Fixed drug eruptions

Abstract

Fixed Drug Eruptions (FDEs) are a localized response to medications that typically appear as Well-Demarcated erythematous dusky patches or plaques. They may be solitary, multiple, or generalized. The initial eruption of a FDE appears 1 week Post-Drug exposure, whereas subsequent exposures to the same drug lead to development of lesions within 30 min to 24 h. Despite the number of occurrences, these patches and plaques resolve within 2-3 weeks of discontinuing the offending agent, often leaving Post-Inflammatory hyperpigmentation. NSAIDs (Non-Steroidal Anti-Inflammatory drugs), tetracyclines, Trimethoprim-Sulfamethoxazole, sedatives including barbiturates, benzodiazepines and chlordiazepoxide, and Anti-Convulsants are the most commonly reported drugs causing FDE. Certain drugs have a predilection for causing particular subtypes of FDE, as well as mucosal involvement. Histologically, FDEs present with a vacuolar dermatitis occurring at the Dermo-Epidermal junction. Lymphocyte infiltration and hydropic degeneration of keratinocytes develop over the first 24 h following exposure, which can progress to separation of the dermis and epidermis with subepidermal bullae formation. The immunologic mechanism of FDE involves activation of CD8+ T cells that release interferon gamma, granzymes, and perforins, leading to recruitment of neutrophils, CD4+ T cells, mast cells, and occasionally eosinophils. Diagnosis of FDE is largely clinical and treatment is comprised of discontinuing the offending drug and treating symptoms, such as pruritus and pain. However, if the offending agent is unclear, patch testing or oral Re-Challenge at Sub-Therapeutic doses are the preferred diagnostic tests.