Treatment of liver hemochromatosis. What is Hemochromatosis? Increased iron content in the body hemosiderosis hemochromatosis

The general definition of diseases associated with increased accumulation of iron in the liver includes the following criteria: 1) cirrhosis and fibrosis of the liver with an initial predominant accumulation

iron in parenchymal cells, as well as with its presence in stellate reticuloendotheliocytes; 2) deposition of iron in other organs, including the pancreas, heart, pituitary gland; 3) increased absorption of iron, which leads to its adsorption and accumulation.

The clinical concept of siderosis (iron accumulation disease) includes idiopathic (hereditary) hemochromatosis and hemochromatosis syndrome due to the influence of various etiological factors: anemia, alcoholic cirrhosis, increased intake of iron into the body, as well as hemosiderosis with massive transfusions, chronic hemodialysis,

A number of researchers refer to this group such early stages of the disease, when there is iron deposition in the parenchymal cells of the liver, but there are no signs of cirrhosis and fibrosis, especially if these patients belong to families with a hereditary disorder of iron metabolism. Isolation and treatment of patients at this stage can be crucial to prevent complications of hemochromatosis. There is strong evidence that iron deposition in hepatocytes is toxic, while increased iron deposition in mature reticuloendotheliocytes is quite benign.

Despite the fact that there are some deviations from the above definition, the classification of siderosis, based on the principle of preferential accumulation of iron in parenchymal or mature reticuloendothelial cells, is generally accepted.

The term hemosiderosis is used to describe conditions with a predominant accumulation of iron in the cells of the reticuloendothelial system (the system of phagocytic macrophages). Hemosiderosis occurs without documented cases of cirrhosis; in the future, we will consider only disorders with a predominant deposition of iron in parenchymal cells - hemochromatosis.

Hemochromatosis differs from hemosiderosis in that, firstly, the iron-containing pigment accumulates mainly in parenchymal cells, and secondly, the accumulation of the pigment leads to damage to tissues and organs.

From a clinical standpoint, it seems to us most important to emphasize the need to distinguish between idiopathic hemochromatosis as an independent nosological unit and hemochromatosis as an iron accumulation syndrome in a number of diseases.

The main indicators of iron metabolism. The content of iron in the body of an adult is 4-5 g, more than half of this amount is in hemoglobin and 15% in skeletal muscles as iron not included in heme; 35% of iron is deposited in the liver, spleen, bone marrow. The liver is the main depot organ, which normally contains up to 500 mg of iron. Various enzymes (catalase, cytochromes) contain a minimum amount of iron.

The iron storage protein is ferritin, and the transport protein is transferrin. With normal metabolism, iron deposited in hepatocytes in the form of ferritin is not detected in the Perls reaction.

A healthy person loses about 1 mg of iron per day, and women during menstruation - another 15-20 mg per month. The greatest loss of iron (about 70%) occurs through the gastrointestinal tract, the rest of the iron is lost in the urine and through the skin. A normal diet contains 10-11 mg of iron, of which only 1-2 mg is absorbed; with iron deficiency anemia, iron absorption rises to 3 mg / day. Patients with hemochromatosis continue to adsorb increased portions of iron. Excessive deposition of iron in tissues, primarily in parenchymal and stellate reticuloendotheliocytes of the liver, occurs in the form of hemosiderin pigment. Hemosiderin is a brownish-yellowish pigment with a granular structure; normally, it is not detected in the liver tissue. Microscopic examination of hemosiderin is detected by the Perls reaction in hepatocytes of the periportal zones of the hepatic lobules. The place of intracellular localization of hemosiderin are lysosomes. All liver damage caused by high iron content is collectively called siderosis.

10.2.1. Idiopathic (hereditary) hemochromatosis

Idiopathic hemochromatosis (siderophilia, primary hemochromatosis, hereditary iron storage disease), the former names of the disease are bronze diabetes, pigmentary cirrhosis.

Idiopathic hemochromatosis is a hereditary disease of metabolic disorders with high absorption of iron in the intestine and its primary deposition in hepatocytes. Increased deposition of iron in hepatocytes leads to fibrosis, disruption of liver architectonics up to cirrhosis. In other organs, especially the endocrine glands, heart, skin, mucous membranes, pancreas, morphological and functional changes associated with iron deposition are also found.

The main link in the pathogenesis is, apparently, a genetic defect in the enzyme systems that regulate the absorption of iron in the intestine during its normal intake with food.

The disease is transmitted in an autosomal recessive manner. A clear relationship has been established between idiopathic hemochromatosis, a congenital enzyme defect leading to the accumulation of iron in the internal organs, and HLA histocompatibility antigens, especially A3, B14, in the UK and Australia - also with HLA-B7. The fact that the proband has two HLA haplotypes indicates a high risk in siblings, but not in offspring. To more accurately determine the risk in relatives, it is important to simultaneously examine the level of serum ferritin and histocompatibility antigens. The gene that controls the content of iron in the body

nism, is located in the 6th chromosome. Genotypic study of a number of histocompatibility antigens of the HLA system, controlled by the 6th pair of chromosomes, fully confirmed the recessive type of inheritance.

Frequency. In the UK and the Scandinavian countries, idiopathic hemochromatosis is detected very rarely, in the countries of Central Europe it is much more common and amounts to 0.01-0.07%. In the US, the frequency ranges from 0.001 to 0.1% of the general population.

Men get sick about 10 times more often than women, usually at the age of 40-60 years, women - in most cases after menopause,

Morphological changes. The skin and internal organs have a rusty-brown or chocolate color. The liver is especially strongly pigmented. In a light-optical study, hepatocytes, especially perigyrtal ones, are overflowing with hemosiderin, which gives a positive Psrlsa test for iron. Hemosiderin is also detected in stellate reticuloendotsliocytes, but in much smaller quantities than in hepatocytes.

