To assess the role of platelets and lymphocyterelated immunological mechanisms in livedo vasculopathy (LV) and cutaneous small vessel vasculitis (CSVV). Livedo vasculopathy is thought to be related to the thrombotic occlusion of small and medium-sized dermal vessels. Cutaneous small vessel vasculitis comprises a heterogeneous group of disorders in which the main pathogenetic events could be modulated by circulating cytokines.Design: Case series study of 2 groups of patients affected respectively with LV and CSVV. Setting: A large clinical and research institute for the study and treatment of cutaneous diseases. Patients: Consecutive patients with clinically and histologically proved idiopathic LV (n = 8) and CSVV (n = 20) were studied and compared with healthy donors (n = 20). Patients with potentially correlated systemic diseases were excluded. Main Outcome Measures: Surface expression of platelet P-selectin and circulating level of interleukin (IL) 1␤, tumor necrosis factor ␣ (TNF-␣), IL-8, IL-2, and soluble IL-2 receptor.Results: The IL-2 and soluble IL-2 receptor levels were significantly higher in serum samples from patients with

We recently demonstrated strong genetic linkage between the type VII collagen gene (COL7A1) and both the dominant and recessive forms of dystrophic epidermolysis bullosa. In this study, we searched for mutations in dominant dystrophic epidermolysis bullosa using polymerase chain reaction amplification of segments of COL7A1, followed by heteroduplex analysis. Examination of the polymerase chain reaction corresponding to exon 73 revealed a heteroduplex resulting from a G-to-A transition at nucleotide 6127 in the triple-helical domain of COL7A1, which converted a glycine residue to an arginine (G2043R). The dominant dystrophic epidermolysis bullosa phenotype in this family probably arose because of a dominant negative effect of this mutation in COL7A1, resulting in the formation of structurally abnormal anchoring fibrils.

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Molecular analysis of p53 and patched (PTCH), two candidate tumor suppressor genes for non-melanocytic skin cancer, was performed in skin tumors from six patients aected by the cancer-prone disease xeroderma pigmentosum (XP). UV-speci®c p53 mutations were detected at a frequency of 38 ± 50% in all the tumor types analysed, including melanomas. Additional analysis of PTCH mutations in the subset of eight basal call carcinomas (BCC) revealed a very high mutation frequency of this gene (90%) which exceeded that detected in the p53 gene in the same tumors (38%). PTCH mutations were predominantly UV-speci®c C4T transitions. This mutation pattern is dierent from that reported in BCC from normal donors where PTCH mutation frequency is 27% and mutations are frequently deletions and insertions. These ®ndings suggest that PTCH mutations represent an earlier event in BCC development than p53 alterations and that the inability of XP patients to repair UV-induced PTCH mutations might signi®cantly contribute to the early and frequent appearance of BCC observed in these patients. Oncogene (2000) 19, 463 ± 467.Keywords: skin cancer; XP; p53; PATCHED; UV light Mutations in a number of genes have been associated with the genesis of human skin cancer. The inactivation and/or mutation of the p53 gene has been implicated as an important factor in the pathogenesis of UV lightinduced non-melanocytic skin cancers (NMSC), i.e. basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). All p53 mutations detected in these tumors are indeed consistent with the mutagenic action of UV light as inferred from in vitro studies (reviewed in Dogliotti et al., 1998). More recently, a set of members of the Sonic hedgehog (SHH) signaling pathway, which is required for correct embryonic patterning, have been shown to be directly and speci®cally involved in BCC development. In particular, inactivating mutations of patched (PTCH), a SHH receptor that acts negatively on this signaling pathway, have been found both in familial and sporadic BCC (reviewed in Gailani and Bale, 1997). Other alterations in the same signaling pathway have also been reported in sporadic BCC, namely the activation of the transcription factor Gli1 in basal cells (Dahmane et al., 1997) and activating mutations of shh (Oro et al., 1997) and smoothened (smo) . Interestingly, the analysis of PTCH mutations in BCC shows that, dierently from what was observed in the p53 gene, almost half of the mutations identi®ed are frameshift mutations or rearrangements which are not typical of UV mutagenesis (Hahn et al., 1996;Johnson et al., 1996;Gailani et al., 1996;Unden et al., 1996;Chidambaram et al., 1996;Wolter et al., 1997;Wicking et al., 1997;Aszterbaum et al., 1998). The role of UV radiation in the genesis of alterations of the PTCH gene is then questionable.In addition to p53 and PTCH, other genes which control the susceptibility to skin cancer are those defective in the cancer-prone hereditary disorder xeroderma pigmentosum (XP). The biochemical defect in most XP patients (seven comp...

CD30+ anaplastic large cell lymphoma is a primary cutaneous lymphoproliferative disorder with a high rate of spontaneous regression (almost 25%). The suggested therapies are radiation, surgery and methotrexate. We describe two patients with nonregressing primary cutaneous CD30+ T-cell lymphoma that was successfully treated with topical imiquimod 5% cream (Aldara, 3M) three times weekly for 6 weeks. In both cases we obtained complete clinical remission, confirmed by histology. No recurrences were observed during the following 8 months. We consider that topical application of an immune response modifier, such as imiquimod, could be a good alternative to other potentially more dangerous or aggressive treatments.