Summary
Background Perturbations in the expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers. Differentially expressed miRNAs have not been systematically ...evaluated in basal cell carcinoma (BCC) of the skin.
Objectives To initiate a microarray‐based miRNA profiling study to identify specific miRNA candidates that are differentially expressed in BCC.
Methods Patients with BCC (n = 7) were included in this study. Punch biopsies were harvested from the tumour centre (lesional, n = 7) and from adjacent nonlesional skin (intraindividual control, n = 7). Microarray‐based miRNA expression profiles were obtained on an Agilent platform using miRBase 16 screening for 1205 Homo sapiens (hsa)‐miRNA candidates. To validate the microarray data, the expression of seven dysregulated miRNAs was measured by TaqMan quantitative real‐time reverse transcription polymerase chain reaction.
Results We identified 16 significantly upregulated (hsa‐miR‐17, hsa‐miR‐18a, hsa‐miR‐18b, hsa‐miR‐19b, hsa‐miR‐19b‐1*, hsa‐miR‐93, hsa‐miR‐106b, hsa‐miR‐125a‐5p, hsa‐miR‐130a, hsa‐miR‐181c, hsa‐miR‐181c*, hsa‐miR‐181d, hsa‐miR‐182, hsa‐miR‐455‐3p, hsa‐miR‐455‐5p and hsa‐miR‐542‐5p) and 10 significantly downregulated (hsa‐miR‐29c, hsa‐miR‐29c*, hsa‐miR‐139‐5p, hsa‐miR‐140‐3p, hsa‐miR‐145, hsa‐miR‐378, hsa‐miR‐572, hsa‐miR‐638, hsa‐miR‐2861 and hsa‐miR‐3196) miRNAs in BCC compared with nonlesional skin. Data mining revealed connections to many tumour‐promoting pathways, such as the Hedgehog and the mitogen‐activated protein kinase/extracellular signal‐regulated kinase signalling cascades.
Conclusions This study identified several miRNA candidates that may play a role in the molecular pathogenesis of BCC.
Background
Fumaric acid esters (FAEs) are an established systemic treatment for moderate‐to‐severe psoriasis. However, the long‐term clinical safety and effectiveness of continuous FAE monotherapy ...and combination therapy have not been established.
Objective
To examine the long‐term safety and effectiveness of FAEs as monotherapy and in combination with phototherapy or methotrexate in patients with psoriasis treated at a single centre in Germany.
Methods
This monocentric, retrospective observational study, with a follow‐up period of up to 32.5 years, included 859 patients: 626 received FAE monotherapy, 123 received FAEs with concomitant phototherapy and 110 received FAEs with methotrexate.
Results
Approximately half of patients (49.0%) reported adverse events (566 total events), most of which involved the gastrointestinal tract. Serious adverse events were reported in 2.3% of patients, but none were deemed to have a causal relationship with any of the treatment regimens. Adverse events leading to treatment discontinuation were observed in 12.9% of patients. A median duration of 1 year was observed in all three treatment subcohorts (P = 0.70) from initiation of FAE treatment to a 50% response rate, where response was defined as achieving a cumulative static Physician's Global Assessment (PGA) score of ‘light’ and at least a 2‐point reduction in baseline PGA. A 50% response rate for the cumulative Psoriasis Area and Severity Index 75 was achieved in the FAE monotherapy subcohort after a median of 3 years of treatment, in the FAEs + phototherapy subcohort after 6.7 years and in the FAEs + methotrexate subcohort after 8.1 years (P = 0.001).
Conclusion
According to our data, FAEs as monotherapy or in combination with phototherapy or methotrexate are safe and beneficial for long‐term clinical use. However, multicentre, randomized controlled trials are required to establish the clinical value of monotherapy versus combination therapy and the optimal treatment duration.
Summary
Background Little is known about the association of human polyomaviruses (HPyVs) other than Merkel cell polyomavirus (MCPyV) with nonmelanoma skin cancer.
Objectives To evaluate the ...presence of HPyV6, HPyV7, trichodysplasia spinulosa‐associated polyomavirus (TSV), also called HPyV8, and the recently discovered HPyV9 in basal cell carcinoma (BCC), actinic keratosis (AK), squamous cell carcinoma in situ (SCCis), squamous cell carcinoma (SCC), keratoacanthoma (KA), microcystic adnexal carcinoma (MAC) and atypical fibroxanthoma (AFX).
Methods Archival paraffin‐embedded samples (n = 193: 41 BCC, 31 AK, 8 SCCis, 52 SCC, 42 KA, 5 MAC and 14 AFX) were analysed for the presence of the respective HPyV by polymerase chain reaction (PCR). HPyV DNA loads (HPyV DNA copies per β‐globin gene copy) were determined in all HPyV‐positive samples by quantitative real‐time PCR. Immunohistochemical analysis of MCPyV large T‐antigen (LTA) expression was performed using the monoclonal antibody CM2B4.
