Acute intermittent porphyria- a genetically determined disease caused by lesions of the central nervous system, less often - the peripheral nervous system, periodic pain in the abdomen, increased blood pressure and pink urine due to the large amount of porphyrin precursor in it.

What provokes / Causes of Acute intermittent porphyria:

The disease is genetically determined, transmitted in an autosomal dominant manner.

More often the disease affects young women, girls and is provoked by pregnancy, childbirth. It is also possible to develop the disease due to the intake of a number of drugs, such as barbiturates, sulfa drugs, analgin. Most often, exacerbations are noted after operations, especially if sodium thiopental was used for premedication.

Pathogenesis (what happens?) during Acute Intermittent Porphyria:

The disease is based on a violation of the activity of the enzyme uroporphyrinogen I-synthase, as well as an increase in the activity of 6-aminolevulinic acid synthase.

The clinical manifestations of the disease are characterized by the accumulation of the toxic substance 8-aminolevulinic acid in the nerve cell. This compound is concentrated in the hypothalamus and inhibits the activity of cerebral sodium-potassium-dependent adenosine phosphatase, which leads to disruption of ion transport across membranes and impairs nerve function.

In the future, demyelination of the nerves, axonal neuropathy develop, which determines all the clinical manifestations of the disease.

Symptoms of Acute Intermittent Porphyria:

The most characteristic symptom of acute intermittent porphyria is abdominal pain. Sometimes severe pain is preceded by a delay in menstruation. Often, patients are operated on, but the cause of the pain is not found.

In acute porphyria, the nervous system is affected by the type of severe polyneuritis. It begins with pain in the extremities, difficulty in movements associated with both pain and symmetrical movement disorders, primarily in the muscles of the extremities. If the muscles of the wrist, ankle, hand are involved in the pathological process, then almost irreversible deformities can develop. With the progression of the process, paresis occurs in four limbs, in the future, paralysis of the respiratory muscles and death are possible.

Also, the central nervous system is involved in the process, as a result of which convulsions, epileptiform seizures, delirium, hallucinations appear.

In most patients, blood pressure rises, severe arterial hypertension is possible with an increase in both systolic and diastolic pressure.

The doctor should stop taking some seemingly harmless drugs, such as valocordin, bellaspon, belloid, theofedrine, containing phenobarbital, which can exacerbate the disease. The exacerbation of this form of porphyria also occurs under the influence of female sex hormones, antifungal drugs (griseofulvin).

Severe neurological disorders are often the cause of death, but in some cases, neurological symptoms subside, followed by remission. In connection with such a characteristic clinical picture of the disease, it was called acute intermittent porphyria.

It should be noted that not all carriers of the pathological gene have the disease manifested clinically. Often, relatives of patients, especially men, have biochemical signs of the disease, but there are no and have not been any clinical symptoms. This is a latent form of acute intermittent porphyria. In such people, when exposed to adverse factors, a severe exacerbation may occur.

Diagnosis of Acute Intermittent Porphyria:

Diagnosis of acute intermittent porphyria is based on the detection in the urine of patients with precursors for the synthesis of porphyrins (the so-called porphobilinogen), as well as 6-aminolevulinic acid.

Differential diagnosis of acute intermittent porphyria carried out with other, rarer, forms of porphyria (hereditary coproporphyria, variegated porphyria), as well as with lead poisoning.

Lead poisoning is characterized by abdominal pain, polyneuritis. However, lead poisoning, unlike acute porphyria, is accompanied by hypochromic anemia with basophilic puncture of erythrocytes and high serum iron. Anemia is not characteristic of acute porphyria. In women suffering from acute porphyria and menorrhagia, chronic post-hemorrhagic iron deficiency anemia is possible, accompanied by a low serum iron content.

Treatment for Acute Intermittent Porphyria:

First of all, all drugs that lead to an exacerbation of the disease should be excluded from use. Do not prescribe analgin, tranquilizers to patients. With severe pain, narcotic drugs, chlorpromazine are indicated. With a sharp tachycardia, a significant increase in blood pressure, it is advisable to use inderal or obzidan, with severe constipation - prozerin.

A number of drugs (primarily glucose) used in acute intermittent porphyria are aimed at reducing the production of porphyrins. A diet high in carbohydrates is recommended, concentrated glucose solutions are administered intravenously (up to 200 g / day).

A significant effect in severe cases gives the introduction of hematin, but the drug sometimes causes dangerous reactions.

In severe cases of acute porphyria, in case of respiratory failure, patients need long-term controlled ventilation of the lungs.

