CLDN1 knock out keratinocytes as a model to investigate multiple skin disorders.

The transmembrane protein claudin-1 is critical for formation of the epidermal barrier structure called tight junctions (TJ) and has been shown to be important in multiple disease states. These include neonatal ichthyosis and sclerosing cholangitis syndrome, atopic dermatitis and various viral infections. To develop a model to investigate the role of claudin-1 in different disease settings, we used CRISPR/Cas9 to generate human immortalized keratinocyte (KC) lines lacking claudin-1 (CLDN1 KO). We then determined whether loss of claudin-1 expression affects epidermal barrier formation/function and KC differentiation/stratification. The absence of claudin-1 resulted in significantly reduced barrier function in both monolayer and organotypic cultures. CLDN1 KO cells demonstrated decreases in gene transcripts encoding the barrier protein filaggrin and the differentiation marker cytokeratin-10. Marked morphological differences were also observed in CLDN1 KO organotypic cultures including diminished stratification and reduced formation of the stratum granulosum. We also detected increased proliferative KC in the basale layer of CLDN1 KO organotypic cultures. These results further support the role of claudin-1 in epidermal barrier and suggest an additional role of this protein in appropriate stratification of the epidermis.

What you need to know about common skin problems in older adults.

Skin ageing is a multifaceted process impacted by both intrinsic and extrinsic factors. Drier and less elastic skin with declining sebum levels in older age makes ageing skin more vulnerable to various skin conditions, including infections, inflammatory dermatoses, and cancers. Skin problems are common among older adults due to the effects of ageing, polypharmacy and multimorbidity impacting not only physical health but wellbeing and quality of life. In the UK, older adults in geriatric medicine wards may present with various skin conditions. Hospitalised older individuals may have undiagnosed skin problems unrelated to their admission, making hospitalisation an opportunity to manage unmet needs. Asteatotic eczema, incontinence associated dermatitis, seborrhoeic dermatitis, chronic venous insufficiency, and cellulitis are common disorders clinicians encounter in the geriatric medicine wards. This article outlines the importance of performing comprehensive skin assessments to help diagnose and commence management for these common conditions.

An Over-the-Counter Healing Ointment: Benefits in Dry Skin and Wound Healing.

BACKGROUND: The use of ointments can be beneficial for dry, chapped, or cracked skin and also for supporting wound healing. We describe the results of 2 studies with an over-the-counter healing ointment (HO) to evaluate the effects on skin hydration and in the setting of wound healing after dermatologic procedures.  Methods: Study 1 was a single-center, in-use study using HO on qualified areas at least once daily for 4 weeks in subjects with dry, cracked body skin and self-perceived sensitive skin. Study 2 was a multi-center study of wound healing in subjects using HO on a daily basis after having dermatologic surgical procedures.  Results: In Study 1, there was a significant reduction in skin dryness after 1 and 4 weeks of HO use (P<0.05). Image analysis of the skin revealed a significant increase in skin smoothness after the first application of HO in 100% of subjects (P<0.05). Tolerability and safety were excellent, and HO was well-perceived by subjects throughout the study. In Study 2, HO improved clinical assessments at all time points compared with baseline with a decrease in erythema, edema, scabbing/crusting, and an improvement in overall wound appearance (P<0.05). There was no worsening or significant increase in measures for tolerability parameters at any study visits. Additionally, HO achieved a favorable perception by study subjects.  Conclusions: HO has a well-established safety profile and has been shown to improve both skin hydration and the overall wound healing process after dermatologic surgical procedures. J Drugs Dermatol. 2024;23(5):360-365. doi:10.36849/JDD.8224.

Paradoxical and bimodal immune-mediated dermatological side effects of TNF-α inhibitors: A comprehensive review.

INTRODUCTION: Due to the increasing prevalence of immune-mediated diseases such as psoriasis, lichen planus, rheumatoid arthritis and inflammatory bowel disease, dermatologists have turned to new biologic drugs known as DMARDs (disease-modifying anti-rheumatic drugs) in recent years. AREAS COVERED: In this study, we evaluate the immune-mediated dermatological side effects of DMARDS by reviewing and analyzing previous peer-reviewed research on the effects of TNF-α inhibitors in the treatment of skin diseases, as well as adverse effects of these drugs and some of the main causes of these effects. EXPERT OPINION: DMARDs are very effective in improving control of the above diseases. TNF-α inhibitors are an important group of DMARDs that are widely used. The paradoxical adverse events (PAEs) associated with the use of TNF-α inhibitors are divided into three categories: true paradoxical, borderline paradoxical, and non-paradoxical. True PAEs include conditions for which TNF-α inhibitors are approved for treatment. Borderline PAEs are considered to occur with this class of drugs for which there is no definite approval but for which there is sufficient evidence. Although these events are rare, early recognition of the accused drug and appropriate decision-making may prevent progression of complications and irreversible side effects.

