Dermatology:

Scabies, caused by the Sarcoptes scabiei var hominis mite burrowing into the skin, is a highly contagious disease characterized by intense nocturnal itching. Its global impact is considerable, affecting more than 200 million individuals annually and posing significant challenges to healthcare systems worldwide. Transmission occurs primarily through direct skin-to-skin contact, contributing to its widespread prevalence and emergence as a substantial public health concern affecting large populations. This review presents consensus-based clinical practice guidelines for diagnosing and managing scabies, developed through the fuzzy Delphi method by dermatology, parasitology, pediatrics, pharmacology, and public health experts. The presence of burrows containing adult female mites, their eggs, and excreta is the diagnostic hallmark of scabies. Definitive diagnosis typically involves direct microscopic examination of skin scrapings obtained from these burrows, although dermoscopy has become a diagnostic tool in clinical practice. Treatment modalities encompass topical agents, such as permethrin, balsam of Peru, precipitated sulfur, and benzyl benzoate. In cases where topical therapy proves inadequate or in instances of crusted scabies, oral ivermectin is recommended as a systemic treatment option. This comprehensive approach addresses the diagnostic and therapeutic challenges associated with scabies, optimizing patient care, and management outcomes.

As medicine advances, cures are being found for diseases that were previously considered incurable, as is the case for some types of cancer. Traditionally, the term cure is reserved for resolution of disease, both at a clinical and a molecular level, which continues after cessation of treatment. Biologic therapies have revolutionized the definition of remission in severe psoriasis, with some patients achieving long-lasting disease suppression, but the disease nearly always relapses on withdrawal of the drug. Our improved understanding of the pathomechanisms of psoriasis, coupled with anecdotal reports of long-term clearance of the disease after cell-based therapies, leads us to the hypothesis that psoriasis is curable. We propose that cure of psoriasis can be achieved by restoring immune homeostasis through a combinatorial, personalized medicine approach encompassing early intervention to include biologics, advanced therapeutics, and lifestyle modification.

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Neglected tropical diseases (NTDs) affect over a billion individuals worldwide, predominantly in low-income countries in tropical and subtropical areas. These diseases frequently result in chronic and debilitating health conditions that significantly diminish the quality of life, often leading to social isolation. The frequent dermatological manifestations underscore the role of dermatologists in managing NTDs. This editorial highlights the crucial role of dermatologists in diagnosing and treating NTDs, focusing on four key diseases: Monkeypox (Mpox) infection, scabies, leprosy, and leishmaniasis.

Cutaneous melanoma (CM) and pancreatic cancer are aggressive tumors whose incidences are rapidly increasing in the last years. This review aims to provide a complete and update description about mutational landscape in CM and pancreatic cancer, focusing on similarities of these two apparently so different tumors in terms of site, type of cell involved, and embryonic origin. The familial forms of CM and pancreatic cancers are often characterized by a common mutated gene, namely CDKN2A. In fact, a germline mutation in CDKN2A gene can be responsible for the development of the familial atypical multiple mole and melanoma syndrome (FAMMM), which is characterized by melanomas and pancreatic cancer development. Sporadic melanoma and pancreatic cancer showed different key-driven genes. The open-access resource cBioPortal has been explored to deepen and investigate the common mutational landscape of these two tumors. We investigated the common mutated genes found in both melanoma and pancreatic cancer with a frequency of at least 5% of tested patients and copy number alterations with a frequency of at least of 3%. Data showed that 18 mutated genes and 3 copy number alterations are present in both melanoma and pancreatic cancers types. Since we found two patients that developed both melanoma and pancreatic cancer, we compared mutation landscape between the two tumors and identified a pathogenic variant in BRCA2 gene. This review gives valuable insights into the genetic underpinnings of melanoma and pancreatic cancer, urging the continued exploration and research of new genetic biomarkers able to identify patients and families at high risk of developing both cancers and to address to screening and to an effective clinical management of the patient.

