Porphyria cutanea tarda is the most common subtype of porphyria. The disease is named because it is a porphyria that often presents with skin manifestations later in life. The disorder results from low levels of the enzyme responsible for the fifth step in heme production. Heme is a vital molecule for all of the bodys organs. It is a component of hemoglobin, the molecule that carries oxygen in the blood. Hepatoerythropoietic porphyria has been described as a homozygous form of porphyria cutanea tarda, although it can also be caused if two different mutations occur at the same locus. Symptoms and signs
Porphyria cutanea tarda (PCT) is recognized as the most prevalent subtype of porphyritic diseases.PCT is characterized by onycholysis and blistering of the skin in areas that receive higher levels of exposure to sunlight. The primary cause is a deficiency of uroporphyrinogen decarboxylase (UROD), a cytosolic enzyme that is a step in the enzymatic pathway that leads to the synthesis of heme. Behind the direct cause there are a number of genetic and environmental risk factors.Patients who are diagnosed with PCT typically seek treatment following the development of photosensitivities causing blisters and erosions on exposed areas of the skin. This is usually observed in the face, hands, forearms, and lower legs. Healing is slow and leaves scarring. Though blisters are the most common skin manifestations of PCT, other skin manifestations include hyperpigmentation (similar to a tan) and hypertrichosis (mainly on the cheeks) also occur.
The oxidized porphyrins initiate degranulation of dermal mast cells, which release proteases that catabolize the surrounding proteins. This begins a cell-mediated positive feedback loop which matches the description of a type 4 delayed hypersensitivity reaction. The resulting blisters, therefore, do not appear immediately but begin to show up 2–3 days after sun exposure. Due to the highly conjugated structure of porphyrins involving alternating single and double carbon bonds, these compounds exhibit a deep purple color, resulting in the discoloration observed in the skin. Excess alcohol intake decreases hepcidin production which leads to increased iron absorption from the gut and an increase in oxidative stress. This oxidative stress then leads to inhibition of uroporphyrinogen decarboxylase, creating an excess of uroporphyrinogen III which is oxidized from the relatively harmless porphyrinogens into their oxidized porphyrins form. Concentrated instances of oxidative stress (alcohol, physical trauma, psychological stress, etc.) cause the liver to hemorrhage these porphyrins into the blood stream where they are then susceptible to oxidation.The strong association of PCT with Hepatitis C virus infection is not entirely understood. Studies have suggested that the cytopathic effect of the virus on hepatocytes can lead to the release of free iron. This iron can disrupt the activity of cytochrome p450, releasing activated oxygen species. These can oxidize the UROD substrate uroporphyrinogen, which can result in the inhibition of UROD and lead to deficient activity of this key enzyme.Excess alcohol use is frequently associated with both inducing PCT and aggravating a preexisting diagnosis of the disorder.