Lipid metabolism disorders: causes, symptoms, diagnosis, treatment

Hyperlipidemia is found in 10-20% of children and 40-60% of adults. It can be primary, genetically determined, or develop secondarily due to dietary disorders, various diseases leading to metabolic disorders (insulin-dependent diabetes, chronic pancreatitis, alcoholism, liver cirrhosis, nephrosis, dysglobulinemia, etc.).

The main forms of lipoprotein metabolism disorders:

1. Familial lipoproteinemias (genetically determined)
   1. abetalipoproteinemia;
   2. hypobetalipoproteinemia;
   3. analphalipoproteinemia (Tangier disease)
2. Primary hyperlipoproteinemia (types IV)
3. Secondary hyperlipoproteinemia
4. Lipidoses
   1. sphingomyelinosis (Niemann-Pick disease);
   2. glucocerebrosidosis (Gaucher disease);
   3. metachromatic lipodystrophies (sulfatide lipidoses);
   4. ceremitrihexidosis (Fabry disease).

The most important in dermatological practice are primary hyperlipoproteinemias, and of the lipidoses, Fabry disease.

Primary hyperlipoproteinemia, or familial hyperlipoproteinemia, develops as a result of genetic disorders of lipoprotein metabolism, which leads to an increase in the concentration of cholesterol and triglycerides in the blood plasma. DS Frederickson and RJ Lewy (1972) subdivide this type of lipoproteinemia into five types.

Hyperlipoproteinemia type I - primary triglyceridemia, or hyperchylomicronemia, is an autosomal recessive disease caused by functional deficiency or absence of lipoprotein lipase. It is rare and develops in early childhood.

Hyperlipoproteinemia type II is genetically heterogeneous, characterized by an increase in the content of cholesterol II in the blood plasma against the background of a normal level of triglycerides (type IIa) or its increase (type IIb). The primary defect is a mutation of the genes encoding receptors for low-density lipoproteins. The clinical picture is most pronounced in homozygotes, usually develops in early childhood, in the form of tuberous, tendinous, flat xanthomas, intertriginous xanthelasmas have a more severe prognosis.

Hyperlipoproteinemia type III is inherited, apparently, in both autosomal recessive and autosomal dominant patterns. The primary defect is a modification or absence of apoprotein E2. There is a sharp increase in the level of cholesterol and triglycerides in the blood, skin lesions in the form of flat xanthomas of the palms, less often - tuberous, tendinous xanthomas and xanthelasmas.

Hyperlipoproteinemia type IV may be carbohydrate-induced or familial, inherited in an autosomal dominant manner. It is characterized by a significant increase in triglyceride levels and the presence of eruptive xanthomas.

Hyperlipoproteinemia type V is characterized by accumulation of chylomicrons and triglycerides in plasma. The clinical picture is similar to that of hyperlipidemia type I. The nature of inheritance is unclear, a multifactorial nature cannot be ruled out.

In primary hyperlipoproteinemias, lipid deposits are found in the skin with the formation of various types of xanthomas. Lipid deposits cause a slight inflammatory reaction and new formation of collagen fibers.

The following forms of xanthomas are distinguished: flat (including xanthelasma), multiple nodular (eruptive), disseminated, juvenile xanthogranuloma, tuberous, tendinous.

Flat xanthoma may be limited or widespread. Limited xanthoma is most often located on the skin of the eyelids (xanthelasma) in the form of a flat yellow lesion, ovoid or ribbon-like outlines. In cases of generalized flat xanthomas, if hyperlipidemia is not detected, it is necessary to exclude lymphoproliferative diseases, myeloma and other systemic diseases.

Pathomorphology. In the upper parts of the dermis, clusters of foamy cells are found, located both diffusely and in the form of wide strands. Their cytoplasm is filled with birefringent lipids, as a result of which, when stained with hematoxylin and eosin, they look light, and when stained with Sudan, they look orange. Xatom cells usually have one nucleus, but there are also multinuclear cells, such as foreign body cells (Touton cells). Among them, there may be histiocytes and lymphoid cells. Fibrosis is usually not observed.

Multiple nodular (eruptive) xanthoma is characterized by an eruption of numerous painless nodules, usually hemispherical, the size of a lentil, yellowish or yellowish-orange in color with a crown of erythema around it. Perifollicular and follicular xanthomatosis with cystic changes in the hair follicles have been described.

Pathomorphology. In the early stages of development, clusters of xanthomatous cells, histiocytes, and neutrophilic granulocytes are found. Foam cells are rare. Histiocytes contain many fatty acids and triglycerides, and to a lesser extent, cholesterol esters.