Antibody-drug conjugates (ADCs) are a new and emerging category of oncologic treatments that combine the target specificity of a monoclonal antibody with a cytotoxic payload. These drugs are associated with unique cutaneous toxicities that vary across agents. Currently, there are eleven ADCs with regulatory approval for solid and liquid tumors and over 80 ADCs currently in clinical development, it is critical for dermatologists to recognize and appropriately mitigate the cutaneous toxicities associated with these therapies. This clinical review will summarize the novel mechanisms and indications of approved ADCs, discuss dermatologic toxicities demonstrated in clinical trials and postmarketing studies, and impart recognition and management guidance when encountering these reactions to help maintain patients safely and comfortably on their medications.

Murine models are vital preclinical and biological tools for studying itch. In this paper, we explore how these models have enhanced our understanding of the mechanisms underlying itch through both acute and chronic itch models. We provide detailed protocols and recommend experimental setups for specific models to guide researchers in conducting itch research. We distinguish between what constitutes a bona fide pruritogen versus a stimulus that causes pruritogen release, an acute itch model versus a chronic itch model, and how murine models can capture aspects of pruritus in human disease. Finally, we highlight how mouse models of itch have transformed our understanding and development of therapeutics for chronic pruritus in patients.

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Abstract: Roflumilast, the third phosphodiesterase-IV (PDE4) inhibitor approved for use in dermatology, is indicated for topical treatment of psoriasis, seborrheic dermatitis, and atopic dermatitis, whereas its two predecessors, apremilast and crisaborole, are indicated for oral treatment of psoriasis and topical treatment of atopic dermatitis, respectively. All three are rationally designed PDE4 inhibitors, but roflumilast is the most potent and effective among the three with in vitro inhibitory constant IC value of: 0.7 nM (roflumilast), 0.14 μM (apremilast), and 0.24 μM (crisaborole), with differences of over 3 orders of magnitude. PDE4 is a 3',5'-cyclic adenosine monophosphate (cAMP, an intracellular secondary messenger) hydrolase consisting of at least 4 subtypes of exon-spliced isoforms, which are primarily expressed in immune cells for inflammatory response. PDE4 inhibition lengthens the duration of cAMP signals and increases cellular cAMP concentrations, generating anti-inflammatory effects. We examined the physicochemical principles that make PDE4 inhibitors effective and propose chemical modifications to improve them. Sequence alignment of the catalytic domains of all PDEs identified many previously unreported invariant residues. These residues bind one Zn and one Mg ions plus five structural water molecules for orienting an attacking μ-hydroxyl/μ-oxo anion and for stabilizing two non-bridging phosphate oxygen atoms. The arrangement of the two divalent metal ions in PDEs is not related to that of the classic mechanism for general phosphoryl transfer.

In this CME, we review 2 specific categories of ulcers: inflammatory (where inflammation is the primary pathologic process leading to ulceration) and vaso-occlusive (where occlusion is the primary process). Inflammatory ulcers include pyoderma gangrenosum and vasculitides, whereas livedoid vasculopathy, calciphylaxis, and Martorell ulcers are vaso-occlusive ulcers. Determining the causes of ulcers in these conditions may require laboratory evaluation, biopsy, and imaging.

In the second part of this CME, we present an approach for the management of inflammatory and vaso-occlusive ulcers and highlight the need for further research in this field. The 3 overarching principles for management are etiology-specific treatment, ulcer care, and consideration of patient comorbidities and risk factors for poor healing. Both etiology-specific treatment and management of patient comorbidities and risk factors often require collaboration with providers from other specialties. Ulcer care is governed by tissue debridement, infection control, management of moisture imbalance, and epithelial edge advancement. As wound healing is a dynamic process, management should be adapted to changes in the status of the ulcer.

Bacteria constitute the most abundant life form on earth, of which the majority exist in a protective biofilm state. Since the 1980s, we have learned much about the role of biofilm in human chronic infections, with associated global healthcare costs recently estimated at ~$386 billion. Chronic wound infection is a prominent biofilm-induced condition that is characterised by persistent inflammation and associated host tissue destruction, and clinical signs that are distinct from signs of acute wound infection. Biofilm also enables greater tolerance to antimicrobial agents in chronic wound infections compared with acute wound infections. Given the difficulty in eliminating wound biofilm, a multi-targeted strategy (namely biofilm-based wound care) involving debridement and antimicrobial therapies were introduced and have been practiced since the early 2000s. More recently, acknowledgement of the speed at which biofilm can develop and hence quickly interfere with wound healing has highlighted the need for an early anti-biofilm strategy to combat biofilm before it takes control and prevents wound healing. This strategy, referred to as wound hygiene, involves multiple tools in combination (debridement, cleansing, and antimicrobial dressings) to maximise success in biofilm removal and encourage wound healing. This review is intended to highlight the issues and challenges associated with biofilm-induced chronic infections, and specifically address the challenges in chronic wound management, and tools required to combat biofilm and encourage wound healing.

