Mesenchymal dysproteinoses of the skin: causes, symptoms, diagnosis, treatment

In mesenchymal dysproteinoses, protein metabolism is disrupted in the connective tissue of the dermis and vessel walls. Metabolic products accumulate, which can enter with the blood or lymph or are formed as a result of incorrect synthesis or disorganization of the main substance of the dermis and its fibrous substances. Mesenchymal dystrophies of the skin include, as in other organs, mucoid swelling, fibrinoid changes, hyalinosis and amyloidosis.

The main protein of connective tissue is collagen, which, along with glycosaminoglycans, is part of collagen, elastic and reticulin fibers, as well as basal membranes. Sometimes mucoid swelling, fibrinoid change and hyalinosis are the result of disorganization of connective tissue, formed with increased tissue-vascular permeability (plasmorrhagia), destruction of connective tissue elements and formation of protein complexes.

Mucoid swelling is a concept first introduced by A.I. Strukov (1961) and is a reversible metabolic disorder of connective tissue consisting of accumulation and redistribution of glycosaminoglycans in the ground substance. Due to the hydrophilicity of glycosaminoglycans, tissue and vascular permeability increases, resulting in the release of plasma proteins (globulins) and glycoproteins, which leads to swelling of the intercellular substance. In this case, the ground substance becomes basophilic, and when stained with toluidine blue, it acquires a pinkish-lilac color (metachromasia). Collagen fibers swell and undergo fraying, which can be accompanied by a cellular reaction in the form of lymphocytic, plasmacytic and histiocytic infiltrates. Mucoid swelling occurs mainly in the walls of arteries, in the dermis in collagen diseases (lupus erythematosus, scleroderma), allergic dermatitis, hypoxia, and thyroid dysfunction.

Fibrinoid swelling of connective tissue is an irreversible metabolic disorder, in which fibrinoid is formed, which is not found in the norm. Fibrinoid-altered areas are sharply eosinophilic, stained yellow by the Van Gieson method, often homogeneous. At the beginning of the process, glycosaminoglycans are detected in these areas, metachromatically stained lilac by toluidine blue, later giving a sharply positive PAS reaction. In the terminal stages (fibrinoid necrosis), destruction of connective tissue occurs with the formation of amorphous detritus. It is pyroninophilic when stained by the Braté method, PAS-positive and diathetase-resistant. Fibrinoid changes in the connective tissue of the dermis develop in allergic vasculitis, sometimes with the formation of fibrinoid in the vascular walls themselves, in rheumatic nodules, in lupus erythematosus, especially in the subepidermal parts of the skin, and in the Arthus phenomenon.

There is no single opinion regarding the composition and origin of fibrinoid. There are fibrinoids of different composition and structure in diseases caused by various pathogenetic factors. Among these factors, SP Lebedev (1982) considers the main ones to be the destruction of collagen fibers, changes in the polysaccharide composition of the main substance of connective tissue and an increase in vascular permeability, which ensures the exudation of high-molecular proteins and glycoproteins of blood plasma. In diseases caused by immune disorders, fibrin formation is associated with immune complex damage to the microcirculatory bed and connective tissue, which is especially pronounced in systemic lupus erythematosus, when the action of immune complexes causes tissue destruction and fibrin insudation. In immune complexes, complement and fibrin predominate, which is why this fibrinoid was named "fibrinoid of immune complexes", "fibrinoid of destruction". Fibrinoid formed as a result of angioneurotic disorders (plasmorrhagia) is called insudation fibrinoid.

Hyalinosis is a dystrophic process that mainly concerns connective tissue and is expressed in the deposition of homogeneous eosinophilic masses of various compositions. Occasionally, the names "colloid", "hyaline or colloid bodies" are used as synonyms.

Hyaline is a fibrillar protein that includes plasma proteins (fibrin). Immunohistochemical methods reveal immune globulins, complement components, and lipids in it. Hyaline is stained in the dermis with acidic dyes (eosin, acid fuchsin), is PAS-positive, and diastasis-resistant. There are three types of hyaline: simple, formed as a result of the release of unchanged blood plasma in angioneurosis; lipohyaline, containing lipoids and beta-lipoproteins (in diabetes mellitus); and complex hyaline, consisting of immune complexes, fibrin, and necrotically altered areas of the vascular wall (for example, in collagen diseases). Hyaline is found in the dermis in hyalinosis of the skin and mucous membranes, porphyria, and cylindroma. In addition to systemic hyalinosis, local hyalinosis occurs as a result of sclerosis in scars, in scarring necrotic tissue. In places of fibrinoid changes.

An example of systemic hyalinosis of the skin is hyalinosis of the skin and mucous membranes (Urbach-Wiethe syndrome), which is an autosomal recessive disease that occurs in the first years of life and is characterized by the deposition of extracellular amorphous masses in the connective tissue of the skin, mucous membranes and internal organs. It is believed that collagen metabolism is primarily disrupted. Skin manifestations consist of the development of densely located yellowish-whitish nodules mainly on the skin of the face (especially the eyelids and lips), fingers, elbow folds, armpits, and knee joints. Due to the nodules, infiltrated foci with a waxy, coarse, sometimes hypertrophic, warty surface appear, resembling acanthosis nigricans. It is possible, especially in early childhood, the appearance of itchy vesicles, blisters, varioliform elements, erosions, ulcerations, leading to smallpox-like scarring, dyschromia. Similar and, as a rule, earlier occurring changes are observed in the oral cavity on the mucous membrane of the cheeks, resembling leukoplakia, or in the form of ulcers with scarring on the tonsils, with periodic inflammatory reactions, including in the form of granulation in the pharynx and larynx. Damage to the latter causes the earliest symptom - hoarseness in infancy. Macroglossia is observed. Other mucous membranes are also affected, hypo- and aplasia of the teeth, especially the upper incisors, slow growth of nails and hair are often encountered.

Pathomorphology. The so-called infiltrative foci show a typical picture of hyalinosis with deposition of homogeneous weakly eosinophilic PAS-positive, diastase-resistant substances in the dermis. These substances are positively stained with Sudan III, shards, Sudan black, and phospholipids are detected in them. In the early stages of the process, homogeneous masses are deposited in the walls of capillaries and in the area of eccrine sweat glands, which then atrophy; in subsequent stages, ribbon-like homogeneous masses appear, in which there may be cracks in places - places of lipid deposition. Similar changes are also observed in clinically unchanged skin, but they are expressed much less strongly. Electron microscopic examination showed that among normal collagen fibers, filaments of various sizes appear, located in an amorphous fine-grained material, closely associated with active fibroblasts producing these masses. In hyalinosis, as a result of transudation, the capillary basement membranes change. They thicken significantly, become multilayered, which is associated with an increase in the amount of collagen types IV and V.

[ 1 ]