Results MCPyV DNA was found in 29% of BCC, 19% of AK, 25% of SCCis, 27% of SCC, 29% of KA, 0% of MAC and 29% of AFX. MCPyV DNA loads never exceeded 0·3 MCPyV DNA copies per β‐globin gene copy (median 0·004). In the immunohistochemical analysis of MCPyV LTA expression, all evaluated samples (32 MCPyV DNA‐positive samples) were LTA negative. HPyV6 DNA was found in 7% of BCC, 3% of AK, 12% of SCCis, 4% of SCC, 5% of KA, and 0% of MAC and AFX. HPyV6 DNA loads never exceeded 0·7 HPyV6 DNA copies per β‐globin gene copy (median 0·015). None of the 193 samples was positive for HPyV7, TSV or HPyV9 DNA.
Conclusions Our findings argue against a pathogenic role for MCPyV, HPyV6, HPyV7, TSV and HPyV9 in the analysed types of non‐Merkel cell carcinoma skin cancer.
: Hidradenitis suppurativa (HS) – a rather common, very chronic and debilitating inflammatory skin appendage disorder with a notoriously underestimated burden of disease – has long been a playground ...for the high priests of nomenclature: Ask a bunch of eminent dermatologists and skin pathologists to publicly share their thoughts on what causes HS, and they will soon get entrenched in a heated debate on whether this historical term is a despicable misnomer. Fortunately, the recently founded Hidradenitis Suppurativa Foundation (HSF; http://www.hs‐foundation.org), to which EXP DERMATOL serves as home journal, has broken with this unproductive tradition and has encouraged publication of the current CONTROVERSIES feature. This is exclusively devoted to discussing the pathobiology of this chronic neutrophilic folliculitis of unknown origin. Although traces of terminological bickering remain visible, it does the HS experts in our virtual debate room credit that they engage in a constructive and comprehensive dissection of potential pathogenesis pathways that may culminate in the clinical picture we know under the competing terms HS or acne inversa. These experts sketch more often complementary than mutually exclusive pathogenesis scenarios, and the outlines of a conceivable consensus on the many open pathobiology questions begin to emerge in these CONTROVERSIES. Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy.
Histology represents the gold standard for morphological investigation of the skin, though biopsy may alter the original morphology, is non-repeatable on the same site and always requires an ...iatrogenic trauma. In the past decade, advances in optics, fibre as well as laser technology have enabled the development of a novel non-invasive optical biomedical imaging technique, optical coherence tomography (OCT). The latter is based on a classic optical measurement method known as low-coherence interferometry that enables non-invasive, high resolution, two- or three-dimensional, cross-sectional imaging of microstructural morphology in biological tissue in situ. Using conventional OCT with a lateral resolution of 10–15
μm, the stratum corneum of glabrous skin (palmoplantar), the epidermis and the upper dermis can usually be identified, as well as skin appendages and blood vessels. For example, non-invasive monitoring of cutaneous inflammation, hyperkeratotic conditions and photoadaptive processes is possible by means of OCT. Furthermore, the development of high-output broadband light sources, e.g. femtosecond Ti:sapphire laser, might soon enable ultrahigh image resolutions of about 1
μm in order to investigate skin tissue on the cellular level, which could potentially allow the differentiation between benign and malignant tissues. Beyond a high resolution morphology in OCT images, tissue characterization by additional local physical parameters, such as the scattering coefficient and refractive index may be of great value, in particular in cosmetics and the pharmaceutical industry. Functional OCT imaging based on spectroscopy, tissue birefringence, elastography and Doppler flow reveals further information on tissue properties and represents an important progress of OCT technique in the field of dermatology. Therefore, the advanced versions of OCT technique might not only lead to significant new insights in skin physiology and pathology, but also in diagnosis and therapeutic control of cutaneous disorders with respect to non-invasive diagnosis of conditions and monitoring of disease activity in addition to treatment effects over time.
Background
Fumaric acid esters (FAEs) are used to treat psoriasis and are known to cause lymphopenia in roughly 60% of the patients. Much remains to be elucidated about the biological effects of FAEs ...on lymphocytes.
Objective
To evaluate the influence of long‐term FAE (Fumaderm®) treatment on peripheral blood CD4+ and CD8+ T cells, CD19+ B cells and CD56+ natural killer (NK) cells in psoriasis.
Methods
In this single‐centre retrospective observational subcohort study, we obtained leucocyte and lymphocyte subset counts before initiating FAE therapy in 371 psoriasis patients (mean age, 47.8 years; 63.3% males) and monitored them during treatment (mean treatment duration, 2.9 years). Multiparametric flow cytometry was used for immunophenotyping.
Results
FAEs significantly reduced the numbers of CD4+ T, CD8+ T, CD19+ B and CD56+ NK cells. Among lymphocyte subsets, the mean percentage reduction from baseline was always highest for CD8+ T cells, with a peak of 55.7% after 2 years of therapy. The risk of T‐cell lymphopenia increased significantly with the age of the psoriasis patients at the time that FAE therapy was initiated. It was significantly decreased for the combination therapy with methotrexate and folic acid (vitamin B9) supplementation. Supporting evidence was found suggesting that T‐cell lymphopenia enhances the effectiveness of FAE therapy.
