Arthritis & Rheumatism

Kremer, Joel M.; Lee, Joong K.

doi: 10.1002/art.1780310501pmid: 3288222

Twenty‐five patients have completed a mean of 53 months of treatment with methotrexate (MTX) as part of a prospective study of the long‐term safety and efficacy of the drug. Since the times of the last report (at a mean of 29 months), the mean dosage of MTX has increased from 12.4 mg/week to 14.6 mg/week, whereas the mean prednisone dosage has decreased from a baseline of 7.1 mg/day to 1.9 mg/day. A significant improvement from baseline in all clinical parameters tested was maintained, and response to therapy did not vary significantly between the assessment at 29 months and that at 53 months. Toxic reactions were as common during months 30–53 as during the first 29 months of the study, with patterns of toxic reactions remaining consistent within each patient. Radiologic evidence of disease progression was not seen before 24 months of MTX treatment, but after this time, it was observed in some patients. We conclude that many clinical features of long‐term MTX therapy are distinctly different from what might have been expected after the short‐term trials.

Hafström, Ingiäld; Ringertz, Bo; Gyllenhammar, Hans; Palmblad, Jan; Harms‐Ringdahl, Mats

doi: 10.1002/art.1780310502pmid: 2837251

Fourteen patients with rheumatoid arthritis (RA) were studied before, during, and after a 1‐week total fast. Disease activity decreased, as did the neutrophil release of lysozyme induced by the ionophore A23187. The ability of zymosan‐activated RA patient serum to aggregate control neutrophils was reduced, together with serum concentrations of C3. The relative contents of arachidonic acid and eicosapentaenoic acid were increased in serum, platelets, and neutrophils, whereas levels of linoleic acid and linolenic acid were unchanged. Fasting also reduced the release of leukotriene B4 from neutrophils. We thus conclude that a reduced ability to generate cytotaxins, reduced release of enzyme, and reduced leukotriene formation from RA neutrophils, together with an altered fatty acid composition of membrane phospholipids, may be mechanisms for the decrease of inflammatory symptoms that results from fasting.

Parker, Jerry C.; Frank, Robert G.; Beck, Niels C.; Smarr, Karen L.; Buescher, Keith L.; Phillips, Les R.; Smith, Elaine I.; Anderson, Sharon K.; Walker, Sara E.

doi: 10.1002/art.1780310503pmid: 2454118

To examine the effectiveness of a cognitive‐behavioral pain management program for patients with rheumatoid arthritis, three patient groups were studied: a cognitive‐behavioral group (CB), an attention‐placebo group, and a control group. The CB group received a comprehensive, 12‐month pain management program that taught coping strategies such as problem‐solving techniques, relaxation training, strategies for attention diversion, and training in family dynamics and communication. Dependent measures included pain, coping strategies, psychological status, functional status, and disease status. Data analysis at 12 months revealed benefits for the CB group in the area of enhanced coping strategies. Specifically, the CB subjects showed significantly greater use of coping strategies and significantly more confidence in their ability to manage pain. The findings are discussed in terms of the importance of enhanced self‐efficacy and personal control for patients with rheumatoid arthritis.

Stabrun, Anne E.; Larheim, Tore A.; Höyeraal, Hans M.; Rösler, Marek

doi: 10.1002/art.1780310504pmid: 3377867

The pathogenesis of reduced mandibular dimensions and asymmetry was studied in 103 patients with juvenile rheumatoid arthritis. Abnormalities of the temporomandibular joint were intimately related to mandibular growth disturbances. Unilateral joint abnormality resulted in jaw asymmetry and underdevelopment on the affected side. Duration of disease and of corticosteroid therapy, age at disease onset, and age when the data were recorded were correlated with the size of the mandible. Our findings did not support a hypothesis of cervical spine involvement as an etiologic factor of reduced mandibular size.

Rothenberg, R. J.; Graziano, F. M.; Grandone, J. T.; Goldberg, J. W.; Bjarnason, D. F.; Finesilver, A. G.

doi: 10.1002/art.1780310505pmid: 3288223

Although the use of methotrexate (MTX) is gaining acceptance in the treatment of several connective tissue diseases, there is little evidence of its therapeutic value in systemic lupus erythematosus (SLE). We examined the response to MTX in patients with steroid‐resistant SLE in an open, unblinded study. Of 10 SLE patients treated with MTX (7.5 mg/weekly), 7 showed improvement. The other 3 stopped therapy because of lack of response or because of side effects. Improvements were noted within 3 months in responding patients. These promising observations suggest that controlled studies of MTX for the treatment of SLE are justified.

Netter, Hans Jürgen; Guldner, Hans Herbert; Szostecki, Carin; Lakomek, Heinz‐Jürgen; Will, Hans

doi: 10.1002/art.1780310506pmid: 2454119

A human liver complementary DNA expression library was screened using sera from patients with high titers of autoantibodies, to search for clones expressing major autoantigens that are relevant in connective tissue diseases. One of the clones isolated expressed a major epitope(s) that was immunoreactive with anti‐U1 RNP sera, as shown by several techniques. Affinity‐purified autoantibodies from the cloned RNP protein specifically recognized the 68‐kd U1 RNP protein of HeLa cell nuclear extracts. All sera containing anti‐U1 RNP antibodies detected by immunodiffusion, counterimmuno‐electrophoresis, or immunoblotting also recognized the cloned RNP protein. The RNP antigen‐expressing bacterial colonies and the partially purified cloned RNP fusion protein have been applied to fast and sensitive immunologic assays for the detection and quantification of anti‐U1 RNP antibodies.

