Biomedical subjects
Publications and source records attributed to W S Wilke.
Fibromyalgia is characterized by diffuse pain, multiple tender points, fatigue, and sleep disturbance. Its frequent concurrence with rheumatic diseases modifies the clinical picture of the "primary" disease. This article reviews new information about the etiopathogenesis and treatment of this syndrome.
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Research from several groups of investigators indicates that some patients with chronic fatigue syndrome have abnormal vasovagal or vasodepressor responses to upright posture. If confirmed, these findings may explain some of the symptoms of chronic fatigue syndrome. There is also speculation that neurally mediated hypotension may be present in fibromyalgia. This article discusses the original research in this area, the results of follow-up studies, and the current approach to treating patients with chronic fatigue syndrome in whom neurally mediated hypotension is suspected.
Methotrexate has proven to be a safe, effective, long-term therapy for rheumatoid arthritis. Its property as a corticosteroid-sparing drug in rheumatoid arthritis has been recognized and its potential has been explored in other inflammatory and autoimmune diseases. This article describes and analyzes the use of methotrexate for a wide variety of diseases, some of which are not the usual province of rheumatologists, to provide some guidance concerning its role for treatment. Methotrexate therapy seems promising for systemic lupus erythematosus, inflammatory myopathy, inflammatory eye disease, inflammatory bowel disease, and some manifestations of sarcoidosis. Its role in other diseases is not as well defined.
Giant cell arteritis and Takayasu arteritis are separate but similar idiopathic diseases clinically characterized by constitutional symptoms, shared surrogate markers of systemic inflammation and indistinguishable granulomatous pan-arteritis of large vessels. This review emphasizes and analyses changing perceptions about the diseases. Recent series suggest that aortic involvement in giant cell arteritis may be more common than was previously appreciated. The case for and against inflammatory arthritis in giant cell arteritis is discussed. Ethnic new geographical variation in Takayasu arteritis-disease expression is reviewed. New philosophies of treatment are presented for both diseases. Prognosis in giant cell arteritis and its relationship to treatment is analysed. The utility of the laboratory for diagnosis and monitoring disease activity is appraised for each.
Recognition of fibromyalgia is crucial to avoid extraneous, costly diagnostic testing and ineffective, potentially dangerous therapy. Furthermore, failure to recognize that symptomatic physiologic change does result in a patient's response to stress demeans the legitimate importance of psychiatric disease. The keys to successful therapy are (1) specific pharmacologic manipulation of important processes and prognostic factors, (2) participation in aerobic exercise, which increases time spent in stages 3 and 4 (non-rapid eye movement) sleep and reduces stress, and (3) education, which reduces worry and perceived stress.
Rheumatoid patients with intractable knee effusions may benefit from medical or radio-isotopic synoviorthesis. These offer more convenient, less costly alternatives to surgery with similar long-term outcome. Temporary symptomatic relief may be obtained, but disease progression is unaffected. Potential adverse effects include development of osteoarthrosis with osmic acid and teratogenicity and mutagenicity with alkylating agents and radioisotopes.
Long-term outcome for the majority of patients with fibromyalgia is sufficiently disappointing so that most patients can be considered to have "resistant" disease. Among published treatments, education, active exercise, and nighttime antidepressant medications perform best. Patients eligible for treatment include those with primarily regional symptoms, wide-spread pain without 11 or fewer tender points, or "typical patients" as defined by the American College of Rheumatology criteria. Factors important in the process of prognosis of the syndrome should be identified and addressed in an integrated therapeutic program in order to positively influence outcome.
