Xeroderma pigmentosum

Xeroderma pigmentosum is an autosomal recessive genetic disorder of DNA repair. The disease is caused by mutations in genes that are involved in the repair of DNA damaged by ultraviolet radiation 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 equal frequency in both sexes, all races and ethnic groups, with a frequency of 1:250,000

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Causes xeroderma pigmentosum

Xeroderma pigmentosum is a hereditary disease, transmitted by an autosomal gene from parents, relatives and has a familial nature. Lunch (1967) in one family of seven brothers and sisters found clinical signs of xeroderma pigmentosum in five of them.

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Pathogenesis

Deficiency of UV endonuclease enzymes in the patient's cells (in fibroblasts) or their complete absence play an important role in the development of the disease. This enzyme is responsible for the reproduction of DNA damaged by ultraviolet rays. According to other sources, deficiency of DNA polymerase-1 enzyme plays an important role in the development of the disease in some patients. The disease most often develops under the influence of rays with a wavelength of 280-310 nm. It is believed that pigment xeroderma develops due to the entry of various photodynamic substances into the body or an increase in porphyrins in the human biological environment.

In the early stages of the disease, hyperkeratosis, atrophy of the epidermis focus, thinning of the Malpighian layer, an increase in melanin granules in the basal layer of cells, and chronic inflammation infiltrate in the upper layer of the dermis (mainly around blood vessels) are observed. Subsequently, degenerative changes are detected in collagen and elastic fibers, and at the tumor stage, signs characteristic of skin cancer are revealed.

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Symptoms xeroderma pigmentosum

Men and women are equally affected by this disease. The disease begins in early childhood in spring or summer. The patient's skin is especially sensitive to sunlight. Therefore, the first rash in the form of hyperpigmentation, similar to a mole, appears on areas of the skin exposed to sunlight. The rash increases, erythema intensifies, becomes dark brown, telangiectasia, angioma and atrophy appear. Subsequently, papillomas and warts grow (mainly on the skin of the face and neck), spots and ulcers appear. As a result of ulcer scarring, the nose becomes thinner ("bird's beak"), the eyelid everts. Papillomas usually develop into malignant tumors. Pigmented xeroderma, as a rule, occurs together with spinocellular cancer, melanosarcomas.

Stages

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

During the inflammatory (erythematous) stage, swelling, red spots, and sometimes blisters and vesicles appear on areas of skin exposed to sunlight (face, neck, upper chest, arms, hands). There is almost no rash on areas not exposed to sunlight.

With hyperpigmentation, light brown, brown hyperpigmented spots similar to moles appear in place of the red spots.

With atrophy, the skin dries out, becomes thinner, and wrinkles. Numerous small, stellate telangiectasias and scars with a shiny surface are observed on the skin of the lips and nose. Due to atrophy and scars, microtomy (reduction of the mouth opening), ectropion, thinning of the ears and nose, atresia of the nasal opening and mouth develop. In 80-85% of patients, the eyes are affected: conjunctivitis, keratitis, damage to the cornea and mucous membrane, and weakening of vision are noted. Dyschromia, telangiectasia, hyperkeratotic changes and tumors are observed on the skin of the eyelids.

With hyperkeratosis, warty tumors, papilloma, keratoacanthoma, fibroma, angiofibrioma and other benign tumors appear in the above-described pathological foci. Therefore, some scientists include pigment xeroderma in the group of precancerous diseases.

After 10-15 years from the onset of the disease, malignant skin tumors (basalioma, endothelioma, angiosarcoma) appear in atrophically altered foci and pigment spots. The tumors are destroyed in a short time, metastasize to internal organs and lead to death. In the internal organs and tissues of some patients, general dystrophic changes are observed (syndactelia of the second and third toes, dental dystrophy, complete hair loss, etc.).

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Forms

The neurological form of xeroderma pigmentosum manifests itself in two syndromes.

Reed syndrome is characterized by clinical manifestations of xeroderma pigmentosum and microcephaly, idiopathy, and slow growth of the skeletal system. In the neurological form of the disease, DNA reparation is difficult and X-ray therapy leads to an increase in the main pathological foci.

De Sinctis-X Cocchione syndrome is characterized by the following clinical signs:

• development of clinical signs of xeroderma pigmentosum on particularly photosensitive skin;
• early appearance of malignant tumors;
• simultaneous course of spastic paralysis, microcephaly and dementia;
• congenital deformities and dwarfism;
• underdevelopment of the gonads;
• frequent miscarriages;
• recessive transmission by inheritance.

According to some dermatologists, Santis-Cacchione syndrome is not an independent disease, but a severe and fully expressed clinical manifestation of xeroderma pigmentosum.

Genetic forms

Types	Gene	Locus	Description
Type A, I, XPA	XPA	9q22.3	Xeroderma pigmentosum (XP) group A – classic 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 Group D or De Sanctis-Cacchione Syndrome
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	RAD2ERCC5	13q33	XP group G and COFS syndrome (cerebro-oculo-facioskeletal syndrome) type 3
Type V, XPV	POLH	6p21.1-p12	Variant Xeroderma Pigmentosa

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Differential diagnosis

The disease should be distinguished from poikiloderma, chronic X-ray dermatitis, spotted scleroderma, urticaria pigmentosa, and Bazin's disease.

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Treatment xeroderma pigmentosum

Antimalarial drugs (delagyl, plaquenil, resoquin, etc.), protecting DNA from ultraviolet rays, inhibit the depolymerization process, reduce the sensitivity (photosensitization) of the skin to sunlight. These drugs have anti-inflammatory and hyposensitizing properties. It is recommended to conduct general therapy together with vitamin therapy (B1, B2, PP, B6, B12, A, E), antihistamines (tavegil, diphenhydramine, suprastin), desensitizing agents (sodium thiosulfate, 10% calcium chloride intravenously 10 ml).

For local treatment, sunscreen creams and ointments are used.

In the tumor form of pigment xeroderma, surgical methods, liquid nitrogen and laser beams are used. To protect yourself from sunlight, you must wear loose clothing, sun hats and gloves.

Forecast

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

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