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Background: Autosomal dominant adermatoglyphia (ADG) is characterized by lack of palmoplantar epidermal ridges. Recently, ADG was found to be caused in one family by a mutation in SMARCAD1, a member of the SNF subfamily of the helicase protein superfamily., Objectives: To investigate the genetic basis of ADG., Methods: We used direct sequencing and global gene expression analysis., Results: We identified three novel heterozygous mutations in SMARCAD1 (c.378 + 2T > C, c.378 + 5G > C and c.378 + 1G > A) in a total of six patients. Surprisingly, all four ADG-causing mutations identified to date disrupt a single conserved donor splice site adjacent to the 3' end of a noncoding exon and are predicted to result in haploinsufficiency for a skin-specific isoform of SMARCAD1. These data indicate a pivotal role for the SMARCAD1-skin specific isoform in dermatoglyph formation. In order to better understand the consequences of ADG-associated mutations, we ascertained the global transcription profiles of primary keratinocytes downregulated for SMARCAD1 and of patient-derived keratinocytes. A total of eight genes were found to be differentially expressed in both patient-derived and knocked down keratinocytes. Of interest, these differentially expressed genes have been implicated in epidermal ontogenesis and differentiation, and in psoriasis, which is characterized by abnormal finger ridge patterns., Conclusions: The present data suggest that ADG is genetically homogeneous and result from perturbed expression of epidermal differentiation-associated genes., (© 2014 British Association of Dermatologists.)

Background: The ribosomal protein S6 is part of the translation machinery and is activated by phosphorylation via the mammalian target of rapamycin pathway, which is activated in psoriatic skin., Objectives: To investigate which S6 sites are phosphorylated in psoriasis and atopic dermatitis (AD), and to study whether S6 phosphorylation is associated with inflammation and/or keratinocyte hyperproliferation., Methods: Healthy skin and skin lesions of patients with psoriasis and AD were investigated by immunostaining using antibodies that stain proliferating cells, leucocytes and distinct phosphorylated sites of S6., Results: All psoriasis and AD lesions revealed abnormal S6 phosphorylation in the epidermis. The extent of S6 phosphorylation was diverse, generally stronger in psoriasis and correlated, in both diseases, with inflammation. S6 showed differential phosphorylation in distinct epidermal layers, which was most pronounced in hyperproliferative regions., Conclusions: Differential S6 phosphorylation may have a role in abnormal keratinocyte proliferation/differentiation., (© 2014 British Association of Dermatologists.)

Ichthyosis with confetti (IWC) was first described as ichthyose en confettis and subsequently as congenital reticular ichthyosiform erythroderma. Because of the development of hundreds to thousands of pale, normal-appearing confetti-like spots during childhood, the disease was named IWC. Patients with IWC show erythroderma, prominent scaling and palmoplantar keratoderma. Our female index patient was described in 1990 as the fourth patient reported worldwide; at that time she did not show any confetti-like spots. She was periodically examined at our clinic from birth until adulthood; hence we are able to describe the natural course of IWC in detail for the first time. We furthermore identified two novel deletions in KRT10, one of them leading to a frameshift and consequently to an arginine tail of keratin 10. Our report is the first independent confirmation of the KRT10 gene defect and revertant mosaicism mechanism in patients with IWC and it expands the clinical findings., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

A new syndrome with poikiloderma was described by Clericuzio et al. in 1991.(1) They reported 14 Navajo native Americans, including eight siblings, developing in the first year of life an erythematous rash, which started on the limbs and spread over the trunk and the face. This rash evolved into poikiloderma. All patients had recurrent bacterial infections. First published as Navajo poikiloderma this syndrome is now known as poikiloderma with neutropenia (PN, OMIM 604173). The inheritance is autosomal recessive, and mutations in a new gene, C16orf57, were recently described in two kindreds.(2) Because of the phenotypic overlap between Rothmund-Thomson syndrome (RTS) and PN, a few patients have been reclassified as mutations in the RECQL4 gene for RTS were absent.(2-5) Until now 27 patients have been described with clinical PN.(1-3,5-8) Here, we report the sixth family with PN outside the Navajo population. We found the previously unreported mutation c.243G>A, p.W81X in the C16orf57 gene, thus confirming the relation of this gene to the disease.(2,6) Because the molecular genetic diagnosis is not always available, we propose clinical and laboratory diagnostic criteria for PN., (© 2010 The Authors. BJD © 2010 British Association of Dermatologists.)

Leprosy is still an important and debilitating disease with a broad clinical spectrum. However, this disease occurs most often endemically, and as an imported disease it can also still be recognized in the nonendemic industrialized world.

Background: Bullous pemphigoid (BP), pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune bullous diseases characterized by the presence of tissue-bound and circulating autoantibodies directed against disease-specific target antigens of the skin. Although rare, these diseases run a chronic course and are associated with significant morbidity and mortality. There are few prospective data on gender- and age-specific incidence of these disorders., Objectives: Our aims were: (i) to evaluate the incidence of BP and PV/PF in Swiss patients, as the primary endpoint; and (ii) to assess the profile of the patients, particularly for comorbidities and medications, as the secondary endpoint., Methods: The protocol of the study was distributed to all dermatology clinics, immunopathology laboratories and practising dermatologists in Switzerland. All newly diagnosed cases of BP and pemphigus occurring between 1 January 2001 and 31 December 2002 were collected. In total, 168 patients (73 men and 95 women) with these autoimmune bullous diseases, with a diagnosis based on clinical, histological and immunopathological criteria, were finally included., Results: BP showed a mean incidence of 12.1 new cases per million people per year. Its incidence increased significantly after the age of 70 years, with a maximal value after the age of 90 years. The female/male ratio was 1.3. The age-standardized incidence of BP using the European population as reference was, however, lower, with 6.8 new cases per million people per year, reflecting the ageing of the Swiss population. In contrast, both PV and PF were less frequent. Their combined mean incidence was 0.6 new cases per million people per year. CONCLUSIONS; This is the first comprehensive prospective study analysing the incidence of autoimmune bullous diseases in an entire country. Our patient cohort is large enough to establish BP as the most frequent autoimmune bullous disease. Its incidence rate appears higher compared with other previous studies, most likely because of the demographic characteristics of the Swiss population. Nevertheless, based on its potentially misleading presentations, it is possible that the real incidence rate of BP is still underestimated. Based on its significant incidence in the elderly population, BP should deserve more public health concern.

