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in category dermatology

52 results found. For more information, click each entry to expand.

1: Deep skin dysbiosis in vitiligo patients: link with mitochondrial and immune changes
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Posted 30 Jul 2020

Deep skin dysbiosis in vitiligo patients: link with mitochondrial and immune changes
1,178 downloads medRxiv dermatology

Hanene Bzioueche, Kotryna Simonyte Sjodin, Christina E West, Abdallah Khemis, Stephane Rocchi, Thierry Passeron, Meri K Tulic

Rationale: Vitiligo is an autoimmune-disease characterized by patchy, white skin due to melanocyte loss. Commensal cutaneous or gut dysbiosis have been linked to various dermatological disorders. Here, we studied skin and gut microbiota of vitiligo patients compared to healthy controls. Methods: We recruited 20 subjects and obtained swabs and biopsies from lesional and non-lesional skin, stool and blood from each individual (total 100 samples). Results: We detected reduced richness and distribution of microbiota in stool of vitiligo subjects compared to controls (P<0.01). Skin swabs had greater alpha-diversity than skin biopsies (P<0.001), however only trends were seen between groups when examining microbiota at the skin surface. This was in contrast to sampling deeper layers of skin from the same patients which showed decreased richness and distribution of species (P<0.01) but greater phylogenetic diversity (P<0.01) in lesional compared to non-lesional sites. Biopsy microbiota from the lesional skin had distinct microbiota composition which was depleted of protective Bifidobacterium and enriched in Terenicutes, Streptococcus, Mycoplasma and mitochondrial DNA (P<0.001); the latter was linked with increased innate immunity and stress markers in the blood of the same patients (P<0.05). Conclusion: These data describe vitiligo-specific cutaneous and gut microbiota and, for the first time in humans, a link between mitochondrial alteration, innate immunity and skin microbiota.

2: The spectrum of COVID-19-associated dermatologic manifestations: an international registry of 716 patients from 31 countries
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Posted 25 May 2020

The spectrum of COVID-19-associated dermatologic manifestations: an international registry of 716 patients from 31 countries
1,151 downloads medRxiv dermatology

Esther E. Freeman, Devon E. McMahon, Jules B Lipoff, Misha Rosenbach, Carrie Kovarik, Seemal R Desai, Joanna Harp, Junko Takeshita, Lars E French, Henry W Lim, Bruce H Thiers, George J Hruza, Lindy P Fox

Question: What are the cutaneous manifestations associated with COVID-19 and do they provide insight into the pathophysiology or prognosis? Findings: In this international registry-based case series of 716 patients representing 31 countries, the most common dermatologic morphologies encountered in the 171 COVID-19 confirmed case included morbilliform, pernio-like, urticarial, macular erythema, vesicular, papulosquamous, and retiform purpura. Retiform purpura was seen exclusively in critically ill, hospitalized patients. Meaning: COVID-19 is associated with a spectrum of skin findings in affected patients. These cutaneous manifestations may vary depending on the severity of COVID-19.

3: Trends in Medicare Reimbursement, Use Rates, and Overall Expenditure for Skin Cancer Procedures: 2012-2017
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Posted 30 May 2020

Trends in Medicare Reimbursement, Use Rates, and Overall Expenditure for Skin Cancer Procedures: 2012-2017
1,121 downloads medRxiv dermatology

Pranav Puri, Sujith Baliga, Mark R. Pittelkow, Puneet K. Bhullar, Aaron R. Mangold

The treatment of skin cancers represents a growing share of healthcare expenditures. At the same time, Medicare reimbursement rates for physician services have declined with respect to inflation. The objective of this study was to describe the economic effects of declining Medicare reimbursement for skin cancer procedures. In this ecological study, we used the Medicare Physician Supplier and Other Provider Public Use File (POSPUF) to analyze trends in Medicare reimbursement rates, use rates, and overall Medicare expenditures for skin cancer procedures from 2012 to 2017. We adjusted reimbursement rates for inflation by converting payment amounts into units of 2017 dollars. From 2012 to 2017, overall inflation-adjusted Medicare expenditure on skin cancer procedures increased 9%. Over this time period, inflation-adjusted Medicare reimbursement rates declined for each procedure class, with the exception of shave excision. Concurrently, the use rate of Mohs micrographic surgery increased 23%, while the use rate for all other skin cancer procedure classes declined. In summary, this study describes trends suggesting declining Medicare reimbursement rates have been associated with increasing use rates for higher cost skin cancer procedures. Clinicians and policy makers should collaborate to develop value-based payment models that incentivize patient outcomes rather than procedural volumes.

