What is an epidermal nevus?

An epidermal nevus is a common birthmark that causes the skin to be a different texture than the rest of the skin. It is often seen at birth or in early childhood.     

RXRα ablation in epidermal keratinocytes enhances UVR-induced DNA damage, apoptosis, and proliferation of keratinocytes and melanocytes

We show here that keratinocytic nuclear receptor retinoid X receptor-α (RXRα) regulates mouse keratinocyte and melanocyte homeostasis following acute UVR. Keratinocytic RXRα has a protective role in UVR-induced keratinocyte and melanocyte proliferation/differentiation, oxidative stress-mediated DNA damage, and cellular apoptosis. We discovered that keratinocytic RXRα, in a cell-autonomous manner, regulates mitogenic growth responses in skin epidermis through secretion of heparin-binding EGF-like growth factor, GM-CSF, IL-1α, and cyclooxygenase-2 and activation of mitogen-activated protein kinase pathways. We identified altered expression of several keratinocyte-derived mitogenic paracrine growth factors such as endothelin 1, hepatocyte growth factor, α-melanocyte stimulating hormone, stem cell factor, and fibroblast growth factor-2 in skin of mice lacking RXRα in epidermal keratinocytes (RXRα(ep-/-) mice), which in a non-cell-autonomous manner modulated melanocyte proliferation and activation after UVR. RXRα(ep-/-) mice represent a unique animal model in which UVR induces melanocyte proliferation/activation in both epidermis and dermis. Considered together, the results of our study suggest that RXR antagonists, together with inhibitors of cell proliferation, can be effective in preventing solar UVR-induced photocarcinogenesis.     

Connections between nerve endings and epidermal cells: are they synapses?

Abstract: Based on electron microscopy and confocal scanning microscopy, contacts between sensory axons and the cells of the epidermis have been described: with keratinocytes, Langerhans cells, melanocytes and Merkel cells. We would like to initiate a debate on this question: “Are neuro‐epidermal connections synapses?”. Anatomically, neuro‐epidermal junctions can be considered as synapses in our opinion. If neuro‐epidermal junctions are synapses, they probably belong to the family of en passant synapses, with nerve endings passing along epidermal cells and occasionally connecting to them. In conclusion, we suggest that neuro‐epidermal junctions could be considered as true synapses, but this does not exclude non synaptic interactions.     

What is special about adalimumab?

Adalimumab is the first fully human anti-tumor necrosis factor (TNF-alpha) monoclonal antibody and it binds to both soluble and cell-bound TNF-alpha, modulating biological responses linked to this cytokine. Different trials have probed the efficacy of adalimumab even after one week, and accumulated experience in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease shows adalimumab as a safe drug sharing a similar adverse effects profile with the other anti-TNF-alpha molecules. Specific features of adalimumab are revised.     

What is the news? A difference between men and women

It is a common observation that women and men react differently to stress and illness. We questioned 63 consecutive patients with pityriasis rosea and found that the women were overwhelmingly more likely than men to ask to hear unpleasant information before positive information.     

Proliferation and interferon-γ receptor expression in psoriatic and healthy keratinocytes are influenced by interactions between keratinocytes and fibroblasts in a skin equivalent model

Epidermal-dermal interactions were studied in a skin equivalent model. Six combinations of keratinocytes and fibroblasts from healthy and psoriatic skin were used. TPA (12-O-tetradecanoylphorbol-13-acetate) was used to determine whether the expression of the IFN- receptors in keratinocytes was related to epidermal differentiation and proliferation. These phenomena were assessed by immunohistochemistry. In all epidermal outgrowths, the epidermal growth factor receptor was expressed throughout the epidermis, cytokeratin 16 suprabasally, and filaggrin and involucrin in its superficial part. The IFN- receptor was expressed throughout the epidermis, but was unevenly distributed. The expression of the IFN- receptor was quantified by confocal laser scanning microscopy both in the whole of epidermis and in areas with the strongest intensity. The total amount varied to a minor degree in the epidermal outgrowths of different origins and was unaffected by TPA. In high-intensity areas interactions between keratinocytes and fibroblasts did influence the amount of IFN- receptor expression and TPA decreased the expression by 13%. There was no correlation between the proliferation rate and the expression of the IFN- receptor. Psoriatic and healthy keratinocytes were equally well differentiated in the skin equivalents. The interferon- receptor was similarly expressed under these conditions. The growth rate, assessed by Ki-67-positive nuclei in the basal layer, was highest in healthy keratinocytes. Keratinocytes from psoriatic lesions increased their growth rate when cocultured with psoriatic fibroblasts compared with normal ones, indicating that fibroblasts may be of importance for epidermal hyperproliferation in psoriatic lesions.     

What do we know about palmoplantar pustulosis?

Palmoplantar pustulosis is characterized by a chronic eruption of sterile pustules on palms and soles. The disease affects mainly women in the sixth and seventh decade of life. Some authors consider palmoplantar pustulosis a separate entity, whereas others consider it a condition in the spectrum of psoriasis. Aim of this study was to summarize the most recent data about PPP which aimed at establishing the nosological position of palmoplantar pustulosis. A systematic search of published literature was carried out. General characteristics of patients with PPP in different populations were present. We reviewed histological, immunological and genetic studies, as well as treatment options for PPP. PPP presents with clinical features, which are not present in psoriasis; however, the common coexistence of psoriasis vulgaris and/or positive family history for psoriasis indicates at least a close relationship between PPP and psoriasis. At present, there are not sufficient data to exclude PPP from psoriasis group.     

What do trainee hairdressers know about hand dermatitis?

