Small bone lesions resembling erosions can frequently be found in bilateral wrist MRI of healthy individuals.

OBJECTIVE: To examine magnetic resonance imaging (MRI) scans for bone lesions typical of rheumatoid arthritis (RA) in the wrist joints of healthy individuals. METHODS: Thirty-one symptomless healthy persons (13/18 men/women), mean age 49 years (range 32-64 years), were included. MRI scans and radiographs of both wrists were obtained (62 wrists). The MRI scans and the radiographs were evaluated by two specialists according to the OMERACT recommendations and the Larsen method, respectively. RESULTS: MRI showed erosive-like lesions in either one or both wrists in 14 [45%, 95% confidence interval (CI) 27-64] out of 31 subjects. Altogether, 24 erosive-like changes were found in the 930 wrist bones evaluated (15 bones in each wrist). No more than two lesions per wrist were detected. All the changes were small (22 were grade 1 and two were grade 2; scale 0-10) and were found more often in the older subjects (55 vs. 43 years, p<0.001). Most lesions (54%) were located on the volar side of the wrist and adjacent to the ligament insertions. Intravenous administration of the contrast medium gadolinium diethylenetriaminepentaacetate (Gd-DTPA) was used in 10 subjects, and mild to moderate Gd-DTPA enhancement in the synovial compartments was seen in six of them: five had enhancement in both wrists and one in one wrist. The plain radiographs showed one erosive-like change in the wrist (pisiforme) that was not recorded with MRI. CONCLUSIONS: A few small bone lesions that could potentially be confused as erosions were detected in about half of the normal volunteers. These findings should always be evaluated with reference to the clinical picture.

Similarity between chronic reactive arthritis and ankylosing spondylitis.A 32-35-year follow-up study.

OBJECTIVE: We assessed the long-term outcome of recent reactive arthritis (ReA) during 1973-2007 and ankylosing spondylitis (AS) during 1973-1997 to identify similarities in manifestations of disease. METHODS: Radiographs of the sacroiliac, hand and foot joints were taken at onset and at 8, 20, and in ReA 32 years from entry among recent-onset (<6 months) patients; 60 with ReA and 17 with AS. Sacroiliacal joints using the modified New York 1984 criteria and the Larsen score of 0-100 of 20 joints of hands and feet were assessed. The number of swollen joints, patients with orthopaedic operations or iritis or HLA-B27 or retirement because of spondyloarthritis, and ESR were recorded. RESULTS: The onset age of 60 ReA patients (34 men) was 17-54 years, mean 32 (SD 10) and 51 (85%) were HLA-B27 positive. The number of onset swollen joints was 1-5, mean 2.6 (SD 1.6), while in 40 patients at the 30-year check-up it was 0-3, mean 0.2 (SD 0.6). ESR was at onset mean 55 mm/h (SD 33) and at the 30-year check-up 15 mm/h (SD 11). Yersinia enterocolitica type 3 antibodies were raised in 22 (37%) patients at onset. The end-point Larsen score was 2-6, mean 4 in 6 patients. One ankle joint arthroplasty and five smaller operations had been performed. Bilateral grade 2-3 sacroiliitis developed in 9/60 (15%), and unilateral grade 2-4 in 3. The incidence of iritis was 12/60 (20%). Erosive arthritis or iritis or sacroiliitis developed in 24/60 (40%) participants. Thirteen (22%) retired because of arthritis while five died. Of 17 AS patients (8 men), whose age was initially 21-50 years, mean 33 (SD 10), 11 (65%) had rheumatic symptoms years before our first examination. All were HLA-B27 positive and developed grade 2-4 bilateral sacroiliitis during the 20-year follow-up. The end-point Larsen score was 2-22, mean 9 (SD 8) in 5 patients. Hip arthroplasties were performed in one and small-joint operations in 3. ESR was at onset mean 54 mm/h (SD 29), and at the last measurement mean 26 mm/h (SD 21). Iritis was found in 5/17 (29%); seven (41%) retired due to AS; five died. CONCLUSION: Our community-based inception cohorts show that with time, among a number of similarities most often sacroiliitis, peripheral arthritis and iritis developed in both chronic ReA and AS. These HLA-B27-related diseases would appear to be identical. The differences between patients depend on the chronicity of the sickness. The hypothesis that HLA-B27 is related to chronicity of disease seems to be valid.

