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Summary Background Pseudoxanthoma elasticum (PXE) is a genetic disorder due to mutations in the gene encoding the transmembrane transporter protein adenosine triphosphate binding cassette (ABC)-C6, resulting in calcification of elastic fibres in the skin, eyes and cardiovascular system. Objectives To evaluate the diagnostic criteria for PXE based on molecular data. Methods Of 10 families with a positive history of PXE 142 subjects were investigated for clinical symptoms, histological findings and genetic haplotype analysis. Results Of these, 25 subjects were haplotypic homozygous for PXE and 23 had typical clinical and histopathological manifestations. Two of the 25 patients showed such marked solar elastosis and macular degeneration that PXE could not be confirmed clinically. Sixty-seven subjects were haplotypic heterozygous carriers and 50 were haplotypic homozygous unaffected. Of these 117 subjects, 116 showed no cutaneous or ophthalmological signs of PXE. In one of the 50 haplotypic homozygous unaffected patients important solar elastosis and scarring of the retina mimicked PXE lesions. Only four of the 67 haplotypic heterozygous carriers had biopsies of nonlesional skin; all were histopathologically normal. Conclusions In our patients, PXE presents as an autosomal recessive genodermatosis. Correlation of haplotype and phenotype confirmed actual major diagnostic criteria. In patients with marked solar elastosis and/or severe macular degeneration clinical diagnosis can be impossible and molecular testing is needed to confirm the presence of PXE. To the best of our knowledge our large study compares for the first time clinical findings with molecular data.

The potential carcinogenic risk of bath PUVA therapy was compared to that of systemic (oral) PUVA. An analysis of the epidemiological data on cancer risk following bath PUVA with trimethylpsoralen does not support the conclusion that bath PUVA per se is less carcinogenic than systemic PUVA with 8-methoxypsoralen (8-MOP). Pharmacokinetic studies indicate that both the concentration of 8-MOP in the target organ for PUVA carcinogenicity (skin) at the relevant time point (time point of UVA irradiation) and the extents of biological effects in the skin are comparable following bathwater or systemic 8-MOP administration. Furthermore, the therapeutic effects of PUVA arise from the same photochemical reaction mechanisms as do the carcinogenic effects. Theoretically, the ratio of (desired) cytotoxic versus (undesired) mutagenic effects could increase with increasing efficiency of the PUVA therapy itself. On the basis of the available evidence, it is concluded that all forms of PUVA therapy, independently of the route of 8-MOP administration, contribute to a small but dose-dependent increase in nonmelanoma skin cancer risk.

Background: Photodynamic therapy (PDT) of superficial basal cell carcinomas using endogenous protoporphyrin IX generated by topically applied 5-aminolevulinic acid (5-ALA) is an innovative and clinically encouraging approach. Objective: This paper reports on the first results of an ongoing clinical study on photodynamic therapy of 55 basal cell carcinomas in 19 patients. Methods: Because of the chemical instability of 5-ALA, a novel nanocolloid lotion was developed. This formulation was applied to the lesions under occlusive dressing 6 h before irradiation with visible light from an unfiltered halogen lamp. Light-induced fluorescence was used to ascertain the superficial extension of the tumors. The response to the therapy was assessed by visual inspection and in 13 patients also by biopsies. Results: After a single treatment, 47 (85%) basal cell carcinomas showed a complete response at a follow-up time of at least 6 months. For the remaining 8 (15%) lesions, a partial response was observed, indicated by a marked reduction of the tumor size. The treatment modality without local anesthetics was well tolerated by all patients, with only slight discomfort during light irradiation. Conclusion: Our results indicate that 5-ALA-PDT with our novel formulation, a nanocolloid lotion, is a highly effective and convenient therapy for the treatment of superficial basal cell carcionomas. Its use in the treatment of nodular tumors needs further investigations.