Xeroderma pigmentosum, also called moonshine disease, is understood by physicians to be a skin disease caused by a genetic defect. Affected individuals exhibit a pronounced UV intolerance and therefore usually have to avoid sunlight completely. The disease is as yet incurable. Xeroderma pigmentosum is a very rare, genetic disease of the skin and mucous membranes, which is characterized primarily by hypersensitivity to ultraviolet light (UV light). A xeroderma pigmentosum has an infamous (unfavorable) course, usually characterized by skin cancers.
What is xeroderma pigmentosum?
Xeroderma pigmentosum is a severe skin disease characterized by neurological deficits and, most importantly, marked UV intolerance. Painful skin inflammations occur, which later develop into malignant ulcers. Since the disease not infrequently leads to an early death already in the first decade of life, the affected persons are mostly children, who are colloquially also called moonlight children. However, cases are also known in which affected persons reached the age of 40. Xeroderma pigmentosum occurs very rarely; however, strong regional differences can be observed. In Germany, about 50 children are affected by the genetic defect, in the United States there are about 250. Thus, moonshine disease is a genetically determined disease that manifests itself already in childhood by a hypersensitivity of the skin and mucous membranes to UV light. Accordingly, typical symptoms of xeroderma pigmentosum are excessive sunburn reactions in the form of inflammations already after very short contact with sunlight (especially face, hands, arms), prematurely aging skin that is wrinkled and has brown-reddish or freckle-like pigmentation, as well as tumors on the skin and eyes that can degenerate malignantly in the further course of the disease (squamous cell carcinomas, melanomas, basaliomas). Furthermore, xeroderma pigmentosum causes telangiectasia (dilatation of the small blood vessels), keratitis (inflammation of the cornea) and, in about one fifth of those affected, neurological disorders (sensory disturbances, movement disorders, hearing loss). Depending on the specific expression of the present genetic defect, a total of seven or eight forms of xeroderma pigmentosum (A to G and V) can be differentiated.
Causes
The causes of xeroderma pigmentosum lie in a genetic defect that is inherited recessively. The so-called repair enzymes of the DNA are damaged in this case and cannot repair skin damage caused by UV radiation as in healthy people. Xeroderma pigmentosum is due to an autosomal recessively inherited gene defect in the DNA repair system, as a result of which the DNA damage caused by UV light can no longer be repaired by the skin and mucous membrane cells. The UV-B rays, which are not filtered out by the earth’s atmosphere, cause the synthesis of thymidine dimers in skin cells, which are a compound of two thymidine building blocks. In a healthy organism, these compounds, which are harmful to cells, are recognized by a DNA repair system consisting of enzymes and are released from the DNA. In xeroderma pigmentosum, this repair system is disturbed by a genetic defect and there is a deficiency of the DNA repair enzymes or DNA endonucleases involved in this process.
DNA endonucleases involved in this process, these connections are not dissolved, so that the affected skin or mucous membrane cells can die or degenerate into cancer cells. Accordingly, xeroderma pigmentosum is often accompanied by skin cancer already in childhood. Any exposure to sunlight therefore leads to painful inflammations, which cannot regenerate on their own. Doctors divide the disease into different types, depending on where exactly the defective gene is located. Some of these types of the disease are not only characterized by the already mentioned hypersensitivity to sunlight, but are also associated with neurological disorders such as hearing loss, movement disorders or even a significant reduction in intelligence. For a child to be born with xeroderma pigmentosum, both parents must have the predisposition.