Prospective meta-analysis of interleukin 1 gene complex polymorphisms confirms associations with ankylosing spondylitis.

OBJECTIVES: The aim of the current study was to determine the contribution of interleukin (IL)1 gene cluster polymorphisms previously implicated in susceptibility for ankylosing spondylitis (AS) to AS susceptibility in different populations worldwide. METHODS: Nine polymorphisms in the IL1 gene cluster members IL1A (rs2856836, rs17561 and rs1894399), IL1B (rs16944), IL1F10 (rs3811058) and IL1RN (rs419598, the IL1RA VNTR, rs315952 and rs315951) were genotyped in 2675 AS cases and 2592 healthy controls recruited in 12 different centres in 10 countries. Association of variants with AS was tested by Mantel-Haenszel random effects analysis. RESULTS: Strong association was observed with three single nucleotide polymorphisms (SNPs) in the IL1A gene (rs2856836, rs17561, rs1894399, p = 0.0036, 0.000019 and 0.0003, respectively). There was no evidence of significant heterogeneity of effects between centres, and no evidence of non-combinability of findings. The population attributable risk fraction of these variants in Caucasians is estimated at 4-6%. CONCLUSIONS: This study confirms that IL1A is associated with susceptibility to AS. Association of the other IL1 gene complex members could not be excluded in specific populations. Prospective meta-analysis is a useful tool in confirmation studies of genes associated with complex genetic disorders such as AS, providing sufficiently large sample sizes to produce robust findings often not achieved in smaller individual cohorts.

Occurrence of sacroiliitis in patients with seronegative oligoarthritis.

The aim of this study was to investigate sacroiliitis in patients with seronegative oligoarthritis. Thirty consecutive patients with seronegative oligoarthritis and no other signs of spondylarthropathy were included. Sacroiliac (SI) joints were investigated by both radiography and magnetic resonance imaging. HLA B27 antigen was studied and family history was reexamined in 2006. Five patients had sacroiliitis. Additionally, 15 patients had HLA B27 antigen or family history of either psoriasis or ankylosing spondylitis. Our conclusion is that during the first decade of seronegative oligoarthritis, HLA B27 antigen, family history, and especially imaging of SI joints reveal in two thirds of the patients the spondylarthritic nature of their disease.

The development of bone mineral density and the occurrence of osteoporosis from 15 to 20 years of disease onset in patients with rheumatoid arthritis.

OBJECTIVE: To ascertain the occurrence of osteoporosis and the development of central bone mineral density (BMD) in long-term rheumatoid arthritis (RA) METHODS: BMD of the lumbar spine (L2-L4) and the femoral neck were measured by dual-energy X-ray absorptiometry in a cohort of 59 patients (49 women and 10 men) with rheumatoid factor-positive RA followed up for 20 years. BMD measurements were obtained at the 15- and 20-year follow-up visits. RESULTS: At the 15-year check-up the mean age was 61 (SD 13)for men and 54 (SD 11) years for women. Bone densitometry of these patients revealed decreased BMD at both lumbar spine and femoral neck, the mean T-scores being -1.1 [95%CI: -1.6 to -0.6] and -1.3 [95%CI: -1.6 to -1], respectively). Eighteen (31 %) patients thus had osteoporosis (BMD T -score < or = -2.5) and 32 (54%) patients were osteopenic (BMD T-score -1.0 to -2.5). However, when compared with reference values, the decreases in central bone mineral in this patient group were of low degree; the mean Z-score -0.2 [95%CI: -0.7 to 0.2] at the lumbar spine and -0.5 [95%CI: -0.8 to -0.3] at the femoral neck, respectively. After the subsequent five years the mean Z-score increased 0.45 [95%CI: 0.32 to 0.58] at the lumbar spine and the mean T-score decreased -0.20 [95%CI: -0.32 to -0.08] at the femoral neck. ESR, Larsen score, gender and cumulative dose of prednisolone during the 5 year follow-up and HAQ-index were used as explanatory parameters of BMD change between the 15- and 20-year follow-ups. None of these parameters explained the BMD change. CONCLUSION: We conclude that in long-term RA central bone densities seemed to be only moderately decreased after 15 years from eruption of RA. No essential change in central BMD was found after the consecutive 5 years.

