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.