Pregabalin-Induced Bullous Pemphigoid: A Case Report of a Rare Drug-Triggered Autoimmune Skin Disorder.

Bullous pemphigoid (BP) is a common autoimmune blistering disorder primarily affecting the elderly, characterized by intense pruritus and tense bullae on the skin. We report the case of a 75-year-old female with a history of breast cancer who developed BP on both feet following the initiation of pregabalin for pain management. Histopathological examination confirmed BP, and symptoms improved with topical corticosteroid treatment and discontinuation of pregabalin. This case highlights the potential of pregabalin to induce BP and underscores the importance of recognizing medication-induced bullous diseases for prompt diagnosis and management.

Efficacy and Safety of Upadacitinib in Moderate-to-Severe Atopic Dermatitis: A Meta-Analysis.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder. Topical corticosteroids are the cornerstone of therapy in mild AD, whereas the JAK inhibitor upadacitinib is approved in the United States, Europe, and other countries for treating moderate-severe AD in adults and children over 12 years old whose disease is not adequately controlled with other systemic drugs, including biologics. The objective of this meta-analysis was to assess the overall efficacy and safety of upadacitinib in moderate to severe AD. All randomized controlled trials (RCTs) evaluating the efficacy and safety of upadacitinib in moderate to severe AD were included in the meta-analysis. The pooled analysis revealed a significant proportion of patients achieving Eczema Area and Severity Index-75 (EASI 75) (R.R. = 3.86; 95% CI = 3.12 to 4.78, p < 0.00001), EASI 100 (R.R. = 13.09; 95% CI = 7.40 to 23.17, p < 0.00001), Worst Pruritus Numerical Rating Score (WP-NRS) response (R.R. = 4.44; 95% CI = 3.72 to 5.29, p< 0.00001), and validated Investigator's Global Assessment (v-IGA) (RR = 5.96; 95% CI = 4.79 to 7.41, p < 0. 00001) in the upadacitinib arm compared to the placebo arm. Moreover, the pooled analysis also suggested that treatment-emergent adverse events (TAEs) were relatively higher with upadacitinib than with placebo, but were mild and easily manageable (R.R. = 1.15; 95% CI = 1.09 to 1.23, p<0.00001). This meta-analysis showed that upadacitinib had a significant beneficial effect and tolerable adverse effect profile in patients with moderate and severe AD. Dose regimens of 15 mg and 30 mg seemed to have similar benefits. However, further trials are needed to assess long-term efficacy and safety profile.

Confirming the enzymatic activity and neurodevelopmental trajectory of PYCR1 mutation in one child with autosomal-recessive cutis laxa type 2.

Autosomal-recessive cutis laxa type 2 (ARCL2) is a rare genetic disorder caused by pyrroline-5-carboxylate reductase 1 (PYCR1) mutations and characterized by loose and sagging skin, typical facial features, intrauterine growth retardation, and developmental delay. To study the effect of PYCR1 mutations on protein function and clinical features, we identified a homozygous missense mutation c.559G > A (p.Ala187Thr) in PYCR1 in a Chinese child with typical clinical features, especially severe developmental delays. The three-dimensional (3D) model showed the modification of the hydrogen bonds produce a misfolding in the mutant PYCR1 protein. Mutagenesis and enzyme assay study revealed decreased activity of the mutant protein in vitro, indicating that this mutation impairs PYCR1 function. Our findings confirmed abnormal enzymatic activity and neurodevelopmental trajectory of this PYCR1 mutation.

Exploring the Co-occurrence of dermatophyte infection and ichthyosis: A report of 3 cases.

