Rheumatoid arthritis Flashcards

1
Q

Define rheumatoid arthritis. What joints does it mostly affect.

A

A chronic, autoimmune condition which causes inflammation of joints, resulting in pain, stiffness and swelling.
Mainly affects the joints of the fingers, wrist, ankles and feet.

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2
Q

Describe the pathophysiology of Rheumatoid arthritis (activation of immune response)

A

Presence of genetic factors and exposure to environmental risk factor causes modification of self antigens by citrullination (arginine is converted to citrulline).
This modification causes self-antigens to be detected as foreign by antigen presenting cells. APCs become activated to initiate an immune response.

APCs migrate to lymph nodes and activate Helper T cells which go on to activate B cells in the germinal centre. B cells proliferate and differentiate to produce plasma cells. Plasma cells make autoantibodies against the self-antigens. The autoantibodies and T cells migrate to joint tissue.

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3
Q

Describe the immune response of RA in the joint tissue (synovial membrane and fluid)

A

In the synovial membrane:
Helper T cells - promote inflammation and secrete IL-17 and interferon gamma. IL-17 stimulate macrophage activity, promote activation of Fibroblast Like Synoviocytes and expression of RANKL for bone resorption.

Macrophages: are usually quiescent in synovial tissue. But in RA, they secrete TNF alpha, IL1 and IL6. These cause inflammation and stimulate the FLS to become active and proliferate.

Fibroblast like synoviocytes: Once activated by cytokines, FLS proliferate to produce the pannus - thick, swollen synovial membrane with granulation tissue.

Plasma cells: they assist inflammation through cytokines and antibodies.

IN SYNOVIAL FLUID:
neutrophils: produce proteases and reactive oxygen species that promote bone and cartilage erosion, and contributes to inflammation.

Angiogenesis: occurs too, as a blood supply is needed for leukocyte migration and formation of the inflammatory pannus.

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4
Q

What is the specialised type of cell in synovial membrane and what is its function? What feature doe they contain abundantly

A

Fibroblast Like Synoviocytes (FLS) - produce synovial fluid. Have lots of rough ER.

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5
Q

Which immune cell is most abundantly found int eh synovial tissue in RA? and how much is there?

A

Helper T cells (50%)

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6
Q

What are the 2 main autoantibodies in RA, what do they targets and what immune response do they have on the joint?

A

Rheumatoid factor (IgM): targets the Fc portion of IgG antibodies, forms an immune complex and deposits in synovial fluid.

Anti-cyclic citrullinated peptide antibody: targets citrullinated proteins such as fibrin and filaggrin.

The autoantibodies and to their targets and form immune complexes which accumulate in the synovial fluid. They activate the complement system.

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7
Q

What is citrullination?

A

Conversion of arginine residues to citrullinate

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8
Q

List the changes that RA causes to synovial joints

A

Inflammation and hypertrophy of synovium (synovial membrane)
Cartilage erosion
Bone erosion

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9
Q

What are the risk factors of RA

A

Genetic:
HLA DR1 or HLA DR4

Non-genetic: 
Female
Middle aged
Smoking 
Infection 
Obesity
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10
Q

what are the symptoms of RA?

A
Joint pain
Joint stiffness which is usually worse in the morning (longer than 30 mins)
Warm, red, swollen joints
Fatigue
Fever
Poor appetite
Weight loss 
Sweating
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11
Q

Describe the diagnosis of RA

A

Specific blood tests: can help with diagnosis but aren’t always accurate

Rheumatoid Factor: naturally present in people but raised levels are indicative of RA. (higher the value, the worse the prognosis)

Anti CCP: can be used for those who tested negative for RF. Only found in 70% of people with RA.

Raised CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate) also indicate inflammation can be used for diagnosis.

X-rays and MRIs: allow you to identify bony erosions but not good for diagnosis because these features are seen in late disease progression.

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12
Q

Why are the specific blood tests for RA not always accurate?

A

Only 50% of those with RA test positive for RF and not everyone with RA has the anti-CCP.

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13
Q

Describe the traditional treatments for RA, including examples.

A

DMARDs (disease modifying anti-rheumatic drugs) - they slow down disease progression and relieve symptoms by reducing pain and inflammation. They usually work better in combination.

e.g. methotrexate (usually given first), hydroxychloroquine, sulfasalazine, leflunomide.

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14
Q

What other drugs can be used in symptom relief of RA

A

NSAIDs - relieve pain but odnt stop disease progression
PAracetamol
Corticosteroids: used in combination with methotrexate. Work faster than DMARDs and can control symptoms but not prevent further damage

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15
Q

Describe novel therapeutic approaches designed at reducing the immune response in RA and give examples

A

Biological agents
Tumour necrosis factor inhibitors: etanercept, infliximab, adalimumab and golimumab.

Abatacept (inhibits T cell activation)
Tocilizumab (IL6 inhibitor)
Rituximab (works against the CD20 protein found on B cell surface)

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16
Q

What are patients advised to take alongside corticosteroids and why?

A

Vitamin D and calcium supplements as corticosteroids can reduce bone mineral density

17
Q

As RA is a systemic disease, what other body parts does it affect?

A

Skin: contributes to module formation
Cardiovascular: increase plaque formation and risk of myocardial infarction and stroke.
Liver: produces more hepcidin which contributes to anemia.
Neurological: fatigue and depression
musculoskeletal: osteopenia, muscle wastage (breaks down proteins in muscle)

18
Q

Describe the deformities caused by Rheumatoid arthritis

A
Ulnar deviation (fingers all deviate to the ulnar side )
Boutonneire deformity (PIP flexion and DIP hyperextension)
Swan neck deformity (DIP flexion and PIP hyperextension)
19
Q

Apart from drug therapy describe the management of RA

A

Physiotherapy
Occupational therapy
Surgery:
Carpal tunnel release
Release of tendons to treat abnormal bending
Arthroscopy to remove inflamed joint tissue
Joint replacement

20
Q

describe the impact and long term consequences of RA

A

Lung disease: increased risk of inflammation and scarring of lung tissue
Heart problems: atherosclerosis, CAD, Pericarditis
Carpal tunnel syndrome
Scleritis or vision loss
Anemia

Disability
Loss of independence
Depression