Polymyositis (PM) and dermatomyositis (DM) represent autoimmune diseases in which muscle is inappropriately targeted for immune-mediated destruction. Both of these inflammatory myopathies can produce systemic complications that include vasculopathy (Raynaud's phenomenon), arthritis, dysphagia, cardiac dysfunction, and interstitial lung disease. Clinically, the presence of a pathognomonic skin rash (Gottron's rash) distinguishes dermatomyositis from polymyositis. These two entities also differ histologically, reflecting potential differences in their immunopathogenesis. While DM is characterized by pervasive B cells, CD4+ T cells, and membrane attack complex formation (terminal complement components C5-C9), the immunohistologic hallmarks of deposition. Thus, DM appears to result from immune complex-triggered vascular/perivascular inflammation, whereas, PM stems from T cell-mediated cytolysis/dysfunction of muscle cells.
Dr. Oddis' primary research interest includes the clinical, epidemiologic and serologic aspects of idiopathic inflammatory myopathy. He has written extensively on the diagnosis and management of patients with myositis including use of novel immunosuppressive agents such as tacrolimus. Dr. Oddis is the principal investigator on a recently awarded 5-year NIAMS contract (10/04-10/09) to study the efficacy of a novel biologic agent, rituximab, in adult and pediatric myositis. He has been a co-investigator on two NIH-funded osteoarthritis trials; one (DOXY study) tested the efficacy of doxycycline in preventing the progression of knee osteoarthritis in middle-aged women and the second (GAIT) is assessing the effect of glucosamine and chondroitin sulfate on the pain of osteoarthritis and its radiographic progression. He serves as the Director of the Fellowship Training Program and the Medical Director for outpatient services.
Rheumatoid arthritis (RA) is a form of arthritis that has inflammation in the lining of the joints (synovium) and at times in internal organs. This inflammation separates RA from the most common form of arthritis, osteoarthritis. RA can affect any joint with synovium, especially in the hands, feet, knees, shoulders, and hips. The course of RA is variable and unpredictable with damage occurring to joint cartilage, tendons, ligaments, and bone.
Dr. Morelands' research focuses on therapies for various autoimmune diseases (rheumatoid arthritis, vasculitis, systemic lupus erythematosus, spondyloarthropathies) and osteoarthritis. He and collaborators have established multicenter collaborative efforts in several areas of research. Examples of active research include evaluating genetic and environmental factors in pathogenesis of African Americans with rheumatoid arthritis, evaluating efficacy (and molecular mechanisms) of various disease modifying agents used to treat rheumatoid arthritis, and new approaches aimed at developing disease remission for patients with rheumatoid arthritis.
Scleroderma is characterized by hardening and thickening (sclera) of the skin (derma). There are two forms of the disease. Systemic scleroderma (systemic sclerosis) is capable of causing serious, potentially fatal internal organ involvement, while localized scleroderma affects the skin only.
Both systemic and localized scleroderma are disorders in which the patient's immune system is activated and leads to tissue damage, with the end result being excessive deposition of collagen (fibrosis). Distinct subsets of patients have now been identified which assist in identifying future risks and help to direct treatment approaches.
The UPMC Scleroderma Clinic has specialized in the diagnosis and treatment of scleroderma for over 50 years. We have evaluated over 5000 scleroderma patients. Our physicians are recognized as leaders in the field and have authored over 300 publications on scleroderma in the medical literature. We offer a comprehensive approach to diagnosis and treatment the latter tailored to the needs of the individual patient.
Diagnosis of Systemic Sclerosis
Although this disease can affect many organ systems, 99% of patients have each of the following: 1) Raynaud phenomenon (color changes at the tips of the fingers on cold exposure or with emotional stress), 2) sclerodactyly (skin thickening of the fingers), or 3) a positive antinuclear antibody (ANA) test. A patient with none of these 3 findings is highly unlikely to have systemic sclerosis. A skin biopsy is not necessary to confirm the diagnosis. Rheumatologists establish the diagnosis of scleroderma on the basis of patient history, physical examination, ANA and other laboratory testing.
Other Common Symptoms and Signs
Treatment depends on the patient's disease subtype. When there is internal organ involvement present or an increased risk of such involvement, immune system suppressing drugs are used. Raynaud phenomenon is treated with blood vessel dilators, joint pain with anti-inflammatory drugs and heartburn with stomach acid-blocking medications. A vigorous exercise program is often recommended to prevent loss of joint motion and to strengthen the muscles surrounding affected joints.
