Severe drug reactions are emergencies, and USMLE Step 2 CK expects you to recognize them and act fast. These three dermatology practice questions cover Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and DRESS syndrome, plus how to prevent them. Pick your answer first, then open the explanation.
Question 1: Skin peeling and mouth sores after starting a new drug
A 34-year-old woman started lamotrigine for bipolar disorder 2 weeks ago. She now has fever, painful erosions of the lips, mouth and eyes, and dusky red skin lesions that have blistered and peeled over 40% of her body surface. Nikolsky sign is positive. Which of the following is the most important first step in management?
A. Start high-dose oral prednisone and continue lamotrigine B. Stop lamotrigine and transfer her to a burn unit or ICU C. Start oral antibiotics and discharge with follow-up D. Reduce the lamotrigine dose E. Apply topical corticosteroids to the affected skin
Correct answer: B. Stop lamotrigine and transfer her to a burn unit or ICU
This is toxic epidermal necrolysis (TEN): full-thickness epidermal necrosis involving more than 30% of the body surface, with mucosal involvement. The most important steps are to stop the offending drug immediately and give supportive care in a burn unit or ICU: fluids, wound care, pain control, eye care and infection prevention. Mortality can exceed 30%.
Why the other options are wrong:
Continuing lamotrigine is dangerous; the drug must be stopped permanently.
Discharge is unsafe; these patients lose fluid and protein like burn victims and are at high risk of sepsis.
Reducing the dose is not enough.
Topical steroids do not treat the disease; the role of systemic steroids is controversial (cyclosporine or IVIG may be used in specialist care).
High-yield: Body surface area: SJS <10%, SJS/TEN overlap 10–30%, TEN >30%. Common causes: allopurinol, anticonvulsants (lamotrigine, carbamazepine, phenytoin), sulfonamides, nevirapine and NSAIDs. Lamotrigine risk is highest when the dose is increased too fast or combined with valproate.
Question 2: Rash, fever and eosinophilia weeks after a new medication
A 60-year-old man started allopurinol for gout 5 weeks ago. He now has fever, a widespread itchy red rash, facial swelling and enlarged lymph nodes. Labs show eosinophilia, atypical lymphocytes and elevated liver enzymes. Which of the following is the most likely diagnosis?
A. Stevens-Johnson syndrome B. DRESS syndrome C. Serum sickness D. Acute urticaria E. Viral exanthem
Correct answer: B. DRESS syndrome
DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) starts 2–8 weeks after a new drug – later than most drug rashes. Features: fever, widespread rash, facial edema, lymphadenopathy, eosinophilia and atypical lymphocytes, and internal organ involvement – most often the liver, also kidneys, lungs and heart. Treatment: stop the drug and give systemic corticosteroids.
Why the other options are wrong:
SJS causes mucosal erosions and epidermal detachment, not eosinophilia with organ involvement.
Serum sickness causes fever, rash and joint pain 1–2 weeks after exposure, with low complement, but not hepatitis with eosinophilia.
Acute urticaria appears within minutes to hours and has no organ involvement.
Viral exanthems do not cause eosinophilia and hepatitis after a new drug.
High-yield: Common DRESS drugs: allopurinol, anticonvulsants, sulfonamides, minocycline and vancomycin. Reactivation of HHV-6 is often seen. Symptoms may flare as steroids are tapered, so taper slowly.
Question 3: Preventing a severe skin reaction before carbamazepine
A 25-year-old man of Han Chinese ancestry is diagnosed with focal epilepsy. His physician plans to start carbamazepine. Which of the following tests should be done before the first dose?
A. HLA-B*57:01 B. HLA-B*15:02 C. HLA-B27 D. TPMT activity E. G6PD level
Correct answer: B. HLA-B*15:02
In patients of Asian ancestry (especially Han Chinese, Thai, Malaysian and Indian), the HLA-B*15:02 allele strongly increases the risk of carbamazepine-induced SJS/TEN. Testing is recommended before starting carbamazepine (and it is also relevant for phenytoin and oxcarbazepine). If positive, choose another drug.
Why the other options are wrong:
HLA-B*57:01 is tested before abacavir (HIV) to prevent hypersensitivity.
HLA-B27 is linked to ankylosing spondylitis and other seronegative spondyloarthropathies.
TPMT is checked before azathioprine and 6-mercaptopurine.
G6PD is checked before dapsone, primaquine and rasburicase.
High-yield: Another key pairing: HLA-B*58:01 and allopurinol-induced SJS/TEN and DRESS, especially in Han Chinese, Korean and Thai patients.
Key takeaways
SJS (<10% BSA) and TEN (>30%) → stop the drug, burn unit/ICU care.
DRESS → 2–8 weeks after the drug; fever, facial edema, eosinophilia, hepatitis; stop drug + steroids.
Before carbamazepine in Asian patients → HLA-B*15:02; before abacavir → HLA-B*57:01.
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Written and reviewed by Dr. Ray Makar, MD, dermatologist with 20 years of clinical practice. Last reviewed: October 2026. For exam preparation only, not medical advice.