The activity of redox enzymes has been established mainly in young regenerating cells free of pigments. In cells loaded with pigments, their activity is weakly expressed or absent (Fig. 30). Gradually, the amount of pigment in hepatocytes increases, their necrosis occurs, fibrosis of the liver tissue joins. Hemosiderin appears in the epithelial cells of the bile ducts and tubules, in the connective tissue.

Fibrous layers dissect the parenchyma into small fragments, in some places false lobules are visible. At the end of the process, a picture of predominantly micronodular cirrhosis develops, which can turn into macronodular. A characteristic feature of cirrhosis in hemochromatosis are wide partitions of mature connective tissue surrounding false lobules.

The pancreas changes especially strongly with hemochromatosis. In addition to a significant deposition of pigment, interstitial inflammation and fibrotic changes are found in it, and atrophy of the islets of Langerhans occurs. Changes in the spleen are similar to those found in other forms of cirrhosis.

Pigment deposition is observed in the spleen, myocardium, pituitary gland, adrenal glands, thyroid gland, parathyroid glands, ovaries, synovial tissue of the joints, and skin. In the skin, the pigment is detected in skin macrophages, fibroblasts, the amount of melanin increases.

clinical picture. The onset of the disease is gradual; characteristic symptoms appear only after 1-3 years. In the initial stage, for a number of years, complaints of severe weakness, fatigue, weight loss, and a decrease in sexual function in men predominate. Often there are pains in the right hypochondrium, joints due to chondrocalcinosis of large joints, dryness and atrophic skin changes, testicular atrophy.

In the advanced stage of the disease, hemochromatosis is manifested by the classic triad: pigmentation of the skin and mucous membranes, cirrhosis of the liver and diabetes.

Pigmentation of the skin and mucous membranes is one of the most frequent and early symptoms of hemochromatosis; according to different authors, it occurs in 52-94% of patients. The severity of pigmentation depends on the duration of the disease. Bronze or smoky coloration of the skin is more noticeable on exposed parts of the body (face, neck, hands), on previously pigmented areas, in the armpits, on the genitals.

Any liver disease leads to dysfunction of other organs and body systems. After all, the liver is the filter of the body, which frees it from toxins, heavy metals, excess hormones, and fat. Hemochromatosis is a hereditary disease of the liver. Such a genetic failure provokes an increase in the absorption of iron in the organs of the digestive system, blood. So, there is an excessive accumulation of iron in tissues and organs. What is hemochromatosis and what are its symptoms? And how to treat such a serious disease?

What is hemochromatosis?

Hemochromatosis is a disease of the liver, which is characterized by a violation of iron metabolism. This provokes the accumulation of iron-containing elements and pigments in the organs. In the future, this phenomenon leads to the occurrence of multiple organ failure. The disease got its name because of the characteristic color of both the skin and internal organs.

Hereditary hemochromatosis is very common. Its frequency is about 3-4 cases per 1000 population. However, hemochromatosis is more common in men than in women. Active development, and the first signs of the disease begin to manifest themselves at the age of 40-50 years. Since hemochromatosis affects almost all systems and organs, doctors of various fields are involved in the treatment of the disease: cardiology, gastroenterology, rheumatology, endocrinology.

Experts distinguish between two main types of ailment: primary and secondary. Primary hemochromatosis is a defect in enzyme systems. This defect provokes the accumulation of iron in the internal organs. In turn, primary hemochromatosis is divided into 4 forms, depending on the defective gene:

• Autosomal recessive classic;
• Juvenile;
• Hereditary non-associated;
• Autosomal dominant.

The development of secondary hemochromatosis occurs against the background of acquired dysfunction of enzyme systems that are involved in the process of iron metabolism. Secondary hemochromatosis is also divided into several types: alimentary, post-transfusion, metabolic, neonatal, mixed. The development of any form of hemochromatosis occurs in 3 stages - without excess iron, with excess iron (without symptoms), with excess iron (with the manifestation of vivid symptoms).

The main causes of hemochromatosis

Hereditary hemochromatosis (primary) is an autosomal recessive disease of transmission. The main reason for this form can be called a gene mutation called HFE. It is located on the short arm on the sixth chromosome. Mutations of this gene provoke violations of iron uptake by intestinal cells. As a result, a false signal is formed about the lack of iron in the body and blood. Such a violation is caused by an increased release of the DCT-1 protein, which binds iron. Consequently, the absorption of the element in the intestine is enhanced.

Further, pathology leads to an excess of iron pigment in the tissues. As soon as an excess of pigment occurs, the death of many active elements is observed, which causes sclerotic processes. The reason for the appearance of secondary hemochromatosis is the excessive intake of iron into the body from the outside. This condition often occurs against the background of the following problems:

• Excessive intake of drugs with iron;
• Thalassemia;
• Anemia;
• Cutaneous porphyria;
• Alcoholic cirrhosis of the liver;
• Viral hepatitis B, C;
• malignant tumors;
• Following a low protein diet.

Symptoms of the disease

Hemochromatosis of the liver is characterized by vivid symptoms. But, the first signs of the disease begin to manifest themselves in adulthood - after 40 years. It is by this period of life that the body accumulates up to 40 grams of iron, which significantly exceeds all permissible norms. Depending on the stage of development of hemochromatosis, the symptoms of the disease are also distinguished. It is worth considering them in more detail.

Symptoms of the initial stage of development

The disease develops gradually. At the initial stage, the symptoms are not expressed. For many years, the patient may complain of general symptoms: malaise, weakness, fatigue, weight loss, decreased potency in men. Further, more pronounced signs begin to join these signs: pain in the liver, joint pain, dry skin, atrophic changes in the testicles in men. After this, the active development of hemochromatosis occurs.

Signs of an advanced stage of hemochromatosis

The main signs of this stage are the following complications:

• Pigmentation of the skin;
• Pigmentation of the mucous membranes;
• Cirrhosis of the liver;
• Diabetes.

