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muscular skeleto > RA > Flashcards

RA Flashcards

1
Q

what is rheumatoid athritis?

A

it is a prototype of chronic inflammatory joint disease

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2
Q

what is the prevalence of rheumatoid athritis?

A

around 1%

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3
Q

what is the male to female ratio of RA?

A

female: male ratio 3:1

5% women, 2% men >55 years age affected

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4
Q

what are the characteristics of rheumatoid arthritis?

A

symmetrical inflammatory polyathritis

affects small and large synovial joints

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5
Q

which joints are involved on presentation of RA?

A

polyarticular joints (affecting many) present in 75% of cases including small joints of hands and feet, large joints, large and small joints

monoarticular joints present in 25% of cases including the knee in 50% of cases

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6
Q

what features are present in RA?

A

circulating anti-globulin antibodies (rheumatoid factors)

associated systemic disturbance

extra articular features

exacerbations and remissions

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7
Q

what are some extra-articular features of RA?

A

scleritis in eye

effusions in lung pleura

effusions in pericardium

splenomegaly in spleen

amyloidosis in kidney and gut

anemia in bone marrow

muscle wasting

skin thinning

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8
Q

what is the genetic susceptibility of RA?

A

60%

gene on short arm chromosome 6, MHC genes

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9
Q

how is the MHC gene affected in the pathogenesis of RA?

A

major histocompatibility genes (MHC) code for the HLA class II molecule expressed on antigen presenting cells (macrophages & T cells)

HLA DR4 subtypes Dw4 & 14 and
HLA DR4 subtype Dw1

the disease associated HLA-DRB1 alleles share an amino acid sequence with normal HLA at positions 70-74 in the third hypervariable regions of the hLA-DR chain (shared epitope)

this is associated with production of anti-citrullinated peptide (CCP) antibodies and worse disease outcomes

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10
Q

how is arthritis initiated in RA?

A

initial event: T cell activation by primed antigen presenting cell

antigen presenting cell releases cytokines: IL-1, TNF-alpha, IL-6

T cell releases IL-2/15/17 for signalling

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11
Q

what is the process during the onset of synovitis in RA?

A

angiogenic cytokines are released from the connection between the APC and T cell

growth of new blood vessels

the cytokines TNF-alpha, IL-1, IL-6, IFN-gamma activate endothelium

lymphocytes, monocytes, neutrophils drawl in along with oedema fluid, become activated and produce more cytokines (positive feedback loop)

IL-1 and OPGL activate osteoclasts and with fibroblasts (MMPs) erode bone and cartilage

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12
Q

what are the pro-inflammatory cytokines in RA?

A

TNF-alpha

IL-1

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13
Q

what are the anti-inflammatory cytokines in RA?

A

soluble TNF receptor

IL-10

IL-1 receptor antagonist

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14
Q

what does the synovial tissue look like in RA and how does it infiltrate bone?

A

hyperplasia of the synovial lining layer which is lying on the outside of the cartilage layer which is just on surface of bone

sub lining inflammatory infiltrate of lymphocytes, plasma cells and macrophages which eventually break through the articular cartilage and access the bone

areas of cartilage loss

synovial granulation

loss of bone trabeculation with infiltrating granulation tissue

pannus is the gathering of inflammatory cells on outside of cartilage and erosion happens when it has infiltrated into the bone

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15
Q

what are the non-genetic risk factors of RA?

A

40% of risk

smoking

microbiota

female sex

western diet

ethnic factors

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16
Q

what is the development and progression of RA?

A

1) susceptibility to RA through risk factors but no detectable autoimmunity, no symptoms or signs
2) preclinical RA caused by initiation of autoimmunity which can be divided into initially increase in cytokines, chemokines and CRP IN CIRCULATION AND THEN EARLY SYMPTOMATIC AUTOIMMUNITY
3) propagation of autoimmunity, divided into early RA and established RA, early is undifferentiated athritis, late is classifiable RA

17
Q

what happens in the initiation of autoimmunity stage?

