Nitritoid reactions: case reports, review, and recommendations for management.

OBJECTIVE: We assessed nitritoid reactions, which are a well recognized side effect of chrysotherapy that occur in roughly 5% of patients taking gold sodium thiomalate (GST). METHODS: Between January 1996 and January 2000, 8 patients followed in our gold monitoring program at Mary Pack Arthritis Centre experienced nitritoid reactions observed by the clinic nurse. We undertook a chart review to determine the risk factors, timing, course, and outcome of nitritoid reactions. RESULTS: Patients' ages ranged from 36 to 69 years, and 7 of 8 were women. Duration of gold therapy prior to nitritoid reactions ranged from 13 months to 13 years. Seven had previously had mucocutaneous reactions, and one experienced gold dermatitis following a nitritoid reaction. Two of 8 patients were taking angiotensin converting enzyme inhibitor agents. Seven reactions were classified as mild, and one was a severe reaction with hypotension, syncope, and angina. CONCLUSIONS: Management includes a high index of suspicion in patients experiencing nausea, flushing, or dizziness following gold injections, switching from GST to gold sodium aurothioglucose, injection in the recumbent position, and observation for 20 minutes after injections in individual patients.

Current and emerging therapies for rheumatoid arthritis, with a focus on infliximab: clinical impact on joint damage and cost of care in canada.

BACKGROUND: Rheumatoid arthritis (RA) is a physically debilitating disease that places an enormous burden not only on individuals and their families but also on the economy. Affecting -1% of the Canadian population, RA is characterized by pain and swelling of joints. Without effective treatment, RA results in joint destruction that often requires surgery. OBJECTIVE: This review summarizes the effect of current and new RA treatments on joint damage, with a focus on infliximab. The health-economic repercussions and potential impact of arresting the joint destruction of RA are discussed. METHODS: Information for inclusion in this review was identified through searches of the MEDLINE and HealthStar databases from 1995 to 2000. Search terms included rheumatoid arthritis, treatment guidelines, economics, and individual drug names. RESULTS: Standard initial RA drug therapy has been aimed at reducing pain and inflammation, whereas use of the more potent disease-modifying antirheumatic drugs (DMARDs) has been reserved for later stages of disease. More aggressive RA treatment involves introducing DMARDs at the earliest stage. The largest single direct cost of RA involves hospital admissions for the correction of joint deformities. Among newer therapies, the anti-tumor necrosis factor-alpha agent infliximab has been shown to arrest radiographic measures of disease progression. CONCLUSIONS: With early and aggressive treatment involving new drugs and drug combinations, it may be possible to ameliorate the physical, social, and economic effects of RA.

Longterm therapy of psoriatic arthritis: intramuscular gold or methotrexate?

OBJECTIVE: To compare the efficacy and toxicity of methotrexate (MTX) and intramuscular (im) gold in the treatment of psoriatic arthritis (PsA). METHODS: Medical records from all patients with PsA attending the gold and MTX clinics at the Vancouver Mary Pack Arthritis Centre between 1971 and 1995 were reviewed. The odds of a clinical response (defined as at least a 50% reduction in active joint count from initial to last visit or for at least 6 months) and the relative risk of discontinuing therapy associated with treatment (MTX or im gold) were calculated after controlling for significant baseline covariates, using logistic regression and Cox regression analyses, respectively. The frequency of side effects and the reasons for treatment cessation were also compared between treatment groups. RESULTS: Eighty-seven patients received 111 treatment courses: 43 of MTX and 68 of im gold. The likelihood of a clinical response was 8.9 times greater (95% CI 1.8; 44.0) with MTX than im gold. Patients were 5 times more likely (95% CI 2.4; 10.4) to discontinue therapy with im gold than with MTX. No major toxicity occurred and frequency of side effects was similar for both treatments. Patients with a longer duration of PsA prior to initiation of study treatment were less likely to achieve a clinical response. CONCLUSION: MTX and im gold are safe and well tolerated in the treatment of PsA. In our experience. MTX was superior to im gold in the likelihood of achieving a clinical response and in permitting an individual to continue longterm treatment. Our data suggest that earlier treatment may be associated with a better response.

