Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology marked by a symmetric, peripheral polyarthritis. It is the most common form of chronic inflammatory arthritis and often results in joint damage and physical disability. Because it is a systemic disease, RA may result in a variety of extraarticular manifestations, including fatigue, subcutaneous nodules, lung involvement, pericarditis, peripheral neuropathy, vasculitis, and hematologic abnormalities.
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 now recognized to be a valuable biomarker of diagnostic and prognostic significance. Advances in ultrasound and magnetic resonance imaging have improved our ability to detect joint inflammation and destruction in RA. The science of RA has taken a major leap forward with the identification of new disease-related genes and further deciphering of the molecular pathways of disease pathogenesis. The relative importance of these different mechanisms has been highlighted by the observed benefits of the new class of highly targeted biologic therapies. Despite these gains, incomplete understanding of the initiating pathogenic pathways of RA remains a sizable barrier to its cure and prevention.
The last two decades have witnessed a remarkable improvement in the outcomes of RA. The historic descriptions of crippling arthritis are currently encountered much less frequently. 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 hour and easing 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 an inflammatory arthritis will present with too few affected joints and other characteristic features 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 have higher scores for physical disability.
Once the disease process of RA is established, the wrists, metacarpophalangeal (MCP), and proximal interphalangeal (PIP) joints stand out as the most frequently involved joints (Fig. 321-1). Distal interphalangeal (DIP) joint involvement may occur in RA, but it usually is a manifestation of coexistent osteoarthritis. Flexor tendon tenosynovitis is a frequent hallmark of RA and leads to decreased range of motion, reduced grip strength, and “trigger” fingers. Progressive destruction of the joints and soft tissues may lead to chronic, irreversible deformities. Ulnar deviation results from subluxation of the MCP joints, with subluxation of the proximal phalanx to the volar side of the hand. Hyperextension of the PIP joint with flexion of the DIP joint (“swan-neck deformity”), flexion of the PIP joint with hyperextension of the DIP joint (“boutonnière deformity”), and subluxation of the first MCP joint with hyperextension of the first interphalangeal (IP) joint (“Z-line deformity”) also may result from damage to the tendons, joint capsule, and other soft tissues in these small joints. Inflammation about the ulnar styloid and tenosynovitis of the extensor carpi ulnaris may cause subluxation of the distal ulna, resulting in a “piano-key movement” of the ulnar styloid. While metatarsophalangeal joint (MTP) involvement is a feature of early disease in the feet, the ankle and midtarsal regions are usually affected later in the course of disease and often predispose to pes planovalgus (“flat feet”). Large joints, including the knees and shoulders, are often affected in established disease, although these joints may remain asymptomatic for many years after onset.
Metacarpophalangeal and proximal interphalangeal joint swelling in rheumatoid arthritis. (Courtesy of the American College of Rheumatology Image Bank.)
Atlantoaxial involvement of the cervical spine is clinically noteworthy because of its potential to cause compressive myelopathy and neurologic dysfunction. Neurologic manifestations are rarely a presenting sign or symptom of atlantoaxial disease, but they may evolve over time with progressive instability of C1 on C2. The prevalence of atlantoaxial subluxation has been declining in recent years, and occurs now in less than 10% of patients. Unlike the spondyloarthritides (Chap. 325), RA does not affect the thoracic and lumbar spine except in very unusual circumstances. Radiographic abnormalities of the temporomandibular joint occur commonly in patients with RA, but they are rarely associated with significant symptoms or functional impairment.
Extraarticular manifestations may develop during the clinical course of RA, even prior to the onset of arthritis (Fig. 321-2). Patients most likely to develop extraarticular disease have a history of smoking, early onset of significant physical disability, and test positive for serum RF. Subcutaneous nodules, secondary Sjögren's syndrome, pulmonary nodules, and anemia are among the most frequently observed extraarticular manifestations. Recent studies have shown a decrease in the incidence and severity of at least some extraarticular manifestations, particularly Felty's syndrome and vasculitis.
Extraarticular manifestations of rheumatoid arthritis.
The most common systemic and extraarticular features of RA are described in more detail in the sections below.