Toxic epidermal necrolysis (TEN) is a rare and acute severe adverse reaction to drugs, characterised by massive apoptosis and widespread epidermal and mucosal detachment. Although no gold standard therapy exists, human i.v. immunoglobulins have recently been described as an effective treatment for this disease. We report a case of phenobarbital-induced TEN in a 59-year-old white woman where the epidermal detachment stopped 48 h after beginning the etanercept treatment with complete healing after 20 days. To the best of our knowledge, this is only the second reported case of TEN successfully treated with etanercept.

Thirteen patients with pachyonychia congenita types 1 and 2 were studied, two of which had a family history of pachyonychia and 11 of which were sporadic cases. Heterozygous mis-sense or small in-frame insertion/deletion mutations were detected in the genes encoding keratins K6a, K16, and K17 in all cases. Three novel mutations, F174V, E472K, and L469R were found in the K6a gene. Two novel mutations, M121T and L128Q were detected in K16. Similarly, three novel mutations, L95P, S97del, and L99P were found in K17. In addition, we identified recurrent mutations N171del (three instances) and F174S in K6a and R94H in K17. Analysis of both phenotype and genotype data led to the following conclusions: (i) K6a or K16 mutations produce the pachyonychia congenita type 1 phenotype, whereas K17 (or K6b) mutations cause pachyonychia congenita type 2; (ii) the presence of pilosebaceous cysts following puberty is the best indicator of pachyonychia congenita type 2; (iii) prepubescent patients are more difficult to classify due to the lack of cysts; and (iv) natal teeth are indicative of pachyonychia congenita type 2, although their absence does not preclude the pachyonychia congenita type 2 phenotype. This study establishes useful diagnostic criteria for pachyonychia congenita types 1 and 2, which will help limit unnecessary DNA analysis in the diagnosis and management of this genetically heterogeneous group of genodermatoses.

Intradermal therapy, known as mesotherapy, is a technique used to inject a drug into the surface layer of the skin. In particular, it involves the use of a short needle to deposit the drug in the dermis. The intradermal microdeposit modulates the drug’s kinetics, slowing absorption and prolonging the local mechanism of action. It is successfully applied in the treatment of some forms of localized pain syndromes and other local clinical conditions. It could be suggested when a systemic drug-sparing effect is useful, when other therapies have failed (or cannot be used), and when it can synergize with other pharmacological or nonpharmacological therapies. Despite the lack of randomized clinical trials in some fields of application, a general consensus is also reached in nonpharmacological mechanism of action, the technique execution modalities, the scientific rationale to apply it in some indications, and the usefulness of the informed consent. The Italian Mesotherapy Society proposes this position paper to apply intradermal therapy based on scientific evidence and no longer on personal bias.

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.