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Mycoplasmas were not isolated from synovial fluid or membrane specimens taken from 41 patients suffering from inflammatory polyarthritis. However, Mycoplasma pneumoniae was isolated in two laboratories and on two occasions from the knee joint of a hypogammaglobulinaemic patient with a chronic polyarthritis.
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(1) An epidemiological study of a rural African community has been carried out in the Western Transvaal. Altogether 801 respondents over 15 years old were examined; radiographs of the hands and feet were obtained in all these individuals. Serological tests for rheumatoid factor were carried out on 516 blood samples. (2) The diagnosis of inflammatory polyarthritis was based on a modification of the Rome Criteria of 1961. Two categories were defined: 'definite' and 'probable' rheumatoid arthritis. (3) In this population inflammatory polyarthritis was much less common and much milder in its manifestations than in European and American peoples. The prevalence of 'definite' rheumatoid arthritis was 0.12% and of 'definite' and 'probable' rheumatoid arthritis combined, 0.87. Such changes as were encountered on clinical and radiological examination were invariably mild; no respondent in the entire survey had clinical features that would have been accepted in the ordinary way as those of rheumatoid arthritis. (4) The latex fixation test (LFT) was positive in 8.9% of the sera tested; the modified LFT aftaer inactivation of the serum at 56 degrees C was positive in 15.1% of cases. Similar findings in West African populations have been explained on the basis of alteration of the immune response by widespread parasitic infections. No obvious aetiological factor of this type was found in the present survey.
A patient with biopsy-proven papular mucinosis, plus the characteristic IgG lambda light chain paraproteinemia, also developed a severe proximal myopathy, seronegative inflammatory polyarthritis, and marked eosinophilia. Muscle enzymes were elevated, EMG was compatible with polymositis, and muscle biopsy revealed an atypical necrotizing vacuolar myopathy. Synovial biopsy revealed an inflammatory synovitis with Class II synovial fluid. No mucin deposition was detectable in muscle or synovium. During 7 years of observation, corticosteroids and various immunosuppressive agents were successively administered with little benefit. Recently, weekly intravenous methotrexate and low-dose oral corticosteroids have resulted in clinical and laboratory improvement. It is suggested that the pathology in papular mucinosis may include serious rheumatic manifestations in addition to the cutaneous involvement.
Peripheral leucocytes from healthy blood-donors were preincubated in polyarthritic serum or normal serum and their adherence to glass tubes in the presence of synovial extract of control extract was measured. Serum from patients with inflammatory polyarthritis significantly reduced the proportion of leucocytes which adhered in the presence of synovial extract, but not control extract. Serum from patients with polyarthritis with visceral manifestations, patients with degenerative or metabolic polyarthritis or rheumatic fever, and controls did not have this effect. The leucocyte sensitising activity was eluted in the IgG fraction of serum, and could be absorbed by both synovial extract and IgG. It is thus probably IgG rheumatoid factor. In vivo, armed leucocytes in polyarthritic patients may bind to synovial tissue initiating or perpetuating the articular inflammatory process.
Relapsing polychondritis (RP) is not a totally rare rheumatic disease. We have seen 23 patients from 1960-1975, and there are now a total of 159 reported cases, which form the basis of this study. RP occurs equally in both sexes, and has a maximum frequency in the fourth decade. 2) Empirically defined diagnostic criteria are proposed, to include the most common clinical features: a) Bilateral auricular chondritis b) Nonerosive sero-negative inflammatory polyarthritis c) nasal chondritis d) Ocular inflammation e) Respiratory tract chondritis f) Audiovestibular damage The diagnosis is based primarly upon the unique clinical features, and is quite certain if three or more criteria are present together with histologic confirmation. 3) Fifty percent of patients present with either auricular chondritis or the arthropathy of RP; but with prolonged follow-up, a majority of patients develop four or more of the above mentioned criteria. 4) Approximately 30 percent of patients have a preceding or coexistent rheumatic or autoimmune disease, which can lead to initial diagnostic confusion. 5) Laboratory and radiographic investigations help mainly to rule out other diagnostic possibilities, with no characteristic abnormalities being present in a majority of patients. 6) On follow-up, three-fourths of our patients required chronic corticosteroid therapy with an average dose of 25 mg per day of prednisone. Corticosteroids decrease the frequency, duration, and severity of flares, but do not stop disease progression in severe cases. 7) The mortality rate has been 30 percent in our series and 22 percent in the other 136 reported cases. Of the 29 cases where the cause of death was known, 17 were from respiratory tract involvement and 9 from cardiac valvular or vasculitic involvement, emphasizing the need to search for critical involvement of either of these organ systems in each patient. 8) Detailed reports of selected cases are presented to illustrate the clinical diagnosis and differential diagnosis, and to demonstrate the need for careful prolonged follow-up. 9) Although the etiology remains unknown, there is a frequent association with, and clinical similarity to, other rheumatic diseases. 10) Careful clinicopathological study of our 23 patients leads us to postulate an underying systemic vascultis as an important pathologic mechanism in RP.
