Reproductive health in women with systemic lupus erythematosus compared to population controls.

OBJECTIVE: To study the reproductive health history in women with systemic lupus erythematosus (SLE) compared to population controls. METHODS: A total of 206 female SLE patients were interviewed regarding demographic and disease data, menstruation, use of contraception and hormone replacement therapy (HRT), infertility, and pregnancies. The control group consisted of 1037 women from the general population of similar age and socioeconomic status living in the same region. RESULTS: In SLE women compared to population controls, mean age at menarche (13.3 vs. 13.2 years) and frequency of infertility (16% vs. 16%) were similar but menopause occurred earlier (44.9 vs. 46.8 years, p = 0.01). Current use of oral contraceptives (OCs) was less common than in controls [18% vs. 28%, odds ratio (OR) 0.55, 95% CI 0.3-1.0] while previous use of progesterone-containing intrauterine devices (IUDs) was more common (13% vs. 5%, OR 3.2, 95% CI 1.9-5.4). Current use of HRT was similar (22% vs. 21%) but SLE patients had started the use earlier (43.2 vs. 47.1 years, p = 0.003). Mean number of pregnancies was lower in SLE patients compared to controls (2.3 vs. 2.5, p = 0.046) and in lupus nephritis patients compared to SLE patients without nephritis (1.9 vs. 2.5, p = 0.01). No difference was found in the occurrence of spontaneous and induced abortions compared to controls, but pregnancy-associated complications were more common in SLE women. CONCLUSION: When compared to population controls women with SLE are normally fertile, use less OCs and more IUDs, have earlier menopause and use HRT as frequently. Family size is reduced, especially in lupus nephritis patients, and pregnancy-associated complications are more common.

Screening test for rheumatic diseases: a combined enzyme immunoassay of rheumatoid factors and antibodies to DNA and extractable nuclear antigens.

Three hundred and one sera from patients with rheumatic and other diseases were investigated using a simple enzyme immunoassay for screening of rheumatoid factors and antinuclear antibodies. The assay had a sensitivity of 77% for systemic lupus erythematosus, 90% for the primary sicca syndrome, and 89% for rheumatoid arthritis. Only 13% of sera from patients with chronic non-rheumatic diseases were positive. The test was further evaluated in a group of patients with suspected rheumatic disease who were followed up for six to 12 months. The test was positive in 16 of 17 sera from patients with connective tissue diseases but in only seven of 36 sera (19%) from patients with non-inflammatory joint diseases. None of the four patients with reactive arthritis was positive by this test. The sensitivity of the assay was comparable with that of the agglutination and immunofluorescence tests for rheumatoid factors and antinuclear factors. For the screening of rheumatoid factor and antinuclear antibodies this kind of test panel offers a simple alternative to the conventional tests for small clinical laboratories and for those in which the autoantibody tests could be automated, as the assay can be performed in one working day and only one dilution of serum is needed to obtain a quantitative result.

Effect of a strict vegan diet on energy and nutrient intakes by Finnish rheumatoid patients.

Dietary intake data of 43 Finnish rheumatoid arthritis patients were collected using 7-day food records. The subjects were randomized into a control and a vegan diet groups, consisting of 22 and 21 subjects, respectively. The subjects in the vegan diet group received an uncooked vegan diet ('living food') for 3 months, and they were tutored daily by a living-food expert. The subjects in the control group continued their usual diets and received no tutoring. Adherence to the strict vegan diet was assessed on the basis of urinary sodium excretion and by the information on consumption of specific food items (wheatgrass juice and the rejuvelac drink). The use of these drinks was variable, and some boiled vegetables were consumed occasionally. However, only one of the subjects in the vegan diet group lacked a clear decrease in urinary sodium excretion. Rheumatoid patients had lower than recommended intakes of iron, zinc and niacin, and their energy intake was low compared to mean daily energy intake of the healthy Finnish females of the same age. Shifting to the uncooked vegan diet significantly increased the intakes of energy and many nutrients. In spite of the increased energy intake, the group on the vegan diet lost 9% of their body weight during the intervention period, indicating a low availability of energy from the vegan diet.

