Lymphocutaneous Sporotrichosis Refractory to First-Line Treatment

Sporotrichosis is a fungal infection endemic in Latin America and has been attributed to the thermodimorphic fungus of the genus Sporothrix. Transmission to humans occurs during a traumatic injury with soil or organic material; additionally, lesions caused by infected cats play an important role in the epidemiology of the disease. The classic treatment of sporotrichosis is performed with itraconazole or potassium iodide; second-line medications, such as amphotericin B and terbinafine, can alternatively be used in cases of first-line drug failure. In the present study, a patient with lymphocutaneous sporotrichosis in the right upper limb exhibited intolerance to itraconazole and potassium iodide, additionally during the period of use; these drugs did not control skin lesions. In this patient, amphotericin B deoxycholate and its liposomal version were used in this patient; and complete recovery of the lesions was observed.

Efficacy and Safety of Topical Dexpanthenol-Containing Spray and Cream in the Recovery of the Skin Integrity Compared with Petroleum Jelly after Dermatologic Aesthetic Procedures

Moisturizers are commonly prescribed after laser and chemical peel aesthetic procedures, but the evidence regarding their efficacy and safety of such use is scarce. We conducted four single-blind, three-week, controlled studies to evaluate the efficacy and safety of topical Dexpanthenol-containing products (Bepantol® spray and Bepantol® cream) using petroleum jelly as a positive control. Skin recovery was assessed after four aesthetic procedures: (1) non-ablative facial laser resurfacing, (2) laser depilation on the external genital and inguinal regions, (3) chemical peel on the external genital and inguinal regions, and (4) ablative facial laser resurfacing. Efficacy was assessed through transepidermal water loss (TEWL) combined with clinical assessment of the skin by the investigators and the participants. In studies (1) and (4), the erythema intensity was evaluated by measuring dermal temperature with a thermal imaging camera. Safety was assessed through adverse event reporting and acceptability through a questionnaire. Dexpanthenol-containing products significantly decreased TEWL and dermal temperature, therefore maintaining skin integrity, promoting its recovery, and reducing erythema. No statistical differences with the positive control were observed. In addition, Dexpanthenol-containing products were well appreciated by the participants from a sensory perspective. These findings suggest that these Dexpanthenol-containing products are adequate for post-procedural care in aesthetic dermatology.

Automatic Segmentation of Skin Regions in Thermographic Images: an Experimental Study

Infrared thermography can be applied in medical applications, such as monitoring skin temperature in inflammatory processes. The possibility for health care professionals and patients to be able to easily, quickly and economically, at anytime and anywhere, monitor the skin temperature distribution through the acquisition of images to control skin infections is extremely important nowadays. This work aims to develop an automatic methodology for the segmentation, identification, analysis and diagnosis of skin inflammation based on thermographic images. The study compares thermographic images from subregions of the hand skin and presents an experimental investigation to segment and identify features in the images automatically. Left and righthand images from two volunteers’ obtained in different conditions, such as cold action, activity action (opening and closing the hand), and friction action (rub both hands), were considered and analyzed. The obtained results demonstrate the feasibility of the implemented procedures and encourage developing and implementing an operating system to monitor skin infections in thermographic images.

Evaluating the impact of decontamination interventions performed in sequence for mass casualty chemical incidents

The Initial Operational Response (IOR) to chemical incidents is a suite of rapid strategies including evacuation, disrobe and improvised and interim decontamination. IOR and Specialist Operational Response (SOR) decontamination protocols involving mass decontamination units would be conducted in sequence by UK emergency services following a chemical incident, to allow for safe onward transfer of casualties. As part of a series of human volunteer studies, we examined for the first time, the effectiveness of UK IOR and SOR decontamination procedures alone and in sequence. Specifically, we evaluated the additional contribution of SOR, when following improvised and interim decontamination. Two simulants, methyl salicylate (MeS) with vegetable oil and benzyl salicylate (BeS), were applied to participants’ skin. Participants underwent improvised dry, improvised wet, interim wet, specialist decontamination and a no decontamination control. Skin analysis and UV photography indicated significantly lower levels of both simulants remaining following decontamination compared to controls. There were no significant differences in MeS levels recovered between decontamination conditions. Analysis of BeS, a more persistent simulant than MeS, showed that recovery from skin was significantly reduced following combined IOR with SOR than IOR alone. These results show modest additional benefits of decontamination interventions conducted in sequence, particularly for persistent chemicals, supporting current UK operational procedures.

