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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Most common drug eruption is morbilliform exanthem: symmetric trunk-first maculopapular rash 1-2 weeks after drug start
- Red flags: mucosal involvement, skin pain, facial edema, fever, lymphadenopathy, blistering, pustules, purpura, eosinophilia, hepatitis, kidney injury
- Common culprit drugs: beta-lactams, sulfonamides, anticonvulsants, allopurinol, NSAIDs, antiretrovirals, vancomycin, immune checkpoint inhibitors
- Management: stop culprit drug when possible; supportive care with topical steroids/antihistamines for mild eruptions
- DRESS = fever + facial edema + morbilliform rash + eosinophilia + organ involvement 2-8 weeks after drug start
Overview
Drug eruptions are medication-related skin reactions. They range from benign self-limited exanthems to life-threatening severe cutaneous adverse reactions. Timing is high-yield: morbilliform eruptions usually occur 7-14 days after starting a new drug; urticaria/anaphylaxis may occur within minutes to hours; fixed drug eruption recurs at the same site; DRESS typically occurs 2-8 weeks after exposure; SJS/TEN often develops within 1-4 weeks. A careful medication history including prescriptions, OTC drugs, supplements, contrast, and recent dose changes is the core diagnostic step.
Epidemiology
Cutaneous adverse drug reactions are common among hospitalized and outpatient patients. Antibiotics, especially beta-lactams and sulfonamides, are frequent triggers. Anticonvulsants such as lamotrigine, carbamazepine, phenytoin, and phenobarbital; allopurinol; NSAIDs; antiretrovirals; and immunotherapies are major severe-reaction culprits. Viral infections, HIV, autoimmune disease, malignancy, polypharmacy, renal dysfunction, and pharmacogenomic susceptibility increase risk.
Clinical Features
Symptoms
Pruritic symmetric maculopapular rash beginning on trunk after recent medication
Hives, wheeze, hypotension, or angioedema soon after medication = immediate hypersensitivity/anaphylaxis
Fever, malaise, facial swelling, lymphadenopathy, or systemic symptoms
Skin pain, eye pain, oral/genital erosions, dysuria, or blistering
Recurrent sharply demarcated dusky patch at same site after medication suggests fixed drug eruption
Signs
Morbilliform exanthem: symmetric erythematous macules/papules on trunk and proximal extremities
DRESS: facial edema, morbilliform eruption, fever, lymphadenopathy, eosinophilia, hepatitis
AGEP: numerous sterile nonfollicular pustules with fever and neutrophilia
SJS/TEN: dusky targetoid lesions, mucosal erosions, skin pain, positive Nikolsky sign
Purpura, necrosis, or palpable purpura suggests vasculitis or severe reaction
Investigations
First-line
Medication timelineList every drug started in the past 8 weeks plus intermittent drugs. Include antibiotics, anticonvulsants, allopurinol, NSAIDs, OTCs, supplements, contrast, and biologics
Severity assessmentVitals, mucosa, skin pain, BSA, facial edema, lymph nodes, blistering, purpura, pustules, organ symptoms
Second-line
CBC with differential and CMPCheck eosinophilia, neutrophilia, atypical lymphocytes, LFTs, creatinine, bilirubin for DRESS/AGEP/systemic involvement
Skin biopsyIf severe, atypical, blistering, purpuric, pustular, or diagnosis uncertain; helps distinguish SJS/TEN, vasculitis, AGEP, bullous disease
UrinalysisIf DRESS or vasculitis suspected to assess renal involvement
Specialist
Patch testing or delayed intradermal testingSelected cases after recovery under allergy/dermatology supervision; not during acute severe reactions
Viral/reactivation testsConsider HHV-6/EBV/CMV in DRESS under specialist care; hepatitis/HIV based on presentation
Management
AAD severe cutaneous adverse reaction principles and AAAAI drug allergy practice principles1
Mild morbilliform eruption
- Stop nonessential culprit medication when possible
- Topical corticosteroids, oral second-generation antihistamines, emollients, and reassurance
- If medication is essential and rash is mild without red flags, continuation may be considered with close monitoring and specialist input
2
Immediate allergic reaction
- Anaphylaxis: IM epinephrine immediately plus airway/oxygen/IV fluids; stop drug and document allergy
- Acute urticaria without anaphylaxis: antihistamines and drug avoidance
3
Severe cutaneous adverse reactions
- SJS/TEN: stop culprit drug, hospitalize in burn unit/ICU, dermatology/ophthalmology, supportive care
- DRESS: stop culprit drug, evaluate organ involvement, systemic corticosteroids often used for significant organ disease with slow taper under specialist guidance
- AGEP: stop culprit drug; supportive care, topical steroids; systemic therapy rarely needed unless severe
- Avoid rechallenge with culprit drug in SCARs; document clearly
4
Patient safety
- Record exact drug, reaction phenotype, date, severity, and contraindicated related drugs
- Consider pharmacogenomic screening when relevant before high-risk drugs in at-risk populations
- Provide written warning for SCARs to prevent accidental rechallenge
Complications
- SJS/TEN: Epidermal detachment, sepsis, ocular scarring, death
- DRESS: Hepatitis, nephritis, pneumonitis, myocarditis, thyroiditis, delayed autoimmune disease
- Anaphylaxis: Airway compromise and shock
- Mislabeling: Inaccurate allergy labels can cause unnecessary broad-spectrum antibiotic use
- Rechallenge: Re-exposure after SCAR can be rapidly fatal
USMLE Step 2 CK Exam Tips
- 1Most common drug eruption = morbilliform maculopapular rash 1-2 weeks after starting antibiotic
- 2Mucosal erosions or skin pain in a drug rash = SJS/TEN until proven otherwise
- 3DRESS timing is later: 2-8 weeks plus fever, facial edema, eosinophilia, hepatitis
- 4AGEP = acute fever + many sterile pustules + neutrophilia after medication
- 5Fixed drug eruption recurs in the exact same location and leaves hyperpigmentation
- 6Do not rechallenge after SJS/TEN or DRESS
- 7Check CBC with differential and CMP when systemic red flags are present
practicetest your knowledge on drug eruptionsApply what you've learnt with USMLE Step 2 CK-style questions from the iatroX Q-Bank — dermatology and beyond.
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