Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. Subsets of responses.

A comparison of placebo, auranofin, and parenteral gold sodium thiomalate therapy in 209 patients with active rheumatoid arthritis was performed in a 21-week prospective, controlled, double-blind multicenter trial. When the 161 patients who completed at least 20 weeks of treatment were analyzed for different degrees of response, no remissions were identified. When 50 percent or greater improvement of pain/tenderness scores were compared for end of trial versus entry values, 9 percent of placebo-treated patients, 34 percent of auranofin-treated patients, and 48 percent of gold sodium thiomalate-treated patients showed important improvement that was statistically significant for both gold treatments. When 50 percent improvement for joint swelling was analyzed, 12 percent of the placebo-treated group, 28 percent in the auranofin-treated group, and 37 percent in the gold sodium thiomalate-treated group showed this degree of improvement. Auranofin almost achieved statistical significance for improvement in joint swelling when compared with placebo (p = 0.07), but gold sodium thiomalate was much better than placebo (p = 0.009). There was no statistically significant difference between the two gold treatments. Thus it appears that a subset of patients had an important response to gold therapy that would not be evident by the usual analyses of mean or median changes. Analysis for predictors of response did not discriminate between responders and nonresponders. Because the trial was limited to 21 weeks of therapy, no prediction of the longer-term-effects, especially for auranofin, should be inferred.

Chlorambucil therapy in rheumatoid arthritis: clinical experience in 28 patients and literature review.

Our clinical experience in 28 patients receiving chlorambucil for rheumatoid arthritis (RA) and the reports on chlorambucil therapy are reviewed. Our study population and other reports generally represent patients with severe RA who had either failed to improve or developed significant toxicity during previous treatment with conventional slow acting anti-rheumatic drugs (SAARDs). Seventy-two percent of patients had a significant clinical improvement during chlorambucil therapy and reports of complete remission are given, although the incidence of remission is unknown. Hematologic complications are often reported, but appeared more frequently in our experience than previously reported. Hematologic toxicity required that chlorambucil be discontinued in the majority of our cases. Two deaths from suspected drug induced malignancies are reported. Although chlorambucil appears to be effective in the control of active RA, the potential for drug induced toxicity and malignancies may outweigh the benefit of continued use of this experimental therapy in RA.

Nodular nonsuppurative panniculitis associated with jejunoileal bypass surgery.

A 32-year-old woman underwent jejunoileal bypass surgery for morbid obesity. Her postoperative course was marked with many of the complications of this type of surgery. In addition, tender, erythematous nodules developed on her legs and abdomen that were grossly and microscopically consistent with nodular nonsuppurative panniculitis. She did not have any condition or disease previously reported to be associated with nodular nonsuppurative inflammation. The nodular panniculitis in this patient appears to be a new complication of small-bowel bypass surgery.

Second-line antirheumatic drugs in the elderly with rheumatoid arthritis: a post hoc analysis of three controlled trials.

This study assessed the relative efficacy and toxicity of second-line antirheumatic drugs in patients 65 years of age or older compared to younger counterparts. The results of three prospective, double-blind, parallel, randomized, multicenter trials were reanalyzed, stratifying outcomes by intervention and patient age. Efficacy was assessed by categorizing patient responses as follows: important improvement, no meaningful change, or progressive disease. Toxicity was analyzed by comparing withdrawal rates due to adverse effects. The three trials compared the following treatments: (1) D-penicillamine 10-12 mg/day versus azathioprine 1.25-1.5 mg/kg/day; (2) gold sodium thiomalate 50 mg intramuscularly weekly versus auranofin 6 mg/day versus placebo; and (3) pulse oral methotrexate 7.5-15.0 mg weekly versus placebo. At baseline, 103 patients age 65 or older were similar to 485 patients less than 65 years of age, with the exception of disease duration in all studies and erythrocyte sedimentation rate in one study. For patients completing each study, efficacy outcomes based on age were not significantly different. Withdrawal rates due to adverse drug reactions were also not significantly different.

Spontaneous nasal septal perforation in patients with rheumatoid arthritis.

Nasal septal perforation is known to be associated with various traumatic and disease states, yet spontaneous nasal septal perforation (SNSP) is relatively rare. SNSP has been reported in three patients with seropositive rheumatoid arthritis (RA) and we report an additional seven patients with SNSP and RA, four of whom were seronegative and none of whom had Raynaud's, in contrast to those reported previously. Manifestations of overt infectious, neoplastic or granulomatous disease have not been found in our seven patients over several years of close follow-up. We have identified no obvious pathogenesis or specific etiology for SNSP. We suggest that SNSP may represent an unusual manifestation of RA previously not well recognized.

Auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. Cooperative systematic studies of rheumatic diseases.

