Dermatopathology of Drug Eruptions

Overview / Definition Drug eruptions refer to a spectrum of skin reactions that occur due to the administration of medications. These eruptions can range from benign rashes to severe reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The clinical presentation can vary widely depending on the drug involved, the route of administration, and the individual's immune response. Epidemiology Drug eruptions are a common cause of cutaneous adverse events, accounting for approximately 2-3% of all hospital admissions due to adverse drug reactions. Certain populations, such as the elderly and those with multiple comorbidities, are at higher risk. Specific drugs, including antibiotics, anticonvulsants, and non-steroidal anti-inflammatory drugs (NSAIDs), are frequently implicated. Pathophysiology / Mechanism The pathophysiology of drug eruptions can involve both immune-mediated and non-immune-mediated mechanisms. Immune-mediated reactions often involve T-cell activation leading to keratinocyte apoptosis. Non-immune mechanisms may include direct drug toxicity or metabolic byproducts acting on the skin. Key mechanisms include: Type I hypersensitivity: IgE-mediated reactions such as urticaria. Type IV hypersensitivity: Delayed-type reactions like contact dermatitis. Direct toxicity: Drugs causing damage to skin cells directly. Autoimmune reactions: Drugs triggering autoimmune processes, e.g., drug-induced lupus erythematosus. Clinical Presentation The clinical presentation of drug eruptions is highly variable and can include: Exanthematous drug eruptions: Maculopapular rashes often occurring 1-2 weeks after exposure. Urticaria: Raised, itchy welts that can appear immediately or within hours. Fixed drug eruption: Well-defined plaques that recur at the same site upon re-exposure. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN): Severe mucocutaneous reactions characterized by extensive skin detachment. Patients may also present wi