Double blind placebo controlled trial of pulse treatment with methylprednisolone combined with disease modifying drugs in rheumatoid arthritis.

OBJECTIVE: To assess whether monthly treatment with intravenous methylprednisolone enhances or accelerates the effect of disease modifying drugs in patients with rheumatoid arthritis. DESIGN: A 12 month double blind, placebo controlled, multicentre trial in which patients with active rheumatoid arthritis were randomly allocated to receive pulses of either methylprednisolone or saline every four weeks for six months. At the start of the pulse treatment all patients were started on penicillamine or azathioprine. SETTING: Four rheumatology departments in Denmark. PATIENTS: 97 Patients (71 women, 26 men) aged 23-84 (mean 60) who had active rheumatoid arthritis of at least four weeks' duration despite treatment with non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES: Monthly clinical recording of morning stiffness, number of tender and swollen joints, blinded observers' evaluation of therapeutic effect, and patients' self assessed condition. Concomitant laboratory measurements of erythrocyte sedimentation rate and concentrations of C reactive protein and haemoglobin. Radiography to determine the number of erosions at the start of treatment and after 12 months. RESULTS: 57 Patients completed the trial, taking the same disease modifying drug throughout. Evaluation four weeks after each pulse treatment and at 12 month follow up showed no significant differences between the methylprednisolone and placebo groups in any of the clinical or laboratory variables. Radiography showed the same degree of progression of erosions in both groups. Evaluation of the total data on 97 patients and on the 57 who completed the trial showed the same lack of significance between the treatment groups. CONCLUSIONS: Intravenous pulse treatment with steroids can be recommended only for rapid temporary relief of flares of disease in patients with rheumatoid arthritis. The response is short lived. Repeated pulses of methylprednisolone at four week intervals do not improve the results of treatment with drugs that induce remission such as penicillamine and azathioprine.

[Neurogenic inflammation and arthritis]. / Neurogen inflammation og arthritis.

Over the past decade, numerous studies have supported the involvement of the sensory and sympathetic nervous system in the regulation of inflammation. This article reviews the neurogenic mechanisms and mediators of the sensory nervous system involved in the generation of inflammatory responses. The implications of neuropeptide-induced immunoregulation are discussed in the context of inflammation in rheumatoid arthritis.

[Still disease in adults]. / Mb. Still hos voksne.

Adult onset Stills disease (ASD), an adult variant of systemic onset juvenile rheumatoid arthritis, is a rare disease entity. The diagnosis is solely a clinical one and often difficult. Clinical and laboratory features are not pathognomonic. The diagnosis of ASD has to be considered in patients with high spiking fever, transient rash, arthralgias, oligo- or polyarticular arthritis, leukocytosis, sore throat, lymphadenopathy and/or splenomegaly, liver dysfunction and high serum ferritin levels. We give a brief review of the clinical features, differential diagnosis, treatment and prognosis.

[Desmopressin in the treatment of hemorrhagic diathesis]. / Desmopressin i behandling af haemoragisk diatese.

Over the past several years, the use of 1-deamino-8-D-arginine vasopressin (DDAVP), a synthetic analogue of vasopressin, has been found to be useful in the treatment of patients with abnormal bleeding tendency. This article is a review of inherited and acquired disorders with prolonged bleeding time in which DDAVP is supposed to shorten the bleeding time. DDAVP is established as effective therapy of the abnormal haemostasis in mild or moderate haemophilia A and von Willebrand's disease. Frequently, DDAVP infusions are used to control bleeding in patients with uraemia. Bleeding time is also significantly shortened in patients with liver cirrhosis, although randomized trials of DDAVP therapy of gastrointestinal bleeding in this group of patients are still needed. Shortening or normalization of the bleeding time with DDAVP has also been observed in patients with inherited platelet dysfunctions, acquired disorders of haemostasis and abnormal haemostasis in chronic myeloproliferative diseases. In addition, preoperative treatment with DDAVP seems to reduce blood loss during surgery.

[Two cases of Still disease in adults]. / To tilfaelde af Morbus Still hos voksne.

