other patients with RA. METHODS: Using a standardized assessment, data were collected on 328 subjects with RA [mean age 60.3 +/- 0.7; 77% women; 76% erosions, 75% positive rheumatoid factor (RF)] seen at one London, Ontario, rheumatology clinic. The data included RA disease duration; presence and duration of RP; presence of nodules, joint damage, telangiectasia, and sclerodactyly; and RF status (+/-), RF value, antinuclear antibodies, and E-nuclear antibodies. RESULTS: The mean RA disease duration was 12 +/- 0.6 years. Seventy-one (22%) had RP and the mean RP duration was 9.2 +/- 1.5 years. Patients presented with RP a mean of 3.8 +/- 1.4 years after the diagnosis of RA. RP status was positively associated with the presence of sclerodactyly (p < 0.001), but not nodules or erosions. Higher RF values were associated with longer RA disease duration (p < 0.002) and longer RP duration (p < 0.01). CONCLUSION: Idiopathic RP may have a different clinical effect on RA than secondary RP; the latter is correlated with more severe RA. Sclerodactyly is associated with erosive arthritis and RP in RA. Higher RF values were indicative of increased RA and RP duration.     

Factors associated with hyperhomocysteinaemia in Mexican patients with rheumatoid arthritis

BACKGROUND: Hyperhomocysteinaemia is a factor related to the development of atherosclerosis in rheumatoid arthritis (RA). However, Hispanics with RA develop high rates of coronary disease; there are no studies about the frequency and factors related to high levels of homocysteine in Mexican patients. OBJECTIVE: To evaluate the prevalence and characteristics associated with hyperhomocysteinaemia in Mexican patients with RA. METHODS: One hundred and fifty-two patients with RA were compared with 153 controls. The assessment in RA included clinical characteristics, disease activity (RADAR), functioning (HAQ-Di and global functional status), comorbidity, and radiological damage. Laboratory determinations included total serum homocysteine (tHcy), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and lipid profile. RESULTS: Median levels of homocysteine were higher in RA compared with controls (11.3 vs. 9.3, p<0.001). Twenty per cent of the patients with RA had hyperhomocysteinaemia (>15 micromol/L) compared with 6% in controls (p<0.001). There was statistical association between hyperhomocysteinaemia in RA with male gender (p<0.001), impairment in the global functional status (p = 0.004), higher radiological damage (p = 0.001), and CRP (p = 0.04). There was no association with RADAR, HAQ-Di, or RF, methotrexate dose or duration of use. In the adjusted multivariate model, the two variables associated with higher risk for hyperhomocysteinaemia were male gender (OR = 4.2, 95% CI 2 to 12, p = 0.006) and higher radiological damage (III-IV) (OR = 3.4, 95% CI 1.3 to 9, p = 0.01). CONCLUSIONS: Our data show a high prevalence of hyperhomocysteinaemia in Mexican patients with RA. More effort is required to evaluate and treat earlier this coronary risk factor.     

Measurement of hand bone mineral content by dual energy x-ray absorptiometry: development of the method, and its application in normal volunteers and in patients with rheumatoid arthritis.

OBJECTIVES--To develop a method of measuring hand bone mineral content (BMC) by dual energy x ray absorptiometry (DXA); to apply this method of measuring hand BMC to normal volunteers to ascertain causes of variability; and to measure hand BMC in patients with rheumatoid arthritis (RA) of varying duration and severity. METHODS--The x ray beam of the Hologic QDR 1000 dual energy x ray absorptiometer was hardened by introducing a perspex-aluminium plate and the analysis software altered to allow for the small tissue bulk of the hand compared with the torso. Ninety five volunteers (46 men age 24-81 and 49 women age 20-83) had scans of both hands. Eight volunteers were assessed repeatedly to establish reproducibility and effect of hand position. Fifty six patients (22 men, 34 women, age range 25-86 years) with RA of differing duration and severity, had hand BMC measurement by DXA. RESULTS--The precision of BMC measurement was 2.3% with no additional variation due to hand position. Hand dominance had no significant effect on BMC. In men, hand BMC correlated with height (r = 0.57, p < 0.0001), weight (r = 0.58, p < 0.0001), forearm span (r = 0.5, p = 0.0006) and hand volume (r = 0.66, p < 0.0001). In women hand BMC correlated with height (r = 0.66, p < 0.0001), weight (r = 0.4, p = 0.003), forearm span (r = 0.3, p = 0.03) and hand volume (r = 0.49, p = 0.0008). After correcting for all these variables, male volunteers had significantly higher hand BMC than female volunteers (p = 0.01) and patients with RA had lower hand BMC than normal volunteers (total hand BMC in male volunteers 90.9 gms, 95% CI 86.9-95, in male patients 81.7 gms, 95% CI 73.7-89.6, p < 0.004, total hand BMC in female volunteers 62.2 gms 95% CI 59.8-64.5, female patients 52.3 gms, 95% CI 48.1-56.5, p < 0.005). In patients with RA, the hand BMC showed an inverse correlation with age (r = -0.44, p = 0.01), disease duration (r = -0.62, p = 0.0003), Larsen's grades (r = -0.62, p = 0.0002) and modified Sharp's method score (r = -0.69, p < 0.0001) in female patients only. CONCLUSIONS--A new, sensitive and reproducible technique of measurement of hand bone mineral content by DXA, has been developed and this method has been applied to normal volunteers and patients with RA. Hand dominance had no significant effect on hand BMC. After correcting for physical size, men have higher hand BMC than women. Hand BMC inversely correlates in women patients with disease duration and other validated methods of assessing radiological outcome in RA. Longitudinal studies are needed to establish its role in monitoring disease progression.     