In the case of positive dynamics, as well as with a noticeable improvement in the condition of patients, massage and therapeutic exercises are used as rehabilitation therapy.

In remission, prevention of exacerbations is necessary, first of all, the exclusion of drugs that cause exacerbations.

The prognosis in case of damage to the nervous system is quite serious, especially when using mechanical ventilation.

If the disease proceeds without severe disorders, the prognosis is quite good. It is often possible to achieve remission in patients with severe tetraparesis, mental disorders. It is necessary to examine the relatives of patients to identify biochemical signs of porphyria. All patients with latent porphyria should avoid drugs and chemicals that aggravate the porphyria.

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Other diseases from the group Diseases of the blood, hematopoietic organs and individual disorders involving the immune mechanism:

Genetic pathologies are the most complex and severe, since it is impossible to completely get rid of them. One such disease is acute intermittent porphyria. This is a hereditary disease in which the amount of porphyrins in the blood increases. This type of pathology is considered one of the most common among all types of genetic porphyria.

During the disease, the accumulation of toxic substances in human organs occurs. Most often, pathology is diagnosed in the fairer sex. Moreover, it can be provoked by pregnancy and childbirth.

Symptoms of the disease

If a patient develops acute intermittent porphyria, the symptoms are:

• Numbness of some areas of the skin.
• Polyneuritis (multiple lesions nerve endings).
• Rash.
• Redness and swelling of the skin.
• Pigmentation and blisters on those areas of the skin that are usually open.
• Microcyst (volume reduction Bladder, in which there is a persistent violation of its functions).
• Psychosis.
• Organic pathological changes in the liver that affect its functionality.
• Anemia.
• Coma.
• Pain in the abdomen, and very strong. They are accompanied by additional nausea and vomiting.
• Destruction of the nail plates.
• Increasing pressure.
• Violation of urination.
• Confusion, fear, hallucinations.
• Paralysis of the respiratory muscles.

It should be noted that the first signs are observed in a patient aged 20 to 40 years in the form of seizures. And they can be repeated often or happen only once in a lifetime. If an attack of pathology develops, then disturbances may appear on the part of the brain stem, the nerves of the skull (oculomotor and facial), and the autonomic nervous system.

Not all carriers show symptoms of porphyria. For example, 80% of them may not be aware of the problem at all. A feature of the attacks of the disease is that in all its forms, the patient's urine changes color and becomes pink, brown or even red.

Acute forms of porphyria are quite rare. Symptoms of the disease are expressed in different ways.

Diagnosis of pathology

In the case of a disease such as acute intermittent porphyria, the diagnosis must be thorough. Mainly used laboratory tests urine and blood, which should reveal the amount of porphobilinogens, the level of porphyrin in plasma. If at least one sample turned out to be pathological, then an additional examination may be prescribed to the patient.

For example, it is important to take an x-ray abdominal cavity which will help to identify intestinal obstruction. In addition, there are some diagnostic criteria that will help make the diagnosis as accurate as possible:

1. During an attack: PBG and ALA are rapidly excreted in the urine.
2. During remission, screening can be done for the degree of decrease in deaminase activity.

In any case, the diagnosis must be differential in order for the therapy of the disease to be truly effective. If the examination was done incorrectly, and the treatment was ineffective, then the patient is expected to die (in 60% of cases).

It is also important that all members of the patient's family pass the tests. This will help in the future to prevent the development of porphyria in offspring.

How does the disease develop?

The mechanism of development of pathology is quite simple. Heme - a non-protein part of hemoglobin - under the influence of certain factors is able to turn into highly toxic substance. This, in turn, corrodes the tissues under the skin.

As a result, the cover begins to turn brown, thinner. Over time, the skin of the patient becomes covered with wounds and ulcers, especially if he is under the influence sunlight. The fact is that ultraviolet leads to damage to already thin tissues.

Developing, the pathological process affects not only the epidermis. They are also affected cartilage tissue nose, ears. Naturally, this deforms them. That is, acute intermittent porphyria brings not only physical, but also moral suffering, since a person cannot look at his disfigured reflection in the mirror.

Reasons for development

Acute intermittent porphyria is a complex and severe disease. The reasons for its development are as follows:

1. Genetic predisposition: pathology is inherited.
2. Too much speed
3. Liver diseases. This is especially true for hepatitis.
4. Severe poisoning with chemicals or salts of heavy metals.
5. Siderosis of Kupffer cells.
6. A lot of iron in the blood.
7. Long-term use of heavy medications: barbiturates, hormones.
8. Chronic alcoholism.