Rab3a regulates melanin exocytosis induced by keratinocyte-conditioned medium

Skin pigmentation relies on melanin and is crucial for photoprotection against ultraviolet radiation-induced toxicity. Melanin is synthesized and stored in melanosomes, within melanocytes and then transferred to keratinocytes. While the molecular players involved in melanogenesis have been extensively studied, those underlying melanin transfer remain poorly characterized. Previously, our group proposed that coupled exo/phagocytosis is the predominant mechanism of melanin transfer in human skin and showed an essential role for Rab11b and the exocyst tethering complex in this process. Using a fluorescence-based assay, we show here that keratinocyte-conditioned medium (KCM) specifically induces melanin exocytosis from melanocytes. Moreover, we found that Rab3a, but not Rab11b, regulates melanin exocytosis upon KCM stimulation. In fact, melanosomes accumulate in melanocyte dendrites upon KCM stimulation, co-localizing with Rab3a mainly in the vicinity of the plasma membrane. Additionally, Rab3a silencing does not affect melanin transfer in melanocyte/keratinocyte co-cultures, in contrast with Rab11b depletion, indicating that Rab11b regulates non-KCM-stimulated melanin exocytosis. Thus, our results suggest the existence of at least two distinct routes of melanin exocytosis: one controlled by Rab11b and another Rab3a-dependent, stimulated by KCM. Furthermore, these results provide evidence that soluble factors secreted by keratinocytes can control skin pigmentation via induction of melanocyte signaling pathways that promote peripheral transport of melanosomes and a Rab3a-mediated exocytosis mechanism.

Comparison of Cytokines in Skin Biopsies and Tape Strips from Adults with Atopic Dermatitis

Skin biomarkers for disease severity and treatment response in atopic dermatitis (AD) are needed. Biopsies cause scarring and tape stripping represents an alternative minimally invasive method for stratum corneum sampling. In this study, we examined the gene expression of cytokines in skin biopsies and cytokines in stratum corneum tape strips collected from adults with AD. We collected punch biopsies and tape strips from healthy controls (<i>n</i> = 6) and subjects with AD (<i>n</i> = 12) at baseline and after 2 weeks of topical treatment with mometasone furoate 0.1% cream. We found that IFN-γ, IL-13, and IL-10 mRNA (biopsies) and IL-1β protein expression levels (tape strips) were significantly increased in lesional AD skin compared to healthy control skin. Treatment with topical corticosteroid led to a significant decrease in mRNA levels for IL-13 and IL-4R but no significant differences in cytokine protein levels measured in tape strips. Finally, we found no significant correlations between cytokine levels in tape strips and mRNA levels in skin biopsies.

Evaluating the impact of decontamination interventions performed in sequence for mass casualty chemical incidents

The Initial Operational Response (IOR) to chemical incidents is a suite of rapid strategies including evacuation, disrobe and improvised and interim decontamination. IOR and Specialist Operational Response (SOR) decontamination protocols involving mass decontamination units would be conducted in sequence by UK emergency services following a chemical incident, to allow for safe onward transfer of casualties. As part of a series of human volunteer studies, we examined the effectiveness of IOR and SOR decontamination procedures alone and in sequence. Specifically, we evaluated the additional contribution of SOR, when following improvised and interim decontamination. Two simulants, methyl salicylate (MeS) with vegetable oil and benzyl salicylate (BeS), were applied to participants’ skin. Participants underwent improvised dry, improvised wet, interim wet, specialist decontamination and a no decontamination control. Skin analysis and UV photography indicated significantly lower levels of both simulants remaining following decontamination compared to controls. There were no significant differences in MeS levels recovered between decontamination conditions. Analysis of BeS, a more persistent simulant than MeS, showed that recovery from skin was significantly reduced following combined IOR with SOR than IOR alone. These results show modest additional benefits of decontamination interventions conducted in sequence, particularly for persistent chemicals, supporting current UK operational procedures.

Profiling Tissue and Biofluid miR-155-5p, miR-155*, and miR-146a-5p Expression in Graft vs. Host Disease

