Introduction
- Rheumatoid arthritis (RA) is a chronic inflammatory arthritis of unknown etiology
- Most common autoimmune inflammatory arthritis in adults
- Persistent synovitis leads to progressive joint destruction and deformity
- Believed to result from the interaction between genetic and environmental factors
Pathophysiology
- A possible autoimmune or infectious triggering incident causes the proliferation of fibroblasts and synovial macrophages
- Perivascular regions are infiltrated by lymphocytes and endothelial cells proliferate followed by growth of new blood vessels which become occluded with inflammatory cells or small clots
- An irregular growth of inflamed synovial tissue develops over time with invasive pannus tissue formation
- The cartilage and bone are then destroyed by the pannus invasion, with bone erosion resulting from generation of osteoclasts by fibroblasts and inflammatory cells
- Further joint destruction and systemic complication development occur with the release of several cytokines, interleukins (IL), growth factors and proteinases
- Anti-citrullinated protein antibody (ACPA), present in patients with RA, binds citrullinated residues on self-proteins (eg fibrinogen, type 2 collagen) resulting in complement activation
- Antibody presence in RA is called seropositive RA
- Rheumatoid factors (RF) participate in the pathogenesis of RA through immune complex formation leading to complement activation and leukocyte infiltration resulting in joint damage and inflammation
- Repeated activation of the patient’s innate immunity is also thought to be the mechanism responsible for environment-triggered RA
Risk Factors
- Include female sex, older age, familial (first-degree relative) and genetic (eg human leukocyte antigen [HLA]-DRB1 gene) factors, high-calorie low-fiber diet, physical inactivity, obesity, low socioeconomic status and level of education, stress
- Environmental risk factors include cigarette smoking, inhalant exposure (eg silica, chemical fertilizers), chronic mucosal or periodontal disease (microbial dybiosis), bacterial and viral infections
- Cigarette smoking increases incidence for developing RA in ACPA-positive patients
- Bacteria (eg Escherichia coli, Helicobacter pylori, Proteus mirabilis, Mycobacteria, Mycoplasma, Streptococcus), viruses (eg Epstein-Barr virus, rubella, parvovirus B19) and periodontal disease (Porphyromonas gingivalis) are strongly associated with the occurrence of RA
Signs and Symptoms
General
- Joint pain and/or swelling
- Typically involves the joints of the fingers, wrists and toes
- Upper and lower extremity joints may also be affected (eg shoulders, elbows, knees, ankles)
- Morning stiffness lasting ≥1 hour
- Myalgia, fatigue, asthenia, weight loss, low-grade fever, depression
- Syndrome of polymyalgia rheumatica may occasionally be present
Early Rheumatoid Arthritis
- Duration of occurrence of RA signs and symptoms is <6 months and meets the classification criteria of RA
Established Rheumatoid Arthritis
- Duration of occurrence of RA signs and symptoms is ≥6 months and meets the classification criteria of RA
Palindromic Rheumatism
- Follows an episodic pattern
- Joints may be affected for hours to days followed by symptom-free periods lasting for days to months
Undifferentiated Arthritis
- Patients with early inflammatory arthritis with a duration between 6 weeks to 1 year and whose disease cannot be clearly diagnosed or differentiated from other forms of arthritis
Extra-articular Involvement
- Anemia, fatigue, pleuropericarditis, interstitial lung disease, neuropathy, scleritis, Sjogren’s syndrome, vasculitis
- Subcutaneous rheumatoid nodules on extensor surfaces of elbows and over Achilles tendons
- Splenomegaly