Raised circulating interleukin-18 levels in reactive AA-amyloidosis.

OBJECTIVE: To study the circulating levels of interleukin-18 (IL-18), a proinflammtory cytokine implicated in the T helper I response, in patients with rheumatoid arthrtitis (RA) with or without amyloidosis. METHODS: Plasma IL-18 levels were studied by enzyme-linked immusorbent assay in 55 RA patients with reactive amyloidosis and in 55 RA patients without amyloidosis matched with respect to age, sex, seropositivity, disease duration and inflammatory activity, as well as in 55 healthy control subjects. RESULTS: Plasma IL-18 levels were significantly elevated in RA patients as compared with control subjects. Those RA patients who had amyloid had significantly higher circulating level of IL-18 than those without amyloid (418.1 +/- 32.1 ng/l versus 317.0 +/- 21.3 ng/l, P<0.02). This difference was not due to differences in inflammatory activity, nor was it related to renalfunction. CONCLUSION: RA is associated with increased levels of plasma IL-18, the levels being significantly higher in patients with amyloid than in those without amyloid The increased level in the amyloidosis patients may reflect the interaction ofamyloid with cellular meatbolic pathways or, possibly, suggest a direct role of IL-18 in amyloidogenesis.

Apolipoprotein E phenotypes in rheumatoid arthritis with or without amyloidosis.

The role of apolipoprotein (apo) E in the pathogenesis of reactive amyloidosis is unclear. Here we evaluated the apoE phenotype distribution and apolipoprotein e allele frequencies in 55 adult patients with seropositive, erosive RA with amyloid and compared them with 55 matched RA patients without amyloid The apoE isotypes were determined by isoelectric focusing and immunoblotting. RA patients without amyloid had more often the apoE 3/3 phenotype (71%) than the RA+A patients (49%, P<0.05) or Finnish control subjects (47%, P<0.01) and the frequency of the apo epsilon3 allele was significantly higher among the RA patients without amyloid than among RA+A patients (P<0.05) or control subjects (P<0.01). The prevalence of the apoE3/4 phenotype among the RA+A patients, although higher, did not significantly differ from the RA patients without amyloid (40% and 26%, respectively, NS) or Finnish control subjects (40% and 35%, respectively, NS). The frequency of the apo epsilon4 allele among the RA+A patients did not signficantly differ from that of RA patients without amyloid (0.23 and 0.13, respectively, NS) or Finnish control subjects (both 0.23). However, the apo epsilon4 frequency of 0.13 among the RA patients without amyloid was significantly lower than that of Finnish control subjects (0.23, P<0.05). We conclude that the prevalence of the apoE4 isotype is not increased in patients with RA complicated by amyloidosis when compared with Finnish control subjects. Since the frequency of the apo epsilon4 allele is significantly decreased in RA patients without amyloid when compared with Finnish control subjects, the presence of the apoE4 in a patient with RA could, though, represent a relative risk factor for developing reactive amyloidosis.

The effect of different indomethacin formulations in young and elderly patients: a comparative controlled clinical trial.

In a double-blind, crossover trial a controlled-release multiple-units indomethacin formulation (50 mg twice daily) was compared with conventional capsules (25 mg twice daily with 50 mg in the evening) in 12 young and 18 elderly in-patients with rheumatoid arthritis. Earlier findings that younger patients preferred a slow-release formulation and the elderly a standard formulation could not be confirmed. As a whole, the duration of morning stiffness was reduced more (p = 0.02) with the controlled-release formulation than with the conventional formulation. During the treatment period (7 days), 4 patients reported side-effects from the conventional capsules, 3 from the controlled-release formulation, and 6 from both treatments; 53% of the patients preferred the controlled-release formulation, while 20% preferred the conventional capsule (p = 0.046).

