Porphyria cutanea tarda
| Classification according to ICD-10 | |
|---|---|
| E80.1 | Porphyria cutanea tarda |
| ICD-10 online (WHO version 2019) | |
The porphyria cutanea tarda (short PCT ) is one of the hepatic forms of porphyria and is the most common subtype of this group of metabolic diseases. Like all porphyrias, it is an enzymopathy . The corresponding disruption lies in the fifth enzymatic step in heme production. PCT can be sporadic (type I), familial (types II and III) and toxic.
Epidemiology
There is a clear androtropy of the disease (5: 1). In parallel to PCT, some patients have hereditary hemochromatosis (iron storage disease). There is also a noticeable coincidence with diabetes mellitus . Inherited mutations of the UROD gene (which codes for URO decarboxylase) are only responsible for about 20% of cases. These familial forms follow an autosomal dominant inheritance. These mutations are not found in the remaining 80% (sporadic cases). The PCT has a prevalence of 1: 2000 to 1: 5000. This includes both familial and sporadic cases. However, the actual extent of this disorder is difficult to assess. Many patients with this genetic abnormality never develop symptoms throughout their life. This is known as the subclinical course. Laboratory values associated with porphyrea cutanea tarda can also be found in healthy individuals. It is therefore not possible to make a diagnosis on the basis of laboratory values alone.
Pathogenesis
Common to all types is a deficiency (weakness) of uroporphyrinogen decarboxylase in the liver. This is an enzyme that is necessary for the synthesis of heme (part of the red blood pigment hemoglobin). In type II, this disorder is also found in other tissues. It should be noted that the adult liver is not a blood-forming organ. The synthesis of the heme in the liver primarily serves to integrate it into the cytochrome P450 proteins that occur there in increased numbers.
URO decarboxylase is the fifth enzyme in the heme biosynthetic sequence. It catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III. This is the final process in the cytosol of the liver cell before the heme completes in the mitochondria . A malfunction or an insufficient amount of this enzyme leads to a build-up of the heme intermediates. These porphyrins are then deposited in various tissues and cause disease symptoms. The liver and skin are mainly affected. The familial forms of PCT (types II and III) are characterized by an enzyme activity of less than 50% of the normal value. This is primarily due to a quantitative deficiency. PCT type I (sporadic form) is less characterized by an insufficient amount of the necessary enzyme than by its malfunction. The URO decarboxylase is largely in an inactive form.
The first manifestation usually takes place in young adulthood. The triggering of the disease is often triggered by external factors. Usually this is ethanol. Increased estrogen or iron levels and exposure to chlorinated hydrocarbons and certain viral infections (hepatitis C) can also provoke the onset of PCT.
Acquired forms of PCT
In the 1950s there was a veritable porphyria epidemic in Anatolia from wheat contaminated with hexachlorobenzene. Chronic hepatitis C infection can also cause PCT.
Hepatoerythropoetic Porphyria (HEP)
HEP is a more severe, homozygous form of PCT. The symptoms can easily be confused with congenital erythropoietic porphyria ( Günther's disease ); here, too, the areas exposed to light can be distorted (loss of nose, lips, auricles and finger parts, blindness). In addition to the metabolic products that are found in PCT, the level of zinc protoporphyrin in the erythrocytes is also increased.
Symptoms
In contrast to the other hepatic porphyrias, PCT is chronic and without neurological symptoms. The course and severity are very variable, so the excretion of porphyrin in the urine can be the only symptom of the disease.
- Skin : The light sensitivity ( photosensitivity ) of the skin is the central symptom of the disease. The PCT thus has the character of a photodermatosis . When exposed to UV radiation, areas exposed to the sun, such as the face, back of the hand or legs, form fluid-filled vesicles (vesicles) and blisters (bullae) due to the porphyrin deposits there. The skin is extremely brittle. Minimal trauma can lead to the formation of these bubbles. At the same time, slightly offset in time, small, white, cystic foci, so-called milia , appear on the skin . The often injured skin of PCT patients has little self-healing potential and is therefore constantly exposed to the risk of infection. Other skin symptoms are pigment shifts (hyper- and hypopigmentation), increased lanugo hair ( hypertrichosis ), livid to brownish complexion, and thickening, scarring and calcification of the skin.
- Liver : The porphyrin deposits lead to an enlarged liver ( hepatomegaly ) and liver dysfunction. The laboratory values show an increase in transaminases . As with any chronic liver damage, the risk of developing liver cancer (hepatocellular carcinoma) is significantly increased with PCT .
- Urine : The urine can be colored pink to brown due to the porphyrin excretion .
diagnosis
Elevated levels of porphyrin are found in blood plasma, urine, and stool. The early intermediate products of heme synthesis are not or only slightly increased (ALA, PBG are essentially normal). Intermediate products are uroporphyrin I and 7-carboxylate porphyrin and isocoproporphyrin. The first two are found in urine and blood plasma, the third mainly in stool. The increase in isocoproporphyrin indicates very specifically a hepatic URO decarboxylase defect.
therapy
- Just omitting the noxious substances (alcohol, iron, estrogen, various medications) can improve the symptoms in some patients and, under certain circumstances, make them disappear completely.
- If this is not enough, bloodletting (phlebotomy) is recommended . Once every one to two weeks, an amount of about 500 ml of blood is drained, this leads to a reduction in the liver iron and thus to the elimination of an important trigger . After five to six sessions there is usually a noticeable improvement in symptoms. Bloodletting also protects against recurrences of the disease. Precise control of serum hemoglobin and serum ferritin is required to avoid sideropenic complications (iron deficiency anemia).
- Pay attention to protection from sunlight.
- Severe courses are treated with low-dose chloroquine (for example 125 mg twice a week). However, overdosing can dangerously worsen the situation. Chloroquine (originally used to treat malaria ) forms complexes with porphyrins that are excreted by the kidneys. Good kidney function is therefore a prerequisite for this therapy option.
- Patients who suffer from severe renal insufficiency in addition to PCT are treated with EPO ( erythropoietin ).
- In addition, regular imaging of the liver should be considered for the early detection of any damage.
Web links
Remarks
- ↑ Formerly also known as cryoglobulinemia . See I. Biro et al. a .: Cryoglobulinaemia porphyria hepatica chronica (porphyria cutanea tarda). Mellet. In: Orvosi Hetilap. Volume 105, 1964, pp. 341-343.
