What is the pathogenesis of rheumatoid arthritis (RA)?

Updated: Mar 05, 2021
  • Author: Howard R Smith, MD; Chief Editor: Herbert S Diamond, MD  more...
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The pathogenesis of RA is not completely understood. An external trigger (eg, cigarette smoking, infection, or trauma) that sets off an autoimmune reaction, leading to synovial hypertrophy and chronic joint inflammation along with the potential for extra-articular manifestations, is theorized to occur in genetically susceptible individuals.

The onset of clinically apparent RA is preceded by a period of pre-rheumatoid arthritis (pre-RA). The development of pre-RA and its progression to established RA has been categorized into the following phases [9] :

  • Phase I -  Interaction between genetic and environmental risk factors of RA
  • Phase II - Production of RA autoantibodies, such as rheumatoid factor (RF) and anti–cyclic citrullinated peptide (anti-CCP)
  • Phase III - Development of arthralgia or joint stiffness without any clinical evidence of arthritis
  • Phase IV – Development of arthritis in one or two joints (ie, early undifferentiated arthritis); if intermittent, the arthritis at this stage is termed palindromic rheumatism
  • Phase V - Established RA

Not all individuals will progress through the full sequence of phases, and studies are current research is investigating ways to identify patients who are at risk of progression, and to delay or prevent RA in those patients. [10]

Synovial cell hyperplasia and endothelial cell activation are early events in the pathologic process that progresses to uncontrolled inflammation and consequent cartilage and bone destruction. Genetic factors and immune system abnormalities contribute to disease propagation.

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