Arthritis and Autoimmune disease

Question 1

what are the types of inflammatory arthritis?

Answer 1

seropositive arthritis- rheumatoid arthritis

seronegative arthritis- psoriatic arthritis, ankylosing spondylitis, reactive arthritis

Question 2

what is monoarthritis and oligoarthritis and which types of arthritis are they associated with?

Answer 2

mono- one joint affected
oligo- fewer than 5 joints affected
types- osteoarthritis, septic, reactive, gout, psoriatic arthritis

Question 3

what is poly arthritis and which type of arthritis is it associated with?

Answer 3

poly- five or more joints affected

types- rheumatoid (occasionally OA, ankylosing spondylitis, psoriatic)

Question 4

what is the pathophysiology of osteoarthritis?

Answer 4

cartilage between joints breaks down
joint space narrows
osteophytes form- bony spurs along joint margins

Question 5

what are the clinical features of osteoarthritis?

Answer 5

joint pain most commonly affecting hip, knee and hand
worse with use, better at rest
no morning stiffness
may have joint swelling (hard)

Question 6

what is the pathogenesis of rheumatoid arthritis?

Answer 6

inflitation of inflammatory cells into the joints leading to proliferation of synoviocytes and destruction of cartilage and bone

Question 7

what are the clinical features of rheumatoid arthritis?

Answer 7

insidious onset
symmetrical, bilateral
mostly affecting small joints (PIP, MCP, wrists, ankle)
joint pain associated with swelling, redness, heat and stiffness
stiffness/pain is worse in the morning or after inactivity
general symptoms- fever, fatigue, weight loss

Question 8

what are the clinical features of psoriatic arthritis?

Answer 8

asymmetric oligoarthritis commonly of wrist, DIP, feet and ankles
joint pain, stiffness and swelling
tenderness of joint and surrounding ligaments and tendons
nail changes- pitting, yellowing, oncholysis (separation of nail from bed)

Question 9

what is ankylosing spondylitis?

Answer 9

chronic inflammatory arthritis primarily affecting the axial skeleton (skull, spine, ribs)

Question 10

what are the clinical features of ankylosing spondylitis?

Answer 10

insidious onset back pain
morning stiffness, improves with activity
tenderness over sacroiliac joints
loss of lumbar lordosis/ exaggerated thoracic kyphosis
asymmetric peripheral arthritis (hip, shoulder, pubic symphysis)
achilles tendonitis, plantar fasciitis
X- ray- squared vertebral bodies

Question 11

what is reactive arthritis?

Answer 11

inflammatory arthritis that typically develops 2-4 weeks following a GI or GU infection

Question 12

what are the clinical features of reactive arthritis?

Answer 12

asymmetrical lower extremity oligoarthritis
acute onset with fever, fatigue
lower back pain is common

Question 13

what are the clinical features of septic arthritis?

Answer 13

single swollen joint with pain on active and passive movement
most commonly affects knee joint
fever and riggers
warm, tender joint, effusion may be present

Question 14

what are the clinical features of gout?

Answer 14

acute joint pain with swelling and redness
often with fever and malaise
mainly affects 1st MTP- toe

Question 15

what is central tolerance?

Answer 15

elimination of self reactive T cells and B cells in the thymus and bone marrow during early development by the process of negative selection

Question 16

what is peripheral tolerance?

Answer 16

mechanisms that inactivate or climate B and T cells in circulation

Question 17

what are the mechanisms of peripheral tolerance?

Answer 17

anergy- inactivation of B/T cells when they fail to receive a second activation signal
suppression- T reg cells suppress immune responses to self antigens
sequestration of antigens behind a physical barrier- T cells entering immune privileged sites (testis, brain) undergo apoptosis via Fas

Question 18

what is molecular mimicry?

Answer 18

infections can mimic self antigens and thus the antibodies produced against the pathogen can react to self cells and cause injury

Question 19

how does chronic autoantibody mediated inflammation occur?

Answer 19

B cell presents self antigen from dead/dying cell on MHC II.
T cell binds to MHC II and activates the B cell and it releases autoantibodies.
autoantibodies bind to self cells forming immune complexes and trigger an inflammatory response which causes more cell injury and establishing a positive feedback loop

Question 20

what is the pathophysiology of myasthenia gravis?

Answer 20

autoantibodies attack the alpha subunit of Nicotinic ACh receptor on skeletal muscles causing receptor internalisation and degradation. this causes a block in neuromuscular transmission preventing muscles from being stimulated

Question 21

what sort of hypersensitivity reaction occurs in myasthenia gravis?

Answer 21

type II hypersensitivity- autoantibody mediated and organ specific

Question 22

what is the pathogenesis of systemic lupus erythematosus (SLE)?

Answer 22

chronic production of IgG antibodies directed at ubiquitous self antigens in all nucleated cells (e.g dsDNA). autoanitgens are released from dead/dying cells and form immune complexes with autoantibodies. these immune complexes are deposited in small blood vessels and cause inflammation leading to more tissue injury.

Question 23

what sort of hypersensitivity reaction occurs in SLE?

Answer 23

type III hypersensitivity- immune complex mediated, systemic disease

Question 24

what sort of hypersensitivity reaction occurs in rheumatoid arthritis?

Answer 24

both type IV- cell mediated, and type III- immune complex mediated

Question 25

what is the mechanism of action and clinical use of leflunomide?

Answer 25

MOA- suppress mononuclear and T cel proliferation, active metabolite inhibits DHODH and important enzyme in pyrimidine synthesis for T cell proliferation
clinical use- 1st line treatment of RA, psoriatic arthritis, prevent transplant rejection

Question 26

what is the mechanism of action and clinical use of methotrexate?

Answer 26

MOA- inhibits human folate reductase, lymphocyte proliferation and production of cytokines and rheumatoid factor
methotrexate- 1st line treatment of RA, anti-cancer

Question 27

what is the mechanism of action and clinical use of sulfasalazine?

Answer 27

MOA- inhibits IL-2 induced T cell proliferation and inhibit IL-1 and IL-2 production by macrophages
clinical use- 1st line treatment of RA, inflammatory bowel disease, ankylosing spondylitis

Question 28

what is the mechanism of action of infliximab and etanercept?

Answer 28

inhibits TNF- alpha