We describe two cases of adult onset Stills disease. Both patients presented with typical features of adult Stills disease: high spiking fever, arthralgia, oligo- and polyarticular arthritis, transient rash, sore throat, lymphadenopathy and leukocytosis. Both patients failed to improve when treated with nonsteroidal antiinflammatory drugs (NSAIDs) and azathioprine, but responded adequately when sulfasalazine was added to the medication. It is suggested that sulfasalazine is a useful adjunct if the clinical response to NSAIDs is not sufficient.

The role of HLA-DR antigens in PPD-stimulated lymphocyte-monocyte interactions.

Autologous monocytes are required for an optimal lymphocyte proliferative response to purified protein derivate of tuberculin (PPD) in vitro and for a mixed lymphocyte culture induced by alloantigens. In the proliferative response to PPD we found that autologous monocytes could be replaced with HLA-DR-compatible monocytes and partly with HLA-DR semi-identical. In spite of a statistically significant difference between autologous and HLA-DR disparate monocytes in their cooperative capacity with PPD-stimulated lymphocytes, replacement in nearly one third of the cases was possible. These findings were supported by more detailed studies in which increasing numbers of allogenic and autologous monocytes were added to the isolated lymphocytes in the presence of PPD. It is concluded that the serologically defined HLA-DR antigens alone give insufficient information of the restriction elements controlling the PPD-stimulated lymphocyte-monocyte interactions.

The frequency of rheumatoid arthritis among relatives of probands with definite ankylosing spondylitis.

We studied families of 23 unrelated HLA-B27 positive probands with definite ankylosing spondylitis to investigate the occurrence of rheumatoid arthritis. The prevalence of RA among these relatives was significant higher (2.91%; 0.02 less than p less than 0.05) than in the control group of 28 healthy individuals (1.02%). These data suggest an increased relative risk of RA in relatives of patients with AS.

A double-blind comparative study of hydroxychloroquine and dapsone, alone and in combination, in rheumatoid arthritis.

Eighty patients with active rheumatoid arthritis (RA) entered a double-blind randomized study of 24 weeks duration, to compare the efficacy and toxicity of hydroxychloroquine, dapsone, and a combination of both drugs in treatment of RA. Evaluation of changes in clinical, laboratory and radiologic variables was based on 63 patients completing the trial. There was no clear difference between the three therapy groups in most inflammatory variables after 24 weeks. However, only patients receiving the combination therapy improved significantly in all clinical and laboratory variables. Nine patients in the combination group and four in each single drug group discontinued during the trial, mainly because of toxicity. Four patients taking the combination therapy withdrew because of hemolytic anemia, and none in the dapsone group. These findings suggest that hydroxychloroquine in combination with dapsone is somewhat more effective and less tolerated than single drug treatments.

The aminoterminal-type-III procollagen peptide and proteoglycans in serum and synovial fluid of patients with rheumatoid arthritis or reactive arthritis.

The concentrations of aminoterminal-type-III procollagen (procollagen N-) peptide, and of proteoglycans were measured in knee-joint synovial fluid and serum from patients with rheumatoid arthritis or reactive arthritis. All synovial fluids contained large amounts of intact propeptide. The synovial fluid: serum propeptide ratios were high, suggesting local propeptide liberation. A correlation was demonstrated between the propeptide concentration in synovial fluid and in serum. In rheumatoid arthritis, the propeptide concentration in synovial fluid was related to local inflammatory activity, and the serum concentration was correlated with the presence of nonspecific markers of inflammation. The presence of smaller propeptide fragments in synovial fluid indicated that some degradation occurred locally. The local metabolic changes were most prominent in patients with joint erosions. Patients with nonerosive rheumatoid arthritis and reactive arthritis had similar synovial fluid propeptide concentrations. The proteoglycan content of synovial fluid was inversely related to the degree of joint destruction, and was highest in patients with reactive arthritis. No correlation was observed between the concentrations of propeptide and proteoglycan in synovial fluid. Intraarticular glucocorticoid injection reduced the levels of propeptide and proteoglycan in synovial fluid.