4: Effectiveness of four oral antifungal drugs (fluconazole, griseofulvin, itraconazole, terbinafine) in current epidemic of altered dermatophytosis in India: A randomized pragmatic trial
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Posted 02 Aug 2019

Effectiveness of four oral antifungal drugs (fluconazole, griseofulvin, itraconazole, terbinafine) in current epidemic of altered dermatophytosis in India: A randomized pragmatic trial
1,099 downloads medRxiv dermatology

Sanjay Singh, Usha Chandra, Priyanka Verma, Vinayak N Anchan, Ragini Tilak

BackgroundDermatophyte infections have undergone unprecedented changes in India in recent past. Clinical trials comparing effectiveness of 4 main oral antifungal drugs are not available. We tested effectiveness of oral fluconazole, griseofulvin, itraconazole and terbinafine in chronic and chronic-relapsing tinea corporis, tinea cruris and tinea faciei. MethodsTwo hundred microscopy confirmed patients were allocated to 4 groups, fluconazole (5mg/kg/day), griseofulvin (10 mg/kg/day), itraconazole (5mg/kg/day), and terbinafine (7.5mg/kg/day), by concealed block randomization and treated for 8 weeks or cure. Effectiveness was calculated based on intention to treat analysis. ResultsAt 4 weeks, 4, 1, 2, and 4 patients were cured with fluconazole, griseofulvin, itraconazole and terbinafine, respectively (P=0.417). At 8 weeks, 21 (42%), 7 (14%), 33 (66%) and 14 (28%) patients were cured, respectively (P=0.000); itraconazole was superior to fluconazole, griseofulvin and terbinafine (P[&le;]0.016). Relapse rates after 4 and 8 weeks of cure in different groups were similar. Numbers-needed-to-treat (NNT) (versus griseofulvin), calculated based on cure rates at 8 weeks, for itraconazole, fluconazole, and terbinafine were 2, 4 and 8, respectively. ConclusionIn view of cure rates and NNT, itraconazole is the most effective drug, followed by fluconazole (daily), terbinafine and then griseofulvin, in chronic and chronic-relapsing dermatophytosis in India. One Sentence SummaryEffectiveness of all four antifungals has declined, with itraconazole being the most effective currently in dermatophytosis in India.

5: High-resolution 3-D imaging for precise staging in malignant melanoma
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Posted 27 Jul 2020

High-resolution 3-D imaging for precise staging in malignant melanoma
973 downloads medRxiv dermatology

Simon F. Merz, Philipp Jansen, Ricarda Ulankiewicz, Lea Bornemann, Tobias Schimming, Klaus Griewank, Zuelal Cibir, Andreas Kraus, Ingo Stoffels, Timo Aspelmeier, Sven Brandau, Dirk Schadendorf, Eva Hadaschik, Gernot Ebel, Matthias Gunzer, Joachim Klode

High-resolution imaging of sentinel lymph nodes (SLN) from melanoma patients is a crucial approach to specify staging and determine individuals requiring adjuvant treatment. Current histologic SLN analysis has the substantial drawback that only a small portion of the node is sampled while most of the tissue is discarded which might explain the high false-negative rate of SLN diagnosis. Therefore, we developed an algorithm-enhanced light sheet fluorescence microscopy (LSFM) approach to three-dimensionally reconstruct the entire SLN with the power to identify single tumor cells. We comprehensively quantified total tumor volume while simultaneously visualizing cellular and anatomical hallmarks of the associated SLN architecture. In a first-in-human prospective study (21 SLN from 11 melanoma patients), LSFM not only identified all metastases seen histologically, but additionally detected metastases not recognized by routine histology. Thus, our 3-D digital pathology approach can increase sensitivity and accuracy of SLN-metastasis detection and potentially alleviate the need for conventional histopathological assessment in the future.

6: The Impact of COVID-19 on Medical Practice: A Nationwide Survey of Dermatologists and Healthcare Providers in Iraq
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Posted 04 Aug 2020

The Impact of COVID-19 on Medical Practice: A Nationwide Survey of Dermatologists and Healthcare Providers in Iraq
950 downloads medRxiv dermatology

Mohammed Shanshal, Hayder Saad Ahmed, Hayder Asfoor, Raad Ibrahim Salih, Shehab Ahmed Ali, Yusif k. Aldabouni

Background: The COVID-19 pandemic has dramatically changed medical practice worldwide. It posed a significant impact on different health services, including dermatology. Methods and objectives: Two online surveys were conducted to determine the prevalence of personal protective equipment-related skin complications (200 healthcare providers were included) and to demonstrate the outbreak s impact on dermatology practice (100 dermatologists were included). Results: In the first survey, the response rate was 72.46%. PPE- related dermatoses were reported by 147 (73%) participants, including frictional dermatitis (51.9%), mechanical acne (33.1%), contact dermatitis (29.9%), nonspecific rash (17.5%), urticaria (9.1%) and skin infections (3.2%). The response rate of the second survey was 64%. COVID-19 emerging cutaneous manifestations were recognized by 20% of dermatologists, including maculopapular rash (41.67%), urticaria (37.50%), chilblain (25%) and vasculitis (16.67). Telemedicine was provided by 73% of the dermatologists. The relapse rates of psoriasis, atopic dermatitis, rosacea, vitiligo and alopecia areata were noticeably increased as observed by 62%, 50%, 20%, and 4% of dermatologists, respectively. Most dermatologists (89%) reported minimal use of immunosuppressive drugs amid the pandemic. Conclusions: This article highlights the pivotal role of dermatologists in the leading edge during the current health crisis and how they adapt to these unfamiliar circumstances to meet the challenges. It documents the emergence of PPE-related dermatoses among healthcare providers and the impact of COVID-19 on different aspects of dermatology practice.