Correlations between clinical facets of outcome in rheumatoid arthritis.

At 8-year follow-up of 103 patients with rheumatoid arthritis, an X-ray index based on Larsen's score for the hands, wrists, ankles and feet showed a high correlation with the joint score (0.75 by Spearman's rank correlation), the function score (0.68), ESR (0.61), and CRP (0.64). These results suggest that Larsen's method of scoring both the hands and feet is a valid single method to assess long-term outcome in rheumatoid arthritis.

Synovial fluid acid phosphatase in seropositive and seronegative arthritides.

Synovial fluid acid phosphatase was investigated in 82 arthritic patients with hydropsy in a knee joint. 39 of the patients were seropositive and 43 seronegative. 36 of the seropositive group had erosive rheumatoid arthritis. The mean synovial fluid acid phosphatase in the seropositive group, 11.6 U/l (SD +/- 8.4), was significantly higher (p less than 0.001) than in the seronegative group, 6.5 U/l (SD +/- 4.8).

Conventional monotherapy compared to a "sawtooth" treatment strategy in the radiographic progression of rheumatoid arthritis over the first eight years.

OBJECTIVE: To describe the treatment with disease-modifying antirheumatic drugs (DMARDs) in two inception cohorts of rheumatoid arthritis (RA) patients and to compare their radiographic outcomes. METHODS: A recent onset RA cohort was collected in Heinola in 1973-1975, and another in Jyväskylä in 1983-1989. The cohorts were followed up prospectively and treated with available DMARDs. The radiographic outcomes of 103 and 85 seropositive cohort patients from Heinola and Jyväskylä respectively were assigned Larsen scores (0-100) for their wrist, hand and foot radiographs in years 0, 1, 3, and 8, and compared with each other. RESULTS: In this study it was seen that DMARD treatment for RA became more extensive over time. The earlier cohort patients were treated with gold sodium thiomalate, chloroquine and D-penicillamine, while 8 additional DMARDs and various DMARD combinations were used for the later cohort patients. At the 8 year visit, 23%, 33%, and 2% of the Heinola patients, and 6%, 45%, and 21% of the Jyväskylä patients respectively were being treated with chloroquine, other single DMARDs, or DMARD combinations. Destruction in the peripheral joints remained lower in the more extensively treated cohort; from 0 to 8 years the median Larsen score increased from 1 to 25.5 and from 0 to 12 (p = 0.001) for the Heinola and the Jyväskylä patients, respectively. CONCLUSION: Our result supports a role of DMARDs in preventing joint destruction in RA in the long-term.

Prediction of 20-year outcome at onset of seropositive rheumatoid arthritis.

OBJECTIVE: With the advent of new and expensive antirheumatic treatments with potentially serious side effects, it would be essential to identify as early as possible those rheumatoid arthritis (RA) patients who have a poor prognosis. Here study was made of the prognostic value of different markers recorded at the onset of RA. METHODS: At the 20-year follow-up of our prospective study, 66 patients had rheumatoid factor-positive (RF+) RA. At commencement of follow-up (disease duration < 6 months), the prognostic value of 19 demographic, laboratory, clinical and radiographic variables was tested to explain the 20-year Larsen score for peripheral joints and the Health Assessment Questionnaire (HAQ) index using Somers'd for asymmetrical associations. RESULTS: An association was observed between onset blood platelets (0.17), serum IgG (0.18), the onset Larsen score (0.33) and the 20-year Larsen score. Old age (0.30), serum orosomucoid (0.17), the function score (0.28), morning stiffness (0.28), and grip strength (0.24) were associated with the 20-year HAQ. CONCLUSION: The correlation between the investigated entry variables and end-point outcome was poor. In our discussion we conclude that the most important prognostic factor in RF + RA is the treatment.

Radiographic remission in seropositive rheumatoid arthritis. A 20-year follow-up study.