A

post-translational modification (citrullination)

loss of immunotolerance at mucosal sites

autoantibody formation: ACPAs and RF

18
Q

what is diagnostic test for RA?

A

MRI is sensitive imaging of synovitis

ultrasound - increased doppler activity

agglutination tests for circulating anti-globulin antibodies (rheumatoid factors) (IgM RF)

19
Q

what are the two agglutination tests for IgM rheumatoid factor?

A

latex tests uses polystyrene particles carrying absorbed human iGG which agglutinate iGM rheumatoid factor

sheep cell tests

20
Q

what is the sensitivity and specificity of IgM rheumatoid factors?

A

reasonable sensitivity: positive in 70-80% patients with RA

not very specific: some infections and autoimmune diseases and present in 5-10% of healthy people

21
Q

what is the sensitivity and specificity difference of rheumatoid factos and anti-cyclin citrullinated peptide (anti-CCP) antibodies?

A

anti-CCP:

only slightly better sensitivity : eventually positive in 96-98% RA patients, 50% in early RA (3-6 months of symptoms)

much better specificity-very few false positivies, 93% patients with anti-CCP antibodies and undifferentiated inflammatory arthritis progress to RA in 3 years

22
Q

what is the link between smoking and autoimmune Rheumatic disease?

A

smoking is important for anti-CCP+ and RF+ RA but not sero negative disease

smoking interacts with HLA-DR shared epitope genes conferring high risk of anti-CCP+ RA

without smoking, 33% cases would not have occured in sweden

23
Q

what is the approach to RA treatment?

A

analgesia/ physio/ occupational therapy

NSAIDS

DMARDS

current approach is early intervention and suppress all inflammation with DMARDS to control symptoms and delay disease progression

all patients with persistent inflammatory joint disease (>6-8 weeks) already receiving simple analgesics and NSAIDS considered for referral for specialist rheumatology opinion and DMARD therapy- within 12 weeks

24
Q

what are the DMARDS used in RA?

A

methotrexate

sulphasalazine

hydroxychloroqine

leflunomide

25
Q

what is the 2010 RA classification criteria?

A

redefined paradigm of RA

focussed on features of early disease that predict erosions and persistent signs (serology, duration>6 weeks, acute phase response)

need for early diagnosis and initiation of effective disease suppressive therapy

26
Q

TNF inhibitors and treatment of RA

A

revolutionised treatment of aggressive RA

all agents have equal efficacy

30% patients fail to respond , could respond to another

poorer response in females, smokers, higher baseline HAQ scores, higher baseline CRP , anti-CCP+ patients

infliximab, etanercept

27
Q

what other targeted DMARDS are there for RA?

A

IL-1: anakinra

IL-6: tocilizumab

B cells: retuximab

28
Q

what are the 2009 UK NICE guidelines for use of biologics in RA adults?

A

adalimumab, etanercept, infliximab (TNF antagonist) : active disease, failed 2 DMARDS including methotrexate> 6 month duration, combine with methotrexate

retuximab: severe & active disease, failed DMARD and at least 1 TNF-antagonist, combination with methotrexate, discontinue if response inadequate

29
Q

what are the recent additional synthetic targeted therapies for RA?

A

kinase inhibitors

janus kinas inhibitors: JAK 1,2,3: tofacitinib

JAC 1&2: baricitinib

tyrosine kinase inhibitor: fostamatinib

these now used as third-line agents

30
Q

what are the two different types of DMARDS?

A

biological

targeted synthetic

31
Q

what is the therapeutic strategy of RA?

A

early diagnosis and immediate treatment initiative

methotrexate plus low-dose glucocorticoid

upon failiure: stratify to risk factors present- add biological agent,
with risk factors absent, switch to (or add) another csDMARD plus glucocorticoid and then go to biological agent

after, switch to any other biologic agent (even within same class) plus methotrexate or a tsDMARD

32
Q

how to follow up RA patients?

A

use composite measure of disease activity that comprises joint counts

aim at clinical remission (ACR-EULAR criteria) or at least low disease activity within 6 months

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