SM_234a: Rheumatoid Arthritis

Question 1

Rheumatoid arthritis is _____

Answer 1

Rheumatoid arthritis is a chronic inflammatory joint disease of autoimmune nature characterized by the development of autoantibodies

(more common in women, occurs earlier in women)

Question 2

Risk factors for RA include ____, ____, ____, ____, ____, and ____

Answer 2

Risk factors for RA include genetic, epigenetic, female sex, smoking, dust inhalation, and microbiota (periodontal disease, gut microbiome)

Question 3

Shared epitope is a ______

Answer 3

Shared epitope is a specific amino acid motif commonly encoded by alleles of the HLA-DR loci that confers genetic susceptibility to development of RA

(specific class II HLA antigen loci show strong association with RA, HLA-DRB1*01 and HLDRB1*04 are among strongest risk factors, many loci harbor RA susceptibility variants of variable strength)

Question 4

Locus involves in RA is _____

Answer 4

Locus involves in RA is HLA DR

Question 5

Environmental risk factors for RA are ____, ____, and ____

Answer 5

Environmental risk factors for RA are smoking, dust inhalation, and microbiota

• Risk from smoking increases in a graded fashion
• Dust inhalation
• Periodontal disease increases risk of developing RA
• Gut microbiome changes in RA

Question 6

Healthy synovium has ____ and has a sublining of ____, ____, ____, and ____

Answer 6

Healthy synovium has an intimal lining of macrophage-like and fibroblast-like synoviocytes and sublining of fibroblasts, adipocytes, blood vessels, and immune cells

• Intimal lining is a delicate and leaky and allows free movement of cells and proteins into synovial fluid

Question 7

Healthy synovium functions to _____ and _____ during homeostasis

Answer 7

Healthy synovium functions to produce lubricants for cartilage and provide nutrients to cartilage during homeostasis

Question 8

In RA, pathological changes of the synovium include ____, ____, ____, and ____

Answer 8

In RA, pathological changes of the synovium include expansion of intimal lining with activated synoviocytes producing pro-inflammatory cytokines, infiltration of adaptive immiune cells into synovial sublining with hypervascularity, formation of a pannus, and activation of osteoclasts to degrade bone

Question 9

Pannus is an _____

Answer 9

Pannus is an invasive destructive front of synovial tissue attached to the articular surface

Question 10

Describe pathological changes in the RA synovium

Answer 10

RA synovium pathological changes

• Intimal lining greatly expands with activated synoviocytes producing pro-inflammatory cytokines
• Infiltration of adaptive immune cells into synovial sublining with hypervascularity
• Pannus: invasive, destructive front of synovial tissue attached to the articular surface
• Activated osteoclasts degrade bone

Question 11

Pannus is formed by ____, ____, and ____

Answer 11

Pannus is formed by the expansion of activated synoviocytes, infiltration of immune cells, and hypervascularity

Question 12

Describe the disease coure of RA

Answer 12

RA disease course

• Pre-clinical: citrullination
• Early: synovitis
• Established: joint damage

Question 13

Pre-clinical RA is characterized by _____

Answer 13

Pre-clinical RA is characterized by citrullination

Question 14

Early RA is characterized by _____

Answer 14

Early RA is characteirzed by synovitis

Question 15

Established RA is characterized by _____

Answer 15

Established RA is characterized by joint damage

Question 16

Describe the disease course and pathogenesis of RA

Answer 16

RA disease course and pathogenesis

• Pre-clinical RA: circulating autoantibodies and pro-inflammatory cytokines are detectable up to 10 years before clinical disease onset
• Citrullination is a key step in RA pathogenesis that leads to immune activation and production of RF and ACPAs
• Synovitis and joint damage are cardinal features of RA driven by pro-inflammatory cytokines IL-1, IL-6, and TNF

Question 17

Describe the HPI of someone with RA and someone with OA

Answer 17

• RA: usually insidious onset of symmetric polyarthritis (>3 joints) especially in joints of hands and feet, joint swelling, decreased ROM in joints, pain and swelling worse in morning, morning stiffness lasting >1 hour, stiffness after rest (gelling)
• OA: insidious, bony enlargement of joints, morning stiffness lasting < 30=60 minutes, stiffness after rest (gelling)

Question 18

RA involves joint _____, while OA involves _____ of joints

Answer 18

RA involves joint swelling, while OA involves bony enlargement of joints

Question 19

Morning stiffness lasts ____ in RA than OA

Answer 19

Morning stiffness lasts longer in RA than OA

Question 20

Describe joints involved in RA

Answer 20

Joints involved in RA

• Hands: metacarpophalangeal joints (MCPs), proximal interphalangeal joints (PIPs), wrists, elbows, shoulders, hips, knees, ankles, metatarsophalangeal joints (MTPs), and cervical spine

(OA involves the DIPs, does not involve MCPs or ankle, and only involves 1st MTP)

Question 21

Physical exam findings in early RA include ____ and ____

Answer 21

Physical exam findings in early RA include symmetric joint swelling / tenderness and palpable swelling / synovial boginess

(in OA there is joint enlargement due to bony hypertrophy in osteoarthritis)

Question 22

Physical exam findings in advanced RA include _____, _____, and _____

Answer 22

Physical exam findings in advanced RA include joint deformity / malalignment, limited ROM, and rheumatoid nodules at pressure points

(MCP joint ulnar deviation and subluxation)