OBJECTIVE: Rheumatoid arthritis (RA) is in most instances a progressive disease. Very little information is available on halting of the radiographic damage, particularly in later phases of the disease. We studied radiographic remission of RA lasting to the end of follow-up, covering the period 1973-96. METHODS: Radiographs of hands and feet were taken at onset and at 1, 3, 8, 15 and 20 years from entry in 102 cases of recent onset (< 6 months) seropositive and erosive RA. A Larsen score of 0-100 was formed for 20 joints of hands and feet. If the score did not worsen by more than one point between one of the above time points and the end of the study, the patient was considered to be in remission. RESULTS: Remission was confirmed in 27 (26%) of the patients. In 3 cases the remission was from the 1-year check-up, in 5 from the 3-year check-up, in 6 from the 8-year check-up and in 13 cases from the 15-year check-up. Some of the remission cases had a mild disease from the outset, but there were cases in which the disease process had led to marked joint destruction before slowing down. CONCLUSION: This data may serve as a basis for comparison with subsequent cohort studies on new treatments-of-choice.

Is seropositive rheumatoid arthritis becoming less severe?

We have followed a community-based cohort of recent-onset arthritis for eight years. In addition to Waaler-Rose and latex agglutination tests we used class-specific enzyme immunoassay for the determination of rheumatoid factors (RFs). Eighty-seven patients had erosions by the end of the follow-up period. The seropositive cases in each RF assay were divided into three groups of equal size according to the mean strength of RF reactivity for three or four available follow-up specimens. The radiological index values in the high-titer groups were no higher than the values for the seropositive cases on average. Thus, no severity gradient according to RF titer could be demonstrated.

Atlantoaxial disorders in rheumatoid arthritis associate with the destruction of peripheral and shoulder joints, and decreased bone mineral density.

OBJECTIVE: To evaluate whether cervical spine changes are associated with the destruction of shoulder or peripheral joints and with bone mineral density (BMD) in patients with long-term RA. METHODS: An inception cohort of 67 patients with seropositive and erosive RA were followed up for 20 years. Cervical spine, shoulder, hand and foot radiographs, and the BMD of the lumbar spine and femoral neck were evaluated. RESULTS: A positive relationship was detected between the occurrence of atlantoaxial disorders and the destruction of both shoulder (p < 0.001) and peripheral (p = 0.001) joints. In addition, the severity of anterior atlantoaxial subluxation and atlantoaxial impaction positively correlated with the grade of destruction in the evaluated joints. Furthermore, patients with atlantoaxial disorders presented decreased BMD of the femoral neck (p = 0.019). The occurrences of subaxial subluxations (SAS) and subaxial disc space narrowings only associated with higher onset age of RA. CONCLUSIONS: Patients with severe RA and osteoporosis have an increased risk for atlantoaxial disorders. The co-existence of shoulder destruction and cervical spine disorders makes the differential diagnosis of shoulder and neck pain challenging.

Prevalence of Sindbis-related (Pogosta) virus infections in patients with arthritis.

OBJECTIVE: To determine the role of Pogosta virus as a triggering infection in non-specific arthritis. METHODS: Serum samples of 142 patients with acute arthritis were screened for the evidence of Pogosta virus infection. Serological tests for Chlamydia trachomatis, salmonella, parvovirus B19, and Borrelia burgdorferi were also carried out. As verified later, 78 of the patients had rheumatoid arthritis and 63 seronegative poly- or oligoarthritis, while one had systemic lupus erythematosus. RESULTS: In the early stage of the joint symptoms 4 patients with rheumatoid arthritis, 1 with seronegative polyarthritis and 1 with systemic lupus erythematosus had recent Pogosta virus infection. Four of them had probably had Pogosta disease at the time of the onset of arthritis. In 11 patients with a diagnosis of seronegative arthritis, serological evidence of preceding infection due to salmonella or Chlamydia trachomatis was found, strongly suggesting classical reactive arthritis in these cases. CONCLUSIONS: Our study suggests that also a Sindbis virus infection may be associated both to an acute joint inflammation as a part of Pogosta disease or chronic arthritis. At present, this possibility still needs further research.

The prediction of radiological destruction during the early stage of rheumatoid arthritis.

