Pigmented xeroderma

Pigment xeroderma is an autosomal recessive genetic disorder of DNA repair. The disease is based on mutations in genes that are involved in the repair of damaged DNA under the influence of ultraviolet and other toxic substances.

Most often, this disease affects children, who are also called "children of the night." Frequent complications of the disease are basal cell carcinoma and other malignant neoplasms of the skin, metastatic malignant melanoma and squamous cell carcinoma.

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Epidemiology

The disease occurs with the same frequency in both sexes, all races and ethnic groups, with a frequency of 1: 250000

[2], [3], [4]

Causes of the pigmentary xeroderma

Pigment xeroderma is a hereditary disease transmitted by an autosomal gene inherited from parents and relatives and has a family character. Lunch (1967) in a family of seven brothers and sisters in five revealed the presence of clinical signs of pigment xeroderma.

[5], [6], [7], [8]

Pathogenesis

In the emergence of the disease, an important role is played by the deficiency of enzymes of the UV endonuclease in the cells of the patient (in fibroblasts) or its complete absence. This enzyme is responsible for the reproduction of DNA, affected by ultraviolet rays. According to other information, in some patients, the lack of DNA-polymerase-1 enzyme plays an important role in the onset of the disease. The disease most often develops under the influence of rays having a wavelength of 280-310 nm. The opinion is expressed that pigmentary xeroderma develops due to ingestion of various photodynamic substances or porphyrins in the human biological environment.

In the early period of the disease, hyperkeratosis, atrophy of the epidermal focus, refinement of the malpighian layer, increase in melanin granules in the basal layer of cells, infiltration of chronic inflammation on the upper layer of the dermis (mainly around the blood vessels) are observed. Later, collagen and elastic fibers reveal degenerative changes, and at the stage of tumors - signs characteristic of skin cancer.

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Symptoms of the pigmentary xeroderma

Men and women are affected by this disease in the same way. The disease begins with the earliest childhood in spring or summer. In this case, the patient's skin is especially sensitive to sunlight. Therefore, the first rash in the form of hyperpigmentation, similar to a mole, appears on the skin areas affected by sunlight. The rash increases, erythema intensifies, becomes dark brown, there is telangiectasia, angioma and atrophy. In the subsequent growth of papilloma and warts (mainly on the skin of the face, neck), the appearance of spots and ulcers. As a result of scarring of ulcers, the nose becomes thinner (the "bird's beak"), the eye lid turns out. Usually papillomas turn into malignant tumors. Pigment xeroderma, as a rule, occurs together with spinal-cell carcinoma, melanosarcomas.

Stages

In the clinical course of pigmentary xeroderma, five stages are distinguished: inflammatory (erythematous), hyperpigmentation, atrophy, hyperkeratosis and malignant tumors.

In the inflammatory (erythematous) stage, swelling, red spots, and sometimes bubbles and vesicles appear on skin areas exposed to sunlight (face, neck, upper chest, hands, hands). In areas that are not exposed to sunlight, there is almost no rash.

When hyperpigmentation in place of red spots appear similar to birthmarks light brown, brown hyperpigmentation spots.

With atrophy, the skin dries out, thinens, wrinkles. On the skin of the lips and nose there are many small, star-shaped telangiectasias, scars with a shiny surface. Due to atrophy and scars, a microtomy develops (a decrease in the mouth opening), an ectopion, a thinning of the ears and nose, an atresia of the opening of the nose and mouth. In 80-85% of patients, the eyes are affected: conjunctivitis, keratitis develop, horn and mucous membrane damage, weakening of vision. Dyschromia, telangiectasia, hyperkeratotic changes and tumors are observed on the skin of the eye lids.

In hyperkeratosis, wart tumor, papilloma, keratoacanthoma, fibroma, angiofibrioma and other benign tumors appear in the above pathological foci. Therefore, some scientists include pigmentary xeroderma in the group of precancerous diseases.

After 10-15 years from the onset of the disease, malignant skin tumors (basal cell, endothelioma, angiosarcoma) appear in atrophically altered foci and pigmented spots. Tumors in a short time are destroyed, give metastases to internal organs and lead to death. In the internal organs and tissues of some patients, general dystrophic changes are observed (syndeclium II, third toe, dystrophy of the teeth, complete hair loss, etc.).

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Forms

The neurological form of pigmentary xeroderma is manifested by two syndromes.

In the syndrome, clinical manifestations of pigmentary xeroderma and microcephaly, idiopathy, a slowdown in the growth of the skeleton are observed. With a neurological form of the disease, DNA repair is difficult and x-ray therapy leads to an increase in the main pathological foci.

The syndrome of Sanctis-Kakkione (De Sinctis-X Cocchione) is manifested by the following clinical signs:

• development of clinical signs of pigmentary xeroderma on especially photosensitive skin;
• early appearance of malignant tumors;
• simultaneous course of spastic paralysis, microcephaly and dementia;
• congenital deformations and dwarfism;
• underdevelopment of gonads;
• frequent miscarriages;
• recessive transfer by inheritance.

According to some dermatologists, Santis-Kakkione syndrome is not an independent disease, but a severe and completely pronounced clinical manifestation of pigmentary xeroderma.

Genetic forms

Types	Gene	Locus	Description
Type A, I, XPA	XPA	9q22.3	Pigment xeroderm (XP) of group A - classical form
Type B, II, XPB	XPB	2q21	XP group B
Type C, III, XPC	XPC	3p25	XP Group C
Type D, IV, XPD	XPD ERCC6	19q13.2-q13.3, 10q11	XP of group D or Syndrome De Sanctis - Kakkione
Type E, V, XPE	DDB2	11p12-p11	XP Group E
Type F, VI, XPF	ERCC4	16p13.3-p13.13	XP group F
Type G, VII, XPG	RAD2 ERCC5	13q33	XP group G and COFS-syndrome (cerebro-oculo-facial-skeletal syndrome) of type 3
Type V, XPV	POLH	6p21.1-p12	Variant Pigment Xeroderma

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Differential diagnosis

The disease should be distinguished from poikiloderma, chronic x-ray dermatitis, spotted scleroderma, pigmentary urticaria, Bazin's disease.

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Treatment of the pigmentary xeroderma

Antimalarial drugs (delagil, plakvenil, resohin, etc.), protecting DNA from ultraviolet rays, inhibit the process of depolymerization, weaken the sensitivity (photosensitization) of the skin to the sun's rays. These drugs have anti-inflammatory and hyposensitizing properties. It is recommended to carry out general therapy together with vitamin therapy (B1, B2, PP, B6, B12, A, E), antihistamines (tavegil, dimedrol, suprastin), desensitizing agents (sodium thiosulfate, 10% calcium chloride 10 ml ).

As a local treatment, photoprotective creams and ointments are used.

In the tumor form of pigmentary xeroderma, the surgical method, liquid nitrogen and laser beams are used. To protect from sunlight, you must wear loose clothing, panamas and gloves.

Forecast

The majority of patients (2/3) die before reaching the age of 15. Some patients can live up to 40-50 years.

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