Biomedical subjects
Stuart M Levine
Publications and source records attributed to Stuart M Levine.
Cancer and myositis: new insights into an old association.
PURPOSE OF REVIEW: The association between the idiopathic inflammatory myopathies and the development of malignancy has been appreciated for nearly a century, but its meaning and significance have remained unclear. Significant advances in our understanding of the epidemiology and pathophysiology of this association have recently been made. This review will describe the major epidemiological evidence linking inflammatory myopathies with cancer, and will use this evidence to highlight a recently proposed model for the development of cancer-associated myositis. RECENT FINDINGS: The temporal relationship between the development of cancer and myositis is reminiscent of that seen in neurological paraneoplastic disorders, in which antigens targeted for an immune response are expressed at high levels in the inciting tumor and the affected neuronal tissue. It has also recently been observed that regenerating cells in myositis muscle, but not its normal counterpart, express high levels of myositis-specific autoantigens. These same antigens are expressed at high levels in several cancers known to be associated with the development of myositis, but not in corresponding normal tissue. SUMMARY: These observations suggest a model of paraneoplasia focusing on common autoantigen expression and immune targeting between cancer tissues and muscle tissue in myositis.
Anti-aminoacyl tRNA synthetase immune responses: insights into the pathogenesis of the idiopathic inflammatory myopathies.
PURPOSE OF REVIEW: One of the most striking humoral characteristics of the idiopathic inflammatory myopathies is the specific targeting of components of the translational machinery by the immune system. The most commonly targeted of these components are the aminoacyl tRNA synthetase (ARS) molecules. However, the relation between the immune responses to these molecules and the pathogenesis of the inflammatory myopathies remains obscure. This review will examine recent evidence that explores the links between the ARS molecules, inflammation, and apoptosis, with the aim of furthering our current understanding of the underlying pathogenesis of the myositis syndromes. RECENT FINDINGS: Several of the ARS molecules and their proteolytic fragments generated during inflammation and apoptosis have recently been shown to possess chemoattractant properties. The liberation of these fragments in the muscle microenvironment under certain circumstances may provide a proinflammatory context and lead to the influx of lymphocytes, macrophages, and specialized antigen-presenting cells to the site of muscle injury. The subsequent processing and presentation of these autoantigen fragments on major histocompatibility complex class I and II molecules may generate an ARS-specific autoimmune response, which may be responsible for amplification and propagation of muscle injury in these diseases. SUMMARY: The striking association between the inflammatory myopathies and anti-ARS antibodies implies a role for the ARS molecules in the pathogenesis of these syndromes. Recent data suggest that ARS molecules and their proteolytic fragments generated during the cell death process may be responsible for priming and sustaining a specific immune response in situ in myositis. How these molecules become altered and access the immune system in the disease microenvironment is an area of ongoing investigation.
Gastrointestinal involvement in polyarteritis nodosa (1986-2000): presentation and outcomes in 24 patients.
PURPOSE: Gastrointestinal involvement in polyarteritis nodosa carries a poor prognosis. A 1982 review from our institution reported acute abdominal syndromes in 31% of patients with polyarteritis nodosa, and that all 5 patients with acute surgical abdomens died. We reviewed our more recent experience to determine if outcomes have changed since. SUBJECTS AND METHODS: We reviewed the records of all patients with polyarteritis nodosa in our vasculitis database between 1986 and 2000. Inclusion criteria were a diagnosis of polyarteritis nodosa, symptoms or signs of gastrointestinal involvement, and either a mesenteric angiogram consistent with polyarteritis nodosa or histopathologic proof of a medium-vessel vasculitis. We calculated a prognostic (5 factor) score for all patients. RESULTS: We identified 24 patients with polyarteritis nodosa who had gastrointestinal involvement during their illness. Thirteen (54%) of the patients developed acute surgical abdomens, 3 of whom died (P = 0.02 by comparison with the historical cohort). Mean (+/- SD) prognostic scores were higher among patients in the acute abdomen group compared with those who did not have acute abdominal syndromes (1.7 +/- 0.9 vs. 0.6 +/- 0.7, P = 0.002), corresponding with the observed mortality in these groups. CONCLUSION: Gastrointestinal involvement occurs commonly in polyarteritis nodosa and carries a poor prognosis. Compared with a historical cohort at our institution, mortality from this complication may have decreased, perhaps because of earlier diagnosis.
Giant cell arteritis.
Giant cell arteritis (GCA), the most common form of systemic vasculitis in adults, preferentially involves large and medium-sized arteries in patients over the age of 50. The classic manifestations are headache, jaw claudication, polymyalgia rheumatica (PMR), and visual symptoms, but 40% of patients present with a wide range of occult manifestations. Early diagnosis and treatment with prednisone can prevent blindness, the most feared complication of GCA. The pathogenesis of GCA is T-cell dependent and antigen driven. Clinical subsets of GCA appear to result from variable cytokine expression. The risk of developing thoracic aortic aneurysm is increased more than 17-fold in patients with GCA. GCA can also involve large arteries, especially the subclavian and axillary arteries. Color Doppler ultrasound, magnetic resonance imaging, and positron-emission tomography scanning are providing insights into the extent and pathogenesis of the disease but have not replaced temporal artery biopsy as the gold standard for securing the diagnosis. Two recently completed double-blind, placebo-controlled trials concerning whether methotrexate plus prednisone is more effective than prednisone alone reached conflicting conclusions.