An ontological analysis of a dataset of curated dermatological gene disease associations (G2P-Skin).

DR. JAMES NEVINS HYDE, one of the most distinguished American dermatologists, was born at Norwich, Connecticut, on June 21, 1840, the son of a merchant. He received his medical education at the College of Physicians and Surgeons, New York, and qualified in 1869 at the University of Pennsylvania in Philadelphia. From that date until his death he practised in Chicago, where he was the principal pioneer in dermatology. His first appointment was that of lecturer in dermatology at the Rush Medical College from 1873 until 1876, when he was made professor of dermatology in the Northwestern University. Three years later he became professor of dermatology, genito-urinary and venereal diseases at Rush Medical College, and from 1902 until 1910 he held the chair of dermatology at the University of Chicago. He was also attending dermatologist to several hospitals in Chicago. His literary output was considerable. In addition to his principal work, “A Practical Treatise on Diseases of the Skin”, which first appeared in 1883 and ran through eight editions, he contributed more than a hundred articles to dermatological literature. Hyde enjoyed an international reputation as shown by his membership of the dermatological societies of France, Italy, Berlin and Vienna. He was twice president of the American Dermatological Association and was secretary for America at the Fifth International Dermatological Association held in Berlin in 1904. He died suddenly at the age of seventy on September 6, 1910.

Phakomatosis pigmentovascularis type IIIb: A case associated with Sturge-Weber and Klippel-Trenaunay syndromes

Skin disease and its treatment may have radiological connotations. Though this article is not a comprehensive account of dermatological and radiological associations, it provides an eclectic selection of some common and some rare clinical entities, which the practicing radiologist may recognize or remember.

Skin and eyes share a common embryological origin from the embryonic surface ectoderm. Ocular manifestations are one of the most important and common associations of dermatological diseases. Currently, there are few comprehensive reviews of the ocular manifestations of dermatological diseases. We have reviewed more than 40 published articles related to the ocular manifestations of the most important dermatological diseases. The search included Pubmed, Google Scholar, and Cochrane databases from 2014 to 2019. This review was divided into three parts including infections, inflammatory, genetics, connective tissue, autoimmune, neoplasms, and drug-related disorders. We excluded metabolic, endocrine, and nutrition-related dermatological diseases. The relationship of ocular manifestations and dermatological diseases is important to recognize for appropriate management since many dermatological diseases can manifest initially with ocular findings. In this part, we summarized the most common and significant ocular findings in infectious and inflammatory dermatological disorders with appropriate referral recommendations to ophthalmology.

BackgroundFrailty is associated with a variety of diseases, but the relationship between frailty and psoriasis remains unclear.MethodsFirst, we conducted a two‐sample Mendelian randomization based on genome‐wide association studies (GWAS) to investigate genetic causality between frailty index and common diseases in dermatology. Inverse variance weighted was used to estimate causality. Second, expression quantitative trait locus (eQTLs) analysis was conducted to identify the genes affected by Single nucleotide polymorphisms (SNPs). Third, we performed function and pathway enrichment, transcriptome‐wide association studies (TWAS) analysis based on eQTLs.ResultsIt was shown that the rise of frailty index could increase the risk of psoriasis (IVW, beta = 0.916, OR = 2.500, 95%CI:1.418‐4.408, p = 0.002) through Mendelian randomization (MR), and there was no heterogeneity and pleiotropy. There was no causality between the frailty index and other common diseases in dermatology. We found 31 eQTLs based on strongly correlated SNPs in the causality. TWAS analysis found that the expressions of four genes were closely related to psoriasis, including HLA‐DQA1, HLA‐DQA2, HLA‐DRB1 and HLA‐DQB1.ConclusionIt suggested that the frailty index had a significant positive causality on the risk of psoriasis, which was well documented by combined genomic, transcriptome, and proteome analyses.

Autoimmune encephalitis associated with autoimmune blistering diseases: A case series and retrospective review

Prisoners have heightened health needs, and only recently has the importance of skin diseases in this group been recognized. The aim of this study was to estimate the prevalences of dermatological diseases among prisoners in the jails of southern Lazio and to investigate the determinants of these. A cross-sectional study was carried out in three jails in southern Lazio. Retrospective data collection for sociodemographic characteristics, lifestyle habits, and health status was realized using patients' charts. The study sample consisted of 2653 male prisoners detained during 1995-2000. A total of 7.9% of the sample were found to have dermatological disease. The most common diseases were nonspecific dermatitis (3.1%), acne (1.5%), mycosis (1.4%), and scabies (0.7%). Multiple regression analyses were conducted to establish the associations of skin diseases with substance addiction status and age. In addition, a highly significant association emerged between length of detention and rate of dermatological disease. This study shows that habitual offenders, foreign inmates, prisoners serving long sentences, and prisoners who are illiterate are the most affected by dermatological disease. The conditions of detention may be the main reason; preventative strategies such as limiting overcrowding and the provision of electronic case sheets and a centralized database to collect and maintain patient clinical data might be effective in improving public health in jails.

