Antimalarial drugs in the treatment of rheumatological diseases.
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Antimalarials↗
Biomedical subjects
R I Rynes
Publications and source records attributed to R I Rynes.
Ophthalmologic considerations in using antimalarials in the United States.
Ophthalmologic considerations continue to be important in the use of antimalarials. In the United States, hydroxychloroquine is prescribed much more frequently than chloroquine. Despite the favorable safety record, potential retinal problems cause patients to often be afraid to take antimalarial medicine. Ophthalmologic visits are recommended every three months by the drug manufacturer, but most often are scheduled every six months by physicians. Ophthalmologic examination includes questioning about visual symptoms, visual acuity tests, careful fundoscopic evaluation and a visual field assessment. Amsler grid self evaluation is not yet wide-spread.
Antimalarials↗
Every-other-week methotrexate in patients with rheumatoid arthritis. A double-blind, placebo-controlled prospective study.
OBJECTIVE: To determine if patients with rheumatoid arthritis (RA) that is stable with weekly methotrexate (MTX) therapy could be switched to an every-other-week regimen of MTX. METHODS: Forty-seven patients with classic or definite RA who had received MTX for at least 8 months were studied. Clinical measurements consisted of the number of tender and swollen joints, physician and patient global evaluation of disease activity on a 5-point scale, grip strength, patient evaluation of pain, morning stiffness, and the interval to onset of fatigue from time of awakening. Laboratory measures included the erythrocyte sedimentation rate (ESR), rheumatoid factor, C-reactive protein (CRP), and baseline serum folate levels. Uptake of MTX was measured with tritiated thymidine from peripheral blood mononuclear cells (PBMC) from patients ex vivo. Serum measures of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF alpha) were performed in sera, and TNF alpha was also measured on PBMC supernatants. RESULTS: Twelve of the 23 patients receiving every-other-week MTX (52%) were able to complete 6 months of this treatment without experiencing a disease flare. Eleven of the 23 patients receiving every-other-week MTX (48%) withdrew from the study before completing 6 months of treatment, because of a flare. No significant differences in clinical or laboratory parameters were seen when the 24 patients receiving weekly MTX were compared with the 12 patients in the every-other-week MTX group who successfully completed 6 months of the study. None of the changes in serum cytokine levels were significantly different between the patients receiving MTX weekly versus those receiving it every other week, and changes in ESR and CRP did not differ between groups. Age, sex, RA disease duration, MTX weekly dose or duration, baseline joint counts, or serum folate status did not predict a flare. Tritiated MTX uptake did not differ between groups. CONCLUSION: Some patients with RA that is stable on weekly dosing are able to change to every-other-week dosing without experiencing a flare in their disease activity.
Aged↗
Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Clinical and immune correlates.
OBJECTIVE: To determine the following: 1) whether dietary supplementation with fish oil will allow the discontinuation of nonsteroidal antiinflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA); 2) the clinical efficacy of high-dose dietary omega 3 fatty acid fish oil supplementation in RA patients; and 3) the effect of fish oil supplements on the production of multiple cytokines in this population. METHODS: Sixty-six RA patients entered a double-blind, placebo-controlled, prospective study of fish oil supplementation while taking diclofenac (75 mg twice a day). Patients took either 130 mg/kg/day of omega 3 fatty acids or 9 capsules/day of corn oil. Placebo diclofenac was substituted at week 18 or 22, and fish oil supplements were continued for 8 weeks (to week 26 or 30). Serum levels of interleukin-1 beta (IL-1 beta), IL-2, IL-6, and IL-8 and tumor necrosis factor alpha were measured by enzyme-linked immunosorbent assay at baseline and during the study. RESULTS: In the group taking fish oil, there were significant decreases from baseline in the mean (+/- SEM) number of tender joints (5.3 +/- 0.835; P < 0.0001), duration of morning stiffness (-67.7 +/- 23.3 minutes; P = 0.008), physician's and patient's evaluation of global arthritis activity (-0.33 +/- 0.13; P = 0.017 and -0.38 +/- 0.17; P = 0.036, respectively), and physician's evaluation of pain (-0.38 +/- 0.12; P = 0.004). In patients taking corn oil, no clinical parameters improved from baseline. The decrease in the number of tender joints remained significant 8 weeks after discontinuing diclofenac in patients taking fish oil (-7.8 +/- 2.6; P = 0.011) and the decrease in the number of tender joints at this time was significant compared with that in patients receiving corn oil (P = 0.043). IL-1 beta decreased significantly from baseline through weeks 18 and 22 in patients consuming fish oil (-7.7 +/- 3.1; P = 0.026). CONCLUSION: Patients taking dietary supplements of fish oil exhibit improvements in clinical parameters of disease activity from baseline, including the number of tender joints, and these improvements are associated with significant decreases in levels of IL-1 beta from baseline. Some patients who take fish oil are able to discontinue NSAIDs without experiencing a disease flare.
Anti-Inflammatory Agents, Non-Steroidal↗
Exercise for rheumatoid arthritis.
