Rheumatoid%20arthritis Signs and Symptoms

• 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

• Prevalence worldwide is approximately 0.24% 
• Least common in East/Southeast Asians than with Western European and North American ethnic groups 
• More prevalent in women than men with risk increasing with older age   

• 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 rheumatoid arthritis, binds citrullinated residues on self-proteins (eg fibrinogen, type 2 collagen) resulting in complement activation 
  • Antibody presence in rheumatoid arthritis is called seropositive rheumatoid arthritis 
• Rheumatoid factors (RF) participate in the pathogenesis of rheumatoid arthritis 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 rheumatoid arthritis  

• 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), and bacterial and viral infections  
  • Cigarette smoking increases incidence for developing rheumatoid arthritis 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 rheumatoid arthritis

General 

• Joint pain and/or swelling
• Morning stiffness lasting ≥1 hour
• Myalgia, fatigue, weight loss, low-grade fever, depression
• Typically involves the joints of the fingers, wrists, toes
  • Upper and lower extremity joints are also affected (eg shoulders, elbows, knees and ankles)
• Syndrome of polymyalgia rheumatica may occasionally be present

Early Rheumatoid Arthritis

• Duration of occurrence of rheumatoid arthritis signs and symptoms is <6 months and meets the classification criteria of rheumatoid arthritis

Established Rheumatoid Arthritis

• Duration of occurrence of rheumatoid arthritis signs and symptoms is ≥6 months and meets the classification criteria of rheumatoid arthritis

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