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.

Clinical Features of Cutaneous Paraneoplastic Syndromes in Hodgkin Lymphoma.

Cutaneous paraneoplastic syndromes due to Hodgkin lymphoma present with a wide spectrum of clinical manifestations from generalized pruritus to exfoliative erythroderma. We summarize the clinical findings and outcomes of 14 patients with Hodgkin lymphoma and associated cutaneous paraneoplastic syndromes treated at Mayo Clinic over the past 3 decades. Cutaneous paraneoplastic syndromes may be present at the time of lymphoma diagnosis, whereas in other patients, it may appear at the time of relapse, including patients with initial absence of cutaneous manifestations during the initial lymphoma presentation. Our results indicate that complete resolution of the paraneoplastic syndrome is associated with significantly improved overall survival. Recognition of cutaneous paraneoplastic syndromes is a crucial surrogate of relapsed malignancy and treatment requires targeting the underlying malignancy.

Signatures of epigenetic, biological and mitotic age acceleration and telomere shortening are associated with arsenic-induced skin lesions.

Chronic arsenic exposure is a global health hazard significantly associated with the development of deleterious cutaneous changes and increased keratinocyte cancer risk. Although arsenic exposure is associated with broad-scale cellular and molecular changes, gaps exist in understanding how these changes impact the skin and facilitate malignant transformation. Recently developed epigenetic "clocks" can accurately predict chronological, biological and mitotic age, as well as telomere length, on the basis of tissue DNA methylation state. Deviations of predicted from expected age (epigenetic age dysregulation) have been associated with numerous complex diseases, increased all-cause mortality and higher cancer risk. We investigated the ability of these algorithms to detect molecular changes associated with chronic arsenic exposure in the context of associated skin lesions. To accomplish this, we utilized a multi-algorithmic approach incorporating seven "clocks" (Horvath, Skin&Blood, PhenoAge, PCPhenoAge, GrimAge, DNAmTL and epiTOC2) to analyze peripheral blood of pediatric and adult cohorts of arsenic-exposed (n = 84) and arsenic-naïve (n = 33) individuals, among whom n = 18 were affected by skin lesions. Arsenic-exposed adults with skin lesions exhibited accelerated epigenetic (Skin&Blood: + 7.0 years [95% CI 3.7; 10.2], q = 6.8 × 10-4), biological (PhenoAge: + 5.8 years [95% CI 0.7; 11.0], q = 7.4 × 10-2, p = 2.8 × 10-2) and mitotic age (epiTOC2: + 19.7 annual cell divisions [95% CI 1.8; 37.7], q = 7.4 × 10-2, p = 3.2 × 10-2) compared to healthy arsenic-naïve individuals; and accelerated epigenetic age (Skin&Blood: + 2.8 years [95% CI 0.2; 5.3], q = 2.4 × 10-1, p = 3.4 × 10-2) compared to lesion-free arsenic-exposed individuals. Moreover, lesion-free exposed adults exhibited accelerated Skin&Blood age (+ 4.2 [95% CI 1.3; 7.1], q = 3.8 × 10-2) compared to their arsenic-naïve counterparts. Compared to the pediatric group, arsenic-exposed adults exhibited accelerated epigenetic (+ 3.1 to 4.4 years (95% CI 1.2; 6.4], q = 2.4 × 10-4-3.1 × 10-3), biological (+ 7.4 to 7.8 years [95% CI 3.0; 12.1] q = 1.6 × 10-3-2.8 × 10-3) and mitotic age (+ 50.0 annual cell divisions [95% CI 15.6; 84.5], q = 7.8 × 10-3), as well as shortened telomere length (- 0.23 kilobases [95% CI - 0.13; - 0.33], q = 2.4 × 10-4), across all seven algorithms. We demonstrate that lifetime arsenic exposure and presence of arsenic-associated skin lesions are associated with accelerated epigenetic, biological and mitotic age, and shortened telomere length, reflecting altered immune signaling and genomic regulation. Our findings highlight the usefulness of DNA methylation-based algorithms in identifying deleterious molecular changes associated with chronic exposure to the heavy metal, serving as potential prognosticators of arsenic-induced cutaneous malignancy.

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.

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.

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.

A novel multi-task learning network for skin lesion classification based on multi-modal clues and label-level fusion.

In this paper, we propose a multi-task learning (MTL) network based on the label-level fusion of metadata and hand-crafted features by unsupervised clustering to generate new clustering labels as an optimization goal. We propose a MTL module (MTLM) that incorporates an attention mechanism to enable the model to learn more integrated, variable information. We propose a dynamic strategy to adjust the loss weights of different tasks, and trade off the contributions of multiple branches. Instead of feature-level fusion, we propose label-level fusion and combine the results of our proposed MTLM with the results of the image classification network to achieve better lesion prediction on multiple dermatological datasets. We verify the effectiveness of the proposed model by quantitative and qualitative measures. The MTL network using multi-modal clues and label-level fusion can yield the significant performance improvement for skin lesion classification.

Potential of Curcumin in the Management of Skin Diseases.