The literature about the treatment of giant cell arteritis (GCA) is diverse and often includes patients with polymyalgia rheumatica (PMR) who do not have concurrent features of GCA. Consequent heterogeneity has contributed to controversy in the analysis of clinical data. Nevertheless, we have critically reviewed this literature to derive a rational approach to initial and maintenance corticosteroid (CS) therapy and thus define "CS-resistant GCA." In this article, the authors review what has been written about the treatment of presumed CS-resistant disease. Although firm recommendations are lacking, the authors provide algorithms for the treatment of GCA patients who fail to respond to initial CS therapy or who require potentially toxic maintenance-dose CS therapy. A study design that may help to resolve the dilemmas that were found during our analysis is also outlined.
Chronic fatigue syndrome (CFS), as currently described in the working criteria proposed by the Centers for Disease Control and Prevention (Atlanta), may be associated with multiple, distinct, and possibly unique clinical and/or etiopathogenic subsets. Sjögren's syndrome (SS) is a disease of unknown etiology that is characterized by dryness of the mucous membranes and a variety of autoimmune phenomena and conditions. Subjective manifestations of SS such as neurocognitive dysfunction and fatigue have been stressed by some observers. We have detected a large number of patients with unrecognized SS-like illness in a clinical specializing in CFS and believe the relationship to be more than casual. From January 1991 through April 1992, 172 patients were evaluated for CFS; the SS cohort consisted of 27 females (mean age, 41.9 years). Sixteen of these patients had previously been found to have CFS by a physician, and 11 were self-referred. All patients complained of severe, dominating, chronic fatigue. Complaints of myalgia were prominent; 20 of 27 patients met the criteria for fibromyalgia. Neurocognitive complaints and/or a history of neuropsychiatric disease was frequent. Results of Schirmer's test were abnormal for 16 of 27, and results of minor salivary-gland biopsy were abnormal for 20 of 25. Antibodies to nuclear antigen were present in 16 of 27, but anti-Ro was present in only 1 of 21. In the SS group, 13 of 27 patients met eight or more CDC minor criteria for CFS, and 18 of 27 met six or more of the criteria.(ABSTRACT TRUNCATED AT 250 WORDS)
The past few years have witnessed changing perceptions about rheumatoid arthritis (RA); it is now considered a serious systemic disease that confers not only physical and social morbidity but also earlier mortality. The long-term outcome of sequential monotherapy based on the therapeutic pyramid has been disappointing. A review of prognostic factors, acute disease activity measures, functional measures, and the results of preliminary trials with combination therapy suggests that specific goals of treatment can be established and that logical, aggressive treatment in early disease can be accomplished. These goals should include prompt control and continuous reduction of the active joint count to < or = 4 and normalization of acute-phase reactants. The "graduated-step paradigm" of treatment designed with these goals in mind is described, and a retrospective series that gives an estimate of outcome with its use is reported.
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BACKGROUND: Methotrexate is a second-line anti-inflammatory agent used in the treatment of rheumatic diseases. At low doses (12.5 mg/week), it is associated with few serious side effects. METHODS: Twenty-two patients (5 men, 17 women) with chronic noninfectious ocular inflammatory disease, who had not responded to or who had become intolerant of corticosteroid or alternate cytotoxic agents, were treated weekly with oral low-dose, pulse methotrexate. Treated diseases included chronic uveitis-vitreitis (9), scleritis (4), inflammatory pseudotumor (3), orbital myositis (3), and retinal vasculitis (3). RESULTS: Follow-up ranged from 2 to 39 months (mean, 11 months). Response time ranged from 3 to 9 weeks (mean, 5 weeks) after implementation of methotrexate therapy. Sixteen of 22 patients had reduction of inflammatory activity. Fourteen of these 16 patients were able to taper or discontinue corticosteroid therapy. Five patients had complete remission of their disease; six patients did not respond to methotrexate. CONCLUSION: Treatment with low-dose methotrexate appears to be effective therapy for steroid-resistant ocular inflammatory disease.
