K. Kaarela

Finnish HLA studies confirm the increased risk conferred by HLA-B27 homozygosity in ankylosing spondylitis

Objective: To determine the influence of HLA-B27 homozygosity and HLA-DRB1 alleles in the susceptibility to, and severity of, ankylosing spondylitis in a Finnish population. Methods: 673 individuals from 261 families with ankylosing spondylitis were genotyped for HLA-DRB1 alleles and HLA-B27 heterozygosity/homozygosity. The frequencies of HLA-B27 homozygotes in probands from these families were compared with the expected number of HLA-B27 homozygotes in controls under Hardy–Weinberg equilibrium (HWE). The effect of HLA-DRB1 alleles was assessed using a logistic regression procedure conditioned on HLA-B27 and case–control analysis. Results:HLA-B27 was detected in 93% of cases of ankylosing spondylitis. An overrepresentation of HLA-B27 homozygotes was noted in ankylosing spondylitis (11%) compared with the expected number of HLA-B27 homozygotes under HWE (4%) (odds ratio (OR) = 3.3 (95% confidence interval, 1.6 to 6.8), p = 0.002). HLA-B27 homozygosity was marginally associated with reduced BASDAI (HLA-B27 homozygotes, 4.5 (1.6); HLA-B27 heterozygotes, 5.4 (1.8) (mean (SD)), p = 0.05). Acute anterior uveitis (AAU) was present in significantly more HLA-B27 positive cases (50%) than HLA-B27 negative cases (16%) (OR = 5.4 (1.7 to 17), p<0.004). HLA-B27 positive cases had a lower average age of symptom onset (26.7 (8.0) years) compared with HLA-B27 negative cases (35.7 (11.2) years) (p<0.0001). Conclusions:HLA-B27 homozygosity is associated with a moderately increased risk of ankylosing spondylitis compared with HLA-B27 heterozygosity. HLA-B27 positive cases had an earlier age of onset of ankylosing spondylitis than HLA-B27 negative cases and were more likely to develop AAU. HLA-DRB1 alleles may influence the age of symptom onset of ankylosing spondylitis.

Secondary Amyloidosis has Decreased in Patients with Inflammatory Joint Disease in Finland

Abstract: We studied whether the high incidence of secondary amyloidosis (SA) is a consistent finding in patients with inflammatory joint disease. A total of 4508 biopsies of patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis were studied at the Rheumatism Foundation Hospital during 1987–1997. The results show that the annual number of findings of SA was reduced from 68 to less than 10. We suggest that a change in medication towards more frequent use of cytostatic agents is the reason for the reduction in incidence of SA.

The Value of the ACR 1987 Criteria in Very Early Rheumatoid Arthritis

We assessed the sensitivity and specificity of the ACR 1987 revised criteria for rheumatoid arthritis (RA) in 121 patients with recent-onset (< or = 6 months) RA, 68 with reactive arthritis (ReA), 19 with ankylosing spondylitis (AS), and 13 with psoriatic arthritis (PsA). The sensitivity of each single criterion ranged 8.3-90.9% and specificity 52.0-100%. The sensitivity of four fulfilled criteria was 83.5% and specificity 86.0%. In ReA 11.8%, AS 5.3%, and PsA 38.5% of patients fulfilled four criteria respectively. Thus at the beginning of RA, 83% of patients could be diagnosed correctly by using the ACR 1987 criteria, and the remaining 17% had seropositive and/or erosive arthritis at the onset. The suitability of the radiographic ACR criteria is discussed.

Bone destruction, upward migration, and medialisation of rheumatoid shoulder: a 15 year follow up study

