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

Patho-3-Autoimmunity & Inflammation of MSK Flashcards

1
Q

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

A
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2
Q

Patterns of extra-articular disease for RA (x5)

A
  • subcutaneous nodules
  • lung nodules
  • scleritis/episcleritis
  • vasculitis
  • spleen (neutropenia)
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3
Q

Patters of extra-articular disease for SLE (x7)

A
  • skin & mucosa
  • kidneys
  • lungs
  • serosa
  • CNS
  • thromboemoblic disease
  • placenta
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4
Q

Patterns of extra-articular disease for Myositis (x2)

A
  • oesophags
  • pulmonary fibrosis
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5
Q

Patterns of extra-articular disease for seronegative arthritis

A
  • pulmonary fibrosis
  • iritis
  • skin
  • GI
  • genitourinary
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6
Q

Patterns of extra-articular disease for Sjogren’s syndrome

A
  • exocrine glands
  • skin & mucosa
  • nerves
  • GI
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7
Q

RA epidemiology

A
  • global disease
  • 1% population prevalence
  • more common in some ethnic groups
  • increase in incidence gradual from 30-85yrs
  • F > M (2:1)
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8
Q

Joint features for RA (x7)

A
  • 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
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9
Q

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

A

True

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10
Q

Clinical manifestations of RA

A

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)
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11
Q

Pattern of joint involvement in RA

A

Affects small distal joints first before moving on to affect others

  1. wrist - 80%
  2. Metatarso-phalangeal - 90%
  3. metacarpo-phalangeal/proximal interphalangeal - 90%
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12
Q

Does axial skeleton tend to be involved with RA?

A

no

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13
Q

Pathohistology of RA - synovial inflammation & differentiation

A
  • complex inflammatory inflitrate & abnormal differentation of synovium (pannus)
  • angiogenesis –> cellular infiltrate –> cytokine secretion –> T & B cell activation –> tissue oedema & fibrin
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14
Q

Extra-articular manifestations of RA

A
  • 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
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15
Q

Discuss features of Rheumatoid Factor for RA

A
  • 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)
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16
Q

Discuss features of Anti-Cyclic Citrullinated Peptide Ab for RA

A
  • more specific for RA but not more sensitive (compared to RF)
  • citrulline = modified version of a.a. arginine
  • Citrullination = more common in RA
17
Q

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

A

RF = more sensitive

Anti-CCP = more specific

18
Q

What genome is involved in RA?

A

HLADRB1

19
Q

What is Seronegative Arthritides?

A

inflammatory arthridites NOT associated with RF

20
Q

Examples of Seronegative Arthridites

A

PAIR

  • Psoriatic arthritis
  • Ankylosing spondylitis
  • arthritis associated with IBD
  • reactive arthritis
21
Q

Seronegative arthritides are more common in males or females?

A

Males

22
Q

Clinical manifestations of Seronegative arthritides (x6)

A

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
Q

What is Ankylosing Spondylitis?

A

chronic inflammatory disease of spine & sacroiliac joints

24
Q

Psoriatic arthritis

A

Joint pain & stiffness associated with psoriasis

25
Q

IBD

A

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

26
Q

Reactive arthritis

A

Classic triad of symptoms:

  • conjunctivitis
  • urethritis
  • arthritis

‘cant see, can’t pee, can’t bend my knee’

27
Q

Extra-articular manifestations of Seronegative arthridites (x5)

A
  • iritis (anterior uveitis)
  • enteritis
  • urethritis
  • skin disease
  • aortitis & conduction defects
28
Q

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

A

HLA-B27

29
Q

HLA-B27 & pathogenesis

A

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

30
Q

Other polymorphism associated with Seronegative arthridities

A

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

31
Q

Systemic Lupus Erythematosus

A

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
Q

Pathology of SLE

A

inflammation with auto-Ab deposition in end-organs

33
Q

Key auto-Ags for SLE

A
  1. chromatin
  2. ribonucleases
  3. phospholipids
34
Q

Key findings of auto-Abs in SLE

A
  • dsDNA Ab titre (not ANA) - reflects disease activity
  • Hypo-complementaemia with disease activity
  • defective acute phase response - CRP
35
Q

Characteristics of auto-Ab response in SLE

A
  • 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
36
Q

Clinical manifestations of SLE

A

RASH OR PAIN

  • Rash
  • Arthritis
  • Soft tissues/serositis
  • Hematological disorders
  • Oral ulcers
  • Renal disease
  • Photosensitive , postive VDRL/RPR
  • Antinuclear antibodies
  • Immunosuppressanta
  • Neurologic disorders
37
Q

Relationship between apoptosis and lupus autoantigens

A
  • 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
Q

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

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

Block 6 - MSK (5 decks)

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