Leukemia: neurologic complications
Mar. 20, 2018
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What is xeroderma pigmentosum?
Xeroderma pigmentosum (pronounced: zer-o-der-ma/pig-men-toe-sum) is a very rare inherited disease that causes extreme sensitivity to the sun’s ultraviolet rays. Unless patients with xeroderma pigmentosum are protected from sunlight, their skin and eyes may be severely damaged. This damage may lead to cancers of the skin and eye. Xeroderma pigmentosum has been identified in people of every ethnic group all over the world.
What are the signs of xeroderma pigmentosum?
The eyes of a person with xeroderma pigmentosum are often painfully sensitive to the sun and may easily become irritated, bloodshot, and clouded. Noncancerous and cancerous growths on the eyes may occur.
All three common types of skin cancer (basal cell carcinoma, squamous cell carcinoma, and melanoma) occur much more often in people with xeroderma pigmentosum. Basal cell and squamous cell carcinomas usually do not spread to internal organs, but they do destroy the local skin and underlying tissues. Melanoma can be fatal if it is not removed before it has spread to internal organs.
Many persons with xeroderma pigmentosum will get an unusually severe sunburn after a short sun exposure. The sunburn will last much longer than expected, perhaps for several weeks. This type of sunburn will usually occur during a child’s first sun exposure, and it may be a clue to the diagnosis of xeroderma pigmentosum. However, some people with xeroderma pigmentosum will not get a sunburn more easily than others, and the disease will be undetected until unusual skin changes appear overtime.
Most patients with xeroderma pigmentosum will develop many freckles at an early age. Continued sun exposure will lead to further changes in the skin, including irregular dark spots, thin skin, excessive dryness, rough-surfaced growths (solar keratoses), and skin cancers. These skin changes will resemble those of elderly people who have spent many years in the sun. In people with xeroderma pigmentosum, these changes caused by sun damage often begin in infancy, and almost always before age 20.
Other medical problems: In addition to skin and eye changes, about 20% of patients with xeroderma pigmentosum may have one or more nerve-related problems including the following: deafness, poor coordination, spastic muscles, or developmental delay. A few people with xeroderma pigmentosum will have all of these problems, and some also may be very short and may not develop normal sexual characteristics. Some people with xeroderma pigmentosum will develop only mild neurological symptoms in late childhood or adolescence. Whenever neurological problems do occur, however, they usually tend to worsen over time.
What causes xeroderma pigmentosum?
Two factors combine to cause the abnormalities in xeroderma pigmentosum. First, a person inherits traits from each parent which, when combined, lead to an unusual sensitivity to the damaging effects ultraviolet light. Second, exposure to the sun, which contains ultraviolet light, leads to changes in the skin and eyes.
Problems with DNA damage and repair: Ultraviolet light damages the DNA in cells and disrupts normal cell functioning. DNA (deoxyribonucleic acid) within our genes contains all the coded information needed to direct cell functions. Damaged DNA is mended by the DNA repair system. But the DNA repair systems of people with xeroderma pigmentosum do not function properly. As a result, unrepaired DNA damage builds up and causes cancerous cell changes or cell death.
How is xeroderma pigmentosum diagnosed?
Xeroderma pigmentosum can usually be diagnosed in the laboratory by measuring the DNA repair defect. This test is performed on skin or blood obtained from the patient. Soon, only a few cells may be needed to make this diagnosis.
Different types of xeroderma pigmentosum: There are eight genetic types of xeroderma pigmentosum. Each type is characterized by a different genetic change in the DNA repair system. Seven of the eight types show reduced activity in one DNA repair system. The eighth form shows reduced activity in another DNA repair system. This last type of xeroderma pigmentosum is referred to as the “variant” form, while the other seven types are known as groups A, B, C, D, E, F, and G.
Can xeroderma pigmentosum be treated?
There is no cure for xeroderma pigmentosum, but much can be done to prevent and treat some of the problems it causes:
• protection from ultraviolet light
• frequent skin and eye examinations
• prompt removal of cancerous tissue
• neurological examination
• psychosocial care
Problems from ultraviolet light: As soon as the diagnosis of xeroderma pigmentosum is suspected, a patient should be completely protected from ultraviolet rays. This will greatly reduce the frequency and severity of skin and eye problems (including cancers).
There are two types of ultraviolet light: short wavelength and long wavelength. The main source of harmful, short wavelength ultraviolet light is sunlight. These ultraviolet rays are also found in the light given off by germicidal lamps, artificial sunlamps (including those found in tanning booths), and mercury vapor lamps. Ultraviolet-measuring instruments, if available, may be used to detect sources of ultraviolet radiation.
The small amount of long wavelength ultraviolet light from sunlight that has passed through window glass (or produced by unfiltered day-light fluorescent bulbs) is of less risk but probably should be avoided. Regular incandescent light bulbs do not give off ultraviolet light. To limit a person’s exposure to harmful ultra-violet rays, outdoor activity should be restricted to nighttime.
