other autoimmune disorders

Question 1

commonly affected by Rheumatoid arthitis?

Answer 1

females, 40-70 yo

symptoms wax and wane for life; morning stiffness that gets better with movement

Question 2

what is activated in pathogenesis of RA

Answer 2

CD4 T cells

Question 3

what allele is present in RA

Answer 3

HLA-DRB1

Question 4

what antigen is present in RA?

Answer 4

arthritogenic antigen is CCP peptide = a citrilinated protein
(arginine is converted to citruline)

Question 5

how does synovitis and pannus occur in Rheumatoid arthritis?

Answer 5

CD4+ T cell activation –> cytokine release (esp. TNF-alpha)
o Upregulate endothelial adhesion molecules-inflammatory cell influx into synovium
o Promote B cell hyperactivity (CD4+ T cell-dependent)- production of rheumatoid factor (RF) and antibodies to citrulline-modified peptides (CCP antibodies)

Pannus = inflamed synovium (tissue around joint)
o Acute and chronic inflammation with synovial cell hyperplasia + Neutrophils in synovial fluid (highly cellular fluid)
o Spread of pannus –> invasion into cartilage and bone
o Fibrous then bony ankylosis –> Deformed joint; loss of function

Question 6

3 clinical stages of RA presentation

Answer 6

• Stage 1 - Gradual onset fatigue, weight loss, weakness and vague musculoskeletal discomfort (10% acute); early joint swelling
• Stage 2 - Small joints of hand and feet, symmetrical
• Stage 3 - Wrists, ankles, elbows, knees, cervical spine ; deformities and bony fusion
–> destruction of tendons, ligaments, and joint capsule

**pain tenderness and swelling in stages 2 and 3

Question 7

xray findings of RA

Answer 7

Juxta-articular osteopenia, bone erosions, and narrowed joint space from cartilage loss

Question 8

RA prognosis with Rf+ and RF-

Answer 8

RF+ poor prognosis

RF- good prognosis

Question 9

is RF specific to RA?

Answer 9

no, can appear with other diseases

Question 10

rheumatoid factor

Answer 10

• Auto Ab (usually IgM) to Fc portion of IgG
• Immune complexes-sera, synovial fluid and membrane
• Augments joint inflammation, induce vasculitis

high RF titer = severity increased

Question 11

mechanism for bone and cartilage destruction

Answer 11

• Neutrophils & synoviocytes release protease and elastase
• Macrophage and synoviocytes release IL-1 & TNF-α which induce:
o collagenase (cartilage & bone)
o osteclast activating factor-bone resorption
o endothelial cell adhesion molecules

Question 12

rheumatoid nodule is seen with what three conditions

Answer 12

RA
SLE
rheumatic fever

Question 13

rheumatoid nodule

Answer 13

• Pressure regions (ulnar aspect of forearm, elbows, occiput, lumbosacral area); Firm, moveable, non-tender, round to oval
• Central fibrinoid necrosis surrounded by epithelioid histiocytes, lymphs, plasma cells (granuloma)
• Also can be in Cardiac location - Bundle of His-arrythmia
• Or Lung location- fibrosis, respiratory failure

Question 14

where does rheumatoid nodule occur? causes what?

Answer 14

heart - bundle of his - arrythmias

lung location - fibrosis and respiratory failure

Question 15

rheumatoid vasculitis

Answer 15

• Associated with severe disease, rheumatoid nodules, and high RF titers
• small to medium arteries
• digital artery –> peripheral neuropathy, ulcers, gangrene
• leukocytoclastic venulitis–> purpura, skin ulcers, and nail bed infarction

Question 16

scleroderma

mechanism
who is more likely

Answer 16

systemic sclerosis, Chronic disease (CVD type)

black females between 50-60s

• Immune mediated vascular injury –> vascular instability, narrowing, and organ ischemia
• Fibroblast activation –> excessive collagen in skin

Question 17

diffuse scleroderma

Answer 17

Widespread skin involvement
involved skin is proximal to elbows/knees
 Severe multiple organ involvement and decreased survival
 Anti-topoisomerase autoantibody

Question 18

limited scleroderma

Answer 18

Skin invovlement confined to fingers, forearms, and face; with visceral involvement limited and late

Better prognosis than diffuse scleroderma

Sub-group-CREST (anti-centromere autoantibody)
• Calcinosis – Raynaud’ s – Esophagyeal dysfunction – Sclerotdactyly – Telangetasia

Question 19

CREST

Answer 19

syndrome associated with limited scleroderma

anti-centromere antibody

calcinosis, raynauds, esophageal dysfunction, sclerodactyly, telangestasia

Question 20

raynauds

Answer 20

 Vasospasm of digital arteries in response to cold or emotional stress; can lead to digital necrosis due to vascular indufficiency

present in crest or scleroderma

Question 21

early phase skin changes in scleroderma

Answer 21

inflammatory (CD4, macrophages); peak 2-3 years; swelling of fingers, and hands first; desquamation
 Edema and dermal, perivascular lymphocytes

Question 22

late phase skin changes in scleroderma

Answer 22

 dense fibrosis and atrophy; inflammatory infiltrates disappear
 Fibrosis and atrophy
 Ex: face  absence of wrinkles, tight skin, and down turned/fixed open mouth
 Calcinosis
• Advanced calcinosis =ulcerations and autoamputation of digits

Question 23

microvasculature changes in scleroderma

Answer 23

NAILS!

 Nail fold capillaroscopy  Decreased capillary loops; dilated capillary loops

Question 24

scleroderma renal crisis

Answer 24

o Fibrotic Intimal thickening of interlobular arteries and accompanying hypertension
-Hyper-reninemia –> Malignant hypertension and rapid insufficiency
—affects Interlobular and arcuate arteries
 Treat with: Angiotensin-converting enzyme (Ace) inhibitor

Question 25

what do you treat scleroderma renal crisis with?

Answer 25

ACEi

Question 26

pulmonary changes in scleroderma

Answer 26

o Interstitial fibrosis –> Pulmonary hypertension with cor pulmonale.

Question 27

GI changes with scleroderma

Answer 27

o Neural dysfunction, smooth muscle atrophy, fibrosis
 Gastro-esophageal reflux-Barrett esophagus
 Dysphagia
 Malabsorption-small intestinal atrophy
 Intestinal pseudo-obstruction
 Small intestinal bacterial overgrowth

Question 28

treatment for scleroderma

Answer 28

supportive care

no treatment really to alter the course of disease