Erythropoietic protoporphyria (EPP) is an inherited disorder of the
haem metabolic pathway characterised by accumulation of
protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. EPP has been reported worldwide, with prevalence between 1:75,000 and 1:200,000. It usually manifests in early infancy upon the first sun exposures. EPP is characterised by cutaneous manifestations of acute painful photosensitivity with
erythema and oedema, sometimes with
petechiae, together with stinging and burning sensations upon exposure to sunlight, without
blisters. These episodes have a variable severity depending on the exposure duration and may result in chronic permanent lesions on exposed skin. As
protoporphyrin is a lipophilic molecule that is excreted by the liver, EPP patients are at risk of
cholelithiasis with obstructive episodes, and chronic
liver disease that might evolve to rapid
acute liver failure. In most patients, EPP results from a partial deficiency of the last
enzyme of the
haem biosynthetic pathway,
ferrochelatase, EC 4.99.1.1/FECH (encoded by the FECH gene). EPP appears to be inherited as an autosomal dominant disease, the clinical expression of which is modulated by the presence of the hypomorphic FECH IVS3-48C allele trans, but recessive inheritance with two mutated FECH alleles has also been described. In about 2% of patients, overt disease was recently shown to be caused by gain-of-function mutations in the erythroid-specific
aminolevulinic acid synthase 2 (ALAS2/ALAS, EC 2.3.1.27) gene and named X-linked dominant protoporphyria. 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. Investigations for hepatic involvement,
ferrochelatase activity level, genetic analysis (FECH mutations, presence of the hypomorphic FECH IVS3-48C allele trans and ALAS2 mutations) and family studies are advisable. Differential diagnosis includes phototoxic drug reactions,
hydroa vacciniforme,
solar urticaria,
contact dermatitis, angio-oedema and, in some cases, other types of
porphyria. Management includes avoidance of exposure to light, reduction of
protoporphyrin levels and prevention of progression of possible
liver disease to
liver failure. As the major risk in EPP patients is
liver disease, a regular follow-up of hepatic involvement is essential. Sequential hepatic and
bone marrow transplantation should be considered as a suitable treatment for most severe cases of EPP with hepatic involvement. EPP is a lifelong disorder whose prognosis depends on the evolution of the hepatic disease. However, photosensitivity may have a significant impact on quality of life of EPP patients.