Classical Rheumatoid Arthritis Research Articles

Effect of calcitonin on bone histomorphometry and bone metabolism in rheumatoid arthritis

Twenty-four women (mean age +/- SD 49 +/- 13 years) with classical or definite rheumatoid arthritis (disease duration 15 +/- 8 years) were treated with synthetic salmon calcitonin (SCT) nasal spray 200 IU three times a week for 3 months. Bone biopsies from the iliac crest were taken before and after SCT treatment. Histomorphometrical quantification of undecalcified bone sections was made using the manual point-counting method. SCT decreased the resorption surface of trabecular bone (ES/BS) significantly (P less than 0.001). There was also a significant increase (P less than 0.05) in trabecular bone volume (BV/TV) after 3 months of treatment, whereas no statistically significant changes were found in osteoid parameters. There were no significant changes in biochemical analyses of bone metabolism. We conclude that SCT might be useful in the prevention of bone loss in RA.

Treatment of early rheumatoid arthritis with rifampicin.

Following a report that seven of 20 patients with rheumatoid arthritis (RA) had come into clinical and laboratory remission after treatment with rifampicin, and that six of the seven responders had a disease duration of less than three years, 21 patients with classical or definite RA of recent onset were treated with 600 mg rifampicin and 300 mg isoniazid daily for six months. Fourteen of 21 patients completed six months' treatment, but there was no significant improvement in the mean values of the clinical and laboratory parameters measured. The improvement suggested by preliminary studies in patients with early RA is not seen in this larger group. In patients with a disease duration of less than 18 months, however, there was a significant decrease in the erythrocyte sedimentation rate and the serum concentrations of C reactive protein after treatment for six months, although there was no significant clinical improvement. Future studies of this drug in patients with RA should concentrate on this group.

Rheumatoid arthritis in women: Incidence rates in group health cooperative, seattle, washington, 1987–1989

As part of a prospective case-control study of newly diagnosed rheumatoid arthritis (RA) in women, we identified all cases of probable, definite, or classic RA diagnosed in 1987-1989 in 18-64-year-old women who were members of a health maintenance organization based in the Seattle, Washington area. Using both the 1958 and the 1987 American Rheumatism Association criteria for the diagnosis of RA and enrollment data from the health maintenance organization, we calculated the incidence by age and diagnostic class. Rates of RA incidence in women increased steadily with age. The incidence of probable, definite, or classic RA ranged from 13.1 per 100,000 person-years at risk for 18-29-year-old women to 82.1 per 100,000 person-years for 60-64-year-old women. The overall incidence rate, age-adjusted to the 1980 US female population, was 27.9/100,000 person-years. The overall incidence rate for definite/classic RA, age-adjusted to the 1980 US female population, was 23.9 per 100,000 person-years. When compared with adjusted rates of incidence of definite RA in Rochester, Minnesota, in 1950-1974, the incidence rates we found were 44.7% lower. Methodologic differences, changes in diagnostic criteria, and a declining incidence of RA among women over time may all be partial explanations for these results. The possible effects of reproductive factors, including oral contraceptives use, are discussed.

Coexistent Felty's syndrome and palindromic rheumatism.

Palindromic rheumatism is a syndrome of intermittent abrupt onset monoarthritis with asymptomatic intercritical periods of variable duration, which commonly evolves into rheumatoid arthritis. Felty's syndrome consists of leucopenia (selective neutropenia) and splenomegaly, usually occurring in longstanding classic rheumatoid arthritis. Felty's syndrome can be confused with the more recently recognised rheumatoid arthritis associated large granular lymphocyte proliferative disease. This paper describes a patient with palindromic rheumatism presenting with Felty's syndrome in whom large granular lymphocyte proliferative disease was ruled out by lymphocyte phenotyping.

