Patho-3-Autoimmunity & Inflammation of MSK Flashcards Preview

Block 6 - MSK > Patho-3-Autoimmunity & Inflammation of MSK > Flashcards

Flashcards in Patho-3-Autoimmunity & Inflammation of MSK Deck (38):
1

In a table compare & contrast RA, seronegative, SLE & polymyositis in terms of HLA, M:F, distribution & joint complications

Q image thumb

A image thumb
2

Patterns of extra-articular disease for RA (x5)

  • subcutaneous nodules
  • lung nodules
  • scleritis/episcleritis
  • vasculitis
  • spleen (neutropenia)

3

Patters of extra-articular disease for SLE (x7)

  • skin & mucosa
  • kidneys
  • lungs
  • serosa
  • CNS
  • thromboemoblic disease
  • placenta

4

Patterns of extra-articular disease for Myositis (x2)

  • oesophags
  • pulmonary fibrosis

5

Patterns of extra-articular disease for seronegative arthritis

  • pulmonary fibrosis
  • iritis
  • skin
  • GI
  • genitourinary

6

Patterns of extra-articular disease for Sjogren's syndrome

  • exocrine glands
  • skin & mucosa
  • nerves 
  • GI

7

RA epidemiology

  • global disease
  • 1% population prevalence
  • more common in some ethnic groups
  • increase in incidence gradual from 30-85yrs
  • F > M (2:1)

8

Joint features for RA (x7)

  • Chronic symmetrical erosive arthritis
  • Pannus/Synovitis formation
  • tendon subluxation
  • cartilage destruction
  • bone erosion
  • juxta-articular osteoporosis

(Just Cracking Bones Particularly Carpals)

  • functional deformity progresses to fixed deformity

9

T/F: 70% of people with RA will have erosions within 3 years

True

10

Clinical manifestations of RA

For at least 6 weeks:

  • morning stiffness - for at least 1hr
  • swelling in 3+ joints 
  • swelling of wrist, metocarpophalangeal or proximal interphalangeal joints
  • symmetric joint swelling

Hand X-ray changes:

  • erosions or bony decalcification
  • rheumatoid subcutaneous nodules

Serology:

  • RF or anti-citrullinated peptide/protein Abs
  • elevated acute phase reactants (ESR/CRP)

11

Pattern of joint involvement in RA

Affects small distal joints first before moving on to affect others

  1. wrist - 80%
  2. Metatarso-phalangeal - 90%
  3. metacarpo-phalangeal/proximal interphalangeal - 90%

A image thumb
12

Does axial skeleton tend to be involved with RA?

no

13

Pathohistology of RA - synovial inflammation & differentiation

  • complex inflammatory inflitrate & abnormal differentation of synovium (pannus)
  • angiogenesis --> cellular infiltrate --> cytokine secretion --> T & B cell activation --> tissue oedema & fibrin

A image thumb
14

Extra-articular manifestations of RA

  • Rheumatoid nodules - subcutaneously on extensor surfaces
  • Lung disease - pleural effusion, pneumonitis, intersitital lung disease, nodules
  • Pericarditis
  • Vasculitis - cutaneous (digital infarction), peripheral nerves (vasa nervora)
  • Neutropenia + splenomegaly (Fetty's syndrome)
  • Eyes - scleritis, episcleritis

15

Discuss features of Rheumatoid Factor for RA

  • Ab to Fc portion of IgG
  • not specific for RA (b/c RF present in IgG, IgM & IgA)
  • IgM RF correlates best with disease activity & severity (including extra-articular manifestations)

16

Discuss features of Anti-Cyclic Citrullinated Peptide Ab for RA

  • more specific for RA but not more sensitive (compared to RF)
  • citrulline = modified version of a.a. arginine
  • Citrullination = more common in RA

17

Which is a more specific &/or sensitive Ab for RA?

RF = more sensitive

Anti-CCP = more specific

18

What genome is involved in RA?

HLADRB1

19

What is Seronegative Arthritides?

inflammatory arthridites NOT associated with RF

20

Examples of Seronegative Arthridites

PAIR

  • Psoriatic arthritis
  • Ankylosing spondylitis
  • arthritis associated with IBD
  • reactive arthritis

21

Seronegative arthritides are more common in males or females?

Males

22

Clinical manifestations of Seronegative arthritides (x6)

starts in early adulthood

  • sacroiliac joints & axial skeleton
  • sacroilitis 
  • ascending inflammation of spine
  • enthesitis (inflammation of tendon, ligament or joint capsule insertions)
  • dactylitis (inflammation of entire digit)
  • limb joints

 

23

What is Ankylosing Spondylitis?

chronic inflammatory disease of spine & sacroiliac joints

24

Psoriatic arthritis

Joint pain & stiffness associated with psoriasis

25

IBD

Crohn's disease or UC often accompanied by ankylosing spondylitis or peripheral arthritis

26

Reactive arthritis

Classic triad of symptoms:

  • conjunctivitis
  • urethritis
  • arthritis

'cant see, can't pee, can't bend my knee'

27

Extra-articular manifestations of Seronegative arthridites (x5)

  • iritis (anterior uveitis)
  • enteritis
  • urethritis
  • skin disease
  • aortitis & conduction defects

28

............. polymorphism has an association with seronegative arthritides

HLA-B27

29

HLA-B27 & pathogenesis

misfolded HLA-B27 accumulates in ER triggering an unfolded protein response (pro-infammatory)

30

Other polymorphism associated with Seronegative arthridities

abnormality in IL-17 production due to hyper-responsivness to IL-23 by NK or gamma/delta T cells

31

Systemic Lupus Erythematosus

complex autoimmune disease with various clinical manifestations & complex pathogenesis

  • more severe in Africans & Asians
  • F:M = 9:1 - most marked in child-bearing years

32

Pathology of SLE

inflammation with auto-Ab deposition in end-organs

A image thumb
33

Key auto-Ags for SLE

  1. chromatin
  2. ribonucleases
  3. phospholipids

34

Key findings of auto-Abs in SLE

  • dsDNA Ab titre (not ANA) - reflects disease activity
  • Hypo-complementaemia with disease activity
  • defective acute phase response - CRP 

35

Characteristics of auto-Ab response in SLE

  • high affinity, somatically mutated Abs (products of T-dependent & B cell responses, arising from GC reactions)
  • produced form long-lived plasma cells in BM
  • aberrant T cell help - B cell priming, centrocyte rescue in GC

A image thumb
36

Clinical manifestations of SLE

RASH OR PAIN

  • Rash
  • Arthritis 
  • Soft tissues/serositis 
  • Hematological disorders 
  • Oral ulcers 
  • Renal disease 
  • Photosensitive , postive VDRL/RPR
  • Antinuclear antibodies 
  • Immunosuppressanta 
  • Neurologic disorders

37

Relationship between apoptosis and lupus autoantigens

  • accumulation of auto-Ag on blebs of apoptotic cells
  • provide eat me singals to ensure efficient phagocytosis of apoptotic cells (actively anti-inflammatory)
  • impaired phagocytosis of apoptotic cells by monocytes from C1q-deficient pts
  • corrected by addition of C1q

38

4 types of Juvenile Idiopathic Arthritis - compare/contrast clinical, lab, complications & pathogenesis where possible in a table

  1. Systemic
  2. Enthesitis-related
  3. Seropositive
  4. Oligoarthritis

A image thumb