Dermatophyte infections frequently pose diagnostic challenges, especially when occurring alongside ichthyosis, a genetic skin disorder characterized by dry, thickened, scaly skin. This case series outlines three cases where dermatophyte infections overlapped with ichthyosis, emphasizing the complexities in clinical identification and differential diagnosis. Atypical clinical presentations in these cases led to initial misdiagnoses. Ichthyosis, a genetic skin disorder characterized by thickened and scaly skin, creates an environment conducive to dermatophyte settlement, complicating the diagnostic process. The cases highlight the importance of considering fungal infections, even when clinical features deviate from the expected course. A vigilant diagnostic approach, including mycological examinations, is crucial for accurate identification and timely management.

Oral Lichen Planus and Its Therapeutic Approaches: A Case Report.

Lichen planus, a chronic inflammatory skin disorder, presents with pruritic, polygonal, and flat-topped papules and plaques. It encompasses not only the skin but also mucous membranes, nails, and hair follicles. Diagnosis relies on all the clinical and biopsy reports. The etiology of oral lichen planus (OLP) is multifactorial, with genetic, immunological, and environmental factors playing significant roles. Frequently utilized therapies encompass topical corticosteroids, calcineurin inhibitors, and systemic immunomodulatory medications. Management should be tailored to disease severity and the specific site of involvement. Lichen planus can present in papular, hypertrophic, atrophic, erosive, or erythematous forms. In this report, we present a case of a 28-year-old male patient who presented with bilateral white striations on the buccal mucosa and an erythematous lesion on the right buccal mucosa causing significant discomfort. The patient was treated with corticosteroids, resulting in marked symptomatic relief and partial lesion regression over a follow-up period of six months. This case underscores the importance of early diagnosis and tailored therapeutic strategies in managing OLP to improve patient outcomes.

Pemphigus oral lesions area index (POLAI): A new scoring scale for assessing oral pemphigus vulgaris.

OBJECTIVES: Current scales for Pemphigus vulgaris (PV) do not adequately represent the clinical variability of oral lesions. This study aimed to develop an independent scale, the Pemphigus Oral Lesions Area Index (POLAI), for assessment of oral PV exclusively, and compare POLAI, Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Oral Disease Severity Score (ODSS) regarding inter- and intra-observer reliability and validity. MATERIALS AND METHODS: Retrospective cohort included 209 sets of digital-photographs. Additional clinical cohort included 32 PV patients. All visits were assessed by four clinicians using the PDAI, ABSIS, ODSS and POLAI, and were rated by three specialists using the Physician's Global Assessment (PGA). RESULTS: The intraclass correlation coefficient showed the inter-observer reliability with 0.89 and 0.86 for PDAI, 0.87 for ABSIS, 0.93 for ODSS, 0.96 for POLAI, and 0.97 and 0.96 for PGA. Intra-observer agreements showed excellent reliability for all 4 scores. Highest correlation was observed between PGA and POLAI (correlation coefficients were 0.96). The mean time taken to complete each scale was within 1.5 min. CONCLUSION: POLAI is valid for the assessment of oral PV with superior inter- and intra-observer reliability to PDAI, ABSIS and ODSS, and is feasible in clinic.

