Lipid metabolism disorders: causes, symptoms, diagnosis, treatment

Hyperlipidemia is found in 10-20% of children and in 40-60% of adults. They can be primary, genetically determined, or develop secondary on the basis of a violation of diet, various diseases leading to metabolic disorders (insulin-dependent diabetes, chronic pancreatitis, alcoholism, cirrhosis, nephrosis, dysglobulinemia, etc.).

The main forms of impaired lipoprotein metabolism:

1. Family lipoproteinemia (genetically determined)
   1. abetalipoproteinemia;
   2. hypobetalipoproteinemia;
   3. anaphylipoproteinemia (Tangier's disease)
2. Primary hyperlipoproteinemia (type IV)
3. Secondary hyperlipoproteinemia
4. Lipidoses
   1. sphingomyelinosis (Niemann-Pick disease);
   2. glucocerebrosidosis (Gaucher's disease);
   3. metachromatic lipodystrophy (sulfatidlididoses);
   4. ceremidrihexidosis (Fabry's disease).

The most important in dermatological practice are primary hyperlipoproteinemia, and from lipidosis - Fabry's 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. This type of lipoproteinemia DS Frederickson and RJ Lewy (1972) is divided into five types.

Hyperlipoproteinemia type I - primary triglyceridemia, or hyperchylomicronemia, is an autosomal recessive disease caused by functional insufficiency or lack of lipoprotein lipase. Occurs rarely, 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 genes encoding receptors for low-density lipoproteins. The clinical picture is most pronounced in homozygotes, usually developing in early childhood, in the form of tuberous, tendon, flat xanthomas, intertriginous xantelasms have a heavier prognosis.

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

Hyperlipoproteinemia type IV can be induced by carbohydrates or familial, inherited autosomal dominant. It is characterized by a significant increase in the level of triglycerides, the presence of eruptive xanthomas.

Hyperlipoproteinemia of type V is characterized by the accumulation in the plasma of chylomicrons and triglycerides. The clinical picture is similar to that of type I hyperlipidemia. The nature of inheritance is unclear, multifactorial nature is not excluded.

With primary hyperlipoproteinemia, deposits in the skin of lipids are found with the formation of various kinds of xanthomas. Lipid deposits cause a small inflammatory reaction and a new formation of collagen fibers.

Distinguish the following forms of xantham: flat (including xantelasm), multiple nodular (eruptive), disseminated, juvenile xanthogranulem, tuberous, tendon.

Plane xanthoma can be limited and common. Limited xanthoma is most often located on the skin of the eyelids (xantelasm) in the form of a flat focus of yellow color, ovoid or ribbon-like outlines. In cases of generalized flat xanthos. 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, accumulations 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 they appear light when stained with hematoxylin and eosin, and when painted with Sudan, they are orange. Xatomic cells usually have one nucleus, but there are also multi-nuclear cells, such as cells of foreign bodies (Tuton cells). Among them may be histiocytes and lymphoid cells. Fibrosis is usually not observed.

Multiple nodular (eruptive) xanthoma is characterized by the precipitation of numerous painless nodules, more often hemispherical, as large as lentils, yellowish or yellowish-orange with an erythema wound around. Perifollicular and follicular xanthomatosis with cystic changes in hair follicles are described.

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

With the eruptive kaantoma, the disseminated xanthoma is similar. The rash is localized predominantly grouped in skin folds, combined with xanthomas of the oral cavity, upper respiratory tract, sclera and cornea, meninges. The question of nosological affiliation is not resolved. It is assumed that the process is a reactive proliferation of a macrophage-histiocyte system of an unknown nature with secondary xantamization. Some authors associate this disease with histiocytosis, in particular with Hend-Schüller-Christen disease.

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

The pathogenesis is unclear. Some authors consider it to be a reactive proliferation of histiocytes, others express an opinion on the nonwoid nature, as well as its proximity to histiocytosis X, but against this evidence of electron microscopy, which did not reveal Lalgertans granules in the cells of juvenile xanthogranulem.

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

Juvenile xanthogranulem is differentiated from the early stages of the Hend-Schüller-Crischen disease, in which massive accumulations of monomorphic histiocytes are revealed, as well as from its granulomatous stage, and dermatofibroma with lipidization. At the latter, there are no eosinophilic granulocytes and giant cells with nuclei arranged in the form of a corolla typical for xanthogranulema.

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

Pathomorphology. In long-term foci, diffuse or focal clusters of xantom cells are found that remove 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 the outbreaks, along with fibrotic changes, deposits of calcium salts are noted.

Tendival xanthomas are dense, slowly growing tumor-like formations, located in the region of tendons attached to the processes of the ulna, patella and calcaneus. In rare cases, tendinous xanthomas are a syndrome of cerebrospecific xanthomatosis, a rare autosomal recessive disease characterized by the accumulation of cholesterol in the main brain, heart, lungs, retina, and others, and the development of neurological and endocrine disorders, changes in the psyche, coronarosclerosis, cataracts, etc.

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

Histologically, concentrically located accumulations of foam cells around the skin nerves are detected.

Histogenesis. At all kinds of xanthom there are accumulations of cells with a foamy cytoplasm containing lipids (sudanophilic inclusions). These cells are macrophages in different stages of development, which is proved by etymological methods. They are rich in hydrolytic enzymes (leucinamine peptidase, nonspecific esterase and acid phosphate), peroxidase activity in them is absent. Due to the deposition of lipoproteins, active macrophages are transformed into foamy cells of various types depending on the stage of their transformation. So, in the first stage of the process, macrophages have not yet been altered, but already loaded with cholesterol and lipids (type 1 cells), in the second stage there appear classical foam cells with small granules and dense nucleus (type II cells), followed by the third stage - the formation of giant foamy cells, in which electron microscopy revealed lysosomes and phagolysosomes, which indicates their functional activity. They synthesize lipoproteins and phospholipids.

Participate in the pathological process and pericyte vessels, from which, perhaps, typical foam cells are formed. Along with the foamy cells, a large number of tissue basophils are detected in the foci. Histochemically, in the xanthoma cells, triglycerides, fatty acids, phospholipids, cholesterol can be identified.

[1], [2], [3], [4]