Porphyria cutanea tarda

Porphyria cutanea tarda ( PCT short ) is one of the hepatic forms of porphyria and is the most common subtype of this group of metabolic diseases. It's like all porphyrias a enzymopathy. The corresponding perturbation is in the fifth enzymatic step of Hämproduktion. The PCT can be sporadic (type I), family (type II and III) and be toxic due.

Epidemiology

It shows a distinct " Männerlastigkeit " of the disease ( 5-1 ). Parallel to the PCT can be found in some patients hereditary hemochromatosis (iron storage disease ). A striking coincidence (coincidence ) is also found with diabetes mellitus. Inherited mutations of the UROD gene ( encodes the URO decarboxylase ) are responsible for only about 20 % of cases. These familial forms follow an autosomal dominant pattern of inheritance. In the remaining 80 % ( sporadic cases ), these mutations did not find. The PCT occurs with a prevalence of 1:2000 to 1:5000. This includes both the familial and the sporadic cases. The actual extent of this disorder but can be difficult to estimate. Many patients with this genetic variation will never develop life symptoms. This is called subclinical course. Laboratory values ​​that indicate a porphyrea cutanea tarda can also find random. It confirms the medical wisdom that a laboratory value without knowledge of the patient's condition is worthless.

Pathogenesis

All grades of a deficiency (weakness ) of the uroporphyrinogen decarboxylase in the liver is common. This is an enzyme for the synthesis of heme ( a component of the red blood pigment hemoglobin) is needed. In type II there is this error also in other tissues. It should be noted that adult liver is not a hematopoietic organ. The synthesis of heme in the liver is primarily used for integration into the amplified there occurring cytochrome P450 proteins.

The URO - decarboxylase, the fifth enzyme in the heme Biosynthesesequenz. It catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III. This is the last running process in the cytosol of liver cells before the completion of the heme vonstattengeht in the mitochondria. A malfunction or a too small amount of this enzyme leads to an impoundment of Hämzwischenprodukte. These porphyrins then deposited in various tissues and cause disease symptoms. Concerned here are mainly liver and skin. The familial forms of PCT ( Type II and III) are characterized by an enzyme activity of less than 50 % of the standard value. Because this is primarily due to a quantitative deficiency. The PCT type I ( sporadic form ) is characterized less by a too small amount of the necessary enzyme from than by its malfunction. The URO - decarboxylase is here largely in an inactive form.

Onset usually occurs in young adulthood. The triggering of the disease is often triggered by external factors. This is mostly ethanol. Also increased estrogen or iron levels and exposure to chlorinated hydrocarbons and certain viral infections ( hepatitis C) can provoke the outbreak of the PCT.

Acquired forms of PCT

In the 1950s it came to Anatolia into a veritable Porphyrieepidemie through contaminated with hexachlorobenzene wheat. Also, a chronic infection with hepatitis C can cause a PCT.

Hepatoerythropoetische porphyria ( HEP )

The HEP is a serious running, homozygous form of the PCT. The symptoms can be easily confused with the Congenital erythropoietic porphyria ( Günther's disease ), even here there may be distortions in the light-exposed areas come (loss of nose, lips, ears and fingers parts, blindness ). In addition to the metabolites, which can be found in the PCT, the value of zinc protoporphyrin is additionally increased in the erythrocytes.

Symptoms

In contrast to the other hepatic porphyrias, PCT is both chronic and without neurological symptoms. The course and severity are highly variable, the excretion of porphyrin may be the only symptom of the disease in the urine.

  • Skin: The sensitivity to light ( photosensitivity ) of the skin is the main symptom of the disease. The PCT therefore has the character of a photodermatosis. By UV radiation is exposed to the sun places like the face, back of the hands or legs, due to the local Porphyrineinlagerungen liquid -filled blisters ( vesicles) and bubbles form ( bullae). The skin is extremely fragile. Minimal trauma can lead to the formation of these bubbles. At the same time, slightly skewed, arise on the skin as small, white, cystic foci, called milia. The often injured skin PCT patient has low self- healing potential and is thus constantly exposed to a risk of infection. Other symptoms include skin pigmentation ( hyper-and hypopigmentation ), increased lanugo ( hypertrichosis ), livid or brown complexion and thickening, scarring and calcification of the skin.
  • Liver: The Porphyrineinlagerungen lead to liver enlargement ( hepatomegaly ) and liver dysfunction. The laboratory results show an increase in transaminases. As with any chronic liver injury risk for the development of liver cancer ( hepatocellular carcinoma) is significantly increased by the PCT.
  • Urine: The urine may be discolored by Porphyrinausscheidung pink to brown.

Diagnosis

One finds enhanced Porphyrinspiegel in blood plasma, urine and stool. The early intermediates of the heme synthesis are not or only slightly increased ( ALA, PBG are substantially normal). Incidental intermediates are uroporphyrin I and 7- carboxylate porphyrin and Isocoproporphyrin. The first two are found in urine and blood plasma, the third mainly in the stool. The increase in Isocoproporphyrins indicated very specifically indicate a hepatic URO - Decarboxylasedefekt.

Therapy

  • The sole omission of noxious substances (alcohol, iron, estrogen, various medications ) can improve the symptoms and can completely disappear under certain circumstances in some patients.
  • If this is insufficient, a bloodletting ( phlebotomy) is recommended. Once every one to two weeks is drained of blood amount of about 500 ml, this results in a reduction of the liver iron and thus to a loss of an important trigger. After five to six sessions there is usually a noticeable improvement in their symptoms. Also protects the bloodletting against recurrences of the disease. It requires an exact monitoring of serum hemoglobin and serum ferritin to avoid Sideropenic complications (iron deficiency anemia).
  • Attention should be paid to protection from sunlight.
  • Severe cases are with low dose chloroquine ( for example, 125 mg twice a week) treated. However, overdose can worsen the situation dangerous. Chloroquine ( originally intended for the treatment of malaria) forms with porphyrins complexes that are excreted by the kidneys. A good kidney function is therefore a prerequisite for this treatment option.
  • Patients suffering from severe renal impairment in addition to the PCT are treated with EPO ( erythropoietin ).
  • Furthermore, it should, for early detection of any damage, regular imaging of the liver should be considered.
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