Historical background and epidemiology
The characteristic symptom complex was first described by Trousseau in 1871. He identified the combination of diabetes mellitus, skin pigmentation, and liver cirrhosis, linking them to iron accumulation. In 1890, von Recklinghausen introduced the term "hemochromatosis", which reflects the brownish discoloration of the skin and internal organs due to the deposition of melanin and hemoglobinogenic pigments.
Idiopathic hemochromatosis has numerous synonyms: primary hemochromatosis, siderophilia, hereditary iron storage disease. In the past, it was also referred to as "bronze diabetes" and pigmentary cirrhosis.
The prevalence of the disease varies: it is extremely rare in the UK and Scandinavia, the frequency is 0.01–0.07% in Central Europe, and ranges from 0.001 to 0.1% in the USA. Men are affected 10 times more often than women, with the disease typically manifesting between the ages of 40 and 60. In women, the pathology usually manifests after the onset of menopause.
Pathogenesis and clinical presentation
Idiopathic hemochromatosis is based on a genetically determined metabolic disorder (autosomal recessive inheritance). The primary link in pathogenesis is a defect in the enzyme systems that regulate intestinal iron absorption. The metal enters in excess and is primarily deposited in hepatocytes.
The disease develops gradually, with characteristic symptoms forming over 1–3 years. In the fully developed stage, the classic triad appears:
- Pronounced pigmentation of the skin and mucous membranes.
- Liver cirrhosis.
- Diabetes mellitus.
The skin and internal organs acquire a specific rusty-brown or chocolate color. In the skin, the pigment accumulates in dermal macrophages and fibroblasts, while concurrently the amount of melanin in melanocytes increases.
Pathological anatomy of the liver
The liver is the main target organ of the disease. Macroscopically, it is heavily pigmented. Biopsy reveals massive deposition of hemosiderin (giving a positive Perls' reaction).
Dynamics of microscopic changes:
- Accumulation: hepatocytes (especially periportal ones) become overloaded with hemosiderin. There is significantly less pigment in stellate reticuloendothelial cells (Kupffer cells).
- Damage: the increasing volume of pigment leads to a decrease in the activity of oxidation-reduction enzymes. Necrobiosis and necrosis of hepatocytes begin.
- Late stages: hemosiderin is detected in the epithelium of the bile ducts and connective tissue.
- Fibrosis: fibrous tissue proliferates in place of the dead cells. Septa form, dividing the parenchyma into small monolobular false lobules.
The outcome is micronodular liver cirrhosis, which can transform into macronodular cirrhosis. A characteristic morphological feature is the presence of broad bands of mature connective tissue surrounding the false lobules.
Extrahepatic manifestations and diagnostics
In addition to the liver, iron is deposited in other organs, causing sclerosis and dystrophy:
- Pancreas: pigment accumulation causes interstitial inflammation, fibrosis, and atrophy of the islet apparatus (the cause of diabetes development).
- Spleen: changes are secondary in nature and associated with portal hypertension against the background of cirrhosis.
- Systemic lesions: the pigment is found in the myocardium, joint synovial membranes, and endocrine glands (pituitary, adrenal glands, thyroid and parathyroid glands, ovaries).
Diagnosis is based on laboratory data: hyperferremia, elevated ferritin levels, and transferrin saturation with iron greater than 50% (normal range 16–45%).
Prognosis and causes of death
The course of hemochromatosis is prolonged, especially in elderly patients. Timely therapy can prolong life by several decades.
Main causes of death:
- Hepatic failure.
- Bleeding from esophageal and gastric varices.
- Primary liver cancer (develops in 6–42% of cases, requiring regular ultrasound and monitoring of α-fetoprotein levels).
- Heart failure, diabetic coma, and intercurrent diseases.
Briefly: answers to topical questions
What morphological changes occur in the heart in hemochromatosis?
In hemochromatosis, the heart undergoes a specific accumulation of iron-containing pigment, leading to the development of sclerosis and dystrophy.
- Myocardial infiltration — deposition of pigment directly into the heart muscle.
- Sclerosis and dystrophy — structural changes in heart tissues associated with excessive iron deposition.
These infiltrative processes affect the very structure of the heart and can lead to the development of heart failure, as well as act as an intrinsic cause of bradyarrhythmias and conduction disorders.
What are the main causes for the development of secondary hemochromatosis?
The main confirmed sources and causes of secondary iron accumulation are anemias, alcoholic liver disease, and transfusion-related hemochromatosis.
- Anemias — noted as a condition in which hereditary hemochromatosis should be distinguished from secondary hemosiderosis.
- Alcoholic liver disease — also noted as a cause of secondary hemosiderosis.
- Blood transfusions — associated with post-transfusion secondary hemochromatosis, for which chelation therapy may be used.
The classic triad of symptoms in the advanced stage is easily remembered by the acronym PCD: Pigmentation of the skin, Cirrhosis of the liver, Diabetes.
Class and exam questions
How to distinguish idiopathic hemochromatosis from secondary siderosis?
Their histological picture is identical. The precise method is the quantitative determination of iron by spectrophotometry during tissue incineration. The criterion for primary hemochromatosis is an iron content above 1.5% of the dry weight of the liver.
What is the essence of the desferrioxamine test?
This is a test for urinary iron excretion. Normally, after intramuscular administration of 0.5 g of desferrioxamine, less than 1.5 mg of iron is excreted per day. In hemochromatosis, this indicator rises to 10 mg.
Why does diabetes mellitus develop in hemochromatosis?
Excess iron is deposited in the pancreas. This leads to interstitial inflammation, proliferation of fibrous tissue, and atrophy of the islet apparatus responsible for insulin production.
What else to study on this topic
- Mechanisms of regulation of iron absorption in the intestine
- Morphological differences between micronodular and macronodular cirrhosis
- Pathogenesis of portal hypertension in cirrhosis
- The relationship between hemochromatosis and the development of hepatocellular carcinoma
- Laboratory indicators of iron metabolism: ferritin and transferrin
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