Xeroderma pigmentosum (XP) is a rare but serious inherited disease involving extreme sensitivity to sunlight (photosensitivity), specifically the sun’s ultraviolet (UV) rays. This sensitivity develops during the first few years of life.

Patients with XP typically experience painful and severe sunburns, even after minimal sun exposure. As the disease progresses the skin becomes excessively dry and rough with signs of premature aging.

Signs and symptoms of XP may include:

• Skin atrophy (thinning)
• Irregular dark spots (hyperpigmentation) 
• Growths or tumors

Typically, the eyes of XP patients are also affected and often become irritated, bloodshot and clouded following exposure to UV radiation.

There is no cure for XP and the skin deterioration that occurs with the disease is cumulative and often irreversible. People with this condition often require lifelong protection from sunlight or ultraviolet radiation-emitting agents (e.g., mercury-vapor lamps). XP has severe life-threatening complications that may include:

• Skin cancer
• Cancerous tumors in the eyes and mouth area

Sometimes patients with XP may experience progressive neurological problems, including:

• Developmental (learning) disabilities
• Mental retardation
• Hearing loss that may lead to deafness

Xeroderma pigmentosum (XP) is a rare, inherited disease involving extreme sensitivity to sunlight (photosensitivity), specifically the sun’s ultraviolet (UV) rays. UV radiation can cause extreme damage to the skin and eyes of patients with this disease.

Patients with XP typically experience severe, skin-blistering sunburns, even after minimal sun exposure. These acute sunburns usually last longer than normal, sometimes for several weeks. As the disease progresses, the skin becomes excessively dry and rough, with signs of premature aging similar to that of elderly people who have spent many years in the sun. However, these changes in the skin usually begin in infancy and may include:

• Skin atrophy (thinning)
• Discolorations (hypopigmentation)
• Irregular dark spots (hyperpigmentation)  
• Growths or tumors

Frequently, the eyes of XP patients may also become irritated, bloodshot and clouded following exposure to UV radiation.

XP is extremely rare. According to the Xeroderma Pigmentosum Society, an estimated one out of every million people has XP in the United States. The condition affects both sexes and people of all ethnic groups but certain populations tend to have a higher incidence of the disorder. In Japan, the number of cases is estimated at one per every 100,000 people. Incidence is also increased in North Africa and the Middle East, especially in communities with greater consanguinity (intermarriage of blood relatives).

XP – also called Kaposi disease – was first described in 1870 by dermatologists Ferdinand von Hebra and Moriz Kaposi. Originally called xeroderma, Kaposi later added the pigmentosum to describe the characteristic changes in the skin pigment of people with the disorder. Kaposi first recognized that only the areas of skin exposed to sun were affected and that there was a hereditary component to the disorder. The medical community identified the genes (basic units of heredity for all living organisms) that trigger the skin disease several decades later.

There is no cure for XP and the skin deterioration that occurs with the disease is cumulative and often irreversible. People with this condition often require total, lifelong protection from sunlight or UV radiation-emitting agents (e.g., mercury-vapor lamps, tanning booths). XP has severe, life-threatening complications that may include:

• Permanent skin damage and scarring
  
  
• All forms of skin cancer (basal cell carcinoma, squamous cell carcinoma, malignant melanoma)
  
  
• Cancerous tumors in the eyes and mouth area

Sometimes patients with XP may experience progressive neurological problems, including:

• Developmental (learning) disabilities
• Mental retardation
• Dementia
• Hearing loss that may lead to deafness
• Loss of motor skills

In addition, although rare, XP may co-exist with other extremely rare hereditary disorders, such as:

• Cockayne syndrome (CS). A rare disorder characterized by a failure to grow, impaired development of the nervous system, abnormal sensitivity to sunlight (photosensitivity) and premature aging. Hearing loss, eye abnormalities and severe tooth decay are other common features. Problems with internal organs are also possible in people with CS. In contrast to XP, though, skin cancer is rare in CS.
  
  
• De Sanctis-Cacchione syndrome. This condition is characterized by all the skin and eye problems of XP along with neurological abnormalities, including mental retardation, unusually short stature (dwarfism), and underdevelopment of the sexual reproductive glands (hypogonadism).