Pharmacological Activities of Lonicerae japonicae flos and Its Derivative-"Chrysoeriol" in Skin Diseases.

Chrysoeriol is an active ingredient derived from the Chinese medicinal herb (CMH) "Lonicerae japonicae flos" in the dried flower bud or bloomed flower of Lonicera japonica Thunberg. Dermatoses are the most common diseases in humans, including eczema, acne, psoriasis, moles, and fungal infections, which are temporary or permanent and may be painless or painful. Topical corticosteroids are widely used in Western medicine, but there are some side effects when it is continuously and regularly utilized in a large dosage. Chrysoeriol is a natural active ingredient, nontoxic, and without any adverse reactions in the treatment of dermatological conditions. METHODS: Nine electronic databases were searched, including WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and China National Knowledge Infrastructure (CNKI), without regard to language constraints. The pharmacological activities of chrysoeriol from Lonicerae japonicae flos to fight against skin diseases were explained and evaluated through the literature review of either in vitro or in vivo studies. RESULTS: Chrysoeriol decreased the mRNA levels of proinflammatory cytokines IL-6, IL-1ß, and TNF-α. These were transcriptionally regulated by NF-κB and STAT3 to combat skin inflammation. It also showed promising actions in treating many skin ailments including wound healing, depigmentation, photoprotection, and antiaging. CONCLUSION: The cutaneous route is the best delivery approach to chrysoeriol across the skin barrier. However, toxicity, dosage, and safety assessments of chrysoeriol in a formulation or nanochrysoeriol on the human epidermis for application in skin diseases must be further investigated.

Inferring skin-brain-skin connections from infodemiology data using dynamic Bayesian networks.

The relationship between skin diseases and mental illnesses has been extensively studied using cross-sectional epidemiological data. Typically, such data can only measure association (rather than causation) and include only a subset of the diseases we may be interested in. In this paper, we complement the evidence from such analyses by learning an overarching causal network model over twelve health conditions from the Google Search Trends Symptoms public data set. We learned the causal network model using a dynamic Bayesian network, which can represent both cyclic and acyclic causal relationships, is easy to interpret and accounts for the spatio-temporal trends in the data in a probabilistically rigorous way. The causal network confirms a large number of cyclic relationships between the selected health conditions and the interplay between skin and mental diseases. For acne, we observe a cyclic relationship with anxiety and attention deficit hyperactivity disorder (ADHD) and an indirect relationship with depression through sleep disorders. For dermatitis, we observe directed links to anxiety, depression and sleep disorders and a cyclic relationship with ADHD. We also observe a link between dermatitis and ADHD and a cyclic relationship between acne and ADHD. Furthermore, the network includes several direct connections between sleep disorders and other health conditions, highlighting the impact of the former on the overall health and well-being of the patient. The average R 2 for a condition given the values of all conditions in the previous week is 0.67: in particular, 0.42 for acne, 0.85 for asthma, 0.58 for ADHD, 0.87 for burn, 0.76 for erectile dysfunction, 0.88 for scars, 0.57 for alcohol disorders, 0.57 for anxiety, 0.53 for depression, 0.74 for dermatitis, 0.60 for sleep disorders and 0.66 for obesity. Mapping disease interplay, indirect relationships, and the key role of mediators, such as sleep disorders, will allow healthcare professionals to address disease management holistically and more effectively. Even if we consider all skin and mental diseases jointly, each disease subnetwork is unique, allowing for more targeted interventions.

From GWASs toward Mechanistic Understanding with Case Studies in Dermatogenetics.

