Assessment of pain in patients with juvenile rheumatoid arthritis: relation between pain intensity and degree of joint inflammation.

The relation between pain and joint inflammation in patients with juvenile rheumatoid arthritis has not previously been systematically evaluated. Eighteen patients with juvenile rheumatoid arthritis completed paediatric pain questionnaires and the joints affected were examined by thermography. Although significant correlations were shown between parent and doctor pain intensity ratings and joint temperature, correlations of patient pain intensity ratings and joint temperature were only significant in younger children. The degree of joint inflammation is only one factor of several contributing to the amount of subjective pain experienced by children with juvenile rheumatoid arthritis, indicating the need for a comprehensive assessment of the relatively independent variables of inflammation and pain in children with juvenile rheumatoid arthritis.     

Does sport negatively influence joint scores in patients with juvenile rheumatoid arthritis

Summary The influence of sporting activities performed using joint protective measures on deterioration in hand and lower extremity function was evaluated over 8 years in 62 patients with juvenile rheumatoid arthritis (JRA). Sporting activities usually recommended to patients with JRA, such as cycling and swimming, did not negatively influence hand or lower extremity function as compared to a control group of patients not taking part in sporting activities. Besides cycling and swimming, other sporting activities were only performed by a minority of patients (less than 10%). Decreases in total joint scores of both the hands and lower extremities, showed significant correlations with disease duration in patients taking part and in patients not taking part in sporting activities. Polyarticular onset of disease was associated with higher total joint scores of the hands as compared to pauciarticular onset of disease. In lower extremity function, no difference was found between patients with polyarticular onset and patients with pauciarticular onset. Disease duration of longer than 10 years, accompanied by severe functional deterioration, was followed by low participation in sporting activities. Therefore, we suggest that appropriate sporting activities, such as cycling and swimming, can be advised to patients with JRA regardless of disease duration, since no negative effects were observed in our study over a period of 8 years.     

Predictors of radiographic joint damage in patients with early rheumatoid arthritis

OBJECTIVE: To determine factors at diagnosis, associated with radiographic damage at diagnosis and after one year, in patients with early rheumatoid arthritis (RA). METHODS: New patients with early RA were followed up for one year. Possible prognostic factors were duration of complaints, morning stiffness, disease activity score (DAS28), functional status (Health Assessment Questionnaire (HAQ) score), rheumatoid factor (IgM RF), and C reactive protein (CRP). Outcome was defined as radiographic damage of the hands and feet (Sharp/van der Heijde score). For the statistical analysis, one way analysis of variance and a forward stepwise logistic regression model was used. RESULTS: 130 patients with RA (68% female; median age 64 years, range 21-86) were included. Despite the fact that the median duration of complaints was short (15 weeks, range 2-106) the radiographic damage at diagnosis was significantly correlated with the duration of complaints (p<0.05). Patients with a duration of complaints of >34 weeks had significantly more radiographic joint damage at diagnosis than patients with a shorter duration of complaints. Radiographic progression at one year was correlated with high radiographic joint damage, high CRP level, and a positive IgM RF at entry. CONCLUSIONS: In early RA, the number of radiographic lesions was correlated with a longer duration of complaints at the first visit. Progression of these lesions was predicted by a high baseline joint damage, high CRP level, and a positive IgM RF. Further reduction of the delay in referral and early treatment may further decrease joint damage in patients with recent onset polyarthritis.     

Predicting pain among children with juvenile rheumatoid arthritis

Objective. Children and adolescents with juvenile rheumatoid arthritis (JRA) often report pain as a major symptom that affects their daily activities. Little is known about the factors that contribute to pain, however. Demographic, disease status, and social-psychologic variables were used to predict pain of JRA. Methods. Participants were 37 girls and 23 boys who were 7 to 17 years old. Measures included the Hopelessness Scale for Children, the Sadness Scale from the Differential Emotions Scale—IV, and the Social Support Questionnaire-Revised. A pain visual analogue scale served as the criterion measure. Results. Reported pain was modestly correlated with disease duration and age. A hierarchical regression indicated that the predictor variables accounted for a modest amount of variance in pain scores. Conclusions. The results suggest that the factors contributing to pain in children with JRA are different from those in adults with rheumatoid arthritis (RA). Research is needed to identify the psychologic and socioenvironmental variables that influence pain among children with JRA.     