Safety of self-injection of gold and methotrexate.

OBJECTIVE: We review our experience with safety, efficacy, and practicality of self-administration of gold and methotrexate (MTX) in 40 patients. METHODS: Between 1992 and 1995, 40 patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) followed in the drug monitoring clinics of the Mary Pack Arthritis Centre were taught to self-administer parenteral gold or MTX. Self-injection education was recommended to patients who were stable and improved taking parenteral gold or MTX, and who had not experienced serious side effects. Charts were reviewed to extract and analyze prospectively collected data regarding safety, efficacy, and compliance. RESULTS: Sixty-five percent of patients performed self-injection and 35% received injections at home from a partner. Side effects in the self-injection patients are similar to those observed in clinic patients receiving drug by nurse administration. One MTX treated patient required treatment for interstitial pneumonitis, which developed after 22 weeks on self-injection. Side effects of self-injection included superficial irritation at the injection site in 2 patients and dosing error in 2 patients with no adverse effects. Seventy percent of gold and MTX treated patients continued self-injection after a mean of 34 months. Patients surveyed for satisfaction identified time saving and convenience as major benefits. CONCLUSION: With basic instruction and close supervision, self-injection of antirheumatic drugs is safe in selected patients. Self-injection reduces utilization of health care services, and is convenient and time and cost-saving to the patient.

Hemorrhagic complications of long-term anticoagulant therapy in 7 patients with systemic lupus erythematosus and antiphospholipid syndrome.

OBJECTIVE: To describe the presentation, course, and management of serious hemorrhagic complications of anticoagulant therapy for patients with antiphospholipid syndrome (APS). METHODS: Charts of patients identified with serious bleeding complications from anticoagulation for APS were reviewed. RESULTS: Patients included 6 women and one man with systemic lupus erythematosus (SLE) and one woman with primary APS. One patient had 3 separate hemorrhagic events. There were 6 episodes of subdural hematoma in 5 patients, one episode of pericarditis with tamponade, one episode of hemoptysis, and one episode of ovarian hemorrhage. In 2 patients, symptoms related to hemorrhage were initially attributed to active SLE. Duration of anticoagulation was between one month and 10 years at the time of bleed. International normalized ratio (INR) and prothrombin time were above the intended range in 6/9 episodes. There were no deaths and no permanent sequelae due to bleeding. Anticoagulant therapy was resumed in 6/7 patients. CONCLUSION: The management of APS must include vigilance, patient education, and anticoagulation to maintain the INR between 3 and 3.5. To prevent hemorrhagic complications, low molecular weight heparin is an option that deserves further study.

Reinstitution of gold after gold induced proteinuria.

OBJECTIVE: To assess the benefits and risks to patients who resumed gold after discontinuation of gold because of proteinuria. METHODS: We conducted a review of records of all patients who had resumed gold after discontinuing treatment because of proteinuria. RESULTS: Eight patients developed proteinuria > or = 500 mg/dl while receiving 50 mg weekly doses in the first year of treatment. Proteinuria took a minimum of 4 mo to resolve. No patient had a recurrence of proteinuria when gold was resumed at a lower dosage of 25 mg every 1-2 weeks. This strategy has been successful in 5/8 patients who continue taking gold and are markedly improved compared to pretreatment status after 3-7 years (mean 5 years) of followup. CONCLUSION: The risk of gold induced proteinuria may be dose related and reinstitution of gold at a lower dose is safe in our experience and effective in selected patients.

Treatment of progressive rheumatoid interstitial lung disease with cyclosporine.