Hereditary hemochromatosis, like any other form, is characterized by pigmentation. This is the most frequent and main sign of the transition of the disease to the advanced stage. The severity of the symptom depends on the duration of the course of the disease. Smoky and bronze skin tone, most often manifested in open areas of the skin - face, hands, neck. Also, characteristic pigmentation is observed on the genitals, in the armpits.

Excess iron is primarily deposited in the liver. Therefore, in almost every patient, an increase in the gland is recorded during diagnosis. The structure of the liver also changes - it becomes more dense, painful on palpation. 80% of patients develop diabetes mellitus, and in most cases it is insulin-dependent. Endocrine changes are also manifested in such signs:

• pituitary dysfunction;
• Hypofunction of the epiphysis;
• Violation of the adrenal glands;
• Dysfunction of the sex glands, thyroid gland.

Excessive accumulation of iron in the organs of the cardiovascular system in primary hereditary hemochromatosis occurs in 95% of cases. But, the symptoms of the work of the heart is manifested only in 30% of all cases of the disease. Thus, heart enlargement, arrhythmia, refractory heart failure are diagnosed. There are characteristic symptoms depending on gender. So, men have testicular atrophy, complete impotence, gynecomastia. Women often experience infertility, amenorrhea.

Symptoms of the thermal stage of hemochromatosis

During this period, specialists observe the process of organ decompensation. This manifests itself in the form of the development of portal hypertension, liver failure, ventricular heart failure, exhaustion, dystrophy, diabetic coma. In such cases, mortality occurs, most often, from bleeding of dilated varicose veins of the esophagus, peritonitis, diabetic and hepatic coma. The risk of developing malignant neoplasms increases. A rare form is juvenile hemochromatosis, which actively develops at the age of 20-30 years. Mainly, the liver and cardiac system are affected.

Diagnosis of hemochromatosis

Diagnosis is carried out by a specialist, depending on the main symptom. So, the patient can seek help from a cardiologist, gastroenterologist, gynecologist, endocrinologist, rheumatologist, urologist or dermatologist. At the same time, the diagnostic options are the same, regardless of the clinical manifestations of hemochromatosis. After the initial examination, history taking, patient complaints, laboratory and instrumental studies are assigned to confirm or refute the diagnosis.

According to the results of laboratory tests, it will be possible to make an accurate diagnosis. So, the following indicators will indicate the presence of hemochromatosis:

• High levels of iron in the blood;
• Increasing the level of transferrin and ferritin in the blood serum;
• Increased excretion of iron in urine;
• Low iron-binding capacity of blood serum.

Further, the specialist may prescribe a biopsy of the liver or skin with a puncture. Hemosiderin deposits will be found in the samples taken, which will also indicate hemochromatosis. Hereditary hemochromatosis is established using a molecular genetic study. To establish the degree of damage, the state of the affected internal organs, instrumental diagnostics is required.

The most popular research method is ultrasound of the affected organs. It is possible to assess the condition of the liver, heart, intestines. For a more detailed diagnosis, an MRI or CT scan, X-ray of the joints are prescribed. Additionally, you can conduct a study of liver tests, urine, blood sugar, glycated hemoglobin.

Treatment of hemochromatosis

Therapy of hemochromatosis is necessarily complex. The main objective of this treatment is to remove iron from the body. But, it is very important that the diagnosis is made correctly. Only after that treatment is prescribed. Self-medication is strictly prohibited. So, the first stage of therapy is the intake of iron-binding drugs.

Such drugs, when ingested, begin to actively bind to iron molecules, with their further excretion. For this purpose, a 10% solution of desferal is often used. It is intended for intravenous administration. The course of therapy is prescribed exclusively by the doctor, depending on the severity of the course of hemochromatosis. On average, the course lasts 2-3 weeks.

A prerequisite in the complex treatment of hemochromatosis is phlebotomy. This procedure is also known as bloodletting. Since ancient times, bloodletting has been used to treat various diseases. And hemochromatosis lends itself perfectly to this treatment option. Due to the release, the number of erythrocytes in the total amount of blood decreases. As a result, iron levels also decrease. In addition, phlebotomy quickly eliminates pigmentation, liver dysfunction. But, it is important to comply with all dosages and the rules of the procedure. So, the descent of 300-400 ml of blood at a time is considered acceptable. But with the loss of 500 ml of blood, the patient may feel worse. It is enough to carry out the procedure 1-2 times a week.

During the treatment period, the following conditions should be observed:

• Complete exclusion of alcohol;
• Refusal to take dietary supplements;
• Refusal to take vitamin C, multivitamin complexes;
• Exclusion from the diet of foods with high levels of iron;
• Refusal to consume easily digestible carbohydrates.

To purify the blood, specialists can resort to plasmapheresis, cytopheresis, or hemosorption. Simultaneously with the excretion of iron, it is worthwhile to carry out symptomatic treatment of the liver, heart failure, and diabetes mellitus. Comprehensive treatment of the disease includes the observance of a certain diet.

Diet Hemochromatosis

Compliance with a diet with such a disease plays an important role in the treatment process. So, foods that are a source of large amounts of iron are completely excluded from the patient's diet. These include the following:

• Pork, beef;
• Buckwheat grain;
• pistachios;
• Apples;
• beans;
• Corn;
• Spinach;
• Parsley.

It is worth remembering that the darker the meat, the more this trace element is in it. With hemochromatosis, it is strictly forbidden to drink any alcoholic beverages. The consumption of vitamin C leads to increased absorption of iron. Therefore, ascorbic acid should also be excluded. Experts say that you do not need to completely abandon foods containing iron. You just need to minimize the amount of their consumption.

After all, hemochromatosis is a disease of excess iron. It is worth normalizing its level. But iron deficiency will provoke severe blood diseases. Everything should be in moderation. When compiling a diet menu, you need to replace dark meat with light, buckwheat porridge with wheat. Compliance with such a diet will speed up the healing process, improve the general condition of the patient.

What is the prognosis?