Introduction: Acute graft vs. host disease (aGvHD) is a frequent complication following allogeneic haematopoeitic transplantation (HSCT). Despite recent advances, there are no universally accepted biomarkers to determine development of aGvHD. MicroRNAs miR-146a and miR-155 have been previously associated with aGvHD and show promise as clinically translatable biomarkers. In this study, we performed comprehensive expression profiling of miR-146a, miR-155, and miR-155* expression in aGvHD target tissue and biofluids and relate expression to post-HSCT outcomes.Materials and Methods: MicroRNA expression was assessed by qRT-PCR in gastrointestinal (n = 31) and skin (n = 31) biopsies as well as serum (exploratory cohort n = 34, verification cohort n = 81, diagnostic cohort n = 65) and urine (exploratory cohort n = 30, verification cohort n = 56, diagnostic cohort n = 20) biofluids, including extracellular vesicle (EV) cohorts (serum EV n = 15, urine EV n = 30). Expression was related to aGvHD incidence, severity and overall survival.Results: In GI samples, expression of miR-155 (p = 0.03) and miR-146a (p = 0.03) was higher at aGvHD onset compared to patients with no GvHD. In skin biopsies, expression of miR-155 (p = 0.004) was upregulated in aGvHD patients compared to normal control skin. Expression of miR-146a was higher in aGvHD compared to no aGvHD biopsies (p = 0.002). In serum, miR-155 (p = 0.03) and miR-146a (p = 0.02) expression was higher at day 14 (D14), while in urine expression was elevated at D7 post-HSCT in patients who developed aGvHD compared to those disease-free. This was verified in an independent serum (miR-155 p = 0.005, miR-146a p = 0.003) and urine (miR-155 p = 0.02, miR-146a p = 0.04) cohort, where both microRNAs were also associated with aGvHD by ROC analysis. In serum and urine samples taken at the time of aGvHD symptoms, expression of miR-155 and miR-146a was also elevated (serum miR-155 p = 0.03, miR-146a p &lt; 0.001; urine miR-155 p = 0.02, miR-146a p = 0.02). In contrast, miR-146a and miR-155 were downregulated at D14 in serum EVs and at D7 in urine EVs in patients who developed aGvHD compared to those that remained disease-free, in both an exploratory (serum miR-155 p = 0.02, miR-146a p = 0.06; urine miR-155 p = 0.02, miR-146a p = 0.07) and an independent cohort (serum miR-155 p = 0.01, miR-146a p = 0.02).Conclusions: These results further support a role for miR-155 and miR-146a as non-invasive, clinically relevant biomarkers for aGvHD. However, the link between their involvement in generalized inflammation and in specific pathophysiology requires further investigation at a systemic level.

The Expression of IL-17, in Chronic Spontaneous Urticaria Is Linked to Semaphorin5A

Background: Patients with chronic spontaneous urticaria (CSU), an autoimmune disorder, show increased skin expression of IL-17A and can benefit from treatment with the anti-IL-17A biologic secukinumab. The mechanisms that drive IL-17A expression in CSU are currently unknown, but may involve Semaphorin5A (Sema5A). Objective: To explore the expression, role, and effects of Sema5A in CSU and its link to IL-17A. Material and Methods: We investigated patients with CSU and healthy controls for skin expression of expressing peripheral T cells. Results: Sema5A was highly expressed in the skin of CSU patients as compared to healthy control skin. Both CD4+ T cells and mast cells in CSU skin expressed Sema5A, and many of them expressed both Sema5A and IL-17A. Patients with CSU had significantly higher rates of IL-17A-expressing CD4+ T cells as compared to healthy controls. Incubation with Sema5A increased the rates of IL-17A-expressing CD4+ T cells in healthy controls to CSU levels. Conclusion: Sema5A may drive the expression and effects of IL-17A in CSU. Further studies in larger cohorts are needed to confirm the role of Sema5A in the pathogenesis of CSU and to explore its potential as a therapeutic target.

Spontaneously Resolved Atopic Dermatitis Shows Melanocyte and Immune Cell Activation Distinct From Healthy Control Skin

Atopic dermatitis (AD) typically starts in infancy or early childhood, showing spontaneous remission in a subset of patients, while others develop lifelong disease. Despite an increased understanding of AD, factors guiding its natural course are only insufficiently elucidated. We thus performed suction blistering in skin of adult patients with stable, spontaneous remission from previous moderate-to-severe AD during childhood. Samples were compared to healthy controls without personal or familial history of atopy, and to chronic, active AD lesions. Skin cells and tissue fluid obtained were used for single-cell RNA sequencing and proteomic multiplex assays, respectively. We found overall cell composition and proteomic profiles of spontaneously healed AD to be comparable to healthy control skin, without upregulation of typical AD activity markers (e.g., IL13, S100As, and KRT16). Among all cell types in spontaneously healed AD, melanocytes harbored the largest numbers of differentially expressed genes in comparison to healthy controls, with upregulation of potentially anti-inflammatory markers such as PLA2G7. Conventional T-cells also showed increases in regulatory markers, and a general skewing toward a more Th1-like phenotype. By contrast, gene expression of regulatory T-cells and keratinocytes was essentially indistinguishable from healthy skin. Melanocytes and conventional T-cells might thus contribute a specific regulatory milieu in spontaneously healed AD skin.