Elastic pseudoksantom: causes, symptoms, diagnosis, treatment

Elastic pseudoksantom (syn.: Grenblad-Strandberg syndrome, Touraine's systematized elastorexis) is a relatively rare systemic disease of the connective tissue with a predominant lesion of the skin, eyes, and cardiovascular system. Genetic disease is heterogeneous, includes the dominant and recessive forms. The existence of an acquired elastic pseudoxantomy requires proof.

[1]

Pathogenesis

Changes are detected mainly in the middle and lower parts of the dermis, where elastic fibers are unevenly distributed, thickened, fragmented in the form of lumps, lumps, peculiar twisting beams or granular structures. When stained with hematoxylin and eosin, the accumulation of elastic fibers appear as basophilic masses with fuzzy contours. By the Kossa method, calcium salts are detected in them. Near the modified elastic fibers are clusters of slightly basophilic substances, staining with colloidal iron or alcyanone blue. Collagen fibers are arranged randomly, a large amount of argyrophil fibers is determined. There are giant cells of foreign bodies. A. Vogel et al. (1985) believe that on the basis of histological examination it is possible to distinguish the dominant form of this disease from the recessive one. For the recessive form is characterized by the presence of dark red elastin when stained with methylene blue and para-fuxin. In the circumference of such areas, the main substance is colored diffusely blue, the number of cellular elements is increased. In all cases, calcium is detected. The dominant type is not characterized by the deposition of calcium salts, elastic fibers form an anastomosing network, separated by dense bundles of collagen fibers. Elastic fibers are unevenly thickened, and only in some places they are thinned or revealed in the form of granules. GE Pierard (1984), however, noted no differences in the morphological picture between the dominant and recessive forms of this disease. When electron microscopic examination of the structure of the connective tissue of the papillary and the upper part of the reticular layer of the dermis, as a rule, is not broken. The changes mainly concern the middle and lower parts of the net layer. Elastic fibers contain calcium salts in the form of small electron-dense clusters of various sizes and shapes or thin, like needles, crystals. Granular clusters surrounded by an electron-dense ring of crystalline structures are also described. The fact that such deposits are calcium salts is confirmed by scanning electron microscopy using an x-ray microanalyzer. Calcium salts also contain surrounding macrophages, which indicates the development of foreign body reaction. In addition, in elastic fibers, dystrophic changes in the amorphous part are observed in the form of enlightenment and matrix dissolution, sometimes the presence of vacuoles of various sizes with massive deposition of calcium salts. Similar changes were also found with those in the elastic fibers of senile skin. Observed changes in collagen fibers. A decrease in their number is noted, most of the fibers are not changed, some of them are thickened (up to 700 nm), split into smaller ones, twisted, but with preservation of the periodicity of transverse striation. The simultaneous damage of elastic and collagen fibers can be explained by the participation in their biosynthesis of some common enzymes, the same microenvironment, in which the extracellular stages of their biosynthesis occur.

In the vicinity of collagen and elastic fibers, friable or compact masses of granular and filamentous substance are found, in which electron-dense accumulations of calcium salts and microfibrils with a thickness of 4-10 nm are sometimes visible. There are activated fibroblasts, near the calcified elastic fibers, they are in a state of destruction. In the recessive form, dystrophic changes and calcification are more pronounced than in the dominant form. In the latter case, branching and anastomosing are observed between them with no signs of calcification. Collagen fibers of different diameters, but they are thinner than with a recessive form.

Changes in the structure of elastic and collagen fibers are observed not only in the skin of patients, but also in the mucous membranes of the oral cavity, as well as in the arteries of the stomach, which indicates the systemic nature of the lesion of fibrous connective tissue in this disease. Dystrophic changes, an increase in the number of cytoplasmic processes, a pronounced vacuolization of the cytoplasm of endotheliocytes, and breaks in the basement membrane are detected in small vessels. In the internal elastic membrane there are deposits of calcium salts, changes in elastic fibers, similar to those in the skin. Such changes lead to circulatory disorders, the formation of aneurysms and bleeding.

