EPP is a disorder that is a member of a family of disorders referred to as the porphyrias. Each disease in this family results from deficiencies in a specific enzyme involved in the biosynthesis of heme (also called the porphyrin pathway). The term porphyria is derived from the Greek term porphura which means "purple pigment" in reference to the coloration of body fluids in patients suffereing from a porphyria. The porphyrias are classified on the basis of the tissue that is the predominant site of accumulation of metabolic intermediates. These classifications are "hepatic" or "erythroid". Each disease is also further characterized as being acute or cutaneous dependent upon the major clinical features of the disease. EPP is an autosomal dominant disorder that results from defects in ferrochelatase (also called heme synthase). As the name would imply, EPP is classified as an erythroid porphyria. EPP is the most commonly occurring erythroid porphyria and the third most common porphyria.
EPP has also been referred to as protoporphyria since the disorder results in excess accumulation and excretion of protoporphyrin. The accumulation of protoporphyrin is found primarily in the erythroid cells of the bone marrow, circulating erythrocytes, plasma, and feces.
The ferrochelatase gene (FECH) is located on chromosome 18q21.3 spanning 45 kb and encompassing 12 exons that generate two alternatively spliced mRNAs. These two mRNAs encode two distinct isoforms of ferrochelatase, isoform a contains 429 amino acids and isoform b contains 423 amino acids. More than 50 different mutations have been identified in the FECH gene resulting in EPP. These mutations include missense, nonsense and splicing mutations and both large and small insertions and deletions.
Light-sensitive dermatitis commencing in childhood, usually before 10 years of age, is the presenting finding in erythropoietic protoporphyria. Common symptoms are itching, swelling and painful erythema (skin redness due to capillary congestion) which can develop within minutes on sun-exposed areas of the skin. The cutaneous manifestations of EPP are usually non-blistering in contrast to the other cutaneous porphyrias such as CEP and HEP. Most EPP patients experience only a painful photosensitivity, whereas a small number of them develop liver complications due to the accumulation of excessive amounts of protoporphyrin in the liver. The manifestations in EPP remain fairly stable over the span of many years in afflicted individuals. Unlike in the hepatic porphyrias where distinct precipitating factors (e.g. drugs, steroids) lead to acute manifestations of porphyria, there are no known precipitating factors associated with EPP.
Oral administration of β-carotene has been shown to improve sunlight tolerance in EPP patients. In EPP patients that experience hepatic involvement, treatment with cholestyramine (an intestinal bile acid binding drug used in the treatment of hypercholesterolemia) promotes the excretion of protoporphyrin in the feces reducing the hepatic protoporphyrin levels. The use of cholestyramine also improves the cutaneous symptoms of EPP in some individuals.