Damaging ultraviolet radiation from sunlight is most intense at midday. In some patients, even a few minutes of sun exposure at mid-day may cause a severe sunburn. If daytime exposure is unavoidable, it should be limited to the very early morning or very late afternoon hours—a time of day when your shadow is much longer than your height. When patients with xeroderma pigmentosum are indoors or in a car, the windows should always be closed because glass blocks harmful ultraviolet rays from sunlight.
Tips for protecting children
• Children with xeroderma pigmentosum should not play outdoors during the day unless they are under ultra-violet light-blocking shelters and away from reflective surfaces such as snow, sand, or water. Clouds do not block out harmful rays.
• Special arrangements for children with xeroderma pigmentosum should be made at school to ensure that they are not exposed to sunlight from an open window, that they are not exposed to any unfiltered (bare) fluorescent light bulbs, and that they are not permitted outside for gym, recess, fire drills, or other activities.
Daily protection outdoors
• When patients with xeroderma pigmentosum are outdoors in daylight, they should wear long sleeves, long pants, and wide-brimmed hats. Two layers of clothing protect more than one layer. Tightly woven fabrics generally give more sun protection than loose weaves. Wear clothing that you can’t see the light through. Some companies make light-weight clothing specifically designed to provide a high degree of sun protection.
• Choose eyeglasses or sunglasses specifically labeled to block ultraviolet light completely. Glasses with side-shields protect the eyelids and skin around the eyes. Long hair styles help protect the neck and ears.
• While sun protection by clothing is most effective, any skin not covered by clothing or hair should be protected by sunblocks such as zinc oxide, titanium dioxide, sun-blocking makeup, or sunscreens. Sunscreens with a sun protection factor of 15 or higher should be used. They should be applied at least 30 minutes before going out in the sun. Lip moisturizers containing sun blocking agents also give protection.
• A sunscreen may also be used indoors to protect against unrecognized sources of ultraviolet light.
What else can cause harm besides ultraviolet light?
Laboratory tests indicate that sunlight is the major DNA damaging agent to the cells of patients with xeroderma pigmentosum. However, tobacco smoke and some drugs (such as psoralens, used with ultraviolet light for treating psoriasis) can cause similar DNA damage. People with xeroderma pigmentosum should avoid exposure to tobacco smoke and should not use tobacco products because they are probably at greater risk for developing lung cancer.
What more can I do?
Frequent skin examinations: Patients should be examined often by a family member or another person who has been taught to recognize the signs of skin cancer. Any suspicious spot or growth should be immediately reported to the patient's doctor. Examinations should include the eyes, scalp, ears, mouth, tongue, nostrils, and all other areas of the skin, even those that do not have sun exposure (for example, the buttocks).
Examination by a dermatologist (a doctor specializing in skin disorders) should take place at least every 3 to 6 months. The dermatologist can help detect skin cancers before they have grown or spread to internal organs. A small piece of suspicious skin growths may be removed (biopsied) and examined for cancer.
Prompt removal of cancerous tissue: Skin cancer treatment for patients with xeroderma pigmentosum is similar to that for anyone with skin cancer. Treatment may include removal of the cancer by freezing, use of an electric needle, or surgery. Depending on the size, type, and location of the cancer, a small cancerous growth can usually be treated in a doctor’s office. Large tumors may require extensive surgery and skin grafting. Dermabrasion or removing large portions of skin with grafting has been used for some patients with extensive involvement. X-ray treatment has also been used safely. Precancerous growths, such as solar keratoses, may be frozen with liquid nitrogen.
Other skin treatments: Some patients with xeroderma pigmentosum who have had many skin cancers have prevented new cancers by taking a drug called isotretinoin, a derivative of vitamin A. However, this medicine has serious side effects that prevent its use in all but the most severe cases. A cream containing a DNA repair enzyme is currently being studied.
Frequent eye examinations: Examination by an ophthalmologist (a doctor specializing in the eye) should take place regularly. The ophthalmologist can help detect eye cancers and other lesions before they become a problem. Artificial tears or soft contact lenses may soothe abnormally dry or irritated eyes. If the corneas of the eyes become so clouded that the patient cannot see, a corneal transplant may be considered to restore vision.
Treatment of neurological problems: About 20 percent of patients develop neurological problems. While nothing can prevent or stop these problems from occurring, it is important to be aware of them. Early testing and treatment for potential neurological problems may lessen the unfortunate results of undetected abnormalities. For example, detection of hearing loss and subsequent use of a hearing aid may lessen difficulties in communication and in school. Patients with xeroderma pigmentosum should have periodic neurological examinations.
The role of sun exposure in the development of neurological problems: Researchers do not believe that sun exposure affects the development of neurological problems in patients with xeroderma pigmentosum. The sun’s ultraviolet rays are absorbed by the skin and do not penetrate the brain or other internal organs. But no matter how small his or her sun exposure, a person with xeroderma pigmentosum who is genetically prone to develop neurological symptoms will do so. While the cause of the neurological problems is unclear, it appears that persons with the most severe reductions in their DNA repair ability are the most likely to have such problems.
