Rheumatoid Arthritis Flashcards by Aimee Love

What is arthritis?

Inflammation of the joint

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What is rheumatism?

Umbrella term for conditions causing chronic pain affecting the joints/connective issue

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Give examples of rheumatic diseases

RA
Seronegative arthritis
Gout/pseudogout 
Connective tissue dx 
Systemic vasculitis
Bone disease

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What are the functions of the normal synovium?

Maintain intact tissue surface
Lubrication of cartilage
Controls synovial fluid production and composition
Nutrition of cartilage

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What is the appearance of a rheumatic joint?

Bone eroded
Cartilage thinning
Synovial inflammation
Loss of joint space etc.

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Define rheumatoid arthritis

Chronic autoimmune symmetrical polyarticular inflammatory joint disease and other systemic features

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What joints does RA tend to affect?

MCP, PID, MTP

As disease worsens can affect large joints - shoulder, knees, ankles, elbows

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What type of disease is RA?

Autoimmune

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What is the aetiology of RA?

Interaction of a genetic factor with an environmental factor

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What is the strongest genetic association with RA?

HLA-DR4

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What environmental factors are most associated with RA?

Cigarette smoking
Pathogens (EBV, CMV, E. coli, mycoplasma, periodontal disease)
Gut microbiome

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Repeated insults in a genetically susceptible person leads to:

Modification of our antigens, e.g. IgG antibodies or other proteins, e.g. type 2 collagen
E.g. via citrullination

Immune system doesn’t recognise these antigens to be self anymore

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What is citrullination?

Conversion of arginine into citrulline

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Changes to these proteins, mean the host immune system doesn’t recognise their antigens as self anymore - what does this lead to happening?

Antigens picked up by APC
APC cells carry antigen to lymph nodes and activate T-helper cells
T-helper cells stimulate B cells –> plasma cells –> autoantibodies

T helper cells and autoantibodies reach joint
T cells secrete cytokines, e.g. IF-gamma, IL-17 to recruit macrophages etc.
Macrophages produce TNFa and IL1 and Il6 –> stimulates synovial cells to proliferate –> pannus (made up of scar tissue, and T lymphocytes, macrophages)

Pannus damages cartilage and bone
Activated synovial cells make proteases –> breaks down protein in cartilage

Exposed bone rubs against each other

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Explain the correlation of RANKL and RA

Inflammatory cytokines release in RA, cause T cells to have more of a surface protein RANKL

RANKL allows T cells to bind to RANK protein on osteoclasts –> causing them to break down more bone

Chronic inflammation –> angiogenesis –> more blood cells can make their way to the joint

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What is rheumatoid factor?

IgM antibody that targets the Fc domain of altered IgG antibodies

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What is anti-CCP?

Antibody that targets citrullinated proteins

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What happens when autoantibodies meet their antigens?

They form immune complexes which sit in the synovial fluid and can activate the compliment system –> joint inflammation and injury

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Why are there sometimes extraarticular manifestations in RA?

Inflammatory cytokines can escape from the BS and reach multiple organs
E.g. IL1 and 6 travel to the brain and act as pyrogens –> fever
In skeletal muscles, cytokine can induce protein breakdown
In the skin they lead to rheumatoid nodules

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What is a rheumatoid nodule?

Round collections of macrophages and lymphocytes with a central area of necrosis

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What are the lung manifestations in RA?

Fibrosis can occur, leading to reduced gas exchange

Pleural effusion

What haematological condition is associated with RA?

Iron deficient anaemia

What are flares of RA?

Sudden worsening of condition

Joints become swollen, red, warm and painful

What are common hand deformities in RA?

Ulnar deviation
Butonniere deformity
Swan neck deformity

Describe butonniere deformity

Hyperextension of DIP, flexion of PIP

Describe swan neck deformity

Hyperextension of PIP, flexion of DIP

What white blood cell does the synovial fluid contain in RA?

Neutrophils (esp during acute flares)

What two antibodies are associated with RA?

anti-CCP, RF

How does prognosis differ based on presence of anti-CCP?

Worse prognosis with anti-CCP antibodies

What medicines are used to treat RA?

NSAIDs - acute flares DMARDs (disease modifying antirheumatic drugs) Biologics Corticosteroids (IA, IM, oral)

What are the effect of DMARDs?

Slow disease activity and retard disease progression

What DMARDs do we currently use?

Methotrexate - gold standard Sulfasalazine Hydrochloroquine Leflumomide

What did DMARDs did we used to use?

Gold salts Penicillamine Others

What is the therapeutic regime for RA?

Early, aggressive treatment --> optimal outcomes | Effective suppression of inflammation will improve symptoms, prevent joint damage and disability

What is good about methotrexate?

Effective, well tolerated, cheap Cornerstone of combination treatment (DMARD and biologic) Toxicity predictable and monitorable

In what ways are biologics better than DMARDs?

They work rapidly and are generally well tolerated

In what ways are biologics worse than DMARDs?

They are large complexes so must be given parenterally Important toxicities, e.g. infection, TB, cold, flu High cost Better when co-prescribed with methotrexate Risk of malignancy?

What are current biologics?

``` TNFa inhibitors IL-1 inhibitors (anakinra) Anti B cell therapies (rituximab) Anti T cell therapies (abatacept) IL-6 inhibitors Others ```

When do we give corticosteroids to people with RA?

Rarely - to put them in clinical remission during acute situation Longer you are on them --> less effective they are and the more SEs you get (e.g. cataracts, infections)

What is the classification we use for RA?

2010 EULAR/ACR

Who should be tested for RA according tot he 2010 EULAR/ACR?

Those with: 1. at least 1 joint with definitive clinical synovitis (swelling) 2. synovitis not better explained by another disease

A score of what on the 2010 EULAR/ACR is considered as definite RA?

6 or more out of 10

What is the EULAR/ACR 2010 classification of RA?

A. JOINT INVOLVEMENT 1 large joint - 0 2-10 large joints - 1 1-3 small joints (w/w.o. large joint involvement - 2 4-10 small joints (w/w.o. large joint involvement - 3 >10 joints (at least 1 small joint) - 5 B. SEROLOGY negative RF and ACPA - 0 Low-positive RF or ACPA - 2 High positive RF or ACPA - 3 C. ACUTE PHASE REACTANTS Normal CRP/ESR - 0 Abnormal CRP/ESR - 1 D. DURATION OF SYMPTOMS <6 weeks - 0 6 weeks+ - 1

What is the prevalence of RA?

In which gender is RA more common?

Females (3x more common)

What investigations can you use for RA?

RF, antiCCP, ACPA XRay USS may show effusions, pannus formation

What are the symptoms of RA?

``` Pain Stiffness Immobility Poor function Systemic symptoms ```

What are the signs of RA?

``` Swelling Tenderness Limited RoM Redness Heat ```

What are the non-specific systemic features of RA?

Fatigue/lassitude, wt loss, anaemia

What are the specific systemic features of RA?

Eyes, lungs, nerves, skin and kidneys Long term - CVS (increased risk of atheroma), and malignancy

How do you measure the severity of RA?

Disease activity score (DAS) <2.4 clinical remission >5.1 indicates eligibility for biologic therapy

What is the prognosis for RA?

75% cases diagnosed during working life 33% stopped working within 2 years of diagnosis 50% unable to work due to disability in 10 years 40 sick days p/a