What is the pathophysiology of fixed drug eruptions (FDE)?

Updated: Oct 09, 2020
  • Author: David F Butler, MD; Chief Editor: Dirk M Elston, MD  more...
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Although the exact mechanism is unknown, recent research suggests a cell-mediated process that initiates both the active and quiescent lesions. The process may involve an antibody-dependent, cell-mediated cytotoxic response. [10] CD8+ effector/memory T cells play an important role in reactivation of lesions with re-exposure to the offending drug. [11, 12]

The offending drug is thought to function as a hapten that preferentially binds to basal keratinocytes, leading to an inflammatory response. [13] Through liberation of cytokines such as tumor necrosis factor-alpha, keratinocytes may locally up-regulate expression of the intercellular adhesion molecule-1 (ICAM1). [14] The up-regulated ICAM1 has been shown to help T cells (CD4 and CD8) migrate to the site of an insult. [15, 16]

The newly arriving and residential CD8 cells likely perpetuate tissue damage by their production of the inflammatory cytokines interferon-gamma and tumor necrosis factor-alpha. CD8 cells isolated from active lesions have also been shown to express alpha E beta 7, a ligand for E-cadherin, which may further contribute to the lymphocyte’s ability to localize to the epidermis. Other cell surface molecules, such as CLA/alpha4beta1/CD4a, that bind E-selectin/vascular cellular adhesion molecule-2/ICAM1 help to further attract CD8 cells to the area. [10]

Changes in cell surface markers allow vascular endothelium to select CD4 cells for migration into active lesions. These regulatory CD4 cells likely produce interleukin 10, which has been shown to help suppress immune function, resulting in a resting lesion. [10] As the inflammatory response dissipates, interleukin 15 expression from keratinocytes is thought to help ensure the survival of CD8 cells, helping them fulfill their effector memory phenotypes. Thus, when reexposure to the drug occurs, a more rapid response develops in the exact location of any prior lesions. [10]

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