Xeroderma pigmentosum (XP) is classified into eight complementation groups (or genetic subtypes), based upon different defects in the body’s ability to repair deoxyribonucleic acid (DNA, the molecule that encodes genetic information) damaged by ultraviolet (UV) radiation. These groups include:

• Type A (XPA). Patients with XPA have the lowest level of DNA repair and the most neurological complications (e.g., mental retardation). This type of XP is rare in the United States and most cases have been reported in Japan.
  
  
• Type B (XPB). A very rare type of xeroderma pigmentosum. Patients with XPB may also have a rare disorder characterized by a failure to grow, impaired development of the nervous system, photosensitivity and premature aging (Cockayne syndrome).
  
  
• Type C (XPC). This is the most common type of XP in the United States. Most patients with XPC rarely experience neurological problems.
  
  
• Type D (XPD). This is the second most common type of XP in the United States. Most patients with XPD often have neurological abnormalities (e.g., mental retardation, progressive deafness). Sometimes patients with XPD also have physical characteristics of Cockayne syndrome or trichothiodystrophy, which is characterized by brittle and poorly growing hair.
  
  
• Type E (XPE). This form of XP is also very rare. Patients with XPE often have mild skin symptoms and no neurological problems.
  
  
• Type F (XPF). Most cases of XPF have been reported in Japan. XPF patients may have mild skin and neurological symptoms.
  
  
• Type G (XPG). Patients with XPG may exhibit severe neurological abnormalities in addition to Cockayne syndrome.
  
  
• Variant Type (XP-V). Individuals with XP-V are clinically (but not genetically) identical to other XP patients with skin symptoms but without neurological abnormalities.

Genetic subtypes XPA, XPC, XPD and XP-V make up more than 90 percent of xeroderma pigmentosum cases worldwide, according to the Xeroderma Pigmentosum Society. Subtypes XPB, XPE, XPF and XPG are rare.

People with xeroderma pigmentosum (XP) are extremely sensitive to sunlight, specifically the sun’s ultraviolet (UV) rays. Exposure to UV radiation damages the deoxyribonucleic acid (DNA, the molecule that encodes genetic information) in skin cells and disrupts normal cell functioning. Generally, in healthy people, damaged DNA is repaired by the DNA repair system. However, people with XP have a defective DNA repair system that does not function properly. As a result, unrepaired DNA damage builds up and causes the rapid deterioration observed in the skin of patients with XP, which puts them at very high risk for skin cancer.

Sometimes individuals with XP may also experience neurological complications, such as progressive hearing loss, mental retardation and ataxia (an inability to coordinate muscle movement), among others. This is because the disease also involves the central nervous system (the body system that includes the brain and spinal cord) and causes the premature deterioration of nerve cells in some XP patients. Specifically, the presence of neurological complications in patients with XP correlates with their degree of DNA repair impairment. For instance, patients with the greatest impairment of DNA repair (such as occurs in XPA) are more likely to develop neurodegeneration (deterioration of nerve tissue) and related complications (e.g., ataxia).

Patients with xeroderma pigmentosum (XP) typically experience severe, skin-blistering sunburns even after minimal sun exposure. These acute sunburns usually last longer than normal, sometimes for several weeks. However, at birth, the skin of most babies with XP appears healthy. The skin tissue deterioration that is characteristic of XP usually first appears between the ages of six months and 2 years. In addition, an early onset of freckling often occurs in children with XP before the age of 2. 

Generally, the disease progresses through three stages:

• First stage. This stage is characterized by widespread erythema (rashes), scaling (shedding of skin) and the appearance of freckles over areas exposed to ultraviolet (UV) radiation, beginning initially on the face. With progression of the disease, these symptoms are exacerbated and appear on the lower legs, neck and sometimes the trunk. Though these features tend to diminish during the winter months with decreased sun exposure, as time passes, these changes become more obvious and permanent.
  
  
• Second stage. This stage is characterized by skin atrophy (thinning) and the appearance of spider veins, as well as blotchy areas of hyperpigmentation and hypopigmentation (discoloration) throughout the skin.
  
  
• Third stage. This stage is the most severe and is marked by the appearance of numerous tumors due to prolonged exposure to UV radiation, including basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Skin cancer may occur as early as age 4 or 5, and is more prevalent on the sun-exposed areas of skin.