A 62-year-old man with longstanding rheumatoid arthritis (RA) presented with dyspnea. Active rheumatoid interstitial lung disease was documented by high resolution computed tomography, gallium scan, and bronchoalveolar lavage. He responded to high dose prednisone, but had unacceptable side effects. Chlorambucil and cyclophosphamide were not steroid sparing. After starting cyclosporine 3 mg/kg/day he was able to stop prednisone and his symptoms improved and stabilized. Pulmonary function showed sustained improvement during 2 years of followup. His RA has been well controlled. Side effects have been mild hypertension and increased serum creatinine.

The second course of gold.

OBJECTIVE: To determine the outcomes in patients who receive more than one course of intramuscular gold therapy. METHODS: Gold clinic records of all patients who had received more than one course of gold at the Arthritis Centre, Vancouver, British Columbia were reviewed to extract clinical and laboratory data. RESULTS: Between 1949 and 1992, 1148 patients received injectable gold in the gold clinic of the Arthritis Centre, Vancouver, British Columbia. Forty-two patients received 2 courses and 3 patients 3 courses of gold separated by intervals of greater than 8 months. Twenty-one patients were markedly improved when the first course of gold was discontinued. Twenty of these 21 patients experienced a similar marked improvement from a 2nd course of gold. Three patients who received 3 courses had marked improvement with each course. Only 1 patient who experienced marked improvement with the first course of gold failed to respond to a 2nd course. CONCLUSION: In contrast to the published literature, our experience suggests that the response to the 2nd course of gold is similar to the response to the first in most patients with arthritis.

How low can you go? Use of very low dosage of gold in patients with mucocutaneous reactions.

OBJECTIVE: We identified a group of patients with rheumatoid arthritis (RA) who were sensitive to both the beneficial and the side effects of intramuscular (im) gold treatment and whose disease was well controlled with doses of gold between 2 mg every 6 weeks and 5 mg weekly. We describe the clinical course of these patients and their management aimed at maximizing the effectiveness of gold therapy. METHODS: Patients successfully treated with maintenance doses of im gold (< 20 mg/mo and not more than 10 mg/dose) were identified by chart review. Clinic records were reviewed to extract clinical and laboratory data. RESULTS: The population consisted of 11 female and 2 male patients with RA. Eleven were seropositive and 2 had Felty's syndrome. All developed mucocutaneous side effects within 20 weeks of beginning im gold therapy, at a time when RA had improved markedly compared to pretreatment status. Side effects recurred with sequential dosage adjustments so that doses > 10 mg were not tolerated. Side effects were managed by temporary discontinuation of gold until side effects resolved and resumption of treatment using usually 50% lower dosage. When side effects recurred the dosage was reduced further by 50%. Final maintenance dose was 2 mg every 4 weeks in 1 patient, 2 mg weekly in 1, 3 mg weekly in 3, 5 mg monthly in 1, 10 mg every 3 weeks in 2, 10 mg every 4 weeks in 2, 10 mg every 6 weeks in 1, and 5 mg weekly in 2 patients. All patients improved and 6 are in complete remission. Mean duration of therapy was 5.5 yrs. CONCLUSION: The minimum effective dose of im gold is not known. Dose and dose intervals should be individualized for optimal benefits and tolerability.

An electronic method for measuring joint tenderness in rheumatoid arthritis.

OBJECTIVE: To test the precision of a new electronic method for measuring joint tenderness. METHOD: Joint tenderness was measured in 30 patients with rheumatoid arthritis, using an electronic dolorimeter. The results were compared with joint tenderness counts, which were made according to the American Rheumatism Association (ARA) methods. RESULTS: The intra-observer variability using the electronic method was significantly decreased compared with the conventional ARA joint tenderness counts. CONCLUSION: The electronic method is more efficient for use in clinical trials than is the conventional ARA joint tenderness count.

Low-dose cyclosporin versus placebo in patients with rheumatoid arthritis.

