Papillon-Lefèvre syndrome (PLS) is a rare autosomal-recessive genodermatosis characterized by palmoplantar hyperkeratosis and severe early-onset periodontitis. The development of malignant cutaneous neoplasms within the hyperkeratotic lesions of the syndrome is quite rare. Here, we report on a 51-year-old Japanese woman with PLS associated with recurrent malignant melanoma (MM). Mutation analysis of the cathepsin C gene revealed that the proband was homozygous for a missense mutation, c.415G→A, which is predicted to result in the amino acid substitution p.G139R. Including our case, 4 families have been described as having PLS with MM, 3 of which are Japanese, implying a high incidence of melanoma development in Japanese PLS patients. We suggest that hereditary palmoplantar keratoderma (PPK) in Japanese patients might be predisposed to MM. A literature review revealed that in 18 cases of MM-associated PPK, 13 (76%) were Japanese, suggesting a high incidence of MM in Japanese PPK patients. This tendency might be attributable to the high frequency of acral lentiginous melanoma in Japanese subjects, in contrast to a lower frequency of this subtype in Caucasians.

Dermatitis artefacta is one of a spectrum of factitious diseases etiologically responsible for skin lesions denied by patients. These factors often make it difficult to identify the causative agents of the condition. Herein, we report a case of bullous dermatitis artefacta in a 12-year-old girl, for which a deodorant spray was suspected as the probable cause. Pathological examination revealed subepidermal blistering with full-thickness necrosis of the epidermis, suggesting a thermo- or cryo-induced injury. Psychological testing demonstrated her immaturity and dependence. In searching for the causative agent, we suspected a deodorant spray as a blister-inducing agent. We succeeded in reproducing a similar blister lesion on the volunteer's healthy skin using the same spray. Psychiatric involvement significantly complicates the treatment of factitious diseases, including dermatitis artefacta. Cooperation among dermatologists, psychiatrists and the patient's family members is required for ensuring a favorable prognosis.

b-Thujaplicin (BT), also known as hinokitiol, is a tropolone-related compound found in the heart wood in several cupressaceous plants such as the Hinoki cypress, Chamaecyprais obtuse, and the western red cedar, Thuja Plicata DON.1,2) BT has a wide variety of biological functions, including antibacterial and antifungal activity, 3) acting as an iron chelator for Salmonella typhimurium, 4) anti-tumor activity, 5) and induction of differentiation. 6) Thus far, however, the molecular mechanisms by which BT exerts such a broad spectrum of biological effects have not been elucidated.Metallothioneins (MT) are ubiquitously distributed, low molecular weight proteins with a high cysteine content and high binding capacity for metals such as zinc and cadmium. 7)MT function in zinc homeostasis 7) and detoxification of heavy metals. 8,9) Several experiments have also shown that MT acts as a reactive oxygen species (ROS) scavenger, 10,11) and MT induction has protective effects against oxidative stresses such as anticancer drugs 12) and ultraviolet (UV). 13)MT gene expression is induced not only by heavy metals but also by a wide variety of stress-inducing agents such as ultraviolet, 14) X-ray, 15) hypoxia, 16) hydrogen peroxide, 17) and a number of cytokines including interferon-a and b, TNF-a, and interleukin 1 and 6. [18][19][20][21][22] Recently, we found that BT induces cellular metallothionein in mouse keratinocytes in vitro and in vivo, resulting in reduction of apoptotic cell formation caused by UV-B irradiation. 23)The molecular mechanism underlying MT gene regulation has been extensively investigated (reviewed in ref. 24). In the proximal promoters of MT genes, multiple copies of metal response elements (MREs) reside, and these cis-elements are essential for MT gene induction by zinc and cadmium. MREs were shown to mediate the transcriptional response of MT genes to oxidative stress in mouse hepatoma cells.25) A metal-responsive transcription factor, termed MTF-1, which binds to MREs and activates MT gene transcription, has been cloned from mouse and human. 26,27) Recently, the involvement of protein kinase-C (PKC) has been demonstrated in zinc-and cadmium-induced MT gene expression, as determined by Northern analyses using a specific PKC inhibitor, chelerythrin. 28) However, the precise regulation of MT gene expression by other inducing agents has yet to be elucidated.In the present study, we report the first evidence for BT as a potent transactivator for the human MT-IIA gene. Moreover, inhibition experiments revealed a possible involvement of protein kinase C and reactive oxygen species in the transduction mechanism. MATERIALS AND METHODSChemicals BT was a kind gift from Takasago (Tokyo, Japan). Cycloheximide, H7, chelerythrin, HA1004, and Nacetylcysteine (NAC) were all purchased from Sigma (St. Louis, MO, U.S.A.).Cell Culture The spontaneously transformed human epidermal keratinocyte cell line, HaCaT, (kindly provided by Dr. Husenig) was cultured in Dulbecco's modified minimal essential medium (DMEM) supplemented...

The most life-threatening complication developing in patients with recessive dystrophic epidermolysis bullosa (RDEB) is squamous cell carcinoma (SCC). To improve patient prognosis, early detection of regional lymph node metastasis is required. Herein, we report a patient diagnosed with non-Hallopeau-Siemens RDEB who developed SCC on the left foot with inguinal lymph node swelling. Use of the sentinel node biopsy (SNB) technique favorably minimized defective damage to the inguinal region in this case. Genetic analysis identified one novel COL7A1 mutation, a maternal c.238G > C (p.A80P) and one previously reported mutation, a paternal c.3631C > T (p.Q1211X). A published work review demonstrated that no COL7A1 mutations specific for SCC development in RDEB have previously been identified. It remains unclear if SNB in combination with gene diagnosis is beneficial for the management of SCC in RDEB patients, however, because of the limited number of case reports. To address this issue, COL7A1 mutational analysis should be performed in as many cases of RDEB as possible.

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