In the case of timely detection of hemochromatosis, the patient's life is extended for decades. In general, the prognosis is determined taking into account organ overload. In addition, hemochromatosis occurs in adulthood, when concomitant chronic ailments often develop. If you do not deal with the therapy of hemochromatosis, life expectancy will be a maximum of 3-5 years. An unfavorable prognosis is also observed in case of damage to the liver, heart and endocrine system with this disease.

To avoid the development of secondary hemochromatosis, it is worth following the rules of prevention. The main ones are a rational, balanced diet, taking iron supplements only under the supervision of a doctor, periodic blood transfusion, exclusion of alcohol, observation by a graft in the presence of heart and liver diseases. Primary hemochromatosis requires family screening. After that, the most effective treatment begins.

Hemochromatosis was first described as a separate disease in 1889. However, it was only with the development of medical genetics that it was possible to accurately establish the causes of the disease.

Such a rather late classification was facilitated by the nature of the disease and its rather limited distribution.

So, according to modern data, 0.33% of the world's inhabitants are at risk of developing hemochromatosis. What causes the disease and what are its symptoms?

Hemochromatosis - what is it?

This disease is hereditary and is characterized by a multiplicity of symptoms and a high risk of serious complications and comorbidities.

Studies have shown that hemochromatosis is most often caused by a mutation in the HFE gene.

As a result of a gene failure, the mechanism of iron capture in the duodenum is disrupted. This leads to the fact that the body receives a false message about the lack of iron in the body and begins to actively and in excess synthesize a special protein that binds iron.

This leads to excessive deposition of hemosiderin (glandular pigment) in the internal organs. Simultaneously with the increase in protein synthesis, the gastrointestinal tract is activated, leading to excessive absorption of iron from food in the intestine.

So even with a normal diet, the amount of iron contained in the body is many times higher than the norm. This leads to the destruction of tissues of internal organs, problems with the endocrine system, and immunity.

Classification by types, forms and stages

In medical practice, primary and secondary types of the disease are distinguished. In this case, the primary, also called hereditary, is the result of manifestation. Secondary hemochromatosis is a consequence of the development of abnormalities in the work of the enzyme systems involved in the glandular metabolism.

Four forms of the hereditary (genetic) type of the disease are known:

• classical;
• juvenile;
• hereditary HFE-unassociated species;
• autosomal dominant.

The first type is associated with a classical recessive mutation of a region of the sixth chromosome. This type is diagnosed in the vast majority of cases - more than 95 percent of patients suffer from classic hemochromatosis.

The juvenile type of the disease occurs as a result of a mutation of another gene - HAMP. Under the influence of this change, the synthesis of hepcidin, an enzyme responsible for the deposition of iron in organs, increases significantly. The disease usually appears between the ages of ten and thirty.

The HFE-unassociated type develops when the HJV gene fails. This pathology includes the mechanism of hyperactivation of transferrin-2 receptors. As a result, the production of hepcidin is activated. The difference with the juvenile type of the disease is that in the first case, a gene fails that is directly responsible for the production of an iron-binding enzyme.

Whereas in the second case, a state characteristic of an excess of iron in food is created in the body, which leads to the production of the enzyme.

The fourth type of hereditary hemochromatosis is associated with a malfunction of the SLC40A1 gene.

The disease manifests itself in old age and is associated with improper synthesis of the protein ferroportin, which is responsible for the transport of iron compounds into cells.

Causes of missense mutations and risk factors

A genetic mutation in a hereditary type of disease is a consequence of a person's predisposition.

Studies show that the majority of patients are white residents of North America and Europe, with the largest number of those suffering from hemochromatosis observed among immigrants from Ireland.

At the same time, the prevalence of different types of mutation is typical for different parts of the globe. Men are affected several times more often than women. In the latter, symptoms usually develop after hormonal changes in the body, which occurs as a result of menopause.

Among registered patients, women are 7-10 times less than men. The reasons for the changes are still unclear. Only the hereditary nature of the disease has been irrefutably proven, and there is also a connection between the presence of hemochromatosis and.

While the proliferation of connective tissue cannot be directly explained by the accumulation of iron in the body, up to 70% of patients with hemochromatosis had liver fibrosis.

However, genetic predisposition does not necessarily lead to the development of the disease.

In addition, there is a secondary form of hemochromatosis that occurs in people with initially normal genetics. Some pathologies are also risk factors. So, transferred steatohepatitis (non-alcoholic deposition of adipose tissue), the development of chronic hepatitis of various etiologies, as well as blockage contribute to the manifestation of the disease.

Some malignant neoplasms can also become a catalyst for the development of hemochromatosis.

Symptoms of hemochromatosis in women and men

In the past, only the development of a number of serious symptomatic manifestations made it possible to diagnose this disease.

The patient with excessive accumulation of iron feels chronic fatigue, weakness.

This symptom is characteristic of 75% of those suffering from hematochromatosis. Skin pigmentation is enhanced, and this process is not associated with the production of melanin. The dark shade of the skin acquires due to the accumulation of iron compounds there. Darkening is observed in more than 70% of patients.

The negative effect of accumulated iron on immune cells leads to weakened immunity. Therefore, with the course of the disease, the patient's susceptibility to infections increases - from quite serious to banal and harmless under normal conditions.

About half of the patients suffer, which are expressed in the occurrence of pain.

There is also a deterioration in their mobility. This symptom occurs because an excess of iron compounds catalyzes the deposition of calcium in the joints.

Arrhythmia attacks and the development of heart failure are also possible. A negative effect on the pancreas often leads to. Excess iron causes dysfunction of the sweat glands. In quite rare cases, they are observed.

The development of the disease leads to impotence in men. A decrease in sexual function indicates signs of poisoning of the body with iron compound products. In women, heavy bleeding is possible during the regulation.

An important symptom is an increase in the liver, as well as quite severe pain in the abdomen, in the appearance of which it is not possible to identify systemicity..

