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Background: Pili annulati is an autosomal dominant hair shaft disorder characterized by alternating light and dark bands in hairs of affected individuals. Recently, a locus for pili annulati was mapped to chromosome 12q24.32-24.33 and recombination events defined a critical region of 9.2 cM (3.9 Mb)., Objectives: The aim of the current study was to narrow the size of the candidate region and to identify the pathogenic mutation for pili annulati by analysing the candidate genes., Methods: In three families with 90 individuals, including 40 affected subjects, linkage analysis was performed with 13 microsatellite markers in the candidate region on chromosome 12. Candidate genes were analysed for their expression in hair follicles and other tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) and mutation analysis., Results: Multipoint LOD score analysis for all three families confirmed the locus on the long arm of chromosome 12 with a maximum LOD score of 12.26 at marker D12S357. In two families, recombinations were identified which narrowed the region to 2.9 Mb containing 36 genes. We analysed the candidate genes in this region by RT-PCR and found that 24 were expressed in human hair follicles. Based on the result of the expression analysis, DNA sequencing of the coding region of the candidate genes was performed; this did not result in the discovery of a causal mutation., Conclusion: We reduced the critical interval of pili annulati to 2.9 Mb and excluded mutations in the coding region of all 36 possible candidate genes by sequence analysis.

Background: Metallothioneins (MTs) are ubiquitous proteins with high affinity for heavy metal ions, e.g. zinc, copper and cadmium. In the last decade it has been shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and radiotherapy, and with a poor prognosis., Objectives: To examine the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival., Methods: In a prospective cohort study 760 patients with primary cutaneous melanoma were investigated over 5 years (1993-98) by using a monoclonal antibody (E9) against MT on routinely fixed and paraffin-embedded tissues. In total, 520 patients were able to be followed up for progression of their disease or death due to melanoma and were included for statistical analysis (Fisher's exact test, Mantel-Haenszel chi2 test, Kaplan-Meier curves). MT data, progress-free interval and overall survival were compared univariately and multivariately with other prognostic factors, e.g. Breslow thickness, Clark level, ulceration, localization, age and gender (Cox regression analysis)., Results: The immunohistochemical overexpression of MT in tumour cells (cut-off level > 10% of all tumour cells) in patients with primary melanoma (156 of 520; 30%) was associated with a higher risk for progression of the disease (33 of 45; 73%) and reduced survival (24 of 30; 80%) than MT-negative lesions [364 of 520 (70%), 12 of 45 (27%) and six of 30 (20%), respectively (P < 0.0001)]. Similarly, Kaplan-Meier tumour-free survival and overall survival curves for the comparison of MT-positive and MT-negative tumours gave highly significant advantages for the MT-negative group. In a univariate analysis (comparison with Breslow thickness: relative risk 2.9, 95% confidence interval, CI 1.46-5.76, P = 0.0023 for progression; relative risk 4.19, 95% CI 1.73-10.19, P = 0.0015 for survival), as well as in a multivariate analysis with other prognostic markers, MT overexpression turned out to be a highly significant and independent factor for prognosis in primary melanoma., Conclusions: MT overexpression in primary melanoma is associated with an increased risk for disease progression. This marker is independent from Breslow thickness and helps to identify those thin melanomas (< 1.5 mm) that are at increased risk of progression. Moreover, the immunohistochemical staining of paraffin material is a cheap, easy and widely available technique to gain these results.

Background: Radiation dermatitis is a common side-effect of radiation therapy, but there is no current consensus about its appropriate therapy., Objectives: To compare treatment with topical 0.1% methylprednisolone vs. 0.5% dexpanthenol in a cohort of patients undergoing fractionated radiation therapy for breast cancer., Methods: In a randomized, double-blind design, treatment was initiated at the beginning of radiation therapy and continued for 2 weeks after termination of radiation. Outcomes were compared by three different measures: clinical (symptom score), functional (transepidermal water loss, TEWL) and subjective (quality of life, QOL)., Results: In a preliminary cohort of untreated patients undergoing radiation therapy, clinical signs and TEWL levels increased progressively during radiation therapy, reaching highest values at 5 and 4 weeks, respectively. Although neither topical treatment reduced the incidence of radiation dermatitis, both delayed the emergence of greatest clinical and TEWL scores until approximately 6 and 5 weeks, respectively. With topical corticosteroids, clinical symptoms and TEWL were less pronounced than with dexpanthenol. Whereas general QOL improved after completion of radiation therapy, skin-related QOL declined. However, the skin-related QOL decline could be at least in part reversed by use of topical corticosteroid vs. dexpanthenol-containing emollient., Conclusions: We provide evidence that prophylactic and ongoing use of topical therapy with either topical corticosteroid or a dexpanthenol-containing emollient ameliorates, but does not prevent radiation dermatitis. Our data suggest, but do not prove, a benefit of a topical corticosteroid vs. a dexpanthenol-containing emollient. Further controlled studies with larger cohorts will be needed to determine optimal forms of topical therapy for radiation dermatitis.

Acute graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation but is only rarely observed after solid organ transplantation. We describe a 68-year-old man who developed a maculopapular eruption 7 days following orthotopic liver transplantation for cirrhosis with malignant transformation due to haemochromatosis. At day 20, the patient complained of nausea, vomiting, diarrhoea and fever. Skin biopsy revealed a lymphocytic infiltrate at the dermoepidermal interface, vacuolization of basal cells and epidermal dyskeratosis. Immunohistochemistry showed HLA-DR and intercellular adhesion molecule-1 expression of lesional keratinocytes. HLA-typing of peripheral blood lymphocytes demonstrated circulating lymphocytes of donor origin. Endoscopy revealed extensive erosions of the oesophagus, stomach and duodenum that on histology disclosed multifocal loss of crypts, lymphocytic infiltrates and epithelial cell death. A diagnosis of acute GVHD was made, and high-dose immunosuppressive therapy with azathioprine and methylprednisolone was instituted. The skin and gastrointestinal symptoms subsided within 4 weeks, but the patient died from severe infectious complications 105 days after transplantation. We conclude that acute GVHD is a rare but potentially fatal complication of liver transplantation. Skin lesions are an early sign of acute GVHD and thus represent an important tool for early diagnosis.