Pathophysiology of Rheumatoid Arthritis

What is the score that encompasses a "definite" RA diagnosis?

A score of greater than or equal to 6 out of 10 is classified as "definite" RA

What is the definition of rheumatoid arthritis?

A systemic, progressive inflammatory autoimmune disease of characterized by *symmetric* poly arthritis

What is the prognosis of RA?

10% of patients undergo spontaneous remission within 6months of disease onset Over 50% of patients are unable to work 10years after the disease onset Mortality rate in RA is 2x greater than in the general population Poor prognostic factors include: - Functional limitations based on HAQ-DI or another tool (PAS, CDAI or DAS28) - Extra-articular disease (of which the most common are the rheumatoid nodules) - Positive RF or Anti-CCP antibodies - Bony erosions on radiograph

How do you definitively diagnosis RA?

At least (1) joint with definite clinical synovitis that is not better explained by another disease like gout

Anti-CCP Antibodies

Binds to non-standard amino acid citrulline. It is formed by removal of Amin groups from arginine. In RA, proteins may be transformed to citrulline during the process that leads to joint inflammation. It is highly specific for RA Higher concentrations lead to poorer prognosis Testes for using ELISA assay and reported in ELISA units (EUs)

What two types of joint disfigurations can occur in rheumatoid arthritis?

Boutonniere Swan neck

What is the progression of rheumatoid arthritis pathophysiology?

Chronic inflammation of synovial tissues that lines the joint capsule, known as synovial hyperplasia Tissue proliferation Pannus invades cartilage and bone Joint destruction

What are the genetic and environmental factors leading to rheumatoid factors?

Genetic factors - Certain HLA alleles - 1st degree relative are more likely to develop the disease Environmental factors - Smoking as a factor was established in twin studies - Infectious agents such as the Epstein-Barr virus

What is the Rheumatoid Factor?

Immunoglobulins are directed at the Fc portion of the IgG There are other disease associated with a positive RF but at lower titers than RA Normal titer is <1:20 Higher RF results in a poorer prognosis

What is the epidemiology of rheumatoid arthritis?

It affects about 1% of the adult population Female to male ratio is 3:1 but it is higher in age 15-45 yo females over men It can occur at any age

What can radiography tell us about joint progression?

It can reveal the erosion of the joint over time

What is the pathophysiology of rheumatoid arthritis?

It is the breakdown of self-tolerance It involves the formation of autoantibodies such as the rheumatoid factor Infiltrating CD4+ T-Cells stimulate secretion of IL-1, IL-6 and TNF trigger the release of proteolytic enzymes and stimulate osteoclasts. This results in tissue and bone destruction and joint damage

What are the categories used to classify rheumatoid arthritis?

Number of joints involved Serology Acute phase reactants Duration of symptoms

What are the laboratory abnormalities that are seen in RA?

Rheumatoid Factor Anti-cyclic citrullinated peptide antibodies Acute phase reactants such asESR and CRP

What are the most common extra-articular manifestations in RA?

Rheumatoid Nodules 30-40% of patients develop firm, non-tender nodules that are common in areas subject to repeat trauma and irritation. These areas include the forearm, Achille tendon and sacral prominences They are typically benign but if they are injured, they can cause infection

What is the clinical presentation of Rheumatoid Arthritis?

Symptoms include: - Joint paint/stiffness greater than or equal to 6 weeks - Fatigue - Weakness - Low grade fever - Loss of appetite Signs include: - Tenderness and warmth over the affected joints - *Symmetric* joint involvement - Rheumatoid nodules The clinical presentation of arthritis develops slowly over the course of a few weeks which distinguishes it from gout.

What is the assessment for RA?

The *etiology* of RA includes genetic and environmental factors that lead to the breakdown in self-tolerance, generation of autoantibodies and destruction of joints. We determine the *severity* of RA using disease activity measures and functional classification *Why now?* This may be unknown if they are initial symptoms. Or the why now could be disease progression. This is a progressive disease.

What are the functional classifications used for?

The functional classification is useful in: - Measuring changes in clinical status over time - Functional status shifts during times of disease flare and remission

What are the most commonly involved joints in rheumatoid arthritis?

The wrists Meta-carpalphalangeal (MCP) Proximal interphalangeal (PIP)

What are the less common extra-articular manifestations in RA?

Vasculitis (1%) Sjorgen's Syndrome (10%) - Dry eyes and mouth Pulmonary manifestations that must be differentiated from lung cancer Cardiac issues such as pericarditis and cardiomyopathy that increase risk of cardiovascular mortality Hematologic manifestations such as anemia and Felty's syndrome