Incontinence of the pigment (Bloch-Sulzberg melanoblastosis)

Incontinence of the pigment (Bloch-Sulzberg melanoblastosis) is a systemic ectomeodermal disease inherited dominantly, X-linked to the lethal effect for male embryos.

[1], [2]

Causes and pathogenesis of pigment incontinence

Incontinence of the pigment is due to a mutant dominant gene localized in the X chromosome. The gene is flying for a male fetus. Mostly (90-95%) are sick with women, and men's disease is regarded as the result of a spontaneous mutation.

[3], [4], [5]

The histology of Bloch-Sulzberg melanoblastosis

Histologically, for the first stage, the formation of vesicles containing eosinophils is characteristic. In the epidermis between the vesicles, single dysrhythmic cells are noted. In the dermis, infiltrates are found, consisting of lymphocytes and eosinophils. The second stage is characterized by acanthosis, irregularly - papillomatosis and hyperkeratosis, the presence of numerous dyskeratotic cells. In the basal layer - vacuolization of cells and a decrease in the content of melanin in them. In the dermis, the chronic inflammatory infiltrate with a small number of melophophilic pathogens is detected, penetrating in many places into the epidermis. The third stage is characterized by incontinence of the pigment. The penetration of the pigment into the dermis and its accumulation in melanophages are noted.

Pathomorphology of Bloch-Sulzberg melanoblastosis

Morphological changes in the epidermis reflect the stages of the disease. Spongiosis is observed in the 1st stage with the formation of blisters containing neutrophilic and eosinophilic granulocytes, fibrin. Between the blisters there may be discrete cells. In the II stage - hyperkeratosis with a large number of dysrhythmic cells, acanthosis, papillomatosis, vacuolar degeneration of basal epitheliocytes, a large amount of pigment in the basal layer. In the dermis, edema, infiltrates from lymphocytes, histiocytes are noted. Neutrophilic and zosinophilic granulopitites. Verrux cells contain psoriasis acanthosis, hyperkeratosis, focal parakeratosis, in the dermis - infiltrates from lymphocytes, plasma cells, melanophages. As the formation of pigmented spots (III stage), the bubbles disappear, inflammatory changes decrease, in the upper part of the dermis there are many melanophages. In the IV stage, the areas of thinning of the epidermis, focal hyperkeratosis, a decrease in the amount of melanin in the basal layer of the epidermis are revealed, and a small number of melanophages are located in the mesh layer of the dermis. An electron microscope examination of the skin reveals an increase in the activity of melanogenesis in the I-II stages of the process. Melanocytes have many processes, sometimes penetrating the dermis through the basement membrane. In the prickly layer, a second population of melanocytes was identified. In the pigmentation stage, a large number of melanophages loaded with pigment are detected in the dermis, melanocytes are less active, contain autophagosomes. The transport of melanin is disturbed in epithelial cells. In IV stage melanocytes are inactive, they are rounded, without long processes. The number of melanophages and dermis is reduced.

Histogenesis of pigment incontinence

At the heart of the disease is a violation of the synthesis and transport of melanin by melanocytes. At the beginning of the process, melanogenesis is strengthened, in subsequent stages it decreases markedly, and in the fourth stage of the process melanocytes are functionally completely depleted, and the pigment accumulated in the dermis is gradually resorbed. The instability of chromosomes is noted. It is assumed that the gene is localized in the region of Xp11.2. Probably, the disease develops due to deletion. In contrast to the classical variant, the gene responsible for Ito hypomelanosis is located on chromosome 9-9q-33qter. The role of violations of immune tolerance is possible, to which an autoimmune attack on clones of cells of ectodermal origin having anomalous surface antigens occurs, or premature death of defective clones takes place. Chemotaxis of eosinophils in foci and lesions is probably due to the presence of leukotriene B4.

A special variant of pigment incontinence is the pigmented pigmented dermatosis (syn: Frinschetti-Yadassoni syndrome, reticular pigment negelium dermatosis), which manifests itself usually in the 2nd year of life, in persons of both sexes. An autosomal dominant type of transmission is noted. With this variant of the disease without the inflammatory stage, the hyperpigmentation stage begins in the form of a grid or spots located on the skin of the abdomen, neck, chest, in the area of skin folds. Diffuse or punctate keratodermia of the palms and soles is also characteristic. In patients, there were no abnormalities in mental and physical development.