Curcumin is a polyphenolic molecule derived from the rhizoma of Curcuma longa L. This compound has been used for centuries due to its anti-inflammatory, antioxidant, and antimicrobial properties. These make it ideal for preventing and treating skin inflammation, premature skin ageing, psoriasis, and acne. Additionally, it exhibits antiviral, antimutagenic, and antifungal effects. Curcumin provides protection against skin damage caused by prolonged exposure to UVB radiation. It reduces wound healing times and improves collagen deposition. Moreover, it increases fibroblast and vascular density in wounds. This review summarizes the available information on the therapeutic effect of curcumin in treating skin diseases. The results suggest that curcumin may be an inexpensive, well-tolerated, and effective agent for treating skin diseases. However, larger clinical trials are needed to confirm these observations due to limitations in its in vivo use, such as low bioavailability after oral administration and metabolism.

Unlocking the Power of Light on the Skin: A Comprehensive Review on Photobiomodulation.

Photobiomodulation (PBM) is a procedure that uses light to modulate cellular functions and biological processes. Over the past decades, PBM has gained considerable attention for its potential in various medical applications due to its non-invasive nature and minimal side effects. We conducted a narrative review including articles about photobiomodulation, LED light therapy or low-level laser therapy and their applications on dermatology published over the last 6 years, encompassing research studies, clinical trials, and technological developments. This review highlights the mechanisms of action underlying PBM, including the interaction with cellular chromophores and the activation of intracellular signaling pathways. The evidence from clinical trials and experimental studies to evaluate the efficacy of PBM in clinical practice is summarized with a special emphasis on dermatology. Furthermore, advancements in PBM technology, such as novel light sources and treatment protocols, are discussed in the context of optimizing therapeutic outcomes and improving patient care. This narrative review underscores the promising role of PBM as a non-invasive therapeutic approach with broad clinical applicability. Despite the need for further research to develop standard protocols, PBM holds great potential for addressing a wide range of medical conditions and enhancing patient outcomes in modern healthcare practice.

Dermoscopy to differentiate clinically similar inflammatory and neoplastic skin lesions.

INTRODUCTION: Over the few last decades, dermoscopy has become an invaluable and popular imaging technique that complements the diagnostic armamentarium of dermatologists, being employed for both tumors and inflammatory diseases. Whereas distinction between neoplastic and inflammatory lesions is often straightforward based on clinical data, there are some scenarios that may be troublesome, e.g., solitary inflammatory lesions or tumors superimposed to a widespread inflammatory condition that may share macroscopic morphological findings. EVIDENCE ACQUISITION: We reviewed the literature to identify dermoscopic clues to support the differential diagnosis of clinically similar inflammatory and neoplastic skin lesions, also providing the histological background of such dermoscopic points of differentiation. EVIDENCE SYNTHESIS: Dermoscopic differentiating features were identified for 12 relatively common challenging scenarios, including Bowen's disease and basal cell carcinoma vs. psoriasis and dermatitis, erythroplasia of Queyrat vs. inflammatory balanitis, mammary and extramammary Paget's disease vs. inflammatory mimickers, actinic keratoses vs. discoid lupus erythematosus, squamous cell carcinoma vs. hypertrophic lichen planus and lichen simplex chronicus, actinic cheilitis vs. inflammatory cheilitis, keratoacanthomas vs. prurigo nodularis, nodular lymphomas vs. pseudolymphomas and inflammatory mimickers, mycosis fungoides vs. parapsoriasis and inflammatory mimickers, angiosarcoma vs granuloma faciale, and Kaposi sarcoma vs pseudo-Kaposi. CONCLUSIONS: Dermoscopy may be of aid in differentiating clinically similar inflammatory and neoplastic skin lesions.

Editor's Highlights - May 2024.

Dermatological research and education have predominantly focused on lighter skin types in the past, leading to a significant gap in knowledge and understanding of conditions in darker skin types. This has contributed to disparities in the diagnosis and treatment of diseases in patients with skin of color. In the current issue of the Journal, we highlight four papers on the epidemiology and clinics of skin of color patients but also emphasize the importance of education and research in the dermatopathology of SOC patients.

Predictive Ability of LRINEC Score for Lower Extremity Amputation in Moderate to Severe Diabetic Foot Infection.

OBJECTIVE: To assess the predictive ability of the laboratory risk indicator for necrotising fasciitis (LRINEC) score for lower extremity amputation in patients with moderate to severe diabetic foot infection (DFI). STUDY DESIGN: Observational study. Place and Duration of the Study: Department of General Surgery, Combined Military Hospital, Rawalpindi, Pakistan, from June to September 2023. METHODOLOGY: Patients admitted to the surgical ward with moderate to severe DFI were included by convenience sampling. Patients with severe sepsis, unstable haemodynamics, pressure injuries, and terminal illnesses were excluded. Demographic and clinical data of patients were noted down. LRINEC score was calculated on the day of admission. Final outcome (amputation or otherwise) was recorded on the 30th day the since the day of admission. RESULTS: Two hundred patients with moderate to severe DFI were included. The median age of patients was 56 years (IQR 49-66 years). The median duration of diabetes was 11 years (IQR 4 - 18.75 years). The median LRINEC score at admission was 6 (IQR 3-9). The majority of the patients (65.5%) had some other medical comorbid besides diabetes. Patients who had amputation due to DFI at 30 days post-admission had higher LRINEC scores on admission as compared to those patients who did not have amputation (Median 8 vs. 2, p <0.001). The cut-off point of LRINEC score ≥6.5 at admission had sensitivity of 74% and specificity of 94% in predicting amputation. CONCLUSION: The LRINEC score may be used as an objective scoring system to predict the risk of amputation in patients with moderate to severe DFI in indoor clinical settings. KEY WORDS: Diabetic foot, LRINEC score, Limb loss, Necrotising fasciitis.

