Porphyria Cutanea Tarda (PCT)

Porphyria Cutanea Tarda (PCT) is the most common type of porphyria, and the most treatable. It is also unique among the porphyrias, because it is the only type that does not always have a genetic cause.

The different types of PCT are:

  • Sporadic PCT (also known as acquired or Type 1) is the most common form of PCT. It does not have a genetic cause and is associated with liver cell damage and iron overload.

  • Familial PCT (also known as Type 2) has a genetic cause- a mutation of one copy of the UROD gene. However, not everyone with the gene variant will have symptoms, often it is the gene in combination with other risk factors that will cause symptoms.

Hepatoerythropoietic Porphyria (HEP) is a related ultra-rare porphyria that is caused by a mutation on both copies of the UROD gene. Usually it is severe and symptoms appear in infancy or early childhood, though mild cases in adults have also been reported.

  • Porphyria Cutanea Tarda is associated with damage to liver cells and iron overload. Some of the risk factors are:

    • Hepatitis C infection

    • HIV infection

    • Excessive alcohol use

    • Use of oral estrogens (birth control pills, hormone replacement therapy)

    • A disease called hemochromatosis which causes iron overload

    There are likely other factors that contribute to the development of PCT, but the connection is not well understood. For example, kidney dialysis, lupus and certain chemical exposures appear to be connected.

    It is important to remember that this is a complex disease and the connection between risk factors and developing PCT is not well understood. For example, alcohol use is frequently a triggering factor but PCT is not common in alcoholics.

  • PCT symptoms usually appear in adults over 30 and onset in childhood is very rare. It is slightly more common in men than women. The symptoms of PCT are:

    • Fragile skin that peels or blisters easily- particularly on hands and other sun-exposed areas

    • Blistering skin lesions on sun-exposed areas that may crust over

    • Scarring with hyper or hypo-pigmentation (scars that are lighter or darker than the surrounding skin)

    • Skin thickening or developing waxy, hardened patches

    • Abnormal or excessive hair growth, especially on the face

    • Milia (small white bumps or cysts)

    • Painful onycholysis (fingernails peeling away from the nail bed)

    • Liver abnormalities, including accumulation of iron, accumulation of fat, inflammation, thickening and scarring around the portal vein and cirrhosis

  • Diagnosis of PCT is done using biochemical testing measuring blood, urine and fecal samples. Genetic testing is generally not useful because most cases of PCT do not have a genetic basis.

    When testing for PCT it is important not only to confirm the presence of PCT, but also to rule out acute porphyrias that have similar dermatological symptoms (eg. VP and HCP). This is important because treatment of acute porphyrias is very different from the treatment for PCT. These specialized tests should be conducted by a specialized laboratory, and it is strongly recommended that the lab be consulted prior to ordering tests. Please contact us to find the lab closest to you.

    TESTING FOR PCT

    Plasma Porphyrin Fluorescence Scan: The frontline test for diagnosing a PCT is Plasma Porphyrin Fluorescence Scan testing. Plasma Porphyrin Fluorescence Scan is a test that measures total porphyrins in the plasma. It is useful for detecting several types of porphyria, including PCT, and is the gold standard for VP.

    For this test, a blood sample (plasma is a part of your blood) will be collected. It is important that the sample is protected from light after it is collected and should be kept cold.

    Urine Porphyrins Quantitation: In addition to sending a plasma sample for Plasma Porphyrin Fluorescence Scan testing, a random urine sample should also be sent for Urine Porphyrin Quantitation testing. In PCT, urine porphyrins will be elevated; the concentrations and pattern of porphyrin precursors that are elevated have a distinctive pattern in PCT that will help differentiate it from other types of porphyria. Samples should be protected from light after collection and should be kept cold or frozen from transport to the lab.

    On its own, total urine porphyrin quantitation is not sufficient to diagnose porphyria. This is because urine porphyrins may be elevated in other conditions, such as gastrointestinal bleeds or use of certain medications.

    Porphyrin Quantitation in Feces: measuring porphyrin and porphyrin precursors in feces is helpful for ruling out PCT and diagnosing CEP. For this test, a sample of feces will be collected and the levels of porphyrins and porphyrin precursors in the sample will be measured.

    It is important that fecal samples are protected from light after they are collected and kept cold or frozen when transported to the lab.

    WHERE TO START

    If PCT, or other non-acute porphyria, is suspected, have your physician request a plasma porphyrin fluorescence scan test, as well as a urine porphyrin quantitation test.

    Obtain plasma and urine samples soon after symptoms and send them to the porphyrin specialty lab for analysis. The testing laboratory will provide further guidance as to which samples and tests may be required for follow-up testing, if required.

    ADDITIONAL RESOURCES

  • Porphyria Cutanea Tarda is the most treatable of the porphyrias and, with treatment, symptoms generally resolve within 6-9 months. In general, once symptoms resolve they will not reoccur but relapses do sometimes happen.