S-Ibuprofen versus ibuprofen-racemate

Ibuprofen (ibu) is a racemic 2-arylpropionic acid non-steroidal anti-inflammatory drug whose activity is due mainly to the S-enantiomer. So far only the racemic compound is in clinical use. A double-blind randomized trial was carried out for a 2-week period in 50 patients with classical rheumatoid arthritis (RA) (Steinbrocker II-III) to compare the effectiveness and tolerance of S-ibu (400 mg T.I.D.) with that of the racemic compound (600 mg T.I.D.). Ritchie-index, limitation of movement, joint pain on pressure and pain at night decreased significantly in both groups. Due to lack of effectiveness, the dose had to be increased in 3 patients from the S-ibu group as well as in 6 patients from the racemic group resulting in mean daily doses of 1220 mg S-ibuprofen and 1870 mg racemic ibu. No statistically significant difference could be found between both groups concerning efficacy and unwanted effects. Therefore, S-ibu given alone may be advantageous because the metabolic load to the human body is reduced and patients are more likely to comply with drug doses of 1.2 g/day as compared to 1.8 g/day.

Psoriasis-like skin reaction in a patient with rheumatoid arthritis after sulphasalazine therapy

Presented is a case story of a woman with classical rheumatoid arthritis, who during introduction of sulphasalazine (SASP) therapy developed a severe and lasting psoriasis-like skin reaction.

Laryngeal Involvement in Rheumatoid Arthritis

Twenty-nine female patients with definite or classical rheumatoid arthritis (RA) and 30 controls were studied in order to assess the prevalence of laryngeal involvement in patients with RA and the occurrence of extrathoracic airway obstruction. Laryngeal involvement was assessed by physical examination including direct fiberoptic laryngoscopy, respiratory function tests and low-voltage radiography. Physical examination revealed laryngeal involvement in 17 RA patients (59%), extrathoracic airway obstruction was indicated by spirometry in 4 (14%) and radiography revealed pathological findings in 3 patients (10%). One or more signs of laryngeal involvement were found in 20 patients (69%). Symptoms of breathing difficulties were common (75%) among patients with laryngeal involvement. The erythrocyte sedimentation rate and class-specific rheumatoid factors were not correlated to laryngeal involvement.

Swallowing Problems in Rheumatoid Arthritis

Twenty-nine female patients with definite or classical rheumatoid arthritis (RA) and 30 controls were investigated in order to evaluate oral symptoms, particularly xerostomia, and swallowing difficulties in RA by means of a questionnaire, physical examination, stimulated saliva secretion, labial salivary gland biopsy, esophageal manometry and laboratory blood tests. Xerostomia was reported by 6 patients (21%), compared with no-one in the control group. Four of these 6 patients had decreased stimulated saliva secretion, compared with 2 of the remaining 23 patients. Dysphagia was experienced by 8 patients (28%), compared with one control subject. Dysphagia was associated with disease severity. Esophageal manometry revealed a decrease of the amplitude of the peristaltic pressure complex in the proximal part of esophagus in the RA group, indicating dysfunction of the striated muscles. No correlation was found between dysphagia and esophageal manometry results.

Large Granular T Lymphocytes, Neutropenia and Polyarthropathy: An Underdiagnosed Syndrome?

Thirteen patients with expansion of an unusual subset of T lymphocytes, defined by large size, cytoplasmic granularity and CD3+ CD8+ Leu 7+ surface phenotype, are reported. Although morphologically and/or phenotypically abnormal lymphocytes were found in all patients, only five had an absolute peripheral blood lymphocytosis. Ten patients had a bone marrow lymphocytosis. As in previous series, there was a strong association with neutropenia (12 patients) and polyarthropathy (seven patients). The latter group displayed a wide range of articular disease: classical or definite rheumatoid arthritis in four patients and milder non-erosive disease in the remainder. All 13 patients showed evidence of abnormal B cell function: IgM rheumatoid factor was present in nine patients, neutrophil-specific antibodies in six and all showed an increased level of at least one immunoglobulin isotype. These patients may be difficult to distinguish from those with idiopathic neutropenia and Felty's syndrome. Such a distinction may not be made on clinical grounds alone: critical assessment of lymphocyte morphology, bone marrow examination and analysis of lymphocyte phenotype should be considered in all patients with unexplained neutropenia, particularly in the context of arthritis. It is suggested that the true prevalence of this syndrome may have been greatly underestimated.