Hand dermatitis is an important cause of morbidity in hairdressers. We conducted a questionnaire survey of 121 trainee hairdressers from 2 hairdressing colleges in Burnley (UK). The questionnaire concerned the number and types of hairdressing procedures performed, previous and current medical history, awareness of risks to the skin from hairdressing, and knowledge of hand dermatitis prevention. 17% of the trainees suffered currently from hand dermatitis. This is likely to be due to the large amount of wet work done by apprentice hairdressers, particularly those who worked in salons. 2/3 of trainees were not aware that atopic eczema predisposed to hand dermatitis. Formal pre-school and pre-employment counselling was limited. Knowledge on hand care among trainees was not often translated into practice, with gloves being worn by only 9% when shampooing and 58% when perming. Prevention of hand dermatitis by education and pre-employment counselling is of fundamental importance.     

Roxithromycin downregulates production of CTACK/CCL27 and MIP-3α/CCL20 from epidermal keratinocytes

Cutaneous T cell-attracting chemokine (CTACK)/CCL27 and macrophage inflammatory protein (MIP)-3α/CCL20 are the major inflammatory chemokines involved in skin inflammation. The present study showed that roxithromycin (RXM) suppressed the TNFα-induced production of CCL27 and CCL20 in HaCaT keratinocytes and normal human keratinocytes (NHKs) in a dose-dependent manner. The production of CCL20 induced by TNFα was suppressed by the addition of inhibitors of nuclear factor kappa B (NFκB). RXM suppressed NFκB activity induced by TNFα. RXM, by regulating CCL27 and CCL20, may contribute to the modulation of inflammation.     

Is there a special relationship between CD30‐positive lymphoproliferative disorders and epidermal proliferation?

The relationship between CD30+ lymphoma and epithelial proliferations is not well defined. CD30+ lymphoma and lymphomatoid papulos (LyP) share immunohistochemical epitopes and some other features. A single case of LyP associated with multiple keratoacanthomas (KAs) was recently reported. We report two cases of atypical lymphocytic proliferation with features of CD30+ lymphoma and LyP intimately associated to KA and squamous cell carcinoma (SCC), KA type. This similar combination of an epidermal tumor and apparent involvement with atypical lymphocytic infiltrates raises the possibility of an association between the two entities. We speculate that the association may be more than expected to occur by chance and suggest several mechanisms by which the association may evolve.     

Letter: Pili annulati - What about racial distribution?

Pili annulati is a rare hair shaft abnormality and, as far as we know, there are no published data on pili annulati's racial distribution. To our knowledge, this is the first case reported in an African-American patient.     

Proliferation–differentiation relationships in the expression of heparin-binding epidermal growth factor-related factors and erbB receptors by normal and psoriatic human keratinocytes

The topological relationships between erbB receptors and ligands of the epidermal growth factor family were characterized by immunocytochemistry in normal and psoriatic epidermis and in proliferating and differentiating human keratinocytes in culture. Spatial colocalization of receptors and ligands was assessed by dual immunostaining. Expression of epidermal growth factor receptor (EGFr), erbB2, and erbB3, but not erbB4, was detected throughout the epidermis, although labeling for erbB2 and erbB3 was accentuated in the upper spinous layers, and EGFr was more strongly labeled in basal cells. Of the tested growth factors, heparin-binding epidermal growth factor (HB-EGF) was diffusely expressed throughout normal and psoriatic epidermis and sparsely colocalized with EGFr in all viable epidermal layers, with increased colocalization in psoriatic epidermis. In contrast, betacellulin and heregulin/neu differentiation factor (NDF) alpha were largely restricted in their distribution to the upper spinous and granular layers. Betacellulin was downregulated in psoriatic keratinocytes. Although heregulin/NDF-beta was undetectable in normal epidermis, it was upregulated in psoriasis. Betacellulin and heregulin/NDF-alpha strikingly colocalized with EGFr and erbB3 receptors in the granular layer and in a declining gradient from the granular zone to the basal layer, respectively. Similar patterns were observed in cultured keratinocytes under proliferative conditions and upon differentiation in high-calcium medium. These morphological data collectively suggest divergent functions for members of the growth factor family, and in particular, we propose that betacellulin and heregulin/NDF-alpha are involved in epidermal morphogenesis and/or in maintenance of the differentiated phenotype.     

What is really in control of skin immunity: lymphocytes,dendritic cells,or keratinocytes? facts and controversies

The pathophysiology of atopic dermatitis is still under discussion. Although it is widely accepted that environmental factors and a genetic predisposition are essential, the role of the innate and adaptive immune system and the functional cascade of the cells involved is still unclear. A concept that integrates all immune cells as equally essential has allure. In addition, barrier abnormalities due to mutations of the gene coding for filaggrin and down-regulation of antimicrobial peptides, such as LL-37 and β-defensins 2 and 3, were very recently found to be relevant for the pathogenesis of atopic dermatitis.     

What can we learn about skin of color in dermatopathology?

As the US population becomes increasingly diverse, more patients of color seek dermatologic care and often have concerns that are unique to their skin color. Therefore, it is critically important that the knowledge gap in skin of color dermatology be urgently addressed. In addition to addressing the clinical gap in recognizing dermatologic disease in patients of color, the role of dermatopathology in bridging this gap remains unaddressed. Given the impact that skin color can have on the presentation and subsequent management of dermatologic diseases, understanding the current knowledge of the unique structural and histologic characteristics in skin of color may help give us insight on the role skin color should play in histopathologic diagnosis. In this paper, we bring insights into the role dermatopathology plays in addressing our knowledge of cutaneous disease in patients with skin of color. After we highlight issues to consider, we can begin to identify gaps in knowledge that still exist within dermatopathology that need to be addressed to ensure patients of all backgrounds receive equitable dermatologic care.