    ADDRESSING TRIGGERS

    Triggering infections and conditions, such as HIV, hepatitis C and hemochromatosis should be tested for and treated if present.

    It is important to reduce or avoid risk factors, such as alcohol consumption and oral estrogens (ex. birth control pill, hormone replacement therapy) while symptoms are present, and to moderate their use once symptoms are gone to prevent a relapse.

    PHLEBOTOMY

    The standard treatment for PCT is a series of phlebotomies to reduce iron and porphyrin levels in the liver. Phlebotomies are a simple procedure where blood is removed from a vein. It is also know as bloodletting.

    Phlebotomies continue until they reach a target blood ferritin level (ferritin is an indicator of the body’s iron stores) and achieve remission. Usually this requires 5-8 phlebotomies.

    This treatment is generally more effective if PCT is related to hemochromatosis.

    This treatment is not recommended for patients with anemia. In cases of anemia or where there are concerns about vein access, treatment with hydroxychloroquine may be preferred.

    HYDROXYCHLOROQUINE

    This alternate treatment for PCT involves taking a low dose of chloroquine or hydroxychloroquine (a treatment for malaria). These drugs are generally as effective as phlebotomies. It is important that the dose is low, because a high dose can actually increase liver porphyrins and make skin sensitivity worse.

    These drugs should not be used if you are pregnant, lactating, or have advanced liver disease, psoriasis, retinal disease or glucose-6-phosphate dehydrogenase deficiency. They should also not be taken when other drugs that are toxic to the liver are in use (ex. Alcohol, Tylenol).

    Hydroxychloroquine and chloroquine are also associated with side effects including nausea, vomiting, seizures, muscle weakness and vision damage. Eye damage isn’t likely with the low dose treatment, but it is recommended that an eye exam be conducted before and after treatment, and be aware of signs of vision damage (ex. blurry vision, halos around lights).

    IRON CHELATORS

    Iron chelator drugs help the body get rid of excess iron. As a treatment for PCT, iron chelators are less effective than phlebotomies or hydroxychloroquine, however they may be used in some situations where the two standard treatments may be difficult- for example for someone on hemodialysis.

    MANAGING SKIN SYMPTOMS

    While you are undergoing treatment, you should take steps to protect your skin. Skin symptoms are caused by light, usually sunlight, shining on your skin. It is important to know that not all sun protection advice and products will work to protect you. This is because most sun protection is related to UV light, and the type of light that triggers porphyria skin symptoms is blue-violet light. Light is often referred to by its wavelength: the blue-violet wavelengths that affect porphyria are around 400 nm (~370-430 nm).

    Pain from blisters and exposures can be treated with oral pain medication. Care should be taken to avoid infections by keeping blisters clean and covered. If an infection develops, it can be treated with antibiotics.

    Currently the best way of managing skin symptoms is to avoid blue-violet light. This can include light coming through windows or reflecting off surfaces. Some strategies and tips to protect yourself blue-violet light include:

    • Clothing: Double layers or thick, dark fabrics will block out more light. Long sleeves, wide-brimmed hats, sunglasses, buffs and gloves can help keep you covered. Many people find clothing specifically for sun and UV protection to be helpful.

    • Protecting your hands: Skin on your hands is often exposed to light and may be delicate, and more prone to injury. Gloves can both protect your hands from light and prevent injuries.

    • Stay in the shade. You can also consider carrying an umbrella to make your own shade.

    • Sunscreen: Most sunscreens don’t block blue-violet light and won’t protect your skin from porphyria. Some people find opaque or mineral sunscreens are helpful. These sunscreens sit on top of your skin and form a reflective barrier. Some are tinted, which can help them blend in better.

    • Vitamin D: Avoiding light can result is Vitamin D deficiency, while avoiding light may need to take a Vitamin D supplement.

  • While the symptoms show up on your skin, PCT is a liver disease. There are other liver conditions that are also associated with PCT, but likely not caused by PCT including: fatty liver disease, cirrhosis and lobular necrosis. It is recommended that patients with PCT see a hepatologist to monitor their liver health.

    Hepatocellular carcinoma, a type of liver cancer, does appear to be more common for people who have other liver conditions in addition to PCT. Screening for this cancer is done with an ultrasound every 6-12 months.

  • Porphyria Cutanea Tarda usually doesn’t have a genetic component (sporadic PCT) and therefore can’t be passed on to your children.

    If you have been diagnosed with familial PCT, there is a 50% chance that you will pass the gene on to each of your children. However, their risk of developing PCT is relatively low, as there usually needs to be additional risk factors to trigger symptoms.

    If your PCT is found to be because of hemochromatosis, which is a genetic condition, family members should be tested for this condition. Hemochromatosis is a recessive disorder, which means all of your children will be carriers for this disease, though they would need to inherit another copy of the gene from their other parent in order to be affected.