What factors can increase the risk of developing pathology?

Porphyria (what it is - you already know) can be triggered by:

• Strict diet. It is also a serious burden on the liver, which must work more than usual.
• Stressful state.
• Taking a large number of medications.
• Frequent contact with hazardous chemicals.
• Hormonal changes due to pregnancy or menstruation in women.
• complex infectious pathologies type of hepatitis C.
• Excessive drinking.

In order for the pathology not to bother you again and again, you just need to exclude all the factors listed above, as well as healthy lifestyle life.

Forecast

If a patient is diagnosed with acute intermittent porphyria, the prognosis largely depends on the degree of damage to the nerve endings. Timely therapy can eliminate symptoms within 2-4 days.

If a patient has developed severe motor neuropathy, then the symptoms may not disappear for months or years. The older a person becomes, the less sensitive he is to factors sickening. It reduces the frequency of seizures.

Features of treatment

If a patient is diagnosed with acute intermittent porphyria, treatment should be performed by a hematologist and endocrinologist. Naturally, therapy should be complex. It includes:

• Plasmapheresis (cleansing the blood of toxins with the help of special equipment).
• protection from direct sun rays.
• Splenectomy (removal of the spleen).
• The use of painkillers.
• Using medications to lower blood pressure.
• The use of glucose solution for infusion.
• The use of drugs such as denosine monophosphate and Riboxin.
• The use of agents that promote the excretion of skin porphyrins along with urine.

Porphyria (what it is - described above) requires an integrated approach to treatment. Approximate scheme therapy can be:

1. To begin with, the patient should be hospitalized in a hospital. Here you need to constantly monitor the heart rate, blood pressure and other vital signs.
2. It is important to exclude absolutely all factors provoking an exacerbation of the disease.
3. If a exact reason the pathological condition has not yet been determined, then the patient can be given an infusion of glucose. However, this method of treatment helps only if the attack of porphyria is not severe.
4. It is also important to quickly begin therapy of the patient with hemin. Improvement in this case may occur after 2-4 procedures.
5. Managing symptoms is also an important part of the treatment process. Need to keep an eye on drinking regimen to keep the patient from becoming dehydrated. Paracetamol is needed to relieve pain, as well as narcotic analgesics(available on prescription). Beta-blockers can be used to treat irregular heartbeats as well as pressure problems. The infection should be fought with penicillin or cephalosporins.

General classification

Acute intermittent porphyria is of the following types:

1. Pathology caused by dehydratase deficiency.
2. Hereditary coproporphyria.
3. Variegated porphyria.

What medicines should not be taken?

Acute intermittent porphyria may occur due to exposure to certain drugs. Therefore, it is necessary to know which of them cannot be taken in order not to provoke an attack.

So, if a person has acute intermittent porphyria, the list of prohibited drugs must be known by heart:

• Highly dangerous drugs: Dapsone, Danazol, Diphenylhydantone, Diclofenac, Carbamazepine, Meprobamate, Novobiocin, Chloroquine.
• Potentially dangerous: Clonazepam, Ketamine, Clonidin, Nortriptyline, Rifampicin, Theophylline, Erythromycin, Spironolactone.

Disease prevention

Unfortunately, today doctors cannot offer any complex preventive measures that could prevent disease. However, some tips can be followed for general body support:

1. It is best to stop smoking and drinking alcohol.
2. It is important to eat foods that contain significant amount vitamins, especially group B.
3. Protect your skin from direct exposure to sunlight: goggles, closed clothing, hats or caps are a must when going out!
4. It is better to avoid all those factors that can cause an exacerbation.
5. It is important to seek the advice of a nutritionist so that he can help you choose optimal mode nutrition.

That's all the features of the presented pathology. Be healthy!

168 PRACTICAL MEDICINE

A.R. Akhmadeev, E.V. MUSLIMOVA, M.A. APAKOVA, S.N. TEREKHOVA

Republican clinical Hospital Ministry of Health of the Republic of Tatarstan Kazan State Medical University

Acute intermittent porphyria (case report)

I Akhmadeev Aryslan Radikovich

Head of the Department of Hematology

420141, Kazan, st. Zavoisky, 18, apt. 54, e-mail: [email protected]

The case of acute intermittent porphyria is presented in connection with the rare occurrence of this pathology, various clinical manifestations difficulties in diagnosing the disease.

Keywords: porphyria, heme, abdominal pain, neurological symptoms.