The presence of several symptoms indicates the need for accurate laboratory diagnosis of the disease.

A sign of the disease is high, with a simultaneous low content in erythrocytes. Transferrin iron saturations below 50% are considered a laboratory sign of hemochromatosis.

The presence of complex heterozygotes or homozygous mutations of a certain type in the HFE gene with clinical evidence of excessive iron accumulation indicates the development of hemochromatosis.

A significant increase in the liver with a high density of its tissues is also a sign of the disease. In addition, with hemochromatosis, a change in the color of the liver tissue is observed.

How does it manifest itself in a child?

Early hemochromatosis has a number of features - from the mutations of the corresponding parts of the chromosomes that caused it to a characteristic clinical picture and manifestations.

First of all, the symptoms of the disease at an early age are polymorphic.

Children are characterized by the development of symptoms indicating the presence of a portal. A violation of the assimilation of food develops, a simultaneous increase in the spleen and liver.

With the development of pathology, ascites begins to be severe and resistant to therapeutic effects - dropsy that forms in the abdominal region. Characterized by the development of varicose veins of the esophagus.

The course of the disease is severe, and the prognosis of treatment is almost always unfavorable. In almost all cases, the disease provokes a severe form of liver failure.

What tests and diagnostic methods help to identify pathology?

Several different laboratory diagnostic methods are used to detect the disease.

Initially, blood is taken to study the level of hemoglobin in erythrocytes and plasma.

Iron metabolism is also assessed.

The desferal test helps confirm the diagnosis. To do this, an injection of a glandular preparation is administered, and a urine sample is taken five hours later. Additionally, CT is performed, as well as MRI of the internal organs, which makes it possible to determine their pathological changes - an increase in size, pigmentation, a change in the structure of the tissue.

Molecular genetic scanning allows you to determine the presence of a damaged section of the chromosome. This study, conducted with members of the patient's family, also allows us to assess the possibility of the onset of the disease even before the appearance of its clinical manifestations that disturb the patient.

Principles of treatment

The main methods of treatment are the normalization of readings of the iron content in the body and the prevention of damage to internal organs and systems. Unfortunately, modern medicine does not know the methods of normalizing the gene apparatus.

bloodletting

A common treatment is bloodletting. During initial therapy, 500 mg of blood is removed weekly. After the normalization of iron levels, they switch to maintenance therapy, when blood sampling occurs every three months.

Intravenous administration of iron-binding drugs is also practiced. So, chelators allow you to remove excess substances with urine or feces. However, the short period of action makes it necessary to regularly inject medications subcutaneously with the help of special pumps.

Laboratory control is carried out once every three months. It includes counting the iron content, as well as diagnosing signs of anemia and other consequences of the disease.

Possible complications and prognosis

With early diagnosis, the disease can be effectively controlled.

The duration and quality of life of patients who receive regular care practically do not differ from those of healthy people.

In this case, untimely treatment leads to serious complications. These include the development of cirrhosis and liver failure, diabetes, damage to the veins up to bleeding.

The risk of developing cardiomyopathy and liver cancer is high, and intercurrent infections are also observed.

Related videos

About what is hemochromatosis and how to treat it:

Hemochromatosis is a hereditary disease characterized by a violation of iron metabolism, resulting in an excessive accumulation of this element in the tissues of the body (more than 20 g at a rate of 3-4 g). The name of the nosological form reflects the most characteristic symptom of this disease - intense staining of the skin and internal organs.

A symptom complex typical of hemochromatosis was first described in the second half of the 19th century.

According to statistics, the probability of developing hemochromatosis in the population is 0.33%.

Synonyms: pigmentary cirrhosis, bronze diabetes.

Excessive accumulation of iron in liver tissues

Causes and risk factors

The cause of hereditary hemochromatosis is a genetically determined predisposition associated with a mutation of the genes responsible for the main stages of the metabolism of iron-containing pigments in the body (C282Y and H63D).

Secondary hemochromatosis is formed against the background of the acquired insolvency of the enzyme systems involved in the exchange of iron in the body. The main pathologies leading to the development of secondary hemochromatosis:

• chronic viral hepatitis C and B;
• non-alcoholic steatohepatitis;
• liver tumors;
• leukemia;
• blockage of the pancreatic ducts;
• cirrhosis of the liver;
• thalassemia.

The accumulation of iron in tissues and organs can cause the development of life-threatening conditions - hepatic or diabetic coma, liver and heart failure, bleeding from dilated superficial veins.

Forms of the disease

The main forms of hemochromatosis are primary and secondary, and the primary is not a monogenic disease. Depending on the type of mutation, the following variants of primary (hereditary) hemochromatosis are distinguished:

• autosomal recessive;
• juvenile;
• autosomal dominant;
• associated with a mutation in the type 2 receptor for transferrin.

Stages of the disease

Hemochromatosis has the following stages:

1. Without overloading the body with iron.
2. With iron overload without clinical symptoms.
3. With severe clinical manifestations of pathology.

Symptoms

The early stages of the pathological process are characterized by the presence of such general clinical symptoms of intoxication:

• increased fatigue, progressive weakness;
• loss of appetite;
• weight loss;
• unmotivated weakening of sexual function.

A symptom complex typical of hemochromatosis was first described in the second half of the 19th century.

Excessive accumulation of iron in tissues and organs leads to pain in the joints and right hypochondrium, skin atrophy, testicular atrophy in men.

The classic triad of symptoms of hemochromatosis:

• bronze pigmentation of the skin and mucous membranes;
• diabetes;
• cirrhosis of the liver.

Features of the course of the disease in young people

In young people from 15 to 30 years old, the so-called juvenile form of hemochromatosis is formed, which is characterized by a pronounced overload of the body with iron with a violation of the functional activity of the liver and heart.

Diagnostics

Diagnostic clinical criteria for hemochromatosis:

• diabetes;
• hypogonadism;
• cardiomyopathy;
• skin pigmentation.

