Core Dermatology Diagnoses / CategoriesNeoplastic Benign and Malignant

Xeroderma pigmentosa

Author: Faculty Reviewer:

Publish date: Posted on
Last updated: March 20, 2022

Keywords #

xeroderma pigmentosum
XP
genodermatosis

Diagnosis #

Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by defective DNA repair and inherited in an autosomal recessive fashion [1]. Subtypes of XP include XP-A through -G and XP-V (“variant”) [2]. Individuals with XP are extremely photosensitive and are at a 2,000 to 10,000-fold increased risk for developing skin cancers compared to the general population [3, 4].

Key Concepts #
  • Xeroderma pigmentosum is a rare, autosomal recessive genodermatosis 
  • XP is caused by genetic deficiencies in nucleotide excision repair. 
  • XP patients are exquisitely sensitive to UV damage. 
Epidemiology #

Higher prevalence of XP is seen in Japan, at 1 per 22,000 people. In Western countries, the prevalence is 1-2 per million [5, 6]. Median age of first skin cancer is 9 years old for non-melanoma skin cancers and 22 years old for melanoma [3]. 

Clinical Features #
  • Early onset of lentigines on sun-exposed skin. 
  • Sunburn with minimal exposure to UV light in 50% of XP patients [7]. 
  • Multiple skin cancers, actinic keratoses, poikiloderma, skin atrophy, and telangiectasias.  
  • Many XP patients present with ocular and neurologic symptoms, including photophobia, keratitis, ocular cancers, and progressive neurodegeneration [3, 8]. 
  • 30% chance of neurologic symptoms (mostly in the XP-A group). 
Differential Diagnoses #
  • Ephelides (freckle)
  • Basal Cell Nevus Syndrome
  • Leopard Syndrome
  • Cockayne Syndrome
  • Trichothiodystrophy
  • Cerebro-Oculo-Facial-Skeletal Syndrome
  • UV-Sensitive Syndrome
  • Dyschromatosis Symmetrica Hereditaria
  • Erythropoietic Protoporphyria
Diagnostic Workup #

XP is initially diagnosed clinically, but can be confirmed with genetic testing looking for mutations in causative genes (XPA, XPB/ERCC3, XPC, XPD/ERCC2, XPE/DDB2, XPF/ERCC4, XPG/ERCC5, XP Variant/Polymerase η) [2].

Treatment #

The most important therapy for XP patients is preventative, which includes sun protection and avoidance of UV radiation. Some patients may benefit from reversing their day-night cycles to avoid the sun. Skin exams should be performed every 3-6 months to detect and treat skin cancers. Smoking avoidance and regular eye and neurologic exams are also recommended [9].

References #
  1. Cleaver, J. E. “Defective Repair Replication of DNA in Xeroderma Pigmentosum.” Nature, vol. 218, no. 5142, 1968, pp. 652-656, doi:10.1038/218652a0. 
  2. DiGiovanna, J. J. and K. H. Kraemer. “Shining a Light on Xeroderma Pigmentosum.” J Invest Dermatol, vol. 132, no. 3 Pt 2, 2012, pp. 785-796, doi:10.1038/jid.2011.426. 
  3. Bradford, P. T. et al. “Cancer and Neurologic Degeneration in Xeroderma Pigmentosum: Long Term Follow-up Characterises the Role of DNA Repair.” J Med Genet, vol. 48, no. 3, 2011, pp. 168-176, doi:10.1136/jmg.2010.083022. 
  4. Kraemer, K. H. et al. “The Role of Sunlight and DNA Repair in Melanoma and Nonmelanoma Skin Cancer. The Xeroderma Pigmentosum Paradigm.” Arch Dermatol, vol. 130, no. 8, 1994, pp. 1018-1021. 
  5. Hirai, Y. et al. “Heterozygous Individuals Bearing a Founder Mutation in the Xpa DNA Repair Gene Comprise Nearly 1% of the Japanese Population.” Mutat Res, vol. 601, no. 1-2, 2006, pp. 171-178, doi:10.1016/j.mrfmmm.2006.06.010. 
  6. Kleijer, W. J. et al. “Incidence of DNA Repair Deficiency Disorders in Western Europe: Xeroderma Pigmentosum, Cockayne Syndrome and Trichothiodystrophy.” DNA Repair (Amst), vol. 7, no. 5, 2008, pp. 744-750, doi:10.1016/j.dnarep.2008.01.014. 
  7. Sethi, M. et al. “Patients with Xeroderma Pigmentosum Complementation Groups C, E and V Do Not Have Abnormal Sunburn Reactions.” Br J Dermatol, vol. 169, no. 6, 2013, pp. 1279-1287, doi:10.1111/bjd.12523. 
  8. Brooks, B. P. et al. “Ocular Manifestations of Xeroderma Pigmentosum: Long-Term Follow-up Highlights the Role of DNA Repair in Protection from Sun Damage.” Ophthalmology, vol. 120, no. 7, 2013, pp. 1324-1336, doi:10.1016/j.ophtha.2012.12.044. 
  9. Moriwaki, S. et al. “Xeroderma Pigmentosum Clinical Practice Guidelines.” J Dermatol, vol. 44, no. 10, 2017, pp. 1087-1096, doi:10.1111/1346-8138.13907. 
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