Antibodies to dna in patients with rheumatoid arthritis and juvenile rheumatoid arthritis

Antibodies to double-stranded DNA (DSDNA) were found in 18 patients with RA, in 5 patients with JRA, and in 5 patients with undiagnosed connective tissue disease. Five patients had clinical features consistent with both RA and SLE, 11 with only RA, and 5 with only JRA. Based on these observations, the presence of serum anti-DSDNA antibodies should not be used as a sole criterion in the diagnosis of SLE.     

Clonal analysis of joint fluid T lymphocytes in patients with juvenile rheumatoid arthritis

Synovial fluid (SF) lymphocytes from 4 patients with pauciarticular juvenile rheumatoid arthritis (JRA) and 4 patients with polyarticular JRA were examined for their phenotypic and functional characteristics. In all 8 patients there was a high proportion of activated SF T cells, together with an increased proportion of CD2+CD3- and the presence of CD3+CD4-CD8-WT31- lymphocytes. The functional analysis at the clonal level in 5 patients (427 clones) showed a relevant proportion of cytotoxic T cell clones, which were not confined to typically cytolytic phenotypes, but were also present among CD3+CD4+CD8- cultures. Compared to those with pauciarticular JRA, patients with polyarticular disease had a significantly higher proportion of T cell clones with cytotoxic activity. Although derived from a limited number of patients, our data suggest a direct involvement of T cells in the pathogenetic mechanisms that originate and maintain the articular damage, and the possibility of different or more pronounced T cell reactivities in the clinically more diffuse JRA types.     

Inflammation and damage in an individual joint predict further damage in that joint in patients with early rheumatoid arthritis

OBJECTIVE; Several factors predict joint damage in early rheumatoid arthritis (RA). In the context of a trial in early RA, we studied the relationship between clinical signs in individual joints and their propensity to develop progressive damage. METHODS: The COBRA (Combinatietherapie Bij Reumatoide Artritis) multicenter trial compared the efficacy of prednisolone, methotrexate, and sulfasalazine against sulfasalazine alone in 155 patients with early RA. Two blinded observers interpreted radiographs in sequence (using the Sharp/Van der Heijde scoring system); in each center, one blinded observer performed clinical assessments every 3 months. The current analysis is based on clinical and radiologic data of the individual metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of 135 patients. Conditional stepwise logistic regression analyzed the relationship between damage (progression) and clinical signs at baseline and followup for each of these joints individually in each patient. RESULTS: Combination therapy strongly retarded the progression of damage. Progression was stronger in patients with rheumatoid factor, HLA-DR4, and high levels of disease activity at baseline. At baseline, 6% of the MCP and PIP joints showed damage; after 1 year, disease had progressed in 10% of these joints. Baseline damage, swelling, or pain in a joint independently and strongly predicted the progression of damage in that joint (P < 0.001). Each additional point in the swelling score (range 0-2) tripled the risk for subsequent progression. Each additional point on the Sharp scale (range 0-8 per joint) and each additional point on the pain scale (range 0-3) doubled the risk. The mean pain and swelling scores over the year were even stronger predictors of damage. CONCLUSION: Local expression of early RA disease activity, both at baseline and at 1-year followup, is strongly related to progression of damage in the individual joint.     

Antibodies to DNA in patients with rheumatoid arthritis and juvenile rheumatoid arthritis.

Antibodies to double-stranded DNA (DSDNA) were found in 18 patients with RA, in 5 patients with JRA, and in 5 patients with undiagnosed connective tissue disease. Five patients had clinical features consistent with both RA and SLE, 11 with only RA, and 5 with only JRA. Based on these observations, the presence of serum anti-DSDNA antibodies should not be used as a sole criterion in the diagnosis of SLE.     

Pathogenesis of joint damage in rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by the appearance of progressive joint damage that may be identified only months after the onset of symptoms. Early cartilage and bone erosion is associated with the accumulation of several cell populations in the synovial membrane (SM) and the formation of a proliferating pannus. The synovial sublining layer contains several cell populations including macrophages, T and B lymphocytes, dendritic cells, and polymorphonuclear leukocytes. The lining layer contains large numbers of macrophages and fibroblast-like synoviocytes. The interface between pannus and cartilage is occupied predominantly by activated macrophage populations and synoviocytes capable of secreting destructive proteases in abundance. We have observed that macrophages aggregate preferentially adjacent to the cartilage-pannus junction (CPJ) and express differentiation phenotypes that are absent from the lining layer macrophages of more remote SM. Moreover, in a prospective study, the number of SM macrophages correlated with the degree of joint damage occurring over one year. Similar results were obtained when SM biopsy samples were analyzed and correlated with clinical and radiological changes occurring over 6 years. Macrophages and synoviocytes at the CPJ express matrix metalloproteinase and cathepsin mRNA from the earliest stage of RA. The mechanisms involved in the secretion of tissue degrading enzymes by macrophages and synoviocytes are undergoing further investigation and preliminary results suggest that different regulation pathways may exist.     

