Ichthyosiform erythroderma: causes, symptoms, diagnosis, treatment

The leading symptom of erythroderma is expressed to one degree or another, against the background of which there is peeling of the ichthyosis type. Similar histological changes (except for bullous ichthyosiform erythroderma) correspond to this clinical picture: in the form of hyperkeratosis, acanthosis expressed to varying degrees and inflammatory changes in the dermis.

Ichthyosiform erythroderma includes a large group of congenital diseases: congenital bullous ichthyosiform erythroderma, non-bullous congenital erythroderma (ichthyosis fetalis, lamellar ichthyosis, non-bullous congenital ichthyosiform erythroderma, acicular ichthyosis).

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

Congenital bullous ichthyosiform erythroderma (syn.: epidermolytic hyperkeratosis, bullous ichthyosis) is inherited in an autosomal dominant manner. Mutations of the keratin genes K1 to K10, located in 12q and 17q, respectively, have been detected. The leading clinical sign is erythroderma, which usually exists from birth in the form of widespread erythema with the formation of large flaccid blisters against its background, healing without scarring. With age, blisters do not appear, and hyperkeratosis becomes more pronounced, which makes this form similar in clinical picture to other ichthyosiform erythrodermas. A "soft" form of bullous erythroderma without blisters has been described. Hyperkeratosis is especially significant in the area of skin folds, often has the appearance of horny ridges. Concentric arrangement of ridges on the extensor surface of the joints is characteristic. Skin lesions may include palmoplantar keratoderma. Changes on the face are minor, located mainly in the lower part. Hair and nail growth is accelerated

Pathomorphology. Characteristic signs of epidermolytic hyperkeratosis, acanthosis, compact lamellar hyperkeratosis, thickening of the granular layer with an increase in the number of keratohyalin granules, vacuolization of the cytoplasm of the cells of the granular and spinous layers, which can lead to the formation of blisters. The nasal layer, as a rule, is unchanged. Mitotic activity of the epidermis is sharply increased, the transit time of epithelial cells is shortened to 4 days. Hyperkeratoe has a proliferative character, unlike hyperkeratosis in usual and X-linked ichthyosis, in which retention hyperkeratosis is detected. In the upper parts of the dermis - moderate inflammatory infiltrate with a predominance of lymphocytes. It should be noted that epidermolytic hyperkeratosis is a characteristic, but not specific only for bullous erythroderma sign. Thus, it is found in Werner's palmoplantar keratoderma, epidermal and pilar cysts, epidermal nevi, seborrheic and warty keratoses, leukoplakia and leukokeratosis, on the periphery of foci of squamous cell and basal cell cancer.

Electron microscopic examination reveals thickening of tonofibrils in the basal layer and their lump formation in the spinous layer of the epidermis. In addition, perinuclear edema is observed in the cells of the granular and spinous layers, in the zone of which organelles are absent. In the peripheral sections of the epithelial cells, there are many ribosomes, mitochondria, tonofibrils and keratohyalin granules. In the cells of the granular layer, the size of keratohyalin fanules is sharply increased, and in the intercellular spaces, the number of lamellar granules. Desmosomes appear normal, but their connection with the tonofilaments is damaged, resulting in acantholysis and the formation of blisters.

Histogenesis. According to some authors, the development of the disease is based on abnormal formation of tonofibrils as a result of disruption of the interaction of tonofilaments and interfilamentous substance. Due to the defect in the structure of tonofibrils, intercellular connections are disrupted, which leads to epidermolysis with the formation of cracks and lacunae. An increase in the number of lamellar granules in the upper layers of the epidermis can lead to increased adhesion of horny scales. Changes in tonofibrils are characteristic of this disease, and this sign can be used in antenatal diagnostics. The presence of tonofilament lumps and the absence of tonofibril-keratohyalin granule complexes in the cells of the granular layer distinguish the skin of patients from the skin of healthy fetuses. Epithelial cells with pycnotic nuclei containing tonofilament aggregates are found in the amniotic fluid, which ensures early (14-16 weeks) diagnostics of this disease in fetuses.

