Rheumatoid Arthritis: Clark B

Griffiths B, Situnayake RD, Clark B, Tennant A, Salmon M, Emery P. · Rheumatology and Rehabilitation Research Unit, University of Leeds, City Hospital, Dudley Road, Birmingham, University of Birmingham, UK. · Rheumatology (Oxford). · Pubmed #10952739 links to  free full text

Abstract: OBJECTIVE: There are a significant number of patients with rheumatoid arthritis (RA) of North Indian or Pakistani origin (Asian) now living in the UK. RA has been poorly studied in this racial group. The aim of this study was to compare RA in this Asian group with RA in the indigenous northern European (European) population. It was hypothesized that these two racial groups would have different disease expressions and immunogenetics that could be relevant to pathogenesis, prognosis and therapy. METHODS: One hundred and seven Asian RA patients, who fulfilled the 1987 American College of Rheumatology criteria, were stringently matched for age, sex and disease duration with 107 European RA patients, and were fully assessed. RESULTS: The Asian RA patients had significantly fewer bony erosions [median Larsen score 58.5 (interquartile range 45.5-77.8) vs 68 (52-93) for European patients; P: = 0.0066, Mann-Whitney U:-test] and rarely had nodules (5.7 vs 20%, P: = 0. 0019, Fisher's exact test). The two groups had the same prevalence of rheumatoid factor positivity, number of swollen joints and level of inflammation (C-reactive protein). The Asian RA patients had a reduced prevalence of the conserved third allelic hypervariable region (3AHVR) (45 vs 82%, P: < 0.0001, Fisher's exact test), particularly DRB1*0401 (4.5 vs 55%). However, the prevalence of the conserved 3AHVR was significantly increased in the Asian RA patients compared with Asian controls. By contrast, the Asian patients had more tender joints [13.5 (7-22) vs 5.5 (2-11.8); P: < 0.0001 Mann-Whitney U:-test]. The Health Assessment Questionnaire score was also significantly worse in the Asians compared with the Europeans [median 2.0 (1.13-2.63) vs 1.25 (0.5-2.13), P: = 0.0001). CONCLUSIONS: The Asian patients had similar levels of inflammation and less damage but more pain and disability than the matched European RA patients. Of the known prognostic factors for erosions (rheumatoid factor, conserved 3AHVR, swollen joints and C-reactive protein), only the conserved 3AHVR was reduced in the Asian RA patients, and this was consistent with their less erosive disease. These data also indicate the importance of pain as well as erosive damage in determining disability in Asian patients and stress the importance of adequate pain relief, in addition to disease suppression, when treating Asian RA patients.

Dalbeth N, Clark B, McQueen F, Doyle A, Taylor W. · University of Auckland, Grafton, Auckland, New Zealand. · Arthritis Rheum. · Pubmed #17665492 links to  free full text

Abstract: OBJECTIVE: To identify a valid method to measure radiographic damage in patients with chronic gout. METHODS: The scoring method that best represented radiographic damage in individual joints was analyzed by comparing a gold standard rheumatologist consensus global score with recognized scoring methods, including the Sharp/van der Heijde erosion and narrowing scores, Ratingen destruction score, and Steinbrocker score. Ninety-five proximal interphalangeal joints from 12 patients with gout were included in this analysis. Scoring of hand and feet radiographs from an additional 35 patients with gout was used to analyze the sites to be included in a scoring system and the additional features to be recorded. RESULTS: For individual joints, the combination of the Sharp/van der Heijde erosion and narrowing scores correlated best with the consensus global score. In addition, the limits of agreement were narrowest for the combined Sharp/van der Heijde erosion and narrowing score. All joint areas in the Sharp/van der Heijde rheumatoid arthritis score and the distal interphalangeal joints were affected by chronic gout and contributed to the total score. Additional features (extraarticular erosions, joint space widening, and ankylosis) occurred infrequently, and scoring of these features did not increase the reliability of the total score. The reliability of the total score was high: intraclass correlation coefficient for intraobserver reproducibility was 0.993-0.998 and for interobserver reproducibility was 0.963-0.966. The modified Sharp/van der Heijde score was able to discriminate between early and advanced disease. CONCLUSION: A modified Sharp/van der Heijde system accurately and reliably represents radiographic joint damage in chronic gout.