Qingxiong Ointment and its Active Ingredient, Shikonin Treat Psoriasis through HIF-1 Signaling Pathway.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disorder. Qingxiong ointment (QX) is a natural medicinal combination frequently employed in clinical treatment of psoriasis. However, the active ingredients of QX and its precise mechanisms of improving psoriasis remain unclear. This study elucidated the effects of QX on an Imiquimod (IMQ)-induced mouse model of psoriasis while also exploring the regulation of the active ingredient of QX, shikonin, on the HIF-1 signaling pathway in HaCaT cells. METHODS: A mouse model of psoriasis was established through topical application of IMQ, and the local therapeutic effect of QX was evaluated using dorsal skin tissue with mouse psoriatic lesion and Psoriasis Area Severity Index (PASI) scores, hematoxylin-eosin (HE) staining, and immunohistochemical staining. Elisa and qPCR were employed to identify changes in the expression of inflammation-related factors in the mouse dorsal skin. Immunofluorescence was used to assess changes in the expression of T cell subsets before and after treatment with various doses of QX. HPLC was used to analyze the content of shikonin, and network pharmacology was employed to analyze the main targets of shikonin. Immunofluorescence was used to identify the effects of shikonin on the HIF-1 signaling pathway in IL6-induced psoriasis HaCaT cells. Finally, qPCR was used to identify the differential expression of the HIF-1 signaling pathway in skin tissues. RESULTS: QX significantly reduces PASI scores on the backs of IMQ-induced psoriasis mice. HE staining reveals alleviated epidermal thickness in the QX group. Immunohistochemical analysis shows a significant reduction in ICAM, KI67, and IL17 expression levels in the QX group. Immunofluorescence results indicate that QX can notably decrease the proportions of CD4+ T cells, γδ T cells, and CD8+ T cells while increasing the proportion of Treg cells. Network pharmacology analysis demonstrates that the main targets of shikonin are concentrated in the HIF-1 signaling pathway. Molecular docking results show favorable binding affinity between shikonin and key genes of the HIF-1 signaling pathway. Immunofluorescence results reveal that shikonin significantly reduces p-STAT3, SLC2A1, HIF1α, and NOS2 expression levels. qPCR results show significant downregulation of the HIF-1 signaling pathway at cellular and tissue levels. CONCLUSION: Our study revealed that QX can significantly reduce the dorsal inflammatory response in the IMQ-induced psoriasis mouse model. Furthermore, we discovered that its main component, shikonin, exerts its therapeutic effect by diminishing the HIF-1 signaling pathway in HaCaT cells.

Skin Microbial Composition and Genetic Mutation Analysis in Precision Medicine for Epidermolysis Bullosa.

Epidermolysis bullosa (EB) is an inherited skin disease representing a spectrum of rare genetic disorders. These conditions share the common trait that causes fragile skin, resulting in the development of blisters and erosions. The inheritance follows an autosomal pattern, and the array of clinical presentations leads to significant physical suffering, considerable morbidity, and mortality. Despite EB having no cure, effectively managing EB remains an exceptional challenge due to its rarity and complexity, occasionally casting a profound impact on the lives of affected individuals. Considering that EB management requires a multidisciplinary approach, this sometimes worsens the condition of patients with EB due to inappropriate handling. Thus, more appropriate and precise treatment management of EB is essentially needed. Advanced technology in medicine and health comes into the bioinformatics era. Including treatment for skin diseases, omics-based approaches aim to evaluate and handle better disease management and treatment. In this work, we review several approaches regarding the implementation of omics-based technology, including genetics, pathogenic mutation, skin microbiomics, and metagenomics analysis for EB. In addition, we highlight recent updates on the potential of metagenomics analysis in precision medicine for EB.

Immunomodulatory Plant Natural Products as Therapeutics against Inflammatory Skin Diseases.

Frequently occurring inflammatory skin conditions such as psoriasis, dermatitis, acne, including skin cancer, wounds and other disorders arising out of premature skin aging, deteriorate skin health and adversely impact human life. Even though several synthetic compounds have evolved for treating these skin conditions, natural-product-based therapeutics are gaining popularity with growing evidence of their efficacy and safety for treating skin disorders. Many of these inflammatory skin diseases have underlying disturbances in our immune system and immunomodulatory natural products provide solutions for their effective treatment and aid in understanding the underlying mechanism of such inflammatory skin conditions. Based on this premise, the present review summarizes the possible application of plant-derived immunomodulatory compositions and single molecules for treating inflammatory skin conditions. In vitro, in vivo and mechanistic studies reported the application of selected plant-derived natural products for the treatment of inflammatory skin disorders including, cancer and infections. Several online databases including PubMed, Google Scholar, and Science Direct have been searched for gathering the information covered in this review. Empirical studies demonstrated that most of these natural compounds exhibited therapeutic properties through their immunomodulatory and anti-inflammatory potential supplemented often with anti-microbial, anti-neoplastic, and anti- oxidant activities. Overall, plant-based natural products discussed here are capable of modulating the immune system to minimize or completely suppress the pro-inflammatory markers, scavenge free radicals (ROS), prevent bacteria, fungal, and virus-derived skin infections and often regress skin cancer through the induction of apoptosis. The challenges and opportunities associated with the application of plant-based immunomodulators for skin applications and their safety considerations are also discussed here. The present study indicated that immunomodulatory plant natural products being biologically validated ligands against various biological targets manifested in inflammatory skin diseases, offer an effective, safe and affordable treatment for such disorders affecting skin health. However, further clinical evaluations are needed to substantiate these findings.

