Porphyria - pigmentary exchange disease

Porphyria is a whole group of metabolic diseases, which is based on a violation of the synthesis of heme and some enzymes of the respiratory chain, detoxification, antioxidant system. Hem is a precursor of hemoglobin, a pigment that gives the red color of blood. Hemoglobin is the main carrier of oxygen in the human body.

Transport of hemoglobin is carried out by red blood cells. Enzymes of detoxification and antioxidant system allow a person to deal with the harmful effects of the environment. In porphyria, the body accumulates an excessive content of heme-porphyrin precursors, which is accompanied by intoxication and a number of other clinical signs.

Since heme synthesis occurs in the bone marrow (in particular, in red blood cells - erythrocytes) and in the liver, it is customary in medicine to isolate erythropoietic and hepatic forms of porphyria. Each of them has its own clinical features. Let's take a closer look at the varieties of porphyria, the disease of pigmentation, their causes, symptoms and ways of treatment.

Classification

Porphyria is a heterogeneous disease. In medicine, it is customary to single out two groups of porphyria, taking into account the location of the heme:

• erythropoietic;
• hepatic.

On a clinical course there are:

• acute porphyria (accompanied by a crisis course, with periods of exacerbations and relative remissions);
• porphyria with the predominant lesion of the skin (forms with a chronic course of the disease, mainly with skin symptoms without acute attacks).

To acute porphyria m include:

• porphyria, caused by a deficiency of δ-aminolevulinic acid dehydratase;
• acute intermittent porphyria;
• hereditary coproporphyria;
• variegate porphyria.

To porphyria with cutaneous manifestations include:

• congenital erythropoietic porphyria (Günter's disease, erythropoietic uroporphyria);
• erythropoietic protoporphyry;
• Late skin porphyria (urocoppororphy).

Causes

At the heart of most varieties of porphyria are genetic defects, that is, situations in which harmful factor mutations occur even before birth in hereditary material, which is responsible for the synthesis of heme and enzymes. A child is born with such an "incorrect" set of genes, which subsequently manifests itself as symptoms of porphyria. In total, 8 enzymes are needed for the correct stage of heme creation, the defect of any of them causes porphyria.

The only form of porphyria that can be acquired in the process of life is the late cutaneous porphyria. Its occurrence is usually associated with a toxic effect on the body of alcohol, lead, gasoline, heavy metal salts, with a long intake of estrogen drugs, barbiturates, with a severe form of hepatitis.

The appearance of signs of the disease is sometimes associated with the effect of provoking factors. It can be:

• starvation (a small amount of carbohydrates in food);
• excessive sun exposure;
• transferred infections;
• periods of hormonal changes in the body (puberty, pregnancy, childbirth and so on);
• taking medications (antidepressants, tranquilizers, antiallergic drugs, diuretics, sulfonamides, synthetic female sex hormones and some others).

Usually, such provoking factors are important for late cutaneous porphyria, acute intermittent porphyria, variegate porphyria. On the emergence of erythropoietic varieties of porphyria, they have no effect.

Mechanism of porphyria development

Due to a violation of heme synthesis in blood, progenitor products accumulate: uroporphyrin, coproporphyrin and some others. Uroporphyrin excreted in the urine, coproporphyririne along with bile - into the intestine. However, they are still too much in the body. In high concentrations, porphyrins are toxic compounds, with blood flow they spread throughout the body, getting into various organs and tissues.

Accumulating in the skin, they are the cause of increased sensitivity to sunlight. Under the influence of sunlight, porphyrins in the skin contribute to the appearance of rashes of various kinds, pigmentation. Rashes can lead to the formation of ulcers, in place of which in severe cases there are scars. With the long existence of the disease, such scars can cause contractures of joints, facial disfigurement.

Porphyrins cause a spasm of blood vessels, which is associated with the occurrence of abdominal pain, constipation, a decrease in the amount of urine. All porphyrins fluoresce, giving a red color. That is why the urine of a patient with porphyria is red or pink.

The nervous system is very sensitive to the effects of porphyrins, which causes frequent occurrence of symptoms her defeat (the most varied: from minor pain and itching to paralysis and coma).

