Safety of sodium fluorescein for in vivo study of skin

Background/purpose: Epicutaneous labeling or intradermal injection of the fluorescent sodium fluorescein is being used increasingly to investigate skin conditions in vivo when using non-invasive devices such as confocal scanning laser microscopy. Sodium fluorescein was used intravenously for decades for the examination of the vasculature of the ocular fundus (fluorescein angiography) and as eye drops for diagnosis of corneal erosions. The objective of this article is to systematically review the literature on fluorescein and conclude its safety in cutaneous research to support research planning and evaluations by ethics committees. Methods: A number of databases and the literature about safety and toxicity of fluorescein in animal and human studies were searched and analyzed. Results: Side effects or adverse events reported in the literature were related to intravenous bolus injection. Transient nausea and vomiting may occur. Other adverse events such as vasovagal reaction, cardiac or respiratory effects and anaphylaxes are extremely rare but may be fatal. Intradermal injection may cause mild itch or pain; systemic adverse event was reported. Epicutaneous labeling is associated with no reported problem. A typical local dose is several magnitudes of order smaller than a typical intravenous dose. Conclusion: Fluorescein has been used for many years in medicine for diagnostic purposes and is widely safe, albeit intravenous bolus injection may cause serious adverse reactions. In the literature, we could not trace reports of local or systemic side effects of topical sodium fluorescein except itch and pain on intradermal injection, however, dependent on the fluorescein preparation used. Local dermal application of fluorescein for in vivo study of skin may be considered widely safe.