Effect of zopiclone on sleep quality, morning stiffness, widespread tenderness and pain and general discomfort in primary fibromyalgia patients. A double-blind randomized trial.

Thirty-three patients fulfilling the diagnostic criteria for primary fibromyalgia completed an eight-week double-blind treatment trial with the drug zopiclone. Of outcome measures studied a score expressing subjective sleep quality showed improvement in more than ninety percent of zopiclone patients at 4 weeks and nearly eighty percent at 8 weeks, but similar improvement was also reported by more than sixty percent of the patients on placebo. Patient self-assessment of a treatment effect also showed an advantage for zopiclone, with most patients in the placebo group considering their state as unchanged at 8 weeks. According to examiner assessment, however, half the patients in both groups showed improvement at 8 weeks. For other assessment variables, e.g. dolorimeter assessment of widespread tenderness, visual analogue scales and pain drawings for pain and other subjective feelings of discomfort, the effects of zopiclone treatment were at the same level as those of placebo.

Causes of death in patients with rheumatoid arthritis autopsied during a 40-year period.

We studied causes of death (CoDs) between 1952 and 1991 assessed by a clinician before autopsy and then determined at autopsy by a pathologist in 369 subjects with rheumatoid arthritis (RA) and 370 subjects without RA (non-RA). We analysed clinical data for RA subjects between 1973 and 1991. In RA subjects, leading autopsy-based CoDs were RA, cardiovascular diseases and infections. Between diagnoses of CoDs by the clinician and those determined by the pathologist, RA subjects had lower agreement than did the non-RA regarding coronary deaths (Kappa reliability measure: 0.33 vs. 0.46). In non-RA subjects, autopsy-based coronary deaths showed a decline since the 1970s with no such decline in RA. Between subjects treated at any time during RA with disease-modifying anti-rheumatic drugs and those without, autopsy-based CoDs were similar. Coronary death being less accurately diagnosed in RA subjects may indicate that coronary heart disease in RA patients often remains unrecognized.

Prevalence and mortality rates of systemic lupus erythematosus and causes of death in SLE patients in Finland.

Nationwide prevalence and mortality rates in systemic lupus erythematosus (SLE) were estimated using a computer file of all hospital discharge records and cause of death statistics from 1972 to 1978. Age-specific and sex-specific prevalence rates obtained from 1976 to 1978 and mortality rates from 1972 to 1978. In December 1978 the prevalence of SLE was 28:100 000. The overall mortality rate was 4.7 per million person-years in 1972-78. Active lupus nephritis, vascular events and infections were the most frequent causes of death in SLE patients.

Outcome of systemic lupus erythematosus. A study of 66 patients over 7 years with special reference to the predictive value of anti-DNA antibody determinations.

A cohort of 66 patients with SLE that were thoroughly studied, both clinically and serologically in 1980-81, when they had a mean disease duration of eight years, were evaluated seven years later in order to assess the long-range outcome of the disease. Five patients were lost from follow-up and 12 (20%) died during the follow-up. The estimated 10-year survival was 91%. A total of 30 patients (45%), showed no signs of nephritis at any stage, and in only eight an active nephritis was found during the follow-up. The previous antibody determinations, provided no predictive information regarding the behaviour of the renal manifestations. Arthralgia was the main clinical symptom during the follow-up. Hypertension developed in 23%. At the end of the follow-up the disease was regarded as active in 13% of the patients.

Anti-DNA antibodies of IgA class in patients with systemic lupus erythematosus.

