Protoporphyrin IX-induced phototoxicity: Mechanisms and therapeutics

Pharmacol Ther. 2023 Aug:248:108487. doi: 10.1016/j.pharmthera.2023.108487. Epub 2023 Jun 29.


Protoporphyrin IX (PPIX) is an intermediate in the heme biosynthesis pathway. Abnormal accumulation of PPIX due to certain pathological conditions such as erythropoietic protoporphyria and X-linked protoporphyria causes painful phototoxic reactions of the skin, which can significantly impact daily life. Endothelial cells in the skin have been proposed as the primary target for PPIX-induced phototoxicity through light-triggered generation of reactive oxygen species. Current approaches for the management of PPIX-induced phototoxicity include opaque clothing, sunscreens, phototherapy, blood therapy, antioxidants, bone marrow transplantation, and drugs that increase skin pigmentation. In this review, we discuss the present understanding of PPIX-induced phototoxicity including PPIX production and disposition, conditions that lead to PPIX accumulation, symptoms and individual differences, mechanisms, and therapeutics.

Keywords: Erythropoietic protoporphyria; Heme; Phototoxicity; Protoporphyrin IX; X-linked protoporphyria.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • 5-Aminolevulinate Synthetase
  • Endothelial Cells* / metabolism
  • Humans
  • Protoporphyria, Erythropoietic* / metabolism
  • Protoporphyria, Erythropoietic* / pathology
  • Protoporphyria, Erythropoietic* / therapy
  • Protoporphyrins / metabolism
  • Protoporphyrins / pharmacology


  • protoporphyrin IX
  • Protoporphyrins
  • 5-Aminolevulinate Synthetase