Week 2: Rheumatoid Arthritis

Question 1

Give the definition and clinical picture of rheumatoid arthritis.

Answer 1

• Chronic inflammatory, systemic disease with major targets of the synovial joints.
• symmetrical joint involvement, affects MCPs/PIPs of hands, MTPs, subtalars, intertarsals of feet, and anywhere there’s a synovial joint
• swelling and pain due to joint inflammation
• morning stiffness and fatigue
• primarily affects women, 3:1 female to male in adults. 2-6:1 children

Question 2

What is the role of genetics in rheumatoid arthritis?

Answer 2

• shared epitopes of MHC II alleles: in hypervariable region of HLA-DR4, HLA-DRB1, HLA-DRB1*04 alleles that are assoc. with RA
• The most important genetic risk factors for RA are certain HLA-DRB1 alleles that encode for the shared epitope (SE), a common amino acid sequence in the antigen-presenting portion of the HLA class II molecule
• QR/KRAA - greater risk of developing more severe RA

Question 3

Describe the pathogenesis of RA.

Answer 3

• combo of genetics, insult/trigger, immune response
• initiating event incites inflammation of synovium, proliferation mediated by humoral and cellular response, results in tissue damage
• important proinflammatory cytokines: TNF a, Il-1, Il-6
• synovial intimal lining hyperplasia and a cellular infiltrate
• The inflamed synovium invades cartilage, promoting destruction via osteoclasts, chrondrocytes, and synovial fibroblast
• formation of a pannus is characteristic, composed of granulation tissue, stromal cells, neovascular structures, and heterogeneous leukocytes –>invasion and erosion of cartilage
• bone erosion mediated by osteoclasts
• Can be thought of as disease of ectopic lymphoid tissue

Question 4

What antibodies are found in RA?

Answer 4

• Rheumatoid factors-autoantibodies directed against Fc portion of IgG. Higher levels assoc. with poorer prognosis.
• anti-CPP (cyclic citrulinated peptide) - assoc. with smoking as a trigger
• antibodies against collagen and nuclear components

Question 5

Describe the clinical findings in RA.

Answer 5

1. fusiform swelling of hand: enlargement of PIP joints
2. ulnar deviation of hands and MCP joint subluxation
3. muscle atrophy
4. Rheumatoid nodules: painless granulomas in pressure areas
5. Swan-neck: hyperextension of PIP and hyper flexion of DIP
6. boutonniere deformity: hyperflexion of PIP
7. telescoping digits: shortening of digits, loss of bone substance,
8. arthritis mutilans: severe deformities, subluxation of MCP joints, marked hyperflex/ext. of PIPs
9. protruding metatarsal heads in feet
10. foot deformities: hallux valgus and hammertoes