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Rheumatoid Arthritis > L22 - RA & Autoimmune disease > Flashcards

L22 - RA & Autoimmune disease Flashcards

1
Q

What systems are affected in RA and their symptoms?

A

1) Musculoskeletal - predominantly joints (synovial/diarthroidial joints)
2) Skin - rashes
3) Lungs - nodules
4) Eyes - connective tissue inflamed
5) Peripheral nerves - Tingling and numbness in toes
6) Connective tissue - nodules on tendon/bursae
7) Blood - All things in bloodstream affected; low RBCs, WBCs and platelets

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2
Q

What factors relating to RA contribute to increased mortality?

A

1) blood vessel changes - arterial atheroma/atherosclerosis –> heart attack/stroke
2) neoplasia/cancers esp. lymphoma

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3
Q

Tendons and bursas commonly affected by RA:

A

1) front of knee
2) tip of elbow (lateral epicondyle - tennis elbow & olecranon bursa)
3) side of hip bones

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4
Q

Differences in pattern of body involvement of RA and OA

A

RA: upper limb (shoulder, elbow, wrist), metacarpophalangeal joint, metatarsophlangeal joint, mid tarsal joint
OA: distal interphalangeal joint

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5
Q

Similarities of pattern of joint involvement in RA and OA

A

1) neck
2) lower limb (hip and knee)
3) proximal interphalangeal joint

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6
Q

What happens to synovium in RA?

A

It becomes:

  • hypertrophic
  • hyperplasic
  • hypervascular
  • WBC infiltration
  • panus formation
  • proteoglycan loss at cartilage
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7
Q

Specificity and sensitivity of Rheumatoid Factor?

A

85% and 69% respectively

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8
Q

What are the two main enzymes involved in citrullination of proteins in humans? And where are they expressed?

A

Peptidylarginine deaminase 2 and 4
PAD2 - expressively expressed and found in many tissues
PAD4 - expressed only on neutrophils and eosinophils
(There are 5 isoforms identified in humans)

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9
Q

What activates PAD?

A

Ca2+ from apoptosis
Environmental stressors at mucosal barrier: Lung (smoking, industrialisation)
Mouth
Gut

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10
Q

What are the citrulinnated proteins found in RA patients?

A 
Fibrogen
a-enolase
Vimentin
Fibronectin
Collagen
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11
Q

What are the sensitivities and specificity of ACPA?

A

67% and 95% respective

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12
Q

What is the combined specificity for RA for with ACPA and RF?

A

99%

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13
Q

Normal functions of citrullination

A

Epithelial differentiation
Gene regulation
Immune activation

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14
Q

ACPA functions:

A

Increases self-reactivity, initiates and augments arthrtis in murine models
Recognises native collagen
Activates Fc receptor-positive cells
Activates complement
Certain polymorphisms in PAD4 gene linked to RA
Long latency between the production of AutoAb and the development of symptoms

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15
Q

What are the genetic factors that contribute to RA?

A
  • HLA-DRB1
  • shared epitope hypothesis
  • ethnicity
  • MHC genes (30% of risk)
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16
Q

What are some of the triggers of RA?

A
  • Industrialisation
  • Smoking
  • Peridontal disease
17
Q

What are the modifiers of phenotypic expression in RA?

A
  • oestrogen
  • pregnancy
  • infection
  • adverse life events/stress
18
Q

What is the disease activity of RA in pregnant women?

A
  • Oligosaccharide modification of IgG associated with functional change: galactosylation if IgG found to reduce the inflammatory properties of Ig autoAb (eg RhF)
  • Hypothalamic-pitutary-adrenal axis activity linked to cytokine production
19
Q

Provide examples of how infection links to pathogenesis and disease in RA

A
  • Peridoncal disease - Phorphyromonas gingivalis expresses PAD4, resulting in citrullination of peptides
  • Cytokine production up-regulated in hypothalamus during peripheral inflammation eg. generated by infection (local or systemic). Can result in flares of disease acitivty
20
Q

List the predictors of future RA disease

A
  • Family history of RA
  • Systemic features (eg non-joint - inflammation of lungs, eyes, skin etc)
  • HLA DR4 shared epitope alleles
  • ACPA positive
  • Poor response to treatment
  • Early bone erosion in course of disease
21
Q

What are the measures of current disease severity (disease activity)?

A
  • Patient symptoms
  • Anaemia
  • C-reactive proteins
  • Erythrocyte sedimentation rate (ESR)
  • Signs of joint inflammation
22
Q

What are the immediate and long term treatment goals of RA?

A

Immediate: no pain, dysfunction or disability
Long term: preventation of synoival hypertrophy & hyperplasia –> decreases inflammatory mediators –> prevent damage of cartilage and bone

23
Q

What are the methods of measuring effectiveness of RA treatments?

A

1) Health Assessment Questionnaire (HAQ)
Patient self-rated score from 20qs and visual analogues of pain
2) Disease Activity Score (DAS28)
Based on patient and investigator assessment
-No of swollen joints, tender joints, ESR, patient global health
3) Americal College Rheumatology (ACR20,50,70)
- Improvement calculated as a %
- swelling joint count, ESR, CRP, Hb levels, pain and stiffness (how patient feels)

Rheumatoid Arthritis (5 decks)

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