A Protocol for the Automated Assessment of Cutaneous Pathology in a Mouse Model of Hemichannel Dysfunction.

In this chapter, we provide detailed instructions to perform quantitative reflectance imaging in a mouse model of a rare epidermal disorder caused by hyperactive connexin 26 hemichannels. Reflectance imaging is a versatile and powerful tool in dermatology, offering noninvasive, high-resolution insights into skin pathology, which is essential for both clinical practice and research. This approach offers several advantages and applications. Unlike traditional biopsy, reflectance imaging is noninvasive, allowing for real-time, in vivo examination of the skin. This is particularly valuable for monitoring chronic conditions or assessing the efficacy of treatments over time, enabling the detailed examination of skin morphology. This is crucial for identifying features of skin diseases such as cancers, inflammatory conditions, and infections. In therapeutic applications, reflectance imaging can be used to monitor the response of skin lesions to treatments. It can help in identifying the most representative area of a lesion for biopsy, thereby increasing the diagnostic accuracy. Reflectance imaging can also be used to diagnose and monitor inflammatory skin diseases, like psoriasis and eczema, by visualizing changes in skin structure and cellular infiltration. As the technology becomes more accessible, it has potential in telemedicine, allowing for remote diagnosis and monitoring of skin conditions. In academic settings, reflectance imaging can be a powerful research tool, enabling the study of skin pathology and the effects of novel treatments, including the development of monoclonal antibodies for therapeutic applications.

Punch Biopsy Extraction With Fingers.

Punch biopsies are commonly used in dermatology for diagnosing skin diseases. Traditional methods involve the use of forceps, skin hooks, and scissors, which add to health care costs. The technique described here offers a cost-effective and efficient alternative for obtaining specimens.

Case report: Rubella virus-associated cutaneous granuloma in an adult with TAP1 deficiency.

Rubella virus-associated granulomas commonly occur in immunocompromised individuals, exhibiting a diverse range of clinical presentations. These manifestations can vary from predominantly superficial cutaneous plaques or nonulcerative nodules to more severe deep ulcerative lesions, often accompanied by extensive necrosis and significant tissue destruction. TAP1 deficiency, an exceedingly rare primary immune-deficiency disorder, presents with severe chronic sino-pulmonary infection and cutaneous granulomas. This report highlights the occurrence of rubella virus-associated cutaneous granulomas in patients with TAP1 deficiency. Notably, the pathogenic mutation responsible for TAP1 deficiency stems from a novel genetic alteration that has not been previously reported. This novel observation holds potential significance for the field of diagnosis and investigative efforts in the context of immunodeficiency disorders.

Skin disorders in women with poor obstetric history: MTHFR polymorphisms and importance of preconceptional counseling.

OBJECTIVES: This study focused on the link between skin disorders and Methylenetetrahydrofolate reductase (MTHFR) polymorphisms. METHODS: Study cases were taken from a pre-conceptional care program where patients with poor obstetric history were evaluated in terms of systemic disorders including skin diseases. This retrospective cohort (n = 472) consisted of 110 (23.3%) and 362 (76.7%) women with or without skin disorders, respectively. For ease of analysis, the history of skin diseases was classified into seven categories: (1) acne/rosacea/other acneiform disorders; (2) fungal disease; (3) pruritis/xerosis; (4) psoriasis vulgaris; (5) acrochordons and other benign skin growths; (6) urticaria/dermatitis; and (7) viral diseases. RESULTS: In this retrospective cohort of 472 women, we explored the impact of MTHFR A1298C and C677T polymorphisms on skin disorders. Despite similar allelic frequencies, our findings revealed a statistically significant association between the presence of MTHFR polymorphisms and skin disorders (p = .027). Subgroup analysis indicated significantly higher rates of MTHFR polymorphisms in patients with psoriasis vulgaris (p = .033) and acrochordons (p = .030), highlighting their potential relevance in specific skin disorder subtypes. CONCLUSIONS: The increased prevalence of psoriasis and acrochordons among women with MTHFR deficiency underscores the complex relationship between genetic factors and dermatological health. Our findings emphasized the critical role of MTHFR polymorphisms not only in poor obstetric history but also as significant contributors to skin disorders. This dual association highlights the importance of comprehensive preconception counseling, especially customized for women affected by skin disorders.