LIMITED HETEROGENEITY OF THE HLA CLASS II CONTRIBUTION TO SUSCEPTIBILITY TO RHEUMATOID ARTHRITIS IS SUGGESTED BY POSITIVE ASSOCIATIONS WITH HLA—DR4, DR1 AND DRwlO

Most patients with rheumatoid arthritis (RA) exhibit an HLA class II epitope found on most DR4 and DR1 molecules. We have investigated the possibility of other associations being present in the minority of patients lacking these antigens. One hundred and eighty patients with classical or definite RA and 100 controls were assigned HLA-DR, DQ and DP types by a DNA-based system using sequence-specific oligonucleotides to probe amplified class II alleles amplified by the polymerase chain reaction. The expected associations with DR4 (relative risk 10, P less than 0.0001) and DR1 (relative risk 2.3, P less than 0.001) were observed and only 13% of individuals lacked both of these alleles compared with 54% of age- and race-matched controls. A significant association with DRw10 (P = 0.02) was also observed in the DR4/DR1-negative RA group (3/23 patients compared with 0/54 DR4/DR1-negative controls). No novel associations with other DR, DQ, or DP alleles were evident in contrast to some previous studies. The third allelic hypervariable region of the DR beta chain of DRw10 contains a similar amino acid sequence to that found in many DR4 and DR1 molecules. These results extend this correlation and suggest that this susceptibility determinant may account for the HLA-linked susceptibility in 89% of our cases of RA.

Cystic rheumatoid arthritis: description of a nonerosive form.

In a study of patients with rheumatoid arthritis (RA), 9% (n = 70) were found to have a cystic form. At radiologic examination of these patients with cystic RA, the first abnormality seen consisted of periarticular intraosseous cysts without erosions. The cysts were distributed symmetrically, most often located at the proximal side of the joints and predominantly around the proximal interphalangeal, metacarpophalangeal, and wrist joints of the hands and the first interphalangeal and metatarsophalangeal joints of the feet. Computed tomographic scans showed the peripheral intraosseous location of the cysts. Magnetic resonance images showed that the cysts may contain fluid, inflamed synovia, or both. Cysts can be an important feature in the diagnosis of RA and a supplement to the criteria of the American Rheumatism Association. Osteoporosis, joint-space narrowing, and joint destruction occurred less frequently in patients with cystic RA than in patients with classic RA. Of the patients with cystic RA, 54% were male, and 50% were seronegative. This study is a supplement to and an enlargement on earlier descriptions of cyst predominance in RA.

Lifestyle and the risk of rheumatoid arthritis: cigarette smoking and alcohol consumption.

In a search for aspects of behaviour related to oral contraceptive use which might explain the favourable effect of oral contraception on the onset of rheumatoid arthritis (RA), cigarette smoking and alcohol consumption were studied as possible risk factors. Information on cigarette smoking and alcohol consumption was obtained by interview at the first visit to the outpatient clinic of 135 young women with confirmed definite or classical RA of recent onset and 378 control patients with soft tissue rheumatism or osteoarthritis. The diagnosis in all patients was confirmed by at least two years of follow up. Of the patients with RA, 44/135 (33%) were current cigarette smokers compared with 181/378 (48%) of the controls. The percentage of smokers among the controls was similar to that of women smokers in the general population. The adjusted risk of RA in women who smoked at least one cigarette a day was 0.61 (95% confidence interval (CI) 0.42 to 0.89). Thirty one (23%) patients with RA and 137 (36%) controls were alcohol drinkers. The risk of RA in women who consumed alcohol at least once a day was 0.52 (95% CI 0.33 to 0.84). The low relative risk estimates for cigarette smoking and alcohol consumption were mutually independent and also independent of oral contraceptive use, the presence of the HLA-DR4 antigen, or a positive family history of RA. The low incidence of alcohol consumption in the patients with RA might be due to the discontinuation of alcohol consumption after disease onset. The low incidence of cigarette smoking in the patients might reflect a protective effect of cigarette smoking on RA onset, possibly induced by changes in the immune system.

Pregnancy and the risk of developing rheumatoid arthritis

There have been conflicting reports on, and no plausible biologic explanation for, a protective effect of oral contraceptive (OC) use on the development of rheumatoid arthritis (RA). Therefore, we investigated aspects of behavior related to OC use that could explain the preventive effect of OC on the onset of RA. In the present case-control study, past pregnancy, age at first pregnancy, and pregnancies with adverse outcome were studied as possible risk factors for RA. Interview information on reproductive variables was obtained from 135 young adult women with confirmed definite or classic RA of recent onset, and from 378 control patients with soft tissue rheumatic disorders or osteoarthritis. All patients had at least 2 years of followup to confirm the consistency of the diagnosis. We found a decreased risk of RA in women who had been pregnant. The risk of RA in women who had ever been pregnant compared with women who had never been pregnant was 0.49 (95% confidence interval 0.27-0.91). The earlier the first pregnancy, the lower the risk of RA. Pregnancy with adverse outcome (i.e., gestation less than 25 weeks) did not substantially change the risk of RA (relative risk 0.73, 95% confidence interval 0.50-1.07). The protective effect of pregnancy was independent of OC use, the presence of HLA-DR4, or a family history of RA. Immune modulation by female hormonal influences could be an explanation for the results of the present study.