Psychosocial aspects of xeroderma pigmentosum
Persons with xeroderma pigmentosum and their families face many challenges in daily living. This disease has many long-term physical, emotional, social, and economic consequences. Skin changes, including cancers at an early age and other physical problems, may affect school experiences, employment opportunities, recreational activities, and social relationships. Coping with chronic illness and disability is very difficult. Some people have problems with health insurance or finances while others may feel anxious or depressed. Persons with xeroderma pigmentosum need a great deal of support from family, friends, and their communities to provide encouragement, build confidence, and give hope. Patients with xeroderma pigmentosum and their families may obtain assistance from their physician, nurse, or social worker.
What is the life span of people with xeroderma pigmentosum?
Many people with xeroderma pigmentosum will die at an early age from skin cancer if they are untreated and unprotected from sunlight. However, if a person is diagnosed early, has no severe neurological problems, is protected from ultraviolet light, and followed carefully for early cancer detection, a normal life span is possible. The life spans of most persons with xeroderma pigmentosum will fall between these extremes. A reduced life span is to be expected, but there are great differences among patients with xeroderma pigmentosum.
What part does heredity play?
Xeroderma pigmentosum is a recessive condition. This means that a person must have two xeroderma pigmentosum genes (one from each parent) to develop the disease. Both parents of a person with xeroderma pigmentosum are carriers of the xeroderma pigmentosum trait because each parent has one xeroderma pigmentosum gene and one normal gene. Neither parent has symptoms of xeroderma pigmentosum. Recent advances in understanding xeroderma pigmentosum make it possible to test if someone is a carrier of some forms of xeroderma pigmentosum by analyzing that person’s DNA.
If the parents of a child with xeroderma pigmentosum have another child, will that child also have xeroderma pigmentosum?
There is a one in four chance that any child of the same parents of a patient with xeroderma pigmentosum will also have xeroderma pigmentosum. Xeroderma pigmentosum among affected children in the same family is usually of similar severity. For example, if the first child with xeroderma pigmentosum has severe neurological problems, the next affected child may have similar problems.
Prenatal diagnosis of xeroderma pigmentosum has been done in research laboratories, but it is not a routine test. Parents of a child with xeroderma pigmentosum should seek genetic counseling before considering having another child.
Can a person with xeroderma pigmentosum have children?
Most people with xeroderma pigmentosum have normal sexual development and functioning, and they are able to have children. The advisability of a person with xeroderma pigmentosum becoming a parent would be affected by the person’s own ability to care for a family.
The probability of a person with xeroderma pigmentosum having a child with xeroderma pigmentosum is very small. This would occur only if the other parent also has xeroderma pigmentosum or is a carrier for the xeroderma pigmentosum trait. In some cases, carriers of the xeroderma pigmentosum trait can be detected by a laboratory test of their DNA repair genes. The probability of a person with xeroderma pigmentosum having a child with xeroderma pigmentosum is very small. This would occur only if the other parent also has xeroderma pigmentosum or is a carrier for the xeroderma pigmentosum trait. In some cases, carriers of the xeroderma pigmentosum trait can be detected by a laboratory test of their DNA repair genes.
What research is being done?
Researchers in the United States and throughout the world are learning about xeroderma pigmentosum and trying to correct the DNA repair defect in laboratory-grown cells from patients with xeroderma pigmentosum. The genes causing most types of xeroderma pigmentosum have been identified. Many laboratories in the US, Europe, and Japan are studying xeroderma pigmentosum genes and trying to understand what they do. Clinical studies on skin cancer prevention with oral medications and evaluating patients with unusual features are also being conducted at the National Institutes of Health.
Where can I get more information?
Information for patients and collection of clinical data about symptoms, treatment, and progress of patients with xeroderma pigmentosum is available from the organizations below:
Xeroderma Pigmentosum Registry
Univ of Medicine and Dentistry of NJ
Department of Path
Med Sci Bldg Rm C-520
185 S Orange Ave
Newark, NJ 07103-2714
Support groups have also been formed and can be contacted as follows:
Xeroderma Pigmentosum Society
437 Snydertown Rd
Crayville, NY 12521
Xeroderma Pigmentosum Family Support Group
8375 Folsom Blvd, Suite 201
Sacramento, CA 95826
XP Support Group
2 Strawberry Close
Your dermatologist can answer specific questions about this disease. Additional information may be obtained from these sources:
Task Force on Xeroderma Pigmentosum
American Academy of Dermatology
Schaumburg, IL 60168-4014
National Cancer Institute
Office of Cancer Communications
31 Center Drive MSC 2580
Building 31 Room 10A16
Bethesda, Maryland 20892-2580
1-800-422-6237 (9 a.m. to 4:30 p.m.)
This information was developed by the Warren Grant Magnuson Clinical Center at the National Institutes of Health.
Warren Grant Magnuson Clinical Center at the National Institutes of Health. Understanding Xeroderma Pigmentosum. Available at: https://xpgrupoluzdeesperanza.org/clinical-research-for-xeroderma-pigmentosum/. Accessed January 2, 2018.
The information in this document is for general educational purposes only. It is not intended to substitute for personalized professional advice. Although the information was obtained from sources believed to be reliable, MedLink LLC, its representatives, and the providers of the information do not guarantee its accuracy and disclaim responsibility for adverse consequences resulting from its use. For further information, consult a physician and the organization referred to herein.