7: Incidence and Prevalence of Hidradenitis Suppurativa: A Systematic Review and Meta-analysis
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Posted 22 Nov 2019

Incidence and Prevalence of Hidradenitis Suppurativa: A Systematic Review and Meta-analysis
914 downloads medRxiv dermatology

N. Gill, Robert Gniadecki

BackgroundHidradenitis is a chronic relapsing follicular occlusive disease with a widely variable reported prevalence. The exact prevalence and incidence of HS is unknown. ObjectivesTo perform a systematic review and meta-analysis of the published literature to estimate the global incidence and prevalence of HS. MethodsLiterature searches were performed on Medline, Embase, and Pubmed to identify studies reporting incidence and/or prevalence of HS. Pooled estimates of prevalence and incidence were calculated with a meta-analysis of proportions. ResultsIn total, 12 studies were included (Australia, Brazil, Denmark, France, Germany, Ireland, Israel, UK, USA) comprising a total population of 53,805,690. Eleven studies reported prevalence. The pooled proportion of individuals in the general population with HS was 0.36% (95% CI 0.21 - 0.56). Self-reported HS gave a higher prevalence estimate than clinician-diagnosed HS. HS is more prevalent in women. Average annual incidence of HS was 28.5 cases/100,000 (95% CI 26.8 - 30.1). ConclusionsWe estimated the global prevalence of HS to be 0.36% with 3:2 female predominance and average annual incidence to be 28.5 cases/100,000.

8: Futility of combining griseofulvin and terbinafine in current epidemic of altered dermatophytosis in India: Results of a randomized pragmatic trial
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Posted 25 Sep 2019

Futility of combining griseofulvin and terbinafine in current epidemic of altered dermatophytosis in India: Results of a randomized pragmatic trial
908 downloads medRxiv dermatology

Sanjay Singh, Vinayak N Anchan, Radhika Raheja

BackgroundTreatment responsiveness of tinea has decreased considerably in recent past in India. We tested effectiveness of oral terbinafine plus griseofulvin versus terbinafine alone in tinea corporis, tinea cruris and tinea faciei in a randomized pragmatic open trial. MethodsOne hundred and thirty two microscopy confirmed patients were randomly allocated (ratio 1:1) to two groups, terbinafine (T) and terbinafine plus griseofulvin (T+G). Doses given were as follows: T, oral terbinafine (6 mg/kg/day, maximum 500 mg/day, once daily); T+G, terbinafine (as above) plus oral griseofulvin (children [<18 years] 10 mg/kg/day, adults [18 years or more] 10 mg/kg/day, but not <500 mg and not >1000 mg per day, in two divided doses). Patients were treated for 8 weeks or cure, whichever occurred earlier. ResultsAt 4 weeks, none of the patients were cured in both groups. At 6 weeks, 1(1.5%) and 4 (6.1%) patients were cured in T and T+G groups, respectively (P=0.417). At 8 weeks, 17 (25.8%) and 19 (28.8%) patients were cured in T and T+G groups, respectively (P=0.845). For cure rate at 8 weeks, number needed to treat (NNT) for T+G (versus T), was 33. ConclusionsAddition of griseofulvin to terbinafine does not increase effectiveness of terbinafine in current epidemic of altered dermatophytosis in India.

9: Multidrug therapy with terbinafine plus daily fluconazole is more effective than terbinafine alone or terbinafine plus weekly fluconazole in current epidemic of altered dermatophytosis in India: Results of a randomized pragmatic trial
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Posted 22 Aug 2019

Multidrug therapy with terbinafine plus daily fluconazole is more effective than terbinafine alone or terbinafine plus weekly fluconazole in current epidemic of altered dermatophytosis in India: Results of a randomized pragmatic trial
859 downloads medRxiv dermatology

