Introduction:
Xeroderma pigmentosum (XP) is an autosomal recessive photosensitive disease that is associated with development of skin cancers in sun-exposed areas [1]. The first report on XP as a serious photosensitivity disease with dyschromia was published at the end of the 19th century by Kaposi et al. [2,3]. Photosensitivity in patients with XP is attributed to failure to repair ultraviolet (UV)-induced DNA lesions by nucleotide excision repair or translation synthesis. In 1968, Cleaver observed that cells in patients with XP were abnormal in terms of their ability to repair DNA damage caused by UV light [4]. To date, eight genes, namely, XPA, XPB (ERCC3), XPC, XPD (ERCC2), XPE (DDB2), XPF (ERCC4), XPG (ERCC5), and XPV (POLH), have been implicated in XP. Accordingly, XP is classified into eight subtypes, from XP-A to XP-G and XP-V, each of which has characteristic clinical symptoms [5].
The prevalence of XP is low in Western Europe, with an incidence of 2-3 per million live births [6]. In Japan, on the other hand, the incidence of XP is 1 per 22,000 live births; 55% of affected individuals with XP-A, and there are about 1 million carriers of the XPA founder mutation [7, 8, 9]. In 2015, the Japanese Ministry of Health, Labor and Welfare classified XP as an intractable disease that is eligible for government support [9]. It is known that patients with XP have a 2,000-fold increased incidence of melanoma and a 10,000-fold increased incidence of non-melanoma skin cancer [1]. The recommendations for management of carcinogenic risk in patients with XP are (i) as follows: early diagnosis; (ii) lifelong protection from UV radiation, including avoidance of unnecessary UV exposure, wearing UV-blocking clothing, and use of topical sunscreens; and (iii) surgical resection of skin cancers [5, 9]. However, there is still no curative treatment for XP and no consensus has been reached regarding standard treatment for unresectable XP lesions. There have been several reports suggesting that immune checkpoint inhibitor (ICI) therapy has the potential to improve survival outcomes in patients with difficult-to-treat XP.
In this report, we describe our experience using ICI to treat a patient with XP and multiple systemic metastases of carcinoma.