McQueen FM, Gao A, Ostergaard M, King A, Shalley G, Robinson E, Doyle A, Clark B, Dalbeth N. · Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Sciences, University of Auckland, Park Rd, Private Bag 92019 Auckland, New Zealand. · Ann Rheum Dis. · Pubmed #17491098 No free full text.

Abstract: OBJECTIVES: MRI bone oedema has been observed in early and advanced RA and may represent a cellular infiltrate (osteitis) in subchondral bone. We studied MRI scans from RA patients undergoing surgery, seeking to identify regions of bone oedema and examine its histopathological equivalent in resected bone. METHODS: Preoperative contrast-enhanced MRI scans were obtained in 11 RA patients scheduled for orthopaedic surgery to the hands/wrists or feet. In 9, MRI scans were scored by 2 readers for bone oedema (RAMRIS system). Its distribution with respect to surgical site was investigated. In 4 patients, 7 bone samples were examined for a cellular infiltrate, and this was compared with MRI bone oedema, scored for spatial extent and intensity. RESULTS: Inter-reader intraclass correlation coefficients for bone oedema were 0.51 (all sites) and 0.98 (bone samples for histology). Bone oedema was observed at 60% of surgical sites vs 38% of non-surgical sites. High-grade bone oedema (score >/=50% maximum) was strongly associated with the surgical field (OR 9.3 (3.5 to 24.2), p<0.0001). Bone oedema scores correlated with pain (r = 0.67, p = 0.048) and CRP (r = 0.86, p = 0.01). In 4 of the 7 bone samples, there was concordance between bone oedema and subchondral osteitis. In 3, there was no MRI bone oedema, and osteitis was "slight". CONCLUSION: High-grade MRI bone oedema was common within the field of intended surgery and associated with pain. There was concordance between the presence and severity of MRI bone oedema and osteitis on histology, with an MRI threshold effect due to differences in image resolution.

McKibbin M, Clark B, Isaacs JD, Morrell AJ, Griffiths B, Morgan AW, Gooi HC. · Department of Ophthalmology, St James's University Hospital, Leeds, UK. · Eye. · Pubmed #11767025 No free full text.

Abstract: PURPOSE: To investigate the role of the shared epitope alleles in determining susceptibility to and the phenotype of corneal melting in patients with rheumatoid arthritis (RA). METHODS: The HLA class 1 and 2 genotype was determined for 17 patients with rheumatoid-associated comeal melting by the phototyping method. HLA-DR4 subtyping was performed by PCR sequence-based typing. The frequency of all the shared epitope alleles and, in particular, of the higher-risk *0401 and *0404 alleles, was compared with healthy controls and unrelated RA patients, with and without extra-articular manifestations. A comparison was also made between the shared epitope genotype of the corneal melt patients and local, ocular disease characteristics. RESULTS: Thirteen (76%) patients with corneal melt possessed at least one shared epitope allele and 5 (29%) possessed two alleles. The dominant alleles were variants of the DR4 family, notably the *0401, *0404 and *0408 alleles. Both the allele frequency and a double dose of shared epitope alleles were more common in the three RA patient groups than in the healthy, control group (p < 0.005). Although the frequency of the higher-risk alleles was similar in the three RA patient group, a trend existed for a double dose of higher-risk alleles to be more common in the patients with either corneal melt or other extra-articular manifestations (p > 0.2). No association was found between the number or type of shared epitope alleles and any of the ocular disease characteristics studied. CONCLUSIONS: The results of this study suggest that the shared epitope alleles do not influence the ocular disease phenotype of corneal melt in RA patients. Shared epitope determination of RA patients may help to identify those susceptible to either corneal melt or other extra-articular disease. RA patients with a double dose of higher-risk alleles may have an increased risk of corneal melt.