Sanjay Singh, Bandana Jha, Prakriti Shukla, Vinayak N Anchan

BackgroundTreatment responsiveness of tinea has decreased considerably in recent past in India. We tested effectiveness of oral terbinafine daily plus fluconazole weekly (TFw) and terbinafine daily plus fluconazole daily (TFd) versus oral terbinafine daily (T) in tinea corporis, tinea cruris and tinea faciei in a pragmatic randomized open trial. MethodsOne hundred and seventeen microscopy confirmed patients were allocated to T (6 mg/kg/day), TFw (terbinafine 6 mg/kg/day+fluconazole 12 mg/kg once weekly), or TFd (terbinafine 6 mg/kg/day+fluconazole 6 mg/kg/day) groups by concealed randomization and treated for 8 weeks or cure. Each group included 39 patients. ResultsAt 4 weeks, 9 (23.1%), 8 (20.5%) and 14 (35.9%) patients were cured in T, TFw and TFd groups, respectively (P=0.279). At 8 weeks, number of patients cured was as follows: T 13 (33.3%), TFw 18 (46.2%) and TFd 25 (64.1%). TFd was more effective than T (P=0.012), other comparisons were not significantly different. However, effect size as calculated by number needed to treat (NNT) (versus terbinafine) was 8 for TFw and 4 for TFd. Relapse rates one month after cure were similar in all groups (P=0.664). ConclusionsIn view of cure rates and NNT, terbinafine plus daily fluconazole is more effective than terbinafine alone or terbinafine plus weekly fluconazole in current epidemic of altered dermatophytosis in India. One Sentence SummaryTerbinafine plus daily fluconazole is more effective than terbinafine alone or terbinafine plus weekly fluconazole in current epidemic of altered dermatophytosis in India.

10: Deep neural frameworks improve the accuracy of general practitioners in the classification of pigmented skin lesions
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Posted 08 May 2020

Deep neural frameworks improve the accuracy of general practitioners in the classification of pigmented skin lesions
848 downloads medRxiv dermatology

Maximiliano Lucius, Jorge De All, Jose Antonio De All, Martin Belvisi, Luciana Radizza, Marisa Lanfranconi, Victoria Lorenzatti, Carlos Maria Galmarini

Artificial intelligence can be a key tool in the context of assisting in the diagnosis of dermatological conditions, particularly when performed by general practitioners with limited or no access to high resolution optical equipment. This study evaluates the performance of deep convolutional neural networks (DNNs) in the classification of seven pigmented skin lesions. Additionally, it assesses the improvement ratio in the classification performance when utilized by general practitioners. Open-source skin images were downloaded from the ISIC archive. Different DNNs (n=8) were trained based on a random dataset constituted by 8,015 images. A test set of 2,003 images has been used to assess the classifiers performance at low (300 x 224 RGB) and high (600 x 450 RGB) image resolution and aggregated clinical data (age, sex and lesion localization). We have also organized two different contests to compare the DNNs performance to that of general practitioners by means of unassisted image observation. Both at low and high image resolution, the DNNs framework being trained differentiated dermatological images with appreciable performance. In all cases, accuracy has been improved when adding clinical data to the framework. Finally, the lowest accurate DNN outperformed general practitioners. Physicians accuracy was statistically improved when allowed to use the output of this algorithmic framework as guidance. DNNS are proven to be high performers as skin lesion classifiers. The aim is to include these AI tools in the context of general practitioners whilst improving their diagnosis accuracy in a routine clinical scenario when or where the use of high-resolution equipment is not accessible.

11: TzanckNet: A convolutional neural network to identify cells in the cytology of erosive-vesiculobullous diseases
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Posted 23 Jun 2020

TzanckNet: A convolutional neural network to identify cells in the cytology of erosive-vesiculobullous diseases
817 downloads medRxiv dermatology

Mehmet Alican Noyan, Murat Durdu, Ali Haydar Eskiocak

Tzanck smear test is a low-cost, rapid, and reliable tool which can be used for the diagnosis of many erosive-vesiculobullous, tumoral, and granulomatous diseases. Currently its use is limited mainly due to lack of experience in interpretation of the smears. We developed a deep learning model, TzanckNet, that can identify cells in Tzanck smear test findings. TzanckNet was trained on a retrospective development dataset of 2260 Tzanck smear images collected between December 2006 - December 2019. The finalized model was evaluated using a prospective validation dataset of 359 Tzanck smear images collected from 15 patients during January 2020. It is designed to recognize six cell types (acantholytic cells, eosinophils, hypha, multinucleated giant cells, normal keratinocytes, and tadpole cells). For 359 images and 6 cell types, TzanckNet made 2154 predictions. The accuracy was 94.3 % (95% CI 93.4 to 95.3), the sensitivity was 83.7 % (95% CI 80.3 to 87.0) and the specificity was 97.3 % (95% CI 96.5 to 98.1). The area under the receiver operating characteristic curve was 0.974. Our results show that TzanckNet has the potential to lower the experience barrier needed to use this test, broadening its user base, and hence improving patient well-being.

