Rheumatoid Arthritis Disease Background

Last updated: 10 June 2024

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Introduction

Rheumatoid arthritis (RA) is a chronic, inflammatory arthritis of unknown etiology. It is considered as the most common autoimmune inflammatory arthritis in adults wherein persistent synovitis leads to joint destruction and deformity. It is believed to be a result of the interaction between genetic and environmental factors. 

Epidemiology

The worldwide prevalence of rheumatoid arthritis is approximately 0.24%. It is much less common in East or Southeast Asians than in Western European and North American ethnic groups.

The exact prevalence of the disease in Indonesia is unknown; however, according to the Indonesian Rheumatology Association, it was estimated that at least ≥1.3 million people may have the disease with a low remission rate of 24.5% based on the Indonesia National Registry.   

It is more prevalent in women than men with risk increasing with older age. The disability rate directly correlates with the disease duration.

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 the growth of new blood vessels which become occluded with inflammatory cells or small clots. 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 the generation of osteoclasts by fibroblasts and inflammatory cells. Further joint destruction and systemic complication development occur with the release of several cytokines, interleukins, growth factors, and proteinases. 

Rheumatoid arthritis - pathophysiologyRheumatoid arthritis - pathophysiology


Anti-citrullinated protein antibody (ACPA), which is present in patients with rheumatoid arthritis, binds citrullinated residues on self-proteins (eg fibrinogen, type 2 collagen) resulting in complement activation. Rheumatoid factors participate in the pathogenesis of rheumatoid arthritis through immune complex formation leading to complement activation and leukocyte infiltration resulting in joint damage and inflammation.

The presence of an antibody in rheumatoid arthritis is called seropositive rheumatoid arthritis. Repeated activation of the patient’s innate immunity is also thought to be the mechanism responsible for environment-triggered rheumatoid arthritis.

Risk Factors

Risk factors for the development of 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, and stress.  

Environmental risk factors include cigarette smoking, inhalant exposure (eg silica, chemical fertilizers), chronic mucosal or periodontal disease (microbial dysbiosis), and bacterial and viral infections. Cigarette smoking increases the incidence of developing rheumatoid arthritis in anti-citrullinated protein antibody-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. 

Classification

New Classification Criteria for Rheumatoid Arthritis 

The new classification criteria are developed by the American College of Rheumatology (ACR) Board of Directors and the European League Against Rheumatism (EULAR) Executive Committee. It can be applied to patients at more than one point in the evolution of their signs and symptoms. It is limited only to patients with clinical synovitis in at least 1 joint and synovitis not secondary to other diseases. A total score of ≥6/10 is needed to classify a patient as having definite rheumatoid arthritis. The scoring system based on the number and site of involved joints, serological and acute phase reactants abnormalities, and symptom duration are listed below.

Number and site of involved joints:

  • 5 points for >10 joints, including at least 1 small joint (eg metacarpophalangeal [MCP] joints, proximal interphalangeal [PIP] joints, second to fifth metatarsophalangeal [MTP] joints, thumb interphalangeal joint, wrists)
  • 3 points for 4-10 small joints
  • 2 points for 1-3 small joints
Serological abnormality (at least 1 test result is needed):
  • 1 point for 2-10 large joints (eg shoulders, elbows, hips, knees, ankles) 
  • 3 points for high-positive (>3x upper limit of normal [ULN]) rheumatoid factor or anti-citrullinated protein antibody points for low-positive (≤3x ULN) rheumatoid factor or anti-citrullinated protein antibody
Acute-phase reactants abnormality (at least 1 test result is needed):
  • 1 point for abnormal ESR or CRP
Symptom duration:
  • 1 point for ≥6 weeks
Classification by Severity of Disease

Rheumatoid arthritis can be characterized as mild, moderate, or severe which is best applied to untreated patients. 

Mild Disease

Patients meet the criteria for rheumatoid arthritis and have <6 inflamed joints, with the absence of extra-articular involvement and evidence of bone erosions or cartilage loss on X-ray.

Moderate Disease  

Patients have 6-10 inflamed joints with the presence of some of the following: 
  • Elevated erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)
  • Positive rheumatoid factor (RF) and/or anti-citrullinated protein antibody
  • Appearance of inflammation as well as minimal joint space narrowing
  • Small peripheral erosions on X-ray
  • Absence of extra-articular disease
Severe Disease  

Patients have >20 inflamed joints, elevated ESR and/or CRP, and the presence of ≥1 of the following clinical features: 
  • Anemia of chronic disease and/or hypoalbuminemia
  • Positive rheumatoid factor and/or anti-citrullinated protein antibody
  • Appearance of bone erosions and cartilage loss on X-ray
  • Presence of extra-articular disease