We performed a 10-year retrospective analysis of the frequency of local postoperative infectious complications in methotrexate (MTX)-treated rheumatoid arthritis patients who underwent total joint arthroplasty. Sixty patients, who had a total of 92 joint arthroplasties, were receiving MTX. A comparison group of 61 patients with a combined total of 110 total joint arthroplasties were not receiving MTX. The 2 groups were compared for the occurrence of local postoperative infectious complications and poor wound healing. Eight patients in the MTX group experienced a total of 8 complications (8.7% of procedures). In comparison, 5 patients in the non-MTX group experienced a total of 6 complications (5.5% of procedures), a difference that was not statistically significant (chi 2 = 0.816, P = 0.366). Statistical analysis of many other variables revealed none that could be identified as risk factors for postoperative complications. These results suggest that treatment in the perioperative period with weekly low-dose pulse MTX does not increase the risk of local postoperative infectious complications or poor wound healing in rheumatoid arthritis patients who undergo total joint arthroplasty.
Two hundred rheumatoid arthritis (RA) patients taking low dose methotrexate (MTX) were evaluated for adverse effects. During a mean follow up of 41.5 months, the mean cell volume (MCV) was elevated at some time during the course of treatment in 42 patients. The MCV was normal in the remaining 158 patients. One hundred ninety-eight patients were treated simultaneously with oral folic acid. With the exception of heartburn, which was seen more often in the high MCV group, there was no difference in the frequency of adverse effects attributable to MTX between groups. Severity of side effects and the frequency of MTX dose reduction and MTX discontinuation due to toxicity were also similar between groups. This analysis suggests that elevation of MCV in RA patients treated simultaneously with MTX and folate does not predict MTX toxicity. The authors also discuss the mechanism of action of MTX with regard to folate metabolism.
The last 10 years have witnessed a change in the way rheumatologists view rheumatoid arthritis (RA). It is no longer considered a slowly progressive disease limited to the joints, but rather an aggressive systemic disease that results in clinically significant morbidity early in its course and can contribute to excess mortality. Heightened awareness of the health impact of RA has spurred a search for effective therapy to be applied early in the course of disease for patients with moderate to severe RA. Combinations of disease-modifying antirheumatic drugs (DMARD) have become an increasingly popular alternative to sequential monotherapy. In this report, we review published series of patients with RA who have been treated with combinations of DMARDs, sometimes including chemotherapeutic agents, with some critical comment. Published paradigms of treatment are also reviewed and a new strategy is presented. The "step-down bridge" strategy allows early treatment with at least four DMARDs, but may place some patients with mild disease at an inappropriately high risk of adverse effects. The "sawtooth" strategy gives little guidance as to which DMARD(s) should be chosen for initial treatment. We describe a "graduated-step" strategy that provides numerical grading to match disease severity and disease activity with appropriate initial therapy and that facilitates therapeutic decisions throughout the course of treatment.
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PURPOSE: Methotrexate (MTX), when used to treat malignancy or psoriasis, has been implicated in anecdotal reports as a teratogen or abortifacient in the first trimester of pregnancy. We are unaware of any previous reports that describe the course of gestation and the effect on subsequent offspring in patients treated with low-dose oral MTX for rheumatoid arthritis, and therefore present our experience. PATIENTS AND METHODS: We report on eight women experiencing 10 pregnancies. Mean number of weeks of gestation while taking MTX was 7.5 (range 2 to 20 weeks). Outcome of pregnancies included five full-term babies (FTB), three spontaneous abortions (SAB), and two elective abortions. RESULTS: There were no significant differences in either the FTB or SAB group when considering risk factors including smoking, alcohol, concomitant medications, and age. One of three in the SAB group had recurrent abortions prior to MTX therapy. All five of the FTB group had uncomplicated pregnancies and deliveries. All offspring were of normal height and weight at birth with no physical abnormalities. All children reached growth, development, and intellectual stages normally, and their present mean age is 11.5 years. No observed learning disabilities or medical abnormalities have occurred in any of these children. CONCLUSION: In this uncontrolled study we failed to demonstrate tertogenicity of MTX. However, the possibility of abortion due to MTX use remains.