Hemochromatosis is a hereditary polysystemic disease accompanied by active absorption of iron in the gastrointestinal tract and its subsequent accumulation in internal organs (heart, pancreas, liver, joints, pituitary gland). The hemochromatosis clinic is characterized by bronze pigmentation of the skin and mucous membranes, the development of liver cirrhosis, diabetes mellitus, cardiomyopathy, arthralgia, sexual dysfunction, etc. The diagnosis of hemochromatosis is confirmed by determining increased excretion of iron in the urine, high iron content in blood serum and liver biopsies, as well as by radiography, ultrasound, MRI of internal organs. Treatment of patients with hemochromatosis is based on diet, administration of deferoxamine, bloodletting, plasmapheresis, hemosorption, symptomatic therapy. If necessary, the issue of liver transplantation and arthroplasty is resolved.
Meaning
Hemochromatosis (bronze diabetes, pigmented cirrhosis) is a genetically determined violation of iron metabolism, leading to the deposition of iron–containing pigments in tissues and organs and the development of multiple organ failure. A disease accompanied by a characteristic symptom complex (skin pigmentation, liver cirrhosis and diabetes mellitus) it was described in 1871, and in 1889 was named hemochromatosis for the characteristic color of the skin and internal organs. The frequency of hereditary hemochromatosis in the population is 1.5-3 cases per 1000 population. Men suffer from hemochromatosis 2-3 times more often than women. The average age of pathology development is 40-60 years. Due to the polysystemic nature of the lesion, various clinical disciplines are engaged in the study of hemochromatosis: gastroenterology, cardiology, endocrinology, rheumatology, etc.
In the etiological aspect, primary (hereditary) and secondary hemochromatosis are distinguished. Primary hemochromatosis is associated with a defect in enzyme systems, leading to the deposition of iron in the internal organs. Depending on the gene defect and the clinical picture , there are 4 forms of hereditary hemochromatosis:
- I – classic autosomal recessive, HFE-associated type (more than 95% of cases)
- II – juvenile type
- III – hereditary HFE-unassociated type (mutations in the transferrin receptor type 2)
- IV– autosomal dominant type.
Secondary hemochromatosis (generalized hemosiderosis) develops as a result of acquired insufficiency of enzyme systems involved in iron metabolism, and is often associated with other diseases, and therefore its following variants are distinguished: posttransfusion, alimentary, metabolic, mixed and neonatal.
In the clinical course, hemochromatosis passes through 3 stages: I – without iron overload; II – with iron overload, but without clinical symptoms; III – with the development of clinical manifestations.
Causes
Primary hereditary hemochromatosis is a disease with an autosomal recessive type of transmission. It is based on mutations of the HFE gene located on the short arm of the 6th chromosome. A defect in the HFE gene leads to a violation of transferrin-mediated iron uptake by the cells of the duodenum 12, which results in the formation of a false signal about iron deficiency in the body. In turn, this contributes to increased synthesis of iron-binding protein DCT-1 by enterocytes and enhanced absorption of iron in the intestine (with normal intake of trace elements from food). In the future, excessive deposition of the iron-containing pigment hemosiderin occurs in many internal organs, the death of their functionally active elements with the development of sclerotic processes. With hemochromatosis, 0.5-1.0 g of iron accumulates annually in the human body, and the manifestations of the disease manifest when the total iron level reaches 20 g (sometimes 40-50 g or more).
Secondary hemochromatosis develops as a result of excessive exogenous iron intake into the body. Such a condition can occur with frequent repeated hemotransfusions, uncontrolled intake of iron preparations, thalassemia, certain types of anemia, cutaneous porphyria, alcoholic cirrhosis of the liver, chronic viral hepatitis B and C, malignant neoplasms, following a low-protein diet.
Symptoms
The clinical manifestation of hereditary hemochromatosis occurs at a mature age, when the total iron content in the body reaches critical values (20-40 g). Depending on the prevailing syndromes, hepatopathic (hemochromatosis of the liver), cardiopathic (hemochromatosis of the heart), endocrinological forms of the disease are distinguished.
The disease develops gradually; in the initial stage, nonspecific complaints of increased fatigue, weakness, weight loss, decreased libido prevail. At this stage, patients may be concerned about pain in the right hypochondrium, dry skin, arthralgia caused by chondrocalcinosis of large joints. In the advanced stage of hemochromatosis, a classic symptom complex is formed, represented by skin pigmentation (bronze skin), liver cirrhosis, diabetes mellitus, cardiomyopathy, hypogonadism.