Exploring the impact of diet and nutrition on vitiligo: A systematic review of dietary factors and nutritional interventions.

BACKGROUND: Vitiligo, an autoimmune skin disorder linked to hormonal and genetic factors, results in reduced pigmentation due to a gradual decline in melanocyte activity. This systematic review delves into the role of dietary intervention and nutrition in managing vitiligo. METHODS: A comprehensive search on PubMed, Google Scholar, and European PMC identified 214 studies, with 14 meeting inclusion criteria post-screening. The selected studies primarily explored the impact of dietary supplements on disease activity. RESULTS: Heavy metal exposure, specifically Cd, Pb, and Hg, indicated potential links to heightened reactive oxygen species and vitiligo development. Conflicting evidence emerged regarding the role of trace minerals (Zn and Cu), with some studies suggesting deficiencies and others proposing excesses in vitiligo patients. Vitamins with anti-inflammatory properties like vitamin C, D, and B12, along with antioxidants, were investigated for their potential in repigmentation strategies. Additionally, polyunsaturated fatty acids (PUFAs), especially in varying types of fat consumption, were implicated. Emphasizing the need to reduce reliance on pharmacological and phototherapy interventions, the review uncovers novel roles for dietary supplements as adjuncts or flare reducers. CONCLUSION: While dietary interventions cannot be thought of as a standalone therapy, they still make a case for being used as adjuncts. Large scale clinical trials are warranted to establish strong evidence and protocols, and might also help reduce the dependency on pharmacological methods, which come with their adverse effect profiles.

Identification of Shared Biomarkers and Immune Infiltration Signatures between Vitiligo and Hashimoto's Thyroiditis.

Background: Vitiligo and Hashimoto's thyroiditis (HT) are concomitant autoimmune diseases characterized by the destruction of melanocytes or thyrocytes. We aimed to explore the immunological mechanism of this comorbidity and screen their potential biomarkers. Methods: We downloaded the microarray datasets from the GEO database. Differentially expressed genes (DEGs) and immune-related genes (IRGs) were selected. The immune-related differentially expressed genes (IRDEGs) were obtained by taking the intersection. Candidate biomarkers were elected by Cytoscape software. CIBERSORT was used to depict immune cell infiltration prospects. Correlation analysis was conducted between infiltrating cells and several indicators. The results were validated by real-time quantitative PCR (RT-qPCR). Results: Three datasets and 60 IRDEGs were obtained in total. Pathway enrichment analysis showed that the T cell receptor signaling pathway, IL-17 signaling pathway, receptor-ligand activity, and signaling receptor activator activity were significantly enriched. We screened out four hub genes, including IFNG, STAT1, IL1B, and CXCL10. The ROC curve indicated the highest diagnostic value of CXCL10 in both vitiligo and HT. Immuno-infiltration analysis revealed significant changes in T cell subsets and macrophage subtypes, which were correlated with four hub genes, melanocyte markers, and thyroid-specific antigens. qPCR validated the hub genes in peripheral blood mononuclear cells from patients with comorbidity. Conclusion: IFNG, STAT1, IL1B, and CXCL10, were the key IRDEGs to vitiligo and HT. These genes may participate in the comorbidity by remodeling the immune cell infiltration pattern, and cross-expressed antigens may mediate the common damage of melanocytes and thyroid tissues.