A.R. AHMADEEV, E.V. MUSLIMOVA, M.A. APAKOVA, S.N. TEREKHOVA

Republican Clinical Hospital of Ministry of Health Care of the Republic of Tatarstan Kazan State Medical University

Acute intermittent porphyria (case report)

The case of acute intermittent porphyria is presented in connection with the rare occurrence of this disease, a variety of clinical manifestations, difficulties in diagnosis.

Keywords: porphyria, heme, abdominal pain, neurological symptoms.

Porphyrias are a group of diseases, which are based on a violation of heme biosynthesis, leading to excessive accumulation of porphyrins and their precursors in the body. Most commonly, porphyrias result from inherited defects in the enzymatic systems for heme biosynthesis. Porphyria was most common in the Middle Ages in Sweden and Switzerland, and here, most likely, the myth of vampires originated. This disease is well known in Europe, especially in the royal dynasties. Historian Andrew Wilson writes about this in his book The Victorians (2002). The disease ceased to occur only after the reign of Queen Victoria (1819-1901). Prior to this, in the British royal family hereditary porphyria was a common affliction. It was she who was the cause of the madness of Victoria's grandfather, King George III. Between 1955 and 1959, approximately 4,000 people from southeastern Anatolia (Turkey) are described as suffering from porphyria due to the use of hexachlorobenzene, a fungicide that has been added to wheat germ. The connection between porphyria and vampirism was first stated by Dr. Lee Illis from the UK. In 1963, he submitted to the Royal Society of Medicine a monograph On Porphyria and Etiology.

gie werewolves", which contained very detailed overview historical descriptions of werewolves-bloodsuckers in comparison with the symptoms of porphyria.

Porphyrias can be either hereditary or acquired. All porphyrias are inherited in an autosomal dominant manner, except for congenital erythropoietic porphyria, which is inherited in an autosomal recessive manner. This disease is caused by the accumulation and increased excretion of porphyrins and their precursors (aminolevulinic acid, porphobilinogen). Some porphyrias have an acute debut, such as hereditary coproporphyria, acute intermittent porphyria, or porphyria variegate, and some have a chronic, relatively stable course (congenital porphyria, erythropoietic porphyria). Acute porphyria is characterized by acute attacks neurovisceral symptoms, which may continue long time. These porphyrias are characterized by the following clinical manifestations: abdominal pain, neurological, mental disorders, staining of urine in pink color. Patients with chronic porphyria are more likely to

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PRACTICAL MEDICINE 169

there are skin manifestations diseases, involvement of the liver and nervous system in the pathological process may not be, they are not characterized by acute attacks of the disease. In addition, porphyrias are divided into hepatic and erythropoietic. Erythropoietic porphyrias are quite rare, usually accompanied by hemolysis, photosensitivity, appear in infancy and often lead to lethal outcome.

The most common type of hepatic porphyria is acute intermittent porphyria (API). The cause of the disease is an enzymatic defect in porphobilinogen deaminase, which determines the transition of porphobilinogen to hydroxymethylbilane. As a result, there is an accumulation of heme precursors n-aminolevulinic acid (n-ALA), which has a neurotoxic effect, and porphobilinogen, which gives the urine its characteristic color. The provoking factor may be the use of analgesics, sulfonamides, barbiturates. The following points are characteristic of the AKI clinic:

1) Abdominal pain. It is the most common symptom of the disease and occurs in 99% of cases. Usually these are colicky pains localized in the lower abdomen on the left and lasting from several hours to several days. Rarely, abdominal pain is accompanied by fever, leukocytosis, or peritoneal signs. Nausea and vomiting often occur. There is a very characteristic discrepancy between the patient's complaints and the serious clinical findings. In some cases, the disease is manifested only by paresis without abdominal pain.

2) muscle weakness and neurological disorders. Usually occurs in women reproductive age, characterized by pain in the extremities and tetraparesis. Some patients may present with the disease epileptic seizures(rarely enough).

3) Mental disorders. Typically, patients experience a psychosis that resembles the psychoses of schizophrenia. Diagnostic difficulties can lead to erroneous psychiatric diagnosis, which in some cases leads to hospitalization of patients with AKI in psychiatric hospitals. Anxiety is also a common feature in AKI.