Two hundred eight patients were studied in a prospective, controlled, double-blind multicenter trial comparing auranofin (AUR), gold sodium thiomalate (GST), and placebo. One hundred sixty-one patients completed at least 20 weeks of therapy. Response to a variety of measures of efficacy was generally modest for both gold treatment groups although improvement was continuing in both groups at the end of the study. There was statistically significant improvement with both gold preparations compared to placebo for the number of tender joints, the joint tenderness score, and physician assessment of disease severity. GST was also significantly better than placebo for the joint swelling score. GST demonstrated more improvement in patients with anemia and thrombocytosis compared to the other treatment groups and both gold preparations were superior to placebo in improvement of an elevated erythrocyte sedimentation rate. Twenty-seven percent of patients on GST were withdrawn from the study for adverse drug reaction with rash and stomatitis being the predominant cause. Only 6% of patients on AUR were withdrawn for untoward drug effect. The time of onset of the adverse reactions is discussed. The two gold preparations were similar in efficacy although AUR was better tolerated.

Localized nodular synovitis of the knee: a case report.

A 25-year-old man with chronic swelling of the right knee had a mass that was eventually palpated in the suprapatellar pouch. Arthrotomy and biopsy revealed localized nodular synovitis. Since surgical excision of the mass the patient has been asymptomatic. While localized nodular synovitis generally appears as an internal derangement of the joint, this patient had signs and symptoms of chronic monoarthritis.

Joint pain of recent onset.

A joint pain of recent onset is a common and often challenging problem to the family physician. The many etiologies of acute arthritis require a systematic approach to a careful definition of the problem which is essential to safe and effective therapy. The proper evaluation of joint pain of recent onset requires a detailed history and physical examination as well as a rationally selected battery of laboratory studies. This paper provides the busy physician with a specific approach to the diagnosis of acute joint pain as the basis for precise management.

Arthrocentesis.

Aspiration of the synovial joints is an important part of the diagnostic and therapeutic armamentarium of the physician and may provide vital information that can be obtained in no other way. As with any other technique in medicine, skill and safety in the aspiration of joints can be acquired only through careful study and continued practice in arthrocentesis. When appropriate preparations and precautions are observed, obtaining fluid from synovial joints is safe, relatively pain free, inexpensive, and extremely beneficial to the patient.

Educational objectives in rheumatology for medical students.

Very little information is currently available with respect to what medical students should learn about clinical rheumatology, and an investigation was undertaken to determine what they should know in this area.

Experiment in an early admissions program at the University of Utah College of Medicine.

Thirty-one selected high school graduates were accepted into the College of Medicine prior to any college course work. The program was established to provide greater educational opportunity to the gifted student.

Hematologic and serologic studies in 6-sulfanilamidoindazole arthritis.

6-sulfanilamidoindazole (6-SAI), an antibacterial sulfonamide, is known to cause an acute, self-limited inflammatory reaction in the hind paws of older rats. Administration of 6-SAI results in hyperfibrinogenemia which precedes the onset of clinical arthritis. The hyperfibrinogenemia is associated with the prolongation of dilute blood clot lysis times, appearance of heparin-precipitable fibrinogen, elevations in fibrin degradation products, and complement titers and serum electrophoretic pattern changes that consist of decreased albumin concentrations and increased beta globulin concentrations. Alterations in 6-SAI medicated young rats are less marked and require higher doses.

Rheumatology. What should students know?

The majority of patients with rheumatologic problems are seen and followed by nonrheumatologists. Of concern is the perception that a significant number of United States medical schools do not have adequate teaching programs in the rheumatic diseases. Two thousand two hundred and seventy practicing physicians, trainees, and medical students were surveyed in the Intermountain West to determine what they think undergraduate medical students should learn about rheumatology. Most respondents felt that common diseases and problems should be emphasized and that basic skills in history taking and physical examination are more important than disease related information.

Familial brachydactyly and chondrocalcinosis. Report of a patient, pedigree and review of the literature.

Familial brachydactyly has been recognized for many years but no published accounts report associated chondrocalcinosis. We recently evaluated such a patient and report the occurrence of brachydactyly in 4 generations of his kindred. The pattern of brachydactyly in this pedigree suggest autosomal dominant inheritance that is the mode of inheritance in most kindreds. The prepositus with chondrocalcinosis has longstanding arthralgias of both knees as does at least one other close relative who also has brachydactyly. The possibility that chondrocalcinosis may be part of the syndrome is suggested but awaits further clarification.

Normal erythrocyte sedimentation rate with hyperfibrinogenemia in 6-sulfanilamidoindazole arthritis.

The erythrocyte sedimentation rate (ESR) is the most frequently employed laboratory indicator of inflammatory activity. The plasma fibrinogen concentration is usually increased in inflammatory disorders and is thought to contribute to the ESR elevation, 6-sulfanilamidoindazole induced arthritis in rats produces very high plasma fibrinogen concentrations and increased blood viscosity but no change in ESR.