It arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the red blood cells (erythrocytes), plasma, skin, and liver.

Most patients, if the EPP is not as severe, manifest symptoms with onset of puberty when the male and female hormone levels elevate during sexual development and maintenance.

[citation needed] Prolonged exposure to the sun can lead to edema of the hands, face, and feet, rarely with blistering and petechiae.

[9] EPP photosensitivity symptoms are reported to lessen in some female patients during pregnancy and menstruation, although this phenomenon is not consistent, and the mechanism is not understood.

Ferrochelatase (FECH) catalyzes the insertion of ferrous iron into the protoporphyrin IX ring to form heme.

EPP exhibits both recessive and dominant patterns of inheritance and a high degree of allelic heterogeneity with incomplete penetrance.

Deficiency of FECH results in increased release of protoporphyrin, which binds to albumin in plasma and subsequently undergoes hepatic extraction.

[15][16] EPP is generally suspected by the presence of acute photosensitivity of the skin and can be confirmed by detection of a plasmatic fluorescence peak at 634 nm.

[citation needed] Liver biopsy confirms hepatic disease in EPP by the presence of protoporphyrin deposits in the hepatocytes that can be observed as a brown pigment within the biliary canaliculi and the portal macrophages.

[15] There is no cure for this disorder; however, symptoms can usually be managed by limiting exposure to daytime sun and some types of artificial lighting.

[citation needed] Afamelanotide, developed by Australian-based Clinuvel Pharmaceuticals, was approved in Europe in December 2014 and in the United States in October 2019 for treatment or prevention of phototoxicity in adults with EPP.

[citation needed] Some over-the-counter drugs may help: Bitopertin has been undergoing trials in Australia since 2022 with some success in allowing participants to spend more time in full sunlight without ill effects.

[30] Although erythropoietic protoporphyria symptoms may be temporarily suppressed with cold temperatures, patients have found that this method may extend, or even intensify pain and discomfort.

This has been noted as particularly effective in the hands, forearms, and face, as areas of decreased blood flow may be exposed to the accumulation of protoporphyrins for an extended period.

[35] Erythropoietic protoporphyria was first described in 1953 by Kosenow and Treibs[36] and completed in 1960 by Magnus et al. at the St John's Institute of Dermatology in London.