The laboratory criterion is a transferrin saturation ratio of 45% or more.

The most informative non-invasive diagnostic method is magnetic resonance imaging of the liver, which makes it possible to note a decrease in the signal level due to excessive accumulation of iron in its cellular structures.

According to statistics, the probability of developing hemochromatosis in the population is 0.33%.

Treatment

The main pathogenetic method of treating hemochromatosis is bloodletting, as a result of which an excess amount of iron is eliminated from the body. Pharmacological methods of removing iron based on the intake of iron-binding drugs are also used.

Symptomatic treatment consists of measures aimed at eliminating the manifestations of diabetes mellitus, maintaining the functional activity of the liver and heart.

Possible complications and consequences

In addition to the pronounced toxic effect of excessive iron concentration on the body, its accumulation in tissues and organs can cause the development of life-threatening conditions - hepatic or diabetic coma, liver and heart failure, bleeding from dilated superficial veins.

Forecast

Hemochromatosis is a serious disease, the prognosis of which depends on the degree of iron accumulation in the body and on the compensatory capabilities of the organs and systems involved in the pathological process. Timely started and regularly carried out pathogenetic therapy can increase life expectancy by several decades.

Prevention

Since primary hemochromatosis is hereditary, there are no measures to prevent it. Preventive measures for secondary hemochromatosis include:

• following a diet that limits the intake of foods rich in iron;
• taking iron-binding drugs.

Video from YouTube on the topic of the article:

© Use of site materials only in agreement with the administration.

The history of hemochromatosis as a disease (a symptom complex, a condition characterized by excessive accumulation of iron (Fe) in the body) originates from the end of the 19th century, namely from 1871, but the current name for the pathology stuck only 18 years later (1889) . Hemachromatosis (HC) is also called pigmentary cirrhosis and bronze diabetes, which, in principle, reflects its clinical manifestations: discoloration of the skin (to bronze), all signs of diabetes mellitus and degeneration of the hepatic parenchyma with the development of cirrhosis. In addition, hemochromatosis is called generalized hemosiderosis, von Recklinghausen-Appelbaum disease and Troisier-Anot-Choffard syndrome. The formation of this symptom complex ultimately leads to damage to many organs and to the development of multiple organ failure.

It has been noticed that men suffer from this pathology more often than women (ratio ≈ 1: 8-10) and this is not due to the influence of a defective gene. The female body has the ability to lose not only excess, but also the right amount of iron during menstruation or during pregnancy. On average, the disease manifests itself between 40 and 60 years. Given the defeat of many organs, hemochromatosis is not treated by anyone: a rheumatologist, a gastroenterologist, an endocrinologist, a cardiologist, and other specialists.

Where does excess iron go?

Perhaps someone has heard that, in addition to the known forms of diabetes mellitus (IDDM and NIDDM), there is also a certain variant called bronze (not to be confused with bronze disease - Addison's disease), pigmentary cirrhosis or hemochromatosis, which due to excessive accumulation of iron in the body.

The liver always takes the first blow (hemochromatosis of the liver). At the earliest stage, when other organs have not yet been affected by the "invasion" of iron, the portal zones are already filled with this chemical element. Hemachromatosis of the liver causes the replacement of the hepatic parenchyma with connective tissue (this is fibrosis) in both lobes with the development of cirrhosis, which, in turn, can transform into primary cancer this important organ.

However, the pathological process does not end on the liver, because iron continues to accumulate and its amount can reach 20-60 grams (at a rate of 4-5 g). But he needs to go somewhere and, naturally, he is looking for other parenchymal organs. As a result, iron settles:

• in the pancreas, leading to degeneration of its parenchyma;
• in the spleen;
• in myocardial fibers, creating conditions for the development of sclerosis of the coronary vessels;
• in the epidermis, which from such interventions begins to thin and atrophy;
• in the endocrine glands (adrenals, pituitary, thyroid, testes).

Iron, being deposited in organs and tissues, excites a tissue response to the presence of an element that is unnecessary in such quantities, increasing the rate of lipid peroxidation, which leads to damage to cell organelles, resulting in fibrosis. In addition, along the way, there is a stimulation of collagen production by cells that are responsible for the construction of connective tissue. And it doesn’t matter at all in which organs iron began to accumulate, if the process is not stopped, in the end, everyone will suffer.

The toxicity of Fe lies in the fact that this metal, as an element with variable valence (Fe (II), Fe (III)), is able to easily initiate free radical reactions that damage cell organelles and the genetic material of the cell, increase collagen production and provoke the formation of tumor processes. .

What does bronze diabetes look like?

Accumulating a valuable, in general, metal every day, the body acquires about 1 gram of iron per year, which turns out to be superfluous for the body. With congenital hemachromatosis, these accumulations will be replenished annually and in 20 years will grow into a rather impressive figure: ≈ 20 grams (sometimes up to 50 g). For reference: normally, the body contains about 4 grams of Fe, and this amount is distributed between heme-containing blood proteins (hemoglobin), muscles (myoglobin), respiratory pigments and enzymes. In stock (mainly in the liver), just in case, up to 0.5 g of Fe is stored. The amount of absorbed element correlates with the reserve content, and the more the body needs it, the more iron must come through absorption. In hemochromatosis, increased absorption leads to excessive accumulation.

manifestations of hemochromatosis

Excess iron deposition develops gradually, passing through 3 stages:

• 1st - there is no iron overload yet (tests - calm, clinic - absent);
• 2nd - overload is already taking place, as evidenced by laboratory indicators, but clinically this has not yet manifested itself in any way;
• 3rd - overload of the body with this metal gives characteristic clinical symptoms.