Sera obtained from 53 patients with systemic lupus erythematosus (SLE) were investigated for the presence of immunoglobulin class-specific antibodies against native (ds)DNA and denatured (ss)DNA. The methods employed were the Crithidia luciliae test and an enzyme-linked immunosorbent assay (ELISA), respectively. Anti-dsDNA antibodies of IgG class were seen in 42%, IgM-anti-dsDNA antibodies in 43%, and IgA-anti-dsDNA antibodies in 30% of the patients. There was an association between the presence of both IgG- and IgA anti-dsDNA antibodies and the activity of the disease. Patients with active nephritis also had anti-dsDNA antibodies of IgG and IgA class significantly more often than patients with inactive nephritis or without renal disease. IgG-anti-ssDNA antibodies were seen in 89%, IgM-anti-ssDNA antibodies in 51%, and IgA-anti-ssDNA antibodies in 66% of the patients. Patients with nephritis had low levels of antibodies to ssDNA of IgM class. We suggest that immunoglobulin class-specific anti-DNA antibodies should be determined in the diagnosis and monitoring of SLE.

Antibodies to cytoplasmic intermediate filaments in rheumatic diseases.

Antibodies to 2 types of cytoplasmic intermediate filaments (IMF)--vimentin and cytokeratin filaments--were assayed in sera from various rheumatic diseases by indirect immunofluorescence using cultured human embryonic fibroblasts and an epithelial cell line, PtK 2, as substrates. These antibodies belonged mainly to the IgM class and were detected in most of the sera. Vimentin filament antibodies of IgG or IgA class were frequent in Sjögren's syndrome (43%). Antibodies to another type of IMF, cytokeratin filaments, were also more prevalent in Sjögren's syndrome (64%) than in systemic lupus erythematosus (50%), rheumatoid arthritis (46%) and other hospital patients (8%). Our results show that intermediate filaments are a major target for autoantibodies in rheumatic diseases, especially in Sjögren's syndrome. The presence of intermediate filament IgA antibodies suggest that the stimulus for their production lies at epithelial surfaces.

Profiles of antibodies to histones, DNA and IgG in patients with systemic rheumatic diseases determined by ELISA.

The occurrence of antibodies against the total histone complex and the histone fraction H1, antibodies against denatured (ss) DNA and the synthetic double stranded polynucleotide poly dAT, as well as rheumatoid factors (RF) was determined in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) using enzyme linked immunosorbent assays (ELISA). Antihistone antibodies could be demonstrated at a frequency of about 17% in the patients with systemic rheumatic disease with no differences between the groups, even if there was a tendency for anti-H1 antibodies to occur more often in the SLE and SS patients than in the RA patients. Some of the antihistone antibody activity seen in the RA patients seems to be due to crossreactive RF. All patient groups showed significant IgG anti-ssDNA antibody activity compared to the controls, but the highest antibody levels were seen in the SLE patients. IgG antipoly dAT antibodies occurred significantly more often and at higher levels in the SLE patients than in the other patient groups. Although the individual tests did not readily distinguish the 3 diseases from each other, the antibody profiles were different. Patients with SS had the broadest reactivity, and the SLE patients had antibodies predominantly restricted to polynucleotides.

Neurofilament antibodies in systemic lupus erythematosus.

Autoantibodies against neuronal antigens occur in sera of patients with systemic lupus erythematosus (SLE). These antibodies may have significance in the pathogenesis of neurological complications of SLE. However, the neuronal structures containing the corresponding autoantigens are poorly known. In our study we assayed circulating antibodies against defined neuronal components--neurofilaments--by an enzyme-linked immunosorbent assay (ELISA) using purified neurofilament polypeptides as targets. Circulating neurofilament antibodies (anti-NF) of IgG class were detected in 21% of 28 patients with SLE and in 6% of 17 patients with rheumatoid arthritis and in none of the 14 patients with primary sicca syndrome and 40 blood donors. The presence of anti-NF could also be confirmed by the indirect immunofluorescence technique using frozen sections of rat spinal cord. In one serum, anti-NF cross reacted with vimentin type of intermediate filaments. The antibodies bound both to the 70 kilodalton and the 200 kilodalton polypeptides of neurofilaments as judged by the immunoblotting technique. Two of 6 anti-NF positive patients had neurological complications.

The prognostic value of HLA DR4 and B27 antigens in early rheumatoid arthritis.

