Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Xeroderma Pigmentosum Treatment & Management

  • Author: Linda J Fromm, MD, MA, FAAD; Chief Editor: William D James, MD  more...
 
Updated: Jun 10, 2016
 

Medical Care

The goal of treatment is to protect the patient from sunlight. To this end, regular visits to the dermatologist might be necessary for the purposes of patient education and early detection and treatment of any malignancies.

The use of sunscreens in conjunction with other sun-avoidance methods (eg, protective clothing, hats, eyewear) can minimize UV-induced damage in patients with xeroderma pigmentosum. Sunscreens should be applied to all exposed surfaces (including the hands, the back of the neck, the ears, the lower lips, and the anterior part of the chest) whenever UV exposure is expected. The 2 basic types of sunscreens are physical and chemical.

Physical sunscreens scatter and reflect radiation. They contain large particles, such as titanium dioxide, zinc oxide, red ferric oxide, talc, and kaolin. Physical sunscreens block UV rays, infrared rays, and visible light. Their main disadvantage is that most are opaque, making them less cosmetically acceptable. New advances in physical sunscreens include microfine particles of titanium dioxide or zinc oxide, which are transparent.

Chemical sunscreens absorb UV radiation. Para-amino benzoic acid (PABA) was the first agent developed, but its potential to cause allergic reactions has limited its use. Some agents, such as benzophenones, mainly block UV-A, but they are weak UV-B photoprotectors. Avobenzone (Parsol 1789) has been introduced commercially in the United States. It is a much stronger UV-A photoprotector. Other agents, such as PABA esters, salicylates, and cinnamates, mainly block UV-B. Broad-spectrum chemical sunscreens include a combination of ingredients designed to block both UV-B and UV-A. Many of the new preparations are also designed to be water resistant.

No matter which sunscreen is used, the degree of protection is only partial. The effectiveness of sunscreens is expressed as a sun protection factor (SPF). The SPF is the ratio of the least amount of UV radiation required to produce a minimum erythema reaction with a sunscreen to the amount of the energy required to produce the same erythema without any sunscreen. Usually, sunscreens with a SPF of 15 or greater are recommended.

The Medscape Reference article Sunscreens and Photoprotection provides a detailed discussion of these agents.

Oral retinoids have been shown to decrease the incidence of skin cancer in patients with xeroderma pigmentosum.[20] This therapy is limited by dose-related irreversible calcification of ligaments and tendons.

Chemical therapy with 5-fluorouracil may be useful for actinic keratoses. Giannotti et al[21] suggested in a case report that topical treatment with imiquimod and acitretin is an alternative to surgery. They prescribed imiquimod 5% cream to be applied 3 times weekly in combination with oral acitretin (20 mg/d) for 4-6 weeks. No adverse events were reported during treatment, and the tumors had resolved at the 6-month follow-up visit.

A new approach to photoprotection is to repair DNA damage after UV exposure. This can be accomplished by delivery of a DNA repair enzyme into the skin by means of specially engineered liposomes. T4 endonuclease V has been shown to repair cyclobutane pyrimidine dimers resulting from DNA damage.[8]

Yarosh et al studied in a randomized fashion the effect of topically applied T4 endonuclease V in liposomes in xeroderma pigmentosum patients. Thirty patients were enrolled in this prospective double-blinded study. The annualized rate of new actinic keratoses was 8.2% among the patients assigned T4N5 liposome lotion and 25.9% among those assigned placebo. For basal cell carcinoma, the annualized rates of new lesions were 3.8% in the treatment group and 5.4% in the placebo group. No significant adverse effects were found among any of the patients. The topical application of DNA repair enzymes to the sun-damaged skin of patients with xeroderma pigmentosum lowered the rate of development of 2 forms of these lesions during 1 year of treatment.

Gene therapy for xeroderma pigmentosum is still in a theoretical and experimental stage. Various methods of correcting the defects in xeroderma pigmentosum have been attempted in vitro and in animal studies using viral vectors (adenoviruses and retroviruses) carrying the gene replacement products. Ex vivo skin gene therapy, which refers to grafting skin that has the genetic defect corrected, may be useful in xeroderma pigmentosum in the future.

Next

Surgical Care

The malignancies associated with xeroderma pigmentosum should be completely excised.

