Letters to the Editor
3 Ross CM. Generalized folded skin with underlying lipomatous nevus: the Michelin Tyre baby. Arch Dermatol 1972; 106: 766. 4 Nomura Y, Ota M, Tochimaru H. Self-healing congenital generalized skin creases: Michelin tire baby syndrome. J Am Acad Dermatol 2010; 63: 1110–1111.
1 Ross CM. Generalized folded skin with an underlying lipomatous nevus. “The Michelin Tire baby”. Arch Dermatol 1969; 100: 320–323. 2 Sardana K, Mendiratta V, Kakar N, Sharma RC, Koranne RV, Sethi S. Spontaneously improving Michelin tire baby syndrome. Pediatr Dermatol 2003; 20: 150–152.
Multiple malignant changes and recurrent infections in the skin associated with long-term exposure to ultraviolet light and topical psoralen plus ultraviolet A therapy topical steroids, vitamin D ointment and oral etretinate. For several subsequent years, he engaged frequently in full-body sunbathing, wearing only swimming trunks. In 2008, an area of erosion and scaly erythema appeared on his right chest, with numerous solar lentigines on the
Dear Editor, A 73-year-old male office worker was diagnosed with psoriasis vulgaris in 1985 and received topical whole-body psoralen plus ultraviolet A (PUVA) therapy four times weekly for approximately 10 years (>400 times), with simultaneous treatment with
Figure 1. (a) Close-up view of the patient’s non-exposed back skin. Note the numerous solar lentigines and atrophic skin. Arrows indicate psoriatic lesions. (b) Regions of multiple raised tumors are indicated by circles. Red circles indicate squamous cell carcinoma (SCC) lesions; blue circles indicate solar keratotic lesions. Panels (c) and (d) show a magnified view and histological features, respectively, of the representative SCC lesion indicated by (1) in (b). Panels (e) and (f) show a magnified view and histological features, respectively, of the representative solar keratotic lesion indicated by (2) in (b). Panels (g–j) show results of immunostaining of the solar keratotic lesion (g,i) and of apparently normal adjacent skin (h,j) indicated by (3) in (b) with antibodies against ataxia telangiectasiamutated protein (g,h) and against phospho-histone H2A.X (Ser139) ([i,j]; see text for details). Nuclei in the lesion (g,i) were immunostained with both antibodies; nuclei in apparently normal epidermis adjacent to the lesion (h,j) were immunonegative. ([d,f] Hematoxylin–eosin, [g–j] 3,30 -diaminobenzidine-tetrachloride; original magnifications: [d,f] 9100; [g–j] 9200.)
Correspondence: Sakuhei Fujiwara, M.D. Ph.D., Department of Dermatology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu City, Oita 879-5593, Japan. Email: [email protected]
© 2015 Japanese Dermatological Association
Letters to the Editor
atrophic skin of sun-exposed and non-exposed areas (Fig. 1a). Lesional biopsy revealed atypical keratinocytes in the basal layer of the epidermis, and solar elastosis in the dermis indicative of solar keratosis. The arsenic level in the patient’s hair was normal. In subsequent years, multiple solar keratotic lesions and squamous cell carcinoma (SCC) developed on the extremities and abdomen (Fig. 1b–f). All lesions were excised but, after six of nine excision procedures, postoperative wounds were infected with methicillin-resistant Staphylococcus aureus, with resultant cellulitis. Lymphocyte stimulation tests with phytohemagglutinin or concanavalin A revealed the absence of systemic immunosuppression. Ultimately, 15 solar keratotic lesions and 10 SCC lesions were detected, on both sunexposed and non-exposed areas, as shown in Figure 1(b). In our patient, multiple skin cancers had developed after long-term PUVA therapy, which is known to raise, slightly, the risk of malignancy.1,2 The incidence of skin cancer increases when the cumulative dose of ultraviolet (UV)-A exceeds 1000 J/ cm2 or after more than 400 treatments.2 However, Asian patients with more than 20 malignancies after PUVA therapy are rare.3 Ataxia telangiectasia-mutated protein (ATM) is activated by UV-A4 and ataxia telangiectasia- and Rad3-related protein kinase (ATR) is involved at the early stage of UV-mediated carcinogenesis.5 We stained specimens with antibodies against products of kinases whose expression is associated with DNA damage. One antibody was directed against phosphorylated ATM (Abcam, Cambridge, UK) and one was directed against phospho-histone H2A.X (Ser139) (Merck Millipore, Billerica, MA, USA), which is involved in pathways downstream of both ATM and ATR.6 While solar keratotic lesions on the back and on the right ankle were immunostained with these antibodies (Fig. 1g–j), apparently normal epidermis adjacent to solar keratotic lesions was immunonegative. Positive immunostaining with the first antibody might have been due to activation of the ATM signaling pathway in response to dsDNA breakage during carcinogenesis. Our results suggest that DNA damage was not ubiquitous in epidermal cells and that elimination of recent DNA damage was limited to local areas of epidermis, for example, epidermal stem cells.