The prognostic significance of HLA DR4 and B27 antigens was investigated in a 3-year follow-up of 87 patients with early rheumatoid arthritis (RA). The frequencies of DR1, DR4 and also of B27 were increased and the frequencies of DR2, DR3 and DR7 decreased compared with the normal Finnish population. During the follow-up with antirheumatic treatment, a similar improvement in clinical variables and laboratory measure assessing disease activity was found in both DR4-positive and DR4-negative RA patients. Despite clinical improvement a fast radiological progression in peripheral joints was observed but the presence of DR4 or B27 had no impact on the progression of joint damage. In some patients cervical changes developed early in the course of RA but were not related to DR4 or B27 positivity. The earlier observation of increased prevalence of HLA B27 in the Finnish RA patients was confirmed but the presence of B27 did not modify the clinical picture of RA.

Comparison of intramuscular gold and sulphasalazine in the treatment of early rheumatoid arthritis. A one year prospective study.

We compared the effects of intramuscular gold and sulphasalazine on early, active rheumatoid arthritis in 128 consecutive patients. Intramuscular gold was started in the first 70 consecutive patients and sulphasalazine in the subsequent 58 patients. The patient groups were comparable with regard to clinical characteristics. In both groups clinical and laboratory parameters improved, but there was no significant difference between the two groups. The clinical improvement was most pronounced during the first three months. However, despite the clinical improvement a clear progression in radiological changes was observed in both groups, 40% of the patients taking gold and 48% of patients taking sulphasalazine discontinued the treatment because of adverse drug reactions or inefficacy during the one year follow-up. Adverse drug reactions were the main reason in both groups. These findings suggest that intramuscular gold and sulphasalazine seem to have an equal, positive effect on symptoms and clinical variables, but that radiological progression does occur in most patients none the less.

DNA antibodies and complement in SLE patients. A follow-up study.

Sixty-seven patients with systemic lupus erythematosus (SLE) were followed up for 3-19 months (mean 12) in a prospective study. The activity of SLE was estimated on clinical grounds and correlated with DNA antibody and complement levels. The disease reactivations consisted mostly of articular and cutaneous symptoms. There were 17 relapses and 22 complicating infections during the follow-up period. The levels of antibodies to native, double-stranded (ds) DNA (P less than 0.001) and antibodies to denatured, single-stranded (ss) DNA of IgG class (P less than 0.001) and C3 (P less than 0.001) correlated best with disease activity, which was estimated on the clinical symptoms and signs. These assays were not reliable, however, in predicting minor exacerbations. The levels of IgM class ss-DNA antibodies were significantly higher in SLE patients without nephritis than in SLE nephritis patients. In most cases, the combination of IgG class ss-DNA antibody and complement (C3 and CH50) determinations differentiated SLE relapse from infection.

Effect of age on 3 year outcome in early rheumatoid arthritis.

OBJECTIVE: To investigate the effect of age on clinical and radiological outcome and on efficacy and tolerance of antirheumatic therapy in early rheumatoid arthritis (RA). METHODS: In a prospective 3 year study 113 patients (83 women, 30 men) were divided into 2 groups according to age at onset of disease: before (n = 55) and after 55 years of age (n = 58). For clinical outcome, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, Ritchie index, and number of swollen joints were measured. Radiological progression was analyzed by Larsen score. The principles of the "sawtooth" strategy were applied in the treatment of all patients. RESULTS: At baseline, inflammatory activity (ESR, CRP) and the Larsen score for hands were significantly higher in patients with late onset RA (LORA) and they also developed more extraarticular symptoms compared to patients with early onset RA (EORA). However, no differences were found in Ritchie index, number of swollen joints, or CRP values between the groups. Also during the followup there was a trend toward increased inflammatory activity (ESR) among LORA patients. After the initiation of antirheumatic therapy a parallel improvement in clinical activity was observed in the 2 groups. The frequencies of remissions, side effects, and withdrawals due to drug inefficacy did not differ significantly between the 2 groups. The radiological progression was also comparable. CONCLUSION: The onset of RA was more active in patients with LORA. However, the clinical course and the radiological progression were parallel in LORA and EORA patients. The "sawtooth" therapy was equally tolerated in both patient groups.