Symptoms, complaints and signs
Xeroderma pigmentosum is manifested by such symptoms as extreme photosensitivity, pigmentary changes on the skin, eye disorders, neurological problems, and constant formation of new skin tumors. Photosensitivity is noticeable already in infancy. Thus, after a short exposure to light, the skin often develops severe sunburn with blisters that are difficult to heal. This particularly affects the face, arms or legs. In some patients, however, the skin initially remains inconspicuous after exposure to the sun. However, in all those affected, a large number of so-called moles later develop, which are diagnosed as both benign and malignant skin tumors. The majority of malignant tumors are basaliomas, followed by spinaliomas and melanomas. Basaliomas do not usually metastasize. However, they often lead to disfigurement of the face and affected areas. Melanomas in particular grow very aggressively and are often the cause of premature death in patients. Sometimes the first symptom of xeroderma pigmentosum is also light sensitivity of the eyes. The patient initially reacts very photophobic. Later, chronic corneal and conjunctival inflammation occurs. The visual acuity decreases. Later, there is even a threat of complete loss of eyesight. Tumors can also develop on the eyes. Spinaliomas are most frequently observed there. In the course of the disease, some of the patients also experience progressive neurological symptoms, which can manifest themselves as reduced intelligence, paralysis, and movement disorders.
Diagnosis and course
Xeroderma pigmentosum is usually diagnosed on the basis of presenting symptoms. If xeroderma pigmentosum is suspected, the treating physician can perform a DNA examination to determine the exact type of the disease and then treat it appropriately. Blood and/or skin analysis can be used to determine how well the skin cells are able to repair DNA damage after exposure to UV light. Gene analysis can also determine which form of xeroderma pigmentosum is present in the affected person. Xeroderma pigmentosum has an unfavorable prognosis, since malignant tumors usually appear in the advanced course of the disease and already before the age of 20. However, with early diagnosis and consistent use of protective measures against UV light, this can be positively influenced and more than two thirds of those affected by xeroderma pigmentosum reach the age of 40. The first signs of xeroderma pigmentosum are very rapid severe sunburns or inflammations. The skin discolors, dries out and ages rapidly. From the inflammations, which do not heal properly, malignant tumors of the skin, but also of the eyes, form in the further course. Due to this rapid formation of cancer cells, the life expectancy of those affected is rather low. However, the exact prognosis depends on what type of disease it is and whether it is detected in time.
Complications
The disease xeroderma pigmentosum can significantly restrict the everyday life of the affected person and thereby also reduce the quality of life. Those affected suffer primarily from a very high sensitivity to sunlight, so that even a short exposure to sunlight causes burns and discoloration on the skin. Spots and redness form on the skin, which can also be accompanied by itching. The skin itself appears shriveled by xeroderma pigmentosum and may be covered by scars. In many cases, the patients are ashamed of the symptoms, so that it can often lead to inferiority complexes and thus to a significantly reduced self-esteem in the patient. Especially in children, the complaints can also lead to bullying or teasing, causing them to suffer from psychological symptoms. The skin can also become inflamed. Those affected also suffer from sunburn very often due to the disease, so they are always dependent on sunscreen or protective clothing. Since xeroderma pigmentosum cannot be cured causally, only the individual symptoms can be treated. There are no particular complications, although a positive course of the disease does not occur. Possibly, the disease also reduces the life expectancy of the patient.
When should you go to the doctor?
People who are exposed to intense sunlight often suffer sunburn. It is not always necessary to consult a doctor for this. In most cases, self-help measures are sufficient to achieve the fastest possible relief. In addition, it should be checked whether changes and optimizations can be made in dealing with direct sunlight on the skin. Sunscreen creams can be applied as a preventive measure and the time spent in direct UV light should be minimized. If, despite all efforts, burns or pain occur disproportionately quickly when the skin is exposed to the sun, a visit to the doctor is necessary. Sensitivity to light, limitations of vision or changes in pigmentation on the skin are signs of a disease. A visit to the doctor is necessary so that the causes can be determined and a diagnosis made. Withdrawal from social life, behavioral problems or mood swings are indications of a health disorder.