Usually, the earliest sign of hemochromatosis is the appearance of a specific color of the skin and mucous membranes, expressed mainly on the face, neck, upper extremities, in the armpits and external genitals, skin scars. The intensity of pigmentation depends on the duration of the disease and varies from pale gray (smoky) to bronze-brown. Characterized by hair loss on the head and trunk, concave (spoon-shaped) deformation of the nails. There are arthropathies of the metacarpophalangeal, sometimes knee, hip and elbow joints with the subsequent development of their stiffness.
Almost all patients have liver enlargement, splenomegaly, cirrhosis of the liver. Impaired pancreatic function is expressed in the development of insulin-dependent diabetes mellitus. As a result of damage to the pituitary gland in hemochromatosis, sexual function suffers: men develop testicular atrophy, impotence, gynecomastia; women – amenorrhea and infertility. Hemochromatosis of the heart is characterized by cardiomyopathy and its complications – arrhythmia, chronic heart failure, myocardial infarction.
Portal hypertension, ascites, and cachexia develop in the terminal stage of hemochromatosis. The death of patients, as a rule, occurs due to bleeding from varicose veins of the esophagus, liver failure, acute heart failure, diabetic coma, aseptic peritonitis, sepsis. Hemochromatosis significantly increases the risk of developing liver cancer (hepatocellular carcinoma).
Diagnostics
Depending on the prevailing symptoms, patients with hemochromatosis can seek help from various specialists: gastroenterologist, cardiologist, endocrinologist, gynecologist, urologist, rheumatologist, dermatologist. Meanwhile, the diagnosis of the disease is the same in different clinical variants of hemochromatosis. After assessing the clinical signs, patients are assigned a set of laboratory and instrumental studies to verify the validity of the diagnosis.
Laboratory criteria for hemochromatosis are a significant increase in the level of iron, ferritin and transferrin in the blood serum, an increase in the excretion of iron in the urine, a decrease in the total iron-binding capacity of the blood serum. The diagnosis is confirmed by a puncture biopsy of the liver or skin, in the samples of which the deposition of hemosiderin is detected. The hereditary nature of hemochromatosis is established as a result of molecular genetic diagnostics.
Liver samples, blood and urine glucose levels, glycosylated hemoglobin, etc. are examined to assess the severity of internal organ damage and prognosis of the disease. Laboratory diagnostics of hemochromatosis is supplemented by instrumental studies: radiography of joints, ECG, EchoCG, abdominal ultrasound, MRI of the liver, etc.
Treatment
The main purpose of the therapy is to remove excess iron from the body and prevent the development of complications. Patients with hemochromatosis are prescribed a diet that provides for the restriction of foods with a high iron content (apples, meat, liver, buckwheat, spinach, etc.), easily digestible carbohydrates. It is forbidden to take multivitamins, ascorbic acid, dietary supplements containing iron, alcohol. To remove excess iron from the body, bloodletting is resorted to under the control of hemoglobin, blood hematocrit, ferritin. For the same purpose, extracorporeal methods of hemocorrection can be used – plasmapheresis, hemosorption, cytapheresis.
Pathogenetic drug therapy of hemochromatosis is based on intramuscular or intravenous administration of deferoxamine binding Fe3+ ions to the patient. At the same time, symptomatic treatment of cirrhosis of the liver, heart failure, diabetes mellitus, hypogonadism is carried out. With severe arthropathy, indications for arthroplasty (endoprosthetics of affected joints) are determined. In patients with cirrhosis, the issue of liver transplantation is being resolved.
Prognosis and prevention
Despite the progressive course of the disease, timely therapy can prolong the life of patients with hemochromatosis for several decades. In the absence of treatment, the average life expectancy of patients after diagnosis of pathology does not exceed 4-5 years. The presence of complications of hemochromatosis (mainly cirrhosis of the liver and congestive heart failure) is a prognostically unfavorable sign.
In hereditary hemochromatosis, prevention is reduced to family screening, early detection and initiation of treatment of the disease. To avoid the development of secondary hemochromatosis, rational nutrition, control over the appointment and intake of iron preparations, blood transfusions, refusal to take alcohol, monitoring of patients with liver and blood system diseases.