3. Rheumatoid Arthritis Flashcards Preview

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Flashcards in 3. Rheumatoid Arthritis Deck (43):

Most common cause of death due to rheumatoid arthritis?

CV disease, due to chronic inflammatory state


Articular disease: men v women?

what is major characteristic?

what are the major 2 types?

what is the connection with MHC genes?

Women > men

Major finding is synovial inflammation and sequelae

2 types: seropositive, seronegative

MHC genes: strong linkage with HLA-DR (Class II; antigen presentation to T-lymphocytes)


What is the HLA system?

What does it encode, where does it reside on the chromosome?

The HLA (Human Leukocyte Antigen) system is the loci of genes that encode MHCs (class I and class II).

Relates to immune system function.

Gene locus resides on Chromo 6. Class I (A, B, C) presents peptides from inside cell. Class II (DP, DM, DQ, DR) presents antigens from outside the cell to T-lymphs.

Mutations in HLA may be linked to autoimmune dz.

Impt to match HLAs for transplant compatibility.

Jen cannot remember this to save her life.


Extra-articular disease: men v women? what is the pathology?

men >> women

RF-dependent immune complex deposition

(this type of RA has largely disappeared due to treatment: Articular is the main form)

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what is the best serologic marker for RA?



what is ACPA?

Anti-Citrullinated Protein Antibody.

detects a post-translational modification to arginine that occurs in numerous proteins


what are citrullinated proteins?

proteins that have been deaminated (NH3 removed).

occurs in all cells.

RA happens to make an antibody against these altered proteins

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what does Broken tolerance mean?

the start of RA: the body has started to make ABs against self proteins (ACPA proteins)


in the first few years of RA, are the joints being targeted?

no, the joint involvement occurs years after tolerance is broken and there has been an immune response to self.

Joints are pro-inflammatory -- easy target for tissue injury via immune complex deposition


If a patient has ACPA, what else do we know about their RA?

they must be seropositive.

associated with HLA-DR.


What is the prognosis for seropositive v seronegative forms of RA?

seropositive associated with worse form of disease.

higher morbidity, mortality, extra-articular disease


what happens to around half of seroneg patients?

in half of seroneg pts, RA remits permanently


what is the % of seropos v seroneg patients in early RA (< 6 mo)?

what about late/refractory RA?

Early RA: 50/50 seropos/seroneg

Refractory RA: 85% seropos, 15% seroneg


Important factors to development of RA? (possible reasons why it was not described until 1900s)

tobacco, malnutrition, life expectancy (RA most common 40-60y), dental caries (availability of sugar)


HLA Class I alleles (A, B, C): associated with RA?


but associated with uveitis, ankylosing spondylitis, psoriasis, psoriatic arthritis, decr risk of AIDS after HIV infection, decr risk of neonatal transmission of HIV


HLA Class I alleles (A, B, C): important for what?

-anti-viral responses

-expressed by all nucleated cells

-present antigen to CD8 T cell

-anti-tumor response

-NOT impt for intelligence (per his stupid question)


HLA Class II alleles (DR, DP, DQ): associated with RA?



what is the shared epitope? why is it important?

presence of 4 AAs in the beta chain of HLA-DR.

important because confers 3-4x risk for seropositive RA.

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what is the relationship between ACPA and the shared epitope?

the ACPA is predictive of the shared epitope


why are the joints targeted in RA?

ACPA is developed elsewhere, then the immune complexes are deposited especially in joints.

this explains why the CD4+ Tcell can leave, but inflammation continues (long-lived plasma cells in bone marrow, continued complex formation, continued deposits)

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should RA sx improve with activity?



classic general presentation of RA? (not joint-specific)

progressive bilateral hand pain and morning stiffness, impaired hand strength, presence of clumsiness.

improves with activity, worse with rest.

preceded by systemic fatigue.


joints most affected by RA? joints that are spared?

MCPs, PIPs, wrists, MTPs.

DIP joints relatively spared

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what structure in the joint is being destroyed, leading to pain and loss of function?

synovium of joints becomes inflamed. causes erosion of tendon/ligament, or mis-alignment of joint.


cells present in synovium of RA joint?

inflammation: macrophages making TNF, fibroblasts making cytokines.

sub-synovial: usually fat present here. in RA, some lymphocytes, plasma cells


early sx of RA?

Joints affected?

joint erythema, warmth, swelling, loss of motion, flexion contractures.

possible rheumatoid nodules.

Hands (except DIPs), wrists, elbows, shoulders


late sx of RA?

loss of joint motion (severe), deformities of hands/wrists, metacarpal subluxation, ulnar drift.

PIPs: swan-neck (hyperextension), boutonniere

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RA: what will joints feel like on exam?

especially 2nd MCP will feel squishy, won't be able to feel bony joint below due to presence of inflamed synovium

same features on feet (look at 2nd/3rd MTP)

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what are the best PE tests for RA?

-shake hands; pt will wince

-ask pt to make a claw hand (flexion of PIP and DIP, extension of MCP)


ACPAs represent the 'breaking of immune tolerance'. Are ACPAs made in the joint years prior to onset of synovitis?

NO, they are not made in the joint. They are to modified arginines in multiple proteins, linked to the shared epitope, smoking, and RF.

They rarely disappear with remission (due to long-lived plasma cells)


ACPAs are the best test for RA because?

Specificity, and predictive of poor outcomes if not treated


Besides ACPA, other labs for RA?

test for RF: the IgM antibody against the Fc of IgG.

associated with immune complexes. Sensitive but not specific

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Do you need to do labs to dx RA?

no - just do the handshake and claw tests

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with treatment for RA, what are we trying to prevent?

pain, bone erosion, cartilage loss, joint deformity


when do the joint erosions occur in the timecourse of RA?

occur early, therefore early dx and treatment is very impt.


what are a few med choices for treating RA? which did the lecturer indicate as his favorite?

methotrexate = favorite. immunosuppressant, anti-inf.

others: prednisone, hydroxychloroquine, TNF, IL-6R, rituximab


according to a study in the Netherlands, what is the best strategy for dealing with RA with meds?

sequential monotherapy, changing treatment every few months if not working.

Step-up to combinations (add second agent) if needed. Trial and error involved.


Which lifestyle modification will be most beneficial in treatment of RA: Omega-3 fatty acids, sour cherry juice, weight loss, atkins diet, smoking cessation?

Stopping smoking.

Wt loss also helpful: fat is pro-inflammatory


extra-articular RA occurs primarily in which group:

-Smokers with RA

-Seropos RA

-Women with RA

-Elderly with RA?

Seropositive RA.

Women get more RA, but men get more extra-articular RA

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what is the pathology of extra-articular RA?

immune complex deposition -> vascular compromise (RF-dependent) -> synovial compression of surrounding structures/nerves


what is the relative prevalence of extra-articular RA?

On the decline, except for rheumatoid nodules and interstitial lung disease.

perhaps due to decr smoking, perhaps due to incr treatment of articular RA?


what are some sequelae of extra-articular RA?

-Rheumatoid nodules (on pressure surfaces, like olecranon)

-vasculitis (nerve, digital infarction -> necrosis)

-inflammation of eye (episcleritis/scleritis)

-ILD (mech unknown)


with extra-articular RA, what is one rare spinal complication due to the loss of ligamentous integrity?

C1 and C2 may separate with subluxation of the neck, as occurs with intubation. may lead to paralysis due to bruised spinal cord. may need to do awake intubation so pt can report tingling. get neck images both flexed and extended.

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