We report on a 24-year-old male originating from Yugoslavia with a focal, transgressive palmoplantar keratoderma presumably inherited as an autosomal recessive trait. Associated clinical findings were hyperkeratotic lichenoid papules on the knees and elbows, psoriasis-like lesions in the groins and on the scalp, a spotty or reticulate hyperpigmentation of the face, trunk and extremities and a partial alopecia of the left eyebrow and eyelashes. The patient's sister was affected by similar but less pronounced cutaneous changes. Although our case shares some similarities with other hereditary palmoplantar keratodermas there remain substantial differences. We therefore believe this case to represent a new entity.

Transforming growth factor-beta (TGF-beta) consists of a highly homologous family of multifunctional peptides which are differentially expressed and function in a wide range of target cells. Aberrant expressions of TGF-beta s have been implicated in a number of disease processes, particularly those involving fibrotic and inflammatory lesions, and loss of TGF-beta growth inhibition may play a part in the progression of certain neoplasms. In the present study, we have analysed and compared, by in situ hybridization, mRNA expression of transforming growth factors-beta (TGF-beta 1, TGF-beta 2, TGF-beta 3) and TGF-beta type II receptor (T beta R II), and, by immunohistochemistry, the distribution of TGF-beta 3 protein in normal human skin and in basal cell carcinoma (BCC). The stroma of most BCCs revealed enhanced TGF-beta 1 and T beta R II mRNA expression when compared with normal dermis. A minority of BCCs also showed stromal overexpression of TGF-beta 2 and/or TGF-beta 3 mRNA. However, tumour tissues of all BCCs revealed weaker TGF-beta 3 mRNA and protein expression than normal interfollicular epidermis and hair follicle epithelia, whereas expression of TGF-beta 1 mRNA was comparably weak in tumour tissues and normal skin epithelia. Expression of TGF-beta 2 mRNA, which was clearly detectable in distinct hair follicle epithelia, was only barely detectable in normal interfollicular epidermis and in tumour tissues. In contrast, abundant T beta R II mRNA expression was observed both in normal skin epithelia and tumour tissues. From these findings, we suggest that increased stromal TGF-beta activity induces fibrotic alterations which promote tumour survival and/or progression via paracrine mechanisms, whereas lack of TGF-beta 3 expression by tumour cells may contribute to an autocrine growth control defect in BCCs.

Oral lichen planus (LP) is a relatively common disorder of unknown aetiology. Oral LP occurs most often on the buccal mucosa, but the gingivae, tongue, floor of the mouth, retromalar pads and lips may also be affected. Usually, patients have multiple sites of involvement. We report a 44-year-old patient with a 3-year history of isolated swelling of the lower lip, erosions and crusting. Histology of a biopsy from the lip revealed features of LP. Oral treatment with acitretin and low-dose steroid led to complete resolution of the lesions within 10 weeks. This is the first well-documented case of isolated LP of the lip. Diagnostic difficulties and differential diagnosis are reviewed.

We report a patient who developed infiltrated plaques at the sites of subcutaneous injection of a low-molecular-weight heparin. Skin tests and a lymphocyte transformation test revealed hypersensitivity to sandoparin and heparin sodium. The low-molecular-weight heparins nadroparin and dalteparin were subsequently tolerated without adverse effects. Possible risk factors for sensitization are discussed.

We examined the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], 25-hydroxyvitamin D3 (25OHD3), and vitamin D3 on human keratinocyte proliferation and differentiation in a serum-free or defined culture system. Concentrations greater than 10(-8) M 1,25-(OH)2D3 or 10(-7) M 25(OH)2D3 caused marked inhibition of cell growth. Growth inhibition with high doses of 1,25-(OH)2D3 was not stringent, but was mainly exerted in the G1 phase of the cell cycle. Early release from the cell cycle block restored the proliferation of human keratinocytes. The calcium concentration in the medium had no significant effect on the antiproliferative action of 1,25-(OH)2D3, 25OHD3, and vitamin D3. We also show that human keratinocyte proliferation is enhanced at doses of 1,25-(OH)2D3 and 25OH2D3 of 10(-9) M or less. Enhanced proliferation of human keratinocytes with physiological concentrations of 1,25-(OH)2D3 could only be shown in fully defined medium that contained no vitamin D3, related sterols, or bovine pituitary extract. Human keratinocyte differentiation was enhanced with higher doses of 1,25-(OH)2D3 when cells were grown in the presence of high calcium concentrations. These studies demonstrate that the lower, physiological concentrations of vitamin D3 metabolites are capable of stimulating the proliferation of epidermal keratinocytes grown under selected conditions that eliminate confounding or unidentified medium culture factors. Vitamin D3 metabolites are shown to exert mitogenic trophic effects in cultured human epithelial cells similar to their established activities in vivo.

Two brothers with Darier's disease and concomitant retinitis pigmentosa are reported. To our knowledge, these are the first cases with this combination of symptoms described in the literature. The dermatological conditions occurring with retinitis pigmentosa are reviewed. A disturbance in retinoids or retinoid binding proteins as a possible cause of both diseases is discussed.