ES
CONTACT

DISEASE

ERYTHROPOIETIC PROTOPORPHYRIA (EPP)

What is it?

Erythropoietic Protoporphyria (EPP) is an ultra-rare genetic disorder of heme metabolism, classified among the porphyrias. It is caused, in most cases, by mutations in the FECH gene (ferrochelatase), resulting in a partial deficiency of this key enzyme in the heme biosynthesis pathway. As a consequence, protoporphyrin IX accumulates in red blood cells, the liver, and other tissues, causing extreme photosensitivity.

  •  It is estimated to affect 1 in every 75,000 to 200,000 people in Europe,
    although its prevalence may be underestimated.
  •  It is usually inherited in an autosomal recessive manner, though there are
    cases of dominant inheritance with incomplete penetrance.

What are its symptoms?

The hallmark symptom of EPP is acute cutaneous phototoxicity, which occurs within minutes of exposure to sunlight or intense visible light:

  •  Severe pain, burning, itching, and swelling in sun-exposed areas (hands, face, arms).
  •  Unlike other porphyrias, there is no blister formation, but erythema and chronic skin thickening may occur over time.  Symptoms are not relieved by common painkillers and may last for hours or
  • days after sun exposure.  In some patients (5–20%), progressive liver involvement can occur,
  • potentially leading to severe liver failure.

What do I need to consider?

Diagnosis (Diagnostic Tools)

Diagnosis of EPP is based on clinical features, supported by biochemical and genetic confirmation:

  1. Detection of elevated protoporphyrin IX in red blood cells (with no fluorescence in urine).
  2. Genetic testing to identify mutations in the FECH gene or the ALAS2 gene (in X-linked cases, such as X-linked protoporphyria).
  3. Skin biopsies are not routinely performed but may show subepidermal deposits of granular material.
  4. In cases with liver involvement, monitoring of liver function and porphyrin levels in plasma and feces is essential.

Treatment

There is no definitive cure, but current management includes:

  • Afamelanotide (an analogue of alpha-melanocyte-stimulating hormone): increases sunlight tolerance by promoting melanin production.
  • Beta-carotene: an antioxidant that may offer mild protection in some patients.
  • Cholestyramine or anion exchange resins: help reduce protoporphyrin load in patients with liver involvement.
  • Liver transplant: indicated in cases of end-stage liver failure.
  • Avoiding direct sun exposure is an essential measure for all patients.

EPP is an underdiagnosed disease that can be mistaken for allergies or common dermatologic disorders. Disproportionate pain relative to visible skin damage, following brief sun exposure in children or young adults, should raise suspicion for EPP. A normal blood count with severe post-sun skin symptoms can be a diagnostic clue.

Downloads

No file for download

References

  • Balwani, M., & Desnick, R. J. (2012). The porphyrias: advances in diagnosis and treatment. Blood, 120(23), 4496–4504.
  • Harms, J., et al. (2020). Update on Erythropoietic Protoporphyria and X-Linked Protoporphyria. Dermatologic Clinics, 38(3), 349–357.
  • Holme, S. A., Anstey, A. V., & Badminton, M. N. (2006). Erythropoietic protoporphyria. BMJ, 332(7547), 576–579.
  • Puy, H., Gouya, L., & Deybach, J. C. (2010). Porphyrias. The Lancet, 375(9718), 924–937.
  • Bissell, D. M., et al. (2017). Porphyria Diagnostic Algorithm. American Porphyria Foundation / Porphyrias Consortium.
  • Langendonk, J. G., et al. (2015). Afamelanotide for Erythropoietic Protoporphyria. New England Journal of Medicine, 373, 48–59.
  • Minder, A. E., Minder, E. I., & Schneider-Yin, X. (2020). Treatment options for erythropoietic protoporphyria: An overview. Molecular Genetics and Metabolism, 131(2–3), 259–268.