Drug induced lupus

Question 1

What is drug-induced lupus (DIL)?

Answer 1

DIL is a lupus-like autoimmune reaction triggered by prolonged exposure to certain medications. It presents with systemic symptoms similar to SLE, but does not cause kidney failure or CNS involvement.

Question 2

What is the pathophysiology of drug-induced lupus?

Answer 2

DIL is caused by altered immune response due to drug metabolism, leading to autoantibody formation. Drugs metabolized via N-acetylation (slow acetylators are at higher risk) promote histone modification, which triggers an autoimmune response with anti-histone antibodies.

Question 3

Which autoantibody is most characteristic of drug-induced lupus?

Answer 3

Anti-histone antibodies (highly specific for drug-induced lupus). Anti-dsDNA antibodies are rarely seen in DIL.

Question 4

What are the clinical features of drug-induced lupus?

Answer 4

• Arthralgia/arthritis (most common, symmetric, non-erosive)
• Fever, fatigue, weight loss
• Serositis (pleuritis, pericarditis)
• Myalgias
• Rash (less common than in SLE, no malar rash)
• Does NOT cause renal or CNS involvement.

Question 5

Which medications are most commonly associated with drug-induced lupus?

Answer 5

• Hydralazine (used for hypertension, especially in pregnancy)
• Procainamide (antiarrhythmic, used for ventricular arrhythmias)
• Isoniazid (INH) (used for tuberculosis treatment)
• Minocycline (used for acne, rosacea, and bacterial infections)
• Quinidine (antiarrhythmic, used for atrial fibrillation, malaria)
• TNF-alpha inhibitors (infliximab, etanercept, adalimumab; used for autoimmune diseases)

Question 6

What is the mechanism of action of hydralazine?

Answer 6

Direct vasodilator that reduces afterload by relaxing vascular smooth muscle, especially in arterioles.

Question 7

What are the indications for hydralazine?

Answer 7

• Hypertension (especially in pregnancy)
• Heart failure (reduces afterload, used in African American patients with nitrate therapy)

Question 8

What are the contraindications for hydralazine?

Answer 8

• Coronary artery disease (can cause reflex tachycardia, worsening ischemia)
• Severe aortic stenosis (afterload reduction worsens cardiac output)

Question 9

What are the adverse effects of hydralazine?

Answer 9

• Drug-induced lupus
• Reflex tachycardia (can precipitate angina in CAD patients)
• Fluid retention, peripheral edema
• Headache, flushing

Question 10

What is the mechanism of action of procainamide?

Answer 10

Class 1A antiarrhythmic that blocks sodium channels, slowing conduction and prolonging repolarization.

Question 11

What are the indications for procainamide?

Answer 11

• Ventricular arrhythmias
• Supraventricular tachycardia (SVT)
• Wolff-Parkinson-White syndrome

Question 12

What are the contraindications for procainamide?

Answer 12

• Heart failure (negative inotropic effects)
• Second- or third-degree AV block (without pacemaker)

Question 13

What are the adverse effects of procainamide?

Answer 13

• Drug-induced lupus
• QT prolongation → Torsades de pointes
• Agranulocytosis, leukopenia

Question 14

What is the mechanism of action of isoniazid?

Answer 14

Inhibits mycolic acid synthesis, which is essential for the Mycobacterium tuberculosis cell wall.

Question 15

What are the indications for isoniazid?

Answer 15

• Latent and active tuberculosis
• Prophylaxis for TB-exposed individuals

Question 16

What are the contraindications for isoniazid?

Answer 16

• Active liver disease (risk of hepatotoxicity)
• Peripheral neuropathy (use pyridoxine/B6 to prevent)

Question 17

What are the adverse effects of isoniazid?

Answer 17

• Drug-induced lupus
• Hepatotoxicity
• Peripheral neuropathy (due to pyridoxine/B6 deficiency)

Question 18

What is the mechanism of action of TNF-alpha inhibitors (infliximab, etanercept, adalimumab)?

Answer 18

Block tumor necrosis factor-alpha (TNF-alpha), reducing inflammation in autoimmune diseases.

Question 19

What are the indications for TNF-alpha inhibitors?

Answer 19

• Rheumatoid arthritis
• Psoriatic arthritis
• Inflammatory bowel disease (Crohn’s disease, ulcerative colitis)
• Ankylosing spondylitis

Question 20

What are the contraindications for TNF-alpha inhibitors?

Answer 20

• Active infections (TB, sepsis, fungal infections)
• Multiple sclerosis (can worsen demyelination)
• Heart failure (TNF-alpha is cardioprotective, blocking it may worsen HF)

Question 21

What are the adverse effects of TNF-alpha inhibitors?

Answer 21

• Drug-induced lupus
• Increased risk of infections (TB reactivation, histoplasmosis, candidiasis, etc.)
• Demyelination (contraindicated in multiple sclerosis)
• Heart failure exacerbation

Question 22

How is drug-induced lupus diagnosed?

Answer 22

• Positive ANA (antinuclear antibody)
• Positive anti-histone antibodies (highly specific for DIL)
• Negative anti-dsDNA (differentiates from SLE)
• Normal complement levels (C3, C4 are reduced in SLE but normal in DIL)

Question 23

What is the first-line treatment for drug-induced lupus?

Answer 23

• Discontinue the offending medication
• NSAIDs for mild symptoms
• Corticosteroids for severe cases (e.g., significant serositis, arthritis)

Question 24

Does drug-induced lupus cause kidney failure?

Answer 24

No. Unlike systemic lupus erythematosus (SLE), drug-induced lupus does not lead to nephritis or CNS involvement.