To begin with, successful treatment of Acrodermatitis Enteropathica with the oral administration of diodoquin (diiodohydroxyquinoline) was first reported by Dillaha et al. in 1953 [1]. Later on, clioquinol, which is also known as iodochlorhydroxyquin or 5-chloro-7-iodo-quinolin-8-ol, was generally prescribed as the main treatment for AE. There were reports that this drug enhances zinc absorption in patients. However, the use of clioquinol was epidemiologically linked to subacute myelo-optic neuropathy (SMON), which is characterized by peripheral neuropathy and blindness and has affected more than 10,000 people in Japan. As clioquinol-zinc chelate is considered a mitochondrial toxin, it is one of the main causes of SMON. Furthermore, clioquinol could potently inhibit the 20S proteasome via Cu-dependent and Cu-independent mechanisms and consequently cause cell death due to the intracellular accumulation of misfolded proteins. Additionally, the discontinuation of clioquinol has been reported to lead to the elimination of SMON. Consequently, clioquinol was withdrawn from the market as an oral agent in the 1970s [2, 3].

Moynahan et al. discovered that AE is a zinc deficiency disorder and proposed a treatment with the prescription of zinc supplements. This treatment has proven to be effective, inexpensive, reliable, and non-toxic; as a result, it has become the main source of AE treatment during the last few decades [4].