Description

• There are eight types of porphyrias (cutaneous and noncutaneous), with PCT being the most common and the only one that has an acquired variant. It results in cutaneous manifestations including painful blisters, photosensitivity, skin fragility, burning, and scarring.
• PCT has multiple clinically similar subtypes:
  • Sporadic (type 1) accounts for 80–90% of cases.
  • Inherited (type 2) accounts for 10–20% of cases.
  • Familial (type 3) is rare and accounts for approximately 5% (1).
  • Hepatoerythropoietic porphyria (HEP) is very rare, early onset, and markedly severe subtype.

Epidemiology

• Males and females are equally affected.
• Onset: 3rd to 4th decade of life

Prevalence

• 1 in 10,000 worldwide (2)
• 1 in 25,000 in the United States (1)

Etiology and Pathophysiology

• When UROD enzyme activity becomes <20% of normal, porphyrins accumulate in the liver and are transported to the skin.
• Once in the skin, porphyrins are activated by ultraviolet light forming active oxygen species which cause damage to proteins, lipids, and the basement membranes. This results in complement activation and mast cell degranulation leading to skin fragility and blistering.
• Sun-exposed areas of the body, such as the hands, are affected.
• Sporadic PCT is caused by an acquired deficiency of only hepatic UROD. It’s exacerbated by certain environmental factors such as alcohol, estrogens, chemicals, drugs, viruses, and iron overload.
• Inherited PCT results from an inherited defect in the UROD gene causing decreased enzyme activity. This affects all tissues including erythrocytes.
• Familial (type 3) does not affect the UROD gene directly. There is a decreased hepatic UROD level but normal erythrocyte UROD level. Therefore, it is an inherited defect of an unknown factor (1).
• HEP occurs in early infancy. This affects all tissues.

Genetics

• Type 2, or inherited PCT, is an autosomal dominant condition with incomplete penetrance.
• The UROD gene is located on chromosome 1p34.1 (1). Multiple mutations have been studied that lead to type 2 PCT and HEP.
• Type 3 is an inherited defect that is not directly related to UROD gene.
• HEP is the recessive variant of PCT with homozygous or compound heterozygous mutations on both UROD gene alleles (2).

Risk Factors

• Alcohol
• Hepatitis C
• Estrogens
• Smoking
• HIV
• Diabetes mellitus type 2
• Hemochromatosis (4 times more likely to develop PCT)
• Iron overload
• Dialysis-dependent renal failure (pseudoporphyria cutanea tarda)

Commonly Associated Conditions

• Hepatitis C
• Hemochromatosis
• Alcoholic liver disease
• Hepatocellular carcinoma
• Systemic lupus erythematosus