Symptoms

Each clinical form of porphyria has its own characteristics, and at the same time there is much in common between them. Therefore, it is advisable to consider the signs of porphyria from the position of dividing them into acute and dermal forms.

Signs of acute porphyria

A characteristic feature of all varieties of acute porphyria is the course of the crisis, that is, the alternation of attacks of sudden deterioration of the state with periods of relative remission. Acute attacks, or attacks, can occur with such signs:

• acute pain in the abdomen. There are no symptoms of irritation of the peritoneum. The pain arises suddenly and is so pronounced that it can give the clinic an acute abdomen. Therefore, often such patients undergo unreasonable surgical intervention;
• the allocation of red or pink urine at the time of the attack;
• vegetative disorders. This can be an increase in heart rate, the appearance of heart rhythm disturbances, constipation, nausea and vomiting, increased blood pressure, violation of urination (little urine and rare urge), increased body temperature. All these changes are caused by the toxic effects of porphyrins on the autonomic nervous system;
• polyneuropathy. Signs of polyneuropathy with porphyria are very diverse. It can be pain with a touch of burning sensation in any part of the body, a feeling of crawling, the presence of a foreign body, numbness, total loss sensitivity; it is a movement disorder in the form of weakness in any muscles, up to the paralysis of the respiratory musculature. Sometimes a person during an attack can not move at all;
• changes from the psyche: feelings of anxiety, sudden arousal, hallucinations, delusions, psychomotor agitation. Possible disorders of sleep, depression, mental disorders;
• epileptic seizures;
• an increase in the level of leukocytes in the blood, an increase in the level of hepatic enzymes ALAT and ASAT, hemolytic anemia (that is, a decrease in the number of red blood cells due to their enhanced destruction).

It should be borne in mind that none of the above characteristics is specific. Acute porphyria is characterized by the simultaneous occurrence of a number of symptoms, and only a comprehensive assessment of all changes helps to suspect the presence of porphyria.

And one more nuance: acute attack of porphyria - this is a serious condition, which can even threaten the life of the patient. According to statistics, the risk of death at the time of attack reaches 20%. which is associated with violations of breathing and cardiac activity.

Cutaneous manifestations of porphyria

Pigment rash appears on exposed areas of the body under the influence of sunlight.

Symptoms worsen in the spring and summer months, when a person is more susceptible to insolation. Deferred in the skin uroporphyrin under the influence of sunlight causes the release of histamine and the development of the inflammatory process. Clinically, this is manifested by the appearance of a rash, the appearance of itching, burning. In the open areas of the skin (more on the face, neck, hands), pigmented spots may appear, in their place - bubbles with transparent contents. With continued exposure to the sun, the vesicles grow, burst, and ulcers are formed. Possible attachment of infection and suppuration of ulcers.

In porphyria, the integuments themselves have an increased vulnerability. In place of ulcers, if they are superficial, after healing remains pigmentation of a dirty gray, brownish, brown color. Deep ulcers heal by the formation of scars. This leads to deformity of the joints (and the appearance of contractures), facial disfigurement (deformation of the nose, mating of the mouth). Deformation and destruction of nails are possible. In mild cases with porphyria, there are areas of thickened skin - hyperkeratosis.

Patients with porphyria may suffer from increased hairiness, the so-called hypertrichosis. Sites of excess hair growth are located on the temples, on the face. Eyelashes and eyebrows grow quickly and have a dark color.

Of course, not all forms of porphyria manifest themselves as severe skin lesions. Sometimes the damage to the skin is minimal, for the entire spring-summer period there is only one exacerbation in the form of a small area and depth of lesions of the rash.