144 patients with severe rheumatoid arthritis from six centres were randomised to receive oral cyclosporin or placebo for 6 months. The initial daily dose of cyclosporin was 2.5 mg/kg, which was increased cautiously with monitoring of serum cyclosporin levels and creatinine; the mean stabilisation dose was 3.8 mg/kg. There were significant improvements in the cyclosporin-treated patients compared with the controls in the major outcomes of reduction of active joints (23% improvement), pain (24%), and functional status (16%); global improvement was 27%. In the cyclosporin group serum creatinine increased by a mean of 15.6 mumols/l and mean arterial blood pressure by 6.27 mmHg; these increases were controlled in all but 2 patients by dose adjustment without withdrawal from the study.

Pilot study of etretinate in psoriatic arthritis.

A 2-center pilot study compared clinical and laboratory outcomes in 40 patients with psoriatic arthritis before and after treatment for 8 to 24 weeks with the vitamin A derivative, etretinate. The number of tender joints fell from 22.0 +/- 8.75 before treatment to 11.44 +/- 8.50 after treatment (p = .000). The duration of morning stiffness was 101.95 +/- 62.45 min before therapy and 44.53 +/- 82.10 min after treatment (p = 0.0004). Similar highly clinically and statistically significant improvement was seen in all clinical outcome measures and in the erythrocyte sedimentation rate. Primarily mucocutaneous side effects were seen in 39/40 patients and resulted in treatment termination before 24 weeks in 9 patients.

An experiment in reducing interobserver variability of the examination for joint tenderness.

This experiment was designed to test the feasibility of reducing interobserver variability of the joint examination by agreement on a standard examination. Six rheumatologists independently examined 6 patients with rheumatoid arthritis (RA) in predetermined order, before and after a standardization of examination techniques. Results of an analysis of variance showed a reduction of the percent of variability due to observers from 13.8%, before standardization, to 3.2% after standardization, and an improvement in the percent variability related to patient differences from 70.7%, before standardization, to 86.3% after standardization. Such a reduction in observer variability has a potential for allowing a reduction in sample sizes required for RA clinical trials.

Retinopathy in systemic lupus erythematosus: relationship to disease activity.

Forty-three patients taking chloroquine for systemic lupus erythematosus were followed by one ophthalmologist over a 5-year period. Visual field testing, color vision testing, and fluorescein angiography were performed. Retinopathy was detected in 7 patients (16%), none of whom had hypertension or diabetes mellitus. Retinal abnormalities included cotton-wool spots in 4 patients, microaneurysms in 3, and vascular tortuosity in 4. In 4 patients, these abnormalities were associated with retinal dysfunction, measured in terms of abnormal hue discrimination. In 6 of the 7 patients, the finding of retinopathy coincided with a flare of lupus activity. In 5 patients, retinopathy improved when the disease was controlled.

M-mode and two-dimensional echocardiographic abnormalities in systemic lupus erythematosus.

A prospective clinical and echocardiographic study of 47 patients with systemic lupus erythematosus (SLE) and 46 age- and sex-matched controls showed an increased prevalence of echocardiographic abnormalities in the SLE group. Pericardial abnormalities were identified in ten patients with SLE and in no controls. Excluding mitral valve prolapse, valvular abnormalities were identified in ten patients with SLE (21%) and in three controls (7%). In the patients with SLE, abnormalities included mitral valve leaflet thickening in six, aortic valve thickening in five, and mitral annular calcification in two. The presence of valvular abnormalities correlated with duration but not with severity of SLE. The finding of systolic murmurs in 17 of 47 patients with SLE did not correlate with echocardiographic evidence of valvular disease. In six patients with SLE, valvular abnormalities detected by two-dimensional echocardiography were not seen on M-mode echocardiogram.

Coccidioidomycosis tenosynovitis: case report and review of the literature.

Coccidioidomycosis tenosynovitis is an unusual rheumatological manifestation of Coccidioides immitis infection. We report a case in a 46-year-old man with leukemia. The literature is reviewed and the treatment discussed.