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BACKGROUND: The treatment of rheumatoid arthritis should aim at clinical remission. This multicentre, randomised trial with 2-year follow-up sought evidence on the efficacy and tolerability of combination therapy (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) compared with treatment with a single disease-modifying antirheumatic drug, with or without prednisolone, in the treatment of early rheumatoid arthritis. METHODS: 199 patients were randomly assigned to two treatment groups. 195 started the treatment (97 received combination and 98 single drug therapy). Single-drug therapy in all patients started with sulphasalazine; in 51 patients methotrexate was later substituted. Oral prednisolone was required by 63 patients. The primary outcome measure was induction of remission. Analyses were intention to treat. FINDINGS: 87 patients in the combination group and 91 in the single-therapy group completed the trial. After a year, remission was achieved in 24 of 97 patients with combination therapy, and 11 of 98 with single-drug therapy (p=0.011). The remission frequencies at 2 years were 36 of 97 and 18 of 98 (p=0.003). Clinical improvement (American College of Rheumatology criteria of 50% clinical response) was achieved after 1 year in 68 (75%) patients with combination therapy, and in 56 (60%) using single-drug therapy (p=0.028), while at the 2-year visit 69 and 57 respectively (71% vs 58%, p=0.058) had clinically improved. The frequencies of adverse events were similar in both treatment groups. INTERPRETATION: Combination therapy was better and not more hazardous than single treatment in induction of remission in early rheumatoid arthritis. The combination strategy as an initial therapy seems to increase the efficacy of the treatment in at least a proportion of patients with early rheumatoid arthritis.

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A waterborne Campylobacter jejuni outbreak in the Rheumatism Foundation Hospital in Heinola, Finland, in November-December 1986 is described. 32 patients and 62 members of the staff developed gastrointestinal symptoms. C. jejuni heat-stable serotype 45 was isolated from the faeces of 32 enteritis patients and from none of the controls. No other enteropathogens were found. Positive serological responses to C. jejuni acid extract antigen were detected by enzyme immunoassay in 34% of the symptomatic hospital patients, in 40% of the symptomatic staff members, and in 10% of the controls. The clinical course of the illness was mostly mild and self-limited. No striking progress in the arthritis symptoms of the patients was found after the outbreak. The hospital has its own water supply. C. jejuni of the same serotype as the epidemic strain was isolated from the water of the pipeline system. After a careful examination some aged components of the waterworks were found to be responsible for leaks that resulted in the contamination of the water.

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Patients with rheumatoid arthritis (RA), 500 men and 500 women, aged 40 years and over, together with a control population matched by age and sex were followed up with respect to cause-specific mortality over a 10-year period. The overall mortality was significantly higher in both men and women with RA than in the controls. A statistically significant increase in mortality from all cardiovascular diseases (p less than 0.001) and cardiac diseases (p = 0.004) was observed in men with RA but not in women with RA compared to corresponding controls. No difference in mortality from cerebrovascular diseases was observed between RA patients and controls.

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Patients with rheumatoid arthritis (RA), 500 men and 500 women, aged 40 years and over, together with a control population matched by age and sex, were observed over a 10 year period. The overall mortality was significantly higher in both men and women with rheumatoid arthritis than in the controls due to an excess mortality from infections and cardiovascular and renal diseases. During the follow up 31 patients with RA (12 male, 19 female) and one male control subject died from amyloidosis and 42 RA patients (19 male, 23 female) and one male control from renal diseases. The most important causes of renal deaths were chronic nephritis and renal infections.

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Patients with rheumatoid arthritis (RA), 500 males and 500 females, aged 40 years and over, together with an age and sex matched control population, were observed over a 10-year period. The overall mortality was significantly higher in both men and women with RA than in the controls. During the followup, 42 patients with RA (28 males, 14 females) and 58 control subjects (36 males, 22 females) died from malignant neoplasms, but this difference was not statistically significant. A significant excess of deaths from neoplasms of the hematopoietic system was observed in patients with RA. Subjects without RA had significantly higher mortality rate from cancer of gastrointestinal origin than patients with RA.

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Patients with rheumatoid arthritis (RA), 500 males and 500 females, aged 40 years and over, together with an age- and sex-matched control population, were observed over a 10-year period. Altogether 208 male and 148 female RA patients died during the follow-up period. RA was mentioned on the death certificates of 111 men (53%) and for 96 women (65%). Serious underreporting of RA was observed when the main cause of death was malignant neoplasms and diseases of the circulatory system. The results show that analysis of the causes of death can be highly biased if the RA diagnosis is based only on information on the death certificate.

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The subtype of the proliferating cells in the synovial fluid of patients with rheumatoid arthritis (RA), ankylopoietic spondylarthrosis (SPA), and osteoarthritis (OA) was studied with autoradiography-immunoperoxidase double staining. Of all spontaneously proliferating synovial fluid cells in chronic arthritis, 59 +/- 4% displayed T8 differentiation marker, whereas T4 (21 +/- 4%) and B (2 +/- 1%) cells were few. Of all T4+ and all T8+ lymphocytes, 0.55 +/- 0.1% and 0.90 +/- 0.1%, respectively, incorporated [3H]thymidine. The [3H]thymidine labelling index for B cells was 0.30 +/- 0.1%. This was in contrast to OA, in which no proliferating lymphocytes were observed in the synovial fluid. Our findings suggest that the predominance of proliferating T8+ cells in the synovial fluid reflects an underlying chronic inflammation. Because RA and SPA synovium is a site of intense immunoglobulin production, our finding of the predominance of activated, proliferating T8+ cells may also reflect a dissociation between phenotype and function as a reason for the chronicity of the joint inflammation.