An oil emulsion of purified type II collagen from bovine articular cartilage when injected intradermally into rats induced an inflammatory polyarthritis in 4 of 12 animals. When similarly injected, collagen purified from bonve vitreous induced arthritis in 6 of 12 animals. Studies of humoral and cell-mediated immunity to both collagen preparations demonstrated complete cross-reactivity. It is concluded that vitreous collagen shares the arthritogenic property of cartilage-derived type II collagen and that collagen from the two sources is indistinguishable in arthritogenic and immunologic properties.
When rats were injected intradermally with an oil emulsion of native type II collagen, they developed an inflammatory polyarthritis. The incidence and severity of arthritis increased as the amount of collagen injected was increased. Rats 4 1/2 weeks old were the most susceptible to the development of arthritis, whereas weanling and older animals were relatively resistant. There was no difference in incidence between males and females. Mononuclear cells from peripheral blood, lymph nodes, and spleen were cultured with type II collagen and responded maximally to a collagen concentration of 25 microgram/ml. The earliest detectable response was in peripheral blood mononuclear cell cultures obtained 6 to 8 days after immunization. The response of lymph node and spleen cells tended to lag behind that of peripheral blood cells at the earlier time intervals. Antibodies were detected in sera by hemagglutination at 8 days postimmunization. Quantitation of IgM and IgG antibodies by radioimmunoassay showed good correlation with hemagglutination titers and increased binding of collagen by both classes of antibody in arthritic as compared to nonarthritic animals. It is clear that the development of both humoral and cellular immunity to type II collagen is associated with the development of arthritis and may be important in the pathogenesis of this disease.
Using information theory, the value of radiological and laboratory investigations has been assessed in the diagnosis and management of 67 patients suspected of having inflammatory polyarthritis. There were only three changes in diagnosis made as a result of the investigations. Both the radiological and laboratory tests supplied a small but significant amount of information in improving the physician's confidence in diagnosis. Changes in management occurred more frequently but the final management decision differed from the pre-investigation decision in only 17 of the 67 patients (25%). Radiological examination failed to decrease uncertainty using a simple 'change in uncertainty' measure. Both types of investigation supplied a limited bu significant amount of information towards the final management decision, although the contribution from radiology was only significant when view before the receipt of the results of the laboratory tests. In view of the limited value of the investigations - particularly radiology - in this study, it is important to fully asses present and future diagnostic procedures especially in relation to patient management.
A patient with seronegative inflammatory polyarthritis developed a predominantly motorperipheral neuropathy associated with the use of indomethacin. Three other cases of peripheral neuropathy associated with indomethacin treatment have been reported to the Committee on Safety of Medicines. In all cases the neuropathy regressed when indomethacinwas stopped. Peripheral neuropathy should be recognized as a rare complication of indomethacin therapy and considered in the differential diagnosis of a neuropathy accompanyingrheumatoid arthritis.
Eleven out of 24 patients with systemic sclerosis had radiological features of inflammatory polyarthritis. Juxta-articular osteoporosis was present in 9 patients, erosions in 5 and loss of joint space in 6 patients. Only one patient had a positive rheumatoid factor. Titres of rheumatoid factor, anti-nuclear factor, and plasma viscosity were comparable in patients with and without radiological abnormalities. Measurements of grip strength and finger-palm flexion also were similar in the two groups. However, in individual cases joint or tendon sheath disease was associated with loss of function.
Anti-ENA antibodies have been found in 176 sera which nearly all contained antinuclear antibodies giving a speckled pattern of nuclear fluorescence. The charts of 134 of these 176 patients were available for a thorough clinical study. Among these 134 patients, 59 had a well defined Connective Tissue Disease including 40 SLE, 31 had a limited clinical syndrome made of Raynaud's phenomenon, inflammatory polyarthritis, swollen fingers and hyperglobulinemia and 34 had a complex clinical picture associating signs of more than one connective tissue disease. Some of the patients in this third group could be considered as-having the Mixed Connective Tissue Disease (MCTD) described by Sharp et al. Anti-RNP antibodies were more common in this series than the other anti-ENA antibodies. However, no narrow specificity could be assigned to any of these antibodies. This is true of the non anti-RNP antibodies, the anti-Sm in particular, which were found in 49 patients of whom 32 had SLE existing alone or in association with features of other connective tissue diseases and 17 had another connective tissue disease or the afore-mentioned limited clinical syndrome. In any case, the anti-ECT antibodies never reach the diagnostic value of the anti-DNA antibodies.