Characterization of the DNA-synthesizing cells in rheumatoid synovial tissue.

DNA-synthesizing cells from the rheumatoid arthritis synovial tissue of 7 patients and from 5 patients with traumatic and degenerative joint lesions were studied by incubating fresh synovial tissue samples with tritiated thymidine. Labelled cells were identified using autoradiography. The tissue sections were stained with methyl green pyronine. It was found that 0.66% (range 0.38-1.4) of the cells were labelled with 3H-thymidine whereas in control materials the percentage was 0.17 (range 0-0.38). Approximately half of the labelled subsynovial cells in rheumatoid patients (range 37-67%) were small lymphocytes, according to morphological criteria. About one-tenth of the labelled cells (range 0-17%) looked like medium-sized lymphocytes, while the rest had the characteristics of fibroblasts or were unidentifiable.

Salivary gland involvement in systemic lupus erythematosus. A sialographic study.

Hydrostatic parotid sialography was performed in 46 rheumatological patients, 17 of whom were SLE patients. Signs of atrophy of the parotid gland were noted more often in the SLE group (53%) than in the series as a whole (29%). Strictures in the duct and ductuli were also more common in the SLE group (67%) than in the whole series (50%). Sialectasis was only slightly more common (40%) in the SLE group than in the series as a whole (38%). Two contrast media, Amipaque (metrizamide, 170 mgI/ml) and Urographin 60% (sodium amidotrizoate + meglumin amidotrizoate 10:66, 290 mgI/ml) were used, of which Amipaque proved to be clearly better tolerated. This difference is probably due to the low osmolarity of Amipaque.

DNA antibodies with and without complement-binding ability.

The relationship between immunoglobulin class and complement-binding ability of DNA antibodies was studied by indirect immunofluorescence and Crithidia luciliae (CL) as substrate in the sera of 28 patients with SLE and antibodies to CL-DNA. In 15 of 28 cases the antibodies bound complement and were IgG either alone or in combination with IgA and IgM. In the remaining 13 sera the antibodies were either IgA or IgM and did not bind complement. Only one of nine patients with nephritis had CL-DNA antibodies of IgM alone, whereas that was true for 10 of 19 patients without nephritis. The factors influencing the complement binding were further studied by using purified IgM rheumatoid factors. Their ability to 'mask' the IgG-type CL-DNA antibodies and to inhibit the binding of complement was confirmed. These findings suggest that complement activation in SLE does not occur in patients with IgM-type anti-ds-antibodies or in patients with rheumatoid factor activity.

Circulating DNA-antibodies in systemic lupus erythematosus.

Sera from 57 patients with systemic lupus erythematosus (SLE) were tested for DNA-antibodies by three different methods: a radioimmunological test using the Farr technique, the Crithidia luciliae immunofluorescence assay for anti-double-stranded (native) DNA (anti-ds-DNA), and a solid-phase immunoenzymatic assay for anti-single-stranded (denatured) DNA (anti-ss-DNA) of IgG and IgM classes. There was a positive correlation between the activity of the disease and the levels of ds-DNA-antibodies and IgG anti-ss-DNA. Patients with active nephritis had a higher amount of anti-ds-DNA and anti-ss-DNA of IgG class than patients with inactive nephritis (P less than 0.05 and 0.01, respectively). Patients with SLE nephritis had lower levels of ss-DNA-antibodies of IgM class than patients without nephritis (P less than 0.02). There was a positive correlation between the IgG-anti-ss-DNA/IgM-anti-ss-DNA ratio and the activity score of the disease. These results suggest that the anti-ss-DNA assay may be useful in the follow-up of SLE. Complement fixing anti-ds-DNA and the highest levels of anti-ds-DNA by Farr assay were usually associated with an active disease, especially nephritis and joint involvement.