The approach to treating rheumatoid arthritis is changing. Greater emphasis on the exercise component of physical therapy can improve patients' muscle strength, endurance, and emotional well-being, and may even result in decreased joint inflammation.
Arthritis, Rheumatoid↗
Toxicity of antimalarial drugs in rheumatoid arthritis.
Antimalarials have the lowest incidence of toxicity among the disease modifying antirheumatic drugs (DMARDs). Low daily dose and regular ophthalmologic examination has minimised potential retinopathy. Some toxicity may be related to the lysosomotropic action of antimalarials. DMARD toxicity may affect the variability in response to antirheumatic drugs.
Antimalarials↗
Ophthalmologic safety profile of antimalarial drugs.
The ophthalmologic safety of antimalarial drugs is well established, but absolute safety cannot be assured. Three types of side effects may develop. Corneal deposits and neuromuscular-associated blurred vision are always reversible and therefore benign. Visual loss has occurred in patients with retinopathy. Retinopathy may be divided into true retinopathy and premaculopathy. It is true retinopathy that may be associated with visual loss, while premaculopathy consists of subtle visual field and funduscopic abnormalities. These premaculopathic changes are generally completely reversible with drug discontinuation and have not been shown to progress. Hydroxychloroquine appears safer than chloroquine when currently accepted equivalent doses are used. Fewer than 20 patients with true retinopathy caused by hydroxychloroquine have been reported; more patients have developed true retinopathy when taking chloroquine. The safety profile is most dependent on low daily dose and regular ophthalmologic monitoring. The optimal strategy of ophthalmologic testing has not yet been determined, but visual acuity, funduscopic examination and visual field examination should be monitored. Self-administered ophthalmologic testing with Amsler grids may contribute additional safety but is not a replacement for physician testing.
Antimalarials↗
Painful rheumatic syndromes associated with human immunodeficiency virus infection.
Severe pain is a prominent characteristic of many rheumatic conditions occurring in patients with human immunodeficiency virus (HIV) infection. These conditions may affect joints or soft tissues. Some painful syndromes, such as acquired immune deficiency syndrome-associated arthritis, may be unique to HIV-infected individuals, whereas others, such as Reiter's syndrome, may also occur in patients without HIV infection but appear more severe in infected patients. Joint and soft tissue pain is usually most intense in the lower extremities. The pathogenesis of the pain is not completely understood but may involve subclinical neuropathic disease.
HIV Infections↗
Hydroxychloroquine treatment of rheumatoid arthritis.
A variety of placebo-controlled and open studies have demonstrated the effectiveness of hydroxychloroquine in the treatment of rheumatoid arthritis. The excellent responses to recurrent treatment in a sample patient illustrate the value of hydroxychloroquine. Because low daily doses of hydroxychloroquine are associated with greater ophthalmologic safety, it would be advantageous to use the smallest effective daily dose, but there are no published controlled efficacy studies using daily doses of less than 400 mg. Hydroxychloroquine may best be employed to treat patients with new onset of disease or those in whom disease is not rapidly progressive. Great potential exists for the use of hydroxychloroquine in combination therapy, but optimal utilization of combination regimens will require performances of additional controlled studies.
Anti-Inflammatory Agents↗
Acquired immunodeficiency syndrome-associated arthritis.
A subacute, oligoarthritic syndrome developed in four patients with human immunodeficiency virus (HIV) infection. Three had true acquired immunodeficiency syndrome (AIDS) and all had lymphocyte abnormalities. The arthritis was characterized by extreme pain and disability in three patients and moderate pain in one. Knees and ankles were affected. Symptoms developed over a one- to six-week interval; response to treatment was rapid, especially to intra-articular corticosteroids. Despite the clinical severity of the arthritis, synovial fluids were non-inflammatory and biopsy specimens revealed only mild chronic synovitis. A definite etiology could not be established. None of the patients had recognized infections predisposing to reactive arthritis, and the three patients who underwent tissue typing were HLA-B27-negative. A viral infection, including HIV, is a possible cause. In distinction to these four patients, arthritides with clearly established etiologies developed during this same time period in four other HIV-infected patients.
Acquired Immunodeficiency Syndrome↗
Severe flare of rheumatoid arthritis after discontinuation of long-term methotrexate therapy. Double-blind study.
To determine if long-term methotrexate-induced improvement of rheumatoid arthritis is sustained after the drug is discontinued, 10 unselected patients with responses to weekly oral methotrexate given for at least 36 months (mean 40.1) were randomly assigned to receive methotrexate or identical-appearing placebo tablets for two months. After one month, all five patients receiving placebo had to have the study terminated due to a flare of their disease manifested by statistically significant deterioration in multiple clinical parameters. It is concluded that patients receiving long-term methotrexate must continue the drug to maintain clinical benefits.
Adult↗
Fish-oil fatty acid supplementation in active rheumatoid arthritis. A double-blinded, controlled, crossover study.
