This disease is the most common of the porphyrias and results from a deficiency of the enzyme uroporphyrinogen decarboxylase (UROD). PCT is essentially an acquired disease, but some individuals have a genetic (autosomal dominant) deficiency of UROD that contributes to development of PCT. These individuals are referred to as having "familial PCT". Most individuals with the inherited enzyme deficiency remain latent and never have symptoms.
PCT is one of the hepatic porphyrias. Large amounts of porphyrins build up in the liver when the disease is becoming active. The disease becomes active when acquired factors, such as iron, alcohol, Hepatitis C Virus (HCV), HIV, estrogens (used, for example, in oral contraceptives and prostate cancer treatment) and possibly smoking, combine to cause a deficiency of UROD in the liver. Hemochromatosis, an iron overload disorder, also can predispose individuals to PCT.
The symptoms of PCT are confined mostly to the skin. Blisters develop on sun-exposed areas of the skin, such as the hands and face. The skin in these areas may blister or peel after minor trauma. Increased hair growth, as well as darkening and thickening of the skin, may also occur. Neurological and abdominal symptoms are not characteristic of PCT.
Liver function abnormalities are common but are usually mild, although they sometimes progress to cirrhosis and even liver cancer. PCT is often associated with Hepatitis C infection, which can also cause these liver complications. However, liver tests are generally abnormal even in PCT patients without Hepatitis C infection.
The preferred screening test for PCT is a measurement of porphyrins in plasma. This can differentiate PCT from Variegate Porphyria. The patterns of porphyrins in urine (predominately uroporphyrin and 7-carboxylate porphyrin) and feces (predominately isocoproporphyrin) help to confirm the diagnosis. The presence of an inherited deficiency of UROD can be demonstrated by measuring the enzyme in red blood cells and is present in about 20% of patients with PCT.
Treatment and Prognosis
PCT is the most treatable of the porphyrias. Treatment seems to be equally effective in familial and non-familial PCT. Factors that tend to activate the disease should be removed. The most widely recommended treatment is a schedule of repeated phlebotomies (removal of blood), with the aim of reducing iron in the liver. This actually reduces iron stores throughout the body. Usually, removal of only 5 to 6 pints of blood (one pint every one to two weeks) is sufficient, which indicates that iron stores are not excessively increased in most PCT patients. The best guides to response are measurements of serum ferritin and plasma porphyrins. Phlebotomies are stopped when the ferritin falls to -~20ng/ml. Another treatment approach is a regimen of low doses of either chloroquine (125mg twice weekly) or hydroxychloroquine (100mg twice weekly). Usual dosages of these drugs should not be used because they can cause transient but sometimes severe liver damage and worsening of photosensitivity in PCT patients.
After treatment for PCT, periodic measurement of plasma porphyrins may be advised, especially if a contributing factor such as estrogen exposure is resumed. If a recurrence does occur, it can be detected early and treated promptly. The treatment of PCT is almost always successful, and the prognosis is usually excellent.
PCT, Hepatitis C Virus and HIV
Because PCT is frequently associated with Hepatitis C Virus (HCV) infection, it is worth noting the issues involved in treating a patient with both PCT and HCV infection.
Infection with HCV is much more common than PCT, and most people with HCV do not have PCT. However, at least in some locations, as many as 80 percent of individuals with PCT are infected with HCV. Therefore, HCV needs to be added to the list of factors that can activate PCT alongside alcohol, iron and estrogens. Other hepatitis viruses are seldom implicated in PCT, and it is not known how HCV activates PCT.
There are several different viruses that cause hepatitis. A blood test for HCV infection has not been available for very long. HCV is most readily transmitted from one person to another by blood products. Although most people who are infected with HCV have a history of exposure to blood or needles contaminated with blood, in some cases it is not known how the infection was acquired. HCV (unlike the Hepatitis B Virus and HIV) is seldom transmitted by sexual contact. It is also not readily transmitted by casual contact with other people. Therefore, people infected with HCV are not hazardous unless they somehow expose others to their blood.
It is recommended that patients with PCT be tested for HCV infection. This is done by a blood test that detects antibodies to the virus. If HCV infection is found, it may not change the treatment of PCT (by phlebotomy or low-dose chloroquine). Treatment for PCT is highly successful even in patients with HCV. Therefore, it is reasonable to treat the PCT first and then look into treatment for HCV later.
There are reasons not to treat the HCV infection before treating the PCT. HCV treatment with alpha-interferon and ribavirin is available but is often not effective. Also, liver damage progresses slowly if at all in many people with HCV. However, once the PCT is in remission it is important to assess the amount of liver damage the virus has already caused and to have follow-up visits to a doctor to monitor the liver. In some cases it may be important to treat HCV infection to try and prevent progressive liver damage.
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