Ichthyosiform erythroderma: causes, symptoms, diagnosis, treatment

The leading symptom of erythroderma is expressed in this or that degree, against which there is an ecdysis according to the type of ichthyosis. This clinical picture also corresponds to similar histological changes (with the exception of bullous ichthyosiforme): in the form of hyperkeratosis, to varying degrees of acanthosis and inflammatory changes in the dermis.

To ichthyosiform erythrolermia belongs a large group of congenital diseases: congenital bullous ichthyosiform erythroderma, nebulous congenital erythroderma (ichthyosis of the fetus, plate ichthyosis, nebulous congenital ichthyosiform erythroderma, needley ichthyosis).

Histological differences in the skin with most of the diseases listed above are insignificant and sometimes insufficient for diagnosis. Even electron microscopic research often does not give clear results. In connection with this, autoradiography, the determination of the content of certain substances in the stratum corneum (sulfur, cholesterol, n-alkanes, etc.) is also used to diagnose a number of diseases of this group. However, biochemical markers for most diseases of this group have not yet been detected.

Congenital bullous ichthyosiform erythroderma (syn: epidermolitic hyperkeratosis, ichthyosis bullous) is inherited in an autosomal dominant type. Mutations of keratin genes K1 to K10, located respectively in 12q and 17q, were detected. The leading clinical sign is erythroderma ,. Which exists, as a rule, from birth in the form of widespread erythema with the formation on its background of large flaccid blisters that heal without scarring. With age, bubbles do not appear, and hyperkeratosis becomes more pronounced, which makes this form similar in clinical picture to other ichthyosiform erythroderms. A "soft" form of bullous erythroderma without blisters is described. Hyperkeratosis is especially significant in the area of skin folds, often has the appearance of horny scallops. The concentric arrangement of the scallops on the extensor surface of the joints is characteristic. Defeat of the skin can include palmar-plantar keratoderma. Changes on the face are minor, located mainly in the lower part. Hair and nail growth is accelerated

Pathomorphology. Characteristic features of epidermolytic hyperkeratosis, acanthosis, compact lamellar hyperkeratosis, thickening of the granular layer with an increase in the number of granules of keratogialin, vacuolization of the cytoplasm of cells of granular and prickly layers, which can lead to the formation of blisters. The nasal layer, as a rule, is not changed. The mitotic activity of the epidermis is sharply increased, the transit time of epithelial cells is shortened to 4 days. Hyperkeratoe has a proliferative character in contrast to hyperkeratosis in normal and X-linked ichthyoses, in which retention hyperkeratosis is detected. In the upper parts of the dermis - a moderately pronounced inflammatory infiltrate with a predominance of lymphocytes in it. It should be noted that epidermolytic hyperkeratosis is characteristic, but not specific only for bullous erythroderma. So, he meets with palmar-plantar keratoderma Werner, epidermal and hair cysts, epidermal nevuses. Seborrheic and warty keratoses, leukoplakia and leukokeratosis, along the periphery of the centers of squamous cell and basal cell carcinoma.

With electron microscopic examination there is a thickening of the tonofibrillas in the basal and their clomping in the prickly layers of the epidermis. In addition, the cells of granular and prickly layers are observed perinuclear gland, in the zone of which there are no organelles. In the peripheral regions of epithelial cells, there are many ribosomes, mitochondria, tonofibrils and granules of keratogialin. In the cells of the granular layer, the sizes of keratohyalinic phanules are sharply increased, in the intercellular spaces - the number of lamellar granules. Desmosomes look normal, but their connection with tonofilamentami is damaged, as a result of which acantholysis is observed and bubbles are formed.

Histogenesis. At the heart of the development of the disease, as some authors believe, is the incorrect formation of tonofibrils as a result of a disturbance of the interaction of the tonofilament and the interphylactic substance. In connection with the defect of the structure of the tonofibrilles, intercellular bonds are broken, which leads to epidermolysis with the formation of gaps and lacunae. An increase in the number of lamellar granules in the upper layers of the epidermis can lead to an increase in the adhesion of horny flakes. Changes in tonofibrilles in this disease are characteristic, and this sign can be used in antenatal diagnosis. The presence of clots of tonofilament and the absence of complexes of tonofibril-keratogialin granules in the cells of the granular layer distinguish the skin of patients from the skin of healthy fetuses. In the amniotic fluid, epithelial cells with pycnotic nuclei containing tonofilament aggregates are found, which provides an early (14-16 weeks) diagnosis of this disease in the fetuses.