STUDY OBJECTIVE: to determine the efficacy of fish-oil dietary supplements in active rheumatoid arthritis and their effect on neutrophil leukotriene levels. DESIGN: nonrandomized, double-blinded, placebo-controlled, crossover trial with 14-week treatment periods and 4-week washout periods. SETTING: academic medical center, referral-based rheumatology clinic. PATIENTS: forty volunteers with active, definite, or classical rheumatoid arthritis. Five patients dropped out, and two were removed for noncompliance. INTERVENTIONS: treatment with nonsteroidal anti-inflammatory drugs, slow-acting antirheumatic drugs, and prednisone was continued. Twenty-one patients began with a daily dosage of 2.7 g of eicosapaentanic acid and 1.8 g of docosahexenoic acid given in 15 MAX-EPA capsules (R.P. Scherer, Clearwater, Florida), and 19 began with identical-appearing placebos. The background diet was unchanged. MEASUREMENTS AND MAIN RESULTS: the following results favored fish oil placebo after 14 weeks: mean time to onset of fatigue improved by 156 minutes (95% confidence interval, 1.2 to 311.0 minutes), and number of tender joints decreased by 3.5 (95% Cl, -6.0 to -1.0). Other clinical measures favored fish oil as well but did reach statistical significance. Neutrophil leukotriene B4 production was correlated with the decrease in number of tender joints (Spearman rank correlation r=0.53; p less than 0.05). There were no statistically significant differences in hemoglobin level, sedimentation rate, or presence of rheumatoid factor or in patient-reported adverse effects. An effect from the fish oil persisted beyond the 4-week washout period. CONCLUSIONS: fish-oil ingestion results in subjective alleviation of active rheumatoid arthritis and reduction in neutrophil leukotriene B4 production. Further studies are needed to elucidate mechanisms of action and optimal dose and duration of fish-oil supplementation.
Adult↗
Increased helper/suppressor T-lymphocyte ratio in the cerebrospinal fluid of a patient with neurosarcoidosis.
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Adult↗
Effects of manipulation of dietary fatty acids on clinical manifestations of rheumatoid arthritis.
The effects of manipulation of dietary fatty acids in patients with rheumatoid arthritis were investigated in a 12-week, prospective, double-blind, controlled study. 17 patients took an experimental diet high in polyunsaturated fat and low in saturated fat, with a daily supplement (1.8 g) of eicosapentaenoic acid. 20 patients took a control diet with a lower polyunsaturated to saturated fat ratio and a placebo supplement. Compliance was monitored by plasma lipid gas-chromatographic analysis, Ivy bleeding time, and diet diaries. Results favoured the experimental group at 12 weeks for morning stiffness and number of tender joints. On follow-up evaluation 1-2 months after stopping the diet, the experimental group had deteriorated significantly in patient and physician global evaluation of disease activity, pain assessment, and number of tender joints. The control group had improved in morning stiffness and number of tender joints on follow-up.
Arthritis, Rheumatoid↗
Antimalarial treatment of rheumatoid arthritis: 1985 status.
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Antimalarials↗
A new assay for rheumatoid factor.
This solid-phase immunoassay for detection of rheumatoid factor involves a specially prepared indium surface that renders protein layers visible and therefore does not require tagged protein. Using appropriate discriminatory values, we found agreement with results of a standard latex-fixation test in controls and patients with rheumatoid arthritis. About half of the patients with rheumatoid arthritis that were seronegative by this latex fixation test had positive tests by the present assay. Rheumatoid factor of both the IgM and IgA class may be easily assessed.
Arthritis, Rheumatoid↗
Exacerbation of B27 positive spondyloarthropathy by enteric infections.
Two patients developed reactive arthritis after enteritis secondary to Campylobacter jejuni and Salmonella Group B, respectively. Each patient had an established spondyloarthropathy and was HLA-B27 positive. While enteric pathogens are widely reported to cause reactive arthritis, these patients illustrate that exacerbations of arthritic syndromes may also be precipitated. Our findings support the concept that abnormalities of bowel flora may affect the course of B27 associated arthropathies
Acute Disease↗
Ophthalmologic safety of long-term hydroxychloroquine sulfate treatment.
The fear of retinal toxicity has been a major factor limiting the use of chloroquine and hydroxychloroquine. Patients reported to develop retinal toxicity with visual loss usually took daily dosages higher than those currently in use. Toxicity with low dosages (for example, 250 mg per day chloroquine or 400 mg per day hydroxychloroquine) usually reveals pigment abnormalities; associated loss of vision is rare. When 99 patients treated with hydroxychloroquine for more than one year were studied prospectively, four patients showed evidence of retinal toxicity; none developed visual loss, and all abnormalities were completely reversible after drug discontinuation. All persons receiving antimalarials should be evaluated by an ophthalmologist at baseline and every six months thereafter. Funduscopic examinations and visual field testing with a red object must be included. Although this protocol may detect abnormalities that are not drug related, no loss of vision has developed in patients so monitored.
Adult↗