Rheumatology

Question 1

What are extra-articular manifestations?

Answer 1

Constitutional: weight loss, fatigue, fever, malaise
Cutaneous: easy bruising, soft tissue swelling, R nodules, drying of mucous membranes
Cardiac: pericarditis, pericardial effusion, heart block, valvular incompetence
Lung: pulmonary infiltrates, pleural effusion, pulmonary fibrosis
Eyes: episcleritis, scleritis, dry eyes due to Sjogren’s syndrome
Neuro: proximal myopathy, mononeuritis complex
Vasculitis: microvascular vasculitis
Kidney: glomerulonephritis, vasculitis, due to medications

Question 2

Is there a single test to diagnose RA?

Yes
No

If yes, what is the test?

Answer 2

No, there isn’t a single test to diagnose RA.

Question 3

You must wait until radiological findings are in align with RA before you can start DMARD therapy.

True
False

Answer 3

False.

DMARD should be started prior to radiological findings indicate abnormality.

Question 4

What tests would you order to investigate for RA?

Answer 4

• FBC
• RF and anti-CCF
• ESR and CRP
• ANA, ENA
• Serology for B19, HCV, HBV

Imaging:

• X-ray of large joints
• Joint aspirate & synovial fluid analysis (look for cell count, complement, high protein, low glucose)

Question 5

What are your non-pharmacological managements for RA?

Answer 5

• Exercises helps maintain range of motion and build muscle strength

Question 6

Describe how to use NSAIDs and steroids as part of treatment for RA.

Answer 6

NSAIDs: used for symptomatic pain treatment in RA. There are non-selective COX inhibitors, which inhibit COX-2, decreasing inflammation and pain by modifying prostaglandin synthesis.
E.g. ibuprofen, diclofenac, celebrix (COX-2 selective)

Corticosteroids: reduce inflammation if NSAIDs don’t work.

Question 7

What is DMARDs and what are the main classes involved?

Answer 7

DMARD stands for Disease Modifying Anti-Rheumatic Drugs.

Different classes include methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, anti-TNF agents, IL-6 inhibitors.

Question 8

What is the treatment regime for RA (mild and severe)

Answer 8

Mild: DMARD + NSAID + corticosteroid
Severe: 2 DMARD + NSAID + corticosteroid, OR SURGERY.

Question 9

What is COX-1 function? (2)

Answer 9

1. Thromboxane A2 production for platelet aggregation initiation
2. Prostaglandin production for protective mucosal layer for GIT layer protection (blood flow and secretion of bicarbonate)

Question 10

What is COX-2 function?

Answer 10

Inflammatory cell recruitment, pain mediation and fever through cytokine release and modification of thermostat in the hypothalamus.

Question 11

What are some NSAID side effects?

Answer 11

GIT: ulcers, acute bleeding, erosion, discomfort
Lungs: bronchospasm
CVS: MI and stroke
Increased risk of bleeding
Renal: afferent arterioles vasoconstriction
Anaphylaxis and skin rashes
Hepatotoxicity

Question 12

Corticosteroid

MOA?

Answer 12

Anti-inflammatory and immunosuppression. They bind to the intracellular glucocorticoid receptor. This creates a complex, which translocates to nucleus and interacts with DNA.

• Blocks proinflammatory genes
• Recruits transcription factors to promote anti-inflammatory gene factors
• Inhibition of inflammatory cytokines
• Promotes T-cell apoptosis

Question 13

Corticosteroid

Side effects?

Answer 13

Skin thinning, purpura, ecchymoses 
Weight gain 
Cushing's disease 
Acne 
Striae 
Glaucoma 
Increased intra-ocular pressure
Fluid retention
HTN
AF 
Gastritis, PUD 
Osteoporosis
Myopathy 
Euphoria, insomnia, mania
Hyperglycaemia 
Leucocytosis

Question 14

Methotrexate

MOA?

Answer 14

It is first-line DMARD for RA.
Anti-metabolite of antifolate type. It has cytotoxic and immunosuppressant effects through inhibition of T cell activation, B cell and IL-1. It inhibits DNA synthesis.

Question 15

Methotrexate

Side effects?

Answer 15

GI upset, oral ulcers, alopecia, bone marrow suppression (folate supplements needed), hepatocellular injury

Question 16

Methotrexate

Contraindication? (1)

Answer 16

TERATOGENIC

PREGNANCY

Question 17

Leflunomide

MOA?

Answer 17

Pyrimidine synthesis inhibitor

Immunomodulatory drug inhibiting rapidly dividing cells and WBCs.

Question 18

Leflunomide

Side effects?

Answer 18

Diarrhoea
Rashes
Hepatotoxicity (LFT monitoring)
Respiratory tract infections

Question 19

Leflunomide

Contraindications?

Answer 19

TERATOGENIC

PREGNANCY

Question 20

Hydroxychloroquine

MOA and side effects?

Answer 20

MOA: Immunosuppression of IL-1 and TNF-alpha.

Side effects:

• GI upset
• Interstitial nephritis
• Headache
• Heartburn

Question 21

Anti-TNF agents

Examples and side effects?

Answer 21

Infliximab, etanercept, golimumab

Side effects:

• Abdominal pain
• Nausea
• Headache
• Neutropenia
• Reactivation of TB
• Increased risk of serious infections
• Hepatotoxicity

Screening for latent TB must be completed before starting anti-TNF agents

Question 22

Anti-TNF agents

Contraindications?

Answer 22

Heart failure
Active or latent TB
Active infection
Demyelinating disease