The multifaceted role of autophagy in skin autoimmune disorders: a guardian or culprit?

Autophagy is a cellular process that functions to maintain intracellular homeostasis via the degradation and recycling of defective organelles or damaged proteins. This dynamic mechanism participates in various biological processes, such as the regulation of cellular differentiation, proliferation, survival, and the modulation of inflammation and immune responses. Recent evidence has demonstrated the involvement of polymorphisms in autophagy-related genes in various skin autoimmune diseases. In addition, autophagy, along with autophagy-related proteins, also contributes to homeostasis maintenance and immune regulation in the skin, which is associated with skin autoimmune disorders. This review aims to provide an overview of the multifaceted role of autophagy in skin autoimmune diseases and shed light on the potential of autophagy-targeting therapeutic strategies in dermatology.

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.

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.

Nanocomposites used in the treatment of skin lesions: a scoping review.

OBJECTIVE: To map the nanocomposites used in the treatment of skin lesions. METHOD: A scoping review, according to the Joanna Briggs Institute methodology, carried out on eight databases, a list of references and Google Scholar to answer the question: "Which nanocomposites are used as a cover for the treatment of skin lesions?". Two independent reviewers selected the final sample using inclusion/exclusion criteria using the EndNote® and Rayyan programs. Data was extracted using an adapted form and reported using the PRISMA checklist extension, and the protocol was registered in the Open Science Framework (OSF). RESULTS: 21 articles were selected, with nanofibers, nanogels and nanomembranes as the nanocomposites described in wound healing, alone or in association with other therapies: negative pressure and elastic. Silver nanomaterials stand out in accelerating healing due to their antimicrobial and anti-inflammatory action, but caution should be exercised due to the risk of cytotoxicity and microbial resistance. CONCLUSION: Nanocomposites used in wound treatment are effective in accelerating healing and reducing costs, and the addition of bioactives to nanomaterials has added extra properties that contribute to healing.

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.

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.

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.

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.

Immunogenicity, Effectiveness, and Safety of COVID-19 Vaccines among Patients with Immune-Mediated Dermatological Diseases: A Systematic Review and Meta-analysis.

Immunocompromised individuals, primarily attributable to using immunosuppressants, face heightened COVID-19 risks. Despite the proven efficacy of COVID-19 vaccines, their impact on patients with immune-mediated dermatological diseases remains unclear. This study aims to thoroughly examine vaccine immunogenicity, effectiveness, and safety in immune-mediated dermatological disease patients. Clinical studies in adults that compared vaccinated immune-mediated dermatological disease patients with vaccinated healthy controls or unvaccinated immune-mediated dermatological disease patients in terms of vaccine immunogenicity, COVID-19 infection, adverse events, or exacerbation of immune-mediated dermatological diseases were searched via electronic databases. Seventeen studies (1,348,690 participants) were included. Seroconversion rates between immune-mediated dermatological disease patients and healthy controls were not different. However, among individuals aged ≤55 years, immune-mediated dermatological disease patients had lower mean anti-SARS-CoV-2 IgG levels. Immunosuppressed immune-mediated dermatological disease patients also had lower titres and were less likely to achieve T-cell response. In terms of safety, the risk of adverse events was higher in atopic dermatitis patients, but those with psoriasis had a reduced risk. Additionally, immunosuppressed patients had fewer adverse events. Vaccinated immune-mediated dermatological disease patients had a lower risk of COVID-19 infection than unvaccinated patients but a higher risk than healthy controls; however, disease exacerbation may be induced. In conclusion, immune-mediated dermatological diseases showed a reduced vaccine response in our meta-analysis, yet vaccination remained effective against COVID-19 infection and well tolerated.