eMedicine Specialties > Dermatology > Photo-Related Diseases

Xeroderma Pigmentosum: Differential Diagnoses & Workup

Author: A Hafeez Diwan, MD, PhD, Associate Professor, Department of Pathology, University of Texas MD Anderson Cancer Center
Contributor Information and Disclosures

Updated: Oct 7, 2008

Differential Diagnoses

Acanthosis Nigricans
LEOPARD Syndrome
Bloom Syndrome (Congenital Telangiectatic Erythema)
Lupus Erythematosus, Acute
Cockayne Syndrome
Rothmund-Thomson Syndrome
Ephelides (Freckles)
Werner Syndrome
Hartnup Disease
Hydroa Vacciniforme

Other Problems to Be Considered

Basal cell nevus syndrome
Porphyria

Workup

Laboratory Studies

  • No consistent routine laboratory abnormalities are present in xeroderma pigmentosum patients. The diagnosis of xeroderma pigmentosum can be established with studies performed in specialized laboratories. These studies include cellular hypersensitivity to UV radiation and chromosomal breakage studies, complementation studies, and gene sequencing to identify the specific gene complementation group.
    • In the cellular hypersensitivity to UV radiation and chromosomal breakage studies, the xeroderma pigmentosum fibroblasts are stressed with different doses of UV radiation. Then, chromosomal breakage is evaluated in at least 100-200 cells, with at least 2 replicates for each dose. The cells from the patient are compared with those from the patient's parents (if possible, as they are obligate heterozygotes for xeroderma pigmentosum). Cells from unrelated healthy individuals are used as controls. To eliminate subjectivity, the person evaluating the chromosomal abnormalities is not informed as to which group the slides being examined belong. Prenatal diagnosis of xeroderma pigmentosum can be accomplished using similar chromosomal breakage studies on amniocytes from at-risk fetuses.
    • The xeroderma pigmentosum complementation groups can be determined using cell-fusion techniques followed by assessment of DNA repair or by gene sequencing.
  • Prenatal diagnosis is possible by amniocentesis or chorionic villi sampling. Unscheduled DNA synthesis is the classic method for diagnosis. A modified technique using cultivation of both patient and control cells at the same time has also been described.9 A faster technique is the alkaline comet assay (single-cell gel electrophoresis assay). This method, in addition to being faster, requires fewer cells and does not require radioactivity.10

Other Tests

Electroencephalographic findings may be abnormal.

Histologic Findings

The histologic findings of the first stage of the disease include hyperkeratosis and increased melanin pigment (this corresponds to the clinical freckling) in the basal cell layer (not necessarily accompanied by an increase in the numbers of melanocytes). Some rete ridges may be elongated, whereas other rete ridges may be atrophic. These findings may be accompanied by a chronic inflammatory infiltrate in the upper dermis.

In the second stage, atrophy ensues, and the hyperkeratosis and the hyperpigmentation are more marked. Telangiectasia may be prominent. These findings correspond to poikiloderma. In addition, the epidermis may exhibit architectural disorder and atypia, and the dermis may be elastotic. Therefore, the histologic picture might be indistinguishable from that of actinic keratosis (see Media File 3). The histologic appearances of the various tumors that complicate xeroderma pigmentosum are seen in the third stage of xeroderma pigmentosum.

More on Xeroderma Pigmentosum

Overview: Xeroderma Pigmentosum
Differential Diagnoses & Workup: Xeroderma Pigmentosum
Treatment & Medication: Xeroderma Pigmentosum
Follow-up: Xeroderma Pigmentosum
Multimedia: Xeroderma Pigmentosum
References
[ CLOSE WINDOW ]

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

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

  4. 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].

  5. 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].

  6. 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].

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

  8. 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].

  9. 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].

  10. 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].

  11. 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].

  12. 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].

  13. 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].

  14. 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].

  15. 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].

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

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

  18. Elmets CA, Anderson CY. Sunscreens and photocarcinogenesis: an objective assessment. Photochem Photobiol. Apr 1996;63(4):435-40. [Medline].

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

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

  21. 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].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

xeroderma pigmentosum, skin cancer, XP, photosensitivity, pigmentary changes, premature skin aging, malignant tumors, defective nucleotide excision repair, NER, defect in DNA repair, defective DNA repair

[ CLOSE WINDOW ]

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.

Medical Editor

Craig A Elmets, MD, Director of Dermatology, Departments of Dermatology, Pathology, and Environmental Health Sciences; Professor, The Kirklin Clinic, University of Alabama at Birmingham
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; Merck Consulting fee Independent contractor; Tronox Consulting fee Independent contractor; Amgen Consulting fee Review panel membership; Astellas Consulting fee Review panel membership; Massachusetts Medical Society Salary Employment

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University 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.

Managing Editor

Jeffrey J Miller, MD, Associate Professor, Department of Dermatology, Penn State University, Milton S Hershey Medical Center
Disclosure: Nothing to disclose.

CME Editor

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 None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.