Wound infections recurred after surgery. Thus, probably, local immunosuppressive conditions existed in our patient’s skin. However, the involvement of photoaging in antimicrobialbarrier disruption remains to be clarified. Stress-induced senescence due to UV light yields cells with a senescenceassociated secretory phenotype (SASP) that secrete interleukin (IL)-6, IL-8 and matrix metalloproteinase (MMP).7 MMP may inactivate certain antimicrobial proteins. Such factors might have mediated the recurrent infections after surgery and the development of multiple malignancies.
CONFLICT OF INTEREST:
Haruna HIROSE-MATSUDA,1 Osamu OKAMOTO,1 Takashi SAKAI,1 Akiko ITO,1 Yoshitaka KAI,1 Yutaka HATANO,1 Katsuhiro HANADA,2 Yoshio YAMAOKA,2 Sakuhei FUJIWARA1 Departments of 1Dermatology, and 2Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu City, Japan doi: 10.1111/1346-8138.12835
REFERENCES 1 Halliday GM, Byrne SN, Damian DL. Ultraviolet A radiation: its role in immunosuppression and carcinogenesis. Semin Cutan Med Surg 2011; 30(4): 214–221. 2 Kobayashi K, Morita A, Tsuji T. Topical PUVA for psoriasis and cutaneous carcinogenesis. Jpn J Dermatol 2002; 112: 1247–1251. 3 Goto T, Nishihara Y, Shibata S et al. A case of multiple cutaneous carcinomas arising from psoriasis vulgaris during its clinical course. Nishinihon J Dermatol 2003; 65: 25–29. 4 Zhang Y, Ma WY, Kaji A, et al. Requirement of ATM in UVA-induced signaling and apoptosis. J Biol Chem 2002; 277: 3124–3131. 5 Kawasumi M, Lemos B, Bradner JE, et al. Protection from UVinduced skin carcinogenesis by genetic inhibition of the ataxia telangiectasia and Rad3-related (ATR) kinase. Proc Natl Acad Sci USA 2011; 108: 13716–13721. 6 Riches LC, Lynch AM, Gooderham NJ. Early events in the mammalian response to DNA double-strand breaks. Mutagenesis 2008; 23: 331–339. 7 Kuilman T1, Michaloglou C, Mooi WJ, Peeper DS. The essence of senescence. Genes Dev 2010; 24: 2463–2479.
Erythema multiforme-type drug eruption with prominent keratinocyte necrosis induced by long-term administration of telmisartan Dear Editor, Erythema multiforme (EM), a common skin condition, can be associated with infection and drug administration. While cuta-
neous adverse reaction to drugs, such as antibiotics or anticonvulsants, can present as EM,1 angiotensin II (AngII) blocker-induced EM is relatively rare.1,2 Here, we report a case
Correspondence: Mizue Fujii, M.D., Ph.D., Department of Dermatology, Kitami Red Cross Hospital, Kita 6-jo Higashi 2-chome, Kitami 090-8666, Japan. Email: [email protected]
© 2015 Japanese Dermatological Association