Thus, ultimately, hemochromatosis does not go unnoticed. Organs that have given place to an extra chemical element begin to suffer, losing the ability to perform their functional duties. Symptoms characteristic of hemochromatosis develop:

symptoms of hemochromatosis

1. Apathy, weakness and lethargy;
2. Sealing and enlargement of the liver (hepatomegaly), the release of ferritin from the liver, which has a vasoactive effect, which often causes abdominal pain, sometimes simulating an acute surgical pathology with collapse and even death. With hemochromatosis of the liver, primary cancer (hepatocellular carcinoma) threatens 30% of patients who have already been diagnosed with cirrhosis;
3. Change in the color of the skin (pigmentation), affecting mainly the armpits, vulva, exposed parts of the body;
4. Thinning and dry skin;
5. Decreased sexual activity, impotence, gynecomastia, testicular atrophy (in men), infertility and amenorrhea (in women), hair loss in areas of secondary hair growth (due to insufficient gonadotropic function of the pituitary gland);
6. Cardiac hemochromatosis is a lesion of the heart muscle (up to 90%), often resembling cardiomyopathy, which gives progressive insufficiency of the right atrium and ventricle, arrhythmia and can be complicated by myocardial infarction. Spherical heart (shape) - "iron heart" in other cases suddenly stops, which ends with the death of the patient;
7. Often (in 70 - 75% of patients) diabetes mellitus develops, the cause of which is direct damage to the pancreatic parenchyma. Diabetes with hemochromatosis gives complications inherent in other forms (nephropathy, lesions of the retina and peripheral vessels);
8. Painful changes in many joints (hip, knee, shoulder, wrist, etc.), the cause of which is the deposition of calcium salts. A characteristic symptom is hand tremor, accompanied by pain.

Hemochromatosis can be primary or hereditary (congenital hemochromatosis), resulting from an autosomal recessive metabolic disorder and characterized by increased absorption of Fe in the intestinal tract, and secondary or acquired, the cause of which is some kind of background pathology that promotes increased absorption of Fe in the gastrointestinal tract.

With primary hemochromatosis (PHC) a person is born with a gene from both parents that carries bad information (autosomal recessive inheritance). True, the patient does not know about this for a long time, accumulating this chemical element from day to day. For example, if 5 mg of iron from dietary intake remains in the body daily, then the first symptoms will appear after about 28 years.

Secondary hemochromatosis (SHC) formed at some stage, as a result of certain violations. And then it doesn’t matter for what reason the malabsorption occurred, the fact is that iron accumulates in large quantities in vital organs (heart, liver, individual endocrine glands, joints) and thus interferes with their normal functioning.

Hereditary or primary hemochromatosis

As it turned out, hereditary hemochromatosis (NH) is not a rare disease at all. This was thought earlier, when population genetic analysis on a modern scale was not available.

The assumption of the genetic origin of primary hemochromatosis was confirmed in the 70s of the last century, when the major histocompatibility complex (MHC) was actively studied, and antigens of the HLA leukocyte system were discovered one by one. The gene that controls the concentration of Fe in the body is located on the short arm of chromosome 6, next to the A (A3) locus of the HLA complex. As a result, evidence of an association between hemochromatosis and the genes of the major histocompatibility system was obtained.

Primary hemochromatosis is always hereditary, it appears in the population along with the birth of a new (homozygous) member, but it will manifest itself only after 2-3 decades.

It has now been reliably established that the prevalence of a defective recessive gene (hemochromatosis gene), which carries distorted information about metabolism, accompanied by increased absorption of iron, is not so small - up to 10% among all residents. Homozygous recessive in the general population is up to 0.3 - 0.45%, so the frequency of the hereditary variant due to monozygous carriage varies within the same range (0.3 - 0.45%). This means that in Europe, approximately one person out of three hundred is at risk of being born with such deviations, and 10% of all Europeans, being carriers of the hemochromatosis gene (heterozygotes), cannot be sure that this pathology will never affect them or their children. Clinically pronounced forms of damage to the hepatic parenchyma (hemochromatosis of the liver), associated with a congenital gene defect, appear in the population with a frequency of 2 cases per 1000 people.

Do not relax too much and heterozygotes. Although the probability of developing Fe supersaturation is extremely small (less than 4%), the presence of the hemochromatosis gene is not as harmless as it seems. Carriers may also show signs of accelerated absorption and elevated levels of iron in the body. This happens if a heterozygous carrier has acquired another pathology, accompanied by a violation of iron metabolism, or damage to the hepatic parenchyma, for example, hepatitis C (the clinic will not be so bright, but iron overload will make itself felt) and alcohol abuse.

Hereditary hemochromatosis, until recently, was perceived as a simple monogenic pathology, but now everything has changed and HHC began to be divided depending on the gene defect and symptoms. Four varieties of primary hemochromatosis are designated:

• Type I - the most common (up to 95%) autosomal recessive (classic), HFE-associated, caused by a defect in the HFE gene (point mutation - С282У);
• II type - (juvenile);
• type III - HFE-unassociated (mutation in the type 2 transferrin receptor);
• Type IV - autosomal dominant HC.

The basis for the development of primary congenital hemochromatosis are mutations in the HFE gene, which disrupt the capture of Fe by enterocytes (cells of the duodenum 12) with the direct participation of transferrin, resulting in distorted information that the iron content in the body has fallen below the permissible level. Enterocytes respond to this signal by active production of the iron-binding protein DCT-1, thereby enhancing iron uptake and its accumulation in excessive amounts inside the cell.

Purchased variant

Secondary hemochromatosis or generalized hemosiderosis - acquired hemochromatosis, it is formed against the background of some already existing disease, for example, ineffective erythropoiesis (megaloblastic anemia, refractory anemia in myelodysplastic syndrome), hemolytic anemia, chronic damage to the hepatic parenchyma, saturated ferrotherapy (use of drugs containing iron, in excessive doses) and even excessive consumption of Fe with food. The cause of HHC in such cases is the acquired depletion of enzyme systems that are involved in the exchange of Fe.

liver hemochromatosis

Secondary hemochromatosis is considered parenteral iron overload during transfusions of red blood cells and Fe with dextran (post-transfusion GC). For example, patients with aplastic anemia who receive large amounts of ermassa are somehow overloaded with this chemical element, that is, the parenteral form always has iatrogenic roots. And doctors know that if a patient (without loss of blood) needs repeated administration of donor erythrocytes, then care should be taken to prevent secondary hemochromatosis, which consists in prescribing drugs that can bind excess iron and form chelates with them.