Salicylate hepatotoxicity in patients with juvenile rheumatoid arthritis

Salicylates were administered to 6 patients with juvenile rheumatoid arthritis in doses sufficient to produce a serum salicylate level in excess of 25 mg/100 ml. All 6 patients developed elevations of serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase. In addition, 4 patients had other evidence of hepatic dysfunction. Abnormalities were dose-related and were reversible upon lowering the salicylate dose. Liver biopsies performed in 2 patients revealed a mononuclear cell infiltrate of portal triads in both and scattered single cell necrosis in the parenchyma in 1 case.     

Simple function tests,but not the modified HAQ,correlate with radiological joint damage in rheumatoid arthritis

OBJECTIVE: To test the validity of the Modified Stanford Health Assessment Questionnaire (MHAQ) for assessment of physical disability in rheumatoid arthritis (RA). METHODS: Sixty-one RA patients with mean age of 61 years and median disease duration of four years were included in this cross sectional study. The patients completed the MHAQ. Four simple function tests were performed (walk test, chair test, upper extremity mobility test, and grip strength) and a modified Larsen score was established. Pain score (VAS) and laboratory variables for inflammation were recorded. RESULTS: MHAQ, function tests, pain, and C reactive protein (CRP) showed highly significant mutual correlations (p < 0.01). However, MHAQ did not correlate with Larsen score (R = 0.06; NS), while most function tests did (walk test, R = 0.29; p < 0.05; chair test, R = 0.21; NS; mobility test, R = 0.36; p < 0.01 and grip strength, R = -0.35 p < 0.01). The superiority of function tests was even more pronounced after four years (walk test, R = 0.31; p < 0.05; chair test, R = 0.50; p < 0.01; mobility test, R = 0.49; p < 0.01; grip strength, R = -0.52; p < 0.01; MHAQ, R = 0.34; NS). CONCLUSION: Objective function tests are preferable to MHAQ in the assessment of physical disability in RA.     

Distal interphalangeal joint abnormalities in children with polyarticular juvenile rheumatoid arthritis

Involvement of the distal interphalangeal (DIP) joints was noted radiographically in 24 (43.6%) of 55 patients with polyarticular juvenile rheumatoid arthritis. DIP changes were apparent later in the course of the disease and were less severe than in other affected joints. Soft tissue swelling and joint space narrowing were the most frequent abnormalities in the DIP joints. Erosive changes and angular deformities were uncommon. There was no significant correlation between DIP joint involvement and sex, age at presentation, involvement of the hands and wrists at presentation, or positivity of either rheumatoid factor or antinuclear antibody. There was a strong correlation between the presence of extraarticular signs and symptoms and involvement of the DIP joints; however, this may reflect the greater severity of the disease in these patients generally.     

