There is no cure for XP. Patients have a lower life expectancy (median age of death is 32 years) than the general population.[3]Fassihi H. Spotlight on 'xeroderma pigmentosum'. Photochem Photobiol Sci. 2013 Jan;12(1):78-84.
https://www.doi.org/10.1039/c2pp25267h
http://www.ncbi.nlm.nih.gov/pubmed/23132518?tool=bestpractice.com
However, early diagnosis, strict and consistent ultraviolet radiation (UVR) and daylight protection, and regular cutaneous follow-up to evaluate and treat skin cancers increases life expectancy in patients without neurologic disease.[3]Fassihi H. Spotlight on 'xeroderma pigmentosum'. Photochem Photobiol Sci. 2013 Jan;12(1):78-84.
https://www.doi.org/10.1039/c2pp25267h
http://www.ncbi.nlm.nih.gov/pubmed/23132518?tool=bestpractice.com
[12]Giordano CN, Yew YW, Spivak G, et al. Understanding photodermatoses associated with defective DNA repair: syndromes with cancer predisposition. J Am Acad Dermatol. 2016 Nov;75(5):855-70.
http://www.ncbi.nlm.nih.gov/pubmed/27745641?tool=bestpractice.com
[25]Bradford PT, Goldstein AM, Tamura D, et al. Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair. J Med Genet. 2011 Mar;48(3):168-76.
http://www.ncbi.nlm.nih.gov/pubmed/21097776?tool=bestpractice.com
[26]Nakano E, Masaki T, Kanda F, et al. The present status of xeroderma pigmentosum in Japan and a tentative severity classification scale. Exp Dermatol. 2016 Aug;25 Suppl 3:28-33.
https://www.doi.org/10.1111/exd.13082
http://www.ncbi.nlm.nih.gov/pubmed/27539899?tool=bestpractice.com
The leading causes of mortality are metastatic skin cancer, neurodegeneration, and internal non-cutaneous malignancies. Patients with neurodegeneration have a lower mean age of death (29 years) than patients without neurodegeneration (37 years).[7]Leung AK, Barankin B, Lam JM, et al. Xeroderma pigmentosum: an updated review. Drugs Context. 2022;11:2022-2-5.
https://www.doi.org/10.7573/dic.2022-2-5
http://www.ncbi.nlm.nih.gov/pubmed/35520754?tool=bestpractice.com
[25]Bradford PT, Goldstein AM, Tamura D, et al. Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair. J Med Genet. 2011 Mar;48(3):168-76.
http://www.ncbi.nlm.nih.gov/pubmed/21097776?tool=bestpractice.com
Mortality in patients with neurodegeneration is commonly due to aspiration, infection, or trauma.[2]Moriwaki S, Kanda F, Hayashi M, et al. Xeroderma pigmentosum clinical practice guidelines. J Dermatol. 2017 Oct;44(10):1087-96.
https://www.doi.org/10.1111/1346-8138.13907
http://www.ncbi.nlm.nih.gov/pubmed/28771907?tool=bestpractice.com
Complications
In addition to cutaneous and ocular malignancies, patients are at increased risk of developing solid organ cancers including tumors of the thyroid, lung, uterus, breast, pancreas, brain, stomach, kidney, and testicles; and hematological malignancies such as leukemia.[7]Leung AK, Barankin B, Lam JM, et al. Xeroderma pigmentosum: an updated review. Drugs Context. 2022;11:2022-2-5.
https://www.doi.org/10.7573/dic.2022-2-5
http://www.ncbi.nlm.nih.gov/pubmed/35520754?tool=bestpractice.com
[14]DiGiovanna JJ, Kraemer KH. Shining a light on xeroderma pigmentosum. J Invest Dermatol. 2012 Mar;132(3 pt 2):785-96.
https://www.doi.org/10.1038/jid.2011.426
http://www.ncbi.nlm.nih.gov/pubmed/22217736?tool=bestpractice.com
[43]Nikolaev S, Yurchenko AA, Sarasin A. Increased risk of internal tumors in DNA repair-deficient xeroderma pigmentosum patients: analysis of four international cohorts. Orphanet J Rare Dis. 2022 Mar 4;17(1):104.
https://www.doi.org/10.1186/s13023-022-02203-1
http://www.ncbi.nlm.nih.gov/pubmed/35246173?tool=bestpractice.com
Patients are also at higher risk of developing smoking-induced cancers.[14]DiGiovanna JJ, Kraemer KH. Shining a light on xeroderma pigmentosum. J Invest Dermatol. 2012 Mar;132(3 pt 2):785-96.
https://www.doi.org/10.1038/jid.2011.426
http://www.ncbi.nlm.nih.gov/pubmed/22217736?tool=bestpractice.com
A low threshold for investigation of these malignancies is recommended in all patients.[7]Leung AK, Barankin B, Lam JM, et al. Xeroderma pigmentosum: an updated review. Drugs Context. 2022;11:2022-2-5.
https://www.doi.org/10.7573/dic.2022-2-5
http://www.ncbi.nlm.nih.gov/pubmed/35520754?tool=bestpractice.com
[43]Nikolaev S, Yurchenko AA, Sarasin A. Increased risk of internal tumors in DNA repair-deficient xeroderma pigmentosum patients: analysis of four international cohorts. Orphanet J Rare Dis. 2022 Mar 4;17(1):104.
https://www.doi.org/10.1186/s13023-022-02203-1
http://www.ncbi.nlm.nih.gov/pubmed/35246173?tool=bestpractice.com
Women with XP (mostly XPC gene mutations) often develop premature menopause (before age 40 years).[7]Leung AK, Barankin B, Lam JM, et al. Xeroderma pigmentosum: an updated review. Drugs Context. 2022;11:2022-2-5.
https://www.doi.org/10.7573/dic.2022-2-5
http://www.ncbi.nlm.nih.gov/pubmed/35520754?tool=bestpractice.com
[23]Kraemer KH, DiGiovanna JJ, Tamura D. Xeroderma pigmentosum. In: Adam MP, Everman DB, Mirzaa GM, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; June 20, 2003 [updated 2022 Mar 24].
https://www.ncbi.nlm.nih.gov/books/NBK1397
http://www.ncbi.nlm.nih.gov/pubmed/20301571?tool=bestpractice.com
Gynecologic referral is recommended for pubertal women with XP after menarche to discuss possible premature menopause and the option of preserving eggs for future pregnancies.[23]Kraemer KH, DiGiovanna JJ, Tamura D. Xeroderma pigmentosum. In: Adam MP, Everman DB, Mirzaa GM, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; June 20, 2003 [updated 2022 Mar 24].
https://www.ncbi.nlm.nih.gov/books/NBK1397
http://www.ncbi.nlm.nih.gov/pubmed/20301571?tool=bestpractice.com
See Premature ovarian failure.