In most cases, the eyes of patients with XP are also sensitive to UV radiation. Exposing the eyes to sunlight may be painful (photophobia). In addition, the eyes of XP patients may easily become irritated, bloodshot and clouded following sun exposure. Conjunctivitis (inflammation of the tissue that lines the inside of the eyelid) may occur. As XP progresses, noncancerous and cancerous tumors, which can lead to blindness, may also occur.

In addition, sometimes patients with XP may experience progressive neurological problems (especially individuals with subtypes XPA and XPD), including:

• Developmental (learning) disabilities
• Mental retardation
• Dementia
• Hearing loss that may lead to deafness
• Ataxia (inability to coordinate muscle movements)
• Polyneuropathy (noninflammatory deterioration of the nerves)

Neurological complications may develop during late childhood or adolescence.

To diagnose xeroderma pigmentosum (XP), a physician will perform a visual examination of the patient's skin and eyes. Along with the complete physical examination, the physician will compile a thorough medical history, including checking for a family history of XP. In most cases, clinical diagnosis of XP is based on a patient’s history of skin photosensitivity and tumors.

To further confirm an XP diagnosis, a physician may perform a skin biopsy and blood tests. The physician will then send the skin cell tissue and blood samples to a laboratory for deoxyribonucleic acid (DNA, the molecule that encodes genetic information) testing to measure the DNA repair defect following exposure to ultraviolet (UV) radiation. However, DNA testing is generally not necessary for diagnosis and usually only conducted on a research basis.

Other tests that may be performed include:

• Imaging tests (e.g., MRI, CAT scan). These imaging techniques may show the brain atrophy (deterioration) of some patients with XP with neurological symptoms (e.g., dementia).
  
  
• Audiogram test. This test measures a person’s auditory (hearing) capacity and is useful for screening for hearing loss, which is another neurological complication experienced by some patients with XP.
  
  
• Electromyography test. This test assesses nerve function and helps diagnose causes of muscular problems. An electromyography test may determine the extent of muscular damage in XP patients with ataxia (inability to coordinate muscle movements).

XP can also be diagnosed before birth with prenatal tests, such as:

• Amniocentesis. A type of prenatal test in which amniotic fluid (pregnancy fluid) is removed from the mother’s abdomen with a needle and syringe to check for abnormalities.  
  
  
• Chorionic villus sampling. A prenatal testing method that uses a catheter device inserted into the vagina and cervix to obtain a sample of fetal tissue from the placenta (pregnancy sac) for laboratory analysis. Chorionic villus sampling may detect chromosomal abnormalities in the fetus.

There is no cure for xeroderma pigmentosum (XP) and the skin deterioration that occurs with the disease is cumulative and often irreversible. People with this condition often require total, lifelong protection from sunlight or ultraviolet (UV) radiation-emitting agents (e.g., mercury-vapor lamps, tanning booths).

Once XP is diagnosed, each aspect of the disease may be treated and monitored by a different specialist. A dermatologist specializes in skin conditions and may treat the photosensitivity and skin cancer. An ophthalmologist specializes in eye diseases and may treat conjunctivitis (inflammation of the eyelid and lining) and eye tumors or growths. A neurologist specializes in diseases that affect the nervous system may screen for (and treat) any neurological complications (e.g., learning disabilities).

Treatment of skin cancer, a common complication of XP, centers on the prompt removal of any precancerous and cancerous tissue. For most squamous cell and basal cell carcinomas, which rarely spread, a biopsy is often the only necessary treatment. However, some carcinomas and melanomas, the most severe form of skin cancer, require other forms of cancer treatment. These may include radiation (therapy that uses high-energy rays, such as x-rays, to kill or shrink cancer cells), chemotherapy (drug therapy for inhibiting or destroying cancer cells) and specific skin techniques including:

• Cryosurgery. Freezing the affected area with liquid nitrogen.
  
  
• Curettage and electrodesiccation. Lesion is removed and any remaining layers of cancer cells are scraped away using a curette (circular blade).
  
  
• Surgical excision. Surgical removal of the suspicious lesion and some surrounding healthy tissue.
  
  
• Laser therapy. Narrow beam of intense light that vaporizes growths.
  