The skin barrier can be divided into at least four functional units: chemical, microbial, physical and immunological barriers. The chemical and microbial barriers have previously been shown to exhibit different characteristics in topographically distinct skin regions. There is increasing evidence that the physical and immunological barriers also show marked variability in different areas of the skin. Here, we review recent data on the topographical variations of skin barrier components, the contribution of these variations to the homeostatic function of the skin and their impact on the pathogenesis of specific immune-mediated skin diseases (such as atopic dermatitis and papulopustular rosacea). Recognition of these topographical barrier differences will improve our understanding of skin homeostasis and disease pathogenesis and provide a basis for body site-specific targeted therapies.

Big data and associated approaches to analyse it are on the rise, especially in healthcare settings. This growth is also seen with unique applications in the field of dermatology. While big data offer a plethora of opportunity for improving our current understanding of disease and ability to deliver care, as with any technology innovation, the potential pitfalls should be addressed. In this piece, we highlight opportunities and challenges associated with big data in dermatology. Opportunities include large and novel data sources that may offer a wealth of information, automated detection, classification and diagnostics and improved public health monitoring. Challenges include data quality, issues of interpretability and disparities within artificial intelligence (AI) training data sets. Clinicians and researchers in the field should be aware of these developments within the field of big data to understand how best it may be used toward improving patient care and health outcomes, particularly in the field of dermatology.

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Diabetes mellitus remains a global challenge to public health as it results in non-healing chronic ulcers of the lower limb. These wounds are challenging to heal, and despite the different treatments available to improve healing, there is still a high rate of failure and relapse, often necessitating amputation. Chronic diabetic ulcers do not follow an orderly progression through the wound healing process and are associated with a persistent inflammatory state characterised by the accumulation of pro-inflammatory macrophages, cytokines and proteases. Photobiomodulation has been successfully utilised in diabetic wound healing and involves illuminating wounds at specific wavelengths using predominantly light-emitting diodes or lasers. Photobiomodulation induces wound healing through diminishing inflammation and oxidative stress, among others. Research into the application of photobiomodulation for wound healing is current and ongoing and has drawn the attention of many researchers in the healthcare sector. This review focuses on the inflammatory pathway in diabetic wound healing and the influence photobiomodulation has on this pathway using different wavelengths.

Skin color classification can have importance in skin health, pigmentary disorders, and oncologic condition assessments. It is also critical for evaluating disease course and response to a variety of therapeutic interventions and aids in accurate classification of participants in clinical research studies. A panel of dermatologists conducted a literature review to assess the strengths and limitations of existing classification scales, as well as to compare their preferences and utilities. We identified 17 skin classification systems utilized in dermatologic settings. These systems include a range of parameters such as UV light reactivity, race, ethnicity, and degree of pigmentation. The Fitzpatrick skin type classification is most widely used and validated. However it has numerous limitations including its conflation with race, ethnicity, and skin color. There is a lack of validation data available for the remaining scales. There are significant deficiencies in current skin classification instruments. Consensus-based initiatives to drive the development of validated and reliable tools are critically needed.

Skin in vitro models offer much promise for research, testing drugs, cosmetics, and medical devices, reducing animal testing and extensive clinical trials. There are several in vitro approaches to mimicking human skin behavior, ranging from simple cell monolayer to complex organotypic and bioengineered 3-dimensional models. Some have been approved for preclinical studies in cosmetics, pharmaceuticals, and chemicals. However, development of physiologically reliable in vitro human skin models remains in its infancy. This review reports on advances in in vitro complex skin models to study skin homeostasis, aging, and skin disease.