Treatment and therapy
If xeroderma pigmentosum remains untreated, the life expectancy of affected individuals is only a few years. Therefore, it is essential to consult a medical professional at the first suspicion and, should the diagnosis be made, to take appropriate steps. Xeroderma pigmentosum cannot be cured; however, appropriate treatment can often significantly increase the life expectancy of those affected. This includes consistently avoiding sunlight. Sufferers must not leave the house at all during the day or must wear special UV-repellent clothing. Windows must also be darkened accordingly and covered with UV-repellent film. Therapeutic measures in the case of xeroderma pigmentosum have thus far been limited to minimizing the symptoms and preventing skin cancer through consistent protective measures against UV light and regular check-ups by the dermatologist (skin doctor). These primarily include avoiding daylight (moonshine children), wearing appropriate protective clothing, especially on the arms, neck and face, as well as UV glasses and sun creams with a very high sun protection factor. In addition, it is recommended to have the windows of rooms in which affected persons spend more time and longer periods during the day coated with a special UV light protection film. Promising results have been achieved in clinical tests with a liposome lotion applied to the skin and through which DNA repair enzymes are supplied locally from the outside. A significant reduction of thymidine dimer content and thus of skin damage induced by it could be observed in xeroderma pigmentosum affected individuals, although no complete normalization could be achieved with regard to sensitivity to UV light. However, tests on this therapeutic approach for xeroderma pigmentosum have been discontinued for the time being due to lack of funds. In addition, attempts are being made within the framework of genetic engineering procedures to replace diseased skin areas with healthy skin cells (e.g. from the buttock area) which have been provided with functional DNA repair mechanisms or a normal copy of the defective gene. However, this therapeutic procedure for xeroderma pigmentosum is still in an early research phase. The necessity of these drastic measures usually entails a strong social isolation, not least because of the lack of understanding of the society. Regular visits to the doctor with comprehensive examinations of the skin and eyes can prevent the development of malignant ulcers. Since the skin of those affected is generally very sensitive, it must be creamed frequently and given special care. If sunburn or inflammation has occurred, painkillers can be administered temporarily. The exact type of treatment, however, always depends on the type of disease and the individual manifestation.
Prevention
Since xeroderma pigmentosum is a disease that is hereditary, prevention in the true sense is not possible. If the genetic defect is present in potential parents, they should seek detailed advice from a gynecologist before becoming pregnant. If the disease is diagnosed in a child, appropriate medical steps should be taken as soon as possible so that the affected person can live as long and as symptom-free a life as possible.
Follow-up care
Xeroderma pigmentosum is an incurable disease.There is no treatment for the disease. Affected persons should avoid any contact with UV rays or at least reduce it considerably. Solariums should not be used under any circumstances. Exposure to the radiation there would only further aggravate the symptoms and generally the disease state of those affected. Exposure to sunlight should also be avoided. The everyday life of the affected persons is considerably restricted by the diseased. Any activities as well as occupation must be adapted to the disease. Affected persons must not go outside without appropriate sun protection. Especially in summer, affected persons must be extremely careful and must not make any rash decisions. Affected persons must apply special UV protection, which prevents the rays from penetrating into the organism. Clothing should also be adapted to the disease. The body should be completely covered. For example, hats protect the face from the penetration of UV rays. It is mandatory to cover the body with long pants and long tops. The disease represents a high burden for those affected. Sometimes it is advisable to undergo permanent psychological counseling for dealing with the disease. Affected individuals should also seek the help and support of family members if possible.
What you can do yourself
In this disease, the affected person must reduce UV radiation to a minimum or avoid it completely. As a result, the lifestyle is severely impaired. Natural as well as artificial UV light must therefore only be taken in according to the possibilities and conditions of the organism. Offers like solariums are to be avoided completely. The UV light there would lead to a rapid increase in problems. Likewise, direct exposure to sunlight is to be avoided. In everyday life, the planning of leisure activities or professional activities should be adjusted accordingly. The patient should never leave the house without appropriate sun protection. Especially in the summer months, no rash actions should be taken. The skin should be protected with creams that reduce or block the penetration of UV rays into the organism. In addition, clothing should be adjusted. It is advisable to cover the body almost completely with fabrics or protective accessories. Hats or sunshades help to avoid the exposure of the face to UV radiation. The other parts of the body can be well covered by wearing long pants or long tops. At the same time, care should be taken to ensure that clothing is permeable to air and does not cause a constrictive feeling. Since the disease is a heavy emotional burden, mental strength should be supported by cognitive exercise sessions.