OBJECTIVE To evaluate bone destruction, upward migration, and medialisation of the glenohumeral (GH) joint in a cohort of 74 patients with seropositive and erosive rheumatoid arthritis followed up prospectively. METHODS At the 15 year follow up 148 shoulders were radiographed by a standard method. Bone destruction in the GH joint was examined from the radiographs by four methods, of which three measured the migration and one the remodelling of the humeral head. The distances from the greater tuberosity of the humeral head to the coracoid process (medialisation distance (MD)) and to the articular surface of the humeral head (GA) have been previously developed to evaluate the preoperative offsets of the arthritic GH joint. Medial displacement index (MI) and upward migration index (UI) have been recently developed to evaluate the destructive pattern of the rheumatoid GH joint. Destruction of the GH joints was assessed by the Larsen method on a scale of 0 to 5. The relation between the measurements and the grade of destruction of the GH joints was examined. UI was compared with our previous measurements of the subacromial space. RESULTS Both the MI and the UI had a negative correlation with the GH joint destruction (Larsen grade), r=−0.49 (95% CI −0.36 to −0.60) and r=−0.58 (95% CI −0.46 to −0.68). The UI correlated significantly with the subacromial space, r=0.90 (95% CI 0.86 to 0.93). The mean MI and UI measurements of the non-affected joints were within the reported normal variation. The mean MD collapsed between Larsen grades 4 (83.0 mm) and 5 (65.5 mm). The morphology of the humeral head began to flatten and erode from the grade 3 onwards and medial head destruction was detected at grade 5. CONCLUSIONS Medialisation seems to be preceded by upward migration of the humeral head, indicating rotator cuff damage. Symptomatic Larsen grade 3 shoulders should be intensively followed up by clinical and radiological means. If a total shoulder arthroplasty is considered, an orthopaedic consultation is worthwhile at a sufficiently early stage (Larsen 3 and 4), when soft tissue structures responsible for function are still in proper condition and timing of the operative procedure can be well planned.

Rise in serum C reactive protein after hip and knee arthroplasties in patients with rheumatoid arthritis

OBJECTIVE Serum C reactive protein (CRP) concentration was evaluated in patients with rheumatoid arthritis (RA) undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) to ascertain the postoperative CRP response. METHODS Thirty seven consecutive patients with RA who had undergone THA or TKA were included in the study. The CRP concentration was measured in every patient once preoperatively and every other day for one week postoperatively. RESULTS The peak median CRP concentration (94 mg/l) was achieved on the first and second day postoperatively and was seven times higher than the median preoperative concentration (13 mg/l). CRP declined to the preoperative concentration in about one week. The rise of the CRP concentration was significant (p< 0.001). No infection was encountered in this series. CONCLUSION A rapid rise in the postoperative CRP concentration is normal in patients with RA treated by THA or TKA. The CRP concentration decreases to the preoperative value in about one week. Serial CRP measurements, including at least one preoperative measurement, are needed when the clinical significance of the postoperative CRP values is evaluated. When the postoperative CRP concentration remains raised for several days compared with the preoperative value, or even rises, it may indicate the presence of a complication in these patients.

Interleukin 10 polymorphisms in ankylosing spondylitis

Genetic polymorphisms of the IL10 promoter region have been implicated in many autoimmune diseases, including seronegative spondyloarthropathies. We studied three SNPs (IL10–1087, −824, and −597) and two microsatellites (IL10R and IL10G) lying within the promoter region of IL10 for association with susceptibility to and clinical manifestations of ankylosing spondylitis (AS), a common form of spondyloarthritis. Four hundred and sixty-eight individuals from 182 Finnish families affected with AS were studied. No association between individual IL10 promoter region polymorphisms or marker haplotype was observed with susceptibility to AS, but weak association was noted between the IL10–597 and −824 SNPs and age of disease onset (P=0.01 for each SNP). The IL10.G4 allele was associated with BASFI (corrected for disease duration) (P=0.03). We conclude that IL10 promoter polymorphisms have no significant effect on susceptibility to AS, but may play a minor role in determining age of disease onset and disease severity.

Relationship of ankle joint involvement with subtalar destruction in patients with rheumatoid arthritis.A 20-year follow-up study

