Porphyria cutanea tarda, or PCT, is the most common form of porphyria. Symptoms mainly affect the skin and liver. The disease is readily treatable, although the underlying disorder is incurable.
What is porphyria cutanea tarda?
Porphyria cutanea tarda is one of the so-called porphyrias and, in fact, is the most common subtype of these disorders. Porphyria results from the accumulation of intermediates formed during the synthesis of hemoglobin. Hemoglobin synthesis proceeds in several reaction steps. After each reaction step, a specific intermediate product is formed, which is converted again in a subsequent reaction. If this subsequent reaction does not take place or takes place at a slower rate, the respective reaction product accumulates and is stored in various organs of the body. Thus, the type of porphyria depends on which intermediate product of heme synthesis is involved. In porphyria cutanea tarda, disorders occur in the fifth reaction step of hemoglobin synthesis. The responsible enzyme, uroporphyrinogen decarboxylase, catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III. Inactivity or deficiency of this enzyme leads to porphyria cutanea tarda. Accumulation of uroporphyrinogen III occurs, which is deposited in the skin and liver. In the term porphyria cutanea tarda, the word “cutanea” means skin and the word “tarda” means delayed. Thus, the disease breaks out with a time delay after the intermediate begins to accumulate.
Causes
Thus, the immediate cause of porphyria cutanea tarda is a weakness of the enzyme uroporphyrinogendecarboxylase. This may be a deficiency or inability of this enzyme to function. In about 20 percent of cases, there is a mutation of the UROD gene, which encodes uroporphyrinogen decarboxylase. The corresponding gene is located on chromosome 1. Genetically determined porphyria cutanea tarda is inherited in an autosomal dominant manner. However, in the vast majority of affected individuals, porphyria cutanea tarda is acquired. Certain underlying diseases of the liver can impair the function of uroporphyrinogendecarboxylase. The liver is the central metabolic organ. Complex reactions take place here. In the case of diseases of the liver, however, certain reaction chains can be interrupted, so that the entire metabolism is also subject to disturbances. In the case of uroporphyrinogendecarboxylase, this can mean that this enzyme is either no longer produced or only produced to a reduced extent. Furthermore, its functionality may also be impaired if subsequent reaction chains no longer function. Liver damage caused by alcohol, drugs, other toxins or viral infections such as hepatitis C can also cause or promote porphyria cutanea tarda. Functional impairment of uroporphyrinogen decarboxylase causes accumulation of the heme synthesis precursor uroporphyrinogen III, an intermediate that preferentially accumulates in the skin and liver. Uroporphyrinogen III can absorb sunlight, causing the formation of oxygen radicals. These radicals are very reactive and destroy the skin when exposed to light.
Symptoms, complaints, and signs
Therefore, the central symptomatology in porphyria cutanea tarda represents photosensitivity of the skin. Thus, skin lesions and blisters form in areas exposed to UV radiation from the sun. The face, legs or back of the hands are frequently affected. There, in addition to larger blisters, smaller fluid-filled blisters form. In addition, the skin is very fragile, and the smallest injuries can immediately lead to blisters. Small, white cysts, also known as milia, develop with a time lag. The milia form at sebaceous gland exits and are only a side effect. They have more of a cosmetic significance. Medically significant, however, is the constant injury to the skin caused by bursting blisters. Here, there is a constant risk of developing infections. Other skin symptoms include pigmentary shifts with areas of increased and decreased pigmentation, increased hair on the forehead and face (hypertrichosis), a brownish facial color, and thickening of the skin. In the liver, hepatomegaly (enlargement of the liver) occurs due to the porphyrin deposits. The liver values are significantly increased. At the same time, the risk of liver cancer increases.However, if an underlying disease of the liver is present, the liver symptoms cannot be clearly attributed to porphyria. Due to porphyria excretion, the urine is often pink to brown in color.
Diagnosis and course of the disease
Porphyria cutanea tarda is diagnosed by porphyria determination in blood, urine, and stool. This examination can also distinguish acquired from genetic forms of porphyria cutanea tarda. Increased fecal excretion of isocoproporphyrin indicates the genetic variant.