The Promising Role of Polyphenols in Skin Disorders.

The biochemical characteristics of polyphenols contribute to their numerous advantageous impacts on human health. The existing research suggests that plant phenolics, whether consumed orally or applied directly to the skin, can be beneficial in alleviating symptoms and avoiding the development of many skin disorders. Phenolic compounds, which are both harmless and naturally present, exhibit significant potential in terms of counteracting the effects of skin damage, aging, diseases, wounds, and burns. Moreover, polyphenols play a preventive role and possess the ability to delay the progression of several skin disorders, ranging from small and discomforting to severe and potentially life-threatening ones. This article provides a concise overview of recent research on the potential therapeutic application of polyphenols for skin conditions. It specifically highlights studies that have investigated clinical trials and the use of polyphenol-based nanoformulations for the treatment of different skin ailments.

In Vitro Release of Glycyrrhiza Glabra Extract by a Gel-Based Microneedle Patch for Psoriasis Treatment.

Microneedle patches are attractive drug delivery systems that give hope for treating skin disorders. In this study, to first fabricate a chitosan-based low-cost microneedle patch (MNP) using a CO2 laser cutter for in vitro purposes was tried and then the delivery and impact of Glycyrrhiza glabra extract (GgE) on the cell population by this microneedle was evaluated. Microscopic analysis, swelling, penetration, degradation, biocompatibility, and drug delivery were carried out to assess the patch's performance. DAPI staining and acridine orange (AO) staining were performed to evaluate cell numbers. Based on the results, the MNs were conical and sharp enough (diameter: 400-500 µm, height: 700-900 µm). They showed notable swelling (2 folds) during 5 min and good degradability during 30 min, which can be considered a burst release. The MNP showed no cytotoxicity against fibroblast cell line L929. It also demonstrated good potential for GgE delivery. The results from AO and DAPI staining approved the reduction in the cell population after GgE delivery. To sum up, the fabricated MNP can be a useful recommendation for lab-scale studies. In addition, a GgE-loaded MNP can be a good remedy for skin disorders in which cell proliferation needs to be controlled.

Mechanism of action of adapalene for treating EGFR-TKI-induced skin disorder.

BACKGROUND: Skin disorders are the most common side effect associated with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. It is important to manage skin lesions. Adapalene has been used to treat skin lesions caused by EGFR-TKIs in some cases. The aim of this study was to investigate the functional mechanism of adapalene in erlotinib-induced skin disorder. METHODS: To analyze the effect of adapalene on skin rash, afatinib and adapalene were administered to mice. The relationship between the concentration of adapalene and skin disorders was also examined by analyzing AQP3 expression. A skin lesion model was experimentally established in human skin keratinocytes (HaCaT) by using erlotinib with TNF-α and IL-1ß. We used qRT-PCR to analyze chemokine-induced inflammation and western blotting to analyze the effects of adapalene on the NF-κB signaling pathway. Antimicrobial peptides and adhesion factors were also examined using qRT-PCR. RESULTS: Mice administered 0.01% adapalene had less skin inflammation than mice treated with afatinib alone. The expression level of AQP3 decreased in an adapalene concentration-dependent manner. The mRNA levels of proinflammatory cytokines such as CCL2 and CCL27 in HaCaT cells were significantly reduced by adapalene. The expression of an antimicrobial peptide, hBD3, was upregulated after adapalene treatment. Adhesion factors, such as E-cadherin, were significantly downregulated by EGFR-TKI and significantly upregulated by adapalene treatment. Western blot analysis suggested that erlotinib-induced phosphorylation of p65 was decreased by adapalene. CONCLUSION: We suggest that adapalene may be a possible treatment option for skin disorders induced by EGFR-TKIs.