Robbins, Mark L.; Kornguth, Steven E.; Bell, Carolyn L.; Kalinke, Tom; England, Douglas; Turski, Patrick; Graziano, Frank M.

doi: 10.1002/art.1780310507pmid: 3377868

We used Western blot analysis to examine the occurrence and titer of antibody to cytoskeletal neurofilament protein antigens in patients with neuropsychiatric manifestations of systemic lupus erythematosus (SLE) and in controls. Twenty‐two patients with neuropsychiatric SLE (NPSLE) had an increased incidence of antineurofilament antibody (ANFA) compared with 34 patients with SLE without neuropsychiatric symptoms, 78 patients with other disease processes, and 22 healthy controls. ANFA were found to be directed against the 205,000‐ and 160,000‐dalton proteins of the neurofilament triplet. Patients with a diffuse NPSLE clinical presentation had the greatest frequency of serum ANFA (7 of 12, 58%) compared with all other groups examined. Magnetic resonance imaging and serum anticardiolipin antibody testing were also performed in selected patients with NPSLE. Patients with a focal clinical presentation of NPSLE, positive magnetic resonance imaging findings, and negative serum ANFA had significantly elevated levels of anticardiolipin antibody.

Hopkins, Patricia; Michael Belmont, H.; Buyon, Jill; Philips, Mark; Weissmann, Gerald; Abramson, Steven B.

doi: 10.1002/art.1780310508pmid: 3259882

We measured levels of complement anaphylatoxin split products, C3a and C5a, in the circulation of patients with systemic lupus erythematosus (SLE). In 23 SLE patients who were followed serially, the mean C3a value was 179 ng/ml during stable disease and 550 ng/ml during a disease flare. In 10 patients, C3a levels predicted disease activity, with the C3a value rising from a mean of 183 ng/ml at a time of stable disease to a mean of 242 ng/ml 1–2 months prior to a clinical exacerbation of disease. The mean C3a level in 5 patients with acute dysfunction of the central nervous system (CNS) was 1,297 ng/ml, which is significantly higher than that observed in patients with active disease but without CNS involvement (P < 0.01). C5a levels were also significantly elevated in 4 patients with acute CNS disease. Pathologic specimens from 2 patients who died during an acute lupus flare revealed neutrophils occluding the cerebral and intestinal vessels. Fluorescein angiography in a patient with CNS lupus revealed vasoocclusive retinopathy. In 5 of 7 SLE patients who were pregnant, C3a levels were elevated, with a group mean value of 310 ng/ml. There was a negative correlation (r = – 0.59) between C3a and C3 levels in pregnant patients with SLE, and this finding is consistent with complement activation as the cause of decreasing C3 levels. We suggest that serial measurements of C3a can predict flares of disease in lupus patients and can demonstrate complement activation during pregnancy in women with SLE. In addition, release of C3a and C5a (mediators of inflammation) into the circulation may elicit vascular injury, particularly in patients with lupus cerebritis.

Dauphinée, Michael; Tovar, Zair; Talal, Norman

doi: 10.1002/art.1780310509pmid: 3259883

In this investigation of B cells expressing the CD5 (Leu‐1) cell surface marker, we found increased numbers of these cells in 13 of 19 patients with primary Sjögren's syndrome (SS) (68%), as well as in the rheumatoid arthritis patients. The percentage of B cells that demonstrated increased expression of CD5 was 46% in SS patients, 47% in rheumatoid arthritis patients, 24% in systemic lupus erythematosus patients, and 26% in normal subjects. Over a 2‐year period, CD5 expression on B cells was a stable finding in several patients, except for 2 who required either steroid therapy or combined chemotherapy and irradiation for malignant lymphoma. Both of these patients had clinical remissions and their levels of CD5+ B cells returned to normal. The first patient had a clinical picture of SS/systemic lupus erythematosus overlap, associated with polyclonal B cell activation and decreased production of interleukin‐2 in response to stimulation with phytohemagglutinin. These cellular immune abnormalities returned to normal after the institution of corticosteroids. Our observations suggest a relationship between the CD5+ B cell abnormality and disease activity. The results are discussed in relation to immunoregulatory properties of CD5+ B cells in autoimmune mice and the characteristic predisposition to malignant lymphoma among SS patients.

Sweet, M. Barry E.; Coelho, Angelina; Schnitzler, Christine M.; Schnitzer, Thomas J.; Lenz, Mary Ellen; Jakim, Itzhak; Kuettner, Klaus E.; Thonar, EUGENE J.‐M. A.

doi: 10.1002/art.1780310510pmid: 2967706

Serum levels of keratan sulfate (KS), measured by an enzyme‐linked immunosorbent–inhibition assay, were found to be significantly higher in 31 patients with hypertrophic osteoarthritis (OA) than those in 41 adults without joint disease. Seventy‐seven percent of patients with OA, but only 12% of control subjects, had serum levels which were more than 1 SD above the mean of the control group. Following replacement of a single osteoarthritic hip joint, serum KS levels decreased, at first, in all patients. Subsequently, the concentration of serum KS progressively increased; 6 months following surgery, KS levels were similar or close to the preoperative levels in virtually all patients. The results suggest that patients with hypertrophic OA may have a generalized imbalance of cartilage proteoglycan metabolism. Measurements of serum KS are likely to prove most useful in studying this particular subset of patients with generalized OA.