Interleukin-2, soluble interleukin-2 receptor and tumor necrosis factor in sera from patients with rheumatoid arthritis

Interleukin-2 (IL-2), soluble interleukin-2 receptor (IL-2R) and tumor necrosis factor (TNF) have been measured in sera from 47 patients affected by classic rheumatoid arthritis (RA) using an enzyme-linked immunosorbent assay. The patients were divided into 4 groups as follows: group A, 18 patients with inactive disease; group B, 19 patients with active disease under treatment with non-steroidal antiinflammatory drugs (NSAID) and second-line drugs; group C, 5 patients with active disease under treatment with NSAID and cyclosporine A (CSA) for at least 4 months; group D, 5 patients in the same condition as patients of group C, but treated with azathioprine (AZA) instead of CSA. IL-2 was undetectable in all patients except two, both characterized by active disease. Soluble IL-2R levels were above the upper limit of the normal range in most of the patients studied, but the mean value ( +/- 1 SD) was significantly higher in patients of group B (1,288 +/- 421 U/ml) than in patients of group A (686 +/- 205 U/ml) and group C (842 +/- 414 U/ml). In two patients affected by active RA treated with pulse methylprednisolone therapy (1 g/day for 3 alternate days) the values of soluble IL-2R dropped from 948 to 662 U/ml and from 660 to 518 U/ml, respectively. No statistically significant correlation was observed between the serum level of IL-2R and the RF titre or percentage of C1q-binding activity, respectively. TNF was found within the normal range in all patients except one, who was characterized by active arthritis, high number of rheumatoid skin nodules and extremely high RF titre.(ABSTRACT TRUNCATED AT 250 WORDS)

Rheumatoid knee: role of gadopentetate-enhanced MR imaging.

Physical examination is often insufficient in distinguishing between joint effusion and inflamed synovium in the knee joints of patients with rheumatoid arthritis. The authors prospectively evaluated the role of intravenously administered gadopentetate dimeglumine in distinguishing between these two conditions. Fourteen patients with classic rheumatoid arthritis were examined first by a rheumatologist and then by means of magnetic resonance (MR) imaging with T1- and T2-weighted sequences. T1-weighted images were also obtained following the intravenous administration of gadopentetate dimeglumine. T1-weighted images obtained prior to contrast material administration demonstrated an identical low-intensity signal from both effusion and inflamed synovium, and T2-weighted images demonstrated increased signal intensity in both cases. Intravenous administration of gadopentetate dimeglumine allowed distinction between effusion and abnormal synovium, with the effusion remaining of low signal intensity and the synovium demonstrating enhancement and increased signal intensity. The authors conclude that the use of gadopentetate allows distinction between synovial thickening and joint effusion in the knee, which may affect treatment decisions.

Monocyte activation in early onset rheumatoid arthritis.

Monocytes from peripheral blood and synovial fluid of patients with definite and classic rheumatoid arthritis spontaneously produced significantly greater amounts of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and interleukin-1 beta (IL-1 beta) than samples of peripheral blood from normal controls. Peripheral blood monocytes from patients with rheumatoid arthritis produced significantly greater amounts of PGE2 than control samples when stimulated with lipopolysaccharide. There were no significant differences in the spontaneous release of superoxide or N-acetyl-beta-D-glucosaminidase by peripheral blood monocytes between patients and healthy controls. Both stimulated and unstimulated peripheral blood monocytes from patients with definite or classic rheumatoid arthritis produced significantly greater amounts of PGE2 than samples from normal controls. This was true, regardless of the stage of disease and the presence or absence of roentgenological joint abnormalities. Amounts of N-acetyl-beta-D-glucosaminidase released by peripheral blood monocytes from patients correlated positively with the erythrocyte sedimentation rate (ESR) and negatively with duration of disease. Amounts of IL-1 beta and N-acetyl-beta-D-glucosaminidase released from the peripheral blood monocytes of patients who had had their disease for less than one year were significantly higher than those of normal controls. There were no significant correlations between the types of treatment and the amounts of PGE2, LTB4, IL-1 beta or N-acetyl-beta-D-glucosaminidase released by peripheral blood monocytes in patients with rheumatoid arthritis. The findings suggest that monocytes are activated in patients with rheumatoid arthritis both at the onset of disease and during its chronic phase, and that they produce large amounts of mediators which may have a role in the induction and extension of the inflammatory process which leads to tissue damage.

