Autoimmune Disease 2

Question 1

3 Subsets of SSc

Answer 1

• Diffuse cutaneous involvement
  
  • widespread, rapidly progressing skin thickening - both prox
    and dist)
  • early visceral involvement - lung, heart, kidney
• Limited cutraneous
  
  • restricted, non-progressive thickening on distal extremities
  • slowly overtime organs become involved and usually later in the disease - pumonary arterial hypertension
• Overlap
  
  • SSc + IIM or SLE or RA

Question 2

Auto-antibodies of Systemic sclerosis or scleroderma

Answer 2

• there are 9 associated auto-antibodies
• 90% of ppl have at least one
• the antibody you have can be very predictive of how you behave - this helps with treatment protocol
• they don’t seem to cause the disease, just associated
  
  • except maybe anti-fibroblasts
• ANA in 98% of patients
• Scl-70 other very common one

Question 3

Organ involvement with scleroderma

Answer 3

• skin thickening
• peripheral vascular - raynouds, ulcers etc
• joint contractures, myopathy
• Gastrointestinal
  
  • 75% have dysmotility and dilation of esophagus
• Interstitial lung disease
  
  • 20-25% of ppl with limited SSc end up with this
• congestive heart failure
  
  • fibrosis
• Renal Crisis
  
  • systemic hypertension = rapidly failing kidney
  • 15-20% diffuse

Question 4

SSc pattern of actvation

Answer 4

General:
- Vascular injury leads to activation of immune system leads to actvation of fibroblats with increased amounts of collagen & ECM

• Vascular damage/ EC change
  
  • damage to vasculature increases the level of Endothelium-1
  • ET-1 - vasoconstrictor and fibrogenic
• Damage leads to defective vasculogenesis
  
  • precursors are unable to become endothelial cells in vessels
• this leads to upregulation of immune response
  
  • leukocytes adhesion, migration etc
  • T-cells increased - Th2
  • T-cells reactive to nuclear antigens, caollagen, fibriillin etc
  • Th2 response - IL-4, IL-1, TGF-Beta
• Fibroblasts activated and produce lots of collagen

Question 5

JIA diagnostic criteria

Answer 5

• Age onset 6 weeks

- asymmetric arthritis involving large joints

Question 6

Oligoarticular JIA

Answer 6

• onset 2-4 yrs
• 60% of JIA cases
• <4 joints affected in first 6 mth-
• asymmetrical lower extremity large joints
• 85% ANA+
• 25% uveitis
• RF negative
• perisistent, extended, inactive

Question 7

RF Negative JIA

Answer 7

• > 5 joints
• bimodal - 1-4, 6-12
• 30% all JIA
• ANA+
  
  • basically oligo?
  • asymmetric large and small
    ANA negative
  • ANA -/RF -
  • symmetric similar to RA

Question 8

RF+ JIA

Answer 8

• Basically childhood onset RA
• symmetric in small and large
• Anti-citrullinated antibody (ACCP)
• Extremely erosive
• ANA neg, very little Uvetis
• big problem for growth, retardation and disfigurement

Question 9

Systemic JIA

Answer 9

• Other problems more serious than joint issues
• daily fever, rash,
• lymphadenopathy
• splenomegaly
• polyserositis
• systemic inflammation - high ESR, CRP, PMN, platelets
• Early joint destruction
  
  • wrist, spine, food - ankylosis
  • hip = bad
• monocyclic, polycyclic, persistent

Question 10

JIA Immunologic features, T-cell, B-cell, DC, fibroblasts

Answer 10

• inflammatory foci in joints
• clonal T- and B- cell expansion
• Autoimmune - lots of high autoantibodies
  
  • ANA, RF, ACCP (B-cells)
• Genetic HLA associations
  
  • HLA-DR4 protective
• High Th17, low Tregs
• fibroblasts in synovial - amplify disease, drive osteoclasts, secrete major cytokines

Question 11

JIA cytokine big 3

Answer 11

• TNF-alpha - targeted by etanercept, adalinumab, infliximab
• IL-1 - Anakinra
• IL-6 - Toculizimab

Question 12

Macrophage activation syndrome

Answer 12

• Associated with systemic JIA
• hemaphagocytic
• excessive IL-1, IL-6, IL-18
• IL18 needed for NK development
• IL18 Receptor not working so low NK cells

Question 13

Main cytokines in RA

Answer 13

TNF, IL-1, and IL-6

- main pro-inflammatory cytokines in RA

Question 14

Genetic and environmental assocations + main sign

Answer 14

Genetic - related to MHC-II
Environmental - smoking risk factor,
- usually starts after 1-2 pregnancies, but goes in remission during pregnancy

• Pannus is the hallmark symptom
  
  • synovial fluid grows thicker, with lots of blood vessels

Question 15

Pannus

Answer 15

• synovial join grows thicker with lots of blood vessels and inflammatory cells
• Neovascularization - lots of adhesion molecules to promote WBC migration
• Cellular infiltration - selectins and integrins and cytyokines guide cells
• Pannus cell types
  
  • Type A synoviocytes - macrophages
  • CD4, B-cells
  • Type B - fibroblasts
  • Plasma cells making RF factor

Question 16

RA antibodies

Answer 16

RF - not specific for RA but 85% have it
RF - autoantibody to Fc region of IgG

• Anti-CCP (RF+ poly JIA)
• highly specific for RA - 95%
• against aa citrulline

Question 17

Articular characteristics of RA

Answer 17

• Joints degrade - look like “rat bites”
• erosion of ulnar styloid
• universal finding - arthritis in small joints of hands
  - MCP, PIP, forefoot MTP

Question 18

Extra-articular features of RA

Answer 18

• SKin - very common RA nodules - poximal ulna - calcifications
• Cardiac is most serious - accelerate atherosclerosis - 50% mortality
• pulmonary - chest pain, ILD
• osteroporosis
• vasculitis
• 2nd sjogrens
• infection - another leading cause of death in RA patients
  
  • from both the disease but also the drugs
• nerve entrapments at atlas - joint just falls forward

Question 19

Treatments for RA

Answer 19

• Methotrexate is the best treatment
  
  • high efficacy low toxicity, avoid preggers
  • disease modifying anti-rheumatic drug (DMARD)
• Antimalarials - hydroxycholoroquine (plaquinol)
  
  • DMARD
  • low toxicity, can be mixed
• Sulfasalazine
  
  • often combined with other DMARD
  • anti-inflammatory, immune modulator
• Leflunomide
  
  • DMARD
• Can also use NSAIDs, Temporary Corticosteroids (predisone)
• TNF-alpha inhibitors - biologic therapy