What is Erythropoietic Protoporphyria (EPP)?

From the Guidelines

Erythropoietic protoporphyria (EPP) patients should prioritize sun protection and manage acute episodes with treatments such as beta-carotene, afamelanotide, and vitamin D supplementation, as these interventions can significantly improve quality of life and reduce morbidity. The clinical presentation of EPP is characterized by painful photosensitivity, erythema, and stinging and burning of sunlight-exposed skin beginning in childhood, as noted in a study published in Blood 1.

Diagnosis and Clinical Presentation

The diagnosis of EPP can be supported by the presence of fluorescent erythrocytes in a fresh, unstained blood smear, and the finding of increased levels of protoporphyrin in plasma and erythrocytes 1. A more recent study published in Liver International provides an overview of the different porphyrias, including EPP, and highlights the importance of genetic diagnosis and biochemical testing 1.

Treatment and Management

Treatment of EPP is focused on minimizing the harmful effects of exposure to sunlight and managing the hepatotoxic effects of protoporphyrin, as outlined in a study published in Blood 1. The use of broad-spectrum sunscreens with high SPF, protective clothing, and avoidance of sun exposure, especially between 10 AM and 4 PM, is crucial in preventing symptoms. Additional treatments, such as beta-carotene (120-180 mg/day for adults), can increase skin tolerance to light, although it may take 1-2 months to become effective and can cause harmless skin yellowing.

Quality of Life and Morbidity Considerations

Regular monitoring of liver function is essential, as protoporphyrin can accumulate in the liver, potentially causing complications 1. Vitamin D supplementation (1000-2000 IU daily) is often necessary due to sun avoidance, and some patients may benefit from afamelanotide (Scenesse), a subcutaneous implant that stimulates melanin production, although availability is limited. By prioritizing sun protection, managing acute episodes, and addressing related health issues, patients with EPP can significantly improve their quality of life and reduce morbidity.

From the Research

Definition and Prevalence

• Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway characterized by accumulation of protoporphyrin in blood, erythrocytes, and tissues, and cutaneous manifestations of photosensitivity 2.
• EPP has been reported worldwide, with a prevalence between 1:75,000 and 1:200,000 2.
• The erythropoietic protoporphyrias consist of three ultra-rare genetic disorders of the erythroid heme biosynthesis, including erythropoietic protoporphyria (EPP1), X-linked protoporphyria (XLEPP), and CLPX-protoporphyria (EPP2) 3.

Clinical Manifestations

• EPP usually manifests in early infancy upon the first sun exposures, with cutaneous manifestations of acute painful photosensitivity, erythema, and oedema, sometimes with petechiae, together with stinging and burning sensations upon exposure to sunlight 2.
• Affected patients usually present from early childhood with episodes of severe phototoxic pain in the skin exposed to visible light 3.
• Protoporphyria-related complications include liver failure, gallstones, mild anaemia, and vitamin D deficiency with reduced bone mineral density 3.

Diagnosis

• Diagnosis is established by finding increased levels of protoporphyrin in plasma and red blood cells, and detection of a plasma fluorescence peak at 634 nm 2.
• The quantification of PPIX in erythrocytes with a metal-free PPIX ≥3 times the upper limit of normal confirms the diagnosis 3.
• Genetic testing by sequencing the FECH or ALAS2 gene confirms the diagnosis 4.

Management

• Management includes avoidance of exposure to light, reduction of protoporphyrin levels, and prevention of progression of possible liver disease to liver failure 2.
• Treatment options are scarce and mainly limited to supportive care such as protection from visible light 5.
• Afamelanotide, an alpha-melanocyte-stimulating hormone analogue, is currently the only approved specific treatment that increases pain-free sunlight exposure and quality of life 3, 4.
• Vitamin D should be supplemented, and DEXA scans in adults should be considered 3.
• 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 3.

Complications and Monitoring

• As the major risk in EPP patients is liver disease, a regular follow-up of hepatic involvement is essential 2.
• Sequential hepatic and bone marrow transplantation should be considered as a suitable treatment for most severe cases of EPP with hepatic involvement 2.
• Ongoing monitoring for liver disease, iron deficiency, and vitamin D deficiency is crucial, with management guidance provided in evidence-based consensus guidelines 6.