Inherited complement deficiency states: implications for immunity and immunological disease

The study of complement deficiency states and their influence on immune function has generated new insights and still provides a challenge to continued investigation. The association of classical pathway deficiencies (C1, C4, C2 or C3) with immunological diseases such as SLE and glomerulonephritis has contributed to current knowledge concerning complement-dependent immune complex handling and elimination. Susceptibility to systemic infection with encapsulated bacteria is encountered in most forms of inherited complement deficiency. Recurrent neisserial infection is the only clinical manifestation clearly associated with defects of the membranolytic sequence C5-C9, while deficiency of properdin, a component of the alternative activation pathway, appears to predispose to nonrecurrent meningococcal disease. Inherited complement deficiency is rare, but the perspective is widened by the more common occurence of acquired defects in immunological diseases, and the apparent requirement for efficient complement recruitment in host defense. Another aspect is the possibility that complement deficiency might alleviate or prevent inflammatory symptoms. Notably, complement deficiency has not been reported in classical rheumatoid arthritis. Considerations of this kind would be refuted or modified by findings of complement deficiency in single patients.

Mortality and survival in rheumatoid arthritis: a 25 year prospective study of 100 patients.

One hundred patients with classical (52) or definite (48) rheumatoid arthritis (RA) at one year after onset were followed up for 25 years. By then 63 had died, in one third of whom RA had either directly caused or contributed to death. These patients, at one year after onset of arthritis, had a higher proportion with classical RA and more functional impairment than the rest. Thirty five of the surviving 37 patients were seen for review. Eleven were well with no functional impairment. At one year after onset they had a lower erythrocyte sedimentation rate (ESR) and higher haemoglobin than the others, in whom a poorer outcome was associated with a persistently raised ESR and lower haemoglobin. The initial Rose-Waaler titre was a poor prognostic guide, but a better functional outcome was associated with conversion to seronegativity or a marked fall in rheumatoid factor level.

Postmenopausal hormones and the incidence of rheumatoid arthritis

This case-control study assessed whether postmenopausal use of hormones reduces the incidence of rheumatoid arthritis (RA). Cases had classical or definite RA. Controls were patients with primary osteoarthritis or soft tissue rheumatism. Information on exposure was obtained by telephone interview. Compared to women who had never used postmenopausal hormones before onset of rheumatologic symptoms, adjusted relative risk (95% confidence limits) for past and current users were 0.95 (0.56-1.60) and 0.89 (0.49-1.63), respectively. Among current users, the association was not related to the duration of use. Our results provide little support for the hypothesis that use of postmenopausal hormones has a protective effect on the development of RA.

The effect of dietary fish oil supplement upon the content of dihomo-gammalinolenic acid in human plasma phospholipids

Patients (n = 23) with definite or classical rheumatoid arthritis were given 18 g/day fish oil in gelatin capsules which provided 3.2 g/day EPA and 2.0 g/day DHA. The treatment period was 12 weeks followed by a 4 week washout period. Fish oil supplementation to the diet resulted in a substantial increase in the content of EPA and DHA in each of the plasma fractions examined (PL, TG, and CE). Little change was seen in the AA level of the TG and CE fractions but a modest decrease in AA was seen in PL. However the intake of fish oil caused a significant depression in the content of DGLA in the PL (p<0.005) and CE (p<0.01) fractions relative to baseline values. All changes had reverted to near baseline levels 4 weeks after dietary intervention. Since DGLA is the precursor of PGE 1, which has been shown to be anti-inflammatory, our findings suggest that the anti-inflammatory effects of fish oil consumption could be mitigated by an associated reduction in DGLA.