12: Machine learning applied to atopic dermatitis transcriptome reveals distinct therapy-dependent modification of the keratinocyte immunophenotype
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Posted 19 Dec 2019

Machine learning applied to atopic dermatitis transcriptome reveals distinct therapy-dependent modification of the keratinocyte immunophenotype
791 downloads medRxiv dermatology

K. Clayton, A. Vallejo, S. Sirvent, J. Davies, G. Porter, F. Lim, M.R. Ardern-Jones, M.E. Polak

BackgroundAtopic dermatitis (AD) arises from a complex interaction between an impaired epidermal barrier, environmental exposures, and the infiltration of Th1/Th2/Th17/Th22 T cells. Transcriptomic analysis has advanced understanding of gene expression in cells and tissues. However, molecular quantitation of cytokine transcripts does not predict the importance of a specific pathway in AD or cellular responses to different inflammatory stimuli. ObjectiveTo understand changes in keratinocyte transcriptomic programmes in human cutaneous disease during development of inflammation and in response to treatment. MethodsWe performed in silico deconvolution of the whole-skin transcriptome. Using co-expression clustering and machine learning tools, we resolved the gene expression of bulk skin (n=7 datasets, n=406 samples), firstly, into unsupervised keratinocyte immune response phenotypes and, secondly, into 19 cutaneous cell signatures of purified populations from publicly available datasets. ResultsWe identify three unique transcriptomic programmes in keratinocytes, KC1, KC2, KC17, characteristic to immune signalling from disease-associated helper T cells. We cross-validate those signatures across different skin inflammatory conditions and disease stages and demonstrate that the keratinocyte response during treatment is therapy dependent. Broad spectrum treatment with ciclosporin ameliorated the KC17 response in AD lesions to a non-lesional immunophenotype, without altering KC2. Conversely, the specific anti-Th2 therapy, dupilumab, reversed the KC2 immunophenotype. ConclusionOur analysis of transcriptomic signatures in cutaneous disease biopsies reveals the complexity of keratinocyte programming in skin inflammation and suggests that the perturbation of a single axis of immune signal alone may be insufficient to resolve keratinocyte immunophenotype abnormalities.

13: An acute bleomycin inflammatory and fibrotic mouse model of morphea is dependent upon CXCL9 and CXCR3
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Posted 28 Jun 2019

An acute bleomycin inflammatory and fibrotic mouse model of morphea is dependent upon CXCL9 and CXCR3
717 downloads medRxiv dermatology

Jillian M. Richmond, Dhrumil Patel, Tomoya Watanabe, Colton J. Garelli, Madhuri Garg, Karen Dresser, April Deng, Carol A. Feghali-Bostwick, John E. Harris, Heidi Jacobe

Morphea, or localized scleroderma, is characterized by an inflammatory phase followed by cutaneous fibrosis, which may lead to disfigurement and/or disability. Previous work from our group showed that the CXCR3 ligands CXCL9 and CXCL10 are highly upregulated in lesional skin of morphea patients. Here, we used an acute inflammatory and fibrotic bleomycin mouse model of morphea to examine the role of the CXCR3 chemokine axis in pathogenesis. We first characterized which cells produce the CXCR3 ligands in the skin using the Reporter of Expression of CXCR3 ligands mouse (REX3). We found that fibroblasts contribute the bulk of CXCL9 and CXCL10, whereas endothelial cells are key dual chemokine producers. Macrophages, which have high MFI of chemokine expression, upregulated CXCL9 production over time, fibroblasts CXCL10 production, and T cells dual chemokine expression. To determine whether bleomycin treatment could directly induce expression of these chemokines, we treated cultured REX3 mouse dermis monolayers in vitro with bleomycin or IFN{gamma} with TNF and found that bleomycin could induce low amounts of CXCL9 directly in fibroblasts, whereas the cytokines were required for optimal CXCL9 and CXCL10 production. To determine whether these chemokines are mechanistically involved in pathogenesis, we induced fibrosis in CXCL9, CXCL10, or CXCR3 deficient mice and found that fibrosis is dependent on CXCL9 and CXCR3. Addition of recombinant CXCL9, but not CXCL10, to cultured mouse fibroblasts induces collagen 1a1 mRNA expression, indicating the chemokine itself can contribute to fibrosis. Taken together, our studies provide evidence that acute intradermal bleomycin administration in mice can model inflammatory morphea, and that CXCL9 and its receptor CXCR3 are mechanistically involved in pathogenesis. One Sentence SummaryCXCL9 drives acute morphea pathogenesis in mice.

