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Updated: Nov 9, 2025
Granulocyte-dependent Autoantibody-induced Skin Blistering
Published on: October 12, 2012
[Establishment of animal models of epidermal growth factor receptor inhibitor-related rashes]
Objective:
To establish animal models epidermal growth factor receptor inhibitor-related skin rashes using cetuximab, gefitinib or erlotinib.
Objective:
Female SCID mice were randomly divided into blank control group and high-, moderate-, and low-dose cetuximab groups. The mice in control group received intraperitoneal injection of saline, and those in the 3 cetuximab groups were injected with 80, 40, and 20 mg/kg cetuximab (3 times a week for 4 weeks), respectively. The general skin appearance and skin pathologies of the mice were observed. Female BN rats were randomly divided into blank group, ovalbumin group, gefitinib group and erlotinib group, and in the latter 3 groups, the rats were given ovalbumin (1 mg), gefitinib (37.5 mg/kg), and erlotinib (23.5 mg/kg) by lavage once daily for 45 days, respectively. Skin pathologies of the rats were observed, and serum levels of TNF-α, IL-6 and other inflammatory factors were detected using ELISA.
Objective:
Intraperitoneal injection of cetuximab did not induce typical skin rashes, scabs or obvious skin inflammation in the mice. In female BN rats, lavage of gefitinib caused obvious skin rashes, scabs and exudation, and obvious inflammatory cell infiltration, keratinosis, spinous layer release and epidermal thickening were observed in the skin. No obvious skin inflammation were observed in the rats in the control, ovalbumin or erlotinib groups. While IgE (P=0.061) and TNF-α concentrations (P=0.057) did not differ significantly among the groups, serum levels of IL-6 was significantly higher in gefitinib group than in the blank control group (P=0.016) but similar between erlotinib group and the blank group (P=0.910).
Objective:
Intraperitoneal injection of cetuximab can not induce epidermal growth factor receptor inhibitor-related skin rashes in SCID mice. Lavage of gefitinib, but not erlotinib, can be used to establish models of epidermal growth factor receptor inhibitor-related rashes in BN rats.
Insights
Cetuximab did not induce skin rashes in mice. Gefitinib, but not erlotinib, caused skin rashes and inflammation in rats, establishing a model for epidermal growth factor receptor inhibitor-related skin conditions.
Area of Science:
- Dermatology
- Pharmacology
- Toxicology
Background:
- Epidermal growth factor receptor (EGFR) inhibitors are crucial cancer therapies.
- Skin toxicities are common side effects of EGFR inhibitors.
- Establishing reliable animal models for these skin toxicities is essential for research.
Purpose of the Study:
- To develop and validate animal models for skin rashes induced by EGFR inhibitors.
- To compare the efficacy of cetuximab, gefitinib, and erlotinib in inducing skin toxicities in different animal models.
Main Methods:
- Female SCID mice received intraperitoneal injections of cetuximab at varying doses.
- Female BN rats were administered ovalbumin, gefitinib, or erlotinib via lavage.
- Skin pathologies were assessed, and serum inflammatory markers (TNF-α, IL-6) were measured using ELISA.
Main Results:
- Cetuximab administration did not induce significant skin rashes or inflammation in SCID mice.
- Gefitinib treatment in BN rats resulted in observable skin rashes, scabs, exudation, and inflammatory cell infiltration.
- Elevated IL-6 levels were detected in rats treated with gefitinib compared to controls, while TNF-α and IgE levels showed no significant differences.
Conclusions:
- Intraperitoneal cetuximab is not suitable for modeling EGFR inhibitor-related skin rashes in SCID mice.
- Gefitinib, administered via lavage, effectively models EGFR inhibitor-induced skin rashes in BN rats.
- The BN rat model with gefitinib provides a valuable tool for studying EGFR inhibitor dermatologic toxicities.
