Rheumatoid Arthritis

Question 1

Symptoms of RA

Answer 1

Joint pain - throbbing/aching pain, worse in mornings and after inactivity
Joint stiffness (worse in mornings), swelling, redness, tenderness 
Commonly affects small joints of hands and feet, usually symmetrical 
Tiredness, fever, reduced appetite

Question 2

Risk factors for RA

Answer 2

Women
Smoking
Family history

Question 3

Pathophysiology of RA

Answer 3

Chronic autoimmune inflammatory disease - type III hypersensitivity
Rheumatic factor binds to IgG receptors on macrophages leading to immune complex formation.
Release cytokines that cause inflammation of the synovial membrane, damages underlying cartilage

Question 4

Investigations of RA

Answer 4

Bloods - FBC, CRP, rheumatoid factor, ANA assay
X-ray - hands, wrists, feet, etc
Joint aspiration and synovial fluid analysis

Question 5

Management of RA

Answer 5

DMARDs eg. Methotrexate, sulfasalazine
Anti-TNF agents eg. Infliximab, Rituximab, Adalimumab
NSAIDs eg. Ibuprofen, naproxen
Corticosteroids

Question 6

Mechanism of action of methotrexate

Answer 6

Inhibits purine metabolism, so increases adenosine levels, which acts on GPCRs to reduces T-cell activity

Question 7

ADRs of methotrexate

Answer 7

ADRs: mucositis, bone marrow suppression, hepatitis, cirrhosis, increased infection risk, teratogenesis

Question 8

Mechanism of action of sulfasalazine

Answer 8

Conjugate of Salicylate (5-ASA) and Sulfapyridine.
Sulfapyridine component allows absorbtion but also causes ADRs.
Salicylate is the active component, inhibits T-cell and IL-2 proliferation, reduces neutrophil chemotaxis and degranulation

Question 9

Sulfasalazine ADRs

Answer 9

Myelosuppression, hepatitis, rash, nausea, fatigue, headache, abdominal pain

Question 10

Mechanism of action of Anti-TNF agents

Answer 10

Block TNF-alpha with a monoclonal antibody, reduces inflammation, angiogenesis and joint destruction

Question 11

Mechanism of action of NSAIDs

Answer 11

Competitive inhibitors of COX-1 and COX-2 enzymes, prevent prostaglandin synthesis from arachidonic acid

Question 12

ADRs of NSAIDs

Answer 12

GI - stomach pain, nausea, heartburn, gastric ulcer/bleeding
Renal - reduced blood flow -> reduced GFR
Vascular - increased bruising, risk of haemorrhage
Skin rashes, Steven Johnson syndrome (rare)

Question 13

Complications of RA

Answer 13

Carpal tunnel syndrome
Widespread inflammation -> pulmonary fibrosis, pericarditis, vasculitis
CVS disease

Question 14

Signs of RA

Answer 14

Rheumatoid nodules

Question 15

RA differential diagnosis

Answer 15

Osteoarthritis
SLE
Fibromyalgia
Sarcoidosis