14: Retrospective Assessment of Deep Neural Networks for Skin Tumor Diagnosis
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Posted 15 Dec 2019

Retrospective Assessment of Deep Neural Networks for Skin Tumor Diagnosis
702 downloads medRxiv dermatology

Seung Seog Han, Ik Jun Moon, Jung-Im Na, Myoung Shin Kim, Gyeong Hun Park, Seong Hwan Kim, Kiwon Kim, Ju Hee Lee, Sung Eun Chang

BACKGROUND The aim of this study was to validate the performance of algorithm (http://rcnn.modelderm.com) for the diagnosis of benign and malignant skin tumors. METHODS With external validation dataset (43 disorders; 40,331 clinical images from 10,426 patients; January 1, 2008 - March 31, 2019), we compared the prediction of algorithm with the clinical diagnosis of 65 attending physicians at the time of biopsy request. RESULTS For binary-task classification of determining malignancy, the AUC of the algorithm was 0.863(95% CI 0.852-0.875) with unprocessed clinical photographs. The sensitivity / specificity of the algorithm at the predefined high-sensitivity and high-specificity threshold were 79.1%(76.9-81.4) / 76.9%(76.1-77.8) and 62.7%(59.9-65.5) / 90.0%(89.4-90.6), respectively. The sensitivity/specificity calculated by the clinical diagnosis of attending physicians were 88.1% / 83.8%(Top-3) and 70.2% / 95.6%(Top-1), which were superior to those of algorithm. For multi-task classification, the mean Top-1,2,3 accuracies of the algorithm were 42.6%, 56.1%, 61.9%, and those of clinical diagnosis were 65.4%, 73.9%, 74.7%, respectively. In the reader test with images from 30-patients batches, the sensitivity / specificity of the algorithm at the predefined threshold were 66.9% / 87.4%. The sensitivity / specificity derived from the first diagnosis of 44 the participants were 65.8% / 85.7%, which were comparable with those of the algorithm (Wilcoxon signed-rank test; P=0.61 / 0.097). CONCLUSIONS Our algorithm could diagnose skin tumors at dermatologist-level when diagnosis was made solely with photographs, demonstrating its potential as a mass screening tool in telemedicine setting. However, due to limited data relevancy, the performance was inferior to that of actual medical examination. Clinical information should be integrated with imaging information to achieve more accurate predictions.

15: Causal analysis shows evidence of atopic dermatitis leading to an increase in vitamin D levels
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Posted 23 Apr 2020

Causal analysis shows evidence of atopic dermatitis leading to an increase in vitamin D levels
675 downloads medRxiv dermatology

Daniel R Drodge, Ashley Budu-Aggrey, Lavinia Paternoster

Atopic dermatitis (AD) patients have been observed to have lower vitamin D levels. Previous studies have found little evidence that vitamin D levels causally influence the risk of AD, but the reverse direction has not yet been investigated. Here we used Mendelian Randomization to assess the causal relationship between AD and serum vitamin D levels, using genetic data from the most recent GWA studies of vitamin D and AD. There was little evidence for vitamin D levels causally influencing AD risk (odds per standard deviations increase in log-transformed vitamin D levels =1.233, 95% CI 0.927 to 1.639, P-value =0.150). However, genetic liability for AD raises serum vitamin D levels by 0.043 (95% CI 0.017 to 0.069) standard deviations per doubling of odds of disease (P-value =0.001). The AD-associated filaggrin (FLG) mutation R501X appears to show a particularly strong relationship with vitamin D. However, the relationship between AD and vitamin D holds when R501X is omitted (0.018, 95% CI 0.004 to 0.031, P-value =0.008). We found evidence that AD is causally associated with an increase in serum vitamin D levels. Whilst the AD-associated FLG gene has a particularly strong relationship with vitamin D, other AD SNPs show a consistent direction of effect, suggesting that AD more generally influences serum vitamin D levels.

16: Oral Collagen for the treatment of Dermal Atrophy: A systematic review of human trials
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Posted 19 Jul 2020

Oral Collagen for the treatment of Dermal Atrophy: A systematic review of human trials
672 downloads medRxiv dermatology

