Rheumatoid Arthritis at a Glance
- Affects roughly 1% of the world population.
- Chronic disfiguring inflammatory condition.
- Genetics and environment play a role in etiology.
- Symmetric arthritis of the proximal interphalangeal and metacarpophalangeal joints.
- Skin findings include granulomatous dermatitis, vasculitis, rheumatoid nodules, pyoderma gangrenosum, and Bywater lesions.
- Treatment based on severity of disease.
This chapter discusses common rheumatologic diseases that have predominantly musculoskeletal presentations; however, all of these conditions have cutaneous manifestations.
Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease that is characterized by a debilitating chronic, symmetric polyarthritis with significant extra-articular manifestations, which include rheumatoid nodules, pyoderma gangrenosum, granulomatous dermatitis, vasculitis, and internal organ involvement. The disease process is often progressive, resulting in limitation of joint function. Ultimately, there may be a resultant decline in functional status, possibly leading to premature death. Permanent remission is unusual.
Rheumatoid arthritis has an annual incidence of approximately 0.4 per 1,000 in females and 0.2 per 1,000 in males, with a prevalence of approximately 0.4% to 1% of the adult population in diverse populations worldwide.1–3 Approximately 70% of patients follow a chronic disease course with exacerbations and remissions; 25% have intermittent disease with brief attacks of inflammation followed by remissions; approximately, 5% have an aggressive, malignant form with multiple extra-articular manifestations.4 RA has a peak onset at 50 years of age.1,2
Etiology and Pathogenesis
The exact etiology of RA remains unknown. Genetics plays at least some role in the development, severity, and outcome of the disease in certain patients.5 Furthermore, an association between extra-articular disease and HLA-DR1 and -DR4 genes has been noted in some populations.6
Mechanical stress on joints may initiate an inflammatory response creating an imbalance between the rapid response to trauma and the need to protect self from damage. Patients with seropositive RA (positive rheumatoid factor) have circulating and tissue-bound immune complexes. B cells produce autoantibodies in some RA patients. After binding to antigen, these autoantibodies result in complement fixation and recruitment of polymorphonuclear leukocytes, which result in joint destruction. Possible antigens in RA include heat shock proteins, collagen, and cyclic citrullinated peptides.7 Indeed, antibodies to several citrullinated peptides are enriched in the joints of patients with RA.8
Patients with negative rheumatoid factor (seronegative RA) may not create autoantibodies, but other immune mechanisms are involved. This theory led to the recognition that T cells are important players in the etiology of this disease. In the SKG mouse model, autoreactive T cells are preferentially selected, leading to inflammatory arthritis similar to RA. T cells also activate other cells via cytokines, including osteoclasts, which play a major role in the bone resorption seen in RA. Effector cytokines of the T cell include interferon-γ, interleukin 1, interleukin 17, and tumor necrosis factor-α (TNF-α), many of which have been, or ...