Sensitivity of radiographic changes of hand and foot joints as a diagnostic criterion in patients with rheumatoid arthritis.
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Biomedical subjects
Publications and source records attributed to H Isomäki.
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Although developments in surgical and medical treatment methods have improved the average long-term outcome of rheumatoid arthritis (RA), it still is a severe disease. An 8-year follow-up study of patients with seropositive RA showed a large variation in the outcome. Only 24 percent of patients had no progression in the radiological destruction of the joints of hands and feet. Premature mortality seems to accumulate in patients with a poor outcome. Study of prognostic markers for RA would be of great importance.
To acquire more information on the controversial question of a possible association between rheumatoid arthritis (RA) and insulin dependent diabetes mellitus we searched for insulin dependent diabetes mellitus among patients hospitalized due to RA in 2 rheumatism hospitals in Finland. Nine subjects with insulin dependent diabetes mellitus were found among an annual number of 1460 patients admitted to one of the hospitals due to RA. These figures give a frequency of insulin dependent diabetes mellitus in patients with RA of 0.6% (95% confidence interval 0.2-1.0%), which does not exceed the prevalence of insulin dependent diabetes mellitus among the middle aged population of Finland in general (0.5-0.6%). Accordingly, no overrepresentation of homozygosity for HLA-DR4 was found among the total number of 25 patients with RA as well as insulin dependent diabetes mellitus, though the opposite might be expected as these diseases have a common DR4 association--RA with DR4 and DR1 and insulin dependent diabetes mellitus with DR4 and DR3. Instead, an increased frequency of DR1 (p less than 0.0002) and the antigen combination DR1/4 (p less than 0.01) was found in the subjects with both RA and insulin dependent diabetes mellitus compared with the subjects with insulin dependent diabetes mellitus alone.
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Pressure pain thresholds and pressure pain tolerances on non-trigger-point muscle and bone were measured with a dolorimeter in 46 female patients with primary fibromyalgia and in 50 healthy women of the same age. The pressure pain thresholds and the pressure pain tolerances on both muscle and bone were lower in the fibromyalgia patients than in the healthy controls. All the differences were statistically highly significant, though there was a certain degree of overlapping between the patients and the controls. It is concluded that patients with primary fibromyalgia have a generalized amplification of pain sensitivity, a sign that might be useful in the diagnosis of fibromyalgia.
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To investigate whether the premature death of patients with rheumatoid arthritis (RA) was associated with intramuscular (im) gold treatment or side effects due to gold, a sample of 573 adult patients with RA treated at hospital for the first time during 1961-66 was retrospectively studied for the duration and side effects of im gold treatment as well as death and causes of death. By 1989 a total of 251 patients had died. Gold treatment was not associated with premature death. On the contrary, longterm gold treatment was associated with a high survival rate. Secondary amyloidosis was diagnosed in 28 out of 63 patients, who had gold associated renal disease and who died.
Synovial cells from nine patients with reactive arthritis following Salmonella enteritidis or Salmonella typhimurium infection were examined for salmonella antigens. Extensive bacterial cultures of the synovial fluid were negative. Eight synovial-fluid cell samples stained positively on immunofluorescence with rabbit antisera against heat-killed S enteritidis or S typhimurium or with monoclonal antibodies specific for the causative salmonella lipopolysaccharide (LPS). Synovial tissue from the ninth patient stained positively in the avidin-biotin-peroxidase complex method with the monoclonal antibody. Control samples (synovial-fluid cells from thirteen patients with other rheumatic diseases and synovial tissue from two) were negative. Synovial cells from eight patients and five controls were studied by western blotting with the same monoclonal antibodies. Four of the eight patients but no controls had blots indicating salmonella LPS in the synovial cells. The presence of bacterial LPS in the joint is a common and pathogenetically important feature of reactive arthritis.
The usefulness of ultrasonography in detecting intra-articular effusion of the hip joint is discussed in the light of three cases. In all these patients, effusion was demonstrated by ultrasonography and confirmed by aspiration of inflammatory synovial fluid from the joint, though the joint was clinically symptomless. It is recommended that all rheumatologists use ultrasonography.