Gut microbiota has been associated with dermatological problems in earlier observational studies. However, it is unclear whether gut microbiota has a causal function in dermatological diseases. Thirteen dermatological diseases were the subject of bidirectional Mendelian randomization (MR) research aimed at identifying potential causal links between gut microbiota and these diseases. Summary statistics for the Genome-Wide Association Study (GWAS) of gut microbiota and dermatological diseases were obtained from public datasets. With the goal of evaluating the causal estimates, five acknowledged MR approaches were utilized along with multiple testing corrections, with inverse variance weighted (IVW) regression serving as the main methodology. Regarding the taxa that were causally linked with dermatological diseases in the forward MR analysis, reverse MR was performed. A series of sensitivity analyses were conducted to test the robustness of the causal estimates. The combined results of the five MR methods and sensitivity analysis showed 94 suggestive and five significant causal relationships. In particular, the genus Eubacterium_fissicatena_group increased the risk of developing psoriasis vulgaris (odds ratio [OR] = 1.32, pFDR = 4.36 × 10-3), family Bacteroidaceae (OR = 2.25, pFDR = 4.39 × 10-3), genus Allisonella (OR = 1.42, pFDR = 1.29 × 10-2), and genus Bacteroides (OR = 2.25, pFDR = 1.29 × 10-2) increased the risk of developing acne; and the genus Intestinibacter increased the risk of urticaria (OR = 1.30, pFDR = 9.13 × 10-3). A reverse MR study revealed insufficient evidence for a significant causal relationship. In addition, there was no discernible horizontal pleiotropy or heterogeneity. This study provides novel insights into the causality of gut microbiota in dermatological diseases and therapeutic or preventive paradigms for cutaneous conditions.

Atopic dermatitis (AD), psoriasis (PSO), rosacea, and other related immune skin diseases are affected by multiple complex factors such as genetic and microbial components. This research investigates the causal relationships between specific skin microbiota and these diseases by using Mendelian randomization (MR), and Bayesian weighted Mendelian randomization (BWMR). We utilized genome-wide association study (GWAS) data to analyze the associations between various skin bacteria and three dermatological diseases. Single nucleotide polymorphisms (SNPs) served as instrumental variables (IVs) in MR methods, including inverse variance weighted (IVW), and MR Egger. BWMR was employed to validate results and address pleiotropy. The IVW analysis identified significant associations between specific skin microbiota and dermatological diseases. ASV006_Dry, ASV076_Dry, and Haemophilus_Dry were significantly positively associated with AD, whereas Kocuria_Dry was negatively associated. In PSO, ASV005_Dry was negatively associated, whereas ASV004_Dry, Rothia_Dry, and Streptococcus_Moist showed positive associations. For rosacea, ASV023_Dry was significantly positively associated, while ASV016_Moist, Finegoldia_Dry, and Rhodobacteraceae_Moist were significantly negatively associated. These results were corroborated by BWMR analysis. Bacterial species such as Finegoldia, Rothia, and Streptococcus play crucial roles in the pathogenesis of AD, PSO, and rosacea. Understanding these microbial interactions can aid in developing targeted treatments and preventive strategies, enhancing patient outcomes and quality of life.

16933 Association of depressive disorders and dermatologic diseases using PHQ-2 as a screening tool in a dermatologic center in Bogota, Colombia

Psoriasis is a chronic inflammatory dermatological disease, and there is a lack of understanding of the genetic factors involved in psoriasis in Taiwan. To establish associations between genetic variations and psoriasis, a genome‑wide association study was performed in a cohort of 2,248 individuals with psoriasis and 67,440 individuals without psoriasis. Using the ingenuity pathway analysis software, biological networks were constructed. Human leukocyte antigen (HLA) diplotypes and haplotypes were analyzed using Attribute Bagging (HIBAG)‑R software and chi‑square analysis. The present study aimed to assess the potential risks associated with psoriasis using a polygenic risk score (PRS) analysis. The genetic association between single nucleotide polymorphisms (SNPs) in psoriasis and various human diseases was assessed by phenome‑wide association study. METAL software was used to analyze datasets from China Medical University Hospital (CMUH) and BioBank Japan (BBJ). The results of the present study revealed 8,585 SNPs with a significance threshold of P<5x10‑8, located within 153 genes strongly associated with the psoriasis phenotype, particularly on chromosomes 5 and 6. This specific genomic region has been identified by analyzing the biological networks associated with numerous pathways, including immune responses and inflammatory signaling. HLA genotype analysis indicated a strong association between HLA‑A*02:07 and HLA‑C*06:02 in a Taiwanese population. Based on our PRS analysis, the risk of psoriasis associated with the SNPs identified in the present study was quantified. These SNPs are associated with various dermatological, circulatory, endocrine, metabolic, musculoskeletal, hematopoietic and infectious diseases. The meta‑analysis results indicated successful replication of a study conducted on psoriasis in the BBJ. Several genetic loci are significantly associated with susceptibility to psoriasis in Taiwanese individuals. The present study contributes to our understanding of the genetic determinants that play a role in susceptibility to psoriasis. Furthermore, it provides valuable insights into the underlying etiology of psoriasis in the Taiwanese community.

