Xeroderma Pigmentosum Health Article

Signs and symptoms

People with xeroderma pigmentosum have photosensitive skin. This means that their skin is hypersensitive to the effects of sunlight. Development of cancer at a young age is the most serious consequence. The eyes are also affected. Some people with xeroderma pigmentosum are affected intellectually, but not all. The symptoms a person will have are somewhat predictable based on which mutation he or she has.

Cutaneous symptoms

Skin manifestations usually begin in infancy. Early effects of skin exposure to minimal ultraviolet radiation include acute sunburn, blistering, freckles, increased or decreased pigment, birthmark-like spots, inflammation, dryness, and rough spots. The face, hands, neck, and arms are more severely affected because of increased sun exposure. Multiple scars may develop. The skin is normal at birth.

The average age at which people with xeroderma pigmentosum develop the first skin cancer is eight years. The risk to develop skin cancer is increased 1,000 times over the risk of the general population. A cell accumulates multiple abnormalities in its transition from a normal cell to a cancer cell. Cancers that occur frequently in people with xeroderma pigmentosum include squamous cell carcinoma, basal cell carcinoma, and malignant melanoma. Basal cell cancers are malignant and, if untreated, are characterized by relentless local invasion, but not metastasis elsewhere in the body. Squamous cell cancers are also malignant and, like basal cell carcinomas, tend to be local, although they are occasionally capable of metastasis. Malignant melanoma, as the name implies, is also malignant, but it is much more aggressive than either basal cell or squamous cell cancers of the skin. It is especially threatening because, if not diagnosed and treated early, it commonly will spread to internal organs and can be fatal. Cancer may occur on the eyes, lips, and tongue.

Ocular symptoms

Most people with xeroderma pigmentosum also have extremely light sensitive eyes. Their eyes easily become irritated, red, and swollen. Abnormal growths may appear. Cataracts may occur at an unusually young age.

Other symptoms

The other symptoms associated with xeroderma pigmentosum are variable. Many people who are affected only have eye and skin manifestations. Mental deterioration may occur; when it does, it usually worsens over time. Neurological symptoms are not believed to be associated with sun exposure. Some people have one or a combination of: deafness, poor reflexes, lower intelligence, or spasticity (in addition to ocular and cutaneous symptoms).

Diagnosis

Xeroderma pigmentosum may be suspected based on a person's history of skin changes that occurred after minimal exposure to sunlight. The diagnosis is confirmed

by a blood test or a skin test. The skin or blood cells are sent to a specialty laboratory. Studies are performed to determine whether the cells are hypersensitive to ultraviolet radiation. Scientists may examine whether abnormal changes can be seen in the chromosomes. The type of xeroderma pigmentosum may be determined by genetic studies or other specialized studies.

Genetic testing for xeroderma pigmentosum is complicated because there are eight different genes involved. Genetic tests are usually very specific, looking for a change in one gene. To confirm a diagnosis of xeroderma pigmentosum by DNA testing, scientists must look for multiple changes in eight different genes.

Prenatal diagnosis may be possible, especially if genetic studies have already been performed on an affected sibling and the parents.

Treatment and management

The only treatment for xeroderma pigmentosum is avoiding harmful exposure to ultraviolet radiation and treating/removing growths as they occur. The DNA damage caused by exposure to ultraviolet light accumulates over time and the resulting DNA damage is irreversible.

Life is changed dramatically when a family member has xeroderma pigmentosum. Extreme measures must be taken to completely avoid exposure to the sun. Preventative measures include: sunglasses, tightly woven long-sleeved clothing, wide brim hats, sunblock, and protective window coverings (at home, in the car, and at school). Children do not play outside during the day. All sources of ultraviolet radiation are avoided, even exposure to certain light bulbs. These precautions are critical to survival. Levels of ultraviolet radiation at home and at school can be measured with special instruments. Abnormal skin growths and other symptoms are treated/removed as they arise. Regular visits are made to the eye doctor, dermatologist, and neurologist. Often psychosocial support is also helpful.

Treatments that would deliver DNA repair proteins into the skin of affected patients are under investigation. Some people with xeroderma pigmentosum may be offered other types of medication, like isotretinoin. The dermatologist weighs the benefit of prescribing a medication against the side effects associated with that medication.

Because our bodies have different mechanisms for fixing different forms of DNA damage, people with xeroderma pigmentosum are most susceptible to DNA damage by ultraviolet radiation. Some other exposures have been associated with the type of DNA damage caused by ultraviolet radiation. Therefore, people with xeroderma pigmentosum should also avoid exposure to tobacco and certain other drugs.