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

Ichthyosis fetalis (syn. harlequin fetus) is the most severe form of this group of dermatoses, usually incompatible with life. It is inherited in an autosomal recessive manner. Children without retinoid treatment usually die in the first days of life.

In surviving patients, the clinical picture acquires features of lamellar ichthyosis, although the development of dry ichthyosiform erythroderma has also been described. From birth, the entire skin is red, covered with thick, large, dry, yellowish-brown polygonal scales, penetrated by deep cracks. There is ectropion, the mouth does not close, deformations of the nose and ears are common, the external openings of which are closed by horny masses.

Pathomorphology. Pronounced hyperkeratosis with formation of horny plugs in the mouths of hair follicles. The number of rows of horny scales reaches 30 (normally 2-3), they contain many lipids. The granular layer is thickened, the number of keratohyalin granules is increased. Electron microscopic examination shows that the structure of keratohyalin granules is unchanged. Cell membranes are thickened (premature thickening), the intercellular spaces contain numerous lamellar granules.

Non-bullous congenital ichthyosiform erythroderma is a rare, severe disease inherited in an autosomal recessive manner. The disease begins at birth as erythroderma or "collodion fetus". The entire skin is affected, although partial forms with lesions of the flexor surfaces of the extremities and peeling in certain areas are also described. Against the background of erythema, abundant peeling with silvery small scales is noted, with the exception of the skin of the shins, where they are larger. Ectropion rarely develops, more often - an emphasized tension line between the lower eyelid and upper lip, sometimes baldness is observed. By puberty, a decrease in clinical symptoms is noted.

Pathomorphology. Significant acanthosis, follicular hyperkeratosis, uneven thickening of the stratum corneum, focal parakeratosis. The stratum lucidum is preserved. The granular layer consists of 2-3 rows of cells, keratohyaline granules are coarse and large. Dyskeratotic cells are found in the mouths of hair follicles. The cells of the basal layer contain a large amount of pigment. In the dermis, there is vasodilation, perivascular and perifollicular inflammatory infiltrates. Hair follicles and sebaceous glands are atrophic, their number is reduced, sweat glands are almost unchanged.

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

Spiny ichthyosis is inherited in an autosomal dominant manner, is quite rare, and its place among other types of ichthyosis has not been definitively determined. There are several types of spiny ichthyosis; of these, the most studied histologically are the Ollendorff-Kurt-McLean (epidermolytic) and Reydt types. Due to the rarity of the disease, its clinical picture and pathomorphology have been little studied. The Ollendorff-Kurt-McLean type is more common, characterized by erythema of the face and trunk, present from birth, against the background of which there are linear warty rashes, as well as palmar-plantar keratosis.

Pathomorphology. In the Ollendorff-Kurt-McLean type of prickly ichthyosis, pronounced hyperkeratosis, acanthosis, papillomatosis, vacuolation of spinous epithelial cells, and intercellular edema are observed. In the epidermolytic type of prickly ichthyosis, pronounced vacuolation of the cells of the spinous and granular layers, pycnosis of the nuclei, dyskeratosis with disruption of the connection between individual rows of cells of the spinous layer and rejection of this part of the epidermis together with the stratum corneum are observed. The basal layer is not changed. In an electron microscopic study, L. Kanerva et al. (1984) found perinuclear vacuoles and a peripheral arrangement of tonofibrils in the cells of the granular and spinous layers. The tonofibrils formed reticular fields or were located perpendicular to the nuclear membrane. O. Braun-Falco et al. (1985) found dense, lumpy masses of tonofilaments in epithelial cells. In Reydt type ichthyosis, epithelial cells contain a small number of thin, short tonofilaments without any significant disturbance of their orientation.

The histogenesis of this disease is based on a disruption in the synthesis of tonofilaments, and also, possibly, the inability of lamellar granules to exit the epithelial cells.

Syndromes that include ichthyosiform erythroderma as one of the symptoms have been described: Sjogren-Larsson syndrome, Tau syndrome, KID syndrome, neutral fat accumulation syndrome, Netherton syndrome, CHILD syndrome, Conradi-Hünermann syndrome, etc.

