Rheumatoid arthritis: risk factors, clinical signs, and treatment

Early diagnosis and aggressive treatment are essential to mitigate the cascading events that lead to irreversible joint erosion in rheumatoid arthritis.
Early diagnosis and aggressive treatment are essential to mitigate the cascading events that lead to irreversible joint erosion in rheumatoid arthritis.

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Rheumatoid arthritis (RA) is a chronic and debilitating autoimmune disease that affects the joints, and lives, of more than 1.5 million Americans, or 1 in every 100. The lubricating synovium, which is the tissue that lines the joints, becomes inflamed and thickened when attacked by the immune system, so that painful swelling develops around the joints. This inflammatory process damages the cartilage and erodes the joint spaces between bones, leading to unstable, immobile, deformed, and painful joints.1  The joint destruction of RA is a cascading event, in which pannus, hyperplastic synovial tissue, and cartilage erosion result in subchondral bone, articular capsule, tendon, and ligament damage.2 The joint erosion is irreversible; therefore, early diagnosis and aggressive initial treatment are imperative. 

This article discusses the most prevalent risk factors, as well as the clinical signs and symptoms, associated with RA. Current treatment modalities for and the prognosis of patients with RA are also discussed. 

Epidemiology and etiology

RA is a chronic condition with no known specific cause; however, gender, heredity, genetics, and initiating factors are known risk determinants.3 RA is three times more likely to affect women than men. The peak age at onset in women is in the fourth to fifth decades; in men, the prevalence increases in the sixth to eighth decades.Although RA is not hereditary, certain genetic features can affect the risk for the development of this disease. Research indicates that the presence of rheumatoid factor (RF) in healthy individuals is of a greater significance than was initially understood, as the presence of both immunoglobulin M (IgM) and IgA RF is associated with a seven‐fold risk for seropositive RA.4 Moreover, it has been found that people with specific variants of the human leukocyte antigen (HLA) genes are at higher risk for the development of RA. Today, the best-known genetic risk factor for RA is inheritance of certain HLA-DRB1 alleles, which encode a “shared epitope” that is detected as a distinguishing five-amino-acid sequence.5 

Although the presence of the HLA-DRB1 alleles is not a specific indicator of disease, certain factors can enhance an individual's susceptibility to the development of RA. These include infection, cigarette smoking, and stress, which are all very common in today's society. Bacterial infections, primarily those involving the mouth and/or gut, are environmental factors hypothesized to increase the risk for RA.6 However, the most significant environmental risk factor for RA is smoking.7 In a Finnish population study, it was found that elevated RF levels were found twice as often in both current and former smokers as in nonsmokers; moreover, the proportion of smokers increased among those persons with higher RF titers.Other studies have also demonstrated an association between RF production and frequent cigarette smoking. Even if cigarette smoking is discontinued, once it has induced RF production, the process is irreversible.8 Stress can also exacerbate RA; research indicates that the onset of RA is often preceded by traumatic and/or stressful lifetime events.3 Furthermore, painful flare-ups of RA have been linked to exacerbations of stress. Stress management should be a critical component of the RA treatment plan, as living with a “painful, chronic, and somewhat unpredictable disease can be a significant source of stress in itself.”9 

History and clinical presentation

Before the symptoms of RA become bothersome enough to cause someone to seek medical attention, early symptoms of RA, such as fatigue, muscle pain, low-grade fever, weight loss, and numbness and tingling in the hands, are often present.3 RA is described to have an “insidious” onset characterized by morning stiffness and a vague, prodromal pain in the affected joints. Morning stiffness characteristically lasts longer than 30 minutes. 

RA presents most commonly as a symmetric polyarthritis affecting both small and large joints but particularly, the small joints of the hands and feet.5 The peripheral joints, especially the diarthrodial joints, are most commonly affected. The diarthrodial joints are lined with inflamed synovial membrane, and their bony surfaces are surrounded by hyaline cartilage. In RA, the diarthrodial joints most often involved are the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints of the fingers; the wrists, knees, and ankles; and the metatarsophalangeal (MTP) joints of the toes. The pathologic processes causing the red, inflamed, and dysmorphic joints observed on physical examination include synovial membrane proliferation, angiogenesis, endothelial cell activation, chemotactic stimuli, and the production of proinflammatory cytokines.6 The joint symptoms of RA typically are gradual in onset and include pain, stiffness, redness, warmth to the touch, and swelling. When the hands are assessed during physical examination, grip strength is often noted to be reduced.3 

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