X-linked recessive ichthyosis
X-linked recessive ichthyosis (synonym: black ichthyosis, ichthyosis nigricans). Occurs at a frequency of 1: 6000 in males, the type of inheritance is recessive, linked to the sex, a complete clinical picture is observed only in males. It can exist from birth, but often appears in the first weeks or months of life. The skin is covered with large, brownish, densely attached thick scales, localized mainly on the front surface of the trunk, head, neck, flexor and extensor surfaces of the extremities. Often, the defeat of the skin is accompanied by opacity of the cornea, hypogonadism, cryptorchidism. Unlike usual ichthyosis, an earlier onset of the disease is noted, there are no changes in the palms and soles, the folds of the skin are affected, the manifestations of the disease are more pronounced on the flexor surfaces of the extremities and on the abdomen. As a rule, there is no follicular keratosis.
X-linked recessive ichthyosis is less common than normal and the manifestations of the disease may be similar to those observed in normal ichthyosis. However, this form of ichthyosis is characterized by a number of distinctive clinical features. Dermatosis begins in the first weeks or months of life, but can exist from birth. The skin is dry, covered with small-lamellar, sometimes larger and thick, closely adhering to the surface, dark brown, up to black scales. The process is localized on the trunk, especially on the extensor surfaces of the limbs. Palms and soles are not affected, follicular hyperkeratosis is absent. There is a clouding of the cornea in 50% of patients and 20% of cryptorchidism.
Pathomorphology. The main histological sign is hyperkeratosis with a normal or slightly thickened granular layer. Horny layer is massive, mesh structure, sometimes thicker than normal in places. The granular layer is represented by 2-4 rows of cells, while electron microscopic examination reveals keratohyalin granules of ordinary size and shape. The number of lamellar granules is reduced. The melanin content in the basal layer is increased. The proliferative activity of the epidermis is not disrupted, the transit time is somewhat increased in comparison with the norm. In the dermis, as a rule, changes are not detected.
Histogenesis. As with the usual form of the disease, retention hyperkeratosis breaks down with X-linked ichthyosis, but its origin is different. The main genetic defect in this form of ichthyosis is a deficiency of sterol sulfatase (steroid sulphatase), whose gene is located in the locus Xp22.3. Steroid sulfatase carries out hydrolysis of sulfur esters of 3-beta-hydroxysteroids, including cholesterol sulphate and steroid hormones. In the epidermis of sulfate cholesterol ,. Produced from cholesterol, is located in the intercellular spaces of the granular layer. Due to the disulfide bridges and the polarization of lipids, it takes part in the stabilization of membranes. Its hydrolysis promotes the removal of the stratum corneum, since the glycosidase and sterol sulfatase contained in this layer participate in intercellular adhesion and desquamation. Obviously, in the absence of sterolsudfatazy, the intercellular bonds are not weakened and retentional hyperkeratosis develops. In this case, a high content of cholesterol sulphate is found in the stratum corneum. The decrease or absence of sterol sulfatase was found in the culture of fibroblasts and epitheliolitis, hair follicles, neurofilamentax and leukocytes in patients. An indirect indicator of their insufficiency is the acceleration of electrophoresis of 3-lipoproteins of the blood plasma. Insufficiency of enzymes is also determined in women who carry the gene. Antenatal diagnosis of this type of ichthyosis is possible by determining the content of estrogens in the urine of pregnant women. Arylsulphatase C of the placenta carries out the hydrolysis of dehydroepiandrosterone sulfate, produced by the adrenal glands of the fetus, which is the precursor of estrogens. In the absence of this enzyme, the content of estrogen in urine decreases. Monitoring the development of births in mothers with hormone deficiency has shown that the ethnic manifestations of X-linked ichthyosis are variable. With the biochemical study of enzymes, the X-linked ichthyosis was diagnosed in some cases in patients with a clinical picture of normal ichthyosis. X-linked ichthyosis may be part of more complex genetically determined syndromes. A case of combining skin lesions typical for X-linked ichthyosis with low growth and mental retardation associated with the Xp22.3-pter translocation of the chromosome segment is described.
Syndromes that include ichthyosis as one of the symptoms include, in particular, the syndromes of Refsum and Podlita.
Refsum's syndrome includes, in addition to skin changes resembling ordinary ichthyosis, cerebellar ataxia, peripheral neuropathy, retinitis pigmentosa, sometimes deafness, changes in the eyes and skeleton. In the histological study, along with the signs of normal ichthyosis, vacuolation of the basal layer of the epidermis is detected, in which Sudan III is found to contain fat.
The basis of histogenesis is a defect, expressed in the inability to oxidize phytic acid. Normally, it is not found in the epidermis, but in the case of the Refsum syndrome it accumulates, constituting a significant part of the lipid fraction of the intercellular substance, which leads to disruption of the adhesion of the horny scales and their peeling and disruption of the formation of metabolites of arachidonic acid, in particular, prostaglandins. Involved in the regulation of the proliferation of the epidermis, resulting in the development of proliferative gynerkeratosis and acanthosis.
Podlita syndrome, in addition to skin changes like ordinary ichthyosis, includes hair abnormalities (twisted hair, knotty trichorexis) with their rarefaction, dystrophic changes in nail plates, dental caries, cataracts, mental and physical underdevelopment. Inherited by autosomal recessive type, the basis of the development of the process is a defect of synthesis, transportation or assimilation of sulfur-containing amino acids. Histological changes are the same as in normal ichthyosis.