Sjogren-Larsson syndrome is characterized by a combination of ichthyosiform erythroderma with dental dysplasia, retinitis pigmentosa, mental retardation, epilepsy, spastic paralysis (di- and tetraplegia), and is inherited in an autosomal recessive manner. With age, the inflammatory component becomes barely noticeable, the skin is dry, rough, its pattern is emphasized, resembling the surface of thin velveteen fabric. In this syndrome, a defect in the enzyme involved in the oxidation of fatty alcohols has been identified, as a consequence of a mutation in the aldehyde dehydrogenase gene. Histological examination of the skin reveals changes similar to congenital non-bullous erythroderma, however (follicular hyperkeratosis is absent). Biochemical examination of the stratum corneum reveals a decrease in the content of linoleic acid, apparently as a result of a block of enzymes involved in the formation of unsaturated fatty acids from saturated ones.

Tau syndrome (trichothiodystrophy) includes hair abnormalities such as trichoschisis and nodular trichorrhexis, dementia, short stature, and skin lesions such as ichthyosiform erythroderma. Some patients have increased photosensitivity. It is inherited in an autosomal recessive manner. There is a decrease in the sulfur content of the hair, nail plates, and epidermis, indicating a defect in sulfur metabolism or transport.

KID syndrome (atypical congenital ichthyosiform erythroderma with deafness and keratitis). Symmetrical scaly plaques form on the skin of the cheeks, chin, nose and auricles, keratosis is expressed on the palms and fingers. Alopecia, nodular trichorrhexis, dystrophic changes in the nails, forelocks, pyoderma are common. Histological changes in the skin are similar to those in congenital non-bullous ichthyosiform erythroderma. Histochemical examination of the skin in one case revealed glycogen in smooth muscles, vascular walls, nerves and connective tissue cells, however, in this observation, a combination of glycogenosis and KID syndrome cannot be ruled out.

Neutral lipid accumulation syndrome (Chanarin-Dorfman syndrome) includes skin lesions of the ichthyosiform erythroderma type. myopathy, cataract, deafness, CNS lesions, fatty liver disease, vacuolization of neutrophilic granulocytes. Histological examination of the skin, in addition to the signs characteristic of congenital non-bullous ichthyosiform erythroderma, reveals lipids in the cells of the banal and granular layers of the epidermis. Electron microscopy reveals lipid vacuoles in epithelial cells, fibroblasts and myocytes; the structure of lamellar granules is altered.

Netherton syndrome includes skin lesions in the form of ichthyosiform erythroderma or linear circumflex ichthyosis of Komel. Symptoms of atopy (urticaria, angioedema, bronchial asthma, blood eosinophilia) and multiple hair defects, of which the most common and diagnostically significant are nodular trichorrhexis - bamboo-like hair (trichorrhexis invaginata), alopecia. In some cases, mental retardation and growth disorders are observed. The inheritance type is autosomal recessive. Histologically, in addition to the picture of congenital non-bullous ichthyosiform erythroderma, parakeratosis and vacuolization of basal layer cells are observed. Electron microscopic examination revealed disturbances in the architectonics of hair keratin (dystrophic keratin), leading to keratomalacia. Keratinization disorders are associated with a deficiency of amino acids necessary for this process. Aminoaciduria and immune defects have been found in some patients.

CHILD syndrome is a combination of skin changes of the ichthyosiform erythroderma type with unilateral shortening of the limbs and congenital ectodermal dysplasia. Histologically, in the skin, in addition to signs of non-bullous ichthyosiform erythroderma, thickening of the granular layer and the presence of a small number of dyskeratotic cells in the epidermis are noted.

Skin changes similar to ichthyosiform erythroderma may be observed in newborns with Conradi-Hünermann syndrome (syn. punctate chondrodysplasia) with a presumed X-linked dominant type of inheritance and a lethal outcome in homozygous male fetuses. In older children, linear and follicular atrophoderma, pseudopelade type alopecia, hair structure anomalies, eye, cardiovascular, bone defects develop. Skin changes may also resemble common ichthyosis (the so-called X-linked dominant ichthyosis). Histological examination reveals calcium in the horny plugs located at the mouths of hair follicles. Electron microscopy reveals vacuolization of common epithelial cells, in the granular layer - a decrease in the number of keratohyalin granules, vacuoles containing crystalline structures.

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