Lipidoses: causes, symptoms, diagnosis, treatment

Lipidoses are storage diseases (thesaurismoses), almost always occur with damage to the central nervous system, so they are called neurolipidoses. Skin manifestations are one of the main symptoms only in diffuse angiokeratoma of Fabry (glycosphingolipidosis), in other forms they occur infrequently, possibly due to early death.

Glycocerebrosidosis (Gaucher disease) is a disease based on decreased beta-glucosidase activity; glycocerebrosides accumulate in macrophages (Gaucher cells) of the spleen, bone marrow, lymph nodes, liver, lungs, endocrine glands, neurons of the brain and intramural autonomic ganglia. The disease is inherited in an autosomal recessive manner. There are three clinical variants: I - chronic, II - acute neuropathic (juvenile). III - chronic neuropathic, which are probably caused by different mutations. The main symptoms are hepatosplenomegaly, cerebral dysfunction with seizures, mental retardation, bone damage. Focal or diffuse pigmentation may be observed in the skin, mainly in exposed parts of the body; with splenomegaly - petechiae and ecchymosis. Histologically, an increase in melanin content is detected in the epidermis, and sometimes in the upper part of the dermis.

Niemann-Pick disease is characterized by accumulation of the phospholipid sphingomyelin in neurons and glial cells of the brain and elements of the macrophage-histiocytic system of internal organs. The disease is caused by a defect in sphingomyelinase activity and is inherited in an autosomal recessive manner. The skin is yellowish-brown due to increased melanin content, and xanthomas may be observed. Histologically, in some cases, the amount of pigment in the epidermis increases and individual xanthomatous cells are determined in the dermis.

Angiokeratoma corporis diffuse (Anderson-Fabry disease) is caused by alpha-galactosidase deficiency. W. Epinette et al. (1973) associate it with a decrease in the activity of a-L-fucosidase. Cases of Fabry disease with normal enzyme activity have been described, indicating genetic heterogeneity of the disease. It is inherited recessively, linked to the X chromosome. The clinical manifestations are based on the deposition of lipids in endothelial cells and pericytes of blood vessels, smooth muscle cells, ganglion cells, nerves, corneal epithelium, kidneys, and skin. The skin lesion is characterized by the appearance in childhood or adolescence of numerous small (1-2 mm in diameter) dark red angiokeratomas, mainly on the lower part of the trunk, genitals, thighs, buttocks, almost exclusively in men. Heterozygous women may have changes in the kidneys and eyes, and very rarely in the skin. The prognosis is unfavorable, since renal failure, myocardial infarction, or stroke develop in middle age (40 years).

Pathomorphology. A sharp dilation of the capillaries of the papillary layer of the skin is detected, the walls of which are formed by a single layer of endothelial cells surrounded by loose strands of connective tissue. Epidermal processes and hair follicles undergo atrophy from pressure. Dilated and blood-filled capillaries are sometimes closely adjacent to each other, forming multi-chamber cavities, between which long narrow epidermal outgrowths can be seen.

The upper part undergoes atrophy, sometimes minor vacuolization of the cells of the basal layer of the epidermis is noted. Hyperkeratosis is often very strong, with parakeratosis phenomena, especially when the capillaries of not only the papillary but also the reticular layers of the dermis are affected. Lipids are detected using specific staining methods.

Special fixation of skin biopsies in 1% calcium chloride solution with 10% formalin is required, or the preparations are kept in 10% formalin for 2 days, then in 3% potassium dichromate solution for up to 1 week. After fixation, they are stained using the Tarnovsky method. Lipids are well detected by Sudan Black B and Scarlet. They are birefringent, so they are visible in a polarizing microscope.

Lipids are found not only in angiomatously altered vessels, but also in clinically unchanged skin, fibroblasts, and muscles that raise hair. Lipid deposits are detected by electron microscopy in endotheliocytes, pericytes, and fibroblasts inside large lysosomes in the form of two types of intracellular inclusions surrounded by a double-contour membrane and having a lamellar structure. Lysosomes consist of alternating electron-dense and light bands. Phosphatase activity is detected in most of them, and myelin structures are found in residual bodies.

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