A multicentre double-blind trial in general practice compared Butacote (enteric-coated phenylbutazone) 300 mg daily, ibuprofen 1200 mg daily, and a placebo in the treatment of rheumatic conditions. Each patient recieved two of the three treatments for one month each. Twenty-nine doctors admitted 193 patients. One hundred and sixty-eight patients (sixty-four with inflammatory polyarthritis, and sixty-three with osteoarthrosis) completed the study, which showed that Butacote was significantly better than both ibuprofen and placebo for the relief of pain and morning stiffness, and improvement of function. Butacote was significantly preferred to both ibuprofen and placebo by patients and doctors, to placebo by the patients. Ibuprofen was significantly better than placebo for relief of morning stiffness and for reducing the amount of supplementary analgesics. All three preparations were well tolerated and showed a similar incidence of gastric side-effects. It is concluded from this study that Butacote is more effective and as well tolerated as ibuprofen in the treatment of rheumatic conditions in general practice.
A double-blind trial compared diclofenac with placebo in 44 outpatients. On from each group dropped out with dyspepsia, and one (placebo group) with ineffective treatment. Twenty completers received diclofenac. Dosage was one tablet (25 mg diclofenac) three times daily during the first week. In the second (final) week, most patients had four or six tablets. Diclofenac had significantly greater effect on pain, grip, morning stiffness, joint tenderness and swelling, and in comparison to previous treatments, even though the placebo group required significantly more rescue anaglesic. A few patients in each group had slight dyspepsia. One in the active and six in the placebo group complained of minor central nervous system symptoms. There were no serious side-effects. Haematological, biochemical and urinary analyses showed no clinically important changes. It is concluded that, in the short term, diclofenac (Voltarol) is effective in relieving the symptoms of inflammatory polyarthritis. It is well tolerated as placebo medication, and had no detrimental haematological or biochemical effects.
The relationship of psoriasis and arthritis is controversial. It has been reported that 7 percent of patients with psoriasis have arthritis. In approximately half of these cases, it is a sero-negative inflammatory polyarthritis, two-thirds of which clinically resemble rheumatoid arthritis. A distinctive peripheral arthropathy is displayed by 1 percent of psoriatics. One-fifth of this group, or less than 0.2 percent of psoriatics, suffer deforming arthritis multilans. The epidemiologic, clinical, radiologic, serologic, and genetic evidence for and against psoriatic arthropathy as a unique entity are reviewed. The prognosis of psoriatic arthritis appears to be better than previously suggested. Therapeutic measures are also reviewed.
Description of a case presenting as an inflammatory polyarthritis. A uterine sarcoma was detected one year later and led to the death of the patient. The abnormal protein belonged to the gammal subclass. Biosynthesis experiments, performed on the marrow plasma cells, showed that light chains were not produced and that the molecular weight of the monomeric unit of the serum protein was slightly smaller than that of the protein secreted in vitro, suggesting the occurrence of a secondary and limited extracellular proteolysis.
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The arthritic activity in the initial phase and during manifestation of experimental erysipelas in rats, an animal model for human rheumatoid arthritis, was studied by plethysmometrical methods. The development of body weight and specific pathologic alterations peculiar to the model such as keratitis, thrombosis of the aorta and gangrene of the tip of the tail served as additional parameters. In the volumetric analysis it could be shown that the first arthritic swelling on both hind legs develops symmetrically up to day 6 post infection in rats with about 200 g of body weight-and in contrast-on the 2nd p.i. in younger animals with about 120 g. The first maximal paw volume was measured on day 9 p. i., the greatest decrease in body weight-a reduction of 25%-on day 10 p. i. In addition the reaction of the animal model following the application of steroid and non-steroid symptomatically as well as cytostatically acting antirheumatic drugs was tested. Daily treatment with acetylsalicylic acid, indomethacine or hydrocortisone provoked more or less significant inhibition of arthritic swelling in the paw. Only at the onset of arthritis acetylsalicylic acid was more effective than the other antiphlogistic drugs. No measurable increase of paw volume during cyclophosphamide treatment could be evaluated. None of the antirheumatics used had a positive effect on body weight developement. In hydrocortisone and also in cyclophosphamide treated rats a greater decrease was obtained than in the infected controls. No thrombosis developed after cytostasis with cyclophosphamide. The advantages of this systemic connective tissue disease with regard to its comparability with human rheumatoid arthritis and due to the course of its arthritic manifestation are discussed, together with the disadvantages specific to the model and the experimental conditions.