In addition to post-transfusion hemochromatosis, other forms of this secondary pathology have been identified:

• Alimentary HC - it develops after cirrhosis of the liver, caused by excessive consumption of alcoholic beverages;
• Metabolic - this option is formed due to metabolic disorders in which iron is involved (intermediate thalassemia, some viral hepatitis, malignant tumors);
• Mixed (major beta-thalassemia, anemic syndromes arising on the basis of impaired erythropoiesis);
• Neonatal - iron overload in children in the neonatal period. Pathology manifests itself in the first days of life, is characterized by intrauterine growth retardation and liver failure, rapidly progressing, cuts off the baby's life within a few days.

What happens when the active absorption of Fe begins

Europeans consume ≈ 1 - 20 mg of Fe, which comes (in the form of compounds) with food. In 24 hours, 1-2 mg of the element enters the body through the gastrointestinal tract and the same amount leaves it. In patients who receive less iron, have hereditary hemochromatosis, or suffer from a pathology that occurs with impaired erythropoiesis, the amount of absorbed Fe increases by ≈ 3 times. The absorption process is very active and it is carried out in the small intestine (upper section):

However, all the processes described above go exactly like this if everything is in order in the body with the exchange of iron. But with hemochromatosis, there is an excessive accumulation of iron, and it ceases to fit into the ferritin form. Iron-containing protein molecules begin to break down, forming hemosiderin, the content of which naturally increases during GC, so hemochromatosis is often called hemosiderosis.

It is hard for the transport protein to overload with iron, because it is forced to take not 1/3 of the iron, but more, reaching full saturation. However, this does not help either, since iron still remains and then it begins to move independently (without transferrin) in the form of various compounds with low molecular weight chelators, that is, traps for Fe. This shape allows this chemical element to easily pass into the cell, regardless of whether it is needed there or not. A cell saturated with iron cannot create obstacles for the entry of a new portion of the metal, which naturally becomes superfluous.

Diagnostics

Diagnosis of hemochromatosis does not depend on the origin of the pathological process, it is the same for all variants of the disease.

Excessive accumulation of iron can be suspected based on complaints and clinical symptoms. The fact that a male person may develop hereditary hemochromatosis can be judged by such signs as liver enlargement, asthenia, arthralgia, changes in the activity of transferases (AlT, AST), however, their indicators very rarely have significant deviations from the norm when manifest variants of HCH, even if all the symptoms of liver cirrhosis are present. At the first stage of the diagnostic search, the doctor sends the patient for an ultrasound examination (ultrasound) and magnetic resonance imaging (MRI), in parallel prescribes laboratory tests:

• Genetic testing - determination of point mutations characteristic of the congenital variant (C282U and H63D) in the hemochromatosis gene;
• Serum iron;
• The total iron-binding capacity of the serum (TIBC) or the percentage of saturation of transferrin with iron - this analysis shows how much transport protein involved in the transfer of Fe is contained in the blood serum (normal - approx. 30%);
• Serum ferritin (assessment of Fe reserves in the whole body).

And since all the tests performed indicate the development of HC, then a liver biopsy will be useful, which can finally dispel doubts about the diagnosis. At the initial stage, in young patients, excessive accumulation of Fe will be noticeable only in the cells of the hepatic parenchyma (hepatocytes) and the periportal region. In elderly people, deposits are also noticeable in hepatocytes, and in Kupffer cells, and in cells of the bile ducts. Cirrhosis of the liver with HC is small-nodular (micronodular).

Taking as a basis changes in the liver and detecting the growth of connective tissue (cirrhosis), differential diagnosis should be carried out. Again, a histological examination (biopsy) will help in this, because the replacement of the hepatic parenchyma with connective tissue in case of hepatitis or alcohol abuse will have slightly different signs.

Hepatocellular carcinoma against the background of hemochromatosis can be suspected if the patient's condition has noticeably worsened recently, the liver has greatly increased, and the level of the tumor marker, α-fetoprotein, has increased.

Treatment, prevention, prognosis

Treatment begins with a revision of the diet. All foods that contain iron should be excluded from the diet. Of the drugs, the main ones are deferoxamine, which forms a complex with Fe and helps this element to leave the body. Effective in GC bloodletting, they reduce the size of the liver and spleen, pigmentation, improve liver enzymes, and in some cases facilitate the treatment of diabetes. Often, extracorporeal treatment (hemosorption, plasmapheresis) is carried out simultaneously, which also helps to remove excess iron from the body.

Of course, in the treatment of the underlying pathology (hemochromatosis), symptomatic therapy is not bypassed, because in many patients changes in the liver, heart and other organs have time to occur. In other cases, symptomatic treatment is quite serious, for example, liver transplantation for cirrhosis or endoprosthesis replacement of pathologically altered joints (arthroplasty).

Prevention of hemochromatosis consists in early diagnosis of the disease, which consists not only in determining the level of the element itself (Fe), ferritin, transferrin, but also in carrying out genetic analysis (examination of close relatives of the patient), which is of high importance in asymptomatic cases in young people.

The prognosis for HC is, in principle, not bad if the process has not affected the delicate hepatic parenchyma, without forming cirrhosis of the liver. In this case, hemochromatosis does not affect life expectancy, in the rest it all depends on the degree of liver damage and the duration of iron overload over time. Most often, patients with hemochromatosis die from diabetic and hepatic coma, heart failure, esophageal or gastric bleeding caused by varicose veins, primary liver cancer. However, early diagnosis and timely treatment of HC is quite capable of preventing dire consequences.

Video: lecture on hemochromatosis