Porphyria cutanea tarda (PCT) is a form of long-term porphyria characterised by fragile skin and sore blisters in areas of skin that receive higher levels of exposure to sunlight, such as the face and backs of the hands. These blisters burst easily resulting in erosions, crusts, and superficial ulcers. There is often associated darkened skin color and extra facial hair growth. Healing is typically slow, leading to scarring and milia, while changes such as hair loss, and alterations in nails may also occur. A slightly purplish tint may be seen around the eyes. Scleroderma-like thick skin may develop over fingers, scalp, behind the ears, at the back of the neck, or in the front of the chest. The urine may appear dark. Unlike other porphyrias, PCT does not cause severe illness. The disorder results from a deficiency of uroporphyrinogen III decarboxylase, used in the production of heme, a vital component of hemoglobin. It is generally divided into three types; familial, non-familial, and acquired. The condition can be related to liver disease and a history of excessive alcohol consumption. It is a recognised complication of hepatitis C. Other associated conditions include type 2 diabetes, metabolic syndrome, HIV, SLE, and haemochromatosis. Smoking, and the use of estrogen in males with prostate cancer and females on combined contraceptive pill may also trigger PCT. Renal dialysis may cause retention of porphyrins and cause PCT. Tests generally include blood tests; liver function test, kidney function, complete blood count, ferritin, hepatitis B, hepatitis C, HIV, and HbA1C. Other tests may include checking urine for pinky-red fluorescence with Wood's lamp, testing a 24-hour urine for porphyrins, and skin biopsy. Pseudoporphyria may appear similar. PCT may be distinguished from epidermolysis bullosa acquisita by the presence of excess hair. Treatment for PCT focuses on removing all contributing factors, including alcohol, specific medicines, and managing hepatitis C and metabolic syndrome if applicable. Though typical sunscreens may provide limited protection, more effective alternatives are barrier sunscreens. Wearing a hat and gloves can help. Other treatment options include phlebotomy. An alternative is a low dose of an anti-malarial treatment. Treating co-existing hepatitis C generally helps. Without removing triggering factors, PCT tends to recur. Recurrence in the year following phlebotomy treatment is not common. Individuals with PCT have a 3.5 times higher risk of developing hepatocellular carcinoma. PCT is rare, though it is the most common subtype of porphyria.
Signs and symptoms PCT is typically characterised by fragile skin and sore blisters in areas of skin that receive higher levels of exposure to sunlight, such as the face and backs of the hands. These blisters burst easily resulting in erosions, crusts, and superficial ulcers. There is often associated darkened skin color and extra facial hair growth. Healing is typically slow, leading to scarring and milia, while changes such as hair loss, and alterations in nails may also occur. A slightly purplish tint may be seen around the eyes. Scleroderma-like thick skin may develop over fingers, scalp, behind the ears, at the back of the neck, or in the front of the chest. The urine may appear dark with a hint of reddishness. In addition to the skin lesions, chronic liver disease is very common in patients with sporadic PCT. This involves hepatic fibrosis (scarring of the liver), and inflammation. However, liver problems are less common in patients with the inherited form of the disease. Additionally, patients will often void a wine-red color urine with an increased concentration of uroporphyrin I due to their enzymatic deficiency.
Vitamin, mineral, and enzyme deficiencies Certain vitamin and mineral deficiencies are common in people with porphyria cutanea tarda. The most common deficiencies are beta-Carotene, retinol, vitamin A and vitamin C. Beta-Carotene is required to synthesize vitamin A, and vitamin A is needed to synthesize retinol. A lack of retinol-binding protein is due to a lack of retinol, which is required to trigger its production. Porphyrins interact with iron, absorbing photons to create reactive oxygen species is the mechanism of action causing the itchy, painful blisters of PCT. The reactive oxygen species consume the skin antioxidants beta-carotene, vitamin E, and vitamin C. Supplementation of these three vitamins reduces the oxidation and potentially diminishes the severity of blister formation. No single one of the three vitamins can inhibit the damaging effects of oxidized porphyrins, specifically uroporphyrins and coproporphyrins, but all three working together synergistically are capable of neutralizing their damaging effects.
Genetics
Inherited mutations in the UROD gene cause about 20% of cases (the other 80% of cases do not have mutations in UROD, and are classified as sporadic). UROD makes an enzyme called uroporphyrinogen III decarboxylase, which is critical to the chemical process that leads to heme production. The activity of this enzyme is usually reduced by 50% in all tissues in people with the inherited form of the condition. Nongenetic factors such as excess iron or partially genetic factors such as alcohol use disorder and others listed above can increase the demand for heme and the enzymes required to make heme. 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. The HFE gene makes a protein that helps cells regulate the absorption of iron from the digestive tract and into the cells of the body. Certain mutations in the HFE gene cause hemochromatosis (an iron overload disorder). People who have these mutations are also at an increased risk of developing porphyria cutanea tarda. In 20% of cases where porphyria cutanea tarda is inherited, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to decrease enzyme activity and cause the signs and symptoms of the disorder.
… excerpt ends here. Continue reading the full article.