Congenital nebulous ichthyosiform erythroderma. For a long time, the terms "plate ichthyosis" and "congenital non-bulbous ichthyosiform erythroderma" were considered synonymous. However, morphological and biochemical studies have shown that these are different states.

Ichthyosis of the fetus (blue harlequin fruit) is the most severe form of this group of dermatoses, usually incompatible with life. It is inherited by autosomal recessive type. Children without treatment with retinoids usually die in the first days of life.

In surviving patients, the clinical picture acquires the features of lamellar ichthyosis, although the development of dry ichthyosiform erythroderma is also described. From birth, all skin is red, covered with thick, large, dry, yellowish-brown polygonal scales, permeated with deep cracks. There is an ectropion, the mouth does not close, often the deformities of the nose, ears, the outer openings of which are covered with horny masses.

Pathomorphology. A pronounced hyperkeratosis with the formation of horny plugs in the mouths of the hair follicles. The number of rows of horny scales reaches 30 (in the norm of 2-3), they contain a lot of lipids. The granular layer is thickened, the amount of keratogialin granules is increased. At electron microscopic examination the structure of keratogialin granules is not changed. The cell membranes are thickened (premature thickening), in intercellular spaces there are numerous lamellar granules.

Non-bulbous congenital ichthyosiform erythroderma is a rare serious disease inherited by an autosomal recessive type. The onset of the disease from birth in the form of erythroderma or "collodion fetus." The entire skin is affected, although they describe also partial forms with lesion of the flexural surfaces of the extremities and desquamation in certain areas. Against the background of erythema, there is abundant peeling with silvery small scales, with the exception of the skin of the shins, where they are larger. Ectropion develops rarely, the bowl is an underlined tension line between the lower eyelid and upper lip, sometimes baldness is observed. By the period of puberty, there is a decrease in clinical symptoms.

Pathomorphology. Significant acanthosis, follicular hyperkeratosis, uneven thickening of the stratum corneum, focal parakeratosis. The glossy layer is saved. The granular layer consists of 2-3 rows of cells, keratohyalin granules are coarse, large in size. In the mouth of the hair follicles there are discrete cells. Basal layer cells contain a large amount of pigment. In the dermis - the expansion of blood vessels, the presence of perivascular and perifollicular inflammatory infiltrates. Hair follicles and sebaceous glands are atrophic, their number is reduced, the sweat glands are almost unchanged.

Histogenesis. The main biochemical defect in this disease is an increase in the level of n-alkanes - saturated straight-chain hydrocarbons that do not contain reactive groups; n-alkanes are hydrophobic, they indicate the possibility of their influence on the mitotic activity of the epidermis. For example, one of the alkanes (hexadecane - C16-alkane), when applied locally in an animal experiment, caused psoriasiform hyperplasia of the epidermis. It is believed that n-alkanes are responsible for the hardening of the intercellular substance of the stratum corneum and increasing their content leads to brittleness and excessive hardness of the stratum corneum.

Iglisty ichthyosis is inherited autosomally dominant, it occurs quite rarely, its place among other species of ichthyosis is not definitively determined. There are several types of needle ichthyosis; Of these, the types Ollendorf-Kurt-McLean (epidermolytic) and Reidt are most histologically studied. In connection with the rarity of the disease, its clinical picture and pathomorphology have been little studied. Ollendorf-Kurt-McLean type, characterized by the erythema of the face and trunk existing from birth, is more common, against which there are linearly located verruzed eruptions, as well as palmar-plantar keratosis.

Pathomorphology. With needle ichthyosis, such as the Allendorf-Kurt-McLean, pronounced hyperkeratosis, acanthosis, papillomatosis, vacuolization of thorny epithelial cells and intercellular edema are noted. In the epidermolithic type of needley ichthyosis, pronounced vacuolization of cells of prickly and granular layers, pycnosis of nuclei, dyskeratosis with disruption of communication between individual rows of cells of the prickly layer and rejection of this part of the epidermis together with the stratum corneum are observed. The basal layer is not changed. With electron microscopy, L. Kanerva et al. (1984) found perinuclear vacuoles and the peripheral arrangement of tonofibrils in cells of granular and prickly layers. Tonofibrils formed mesh fields or were located perpendicular to the nuclear envelope. O. Braun-Falco et al. (1985) found dense, crustacean masses from the tonofilament in epithelial cells. With needley ichthyosis of the Reidt type, epitheliocytes contain a small number of thin short tonofilamentes without a special disruption in their orientation.

The basis of the histogenesis of this disease is a violation of the synthesis of tonofilament, and, possibly, the inability of the lamellar granules to escape from the epitheliocytes.

