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.

[4] Patients who are diagnosed with PCT typically seek treatment following the development of photosensitivities causing blisters and erosions on exposed areas of the skin.

[5] Additionally, patients will often void a wine-red color urine with an increased concentration of uroporphyrin I due to their enzymatic deficiency.

[9] Porphyrins interact with iron, absorbing photons to create reactive oxygen species is the mechanism of action causing the itchy, painful blisters of PCT.

UROD makes an enzyme called uroporphyrinogen III decarboxylase, which is critical to the chemical process that leads to heme production.

The combination of this increased demand and reduced activity of uroporphyrinogen decarboxylase disrupts heme production and allows byproducts of the process to accumulate in the body, triggering the signs and symptoms of porphyria cutanea tarda.

[citation needed] While inherited deficiencies in uroporphyrinogen decarboxylase often lead to the development of PCT, there are a number of risk factors that can both cause and exacerbate the symptoms of this disease.

[18] The oxidized porphyrins initiate degranulation of dermal mast cells,[19] which release proteases that catabolize the surrounding proteins.

[citation needed] 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.

It is also felt to increase the uptake of iron in liver cells, leading to further oxidation of uroporphyrinogen by the release of activated oxygen species.

[24] Therefore, alcohol consumption may increase the production of uroporphyrinogen, exacerbating symptoms in individuals with porphyria cutanea tarda.

Laboratory testing commonly reveals high levels of uroporphyrinogen in the urine, clinically referred to as uroporphyrinogenuria.

Primarily, it is key that patients diagnosed with PCT avoid alcohol consumption, iron supplements, excess exposure to sunlight (especially in the summer), as well as estrogen and chlorinated cyclic hydrocarbons, all of which can potentially exacerbate the disorder.

In the absence of iron, which is to be incorporated in the porphyrin formed in the last step of the synthesis, the mRNA of erythroid 5-aminolevulinate synthase (ALAS-2) is blocked by attachment of an iron-responsive element (IRE) binding cytosolic protein, and transcription of this key enzyme is inhibited.

[30] Due to the presence of the chlorine atom, the entire complex is more water-soluble allowing the kidneys to preferentially remove it from the blood stream and expel it through urination.

[29] Complete remission can be seen within 6–12 months as each dose of antimalarial can only remove a finite amount of porphyrins and there are generally decades of accumulation to be cleared.

The exact frequency is not clear because many people with the condition never experience symptoms and those that do are often misdiagnosed with anything ranging from idiopathic photodermatitis and seasonal allergies to hives.