A total of 107 patients with definite rheumatoid arthritis of no longer than six months' duration were observed for three years. The radiological destruction of the hand and foot joints after the follow-up time was compared with 65 anamnestic, clinical, laboratory and radiological variables at the onset of the disease. Of the individual variables, early radiological changes in the joints showed the best correlation with the progress of joint destruction. Grip strength, ESR, serum iron, serum C1 esterase inhibitor, rheumatoid factor and old age also had prognostic value. In multiple regression analysis 15 variables explained about 50% of the variance in the progress of joint destruction.

Development rate of mutilans fingers in patients with rheumatic disease.

OBJECTIVE: To describe arthritis mutilans (AM) deformity during the progression of rheumatic disease. METHODS: The development of mutilans-like hand deformities in 2 patients with juvenile chronic arthritis (JCA) and in 2 patients with adult onset rheumatoid arthritis (RA) are presented. The hands of these patients were evaluated at least at two time points during the course of disease using two different scoring methods based on differently summed Larsen grades of the hand joints. RESULTS: Two patients (one with JCA and one with RA) showed AM changes after a disease period of less than 10 years and 2 not until after 30 years. The patients with adult onset disease were young at the onset of joint disease. Early wrist fusions were performed on both patients showing a slow development rate. CONCLUSIONS: The development rate of AM is very variable, even in patients with the same diagnoses. Wrist fusion prevents shortening of the carpus and may decrease the development rate of AM.

Need and sequence of large joint replacements in rheumatoid arthritis. A 25-year follow-up study.

OBJECTIVE: The aim of the present study was to evaluate the number and sequence of large joint replacements (LJR) performed in long-term rheumatoid arthritis (RA) from an inception cohort of 103 patients with rheumatoid factor (RF)-positive RA followed over 25 years. METHODS: A total of 83 patients attended the 15-year and 68 patients the 20-year follow-up. Patient documents and radiographs were evaluated in the beginning of 2001 and a complementary interview was arranged to assess the number and sequence (timing) of LJRs performed. RESULTS: The cumulative number of LJRs performed for 22 patients (19 women) during the 25 years of follow-up was 41. Seventeen total hip joint replacements (THR) (42% of the total number of 41 LURs) were performed on 13 patients, median time from the diagnosis to the operation being 14 years; 14 total knee replacements (TKR) (34%) on 11 patients (after a median time of 17 years); 3 total shoulder replacements (TSR) (7%) on 3 patients (median time of 18 years); and 7 total elbow replacements (TER) (17%) on 4 patients (median time of 21 years), respectively. Six patients had undergone three or more LJRs during the follow-up period. CONCLUSION: During our 25 years of follow-up, in 27% of RA patients LUR was needed, and 41% of them needed more than one replacement.

Differences in understanding and application of 1987 ACR criteria for rheumatoid arthritis and 1991 ESSG criteria for spondylarthropathy. A pilot survey.

OBJECTIVES: To determine areas of agreement and disagreement among experts in the interpretation of the published criteria for RA (ACR) and spondylarthropathies ( ESSG). METHODS: Thirty-two experts (16 from France and 16 from 10 other countries) replied anonymously to a mailed questionnaire. RESULTS: Tenosynovitis and 'sausage-like' painless swelling of the toes were considered as criteria for RA by 18 and 14 experts, respectively. The definition of symmetry differed widely among experts (symmetry of only one group of joints was sufficient for 13). Twenty-five experts considered erosions of other joints than the wrists and fingers as a criterion for RA, 17 thought that fulfilment of criteria could be achieved cumulatively, and 19 would appreciate clarifications of the current criteria. Among possible clarifications for RA, it was frequently recommended that morning stiffness and nodules be eliminated and that new marker antibodies, X-rays of the feet, and exclusion criteria be added. Twenty-three of the 29 experts who gave an opinion (79%) agreed with the notion of SP in the absence of axial signs and sacroiliitis, 26/31 (84%) indicated that a patient can have both RA and SP, and 19/30 (63%) thought that RA and SP could be regarded as syndromes more than diseases. Only 5/32 experts relied more on the criteria than on their clinical judgement in diagnosing RA. CONCLUSIONS: There would seem to be a needfor the optimisation of RA and ESSG criteria, particularly within the context of early arthritis.