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Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology characterized by a symmetric polyarthritis, the most common form of chronic inflammatory arthritis. Since persistently active RA often results in articular cartilage and bone destruction and functional disability, it is vital to diagnose and treat this disease early and aggressively before damage ensues. RA, a systemic disease, may also lead to a variety of extraarticular manifestations, including fatigue, subcutaneous nodules, lung involvement, pericarditis, peripheral neuropathy, vasculitis, and hematologic abnormalities, which must be managed accordingly.

Insights gained by a wealth of basic and clinical research over the past two decades have revolutionized the contemporary paradigms for the diagnosis and management of RA. Serum antibodies to cyclic citrullinated peptides (anti-CCPs) are routinely included with rheumatoid factor in the diagnostic evaluation of patients with suspected RA, and serve as biomarkers of prognostic significance. Advances in imaging modalities have assisted clinical decision-making by improving the detection of joint inflammation and damage. The science of RA has taken major leaps forward by illuminating new disease-related genes and environmental interactions and elucidating in more detail the molecular components and pathways of disease pathogenesis. The relative contribution of these molecular components and pathways has been further brought to light by the observed benefits of targeted biologic and small-molecule therapies. Despite this progress, incomplete understanding of the initiating events of RA and the factors perpetuating the chronic inflammatory response remains a sizable barrier to its cure and prevention.

The last two decades have witnessed a remarkable improvement in the outcomes of RA. The crippling arthritis of year’s past is encountered much less frequently today. Much of this progress can be traced to the expanded therapeutic armamentarium and the adoption of early treatment intervention. The shift in treatment strategy dictates a new mind-set for primary care practitioners—namely, one that demands early referral of patients with inflammatory arthritis to a rheumatologist for prompt diagnosis and initiation of therapy. Only then will patients achieve their best outcomes.


The incidence of RA increases between 25 and 55 years of age, after which it plateaus until the age of 75 and then decreases. The presenting symptoms of RA typically result from inflammation of the joints, tendons, and bursae. Patients often complain of early morning joint stiffness lasting more than 1 h that eases with physical activity. The earliest involved joints are typically the small joints of the hands and feet. The initial pattern of joint involvement may be monoarticular, oligoarticular (≤4 joints), or polyarticular (>5 joints), usually in a symmetric distribution. Some patients with inflammatory arthritis will present with too few affected joints to be classified as having RA—so-called undifferentiated inflammatory arthritis. Those with an undifferentiated arthritis who are most likely to be diagnosed later with RA have a higher number of tender and swollen joints, test positive for serum rheumatoid factor (RF) or anti-CCP antibodies, and ...

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