In addition to the general features of the clinical course, each species of porphyria has its own. It should be noted some of them:

• erythropoietic uroporphyria (Günther's disease) is characterized by the appearance of symptoms in the first weeks of a child's life. This is a serious disease with a rough skin lesion. Ulcers are scarred only against the background of antibiotic therapy, deform individual parts of the body. Such children may not have hair and nails at all, they can be completely blind. In patients with this form, the spleen is enlarged, the life span of erythrocytes is reduced. At an early age, such patients become disabled, deaths are very frequent;
• erythropoietic protoporphyria is characterized by a more favorable course than the previous form. Characterized by the increased sensitivity of the skin to sunlight, but the degree of skin lesion rarely reaches ulcers and scars. The content of uroporphyrin and co-proporphyrin may be normal in urine and erythrocytes. Sometimes bleeding is possible, associated with damage to the walls of blood vessels. The spleen does not increase;
• acute intermittent porphyria is characterized by a wavy current. Attacks are usually heavy, with severe abdominal pain, muscle paralysis, psychosis, and even confluence in a coma. The risk of death is high. This type of this type of inheritance, that in each generation the disease necessarily manifests itself;
• hereditary coproporphyria also manifests itself in every generation, but the course of the disease is more favorable, which is associated with a lower level of porphyrins in urine, feces and blood;
• Variegate porphyria is similar in symptoms to acute intermittent porphyria; however, with this form, it is possible to defeat the organs of excretion with the development of renal insufficiency;
• Late skin porphyria is more common in men (as they more often abuse alcoholic drinks and smoke, contact with various hepatotoxic substances). The main manifestations are cutaneous, but the dimensions of the liver also increase, and its functional state is disturbed. In such patients, the risk of developing liver cancer is increased.

Diagnostics

Diagnostic process in porphyria is based on a complex of clinical data, as well as on laboratory indicators of increasing the content of porphyrins in urine, feces, serum, in erythrocytes. In the period of acute attacks, this is enough. To clarify the variety of porphyria during remission, it is necessary to determine the activity of enzymes involved in heme synthesis (in blood cells), as well as DNA analysis.

Since porphyria, in most cases, is a hereditary disease, when the diagnosis is made, the patient's relatives should also be examined to determine the latent forms of the disease.

Treatment

To date, medicine does not have the radical means to fight this disease. The main preventive measure of the appearance of symptoms is considered to be protection against sunlight.

Acute attacks of porphyria require mandatory hospitalization. The following preparations are shown:

• Hem Arginate at a dosage of 3 mg / kg per 100 ml of saline for 1-4 days or large doses of glucose intravenously (200-500 g / day). Such measures reduce the production of porphyrins;
• β-adrenoblockers (Obsidan, Anaprilin) ​​for the elimination of vegetative disorders (tachycardia, increased blood pressure, and so on);
• for the treatment of severe pain, opiates (narcotic drugs) are used. It should be noted that analgin, barbiturates, tranquilizers are contraindicated in porphyria, since their use, on the contrary, causes an exacerbation of the disease;
• vitamins C, E, B, folic acid, Riboxin 600-800 mg per day;
• if the application of the above mentioned agents is ineffective, then plasmapheresis courses are conducted. Usually 3-4 courses are sufficient with an interval of several days with the replacement of blood plasma with albumin preparations, fresh frozen plasma and so on.

For the treatment of late cutaneous porphyria, Delagil proved to be very successful. It binds the porphyrins of the skin and removes them in the urine, thereby reducing their content in the skin. Delagil first apply to 0.125 g 2 times a week for 14 days, then to 0.125 g every other day for 14 days, and with good tolerance continue to 0.125 g every day for 3 months. Sometimes a good effect is observed when combining such a method of Delagil with Riboxin for 2-3 months. An alternative to this method of treatment of late cutaneous porphyria is the removal of red blood cells from the body by repeated bleeding (about 400 ml of blood is collected, as in the case of donation). Repeated blood fetuses are performed after determining the level of hemoglobin and proteins in the blood plasma.

Erythropoietic protoporphyria is treated by the use of β-carotene. β-carotene increases the tolerance of sunlight, thus reducing the manifestations of the disease.

So, porphyria is a multifaceted disease with a lot of clinical signs, none of which is specific. Therefore, such a diagnosis is rarely exhibited. In most cases, the cause of porphyria is genetic defects. The disease has a chronic recurrent course. Treatment, in general, is symptomatic, and the main method of prevention is considered to be the minimum exposure to sunlight.