Etiology and Pathophysiology

Although the exact mechanism is unknown, recent research suggests a cell-mediated process that
iniates both the active and quiescent lesions. The process may invove an antibody-dependant, cell-
mediated cytotoxic response. CD8+ effector/memory T cells play an important role in reactivation of
lesions with re-exposure to the offending drug.

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

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 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 further attract CD8 cells to the area.

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. As the inflammatory response
dissipates, interleukin 15 expression from keratinocytes is though to help ensure the survival of CD8
cells, helping them fullfil their effector memory phenotypes. Thus, when reexposure to the drug
occurs, a more rapid response develops in the exact in the exact location of any prior lesions.

Etiology FDE

The major categories of causative agents of fixed drug eruption include antibiotics, antiepileptics,
nonsteroidal anti-inflammatory agents, sildenafil, and phenothiazines, although numerous other
agents and certain food such as cashews and licorice have also been reported as causative agents.
Ingestion of the causative agent may occur via any route, including oral, rectal, or intravenous.

Certain classes of drugs with cross-reactions within a class have been reported to elicit a fixed drug
eruption with qunolones and with non-steroidal anti-inflammatory agents. In some patients, the
reaction may be due to a dye rather than the active ingredient. Fixed drug eruption may be rarely
related to foods, including residual antibiotics in meat products and quinine contained in tonic
water.

While fixed drug eruptions are uncommon with general anesthesia, propofol has been implicated in
causing a drug eruption on the penis.

The most common cause is trimethoprim-sulfamethoxazole. Othe substances implicated to cause

fixed drug eruptions are as follows
Table.Substances Implicated in Fixed Drug Eruption

Acetaminophen Acyclovir
Amlexanox Amoxicillin
Atenolol Barbiturates
Ceftriaxone Celecoxib
Chlorhexidine Chlormezanone
Clioquinol Clopidogrel
Cyproterone acetate Dextromethorph
Docetaxel Eperisone hydrochloride
Finasteride Flecainide
Gabapentin Griseofulvin
Iodinated radiography contrast media Lomeprol
Lamotrigine Lentils
Lormetazepam Magnesium trisilicate
Metramizole Metronidazole
Naproxen Nimesulide
Oxyphenbutazone Paclitaxel
Penicillin Phenazone
Phenylpropanolamine Phenytoin
Prochlorperazine Pseudoephedrin
Sodium benzoate Strawberries
Tetracylines Theophylline
Tolfenamic acid Tosufloxacin
It is though that an antigen from the drug activates cytotoxic T cells in the epidermis. These release
cytokines (inflammatory mediators), such as interferon-y, granzyme B, and perforin. The cytokines,
with helper T cells and neutrophils, destroy the local skin celss( keratinocytes and melanocytes). The
cytotoxyc T cells then remain in the epidermis and release more cytokines when again exposed to
the causative drug

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