No abstract

The patient was a 16-year-old boy who was diagnosed with Crohn's disease at 13 years of age, who was treated with mesalazine, azathioprine, and infliximab. Concurrently, the patient developed small freckle-like pigmented spots on sun-exposed areas, which gradually increased in number. At 14 and 16 years of age, a blue-gray macule and a nodule appeared on his face, respectively. A histopathological examination revealed that the macule had only postinflammatory pigmentation, while the nodule was basal cell carcinoma. The sensitivity to UV-killing by colony formation of the patient's cells was normal but was enhanced by caffeine treatment. In addition, a pathologic mutation in the POLH gene was identified and a diagnosis of xeroderma pigmentosum variant (XP-V) was established. XP-V is a cutaneous type of XP that is commonly diagnosed from middle age after the induction of skin cancer on sun-exposed areas. Our patient had a genetically sensitive background (XP-V), and we considered that immunosuppressive agents for Crohn's disease may have enhanced the photocarcinogenesis at a young age.This finding implies that we should be careful about a skin cancer production and that protection from UV may be essential when pediatric patients with a genetic background of UV sensitivity take immunosuppressive agents.

Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet light with an incidence of 1: 22,000 in Japan. From the clinical symptoms, XP is classified into 3 types, such as XP cutaneous disease, XP neurological disease, and XP/Cockayne syndrome (CS) complex. Genetically, XP is classified into eight distinct groups: A though G and a variant form (V). XPA is the majority (55%) and XPV follows it (25%) in Japanese XP case. Although the frequency of XPD is only 8% in Japan, there are the most diverse clinical symptoms. In contrast to Western XPD reports that there are many cases of XPD neurological disease, there are many patients with XPD cutaneous disease in Japan. In spite of the phenotypic and geographic differences, Japanese XPD cases have not been adequately studied. So, we conducted the clinical, epidemiological, and genetic studies on 19 Japanese XPD cases attended in our institution from 1998 to 2017 using medical records, referral letters, and laboratory data. The mean age at which a final diagnosis of XPD was 35.6 years old and all patients had a history of sunburn. In the clinically analysis, there were 15 cases of XPD cutaneous disease, 1 case of XPD neurological disease, and 3 cases of XP/CS complex. Twelve of the 19 cases had complications of skin malignancies. The age at onset of skin cancer was 44.4 years for cutaneous disease, 12 years for neurological disease, and 2 years for XP/CS complex. By the genetic analysis, we assumed that R601L was associated with cutaneous disease, G47R was associated with severe XP/CS complex, and R636W was associated with mild XP/CS complex. In conclusion, we have conducted the clinical, epidemiological, and genetic studies on 19 Japanese XPD cases. The type of XPD cutaneous disease is dominant in Japanese XPD cases. And clinical type (phenotype) / genotype association is implied in Japanese XPD patients from the confirmed gene mutation.