Possible involvement of zinc deficiency in epidermal growth factor receptor inhibitor‐induced xerotic dermatitis

Abstract

Cancer treatment with epidermal growth factor receptor inhibitors (EGFRIs) often induces severe xerotic dermatitis. Various irritants facilitate development of dermatitis in xerotic skin. As zinc deficiency plays a role in the development of irritant dermatitis, we measured serum zinc levels in 25 patients with xerotic dermatitis due to treatment with EGFRIs. Of these patients, nine were treated with EGFR tyrosine kinase inhibitors and 16 were treated with anti‐EGFR antibody alone or in combination with other anticancer agents. Serum zinc levels of all patients were lower than the normal range of >80 μg/dL, with a mean ± SD serum zinc level of 56.4 ± 11.7 μg/dL. These were correlated with serum magnesium levels in patients. As the serum magnesium level is known to be reduced by the inhibition of EGFR, a similar mechanism may also be involved in decreasing the serum zinc level. Among 21 patients treated with zinc supplementation for more than 2 months, xerotic dermatitis markedly improved, with an increase of serum zinc levels in 16 patients. The other five patients exhibited no significant improvement in their skin condition, and insufficient and unstable increase in serum zinc levels. In conclusion, zinc supplementation may be beneficial in supportive care for patients with EGFRI‐induced xerotic dermatitis.

Cardiovascular toxicity of tyrosine kinase inhibitors during cancer treatment: Potential involvement of TRPM7

“…Hence, downregulation of TRPM7 induced by TKI might affect intracellular concentration of Zn 2+ . Clinical investigations showed reduced serum Zn 2+ as adverse effect of EGFR inhibition and Zn 2+ supplementation was able to reduce dermatitis these patients (185). Of importance, Zn 2+ is a potent antioxidant and its deficiency is associated with mitochondrial and endoplasmic reticulum (ER) stresses, increased ROS production and dysregulation of cellular metabolism (186).…”

A prospective observational study of zinc deficiency symptoms during first-line chemotherapy for gastric and colorectal cancer

“…The skin is known to be one of the systems that is most susceptible to zinc de ciency, hence the rash and itching [1]. We also reported that a zinc homeostasis disorder might cause the development of skin xerosis in patients with colorectal cancer treated with FPOX plus anti-EGFR antibody [22]. The skin conditions and zinc levels appeared to be closely correlated.…”

Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma

“…A case of necrolytic migratory erythema (NME)‐like skin eruptions has been reported in a patient after erlotinib use and has been found to improve with zinc supplementation for a month 17 . A study on patients with EGFR‐TKI‐induced xerotic dermatitis due to zinc deficiency has shown that zinc supplementation can ameliorate their symptoms 18 …”