Learning Objective
By the end of this section, students should be able to identify common musculoskeletal, dermatologic, and connective tissue adverse drug reactions, recognize the causative agents, and recall high-yield clinical pearls, which is critical for USMLE Step 1 pharmacology.
Drug-Induced Musculoskeletal / Skin / Connective Tissue Reactions
| Reaction | Causal Agents | Notes / Clinical Features |
|---|---|---|
| Drug-induced lupus | Hydralazine, Procainamide, Quinidine | Autoimmune-like syndrome; positive antihistone antibodies; usually reversible upon drug discontinuation |
| Fat redistribution / lipodystrophy | Protease inhibitors, Glucocorticoids | Fat accumulates in trunk and dorsocervical region (“buffalo hump”); loss in limbs and face |
| Gingival hyperplasia | Cyclosporine, Ca²⁺ channel blockers, Phenytoin | Overgrowth of gum tissue; maintain oral hygiene |
| Hyperuricemia / gout | Pyrazinamide, Thiazides, Furosemide, Niacin, Cyclosporine | Precipitates painful attacks; monitor uric acid, especially in patients with history of gout |
| Malignant hyperthermia | Inhaled anesthetics (e.g., Isoflurane), Succinylcholine | Triggered in patients with RYR1 mutation; antidote is dantrolene; presents with muscle rigidity, hyperthermia |
| Myopathy / rhabdomyolysis | Statins, Fibrates, Niacin, Colchicine, Daptomycin, Hydroxychloroquine, Interferon-α, Penicillamine, Glucocorticoids | Presents with muscle pain, weakness, elevated CK; severe cases → rhabdomyolysis |
| Osteoporosis | Glucocorticoids, Depot medroxyprogesterone acetate, GnRH agonists, Aromatase inhibitors, Anticonvulsants, Heparin, PPIs | Increased fracture risk; counsel on calcium, vitamin D, weight-bearing exercise |
| Photosensitivity | Sulfonamides, Amiodarone, Tetracyclines, Fluoroquinolones | Sunburn-like reaction; advise sun protection |
| Rash / Stevens-Johnson syndrome (SJS) | Anti-epileptic drugs (esp. Lamotrigine), Allopurinol, Sulfa drugs, Penicillin | Severe mucocutaneous reaction; can be life-threatening |
| Teeth discoloration | Tetracyclines | Staining of developing teeth; avoid in children <8 years and pregnant women |
| Tendon/cartilage damage | Fluoroquinolones | Risk of tendonitis or tendon rupture, especially in the elderly or with corticosteroid use |
Step 1 Pearls
- Hydralazine & Procainamide → drug-induced lupus; monitor ANA/antihistone antibodies.
- Protease inhibitors → fat redistribution; monitor for metabolic complications.
- Statins + fibrates → myopathy; check CK if symptomatic.
- Fluoroquinolones → tendon rupture; avoid in the elderly with steroids.
- Malignant hyperthermia → RYR1 mutation; dantrolene is life-saving.
- SJS → lamotrigine, sulfa drugs, penicillin; severe mucocutaneous reaction.