Conclusions
Monitoring distinct T‐cell subsets rather than just absolute lymphocyte counts may provide more meaningful insights into both the FAE treatment safety and efficacy. We therefore suggest optimizing pharmacovigilance by additionally monitoring CD4+ and CD8+ T‐cell counts at regular intervals, especially in patients of middle to older age. Thus, further prospective studies are needed to establish evidence‐based recommendations to guide dermatologists in the management of psoriasis patients who are taking FAEs and who develop low absolute T‐cell counts.
Background
Previous studies have shown that patients with bullous pemphigoid (BP) are more likely to have neurological diseases (ND).
Objectives
To compare clinical findings in BP patients with and ...without ND and to investigate BP180 autoantibody binding in different neuronal tissues of mammalians.
Methods
Our database was searched for clinical findings of in‐patients with the definitive diagnosis of BP. Moreover, brain tissue of mammalians was treated with serum of BP patients with elevated BP180 autoantibodies using biochip mosaics.
Results
Of 85/161 (52.8%) patients had a history of at least one ND (BP+ND). BP180 (P = 0.018), eosinophils (P = 0.043) and patients' accommodation in nursing homes (P < 0.0001) remained in the logistic regression model as significant independent predictors for the presence of ND in patients with BP. Subgroup analysis of community‐dwelling BP patients revealed 25/93 (26.9%) patients with ND. In this population, the presence of ND also significantly correlated with BP180 (r = 0.26; P = 0.0003) and eosinophils (r = 0.19; P = 0.0087). In the animal model, no BP180‐specific immunofluorescence could be detected.
Conclusions
Our data support results of previous studies detecting significantly increased frequency of ND in BP patients. We have shown that raised BP180 titres and blood eosinophils are independent predictors for the presence of ND in BP patients. However, our experimental data do not support previous results indicating that specific binding of BP180 antibodies in neuronal tissue plays a pathogenetic role in ND.
It has been known since 1851 that atmospheric oxygen is taken up by the human epidermis. The contribution to total respiration
is negligible. Until now the significance for the local oxygen supply of ...the skin has remained unknown. With a newly developed
sensor, the oxygen fluxoptode, it has become possible to make local measurements of the transcutaneous oxygen flux (tc J O 2 ). In this study the sensor was calibrated so that absolute values of tc J O 2 could be reported. At rest, tc J O 2 was determined on normal, humidified skin on the volar forearm of 20 volunteers of different age groups. In order to evaluate
the contribution of the blood flow to the oxygen supply of the skin, tc J O 2 was recorded at the end of a 5 min suprasystolic occlusion of the forearm. At normal skin surface partial oxygen pressure
(163 ± 9 Torr), tc J O 2 was 0.53 ± 0.27 ml O 2 min â1 m â2 . A 5 min interruption of blood flow resulted in an increase of 9.5 ± 6.3 % in tc J O 2 . The value of tc J O 2 was unaffected by the age of the subject. Published data on the oxygen diffusion properties of skin and simulations of intracutaneous
profiles of oxygen partial pressure indicated that under these conditions, the upper skin layers to a depth of of 0.25â0.40
mm are almost exclusively supplied by external oxygen, whereas the oxygen transport of the blood has a minor influence. As
a consequence, a malfunction in capillary oxygen transport cannot be the initiator of the development of superficial skin
defects such as those observed in chronic venous incompetence and peripheral arterial occlusive disease.
Background A new 8% ciclopirox‐medicated nail lacquer (P‐3051), based on a new technology, revealed superior properties in terms of affinity to keratin, nail permeation, and ease of use.
Objective ...This study aims to assess the efficacy and safety of P‐3051 vs. the market 8% ciclopirox nail lacquer.
Methods This is a multicentre, randomized, three‐arm, placebo‐controlled, parallel groups, evaluator‐blinded study. Overall, 467 patients with onychomycosis of at least one big toenail were randomized to receive P‐3051, the reference drug or placebo in a 2 : 2 : 1 ratio for a 48‐week treatment by daily application, followed by a 12‐week follow‐up.
Results The study satisfied its objective by demonstrating that P‐3051 was both superior to placebo and non‐inferior to reference in the complete cure rate after a 48‐week active treatment period. Switching the non‐inferiority to superiority hypothesis, the superiority of P‐3051 vs. reference was nearly significant at week 48 (confirmed at week 52), and it was significant at week 60 (cure rate for P‐3051 is 119% higher than reference; P < 0.05). Altogether, the results on primary endpoint exceed expectations; superiority test was performed also on secondary endpoints to confirm the superiority trend of the study. At the end of follow‐up, percentages of patients who achieved the endpoint ‘responder’ in the P‐3051 group were 66% higher than reference (P < 0.05), and those who achieved the endpoint ‘decrease of diseased nail’ were 40% higher (P < 0.05).
Conclusion Ciclopirox 8% hydrolacquer is more active than reference ciclopirox nail lacquer in the treatment of onychomycosis.
Conflicts of interest
None declared.
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