Symptoms of Xeroderma pigmentosum

An increased light sensitivity is usually already noticeable in toddlers. Even a short stay in the sun can lead to sunburn, which can last for weeks as an inflammatory redness (erythema). After months or a few years, chronic light damage occurs on skin areas exposed to the sun: light or dark spots (de- or hyperpigmentation), dry skin with tissue loss (atrophy) and premature skin aging (actinic elastosis).

Finally, possible precursors of skin cancer (precanceroses) and malignant skin tumors such as basaliomas, spinaliomas and melanomas occur in childhood and adolescence. Scarring and mutilation of the nose and eyes is often observed. Neurological changes are observed in 20% of all XP patients.

These can be reflex disorders, spasticity, movement coordination disorders (ataxia), diseases of the nervous system (neuropathies) and intelligence disorders. Type A patients may experience mental retardation and dwarfism (DeSanctis cacchione syndrome). Eye changes are observed in 40% of patients. The anterior segments of the eye and the eyelids are affected. It can lead to photophobia, conjunctivitis, ulcers and corneal abnormalities (dysplasia of the cornea).

Diagnosis

It is very important that xeroderma pigmentosum is diagnosed as early as possible. If children under two years of age already have spots on sun-exposed skin, one should think of Xeroderma pigmentosum, because children at this age should not normally have such discolorations yet. Children with noticeably rapid redness in the sun should also consult a dermatologist.

The diagnosis itself is made by cultivating cells from the connective tissue (fibroblasts), which are obtained by removing tissue from the skin (biopsy). These are then examined for DNA repair mechanisms, UV sensitivity and faulty DNA synthesis. Different types of disease can be diagnosed by direct gene transfer.

If, after the administration of a certain gene, the DNA repair mechanism is again functioning properly, it is the type in which the given gene is defective. The diagnosis of an embryo in the abdomen (prenatal diagnostics) is also possible by genetic analysis. Xeroderma pigmentosum must be distinguished from other rare syndromes such as Cockayne syndrome, lupus erythematosus and porphyria.

Like XP, Cockayne syndrome is caused by a defect in DNA repair mechanisms, but no pigment disorders or skin tumors occur. Lupus erythematosus is an autoimmune disease, the cause of which is not fully understood, but viruses or UV light are suspected. The body’s defense system reacts excessively against the body’s own cells.

The first symptoms are fever, exhaustion and sensitivity to sunlight. Porphyrias are metabolic diseases that are related to the disturbance of the build-up of the red blood pigment haem. In cutaneous porphyria, a type of porphyria that affects the skin, there are no changes in the skin despite pain when the skin is exposed to direct sunlight.

Only after 12-24 hours does swelling, redness and even extensive burns occur.Other symptoms are scarring, blistering of the skin, tissue death and disfigurement such as loss of nose, lips, auricles. Type D is occasionally associated with trichothiodystrophy. The characteristic syndrome of this disease is short, brittle hair.

About half of the patients have increased photosensitivity, also caused by defects of repair mechanisms of UV light-damaged DNA. There is no therapy for the underlying disease, only absolute avoidance of UV radiation can protect the patients. The light-modified skin must be checked in three to six-month intervals.

Precanceroses must be scraped out (curettage), tumors must be removed surgically. However, research into gene therapy offers hope. This involves introducing a bacterial protein into the body, which then replaces the defective DNA repair mechanisms and takes over the DNA repair.