Many human skin diseases result from the complex interplay of genetic and environmental mechanisms that are largely unknown. GWASs have yielded insight into the genetic aspect of complex disease by highlighting regions of the genome or specific genetic variants associated with disease. Leveraging this information to identify causal genes and cell types will provide insight into fundamental biology, inform diagnostics, and aid drug discovery. However, the etiological mechanisms from genetic variant to disease are still unestablished in most cases. There now exists an unprecedented wealth of data and computational methods for variant interpretation in a functional context. It can be challenging to decide where to start owing to a lack of consensus on the best way to identify causal genetic mechanisms. This article highlights 3 key aspects of genetic variant interpretation: prioritizing causal genes, cell types, and pathways. We provide a practical overview of the main methods and datasets, giving examples from recent atopic dermatitis studies to provide a blueprint for variant interpretation. A collection of resources, including brief description and links to the packages and web tools, is provided for researchers looking to start in silico follow-up genetic analysis of associated genetic variants.

Empowering advanced clinical practitioners in managing acute dermatological emergencies.

Advanced clinical practitioners (ACPs) encounter patients with acute dermatological presentations ranging from minor to life-threatening conditions in both primary and secondary care settings. However, ACPs often feel unprepared to assess and treat patients with dermatological emergencies. This article aims to provide guidance to trainee and qualified ACPs, whether in acute hospital settings or primary care, in understanding the essential aspects to consider when consulting with patients presenting with acute dermatological emergencies. It also emphasises appropriate referrals to relevant specialties for necessary inpatient or outpatient investigations and ensure prompt treatment.

[Photography, medicine and corporeality: the device of the image in the forms of discursive apprehension of the disease]. / Fotografía, medicina y corporalidad: el dispositivo de la imagen en las formas de aprehensión discursiva de la enfermedad.

To study about and reflect on the disease is to highlight the ways of seeing and saying what can a body and its power to be affected before fingerprints or traces that degrade it. This article exposes epistemological research on social representations brackets (where register know doctor) disease from the registry of Clinical Dermatology in the second half of the 19th century. This is resorted to an analysis of medical photographs preserved in archives of Colombia and Spain taking as discursive forms of seeing and saying the disease who have disfiguring effects in the body.

Estudiar y reflexionar sobre la enfermedad es poner de relieve las formas de ver y decir acerca de lo que puede un cuerpo y su potencia de ser afectado ante las huellas o vestigios que lo degradan. Este artículo expone los soportes epistemológicos de una investigación sobre las representaciones sociales (en la que se inscribe el saber médico) de la enfermedad desde el registro de la dermatología clínica durante la segunda mitad del siglo XIX. Para esto, se recurrió a un análisis de fotografías médicas conservada en archivos de Colombia y España y como horizonte discursivo las formas de ver y decir la enfermedad que tiene efectos deformantes en el cuerpo.

Utility of hydroxychloroquine laboratory monitoring in dermatologic and rheumatologic patients.

Hydroxychloroquine (HCQ) is an immunomodulator used in dermatology and rheumatology. Side effects may be observed on routine monitoring studies before they become clinically apparent. The goal of this retrospective chart review was to assess laboratory abnormalities in dermatologic and rheumatologic patients taking HCQ. Medical records of patients prescribed HCQ were retrospectively reviewed. Demographics, reported side effects, and parameters on baseline and follow-up complete blood count (CBC) and comprehensive metabolic panel (CMP) were recorded and graded. Laboratory abnormalities were considered severe if they were grade 3 or greater according to Common Terminology Criteria for Adverse Events v3.0 and persistent if they continued beyond subsequent laboratory testing. Of 646 eligible charts, 289 had monitoring studies for review. There were 35 severe (grade 3 or 4, 35/289; 12%) adverse events that developed, as noted on CBC or CMP. Of these 35 severe adverse events, 25 self-corrected on subsequent testing, and 10 (10/289, 3%) across 9 patients were persistent, including glomerular filtration rate, alanine transferase, alkaline phosphatase, glucose, hemoglobin and lymphopenia abnormalities. Of these 10 abnormalities, 7/10 (70%) were unlikely due to hydroxychloroquine use according to the calculated Naranjo score for each patient. Severe laboratory abnormalities while taking hydroxychloroquine are rare, even in a population with a high rate of comorbidities. Among the abnormalities observed, the majority of them (70%) were likely due to disease progression or a medication other than hydroxychloroquine. CBC and CMP monitoring for the reason of observing abnormalities while on HCQ should be at the discretion of the prescribing physician.

Heterogeneity and plasticity of tissue-resident memory T cells in skin diseases and homeostasis: a review.