Rhydian P Howell-Morris

BACKGROUND Dermal atrophy (DA) or skin "thinning" can cause a substantial impact on quality of life and, due to barrier function damage, further health problems including cutaneous infection, skin tears and lacerations from minor trauma, impaired wound healing and chronic dermal inflammation. Some dietary products are targeted at therapeutic and functional treatments for skin ageing (of which mild DA is a component); however, while dietary collagen is amongst the most popular, particularly in the form of collagen peptides (CPs), in contrast to reviews for both over-the-counter and under prescription topical treatments for DA (e.g. Tretinoin), there is no reviewed literature of human trials testing the efficacy of orally administered collagen treatments applicable to DA; hence this review. OBJECTIVE To review the literature and assess available randomised-controlled trials (RCTs) testing the efficacy of orally administered collagen treatments for any skin properties that relate to the pathophysiology of DA and suggest their potential for medical and general public use in treating DA. EVIDENCE REVIEW METHOD A PubMed search was conducted using "(collagen) AND (supplementation OR treatment) AND (skin OR dermis)", after which titles and abstracts were screened to decide if they matched the inclusion criteria for review. Results were collected up to 1st of August 2019 and no lower limit on the year of publication was set. MAIN RESULTS Five studies with a total of 430 participants were included for review, with participants aged 24-70. Four out of the five studies used female only participants. The five studies used orally administered CPs, with dosage ranging from 570 mg/d to 10 g/d, running from 8 weeks to 6 months and assessed a range of skin properties relevant to DA including dermal thickness, epidermal thickness, dermal density, dermal collagen content, dermal collagen density and dermal elasticity. One of the studies combined CPs with several antioxidant ingredients to form the treatment and the remaining 4 studies used CPs as the only active ingredient. Methods to control for potential confounders were implemented in most studies including limiting exposure to sun, implementing a pre-treatment period of 1 week or more that controlled the use of cosmetics and intake of certain medications, micronutrient supplements and nutraceuticals with those restrictions continuing for the duration of the study. Given the heterogeneity of outcome measures across studies, quantitative analysis of results was not possible. In summary, the study with the antioxidant combined supplement showed a significant improvement in dermal thickness; two of the studies showed improvement in dermal collagen or pro-collagen content; three of the studies showed improvement in dermal elasticity; three studies showed improvement in dermal density or dermal collagen density; and lastly, no human study was found with the stated objective of assessing CPs effect specifically on DA. CONCLUSION Although definitive mechanistic cause-effect conclusions could not be drawn from the existing studies, they are supportive of beneficial effects of oral CP intake for treating characteristics of dermal atrophy. Further elucidation of the exact mode(s) of action that the CP intake has on improving dermal thickness, dermal density, and other skin biomarkers is necessary, with larger studies including more finely divided experimental and dose-response groups. In conclusion, rigorousness of the trials must be improved to establish a cause-effect relationship between the CP intake and the beneficial effects for the skin atrophy, however potential has been demonstrated.

17: Genomic and phenotypic characterization of endotypes in atopic dermatitis
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Posted 20 Apr 2020

Genomic and phenotypic characterization of endotypes in atopic dermatitis
652 downloads medRxiv dermatology

Sandra Smieszek, Bartlomiej Przychodzen, Sarah E. Welsh, Changfu Xiao, Jingyuan Wang, Jennifer Brzezinski, Alyssa Kaden, Michael A Mohrman, Sonja Stander, Gunther Birznieks, Christos Polymeropoulos, Mihael H Polymeropoulos

Background: Atopic dermatitis (AD) is a heritable and heterogeneous inflammatory chronic skin disorder. Utilizing decision tree/ supervised learning of extensive clinical, molecular and genetic data, we aimed to define distinct AD endotypes. Methods: Deep phenotyping and whole-genome sequencing was performed on samples obtained from participants of EPIONE, a phase III study in AD patients with severe pruritus: mild (23%) to moderate (64%) and severe (13%) as determined by validated Investigator Global Assessment scale for Atopic dermatitis (vIGA-ADTM). Three categories of analysis were performed: clinical associations, lab value associations (EOS, IgE, cytokines) and genetic analysis of whole-genome sequencing data Results: Based on a decision tree, we found that mild AD presents with fewer lesions with mild erythema and minimal induration/papulation or oozing/crusting. In contrast, severe AD presents with a larger number of erythematous lesions associated with significant induration/papulation or oozing/crusting. We observe significant differences between severity and eosinophil counts (p < 0.001), IgE (p < 0.001) and Filaggrin (FLG) LOF frequency (OR 2.3 CI 1.6-3.2 p < 0.0001) as well as interleukin pathway genes, specifically IL5RA variants differentiating the groups. Conclusion: Our results suggest significant differences between severity groups across a number of features appear to constitute distinct endotypes with likely distinct causative factors. Differing underlying pathophysiologies indicate endotype knowledge is critical to help guide therapeutic approaches to AD.

18: Risk of Inflammatory Bowel Disease in Psoriasis Patients Treated with Anti-Interleukin-17 Agents: A Bayesian Metaanalysis
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Posted 19 Nov 2019

Risk of Inflammatory Bowel Disease in Psoriasis Patients Treated with Anti-Interleukin-17 Agents: A Bayesian Metaanalysis
639 downloads medRxiv dermatology

N. Gill, M. Pietrosanu, Robert Gniadecki

BackgroundUse of interleukin-17 inhibitors (IL-17i) in psoriasis has been associated with an increased risk of inflammatory bowel disease (IBD). However, the clinical significance of this association is not understood. ObjectivesTo quantify the absolute risk of IBD in patients with psoriasis treated with IL-17i, stratified by known IBD risk factors. MethodsLiterature searches were performed to identify known IBD risk factors and the prevalences were quantified by a meta-analysis of proportions. The Bayesian model was used to estimate the probability of a new-onset or a flare of IBD in patients with psoriasis. ResultsThe prevalence of Crohns disease (CD) or ulcerative colitis (UC) in the general psoriasis population was 0.0010. Use of IL-17i increased the risk of CD to 0.0037 and UC to 0.0028, translating to a number needed to harm (NNH) of 373 for CD and 564 for UC. In patients who had concomitant hidradenitis suppurativa, the use of IL-17i was associated with a decrease in NNH for CD and UC to 18 and 76, respectively, whereas for patients with a family history of IBD, the NNH values were 6 (for CD) and 10 (for UC). ConclusionsIn patients with no risk factors, the probability of IBD flare or onset during IL-17i treatment is negligible and additional IBD screening procedures are not indicated. In contrast, the patients with psoriasis who have hidradenitis suppurativa or first-degree family history of IBD as risk factors should be monitored for signs and symptoms of CD and UC during IL-17i therapy.