Syndromes including ichthyosiform erythroderma are described as one of the symptoms: Sjogren-Larsson syndrome, Tau syndrome, KID syndrome, neutral fat accumulation syndrome, Netherton syndrome, CHILD syndrome, Conradi-Huenermann syndrome, and others.

Sjogren-Larsson's syndrome is characterized by a combination of ichthyosiforme methotredermia with dysplasia of the teeth, retinitis pigmentosa, mental retardation, epilepsy, spastic paralysis (di- and tetraplegia), is inherited by autosomal recessive type. With age, the inflammatory component becomes less noticeable, the skin is dry, rough, the pattern is underlined, resembles the surface of a thin corduroy tissue. In this syndrome, a defect of the enzyme involved in the oxidation of fatty alcohols was revealed, as a consequence of the mutation of the aldehyde dehydrogenase gene. Histological examination of the skin shows changes similar to congenital non-bulbar arrythroderma, however (follicular hyperkeratosis is absent.In biochemical studies in the stratum corneum, a decrease in the content of linoleic acid is evident, apparently as a result of a block of enzymes involved in the formation of unsaturated fatty acids from saturated ones.

Tau syndrome (trichodiodystrophy) includes hair abnormalities such as trichosis and knotty trichorexis, dementia, low growth and skin damage such as ichthyosiform erythroderma. Some patients have increased photosensitivity. It is inherited by autosomal recessive type. There is a decrease in the sulfur content in hair, nail plates and epidermis, which indicates a defect in the metabolism or transport of sulfur.

KID-siidrom (atypical congenital ichthyosiform erythroderma with deafness and keratitis). Symmetric peeling plaques form on the skin of the cheeks, chin, nose and ear shells, keratosis is expressed on the palms and fingers of the hands. Often there are alopecia, knotty trichorexis, dystrophic changes of the nail, chub, pyoderma. Histological changes of the skin are similar to those in congenital non-bulbar ichthyosiform erythroderma. Histochemical examination of the skin in one case revealed glycogen in smooth muscles, vessel walls, nerves and connective tissue cells, however, in this observation, a combination of glycogenase and KID-synlrome is not excluded.

The syndrome of accumulation of neutral fats (Chanarin-Dorfman syndrome) includes a skin lesion of the ichthyosiform erythroderma type. Myopathy, cataract, deafness, CNS damage, fatty liver dystrophy, vacuolization of neutrophilic granulocytes. In the histological examination of the skin, in addition to the signs characteristic of congenital nebulous ichthyosiforme, the lipids in the cells of the banal and granular layers of the epidermis are revealed. Electron microscopy reveals lipid vacuoles in epithelial cells, fibroblasts and myocytes; the structure of the lamellar granules is changed.

The syndrome of Neterton includes a skin lesion in the form of ichthyosiform erythroderma or a linear envelope of the ichthyosis of Komel. Symptoms of atopy (urticaria, angioedema, bronchial asthma, eosinophilia of the blood) and multiple defects in the structure of the hair, of which knotty trichorexis-bamboo hair (trichorrhexis invaginata), alopecia, are the most frequent and diagnostic ones. In some cases, mental retardation and growth impairment are observed. Type of inheritance is autosomal recessive. Histologically, in addition to the picture of congenital nebulous ichthyosiform erythroderma, parakeratosis and vacuolization of basal layer cells are observed. Electron microscopic examination revealed violations of the architectonics of keratin hair (dystrophic keratin), leading to keratomalacia. Disturbances of keratinization are associated with a deficiency of amino acids necessary for this process. In some patients, aminoaciduria, as well as immunity defects, were detected.

CHILD-syndrome - a combination of changes in the skin type of ichthyosoform erythroid with one-sided limb shortening and congenital ectodermal dysplasia. Histologically, in the skin, in addition to the signs of nebulous ichthyosiform erythroderma, the thickening of the granular layer and the presence of a small number of dyseratotic cells in the epidermis are noted.

Skin changes similar to ichthyosiform erythrodermia can be observed in newborns with Conrady-Huenermann syndrome (synovial chondrodysplasia) with a presumed X-linked dominant type of inheritance and a fatal outcome in homozygous male fetuses. In older children, linear and follicular atrophodermia develop, alopecia such as pseudohelps, hair structure abnormalities, eye, cardiovascular, bone defects. Skin changes may also resemble common ichthyosis (the so-called X-spelled dominant ichthyosis). With histological examination in horny plugs. Located in the mouths of hair follicles, calcium is detected. The vacuolization of banal spitelocytes is observed in an ectron-microscopic manner, in the granular layer is the reduction in the number of granules of keratogialin, vacuoles containing crystalline structures.

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