  
• Mohs surgery. The lesion is removed one layer at a time and examined under a microscope. The process is repeated until only healthy tissue remains.
  
  
• Skin grafting and reconstructive surgery. Healthy skin is moved from another area, such as the buttocks or thighs, and replaces cancerous tissue.

For the treatment of eye-related complications in patients with XP, an ophthalmologist may recommend the following:

• Surgery. The surgical removal of any noncancerous and cancerous tumors or growths in the eyes or eyelids.
  
  
• Artificial tears and/or soft contact lenses. The regular use of artificial tear drops and contact lenses may help soothe abnormally dry or irritated eyes in XP patients.
  
  
• Corneal transplant. If the eyes of an XP patient become so clouded that he or she cannot see, a corneal transplant may be considered to restore vision.

Sometimes patients with XP may develop neurological complications including progressive hearing loss, which may lead to deafness, cognitive disabilities and the progressive loss of nerve and muscular functioning. Although nothing can prevent or stop these problems from occurring, early screening and treatment for potential neurological complications may help patients to better cope with these. For instance, early detection of hearing loss and subsequent use of a hearing aid may lessen difficulties in communication for patients with XP.

Many people with xeroderma pigmentosum (XP) die by age 20 from skin cancer. However, if a person is diagnosed early, has no severe neurological complications (e.g., dementia), is protected from ultraviolet (UV) radiation and regularly checked for early signs of skin cancer, a normal lifespan may be possible.

XP patients must avoid UV radiation at all times to protect their skin. If sun exposure cannot be entirely avoided, it should be kept to a minimum and patients should wear wide-brimmed hats, protective clothing with long sleeves, use sunscreen with sun protection factor (SPF) 50 and wear dark, UV-absorbent sunglasses to protect the eyes. The rays of the sun are the strongest, and thus cause the most damage, between the hours of 10 a.m. and 4 p.m. If it is not possible to avoid those hours, patients should seek shade under a tree, umbrella or tent. Sometimes patients may opt to change their lifestyle to completely avoid sun exposure by only going outside at night.

When indoors, XP patients should be protected from unfiltered (bare) fluorescent light bulbs and sunlight coming through windows. A special UV protective film is available to coat windows in homes and cars.

Other steps that XP patients can take to help prevent skin cancer include:

• Avoid other sources of UV radiation. Besides the sun, ultraviolet rays are also found in the light given off by germicidal lamps, artificial sunlamps (such as those used in tanning salons) and mercury-vapor lamps.
  
  
• Avoid cigarette smoke. Laboratory tests indicate that smoking or exposure to tobacco smoke can also result in damage to the skin cells of XP patients in the same way that UV exposure does.
  
  
• Check medications. Some prescription drugs increase a person’s sensitivity to sunlight, putting them at greater risk for sunburn. Common medications that increase sensitivity include diuretics, antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen.

It is recommended that all patients with XP have regular checkups (every three to six months) with their dermatologist and ophthalmologist (eye-care specialist) to monitor their condition. XP patients should also perform frequent self-examinations of the eyes, scalp, ears, mouth, tongue, nostrils and all other areas of the skin, even those not regularly exposed to sunlight (e.g., buttocks), and promptly report any suspicious spots or growths to their physician. XP patients should also have an annual neurological examination, including a hearing evaluation, until the age of 20.

Preparing questions in advance can help parents to have more meaningful discussions with their child’s physicians. Parents may wish to ask their child’s doctor the following questions regarding xeroderma pigmentosum (XP):

1. Do my child’s symptoms indicate XP?
   
   
2. What tests will you use to determine if my child has XP?
   
   
3. Do you have experience treating patients with XP?
   
   
4. What type of XP does my child have? Is the condition terminal?
   
   
5. What may have caused my child to develop XP?
   
   
6. What XP-related complications is my child at risk for? What steps can we take to reduce these risks?
   
   
7. What are my child’s treatment options? How effective are the treatments?
   
   
8. Must my child remain indoors during the day?
   
   
9. What specialists will my child need to see?
   
   
10. How often will my child require skin, vision and neurological examinations?
    
    
11. Will the symptoms of XP change as my child ages?
    
    
12. I have a child with XP. What are the chances that I might have another child with the disease?