Hito's hypomelanosis (achromatic variant of the disease) occurs in early childhood, characterized by the appearance of foci of skin pigmentation, identical in shape and location to areas of hyperpigmentation with a typical form of pigment incontinence, but without the preceding two stages of the process. Distinguish cutaneous and neurocousing forms, which are inherited by autosomal dominant type. With the cutaneous form, the absence of pigment is observed in childhood. In the neurocortical form, in addition to the pigmentation disorder, neurological disorders (mental retardation, convulsive syndrome) and bone anomalies are noted.

Differential diagnosis is performed with zteropathic acrodermatitis, Verbov syndrome, Albright, hydrototic ectodermal dysplasia, in the first stage - with bullous epidermolysis, herpes, epidemic pemphigus of newborns.

Symptoms of melanoblastosis of Bloch-Sulzberg

The disease develops at the birth of a child or in the first days of life. There are several variants of incontinence of pigment: classical variant of Bloch-Sulzberg, grid pigment Francesket-Yadassona and hypomelanozo Ito. The classical variant is characterized by consistently replacing each other with three stages: bullous (inflammatory), papulo-verruccus and pigmented.

The clinical picture depends on the stage of the process. Initially, from birth or, more rarely, in the first days or weeks of life, there are erythema-vesicular, papuleveziculosis eruptions, located mainly on the lateral surfaces of the trunk and proximal limbs with a tendency to strip-like arrangement (I-II stages). Some of the elements become verruccious. After the regression of the rashes (stage III), pigmentation remains in the form of characteristic "splashes", "twists" and bands. Over time, hyperpigmentation is gradually replaced by a mildly expressed atrophy, sclerosis and depigmentation (stage IV). The stage of the disease is sometimes poorly expressed, at the same time there may be bullous, papular and pigmented foci. Often the III stage appears without previous symptoms. This may be the case if the I and II stages have passed in the prenatal period or have been erased and left unnoticed. In addition to skin changes, various ecto- and mesodermal defects are revealed in most patients: tooth abnormalities, hypotrichosis, nail dystrophy, changes in the eyes, skeleton, CNS. The variants of this disease include bullous keratogenic and pigmentary dermatitis, or Asbo-Hansen syndrome, Negeli net pigment dermatosis , or Franceschetti-Jadasson's syndrome, and the colorless form of pigment incontinence is Ito's syndrome, which is not indisputable. It indicates the existence of transitional forms.

Bullous stage (I) of the disease begins at 1-2 weeks of the child's life and is characterized by the precipitation of vesicles and blisters on the erythematous base, papulo- vesiculosis and urticaria. The process is localized mainly on the limbs, lateral surfaces of the trunk. The rash is linear, symmetrical or grouped. The contents of the bubbles are usually clear, when they are opened and dried, small erosions and crusts are formed. Elements of the rash appear seizures, spreading to new areas of the skin. In most patients, the general condition is usually not disturbed. Eosinophilia is found in the blood.

The papulovirusous stage (II) develops approximately 4-6 weeks after birth and is manifested by the formation of cornificatory, hyperkeratotic papules, pustules, verrux sprouts located linearly in the zone of the former vesicles, or randomly. These skin changes persist for several months. Diffuse hyperkeratosis develops on the palms and soles.

The pigmentary stage (III) usually develops in 3-6 months from the onset of the disease and is characterized by the appearance on the spot of the resolved foci of brownish-yellow spots, hyperpigmentation with lighter edges of irregular contours ("mud splatters"). These branched, linear patterns are located mainly on the skin of the abdomen and, more rarely, of the limbs. Sometimes the papulo-verruccus and pigment stages can be observed simultaneously. With time (15-20 years) at the site of hyperpigmentation, mild atrophy develops, hypopigmentation, singled out by some authors as the fourth - atrophic stage of the disease. At this stage, various exo- and mesodermal changes can occur, ophthalmic pathology (strabismus, nystagmus, cataract, optic nerve atrophy, retinal detachment, keratiges, bluish sclera, anomalies of the iris pigmentation), neurologic changes (seizures, epilepsy, oligophrenia, spastic paralysis type tetra- or paraplegia), diseases of internal organs and the musculoskeletal system, dystrophy of nails and hair.

Treatment of incontinence of pigment

There are no effective methods of therapy. In the first stage, small doses of corticosteroids are recommended. In the stage of verrucous growths, neotigazone is effective. Outwardly used aniline dyes, zpiteliziruyushie, anti-inflammatory drugs and products that improve trophic tissue.