The sequencing of the human genome, the identification of common single-nucleotide polymorphisms (SNPs) and haplotype blocks, and advances in microarray technology have enabled the study of complex diseases at a level of detail not previously imaginable. These have aided in the design and analyses of association and linkage studies of many complex diseases including cardiovascular disease. Recent technological advances have enabled the undertaking of large-scale genome-wide association studies (GWAS) that can assay hundreds of thousands of polymorphic sites on hundreds to thousands of individuals to find genomic regions associated with disease. Although results from these experiments enable the identification of smaller regions of association compared with previous studies, as with all linkage and association studies, there is the need for the further investigation of regions of interest for the causal genes or variants. The purpose of this review is to present a detailed demonstration as to how publicly available resources can be used to easily guide more detailed research into genomic regions of interest identified in linkage and association study data. Large-scale projects, such as the Human Genome Sequencing project,1,2 have generated large volumes and varieties of annotated genomic data necessitating the development of Internet-based tools to organize and make practically available these public data. One important tool in human disease research is the web-based graphical genome browsers that use the human genome sequence as the framework on which to organize genomic annotations, providing various ways for researchers to view and extract important information. Currently, there are 3 human genome browsers that have been developed for public use: (1) the National Center for Biotechnology Information (NCBI) Map Viewer3; (2) the University of California Santa Cruz (UCSC) Genome Browser4; and (3) the European Bioinformatics Institute’s Ensembl system.5 Although these genome browsers share common features and …

Linked Article: Cho et al. Br J Dermatol 2021; 184:296–303.

Background and objectiveNail disorders encompass a wide spectrum of conditions, spanning congenital, developmental, infectious, neoplastic, degenerative, dermatological, and systemic diseases. A comprehensive exploration of their clinical manifestations, incidence, and associations is crucial for precise diagnosis and effective management.MethodsThis observational cross-sectional study conducted at B.J. Medical College and Civil Hospital, Ahmedabad involved 300 consecutive patients with nail changes from July 2017 to June 2019 reporting diverse dermatological and systemic conditions. The inclusion criteria involved patients of both genders and all age groups displaying nail changes associated with dermatological and systemic diseases. Data collection entailed a comprehensive clinical history, systemic and dermatological examinations, nail assessment using Dermoscope (DermLite 3, 10x), and supplementary tests. Analyses were performed on Microsoft Excel 2007 software. The study was approved by the Institute Ethics Committee.ResultsAmong the 300 cases, females had a higher prevalence of nail involvement (57%), with a female-to-male ratio of 1.3:1. The most affected age group was 21-40 years, with 6-10 nails typically affected. Notably, housewives showed a higher prevalence. The most frequent nail condition was onychomycosis (24.33%) followed by psoriatic nail changes (20%). Less frequent nail changes involved eczema (5.7%), paronychia (5%), drug-induced (4.3%), lichen planus (3.7%), trauma-induced (3%), twenty nail dystrophy (2.33%), Darier's disease (2%), pemphigus vulgaris (2%), alopecia areata (1.67%), median Heller dystrophy (1.33%), atopic dermatitis (1%), epidermolysis bullosa (1%), racquet nail (1%), leprosy (1%), pityriasis rubra pilaris (0.67%), vitiligo (0.67%), secondary syphilis (0.67%), pachyonychia congenita (0.67%), as well as a case each of total leukonychia, subungual warts, Koenen tumor, and periungual fibroma(0.33%). Systemic autoimmune connective tissue disorders (CTD) accounted for 9%; the most common nail finding observed was nail fold erythema (48.1%) followed by nail fold telangiectasis (44.4%). In systemic sclerosis (SS), the most common finding was nail fold telangiectasia, and in systemic lupus erythematosus (SLE), the most common was nail fold erythema. Scleroderma capillary pattern on nail fold capillaroscopy was found in seven patients with SS, two patients with dermatomyositis, and only one patient with SLE. Nail changes observed in systemic diseases include onychomycosis in diabetes mellitus and chronic renal failure patients, splinter hemorrhages in ischemic heart disease and hypertension, longitudinal melanonychia in HIV, and koilonychia and platynychia in iron deficiency anemia. Other systemic diseases, such as Addison's disease and renal failure, also exhibited various nail changes.ConclusionsBeyond their cosmetic importance, nails hold a vital pathologic role. Proficiency in nail terminology and classification is key for skillful evaluation. Understanding normal and abnormal nail variants, along with their disease associations, benefits diagnosis and tailored management. Nails, often overlooked but accessible, serve as a window into patients' general health and should be an integral part of thorough examinations. This study highlights an intricate clinical panorama of nail disorders, highlighting their significant role in both dermatological and systemic contexts.

Complement bridges the innate and adaptive immune systems, recognizing and eliminating microorganisms and maintaining tissue homeostasis. Perturbations in the complement cascade can be of profound clinical consequence, with dermatological associations including impaired control of infectious agents, predisposition to autoimmune disease (notably systemic lupus erythematosus) and hereditary and acquired angioedema. In this review, the authors describe the fundamentals of the complement cascade and discuss the clinical manifestations of defects in signaling in order to contextualize the rational testing of complement components and functional assays in dermatological practice.