Complications
In most cases, those affected with porphyria cutanea tarda suffer from various skin complaints. This may be associated with limitations in the patient’s daily life. In particular, the reduced aesthetic appearance of the affected person often leads to inferiority complexes or lowered self-esteem. Sometimes depression or other psychological upsets may also develop. However, the underlying disease of porphyria cutanea tarda cannot be cured, so that only the symptoms of this disease can be reduced. Furthermore, porphyria cutanea tarda can cause liver cancer. The liver values themselves are elevated in this disease, so that jaundice can occur. In the worst case, the liver must be completely removed and replaced with a donor organ. Similarly, patients with porphyria cutanea tarda suffer from various pigmentary abnormalities, which can also have a very negative impact on quality of life. Treatment of porphyria cutanea tarda can be done with the help of hormones. However, this does not result in a complete cure. Regular blood sampling is also necessary to prevent high iron levels. Usually, this disease also significantly reduces the life expectancy of the patient.
When should you go to the doctor?
Porphyria cutanea tarda should always be examined and treated by a physician. In this disease, there is no self-healing and, in many cases, worsening of symptoms. As a rule, there is also no complete cure of the disease, as it can only be treated symptomatically. The doctor should be consulted in cases of porphyria cutanea tarda when blisters and lesions form on the skin. UV radiation in particular can promote these complaints. Therefore, if the skin complaints appear suddenly and do not disappear on their own, a doctor must be consulted in any case. Likewise, complaints of the liver can indicate porphyria cutanea tarda and should be examined by a doctor. Treatment of the disease is usually performed by a dermatologist. However, since the risk of liver cancer is also significantly increased, regular screening examinations are very useful. In most cases, however, the patient’s life expectancy is not negatively affected by the disease.
Treatment and therapy
Porphyria cutanea tarda usually cannot be treated causally. However, by using various treatment methods, it is possible to achieve freedom from symptoms to a large extent. For example, in some patients it is sufficient to abstain from alcohol, iron supplements, certain medications or hormone treatment with estrogens in order to drastically improve the symptoms. Since in porphyria cutanea tarda too much iron is also stored in the liver, phlebotomies are performed at certain intervals in an attempt to normalize the iron level. This also improves the symptoms. Furthermore, phlebotomies also protect against recurrences. In severe cases, treatment with chloroquine is also possible. This agent forms complexes with porphyrins and enables its rapid excretion through the urine.
Prevention
Because acquired porphyria cutanea tarda is caused by liver disease, the best prevention is abstention from alcohol and drug abuse. It was found that the majority of patients with acquired porphyria cutanea tarda had liver damage caused by alcohol.
Follow-up
After successful treatment of porphyria cutanea tarda, comprehensive aftercare measures should be taken to prevent recurrence of the disease, as well as to prevent long-term damage. These consist primarily of abstaining from alcohol, certain medications that affect metabolism, and refraining from feeding artificial estrogen.In addition, the intake of iron as a dietary supplement should be refrained from. An additional low-iron diet may also be helpful in preventing the recurrence of porphyria cutanea tarda. However, this should always be discussed with the attending physician. Since blood iron levels must be checked regularly during such a diet to prevent the development of iron deficiency anemia, this requires regular consultation with both parties. In particular, if an iron storage disorder is also present, such a diet is urgently required. In addition, the liver should be regularly examined with imaging techniques (ultrasound, MRI, CT) in order to detect secondary liver diseases at an early stage. Regular examination of liver values in the blood is also necessary to monitor liver function. In addition, the porphyrin levels in the blood, urine and stool should be checked regularly in order to detect a renewed outbreak of the disease at an early stage. If diabetes mellitus is present as an underlying disease, it should be treated separately and comprehensively, because untreated diabetes mellitus increases the likelihood of a new outbreak of porphyria cutanea tarda.
What you can do yourself
There are very few self-help options available to the affected person with porphyria cutanea tarda. As a rule, the disease cannot be treated causally, but only symptomatically, so the patient is dependent on lifelong therapy. In some cases, a change in diet may already be sufficient to combat porphyria cutanea tarda. The affected person should generally avoid alcohol and nicotine. Iron supplements should also no longer be taken, although consultation with the treating physician is of course necessary. Iron levels can be normalized by phlebotomy, although this can only be performed by a physician. In case of drug abuse or alcohol abuse, withdrawal should be performed. If the patient cannot perform the withdrawal by himself, he can also be admitted to a clinic. In many cases of porphyria cutanea tarda, contact with other people affected by the disease also proves to be very useful, so that an exchange of information can take place. Retroactive treatment of liver damage is not possible, so that a reduced life expectancy of the patient can be expected in the case of alcohol abuse.