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Flashcards in Rheumatoid Arthritis Deck (72)
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What is Rheumatoid Arthritis?

A chronic multisystem, autoimmune disease of unknown etiology that has a variety of systemic features, but the hallmark of the disease is persistent inflammatory synovitis usually involving peripheral joints in a SYMMETRICAL distribution.  The persistent synovitis has a propensity to erode cartilage and bone and reduce joint integrity.


Disease course is variable and is likely influenced by genetics and environmental factors 


Patient population for RA?

•Worldwide distribution across all ethnic groups

•Peak incidence ranges from mid-30s to 50s, increasing prevelance with age and 3x more common in females

•Genetic predisposition and familial aggregation confirmed



T or F. RA is associated with increased mortality

T. mortality rates increased about 2 times over general population – RA is not a “non-fatal” disease


What HLA type is most associated with RA risk?

HLA DR4 (30% genetic risk) in the DRB1 area of HLA class II regions 

'shared epitope' allele hypothesis suggest two copies will have very severe disease



What are rheumatoid factors (RF)?

Antibodies directed against the Fc portion (bottom) of IgG. (Usually IgM type, IgG and IgA type have been described)


Rheumatoid Factor is not specific to RA. What other diseases is it common in?

•Rheumatoid arthritis-26 to 90%

•Sjὅgren’s syndrome- 75 to 95%

•Mixed connective tissue disease- 50 to 60%

•Mixed cryglobulinemia (types II and III)- 40 to 100%

•Systemic lupus erythematosus- 15 to 35%

•Polymyositis or dermatomyositis – 5 to 10%


Can RF be present in healthy individuals?

•Healthy individuals: Young: 3-4%, older: 3-25%


Also seen in HEP B/C, sarcoidosis, or B-cell malignancy


What are some other unique Abs seen in populations of RA?

•Anti-CCP antibodies (ACPA)

–Cyclic citrullinated peptide (via PAD4 enzyme conversion of arginine to cytrulline)

–More specific marker of RA than the rheumatoid factor


•Antinuclear antibodies (ANA)

–Seen in 20% of RA patients (more milder RA with these patients)

–(Does not necessarily mean lupus!)


Can ACPAs be found in synovial fluid?

Yes, they can also be produced by synovial tissue B cells 


T or F. ACPAs are predictors of less aggressive disease

F. ACPAs are predictors of more aggressive disease marked by bone and cartilage destruction.

In patients with early undifferentiated inflammatory arthritis, ACPAs are also predictive for individuals who will progress to RA. 


APCAs can also have pathogenic potential. How?

They can activate complement pathways. IgE ACPAs from patients with RA can sensitize basophils and mast cells leading to degranulation. 


Describe the 2010 ACR/EULAR classificaiton criteria for RA diagnosis 

Four components:

-joint distribution (0-5)

-serology (0-3)

-symptom duration (0-1)

-acute phase reactants (0-1)

A combined score of 6+ = definite RA


Describe the joint distrubtion components of RA diagnosis 

1 large joint- 0

2-10 large joints- 1

1-3 small joints- 2 (large joints not counted)

4-10 small joints- 3 (large joints not counted)

10+ joints (at least 1 small joint)- 5


Describe the serology component of RA diagnosis

Negative RF AND negative ACPA- 0

Low Positive RF OR low positive ACPA- 2

High positive RF OR high positive ACPA- 3


Describe the symptom duration component of RA diagnosis

less than 6 weeks-0

over 6 weeks-1 


Describe the acute phase reactant component of RA diagnosis

Normal CRP AND normal ESR-0

Abnormal CRP OR abnormal ESR-1 


Autoimmunity of RA Key Points

1. Evidence of autoimmunity can be present in RA many years before the onset of clinical arthritis.

2. Autoantibodies in RA can either recognize joint antigens such as type II collagen, or systemic antigens such as glucose phosphate isomerase.

3. These autoantibodies can potentially contribute to synovial inflammation through several mechanisms including local activation of complement.


Role of T cell cytokines Key Points 

1. Several subsets of T cells have been implicated in the pathogenesis of RA.

2. Relatively low levels of T cell cytokines are present in RA synovium.

3. The T cell cytokines that are present, such as IFN-γ and IL-17, can be produced by Th1 cells or Th17 cells.

4. Regulatory T cell function, which suppresses activation of other T cells, might be low in RA synovium.

5. The contribution of T cells to synovial inflammation can be through antigen-independent mechanisms such as direct cell-cell contact with macrophages (which causes TNFa and Il-1 release).


T or F. Macrophage and fibroblast cytokines are abundant in RA synovium.

T. Chemokines that recruit inflammatory cells into the joint are commonly produced by macrophages and fibroblasts.


What molecules secreted/produced by macrophages and fibroblasts in the synovium promote inflammation?

proinflammatory cytokines such as IL-1, TNFα, IL-6, IL-15, IL-18, GM-CSF, and IL-33. These and many other factors help perpetuate synovial inflammation.


Are any anti-inflammatory cytokines produced in RA synovium?

Yes, Anti-inflammatory cytokines such as IL-1Ra and IL-10 are produced in rheumatoid synovium, although in amounts insufficient to suppress proinflammatory cytokine function or production.


What are some of the systemic features of RA?

•Fatigue, anorexia, weight loss, weakness, generalized aching and stiffness, low grade fever. These often appear as a prodrome to disease onset and are commonly worse with increases in disease activity (flares)


How does joint impairment present in RA?

There is prolonged morning stiffness (AT LEAST 30 minutes) that may persist for several hours (note that in OA it is brief) and gets better throughout the day.


Joint onset is often insidious and intermittent, not migratory, and eventually develops to a perssitent polyarthritis 


Swelling, warmth, and erhythma (interleukins) seen around impacted joints 


What would analysis of RA synovial fluid show?

–exudative yellow fluid

–elevated number of white blood cells

–reduced viscosity


EARLY Joint involvment in RA

At disease onset:

–RA may begin as an intermittent mono- or oligoarthritis (one or a few scattered joints)

–often involves large peripheral joints such as the knee


What is a 'typical' joint distribution of established RA?

–joint involvement in RA tends to be SYMMETRICAL

–the most characteristic pattern is wrist and proximal hand joint involvement, i.e. metacarpophalangeal (MCP) joints and proximal interphalangeal (PIP) joints

–other joints that frequently become involved include the knees, hips, ankles, elbows, shoulders


Pattern of joint involvement in established RA

the proximal hand (MCPs and PIPs) are most often affected symmetrically, as well as the knees, hips, elbows, shoulders, and ankles 


DIPS are not usually invovled (think OA)


Can the spine be involved in RA?

Yes, typically only the very upper cervical spine (C1-C3) in late/adavnced RA and after several years of disease.


How does spinal involvement in RA present?

May present as only neck pain or may progress to spinal cord progression with symptoms ranging from sensory loss to catastrophic neurologic compromise and sudden death


How can RA cause structural damage and deformity?

•Chronic inflammation

–May weaken tissues and supporting structures e.g. ligaments, joint capsules or may lead to fibrosis and tightening of tissues e.g. lumbical muscles of the hand


•Muscle atrophy from inflammation and disuse


•Deformities occur under normal forces of muscular traction

–Wrist: volar subluxation with radial-ward rotation

–MCP joints: ulnar deviation

–PIP and DIP joints: Swan-neck and Boutonniere deformities