Dermatology · Cutaneous Adverse Drug Reactions
The facts most likely to be tested
The most common form of drug eruption is the exanthematous (morbilliform) drug eruption, typically presenting as symmetric, erythematous macules and papules appearing 7–14 days after drug initiation.
DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a life-threatening emergency characterized by fever, diffuse rash, lymphadenopathy, and internal organ involvement (e.g., hepatitis).
Fixed drug eruption presents as a solitary, dusky, erythematous plaque that recurs in the exact same anatomical location upon re-exposure to the offending agent.
Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are distinguished by the percentage of body surface area (BSA) detachment, with SJS involving <10% and TEN involving >30% BSA.
Nikolsky sign, defined as the lateral displacement of skin leading to denudation with light pressure, is a hallmark clinical finding in SJS/TEN.
Acute Generalized Exanthematous Pustulosis (AGEP) is characterized by the rapid onset of numerous sterile, non-follicular pustules on an erythematous base, often associated with leukocytosis.
The definitive management for all severe drug eruptions is the immediate discontinuation of the suspected offending agent and initiation of supportive care.
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A 45-year-old female presents to the emergency department with a widespread, painful rash that started 3 days ago. She recently completed a 10-day course of allopurinol for gout. Physical examination reveals diffuse erythema and blistering involving 25% of her total body surface area, including the oral mucosa. She exhibits a positive Nikolsky sign upon gentle palpation of the skin. Her temperature is 101.2°F, and she appears toxic.
What is the most likely diagnosis?
Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN) overlap
The patient's presentation of widespread blistering, mucosal involvement, and a positive Nikolsky sign following the initiation of a high-risk medication (allopurinol) is classic for SJS/TEN, which is tested via the clinical criteria of BSA involvement and physical exam findings.
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Etiology / Epidemiology
Most common cutaneous adverse reaction is exanthematous eruption. Beta-lactams and sulfonamides are the most frequent offenders.
Clinical Manifestations
Symmetric, morbilliform rash starting on trunk. Herald patch absent; Nikolsky sign negative in simple eruptions.
Diagnosis
Diagnosis is clinical. Skin biopsy is reserved for atypical cases or suspected DRESS syndrome.
Treatment
Discontinue offending agent. Oral antihistamines and topical corticosteroids for pruritus. Systemic steroids for severe cases.
Prognosis
Resolution typically occurs within 1-2 weeks after drug cessation. Anaphylaxis is the primary acute mortality risk.
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Epidemiology & Etiology
Drug eruptions occur in 2-3% of hospitalized patients. High-risk groups include patients with EBV (amoxicillin rash) and those on allopurinol or anticonvulsants. Onset is typically 7-14 days after initiation of a new medication.
Pertinent Anatomy
The eruption involves the dermis and epidermis. Involvement of mucous membranes suggests more severe processes like Stevens-Johnson Syndrome.
Pathophysiology
Most reactions are Type IV hypersensitivity (T-cell mediated). DRESS syndrome involves HHV-6 reactivation. Cytotoxic T-cell activation leads to keratinocyte apoptosis in severe variants.
Clinical Manifestations
Presents as symmetric maculopapular rash. Red flags include facial edema, lymphadenopathy, or mucosal involvement. Nikolsky sign positivity indicates Toxic Epidermal Necrolysis.
Diagnosis
Diagnosis is primarily clinical history. Skin biopsy is the gold standard to rule out mimics. Labs should include CBC with differential to screen for eosinophilia in suspected DRESS.
Treatment
Immediate discontinuation of the culprit drug is mandatory. Oral antihistamines manage pruritus. Systemic corticosteroids are indicated for severe systemic involvement. Epinephrine is the first-line treatment for anaphylaxis.
Prognosis
Most cases resolve within 14 days. DRESS syndrome carries a 10% mortality rate due to organ failure. Patients must be counseled on cross-reactivity.
Differential Diagnosis
Viral exanthem: usually preceded by prodrome
Stevens-Johnson Syndrome: involves mucosal surfaces
DRESS syndrome: associated with fever and internal organ involvement
Acute Generalized Exanthematous Pustulosis: presents with sterile pustules
Contact dermatitis: localized to area of exposure