Rheumatoid Arthritis

Question 1

RA affects __% of the world population.

Answer 1

RA affects 1% of the world population.

Question 2

Main target of inflammation in RA

Answer 2

The synovium

Question 3

RA is more common in ___.

Answer 3

RA is more common in women (3:1 ratio).

Question 4

Citrullination

Answer 4

a post-translational modification of proteins in which arginine residues are converted to citrulline—occurs at sites of inflammation

Question 5

antibodies against citrullinated epitopes are found to be present in __% of patients with rheumatoid arthritis

Answer 5

antibodies against citrullinated epitopes are found to be present in 70% of patients with rheumatoid arthritis.

Thus, RA seems to be associated with a loss of tolerance to citrullinated proteins

Question 6

Early presentations of rheumatoid arthritis

Answer 6

• Very, very gradual rise in polyarticular inflammation over years in many
• Some start with gradual mono- or oligo-articular arthritis which progresses to polyarticular in its full form
• Rarely, extra-articular symptoms of the rheumatoid arthritis syndrome, such as sclerosis, may present before the arthritic symptoms
• Low-grade fever common and significant weight loss may occur in early disease

Question 7

Pattern of joint involvement for RA

Answer 7

• Smaller joints tend to be first, particularly the PIP, MCP, and MTP
• Larger joints like elbow and knee occur later
• Stiffness for >30 minutes in the morning, usually ~1.5-2 hours

Question 8

Common first complaints for RA

Answer 8

• “My rings no longer fit”
• “The balls of my feet hurt when I walk to the bathroom in the morning”
• “My fingers and wrist hurt when I brush my teeth in the morning”
• “I run my hands in warm water to get them working”

Question 9

Joints involved in Rheumatoid Arthritis

Answer 9

Question 10

Only involvement of the spine in RA

Answer 10

C1-C2 articulation, trouble turning head

Question 11

___ are involved with almost all patients with RA

Answer 11

hands are involved with almost all patients with RA

Question 12

Radiographic findings of RA

Answer 12

Evidence of articular damage after months to years

Bone erosion

Question 13

___ and/or ___ may confirm the presence of synovitis years before findings are possible with X-rays

Answer 13

Ultrasound and/or MRI may confirm the presence of synovitis years before findings are possible with X-rays

Question 14

Signs in late, established RA

Answer 14

• Ulnar deviation of fingers at MCPs
• “Swan neck” deformities -> hyperextension of the PIP joints and flexion at the DIP joints
• “Buttonhole” deformities -> flexion of the PIP joints and hyperextension of the DIP joints
• Rheumatoid nodules -> soft to firm nodular lesions in various shapes from pea- sized to golf ball

Question 15

Answer 15

Swan neck deformity in RA

Question 16

Answer 16

Buttonhole deformity

Question 17

Swan neck vs buttonhole deformity

Answer 17

Question 18

___ may resemble rheumatoid nodules

Answer 18

Gouty tophi may resemble rheumatoid nodules

Distinctions include:

• tophi tend to be firm, nodules are fleshy
• tophi have a pale yellowish tinge and nodules have no specific coloration pattern
• There is no material that can be aspirated (using a needle) from a rheumatoid nodule, while a tophus yields toothpaste like material that under polarizing microscopy shows negatively birefringent needle shaped crystals.

Question 19

Answer 19

Eroded PIP in RA patient

Question 20

RA and carpal tunnel

Answer 20

Early in the course of the disease, synovial proliferation in and around the wrists can compress the median nerve, causing carpal tunnel syndrome

Question 21

RA is symmetric with respect to . . .

Answer 21

. . . both the joint involvement and the compartmental involvement

In the case of the knee the medial and lateral compartments are both severely narrowed in RA, whereas OA usually involves only one compartment

Question 22

___ can dramatically improve function and quality of life and should be considered in patients with severe mechanical damage

Answer 22

Total joint replacements of hips and knees can dramatically improve function and quality of life and should be considered in patients with severe mechanical damage

Question 23

Answer 23

Unilateral loss of cartilage in osteoarthritis

Question 24

Answer 24

Bilateral loss of cartilage in RA

Question 25

Laboratory findings of RA

Answer 25

• Anti-citrullinated self protein antibodies (80% sensitive, 98% specific, often present years prior to official diagnosis)
• Rheumatoid factor: an autoantibody against the human IgG Fc chain (80% sensitive).
• 2,000 - 15,000 WBC / μL with ~70% neutrophils in synovial fluid, may reach 40,000 - 50,000 WBC / μL during a flare
• Gram stain / Culture should always be done if inflammatory arthritis is suspected
• Elevated ESR/CRP in a dose dependent fashion with disease severity

Question 26

Diagnosis of RA

Answer 26

• Unfortunately, no pathognomonic features or simple laboratory findings to make the diagnosis. It is a clinical one that requires history gathering and laboratory testing
• History of arthralgias is important
• Diagnosis officially requires the objective evidence of joint inflammation on examination (synovitis)

Question 27

Differential for RA

Answer 27

• Acute viral syndromes (parvovorus, Hep B and C, rubella, etc.)
• Other forms of inflammatory arthritis (psoriatic, spondylarthropathy, and reative arthritis are often confused for unusual presentations of RA)
• Lupus (may include symmetric poyarthritis affecting hands)
• Poorly controlled and previously undiagnosed gout or pseudogout may look VERY similar to RA
• Osteoarthritis

Question 28

Most genes associated with rheumatoid arthritis are. . .

Answer 28

. . . HLA-DR genes

All the alleles involved share common amino acid sequences in the peptide-binding groove

Question 29

pre-rheumatoid arthritis

Answer 29

Period during which autoantibodies against citrullinated protein antigens may be detected in the blood but the individual has not yet developed the symptoms of rheumatoid arthritis. May last up to 10 years.

Question 30

Mechanisms of ACPA (autoantibody against citrullinated protein antigen) pathogenesis

Answer 30

• Activation of macrophages
• Activation of osteoclasts
• Immune complex formation

Question 31

Phases of pre-arthritis

Answer 31

Question 32

What activated fibroblasts do to the synovium

Answer 32

• Matrix deposition and remodeling
• Chondrocyte catabolism
• Synovial osteoclastogenesis

Question 33

Snapshot of RA inside the synovium

Answer 33