Xeroderma Pigmentosum Treatment & Management

  • Author: A Hafeez Diwan, MD, PhD; Chief Editor: William D James, MD   more...
 
Updated: Nov 29, 2011
 

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 eMedicine 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.[13] 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[14] 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.[15] 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. Yarosh et al[16] 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 ofthese 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.[17]
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Surgical Care

The malignancies associated with xeroderma pigmentosum should be completely excised.

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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.

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Contributor Information and Disclosures
Author

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 and Southern Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Craig A Elmets, MD  Professor and Chair, Department of Dermatology, Director, 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, and Society for Investigative Dermatology

Disclosure: Palomar Medical Technologies Stock None; Astellas Consulting fee Review panel membership; Massachusetts Medical Society Salary Employment; Abbott Laboratories Grant/research funds Independent contractor; UpToDate Salary Employment; Biogen Grant/research funds Independent contractor; Clinuvel Independent contractor; Covan Basilea Pharmaceutical Grant/research funds Independent contractor; ISDIN None Consulting; TenX BIopharma Grant/research funds Independent contractor

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, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

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, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Joel M Gelfand, MD, MSCE  Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

William D James, MD  Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System

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

Disclosure: Elsevier Royalty Other

Additional Contributors

The authors and editors of eMedicine 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. Oct 1987;117(4):457-61. [Medline].

  2. 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. Nov 8 2011;[Medline].

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  5. 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. Oct 2008;29(10):1194-208. [Medline].

  6. 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. Sep 4 2008;27(39):5223-32. [Medline].

  7. 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. Apr 27 2007;26(2):231-43. [Medline].

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

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

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

  11. 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. Dec 2007;27(12):1133-7. [Medline].

  12. 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. Feb 1997;108(2):154-9. [Medline].

  13. 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. Jun 23 1988;318(25):1633-7. [Medline].

  14. 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. Nov 2003;28 Suppl 1:33-5. [Medline].

  15. Yarosh DB, O'Connor A, Alas L, Potten C, Wolf P. Photoprotection by topical DNA repair enzymes: molecular correlates of clinical studies. Photochem Photobiol. Feb 1999;69(2):136-40. [Medline].

  16. Yarosh D, Klein J, O'Connor A, Hawk J, Rafal E, Wolf P. Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Xeroderma Pigmentosum Study Group. Lancet. Mar 24 2001;357(9260):926-9. [Medline].

  17. Zahid S, Brownell I. Repairing DNA damage in xeroderma pigmentosum: T4N5 lotion and gene therapy. J Drugs Dermatol. Apr 2008;7(4):405-8. [Medline].

  18. Cafardi JA, Elmets CA. T4 endonuclease V: review and application to dermatology. Expert Opin Biol Ther. Jun 2008;8(6):829-38. [Medline].

  19. de Laat WL, Jaspers NG, Hoeijmakers JH. Molecular mechanism of nucleotide excision repair. Genes Dev. Apr 1 1999;13(7):768-85. [Medline].

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  21. 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. Oct 21 2011;[Medline].

  22. Subba Rao K. Mechanisms of disease: DNA repair defects and neurological disease. Nat Clin Pract Neurol. Mar 2007;3(3):162-72. [Medline].

  23. Sugasawa K. Xeroderma pigmentosum genes: functions inside and outside DNA repair. Carcinogenesis. Mar 2008;29(3):455-65. [Medline].

  24. Tanaka K, Sekiguchi M, Okada Y. Restoration of ultraviolet-induced unscheduled DNA synthesis of xeroderma pigmentosum cells by the concomitant treatment with bacteriophage T4 endonuclease V and HVJ (Sendai virus). Proc Natl Acad Sci U S A. Oct 1975;72(10):4071-5. [Medline].

 
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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.
 
 
 
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