Previous
Next

Consultations

Consultation with an ophthalmologist is recommended because of the ocular problems associated with xeroderma pigmentosum. The use of UV-absorbing sunglasses should be included as part of the ocular management in patients with this disease. Artificial tears might be used. If corneal opacities supervene, corneal transplants can be performed.

Consultation with a neurologist is also recommended because neurologic abnormalities are seen in 20% of patients with xeroderma pigmentosum.

Previous
Next

Complications

Multiple cutaneous neoplasms develop at a young age in persons with xeroderma pigmentosum. Death is usually caused by metastatic malignant melanoma or squamous cell carcinoma.

Patients with xeroderma pigmentosum are also susceptible to infection and, in some subtypes, neurologic complications.

Previous
Next

Long-Term Monitoring

Patients should receive follow-up care every 3 months. Follow-up care should be focused on educating the patient and the patient's parents about effective sun protection and early recognition of skin cancer.

Genetic counseling should be offered for families at risk. Antenatal diagnosis is possible by amniocentesis or chorionic villi sampling.

Previous
 
 
Contributor Information and Disclosures
Author

Linda J Fromm, MD, MA, FAAD Private Practice, Fromm Dermatology at Health Concepts, Rapid City, South Dakota

Linda J Fromm, MD, MA, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Society for Investigative Dermatology, Association of Professors of Dermatology, North American Hair Research Society

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Craig A Elmets, MD Professor and Chair, Department of Dermatology, Director, Chemoprevention Program Director, Comprehensive Cancer Center, UAB Skin Diseases Research Center, University of Alabama at Birmingham School of Medicine

Craig A Elmets, MD is a member of the following medical societies: American Academy of Dermatology, American Association of Immunologists, American College of Physicians, American Federation for Medical Research, Society for Investigative Dermatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: University of Alabama at Birmingham; University of Alabama Health Services Foundation<br/>Serve(d) as a speaker or a member of a speakers bureau for: Ferndale Laboratories<br/>Received research grant from: NIH, Veterans Administration, California Grape Assn<br/>Received consulting fee from Astellas for review panel membership; Received salary from Massachusetts Medical Society for employment; Received salary from UpToDate for employment. for: Astellas.

A Hafeez Diwan, MD, PhD Associate Professor, Department of Pathology, University of Texas MD Anderson Cancer Center

A Hafeez Diwan, MD, PhD is a member of the following medical societies: College of American Pathologists, Southern Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Marcelo Horenstein, MD, to the development and writing of this article.

References
  1. English JS, Swerdlow AJ. The risk of malignant melanoma, internal malignancy and mortality in xeroderma pigmentosum patients. Br J Dermatol. 1987 Oct. 117(4):457-61. [Medline].

  2. DiGiovanna JJ, Kraemer KH. Shining a light on xeroderma pigmentosum. J Invest Dermatol. 2012 Mar. 132(3 Pt 2):785-96. [Medline]. [Full Text].

  3. Warrick E, Garcia M, Chagnoleau C, Chevallier O, Bergoglio V, Sartori D, et al. Preclinical Corrective Gene Transfer in Xeroderma Pigmentosum Human Skin Stem Cells. Mol Ther. 2011 Nov 8. [Medline].

  4. Gratchev A, Strein P, Utikal J, Sergij G. Molecular genetics of Xeroderma pigmentosum variant. Exp Dermatol. 2003 Oct. 12(5):529-36. [Medline].

  5. Ortega-Recalde O, Vergara JI, Fonseca DJ, Ríos X, Mosquera H, Bermúdez OM, et al. Whole-exome sequencing enables rapid determination of xeroderma pigmentosum molecular etiology. PLoS One. 2013. 8(6):e64692. [Medline]. [Full Text].

  6. Nouspikel T. Nucleotide excision repair and neurological diseases. DNA Repair (Amst). 2008 Jul 1. 7(7):1155-67. [Medline].

  7. Boyle J, Ueda T, Oh KS, Imoto K, Tamura D, Jagdeo J, et al. Persistence of repair proteins at unrepaired DNA damage distinguishes diseases with ERCC2 (XPD) mutations: cancer-prone xeroderma pigmentosum vs. non-cancer-prone trichothiodystrophy. Hum Mutat. 2008 Oct. 29(10):1194-208. [Medline].