Carefully the heredity of a patient with porphyria should be studied. At objective examination peritoneal signs, jaundice, peripheral neuropathy, motor and sensory disturbances may be identified. During a crisis it is possible arterial hypertension, tachycardia due to excitation of the sympathetic nervous system. Laboratory diagnostics includes general analysis urine (pink color of urine is characteristic), a qualitative reaction to porphobilinogen, a complete blood count (leukocytosis is characteristic), biochemical research blood (hyponatremia, hypokalemia, hypochloremia, increased liver enzymes).

In the treatment of porphyria, pathogenetic and symptomatic therapy is distinguished. Pathogenetic therapy: the appointment of gemma arginate - normosang, which stops the formation of porphyrin metabolites and relieves neurological symptoms, the introduction hypertonic solutions glucose, plasmapheresis to remove excess s-ALA, the introduction of riboxin (inhibits the synthesis of s-ALA), vitamins of group B. Symptomatic therapy aimed at eliminating abdominal syndrome(morphine, paracetamol), hypertensive syndrome and tachycardia (propranolol, atenolol), are used sedatives(chlorpromazine, lorazepin), means for stimulating the intestines (prozerin, senna).

Forecast. In the case of AKI, the risk of recurrent attacks of the disease during remission correlates with urinary protoporphylinogen excretion, and low excretion corresponds to a lower frequency of exacerbations.

Acute intermittent porphyria was diagnosed in a patient who was treated at the Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan.

Patient Ya., 33 years old, was transferred to the hematology department from the neurology department of the RCH. Complaints of severe pain in the abdomen, more pronounced near the navel, cramps in the muscles of the lower extremities, difficulty in extension in knee joints and hands, weight loss by 10 kg in 2-3 months, emotional lability, periodic hallucinations. From the anamnesis: on September 25, 2010, she suffered a severe acute physical and mental trauma with loss of consciousness. From 09/30/10 to 10/07/10 was on inpatient treatment in the neurosurgery department of the emergency hospital N 1 with a diagnosis of concussion, facial hematomas. After discharge, the condition did not improve, the appearance of "red urine" was noted, abdominal pain increased, headaches, tachycardia bothered. From October 13, 2010 to October 19, 2010, she was hospitalized at City Clinical Hospital No. 7 with a diagnosis of: Chronic pancreatitis with pronounced pain syndrome, exacerbation. Anemia mild degree. Esophagitis. Brain concussion. arterial hypertension. Despite ongoing therapy, the patient's condition continued to deteriorate and 28.10.10. she goes to surgery department RCH with a diagnosis of acute pancreatitis. In connection with the patient's complaints of convulsions, numbness, weakness in lower limbs after consulting a neurologist, the diagnosis is made: motor polyradiculoneuropathy in the form of a flaccid, predominantly proximal, tetraparesis. On November 2, 2010, she was transferred to the neurological department of the RCH with a diagnosis of Guillain-Barré syndrome. 03.11.10 a qualitative test for porphobilinogen is carried out, which gives positive result(normally the result is negative). On the same day, the patient is consulted by a hematologist. Considering the patient's history, redness of urine, neurological symptoms, laboratory changes, the patient is diagnosed with acute intermittent porphyria. Appropriate therapy is prescribed: glucose infusion, sandostatin, B vitamins, program plasmapheresis. During treatment, the patient notes improvement general well-being, normalization of urine color, laboratory parameters, neurological symptoms are reduced. The patient is discharged in a satisfactory condition with recommendations on adherence to the regimen, diet, examination of the family and relatives for porphyria.

LITERATURE

1. Idelson L.I. Pathogenesis, clinic and treatment of porphyrias. - Ter. archive, 1987. - No. 6. - S. 143-150.

2. Gosmen A., Peters H.A., Cripps D.J., Bryan G.T., Morris C.R. Hexachlorobenzene episode in Turkey. Biomed Environ Sci. March 1989; 2(1):36-43.

3. Pivnik A.V., Podberezin M.M., Pustovoit Ya.S. Acute intermittent porphyria: clinic, diagnosis, treatment. - Problems of hematology and blood transfusion, 1998. - No. 1. - S. 36-42.

4. Karpova I.V., Pustovoit Ya.S., Pivnik A.V. Porphyrin metabolism in patients with acute intermittent porphyria different stages the course of the disease. - Hematol. and transfusiol., 2004. - T. 49, No. 2. - S. 21-26.

5. Pustovoit Ya.S., Pivnik A.V., Karpova I.V. Clinic, diagnosis and treatment of porphyria. - A guide for doctors. - M., 2003.

6. Anderson K.E., Bloomer J.R., Bonkovsky H.L. et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med. Mar 15 2005; 142(6):933-8.

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