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Affected patients usually present from early childhood with episodes of severe phototoxic pain in the skin exposed to visible light. The quantification of PPIX in erythrocytes with a metal\u2010free PPIX \u22653 times the upper limit of normal confirms the diagnosis. Protoporphyria\u2010related complications include liver failure, gallstones, mild anaemia and vitamin D deficiency with reduced bone mineral density. The management is focused on preventing phototoxic reactions and treating the complications. Vitamin D should be supplemented, and DEXA scans in adults should be considered. In EPP1, even in cases of biochemically determined iron deficiency, supplementation of iron may stimulate PPIX production, resulting in an increase in photosensitivity and the risk of cholestatic liver disease. However, for patients with XLEPP, iron supplementation can reduce PPIX levels, phototoxicity and liver damage. Because of its rarity, there is little data on the management of EPP\u2010related liver disease. As a first measure, any hepatotoxins should be eliminated. Depending on the severity of the liver disease, phlebotomies, exchange transfusions and ultimately liver transplantation with subsequent haematopoietic stem cell transplantation (HSCT) are therapeutic options, whereby multidisciplinary management including porphyria experts is mandatory. Afamelanotide, an alpha\u2010melanocyte\u2010stimulating hormone analogue, is currently the only approved specific treatment that increases pain\u2010free sunlight exposure and quality of life.<\/jats:p>","DOI":"10.1111\/liv.16027","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T09:31:06Z","timestamp":1721122266000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Erythropoietic protoporphyrias: Pathogenesis, diagnosis and management"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6108-367X","authenticated-orcid":false,"given":"Anna\u2010Elisabeth","family":"Minder","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetology, and Porphyria Stadtspital Z\u00fcrich Triemli  Zurich Switzerland"},{"name":"Swiss Reference Centre for Porphyrias Stadtspital Z\u00fcrich Triemli  Zurich 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