The class III histone deacetylase (HDAC), SIRT1, is a mammalian homologue of the Saccharomyces cerevisiae chromatin-silencing factor Sir2 that regulates longevity. SIRT1 regulates cell survival via deacetylation of p53 and forkhead transcription factors, and overexpression of SIRT1 is reported to be essential for cell growth and survival in some kinds of cancer. To elucidate the role of SIRT1 in human skin carcinogenesis, we have examined SIRT1 protein expression in 20 cases each of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease (BD), and actinic keratosis (AK) by immunohistochemical analysis. Overexpression of SIRT1 is frequently observed in all kinds of non-melanoma skin cancers included in this study. In particular, strong expression was observed in all cases of BD. In addition, no obvious difference between AK and SCC was observed in the expression of SIRT1, suggesting that overexpression of SIRT1 may have some relevance to the early stage of skin carcinogenesis. We suppose that SIRT1 could be one of the critical targets for future therapy with the aim of inhibiting cell proliferation and promoting apoptosis in non-melanoma skin cancers.

Scherschum et al. proposed diltiazem-associated photodistributed hyperpigmentation as a novel type of drug-induced photosensitive lichenoid eruption. The characteristic clinical features were slate-gray reticulated hyperpigmentation on sun-exposed areas, while lichenoid dermatitis with prominent pigmentary incontinence was noted histologically. Although the clinical and histological features were similar to those of lichen planus pigmentosus, the histological features did not show either compact hyperkeratosis or wedge-shaped hypergranulosis, which are typical histological features of lichen planus. We describe two Japanese cases of diltiazem-associated photodistributed hyperpigmentation, who were successfully treated with topical tacrolimus, and review the published work.

The activation of FGFR3 might be a common feature in the tumorigenesis in seborrhoeic keratosis, although the activation does not induce a typical oncogenic signal in keratinocytes. In addition, OIS due to some oncogenic signals rather than activation of FGFR3 might be involved in the early skin carcinogenesis related to chronic ultraviolet radiation exposure.

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Letters to the Editor 435 since 1990 have reported the use of terlipressin for the treatment of HRS with good outcomes and low risk of adverse effects. Incidence of secondary ischaemic events in HRS differs depending on series from 5% to 29% (1. 2, 8, 9). Significantly, a recent meta-analysis revealed that no permanent interruption of terlipressin was needed because of intolerance ( I ).Undesirable effects are usually mild and disappear by lowering the dose of the drug. i.e. paleness, acral cyanosis, abdominal pain, diarrhoea, headache and self-limiting cardiac arrhythmias. However, serious ischaemic events, such as skin necrosis involving the extremities, scrotum, penis or abdominal skin have been documented (1-3, 5, 6. 8. 9). Obesity, venous insufficiency and spontaneous bacterial peritonitis have been proposed as possible risk factors for the development of ischaemic cutaneous complications (3, 5).Our patient did not have a medical history of ischaemic disease and, at physical examination, he was not obese and showed no signs of venous insufficiency. Repeated negative ascitic cultures ruled out a spontaneous bacterial peritonitis. The doses of terlipressin administered were low. This case is of clinical importance due to the large area of cutaneous necrosis and its rapid occurrence, without resolution after terlipressin withdrawal.In conclusion, we report here a new case of cutaneous necrosis secondary to terlipressin therapy for management of HRS. Although rare, we must bear in mind the possibility of ischaemic complication of terlipresshi.