  8. Bowden NA, Beveridge NJ, Ashton KA, Baines KJ, Scott RJ. Understanding Xeroderma Pigmentosum Complementation Groups Using Gene Expression Profiling after UV-Light Exposure. Int J Mol Sci. 2015 Jul 14. 16 (7):15985-96. [Medline].

  9. Fréchet M, Warrick E, Vioux C, Chevallier O, Spatz A, Benhamou S, et al. Overexpression of matrix metalloproteinase 1 in dermal fibroblasts from DNA repair-deficient/cancer-prone xeroderma pigmentosum group C patients. Oncogene. 2008 Sep 4. 27(39):5223-32. [Medline].

  10. Parlanti E, Pietraforte D, Iorio E, Visentin S, De Nuccio C, Zijno A, et al. An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients. Mutat Res. 2015 Oct 23. 782:34-43. [Medline].

  11. Ito S, Kuraoka I, Chymkowitch P, Compe E, Takedachi A, Ishigami C, et al. XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: implications for Cockayne syndrome in XP-G/CS patients. Mol Cell. 2007 Apr 27. 26(2):231-43. [Medline].

  12. Niedernhofer LJ. Tissue-specific accelerated aging in nucleotide excision repair deficiency. Mech Ageing Dev. 2008 Jul-Aug. 129(7-8):408-15. [Medline].

  13. Schaffer JV, Orlow SJ. Radiation Therapy for High-Risk Squamous Cell Carcinomas in Patients with Xeroderma Pigmentosum: Report of Two Cases and Review of the Literature. Dermatology. 2011 Oct 21. [Medline].

  14. Sethi M, Lehmann AR, Fawcett H, Stefanini M, Jaspers N, Mullard K, et al. Patients with xeroderma pigmentosum complementation groups C, E and V do not have abnormal sunburn reactions. Br J Dermatol. 2013 Jul 25. [Medline].

  15. Lehmann AR, McGibbon D, Stefanini M. Xeroderma pigmentosum. Orphanet J Rare Dis. 2011 Nov 1. 6:70. [Medline]. [Full Text].

  16. Lasso JM, Yordanov YP, Pinilla C, Shef A. Invasive basal cell carcinoma in a xeroderma pigmentosum patient: facing secondary and tertiary aggressive recurrences. J Craniofac Surg. 2014 Jul. 25 (4):e336-8. [Medline].

  17. Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch Dermatol. 1987 Feb. 123(2):241-50. [Medline].

  18. Kleijer WJ, van der Sterre ML, Garritsen VH, Raams A, Jaspers NG. Prenatal diagnosis of xeroderma pigmentosum and trichothiodystrophy in 76 pregnancies at risk. Prenat Diagn. 2007 Dec. 27(12):1133-7. [Medline].

  19. Alapetite C, Benoit A, Moustacchi E, Sarasin A. The comet assay as a repair test for prenatal diagnosis of Xeroderma pigmentosum and trichothiodystrophy. J Invest Dermatol. 1997 Feb. 108(2):154-9. [Medline].

  20. Kraemer KH, DiGiovanna JJ, Moshell AN, Tarone RE, Peck GL. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med. 1988 Jun 23. 318(25):1633-7. [Medline].

  21. Giannotti B, Vanzi L, Difonzo EM, Pimpinelli N. The treatment of basal cell carcinomas in a patient with xeroderma pigmentosum with a combination of imiquimod 5% cream and oral acitretin. Clin Exp Dermatol. 2003 Nov. 28 Suppl 1:33-5. [Medline].

 
Previous
Next
 
Face of a toddler with xeroderma pigmentosum, representative of an early stage of the disease. Note the freckling and the scaling. Courtesy of Neil S. Prose, MD, Duke University Medical Center, Durham, North Carolina.
Back of an adolescent with xeroderma pigmentosum, representing a later stage of the disease. Note the mottled hyperpigmentation and atrophy. Courtesy of Neil S. Prose, MD, Duke University Medical Center, Durham, North Carolina.
Histologic features of actinic keratosis in an individual with xeroderma pigmentosum. Note the atypia of the keratinocytes and the parakeratosis.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.