Question 23

Swan neck deformity in RA is _____

Answer 23

Swan neck deformity in RA is flexion at DIP and hyperextension at PIP

Question 24

Boutonniere deformity in RA is _____

Answer 24

Boutonniere deformity in RA is flexion at PIP and hyperextension of DIP

Question 25

\_\_\_\_\_ and _____ distinguish RA from OA in the hands

Answer 25

Prolonged morning stiffness and sparing of DIP joints distinguish rheumatoid arthritis from OA in the hands

Question 26

RA patients are at high risk for premature \_\_\_\_\_

Answer 26

RA patients are at high risk for premature cardiovascular disease

Question 27

Describe radiographic changes in RA

Answer 27

Radiographic changes in RA * Soft tissue swelling * Periarticular osteopenia * Uniform / symmetric joint space loss * Marginal erosions * Symmetric deformities (swan neck, boutonniere, ulnar deviation, subluxation)

Question 28

Describe late RA changes in the hands

Answer 28

Late RA changes in the hands * Diffuse joint space narrowing * MCP subluxation and ulnar deviation * Demineralization * Marginal erosions at MCPs * Carpal joint space narrowing and erosions

Question 29

\_\_\_\_ may occur in RA due to instability resulting from synovitis of the atlantoaxial joint

Answer 29

Atlantoaxial subluxation may occur in RA due to instability resulting from synovitis of the atlantoaxial joint

Question 30

\_\_\_\_, \_\_\_\_, and ____ are characteristic X-ray findings in RA

Answer 30

Soft tissue swelling, periarticular osteopenia, and marginal erosions are characteristic X-ray findings in RA

Question 31

Laboratory abnormalities in RA include \_\_\_\_, \_\_\_\_, and \_\_\_\_

Answer 31

Laboratory abnormalities in RA include rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), and antinuclear antibody (ANA, in 20-30% of patients)

Question 32

Describe RF in lab testing of RA

Answer 32

RF in lab testing of RA * Autoantibodies with specificity for Fc fragment of IgG * High titers associated with worse prognosis * Sensitivity 66%, specificity 82% * Other disease associations

Question 33

Describe ACPA in lab testing of RA

Answer 33

ACPA in lab testing of RA * Sensitivity 75%, specificity 95% * 35% of patients with negative RF will have positive ACPA * Associated with poor prognosis (erosive disease, extra-articular manifestations)

Question 34

Inflammatory synovial fluid in RA includes \_\_\_\_, \_\_\_\_, and \_\_\_\_

Answer 34

Inflammatory synovial fluid in RA includes 5-50k WBCs, no crystals, and negative culture (general signs of inflammation: anemia of chronic disease, thrombocytosis, elevated ESR, elevated CRP)

Question 35

Positive RF and ACPA blood tests are associated with increased risk of ____ and \_\_\_\_

Answer 35

Positive RF and ACPA blood tests are associated with increased risk of erosive joint disease and development of extra-articular manifestations

Question 36

Describe goals of treatment for RA

Answer 36

Goal of treatment for RA * Reduce joint pain and swelling * Prevent joint damage, minimize disability, and maintain employability * Begin treatment early: best results when meds started within 3-6 months of synovitis onset * Treat to target: goal to attain remission or low disease activity

Question 37

\_\_\_\_ and ____ are used for acute symptom control in RA

Answer 37

NSAIDs and corticosteroids are used for acute symptom control in RA

Question 38

Disease modifying anti-rheumatoid drugs are a diverse group of medications that ____ and \_\_\_\_

Answer 38

Disease modifying anti-rheumatoid drugs are a diverse group of medications that reduce RA symptoms and slow radiographic progression/damage

Question 39

Methotrexate inhibits _____ to \_\_\_\_\_

Answer 39

Methotrexate inhibits dihydrofolate reductase to limit DNA synthesis (most effective) (inhibits vascular proliferation, inhibits neutrophil activation and adherence, inhibits IL-1 and IL-8 production by mononuclear cells, inhibits TNF production by T cells)

Question 40

Leflunomide inhibits _____ to \_\_\_\_\_

Answer 40

Leflunomide inhibits dihydroorotate dehydrogenase to limit DNA synthesis (also inhibits expression of cell adhesion molecules, teratogen)

Question 41

Sulfasalazine suppresses _____ and _____ function

Answer 41

Sulfasalazine suppresses lymphocyte and leukocyte function

Question 42

Hydroxychlorquinone may interfere with \_\_\_\_

Answer 42

Hydroxychlorquinone may interfere with presentation of auto-antigenic peptides

Question 43

Biologic DMARDs are very effective for RA treatment but have increased risk of _____ compared to non-biologic DMARDs

Answer 43

Biologic DMARDs are very effective for RA treatment but have increased risk of infection compared to non-biologic DMARDs

Question 44

Describe the general treatment approach for RA

Answer 44

General treatment approach for RA * Treat to target of remission or low disease activity * Assess disease activity at 6-12 week intervals initially * Taper off prednisone as soon as possible * Maintain DMARD indefinitely once low disease activity attained

Question 45

\_\_\_\_ is the most effective DMARD for RA, and biologic DMARDs are added to non-biologic DMARDs as need to attain ____ and \_\_\_\_

Answer 45

Methotrexate is the most effective DMARD for RA, and biologic DMARDs are added to non-biologic DMARDs as need to attain remission or low disease activity (treat to target)