The ultrasonographic distance between the collum of the femur and the capsule of the hip joint was measured in 88 hips of 75 patients with chronic inflammatory joint disease and with hip joint symptoms or signs. In addition, 10 other hips were measured before soft tissue operation of the hip joint. The ultrasonographic distance was 7 mm or more in 29 out of 33 hips with synovial fluid in joint puncture and in seven out of nine hips with intra-articular effusion or synovitis in open surgery. Intra-articular injection of corticosteroid resulted in a significant decrease in the enlarged ultrasonographic distance, in joints both with and without synovial fluid. Joints not treated with steroid did not show any change. It is concluded that both joint effusion and synovitis without effusion can increase the anechogenic distance between the bone and the joint capsule.
Human rheumatoid factor (RF) paraproteins express two distinct light chain cross-reactive idiotypes defined by the monoclonal antibodies 17.109 and 6B6.6. These germline gene-related cross-reactive idiotypes are both carried on VK3 light chains and are each present on about one-third of IgM RF paraproteins. We assessed the degree to which these idiotypes are represented in polyclonal RFs. We used rheumatoid arthritis (RA) and non-RA RF-positive sera selected from a large cross-sectional population study (the Mini-Finland Health Survey), and sera from a community-based follow-up study of recent-onset RA patients from Heinola, Finland. In the Mini-Finland Health Survey, elevated levels of the 17.109 RF idiotype were seen in sera of 13% of the RA and 19% of the non-RA group; 6B6.6 RF was seen in 26% of the RA and 28% of the non-RA group. In sera of the Heinola follow-up study, 17.109 RF was seen in 12% initially, but in only 3% at 8 years. Similarly, 6B6.6 RF was detected in 25% initially, but in only 7% at 8 years. Ten sera positive for RF prior to the onset of clinical RA were identified from individuals of a second large population study from Finland (North Karelia project); two of these sera exhibited the 6B6.6 idiotype; none exhibited the 17.109 idiotype. The data are consistent with the concept that these germline gene-related cross-reactive RF idiotypes occur frequently in the polyclonal RF of non-RA as well as RA sera, and that in RA the idiotypes may sometimes be reduced or lost as a consequence of somatic diversification of the RF through somatic mutation, usage of new germline genes, or both.
Altogether 53 patients (31 women, 22 men) with definite rheumatoid arthritis were randomly divided into groups of 5-6 patients and treated for one day only with one of the following non-steroidal anti-inflammatory drugs (NSAIDs): acetylsalicylic acid, carprofen, diclofenac, indomethacin, naproxen, proquazone, timegadine, tolfenamic acid or paracetamol, and with prednisolone, in recommended doses. Synovial fluid samples were collected before and after the treatment. White cell count and its differentiation as well as the concentrations of protein, cyclic adenosine-3',5'-monophosphate (cAMP), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were measured from the synovial fluid. Synovial fluid leukocyte counts correlated with PGE2 concentrations, but showed no correlation with LTB4 levels before treatment. Significant changes were seen in the form of lowered PGE2 values following treatment with the clinically and experimentally most potent NSAIDs, and as depressed LTB4 levels following prednisolone treatment. The other markers of inflammation are obviously more resistant, changing only slowly during prolonged treatment, and may thus be, at least in part, secondary to the changes in prostanoids.
We studied IgG antibody levels to synthetic peptides (p62, E11 and E3) from Epstein-Barr nuclear antigen-1 (EBNA-1) protein sequence in sera of patients with rheumatoid arthritis (RA), in pre-RA and in rheumatoid factor (RF) positive non-RA sera from Finland. Anti-E11 and anti-E3 antibody levels were significantly elevated in RA sera, compared with both RF negative and RF positive nonrheumatoid controls. The concentrations of anti-E11 and anti-E3 antibodies in the preillness sera were lower than those in RA sera. Eight-year followup samples of patients with RA had slightly decreased levels of anti-E3 and anti-E11 antibodies compared with samples taken within 6 months of the disease onset. Anti-p62 antibody levels did not differ significantly between any of the groups studied. Thus, elevated levels of antibodies to 2 of the glycine containing EBNA-1 peptides were associated with clinical RA.