Disseminated xanthoma is similar to eruptive keantoma. The rash is localized mainly in groups in skin folds, combined with xanthomas of the oral cavity, upper respiratory tract, sclera and cornea, meninges. The question of nosological affiliation has not been resolved. It is assumed that the process is a reactive proliferation of the macrophage-histiocytic system of unknown origin with secondary xanthemization. Some authors associate this disease with histiocytosis, in particular with Hand-Schüller-Christian disease.

Juvenile xanthogranuloma exists from birth or appears in the first months of life in the form of multiple, usually scattered rashes up to 2 cm in size (rarely larger), of a dense consistency, yellowish or yellow-brown color. In most cases, the process is limited to the skin, but there may also be systemic changes with damage to the spleen, liver, eyes, lungs and blood. It may be combined with neurofibromatosis. The question of the nosological essence of the disease has not been resolved.

The pathogenesis is unclear. Some authors consider it to be a reactive proliferation of histiocytes, others express the opinion about its nevoid nature, as well as its proximity to histiocytosis X, but this is contradicted by electron microscopy data, which did not reveal Lalgertans granules in the cells of juvenile xanthogranuloma.

Pathomorphology. In the early stage, large clusters of histiocytes and macrophages infiltrated with lipids, lymphoid cells and eosinophilic granulocytes are found. Lipids are found among histiocytes and macrophages, as well as in the vacuolated cytoplasm of foam cells. In mature elements, there are foci of granulomatous structure merging with an infiltrate of histiocytes, lymphocytes, eosinophilic granulocytes, foam cells and giant cells of the Touton type. Among them are giant cells, the nuclei of which are arranged in the form of a crown, which is typical for juvenile xanthogranuloma. In old foci, proliferation of fibroblasts and fibrosis are noted.

Juvenile xanthogranuloma is differentiated from the early stages of Hand-Schüller-Christian disease, which shows massive accumulations of monomorphic histiocytes, and from its granulomatous stage, dermatofibroma with lipidation. In the latter, there are no eosinophilic granulocytes and giant cells with nuclei arranged in a corolla typical of xanthogranuloma.

Tuberous xanthomas are fairly large formations, from 1 to 5 cm in size, protruding above the surface of the skin, yellow or orange in color.

Pathomorphology. In long-existing foci, diffuse or focal accumulations of xanthomatous cells are found, removing almost the entire thickness of the dermis. Over time, fibroblasts and newly formed collagen fibers predominate, surrounding groups of foam cells, subsequently completely replacing them. Sometimes, in foci, along with fibrous changes, calcium salt deposits are noted.

Tendon xanthomas are dense, slow-growing tumor-like formations located in the area of tendons attached to the processes of the ulna, patella, and calcaneus. In rare cases, tendon xanthomas are a syndrome of cerebrotendinous xanthomatosis, a rare autosomal recessive disease characterized by the accumulation of cholesterol in the brain, heart, lungs, retina, etc. and the development of neurological and endocrine disorders, mental changes, coronary sclerosis, cataracts, etc.

A very rare variant of xanthomas is the so-called perineural xanthoma, which clinically manifests itself as small, painful, reddish, dense, slightly elevated plaques on the feet, developing in patients with cholecystitis, hepatitis, diabetes mellitus and hyperlipoproteinemia.

Histologically, concentrically arranged clusters of foam cells are found around cutaneous nerves.

Histogenesis. All types of xanthomas have clusters of cells with foamy cytoplasm containing lipids (sudanophilic inclusions). These cells are macrophages in various stages of development, which is proven by etymological methods. They are rich in hydrolytic enzymes (leucine aminopeptidase, nonspecific esterase and acid phosphate), and have no peroxidase activity. Due to the deposition of lipoproteins, active macrophages transform into foam cells of various types depending on the stage of their transformation. Thus, in the first stage of the process, macrophages are not yet changed, but are already loaded with cholesterol and lipids (type 1 cells), in the second stage, classic foam cells with small granules and a dense nucleus appear (type II cells), then comes the third stage - the formation of giant foam cells, in which lysosomes and phagolysosomes were found during electron microscopy, which indicates their functional activity. They synthesize lipoproteins and phospholipids.

Vessel pericytes also participate in the pathological process, from which typical foam cells may be formed. Along with foam cells, a large number of tissue basophils are detected in the foci. Histochemically, triglycerides, fatty acids, phospholipids, and cholesterol can be identified in xanthomatous cells.

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