What You Should Know About New Antirheumatic Medications

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Note the fibular deviation of the hallux at the first MTPJ.
Note the dislocation of the second digit due to severe deformity at the first MTPJ.
What You Should Know About New Antirheumatic Medications
A Guide To New Drugs For The Treatment Of Rheumatoid Arthritis
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Author(s): 
By Peter A. Blume, DPM, Kenneth L. Cornell, DPM, and Robert Schoen, MD

   Rheumatoid arthritis (RA) is a systemic inflammatory polyarthritis that involves small and large joints, and affects approximately 1 percent of the population in the United States.1 The natural progression of the disease leads to irreversible deformity in the hands and feet with destruction of bone and articular cartilage. This may ultimately lead to the loss of function of the extremity. There are numerous extraarticular manifestations of RA (i.e., including vasculitis). They can affect any organ system and result in premature death.

   Over the last decade, there has been tremendous progress leading to improved understanding of the pathophysiology in RA. The inflammatory cytokines, tumor necrosis factor-a (TNF-a), interleukin-1 (IL-1) and interleukin-6 (IL-6), have been identified as key mediators in the inflammatory process of RA.2 The recent advancements in identifying the inflammatory pathways of RA have led to new and improved treatment strategies that specifically target the inflammatory cytokines. Clinically it has become possible to slow the disease process associated with RA.

   Rheumatoid arthritis represents an imbalance of the soluble and cellular mediators of inflammation, resulting in a chronic inflammatory process that allows proliferation of synovial tissue (pannus) around articular cartilage and bone.2 The periarticular synovial membrane is characterized by hyperplasia, increased vascularity and an infiltrate of inflammatory cells. It is theorized that auto-antigens presented to CD4+ T lymphocytes illicit a broad immune response. The activated CD4+T lymphocytes stimulate macrophages, monocytes and fibroblasts to produce the cytokines IL-1, IL-6, and TNF-a.2 The cytokines and activated inflammatory cells cause expression of adhesion molecules and angiogenesis of the periarticular synovium. The adhesion molecules allow binding of inflammatory cells and facilitate their entry into the joint. Activated CD4+T lymphocytes are also thought to stimulate osteoclast production that leads to bone resorption. B cells and plasma cells in the synovium produce rheumatoid factor, an IgM antibody to IgG that activates the complement cascade and initiates cellular chemotaxis.

   Several cytokines involved in the pathologic process of RA have been identified in recent studies. TNF-a and IL-1 have been identified as two key intermediaries of inflammation in RA.2,3 TNF-a is released mainly by monocytes and macrophages, and leads to a pro-inflammatory response in a number of different cell types. TNF-a increases the production of IL-1, IL-6 and IL-8, amplifying the inflammatory response. TNF-a and IL-1 also stimulate fibroblasts, osteoclasts and chondrocytes to release matrix metalloproteinases. This leads to cartilage and tissue destruction. TNF-a stimulates the expression of adhesion molecules on the surface of fibroblasts, allowing the migration of leukocytes into areas of inflammation. IL-1 is produced by monocytes, macrophages, B-cells and activated T-cells in the affected joint. IL-1 also stimulates the release of matrix metalloproteinases in the periarticular synovium from fibroblasts and chondrocytes, resulting in further periarticular destruction.2

How To Diagnose Rheumatoid Arthritis

   Joint damage begins in the early stages of RA so early detection and diagnosis of RA is essential in the clinical management of the disease.4 RA is a symmetric polyarticular arthritis that frequently affects the small joints of the hands, wrists and feet but can involve any synovial joint.

   Upon the clinical examination, one may note joints that are swollen, warm and tender. There may also be a local effusion surrounding the joint. Prolonged morning stiffness lasting more than one hour is a hallmark feature of RA. Patients with RA may have large rheumatoid nodules in the lungs, pericardium, myocardium, the palmar surface of the hands and the plantar surface of the foot.5

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