We examined synovial-fluid cells from 15 patients with reactive arthritis after yersinia infection for the presence of yersinia antigens. Extensive bacterial cultures of the synovial fluid were negative. All the samples were studied by immunofluorescence with use of a rabbit antiserum to Yersinia enterocolitica O:3 and a monoclonal antibody to Y. enterocolitica O:3 lipopolysaccharide. Synovial-fluid cells from 41 patients with other rheumatic diseases served as controls. Synovial-fluid cells from 10 patients with reactive arthritis after yersinia infection stained positively on immunofluorescence; rabbit antiserum and the monoclonal antibody yielded similar results. In most patients the percentage of positive cells ranged from 1 to 10 percent, but in one patient nearly all the cells in the sample stained strongly. Most of the positively stained cells were polymorphonuclear leukocytes, but yersinia antigens were also found in mononuclear phagocytes. All the control samples were negative. Synovial-fluid cell deposits from nine patients were also studied by Western blotting with use of the same antibodies. The results were positive in six of the nine cell deposits from patients with reactive arthritis and in none of the 10 cell deposits from control patients with rheumatoid arthritis. We conclude that in patients with reactive arthritis after yersinia infection, microbial antigens can be found in synovial-fluid cells from the affected joints.
The Mini-Finland Health Survey was designed to analyse the epidemiology of major public health problems. The study covered a representative sample of the Finnish population aged 30 years or over, and initially comprised 8,000 people. Serum rheumatoid factor was determined in 7,124 cases (89%). There were 138 cases of clinical arthritis in the series, corresponding to a prevalence of 1.9% (1.0% in males and 2.7% in females). Fifty-nine of the cases (0.8% of the population) were seropositive, and 50 cases (0.7%) had in their hand radiographs changes characteristic of rheumatoid arthritis. Twelve of the X-ray positive cases were seronegative. One-half of these proved to be seroconversion cases or rheumatoid variants typically seronegative, such as early-onset juvenile rheumatoid arthritis.
Leukotriene B4 (LTB4) synthesis in rheumatoid synovitis was studied using peripheral and synovial fluid polymorphonuclear leukocytes (PMNs) and rheumatic synovial lining cells. No differences were found in LTB4 synthesis between peripheral PMNs from healthy volunteers and rheumatoid arthritis patients. When peripheral and synovial PMNs from the same RA patient were compared, arachidonic acid-induced LTB4 synthesis in synovial fluid PMNs was increased 1.7-7.2 fold, whereas the response to Ca ionophore A23187 stimulation was similar. This suggests 5-lipoxygenase stimulating factor(s) in inflamed joints. Rheumatic synovial lining cells in a primary cell culture produced small amounts of LTB4, the concentrations being less than 0.1 per cent of those of prostaglandin E2 (PGE2). PGE2 synthesis in synovial cells was increased when arachidonic acid or interleukin-1 was added to the culture, whereas LTB4 production remained unaltered. The present results suggest that in inflamed joints LTB4 originates mainly from PMNs whereas synovial lining cells are the source for PGE2.
The effects of 10 ml of evening primrose oil or olive oil, administered twice daily for 12 weeks, on clinical and laboratory signs and on plasma prostaglandins were studied in 18 patients with rheumatoid arthritis. The plasma concentration of PGE2 decreased and that of TxB2 increased in both treatment groups, but no significant improvement could be seen in either group.
The serum concentration of lipids and composition of fatty acids after overnight fasting were studied in 18 patients with rheumatoid arthritis treated for 12 weeks with either 20 ml of evening primrose oil containing 9% of gamma-linolenic acid or olive oil. The serum concentrations of oleic acid, eicosapentaenoic acid, and apolipoprotein B decreased and those of linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid, and arachidonic acid increased during treatment with evening primrose oil. During olive oil treatment the serum concentration of eicosapentaenoic acid decreased and those of high density lipoprotein-cholesterol and apolipoprotein A-I increased slightly. The decrease in serum eicosapentaenoic acid and the increase in arachidonic acid concentrations induced by evening primrose oil may not be favourable effects in patients with rheumatoid arthritis in the light of the roles of these fatty acids as precursors of eicosanoids.