Multicenter, Retrospective Study to Evaluate Necitumumab Plus Cisplatin and Gemcitabine After Immune Checkpoint Inhibitors in Advanced Squamous Cell Lung Cancer in Japan: The NINJA Study.

Introduction: Necitumumab plus gemcitabine and cisplatin (GCN) is a standard therapy for patients with advanced lung squamous cell carcinoma (LSqCC). However, the efficacy and tolerability of GCN in second-line or later treatment for patients previously treated with immune checkpoint inhibitors (ICIs) remain unknown. Methods: This multicenter, retrospective, cohort study assessed the efficacy and tolerability of GCN initiated between November 1, 2019 and March 31, 2022 as second-line to fourth-line treatment in patients with advanced LSqCC who had been pretreated with ICIs. The primary end point was progression-free survival (PFS). Results: A total of 93 patients from 35 institutions in Japan were enrolled. The median PFS, median overall survival (OS), and objective response rate were 4.4 months (95% confidence interval [CI]: 3.8-5.3), 13.3 months (95% CI: 9.6-16.5), and 27.3% (95% CI: 18.3-37.8), respectively. The median PFS, median OS, and objective response rate for second-line, third-line, and fourth-line treatment groups were 4.8 months, 3.8 months, and 4.3 months (p = 0.24); 15.7 months, 11.6 months, and 10.1 months (p = 0.06); and 31.0%, 13.6%, and 37.5% (p = 0.22), respectively. The severity of GCN-related skin disorders was associated with longer PFS (p < 0.05) and OS (p < 0.05). The frequencies of grade ≥3 skin disorders, hypomagnesemia, pneumonitis, and febrile neutropenia were 16.1%, 7.5%, 1.1%, and 4.3%, respectively. There were no treatment-related deaths. Conclusions: GCN for ICI-pretreated patients with LSqCC seems tolerable and offers promising efficacy regardless of treatment line, and ICI pretreatment might enhance GCN efficacy.

A RECALCITRANT SKIN LESION AND SUBSEQUENT INFECTION IN A RECREATIONAL INTRAMURAL MALE ATHLETE: A CASE REPORT.

A 35-year-old intramural male athlete presented to the athletic training staff with a 4.5cm x 2.2cm itchy, painful, swollen, and infected insidious skin lesion on his right lateral malleolus due to an underlying dermatological deficiency. Suspecting infection, the patient was referred to his nurse practitioner and was diagnosed with atopic dermatitis caused by a ceramide deficiency. He was placed on Cefalexin and Mupirocin 2% ointment but returned due to the lesion increasing to 8.5cm x 6cm although infection seemed controlled. He was instructed to use Ceravé™ topical cream, Clobetasol propionate 5%, and consume foods rich in healthy oils (omega-3s, olive oil). Unmitigated, this lesion could have resulted in severe infection and tissue damage. Atopic dermatitis is relatively common in the general population but the appearance in healthy athletes highlights that athletic trainers need to be well-versed in not just apparent causes of skin ailments (i.e., infection), but also root causes.

A Rare Post-infectious Rash: Pityriasis Rubra Pilaris After COVID-19 Infection.

Pityriasis rubra pilaris (PRP) is a rare papulosquamous skin disorder that often presents with erythematous follicular-based hyperkeratotic papules that can become confluent and lead to erythroderma and electrolyte and thermoregulatory imbalances resulting from increased tissue perfusion and skin barrier breakdown. Due to this condition being uncommon, many specialties outside of dermatology are unfamiliar with this entity which poses unique diagnostic and management challenges. This case report involves a 55-year-old woman who presented to the emergency room with erythroderma secondary to PRP. It highlights the relevance of PRP in the context of in-hospital management by presenting the patient's clinical profile, diagnostic workup, and treatment plan. By emphasizing the distinctive clinical features and natural course of the disease, this report aims to enhance the understanding of this uncommon inflammatory skin condition.