Lupus is a chronic inflammatory disease that can affect various parts of the body, especially the skin, joints, blood, and kidneys. The body's immune system normally makes proteins called antibodies to protect the body against viruses, bacteria, and other foreign materials. These foreign materials are called antigens. In an autoimmune disorder such as lupus, the immune system loses its ability to tell the difference between foreign substances (antigens) and its own cells and tissues. The immune system then makes antibodies directed against "self." These antibodies, called "auto-antibodies," react with the "self" antigens to form immune complexes. The immune complexes build up in the tissues and can cause inflammation, injury to tissues, and pain.
Dr. Liang joined the Lupus Center of Excellence at UPMC in September 2008 after completing her Rheumatology fellowship at the Mayo Clinic. Her primary research interests are in cardiovascular disease and atherosclerosis in rheumatoid arthritis and lupus, vasculitis, and the role of immunosenescence in rheumatic diseases.
The word vasculitis means "inflammation of blood vessels." There are many different types of blood vessels in the body. Any particular vessel is part of a large vascular "tree" that includes large and medium sized arteries and smaller and smallest arterial branches (arterioles). These branches eventually reach all the tissues of the body, delivering oxygen and nutrients to a network of tiny vessels, called capillaries, that also remove wastes. The capillaries drain into the venous system. The smallest veins are venules; these connect like the tributaries of a river to form larger and larger veins.
Vasculitis can affect any of these different types of blood vessels. Inflammation can affect the lining of the vessels (endothelium) or the wall of an artery or vein. The damaged vessel does not function normally, and tissues that the vessel normally serves may then be affected. The effects of vasculitis that result from damage to the blood vessel include decreased function due to decreased blood flow (ischemia), death of some or all of an organ due to absent blood flow (infarction), or bleeding into the skin or other part of the body due to rupture of the blood vessel wall. Because vasculitis is a process that involves inflammation, it is usually accompanied by other features such as fever, or symptoms of involuntary weight loss and fatigue.
Banking of Biological Samples and Collection of Clinical Data for Connective Tissue Disease Research
Investigator: Thomas A. Medsger, Jr., MD
Co-Investigators: Division of Rheumatology Faculty Members
Connective tissue diseases are chronic diseases that involve damage of connective tissues such as the lining of the joints, blood vessel walls, muscle, skin, and certain internal organs. These diseases are also known as autoimmune diseases because the body's immune system reacts against its own tissues. Treatment has improved over the past 20 years, but there is still much that is not understood about the complications, causes, and treatments of these diseases.
The purpose of this project is to develop and maintain a Rheumatology Biological Specimen Bank of blood and tissue samples and a parallel Research Databank of computerized medical information. This is to support research of the CTDs and the factors that contribute to their onset and course of these diseases.
Contact person: Mary Lucas (412) 383-8699
Status: Actively Recruiting
T cell-derived cytokines are critical for mediating host defense against infectious disease, but they also mediate disease pathology in autoimmunity. In the last few years a new type of CD4+ T cell was discovered that plays a key role in autoimmunity. Distinct from the classic Th1 and Th2 populations, these cells are termed "Th17" based on their production of the signature effector cytokine IL-17. A number of innate immune cells also produce IL-17, such as gamma delta -T cells, and this cytokine appears to link innate and adaptive immunity in a variety of ways. IL-17 and its receptor are unique in structure and sequence from other known cytokines, and the Gaffen lab was among the first to study signaling mechanisms mediated by this novel family of cytokines. Dr. Gaffen's group takes a variety of biochemical, molecular and in vivo approaches to defining IL-17-mediated Signaling. In addition, members of the Gaffen lab demonstrated that IL-17 is critical for immunity to mucosal fungal infection with the commensal yeast Candida albicans. Research in the Gaffen lab is now heavily focused on defining the biological function of IL-17 and its receptor in the context of the oral mucosa. Lastly, treatment of autoimmune diseases has been revolutionized in the last decade or so by "biologic" drugs that neutralize cytokines, such as etanercept (a TNF receptor antagonist) and tocilizumab (an IL-6 receptor antagonist). Many of these drugs target the Th17/IL-17 pathway, and antibodies to IL-17 are now in clinical trials. Dr. Gaffen's group is attempting to understand the physiological impact of cytokine blockade in humans, particularly with respect to the IL-17 signaling pathway and its effects on susceptibility to mucosal infections such as oral candidiasis.
Sarah Gaffen, PhD
S703 BST South
3500 Terrace Street
Pittsburgh, PA 15261