Skin tissue-resident memory T (Trm) cells are produced by antigenic stimulation and remain in the skin for a long time without entering the peripheral circulation. In the healthy state Trm cells can play a patrolling and surveillance role, but in the disease state Trm cells differentiate into various phenotypes associated with different diseases, exhibit different localizations, and consequently have local protective or pathogenic roles, such as disease recurrence in vitiligo and maintenance of immune homeostasis in melanoma. The most common surface marker of Trm cells is CD69/CD103. However, the plasticity of tissue-resident memory T cells after colonization remains somewhat uncertain. This ambiguity is largely due to the variation in the functionality and ultimate destination of Trm cells produced from memory cells differentiated from diverse precursors. Notably, the presence of Trm cells is not stationary across numerous non-lymphoid tissues, most notably in the skin. These cells may reenter the blood and distant tissue sites during the recall response, revealing the recycling and migration potential of the Trm cell progeny. This review focuses on the origin and function of skin Trm cells, and provides new insights into the role of skin Trm cells in the treatment of autoimmune skin diseases, infectious skin diseases, and tumors.

Development and evaluation of three-dimensional transfers to depict skin conditions in simulation-based education.

Modern medical moulages are becoming increasingly important in simulation-based health professions education. Their lifelikeness is important so that simulation engagement is not disrupted while their standardization is crucial in high-stakes exams. This report describes in detail how three-dimensional transfers are developed and produced so that educators will be able to develop their own. In addition, evaluation findings and lessons learnt from deploying transfers in summative assessments are shared. Step-by-step instructions are given for the creation and application of transfers, including materials and photographic visualizations. We also examined feedback on 10 exam stations (out of a total of 81) with self-developed three-dimensional transfers and complement this with additional lessons learnt. By the time of submission, the authors successfully developed and deployed over 40 different three-dimensional transfers representing different clinical findings in high-stakes exams using the techniques explained in this article or variations thereof. Feedback from students and examiners after completing the OSCE is predominantly positive, with lifelikeness being the quality most often commented upon. Caveats derived from feedback and own experiences are included. The step-by-step approach reported can be adapted and replicated by healthcare educators to build their own three-dimensional transfers. This should widen the scope and the lifelikeness of their simulations. At the same time we propose that this level of lifelikeness should be expected by learners as not to disrupt simulation engagement. Our evaluation of their use in high-stakes assessments suggests they are both useful and accepted.

A Review of the Use of Intravenous Immunoglobulin Therapy in Dermatology.

Intravenous immune globulin (IVIG) is a manufactured blood product commonly used to treat immunodeficiency syndromes, inflammatory disorders, and autoimmune diseases of the skin. The use of IVIG in dermatology has evolved and expanded over time, serving as a useful therapeutic intervention for several inflammatory skin disorders. In addition to demonstrating efficacy in treating several cutaneous pathologies, IVIG also mitigates the need for steroids or other immunosuppressant medications in many dermatologic diseases. This review highlights the evidence for IVIG use across several dermatologic conditions, emphasizing the dosing regimens and safety considerations.

Azulene and Its Derivatives as Potential Compounds in the Therapy of Dermatological and Anticancer Diseases: New Perspectives against the Backdrop of Current Research.

The scientific article focuses on the role of azulene and its derivatives in the therapy of dermatological diseases, presenting the latest laboratory and clinical research as well as prospects for further studies. In a synthetic literature review, various databases such as PubMed, Scopus, Web of Science, and the Database of Polish Scientific Journals were queried to select relevant articles concerning azulene. The conclusions drawn from the thematic analysis of the studies emphasize the multifaceted pharmacological actions of azulene and its derivatives including their anti-inflammatory properties, potential anticancer effects, photoprotective abilities, alleviation of itching, management of atopic dermatitis, and treatment of erectile dysfunction. However, there are certain limitations associated with the application of unmodified azulene on the skin, particularly related to photodecomposition and the generation of reactive oxygen species under UV radiation. These effects, in turn, necessitate further research on the safety of azulene and azulene-derived substances, especially regarding their long-term use and potential application in phototherapy. The authors of this work emphasize the necessity of conducting further preclinical and clinical studies to fully understand the mechanisms of action. Incorporating azulene and its derivatives into the therapy of dermatological disorders may represent an innovative approach, thereby opening new treatment avenues for patients.

Atypical skin conditions of the neck and back as a dermal manifestation of anti-HMGCR antibody-positive myopathy.

BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is an idiopathic inflammatory myopathy (IIM). Though patients with IMNM were not considered to show skin rash, several reports have showed atypical skin conditions in patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-positive IMNM (HMGCR-IMNM). The incidence and phenotype of skin conditions in patients with HMGCR-IMNM are not fully known. RESULTS: Among the 100 IIM patients diagnosed from April 2015 through August 2022, 34 (34%) presented some form of skin condition, with 27 having typical skin rashes; this included 13 patients with dermatomyositis (DM), 8 with anti-synthetase syndrome (ASS), and 6 with IMNM. Meanwhile, 8 of 19 patients with HMGCR-IMNM (42%) presented atypical skin lesions, but no patients with other IIMs did (p < 0.001). Skin eruption with ash-like scales was observed in four HMGCR-IMNM patients, and non-scaly red patches and lumps in the other four patients; accordingly, their skin manifestations were considered as other dermal diseases except for IIM. However, skin and muscle biopsies revealed the atypical skin conditions of patients with HMGCR-IMNM to have the same pathological background, formed by Bcl-2-positive lymphocyte infiltrations. CONCLUSIONS: HMGCR-IMNM patients frequently have atypical skin conditions of the neck and back. Skin biopsy specimens from these lesions showed the same Bcl-2-positive lymphocytic infiltrations as muscle biopsy specimens regardless of the different gross dermal findings. Thus, such atypical skin conditions may be suggestive for HMGCR-IMNM.

[Extra-intestinal manifestations associated with Crohn's disease]. / Extra-intestinale uitingen van inflammatoire darmziekte.

Extra-intestinal manifestations (EIM) associated with Crohn's disease (CD) are frequently observed and can manifest as either the initial symptom or develop later in the disease course following gastrointestinal symptoms. The most common EIM affect the joints, skin, or eyes, with some correlating with active CD activity while others may occur during periods of inactivity. EIM can affect both pediatric and adult CD patients, potentially reducing their quality of life if not promptly identified and treated. Thus, emphasizing the prevalence and clinical presentation is essential to initiate appropriate diagnostic assessments and effectively treat both EIM and the underlying CD. In this case series, we present two pediatric and one adult case where EIM preceded CD diagnosis, resulting in delayed CD diagnosis. Additionally, we outline the most prevalent EIM, their epidemiology, and associated symptoms.

Advances in clinical application of H1 antihistamines in the treatment of skin diseases. / H1æŠ—ç»„èƒºè¯åœ¨çš®è‚¤ç— æ²»ç–—ä¸­çš„ä¸´åºŠåº”ç”¨è¿›å±•.

Histamine receptors are classified into 4 types: H1, H2, H3, and H4, each mediating distinct physiological effects and possessing its corresponding antagonistshat that can be used for the prevention and treatment of various diseases. Among them, H1 antihistamines are the fundamental medications in dermatology and are widely used in many diseases such as urticaria and atopic dermatitis. In recent years, with the emergence of novel antihistamines and the discovery of new potential indications for traditional H1 antihistamines, the clinical application of antihistamines is facing new challenges. Further investigation of the novel mechanism for H1 antihistamines, the use of multiple doses of common drugs and potential indications will furnish vital insights for practical clinical application.

Beyond the surface: unveiling gaps in medical education through eyes of diverse learners.

Inadequate education regarding disease manifestations in diverse skin colors hinders diagnosis and exacerbates health disparities. All levels of medical trainees report low confidence in accurately identifying disease in skin of color (SOC). To help further elucidate these concerns, our research aims to assess medical student confidence in recognizing cutaneous diseases in SOC and their viewpoints regarding SOC education within their institution. An eight-question, open-ended survey was provided to medical students before and after a SOC presentation. The survey assessed participants' confidence in their diagnostic ability and perspectives on educational material. Among the 70 attendees, 58 (82.8%) and 64 (91.4%) completed the pre- and post-seminar surveys, respectively. There was a significant discrepancy in confidence levels when assessing cutaneous manifestations of internal pathology in light (Monk Skin Colors 1-5) versus dark (Monk Skin Colors 6-10) skin (p < 0.009). Notably, 78.7% (37/47) perceived the institutional learning materials as insufficient for SOC. Post-seminar reflections indicated that 87.2% (40/46) of students lacked confidence in diagnosing SOC, with 78.7% (32/46) citing inadequate curriculum coverage as the cause. An additional 8.5% (6/46) identified the predominance of white-centric medical descriptions as a hindrance. Students collectively called for improved educational approaches, including better visual representation of diseases in darker skin. Medical education must continue to strive for increased SOC representation to train competent physicians in treating a diverse patient population and reduce disparities in SOC patients.