HLA-DR-DQ haplotypes and genotypes in Finnish patients with rheumatoid arthritis

OBJECTIVES: To elucidate the contribution of HLA-DR-DQ haplotypes and their genotypic combinations to susceptibility to rheumatoid arthritis, and to evaluate the various models for HLA associated risk for the disease in a series of Finnish patients. METHODS: 322 Finnish patients with rheumatoid arthritis were typed for common north European HLA-DR-DQ haplotypes and compared with a series of 1244 artificial family based control haplotypes. RESULTS: The association of the so called shared epitope (SE) haplotypes (DRB1*0401, *0404, *0408, and *01) with rheumatoid arthritis was confirmed. The DRB1*0401 haplotypes carried a far stronger risk for the disease than the (DRB1*01/10)-(DQA1*01)-DQB1*0501 haplotypes. Seven protective HLA haplotypes--(DRB1*15)-(DQA1*01)-DQB1*0602; (DRB1*08)-(DQA1*04)-DQB1*04; (DRB1*11/12)-DQA1*05-DQB1*0301; (DRB1*1301)-(DQA1*01)-DQB1*0603; (DRB1*1302)-(DQA1*01)-DQB1*0604; (DRB1*07)-DQA1*0201-DQB1*0303; and (DRB1*16)- (DQA1*01)-DQB1*0502--were identified. In accordance with the reshaped shared epitope hypothesis, all the protective DRB1 alleles in these haplotypes share either isoleucine at position 67 or aspartic acid at position 70 in their third hypervariable region motif. However, differences in the disease risk of haplotypes carrying the same DR but different DQ alleles were also found: (DRB1*07)-DQA1*0201-DQB1*0303 was protective, while (DRB1*07)-DQA1*0201-DQB1*02 was neutral. The same haplotypes carried different risks for rheumatoid arthritis depending on their combination in genotypes. CONCLUSIONS: When assessing the influence of HLA genes on the susceptibility to rheumatoid arthritis, not only should the HLA-DR or -DQ alleles or haplotypes be unravelled but also the genotype. The effect of HLA class II region genes is more complicated than any of the existing hypotheses can explain.     

Adipocytokines are associated with radiographic joint damage in rheumatoid arthritis

Objective

Obesity protects against radiographic joint damage in rheumatoid arthritis (RA) through poorly defined mechanisms. Adipocytokines are produced in adipose tissue and modulate inflammatory responses and radiographic joint damage in animal models. The purpose of this study was to examine the hypothesis that adipocytokines modulate inflammation and radiographic joint damage in patients with RA.

Methods

We compared serum concentrations of leptin, resistin, adiponectin, and visfatin in 167 RA patients and 91 control subjects. The independent association between adipocytokines and body mass index (BMI), measures of inflammation (C‐reactive protein [CRP], interleukin‐6 [IL‐6], and tumor necrosis factor α [TNFα]), and radiographic joint damage (Larsen score; n = 93 patients) was examined in RA patients by multivariable regression analysis first controlling for age, race, and sex, and then for obesity (BMI) and inflammation (TNFα, IL‐6, and CRP).

Results

Concentrations of all adipocytokines were significantly higher in RA patients than in controls; for visfatin and adiponectin, this association remained significant after adjusting for BMI, inflammation, or both. Visfatin concentrations were associated with higher Larsen scores, and this association remained significant after adjustment for age, race, sex, disease duration, BMI, and inflammation (odds ratio [OR] 2.38 [95% confidence interval (95% CI) 1.32–4.29], P = 0.004). Leptin concentrations showed a positive association with the BMI (ρ = 0.58, P < 0.01) and showed a negative association with the Larsen score after adjustment for inflammation (OR 0.32 [95% CI 0.17–0.61], P < 0.001), but not after adjustment for BMI (OR 0.86 [95% CI 0.42–1.73], P = 0.67).

Conclusion

Concentrations of adipocytokines are increased in patients with RA and may modulate radiographic joint damage. Visfatin is associated with increased, and leptin with reduced, levels of radiographic joint damage.

     

Elbow joint forces in patients with rheumatoid arthritis

Whilst developing an elbow endoprosthesis, the joint forces were estimated for patients with rheumatoid arthritis. Elbow flexion strength of rheumatoid patients was found to be 45% of normal. Muscle strengths and limb geometry data were found by a dissection technique, which allowed joint forces to be calculated during flexion, extension and abduction efforts. Forces up to 2.4 kN were predicted to act on the distal humerus, with similar forces acting in both radius and ulna. The skeletal structure is well adapted to carry the predicted forces, and onlay-type prostheses are recommended for elbow replacement.     

HLA-DP antigens in patients with pauciarticular juvenile rheumatoid arthritis

The distribution of the recently described HLA-DP antigens was examined in a population of patients with pauciarticular juvenile rheumatoid arthritis and iridocyclitis, in an attempt to further characterize the immunogenetically determined susceptibility to this disease. There was a significantly increased frequency of the HLA-DPw2 antigen in the patients compared with the controls (67% versus 34%; odds ratio 3.9, P = 0.003 by Fisher's exact test). Population studies and family studies showed that this association with HLA-DPw2 was not secondary to linkage disequilibrium with the previously defined HLA-D region markers of disease (HLA-DR5 and HLA-DRw8) in these patients. These data raise the possibility that susceptibility to this form of juvenile rheumatoid arthritis may be regulated by more than one HLA-linked gene.