In the histogenesis of elastic pseudoxanthomas, some authors take the leading role in the deposition of calcium salts in elastic fibers, possibly as a result of the accumulation of calcification inducing polyanions in them. Others believe that calcification causes accumulations of glycosaminoglycans in lesions. Others attach importance not so much to calcification, as to structural anomalies of collagen and elastic fibers associated with a defect in their synthesis. It is assumed that the inability of elastin to the formation of cross-links, or disruption of the process of oxidative deamination, which occurs extracellularly, leads to a violation of elastogenesis. At the same time, large amounts of proteases secreted by fibroblasts can remove areas with hydrophobic amino acids from elastin molecules and destroy cross-links. Histologically, transepidermal excretion of modified elastic fibers can be detected, which, according to WK Jacyk and W. Lechiner (1980), distinguishes the acquired form from the inherited one. It is possible that with different forms of elastic pseudoxantomy structural disorders develop in different ways. The end result of both processes is the same.

The clinical picture of skin lesions with acquired elastic pseudoxantom is similar to hereditary. Periumbilical forms that appear in women are distinguished, in the pathogenesis of which an important role is given to a significant stretching of the abdominal skin as a result of repeated pregnancies or anasarca.

It should be emphasized that in all forms of the disease the rash is localized in places most prone to stretching. With the acquired form of symptoms of damage to the blood vessels, eyes or the digestive tract, as a rule, they are not found. The occurrence of an acquired elastic pseudoxantomy in a patient with chronic renal failure during hemodialysis is described, when conditions for the calcification of elastic fibers can be created due to a violation of the metabolism of calcium and phosphorus.

[2], [3], [4], [5], [6], [7]

Symptoms of the elastic pseudoxantomy

It is clinically manifested as flat, yellowish, grouped papules 1-3 mm in size, often located along the skin lines on the lateral surfaces of the neck, nape, in the axillary and inguinal regions, on the stomach, in the popliteal fossae, on the elbows. The surface of the papules is smooth, the skin in places where the rash is located is loose, often forms folds, which makes it indistinguishable from sluggish skin. Mucous membranes may be affected. Eye changes consist in slowly progressing dystrophic changes in the fundus resulting from the divergence and rupture of the basal lamina (Bruch elastic membrane), localized between the choroid and retina. This leads to the formation of so-called angioid bands. They are detected when examining the fundus in the form of jagged lines or pigmentation bands. Angioid bands are not specific for elastic pseudoxantoms, they are also found in  Chernogubov-Eders-Danlos syndrome, Paget's disease,  Marfan syndrome,  and  sickle cell anemia. They may be the only sign of an elastic pseudoxantomy for many years. Angioid bands are often combined with hemorrhages under the retina and choroid, as well as retinal detachment. In 50% of patients, point changes are noted, leading to a significant reduction in vision. Damages of the cardiovascular system are characterized by hypertension and coronary insufficiency, early atherosclerosis, and a tendency to hemorrhages. In the same family, sibs can have mono-, di-, and three-symptom forms of the disease. The severity of skin and eye symptoms varies considerably.

[8], [9], [10]

Treatment of the elastic pseudoxantomy

Currently, no effective specific treatment has been developed for elastic pseudoxantomy. In stage I of the ophthalmologic lesion, observation is prescribed, it is recommended to avoid the slightest injury to the eyes and wear protective goggles during work and sports. Significant difficulties are the treatment of stage II. There are works on the use of coagulation of angioid bands, tending to the macular zone. Intravitreal injections of monoclonal antibodies that block angiogenesis (for example, bevacizumab) are promising for the treatment of retinal angioid bands. However, reliable data on the effectiveness of this method of treatment is not received. In stage III treatment is ineffective. The goal of therapy is to prevent complications.