ABSTRACT
BACKGROUND: Previous reports have suggested that treatment with the selective estrogen antagonist tamoxifen may be effective in diminishing primary and secondary Raynaud's vasospasm, including cases occurring in the setting of scleroderma. Tamoxifen treatment has also been associated with improvement of retroperitoneal fibrosis and desmoid tumors, conditions also associated with abnormal fibroblast proliferation. Tamoxifen increases production of the immunosuppressive cytokine TGF beta which modulates fibroblast activity. The potential effect of tamoxifen on vascular reactivity and fibrotic lesions raised questions about its utility as a therapeutic agent in scleroderma. OBJECTIVE: To determine the utility of tamoxifen therapy in scleroderma. METHODS: Open label preliminary, prospective, proof of concept study of tamoxifen. RESULTS: Fifteen patients (3 male, 12 female) with scleroderma were enrolled (10 diffuse disease, 5 CREST). Mean age was 55 (34-75) years. Mean duration of scleroderma was 9.3 (1-25) years. Two patients were excluded. For 13 patients, mean duration of treatment was 7 (1.5-32) months. Two of 13 patients treated with tamoxifen experienced transient improvement. They did not appear to have clinical features that identified them as a unique subset. Both patients subsequently relapsed, in one case 12 months, and in the other 24 months after treatment. CONCLUSION: Based on these results, we would not recommend tamoxifen for further large scale studies in scleroderma.
Subject(s)
CREST Syndrome/drug therapy , Estrogen Antagonists/therapeutic use , Tamoxifen/therapeutic use , Aged , CREST Syndrome/pathology , CREST Syndrome/physiopathology , Endpoint Determination , Female , Humans , Male , Middle Aged , Treatment OutcomeSubject(s)
Arnold-Chiari Malformation/surgery , Fatigue Syndrome, Chronic/surgery , Fibromyalgia/surgery , Spinal Cord Diseases/surgery , Arnold-Chiari Malformation/diagnosis , Arnold-Chiari Malformation/physiopathology , Cervical Vertebrae , Diagnosis, Differential , Fatigue Syndrome, Chronic/diagnosis , Fatigue Syndrome, Chronic/physiopathology , Female , Fibromyalgia/diagnosis , Fibromyalgia/physiopathology , Humans , Male , Spinal Cord Diseases/diagnosis , Spinal Cord Diseases/physiopathology , Treatment OutcomeABSTRACT
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.
Subject(s)
Fibromyalgia , Algorithms , Fibromyalgia/classification , Fibromyalgia/diagnosis , Fibromyalgia/etiology , Fibromyalgia/therapy , Humans , PrognosisABSTRACT
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.
Subject(s)
Fatigue Syndrome, Chronic/etiology , Hypotension/complications , Fatigue Syndrome, Chronic/physiopathology , Fibromyalgia/etiology , Fibromyalgia/physiopathology , Humans , Hypotension/drug therapy , Hypotension/physiopathology , Posture , Tilt-Table TestABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antirheumatic Agents/therapeutic use , Connective Tissue Diseases/drug therapy , Inflammation/drug therapy , Methotrexate/therapeutic use , Arthritis, Rheumatoid/drug therapy , Clinical Trials as Topic , Humans , Lupus Erythematosus, Systemic/drug therapy , Myositis/drug therapy , Sarcoidosis/drug therapy , Scleroderma, Systemic/drug therapy , Still's Disease, Adult-Onset/drug therapyABSTRACT
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.
Subject(s)
Takayasu Arteritis , Animals , Diagnosis, Differential , Giant Cell Arteritis/diagnosis , Giant Cell Arteritis/drug therapy , Giant Cell Arteritis/surgery , Humans , Takayasu Arteritis/diagnosis , Takayasu Arteritis/drug therapy , Takayasu Arteritis/surgeryABSTRACT
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.
Subject(s)
Fibromyalgia , Antidepressive Agents/therapeutic use , Depression/complications , Diagnosis, Differential , Fibromyalgia/diagnosis , Fibromyalgia/metabolism , Fibromyalgia/physiopathology , Fibromyalgia/therapy , Humans , Sleep Wake Disorders/complicationsABSTRACT
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.
Subject(s)
Synovial Membrane/drug effects , Synovial Membrane/radiation effects , Synovitis/drug therapy , Synovitis/radiotherapy , Algorithms , Dysprosium/therapeutic use , Gold Radioisotopes/therapeutic use , Humans , Mechlorethamine/therapeutic use , Methotrexate/therapeutic use , Osmium Tetroxide/therapeutic use , Radioisotopes , Synovectomy , Synovitis/surgery , Thiotepa/therapeutic use , Yttrium Radioisotopes/therapeutic useABSTRACT
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.
Subject(s)
Fibromyalgia/therapy , Drug Resistance , Exercise Therapy , Fibromyalgia/complications , Fibromyalgia/drug therapy , Humans , Patient Education as TopicABSTRACT
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.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Giant Cell Arteritis/drug therapy , Drug Resistance , Drug Therapy, Combination , Giant Cell Arteritis/complications , Humans , Methotrexate/therapeutic use , Prospective Studies , Time Factors , Treatment OutcomeABSTRACT
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)
Subject(s)
Fatigue Syndrome, Chronic/complications , Sjogren's Syndrome/complications , Adult , Centers for Disease Control and Prevention, U.S. , Cohort Studies , Diagnosis, Differential , Fatigue Syndrome, Chronic/diagnosis , Fatigue Syndrome, Chronic/epidemiology , Female , Humans , Male , Ohio/epidemiology , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/epidemiology , United StatesABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Rheumatoid/drug therapy , Hydroxychloroquine/therapeutic use , Methotrexate/therapeutic use , Severity of Illness Index , Adult , Arthritis, Rheumatoid/physiopathology , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Male , Methotrexate/adverse effects , Middle Aged , Retrospective Studies , Time Factors , Treatment OutcomeSubject(s)
Arthritis, Rheumatoid/drug therapy , Antirheumatic Agents/administration & dosage , Auranofin/administration & dosage , Azathioprine/administration & dosage , Clinical Protocols , Drug Therapy, Combination , Humans , Hydroxychloroquine/administration & dosage , Methotrexate/administration & dosage , Penicillamine/administration & dosage , Retrospective Studies , Sulfasalazine/administration & dosageSubject(s)
Fibromyalgia , Diagnosis, Differential , Fibromyalgia/diagnosis , Fibromyalgia/etiology , Fibromyalgia/therapy , HumansABSTRACT
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.