Treatment. The general treatment consists in appointing neotigazone in a daily dose of 0.5-1.0 mg / kg or vitamin A in high doses, topically apply emollients and keratolytic agents.
Plate (lamellar) ichthyosis
Plate (lamellar) ichthyosis is a rare serious disease, inherited in most cases by autosomal recessive type. In some patients, a defect of the epidermal transglutaminase was found. Clinical manifestations at birth in the form of a "collodion fetus" or diffuse erythema with lamellar desquamation.
Lamellar (plate) ichthyosis
Lamellar (lamellar) ichthyosis exists from birth, it proceeds heavily. Children are born in the corneous "shell" (collodion fruit) of large, thick, lamellar scales of dark color, separated by deep cracks. Skin and pathological process is widespread and covers the entire skin, including the face, scalp, palms and soles. The majority of patients have a pronounced ectropion, deformity of the ears. On the palms and soles, there is a massive keratosis with cracks, limiting movement of small joints. Dystrophy of nails and nail plates, often as a type of opyhohryphosis, is noted. Sweat and salting are reduced. On the scalp there is pronounced desquamation, the hair is glued together with scales, their thinning is noted. Because of the secondary infection, cicatricial alopecia is observed. Dermatosis can be combined with various developmental anomalies (small growth, deafness, blindness, etc.). The disease lasts a lifetime.
The disease is transmitted autosomal dominantly, can be congenital or begin soon after birth. Men and women get sick the same way. Soon after birth, bubbles appear, opening up, they form erosions, which in turn heal without leaving traces. Then develops the keratinization of the skin right up to the warty layers in the skin folds, the ulnar and popliteal pits. Scales are dark, tightly attached to the skin and usually form a pattern similar to corduroy. The rashes are accompanied by a smell. The repeated appearance of blisters on the keratinized skin, as well as the sloughing of the horny layers, leads to the fact that the skin acquires an absolutely normal appearance. Also there are islets of normal skin in the middle of the keratinization foci - this is a characteristic diagnostic sign. The process is localized only on the skin of the folds, palms and soles. Hair is not changed, it is possible to deform the nails.
Collodion fetus (syn: ichthyosis sebacea, seborrhea squamosa neonatorum) is an expression of various violations of the keratinization process. In most cases (in 60%), the collodion fetus precedes non-bullet recessive ichthyosiform erythroderma. Skin covers of the child at birth are covered with a film of tightly fitting inelastic scales resembling collodions. Under the film, the skin is red, in the area of the folds there are cracks, from which the peeling begins, lasting from the first day of life to 18-60 days. Often there are ectropion, exlabion, changes in the shape of the auricles, the fingers are fixed in a half-bent state with a retracted thumb. In 9.7% of cases, the condition of the collodion fetus is resolved without any consequences.
Described patients who have a normal skin at birth, but in such cases, it is necessary to exclude the X-linked ichthyosis. Usually the entire body, including skin folds, is covered with large, yellowish, sometimes dark, saucer-shaped scales against the background of erythroderma. Almost all patients expressed ectropion, diffuse keratodermia of the palms and soles, marked increase in hair and nails with deformation of the nail plates. Less common are baldness, brachy- and syndactylynia of feet, small growth, deformity and small size of the auricles, cataracts.
Pathomorphology. In the epidermis, moderate acanthosis, papillomatosis (simultaneous growth of papillae of the dermis and epidermis), expansion of epidermal outgrowths and pronounced hyperkeratosis are revealed. The thickness of the stratum corneum exceeds the thickness of the entire epidermis by a factor of 2, normal, in rare cases, focal parakeratosis is observed. The granular layer is mostly unchanged, although sometimes its thickening is observed. In the prickly and basal layers, mitotic activity is increased, associated with increased proliferation of epithelial cells, transit time of which is shortened to 4-5 days. Electron microscopy reveals an increased metabolic activity of epithelial cells, as evidenced by an increase in the number of mitochondria and ribosomes in their cytoplasm. Intracellularly located electron-transparent crystals are found in the stratum corneum, and electron-dense clusters along the cytoplasmic membranes. In some places there are areas of incomplete keratinization with the presence of residues of destroyed organoids and lipid inclusions. Between the horny scales and the granular layer are 1-2 rows of parakeratotic cells. Keratogialine granules are contained in approximately 7 rows of cells, in intercellular spaces - numerous lamellar granules.
Histogenesis. At the heart of the pathological process is the inability of epithelial cells to form a marginal band in the stratum corneum, i.e. The outer membrane of squamous epithelial cells. Electron-transparent crystals, according to L. Kanerva et al. (1983), are cholesterol crystals. Along with the autosomal recessive lamina ichthyosis, an autosomal dominant variant is described, similar in clinical and histological features. However, its distinctive feature is the presence of a wider layer of parakeratotic cells, which indicates a slowing of the keratinization process. The structure of the stratum corneum is not changed.
Treatment. Same as with X-linked ichthyosis.
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Epidermolitic ichthyosis (synonyms: congenital bullous ichthyosiform erythroderma of Broca, ichthyosis bullous, etc.)
Histopathology. In the granular layer, giant granules of keratogialin and vacuolization, cell lysis and the formation of subcorneal multi-chambered blisters, as well as papillomatosis and hyperkeratosis are visible.
Treatment. Same as with other forms of ichthyosis.
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