AIMS In the present study we evaluated radiographically involvement of the ankle joint and its relationship to destruction of the subtalar joint in rheumatoid arthritis (RA). METHODS An inception cohort of 103 patients with seropositive RA was followed over a period of 20 years. Follow-up examinations were conducted after onset, 1, 3, 8, 15, and 20 years from entry. A total of 83 patients attended the 15-year and 68 patients the 20-year follow-up. Radiographic evaluation was performed using a lateral weight-bearing ankle radiograph. A simplified grading was applied for the talocrural joint, in which the ankles (patients) were divided into three groups: no changes, minor changes and major changes. In the end-point analysis the last radiograph was assigned. Subtalar destruction was recorded (Larsen grade > or = 2). Severity of RA in different groups was evaluated using the Larsen score of 0-100 of hands and feet. Difference between patient groups was evaluated using Cuzicks test. RESULTS At the endpoint major changes of the ankles were detected in seven patients (7%) only, minor changes were observed in 17 patients (16%). The first minor involvement of the ankle was observed at the three-year follow-up in two patients. First major changes were detected at the 15-year follow-up in three ankles of two patients. Subtalar pathology preceded that of TC joint in all ankles with major changes. In 17 patients with minor changes, simultaneous subtalar pathology was observed in all but two ankles, while preceding subtalar involvement was radiographically manifest in 13 of 21 ankles. The means of Larsen scores of 0-100 were in the three ankle grading groups 40, 54 and 63, respectively. Cuzicks test for the trend was highly significant (P < 0.001). No reconstructive surgery was performed on the ankle joint during the follow-up, whereas the subtalar joint complex was fused cumulatively in 12 patients. CONCLUSIONS The ankle joint is involved in a late stage of RA and is usually affected only in the patients with severe disease. Subtalar pathology precedes the changes in the talocrural joint almost regularly.

Destruction and arthroplasties of the metatarsophalangeal joints in seropositive rheumatoid arthritis. A 20-year follow-up study.

Destruction and arthroplasties of the metatarsophalangeal (MTP)joints and interphalangeal (IP) joint of the big toe were evaluated in 103 seropositive rheumatoid arthritis (RA) patients in a prospective follow-up study at onset and at 1, 3, 8, 15, and 20 years from entry. A total of 83 patients attended the 15-year follow-up and 68 attended the 20-year follow-up. Data on the forefoot synovectomies and reconstructions performed were obtained from patient documents and radiographs. The radiographs were assigned by the Larsen method; in the end point analysis the last or preoperative radiograph was used. Erosions of Larsen grade > or =2 were present in 6%/ of the investigated 1236 joints at onset and after 20 years in 62%, respectively. At the end point, 24% of the joints were severely damaged (Larsen grade 4-5). The MTP I and IP joints showed the lowest grade of destruction during follow-up, and MTP V the worst destruction. Synovectomies were performed in 24 MTP joints; a total of 75% of these joints were later resected. MTP II-V head resections were performed in 21% and the Keller procedure in 12% of the MTP I joints. Erosive changes occur early in the MTP joints, and their grade of destruction is high; therefore they should be included in radiographic criteria and scores. MTP synovectomies are insufficient treatments for RA without concomitant immunosuppression of the disease.

A 20-year follow-up study of subtalar changes in rheumatoid arthritis.

The destruction of the subtalar joints in 103 seropositive RA patients with recent (< or = 6 months) disease was evaluated radiographically in a prospective follow-up study at onset and at 1, 3, 8, 15, and 20 years from entry. A total of 83 patients attended the 15-year follow-up and 68 the 20-year follow-up. The Larsen grades of the joints were evaluated and the need for surgical treatment considered. At the 15-year follow-up the mean Larsen grade was 1.2 (median 0) and at the 20-year follow-up 1.3 (median 0); at the 20-year follow-up 77 subtalar joints were still assessed as Larsen grade 0. In this series, subtalar fusions were performed in 12 patients only. Spontaneous fusions occurred in 5 hindfeet in 3 patients. The destruction rate of the subtalar joint was lower than in previous retrospective or cross-sectional studies. The need for routine radiographs of ankles in RA patients is questioned.

Reoperation rate after elbow synovectomy in rheumatoid arthritis

The purpose of this study was to evaluate the reoperation rate of elbow synovectomy in patients with rheumatoid arthritis. A total of 103 synovectomies were performed in 88 patients (61 women) with rheumatoid factor-positive rheumatoid arthritis with a mean follow-up of 5.2 years (range, 1-8 years). The survival rate after elbow synovectomy (free from reoperation) was 77% (95% confidence interval, 66%-85%) at 5 years. Eight resynovectomies and fourteen total elbow replacements were performed during the follow-up. No significant improvement in range of motion was detected after synovectomy, but pain relief and patient satisfaction were favorable. Elbows were classified preoperatively (before primary synovectomy) with the Larsen system. All resynovectomies were performed for elbows of grade 0-2 destruction. A significant difference was found between early (Larsen grade 0-2) and late (Larsen grade 3) synovectomies in relation to elbow replacement (P =.002) during the follow-up. Late synovectomy yielded more temporary pain relief with a high rate of elbow arthroplasties.