HLA-DRB1 genotype associations in 793 white patients from a rheumatoid arthritis inception cohort: frequency,severity, and treatment bias

OBJECTIVE: The HLA-DRB1 "shared epitope" (SE) genotypes are associated with rheumatoid arthritis (RA), but it remains controversial whether the association is with incidence, severity, or both, whether there are associations in seronegative patients, and whether different DRB1 alleles that contain the SE have similar effects on RA susceptibility and/or severity. The present study was undertaken to study these issues in a large cohort of patients with RA. METHODS: White patients with RA of <6 months' duration (n = 793) were enrolled in an inception cohort. HLA-DRB1 typing was performed, and patients were categorized into 21 DRB1 genotype groups. The disability index of the Health Assessment Questionnaire was the primary outcome measure. RESULTS: DRB1 associations in seronegative RA patients closely resembled those in controls. Of seropositive patients, 21% had 2 copies of the epitope, 52% had 1 copy, and 27% had none. However, not all genotypes with 1 copy were associated with increased susceptibility; for example, frequencies of DRB1*0404/X and *01/X did not differ from those in controls. Absolute differences between seropositive RA patients and controls were greatest for DRB1*0401 homozygosity (3.8% versus 0.8%, respectively) and *0401/0404 heterozygosity (4.7% versus 1.0%). DRB1*0404 was increased in frequency in seropositive RA but, unlike *0401, an increased frequency was seen only with 2 epitope copies. The relatively rare DRB1*10 had an unexpected association with seropositive RA, being present in 1.7% of seropositive RA patients and 0.7% of controls, and also showed a trend toward association with greater disease severity. The presence of 2 epitope copies was associated with increased frequency of seropositivity and younger age at disease onset, not with disease severity. Treatment indication bias was substantial and may have accounted for some of these effects. HLA-DRB1*0401/0404 was found much more frequently in men and in patients with a lower age at disease onset, and there was a trend toward a higher frequency of *0404/0401 in women. CONCLUSION: This large inception cohort study confirms previously identified major associations and provides additional insights. Only one dominant association was found: *0401, which differs from other SE alleles in a single Lys-for-Arg substitution. The association of the rare DRB1*10 allele has not previously been postulated. Sex associations were confirmed. Associations with seronegative RA were not seen. Not all genotypes containing an SE copy showed increased susceptibility to RA. The association of SE genotypes found in this study related to disease susceptibility rather than severity.     

Influence of hormone replacement therapy on disease progression and bone mineral density in rheumatoid arthritis

OBJECTIVE: Hormone replacement therapy (HRT) is known to exert a positive effect in preventing bone loss and a beneficial effect on the disease activity in rheumatoid arthritis (RA). We evaluated the effects of HRT on bone mineral density (BMD) and on the course of established RA. METHODS: Eighty-eight postmenopausal women with RA were randomly allocated to receive HRT, vitamin D3, and calcium supplementation or vitamin D3 and calcium supplementation alone for 2 years. The effects of additional HRT on laboratory and clinical measures of disease activity, quality of life, and BMD and on radiographic joint damage were investigated. RESULTS: Treatment with HRT suppressed signs of inflammation as shown by reduction in erythrocyte sedimentation rate (ESR) (p = 0.025) and an elevation in hemoglobin concentration (p = 0.007), a better clinical outcome assessed by response on the Disease Activity Score 28 (DAS28) (p = 0.036), increased BMD in the forearm, proximal femur and spine (p < 0.01), and retarded (p = 0.026) progression of joint destruction among patients with radiological progressive disease. No significant effect on quality of life was seen. CONCLUSION: Two years of HRT in women with active RA had significant ameliorating effects on inflammation, DAS28 response, and BMD and was associated with slower progression of radiological joint destruction. The mechanisms by which HRT exerts its effects remain to be elucidated. We suggest HRT can be used in addition to conventional therapy in the management of postmenopausal patients with RA.     

Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis

OBJECTIVES: Smokers have an increased incidence of rheumatoid factor (RF) and rheumatoid arthritis (RA) and one report has also indicated that smoking may also adversely influence the severity of RA. METHODS: Sixty-three women with advanced RA answered a structured questionnaire that included detailed information about their smoking history. The women were also evaluated clinically and radiologically. RESULTS: Heavy smoking (>/= 20 pack-yr) was associated with rheumatoid nodules (P: = 0.01), a higher HAQ score (P: = 0.002) and a lower grip strength (P: = 0.01). Smoking was also associated with more radiological joint damage (P: = 0.02). A positive correlation was observed between smoking and RF levels, in particular IgA RF and a combined elevation of IgM and IgA RF. CONCLUSIONS: Smoking has an adverse effect on disease progression in patients with RA. An association was also observed between smoking and those RF types that predispose to RA and have the highest diagnostic specificity for this disease.