19: Obesity and Race Alter Gene Expression in Skin
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Posted 05 Jun 2020

Obesity and Race Alter Gene Expression in Skin
639 downloads medRxiv dermatology

Jeanne Marie Walker, Sandra Garcet, Jose O Aleman, Christopher E Mason, David C Danko, Simone Zuffa, Jonathan R Swann, James Krueger, Jan L Breslow, Peter R Holt

Obesity is accompanied by dysfunction of many organs, but effects on the skin have received little attention. We studied differences in epithelial thickness by histology and gene expression by Affymetrix gene arrays and PCR in the skin of 10 obese (BMI 35-50) and 10 normal weight (BMI 18.5-26.9) postmenopausal women paired by age and race. Epidermal thickness did not differ with obesity but the expression of genes encoding proteins associated with skin blood supply and wound healing were altered. In the obese, many gene expression pathways were broadly downregulated and subdermal fat showed pronounced inflammation. There were no changes in skin microbiota or metabolites. African American subjects differed from Caucasians with a trend to increased epidermal thickening. In obese African Americans, compared to obese Caucasians, we observed altered gene expression that may explain known differences in water content and stress response. African Americans showed markedly lower expression of the gene encoding the cystic fibrosis transmembrane regulator characteristic of the disease cystic fibrosis. The results from this preliminary study may explain the functional changes found in the skin of obese subjects and African Americans.

20: Timing of PCR and Antibody Testing in Patients with COVID-19 associated dermatologic manifestations
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Posted 04 Jul 2020

Timing of PCR and Antibody Testing in Patients with COVID-19 associated dermatologic manifestations
637 downloads medRxiv dermatology

Esther E. Freeman, Devon E. McMahon, Lindy P Fox, Marlys S Fassett

A recent study from Spain noted 40 patients with chilblain-like lesions in suspected COVID-19.1 None tested PCR positive for SARS-CoV-2, but 30% had detectable antibodies. The rapid increase in chilblain/pernio-like cases during the COVID-19 pandemic is likely SARS-CoV-2-associated. The relationship between skin symptom onset and COVID-19 PCR/antibody test timing, however, remains uncharacterized. We established an international registry for cutaneous manifestations of COVID-19.2, 3 Providers reported time between dermatologic symptom onset and positive/negative COVID-19 laboratory results, when available. From 8 April-30 June, 2020, 906 laboratory-confirmed or suspected COVID-19 cases with dermatologic manifestations were reported, 534 of which were chilblains/pernio.3 Among PCR-tested patients, 57%(n=208) overall and 15%(n=23) of chilblains/pernio cases were PCR-positive. Antibody positivity was 37%(n=39) overall and 19%(n=15) for chilblains/pernio. We evaluated 163 patients with timing information on PCR and/or antibody testing (Table 1). For patients with suspected COVID-19 and any cutaneous manifestation, PCR-positive testing occurred median 6 (IQR 1-14) days after dermatologic symptoms started while PCR-negative testing occurred median 14 (IQR 7-24) days later. For patients with pernio/chilblains, PCR-positivity was noted 8 (IQR 5-14) days after symptoms and negativity median 14 (IQR 7-28) days later. Antibody testing (IgM or IgG) was positive median 30 (IQR 19-39) days after symptom onset for all dermatologic manifestations and 27 (IQR 24-33) days after chilblains/pernio onset. Like Hubiche et al, our data highlight the low frequency of SARS-CoV-2 PCR+ testing in COVID-19 patients with cutaneous manifestations. Positive predictive values for COVID-19 PCR are influenced by viral shedding kinetics, which are difficult to assess in non-respiratory presentations.4 Our data reveal that early PCR testing is more likely to be positive than later testing, even when date-of-onset is defined by cutaneous manifestations rather than systemic symptoms. Most COVID-19 antibody data are from systemically-ill patients; the kinetics of antibody production in mild-to-moderate COVID-19 infections remain unclear.5 Here, positive antibodies resulted median 30 days from disease onset, beyond the frequently used 14-21 day testing window. In outpatients with true infection, many factors influence the likelihood of a positive antibody result: antibody production, test availability, assay sensitivity, and timing of care-seeking in relation to symptom-onset. These variables influence our interpretation of individual test results and our understanding of the association between pernio and COVID-19. More population-level testing data is necessary to optimize diagnostic test timing. Positive identification of COVID-19 in minimally-symptomatic patients, including patients with skin findings, is critical to the public health effort.

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