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Cellular inflammation in rheumatoid arthritis (RA) synovial membrane was studied in biopsy specimens taken at different stages of synovitis and disease. Patients were classified into three subgroups: acute RA, subacute RA, and chronic RA. Inflammatory cells were characterised by a histochemical esterase method and immunohistochemical peroxidase-antiperoxidase (PAP) and avidin-biotin-peroxidase (ABC) staining. The amounts and distribution of inflammatory cells were different in various stages of the synovitis. In acute onset RA monocytes and granulocytes predominated, suggesting that the beginning of rheumatoid inflammation is similar to inflammatory reaction in general. The presence of T cells and also of plasma cells in subacute RA suggests underlying subclinical changes also in apparently healthy joints in RA. The most typical feature of prolonged synovitis in chronic RA was its intensity, characterised by the presence of large T cell and plasma cell infiltrates. Our findings suggest that the immunological mechanisms are secondary to the tissue damage caused by the initial inflammatory events of unknown cause. However, the immunological mechanisms may still play a central role in the aetiopathogenesis, because findings in chronic RA suggest a defective down-regulation of the immune response.

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Five hundred men and 500 women, aged 40 or over, with rheumatoid arthritis, together with a control population matched for age and sex, were observed over 10 years. During that time 352 patients with rheumatoid arthritis (208 men, 144 women) and 221 controls (148 men, 73 women) died. The overall mortality was significantly higher (p less than 0.0001) in both men and women with rheumatoid arthritis than in the controls. Infections and cardiovascular and renal diseases (especially amyloidosis) appeared to be the main causes of death in rheumatoid arthritis.

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A description of the protracted course of kingella monoarthritis is given as an illustration of the importance of accounting for the slow growth, low viable numbers, and fastidious culture requirements of microbes that may be encountered in synovial samples. The practice of carrying out synovial fluid cultures in the same way as blood cultures is recommended.

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The analgesic effect of 10 anti-inflammatory drugs was compared using a single-blind method in 90 patients with rheumatoid arthritis. Each patient received two different drugs, for three days each and each drug was evaluated in 18 patients. After the trial, the patients considered which of the drugs they preferred. The greatest relief from pain was achieved by diclofenac, indomethacin, naproxen and tolfenamic acid, each of these being preferred by the majority of patients and being significantly (p less than 0.01) better than the least effective drugs ketoprofen and proquazone. Acetylsalicylic acid, azapropazone, carprofen and ibuprofen were considered intermediate in efficacy.

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Patients with rheumatoid arthritis, 500 males and 500 females, aged 40 years or over, together with an age and sex matched control population, were observed over a 5-year period. During the follow-up 176 RA patients and 107 controls died. The most common causes of death in RA patients were cardiovascular diseases (86 patients), renal failure (33 patients), infections (23 patients), and malignant neoplasms (21 patients); in the controls, the corresponding data are cardiovascular diseases (53), malignant neoplasms (30), infections (9), and accidents (8).

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In 24 adult RA patients with knee joint synovitis and bilateral hydrops, the worse joint clinically was treated with osmic acid and 50 mg of hydrocortisone acetate, while the better joint clinically was treated with 40 mg of methylprednisolone acetate (Depot Medrol). After 6 months, hydrops was palpable in 8 joints treated with osmic acid and in 15 joints treated with corticosteroid only. Pain relief was more marked in joints treated with osmic acid.

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Ninety-nine adult RA patients with knee joint synovitis were randomized into two groups. The knee joints of the first group (52 patients) were treated with osmic acid and those of the second group (47 patients) with a placebo. After 6 months, the incidence of hydrops and pain was statistically less significant in joints treated with osmic acid. the result was better in joints without advanced radiological destruction. It is concluded that osmic acid is still of benefit in the local treatment of rheumatoid knee joint synovitis at an early stage.

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Among 3115 autopsied patients, rheumatoid arthritis was registered in 41 patients (1.3%). The causes of death of these were correlated with the causes of death of 310 non-rheumatoid autopsied patients. Of the RA patients, 32% died from cardiovascular disease, 24% from infection, 27% from renal failure and 7% from malignant disease. Of the control patients, 42% died from cardiovascular disease, 9% from infection, 3% from renal failure, and 23% from malignant disease. The low frequency of malignant disease as a cause of death in RA patients may be due to a continuous immunological stimulation or due to a missed diagnosis of RA in patients who died from malignant disease.

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In patients with recent inflammatory arthritis HL-A27 was seen in 6 out of 7 patients with ankylosing spondylitis, in 15 out of 18 patients with Reiter's disease, in 9 out of 12 patients with reactive postinfectious arthritis, in 22 out of 45 patients with rheumatoid arthritis, and in 2 out of 14 patients with other types of inflammatory arthritis. In two control series HL-A27 occurred in 46 out of 326 persons and in 3 out of 34 persons. The high frequency of HL-A27 in RA patients is in disagreement with previous results by other investigators. The explanation for this may be either that the diagnostic criteria do not apply at the early stage of the disease, or that there is a high prevalence of HL-A27 associated RA in Finland.

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Patients with rheumatoid arthritis, 500 males and 500 females, aged 40 years or over, and an age- and sex-matched control population were observed over a 3-year period. During the follow-up, 122 RA patients and 69 controls had died. The most common causes of death in RA patients were cardiovascular diseases (57 patients), renal failure (27 patients), infections (19 patients), and malignant neoplasms (11 patients); in the controls, the respective data are: cardiovascular diseases (35 people), malignant neoplasms (21 people), accidents (7 people), and infections (5 people).

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