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The skin barrier is essential for protection against allergens, irritants, and pathogens and is intimately involved in a variety of inflammatory conditions. As such, approaches to treating these inflammatory skin conditions could involve the repair and protection of the skin barrier. This form of treatment can be delivered in the form of skin protectants, though their protective value remains questionable. Evidence suggests that skin protectants could form an additional layer of protection against harmful substances that could penetrate the skin barrier. However, although several studies support the efficacy of skin protectants, others suggest potentially aggravating effects instead. The range of active ingredients included in skin protectant formulas varies widely, which could account for these observed differences. While the use of skin protectants could prove beneficial in populations at higher risk of exposure to irritants, their effectiveness may be hindered by a lack of proper adherence. The findings gathered from the existing literature on skin protectants appear promising, though further investigation must be conducted to better understand their protective effects against conventional barrier repair approaches. J Drugs Dermatol. 2022;21(9):977-982. doi:10.36849/JDD.6705.

Permanent hair dye is the most commonly used anti-aging procedure used by both men and women. However, permanent hair dye can cause irritant contact dermatitis due to ammonia and allergic contact dermatitis due to paraphylenediamine (PPD).This research examined an ammonia-free and PPD-free permanent hair dye in 50 ethnically diverse females 21-91 years of age who were current users of permanent hair dyes. Subjects were patch tested prior to dyeing. Two dye sessions were undertaken at baseline and 2-6 weeks post-baseline depending on the dyeing habits of the subject.50/50 subjects successfully completed the study with no incidence of allergic or irritant contact dermatitis. After 2 dyeing procedures, the dermatologists rated an 87% improvement in hair shine, 90% improvement in hair color, 88% improvement in hair moisturization, 87% improvement in hair porosity, and 88% improvement in hair combability.A MEA-based ammonia-free cream hair color without PPD or resorcinol was safe for use on the hair and scalp of females with diverse hair types and textures.

Despite the widespread use of peripheral intravenous catheters, unscheduled catheter failure before completion of treatment occurs frequently. If a large vein is selected, catheter failures may be prevented despite administering a highly irritant drug. In this study, we attempted to use a catheter that can be placed in a large upper arm vein. The new catheter was 88 mm long but had no guidewire to reduce contamination risk. This study aimed to evaluate the safety of the first-in-human trial for the new catheter with the administration of highly irritant drugs. This study was conducted at a university hospital in Tokyo, Japan. Eight Japanese adults were hospitalized adults with planned administration of non-cancer drugs with high irritant potential using a peripheral catheter. A trained nurse catheterized with the new catheter in the upper arm using ultrasonography. The catheterization site was monitored by staff and a research nurse once every 24 hours for up to 7 days. No adverse events or catheter failure occurred and the catheter placement success rate was 100%. In two patients, a temporary occlusion alarm of the infusion pump occurred, possibly due to the flexion of the catheter base. The new peripheral intravenous catheter did not interrupt medical treatments as is common after placement, but safety administered the irritant drugs. However, because this catheter may be easily affected by the contraction of the muscle at the fixation position, the position and method of catheter fixation in the upper arm need to be carefully considered.

Chemotherapy extravasation can cause severe harm. There is a lack of evidence-based standardization on the surgical management of such injuries beyond the immediate stage. In an algorithm connecting presentation time post-injury with surgical treatment could help standardize future treatment. This study prospectively validated a preset standardized surgical algorithm based on presentation time in a consecutive series between October 2017 and October 2020. Chemotherapeutic agent, site and extent of injury, type of surgery and outcome at a minimum of 6 months' follow-up were collected. Seven thousand six hundred twelve individuals received chemotherapy during that period; 15 patients suffered extravasation injuries, 2 of whom were referred from outside our hospital. This algorithm distinguished: A) beyond the immediate stage and up to 2 days, treated with saline subcutaneous washout (SCWO) and vacuum-assisted closure (VAC) dressing; B) 2 to 5 days, open surgical decompression and VAC dressing; C) 5 to 10 days, non-operative management with surveillance; and D) more than 10 days, radical necrotic excision with or without VAC dressing and tissue reconstruction. In 2 patients in Group A and 3 patients in Group B, all vesicant symptoms resolved. Five of the 6 patients in Group C (3 vesicant, 3 non-vesicant) did not progress into necrosis or infection, and 1 case of vesicant extravasation progressed to a localized ulcer beyond this period and, as surgery was refused, led to a chronic ulcer with stiffness; 2 cases of non-vesicant extravasation developed a recall phenomenon but resolved after the third cycle. Of the 4 patients in Group D, all vesicant, 2 were treated with no complications, 1 had complex regional pain syndrome (CRPS) due to late presentation, and 1, referred with necrotizing fasciitis, underwent above-elbow amputation but died due to septic shock. This study demonstrated a uniform surgical approach in a series of 15 cases; larger studies are still needed to validate the efficacy of this protocol in reducing morbidity. LEVEL OF EVIDENCE: IV.

The use of soap for skin cleansing is common among the population. However, it is possible that it causes damage to skin cells and disrupts the skin barrier.To determine the cytotoxic effect of soaps on in vitro-cultured keratinocytes and to correlate it with clinical irritation.A survey was conducted to find out the most widely used commercial soaps and their number. Subsequently, their cytotoxicity was evaluated in human keratinocyte cultures using the resazurin assay. The soaps with the highest and lowest cytotoxicity were applied to the skin of healthy volunteers to assess their effect on the skin barrier using colorimetry and transepidermal water loss (TEWL) assays.Of the analyzed soaps, 37 % were shown to be toxic to keratinocytes in vitro. The soap with the highest toxicity induced the highest rate of erythema and TEWL, in comparison with the least toxic soap and the vehicle used as the control solution.Soaps marketed for skin cleansing can contain chemical ingredients that damage human keratinocytes and cause skin barrier subclinical irritation. Their use can worsen preexisting dermatoses, generate xerotic or irritant contact dermatitis, and cause atrophy and dermatoporosis.El jabón para el aseo cutáneo es de empleo común entre la población, sin embargo, es posible que cause daño a las células de la piel y modifique la barrera cutánea.Determinar el efecto citotóxico de los jabones en queratinocitos cultivados in vitro y correlacionarlo con la irritación clínica.Se realizó una encuesta para conocer los jabones comerciales más utilizados y su cantidad; posteriormente, se evaluó su citotoxicidad en cultivos de queratinocitos humanos mediante el método de resazurina. Los jabones con mayor y menor citotoxicidad se aplicaron en piel de voluntarios sanos para evaluar su efecto en la barrera cutánea mediante ensayos de colorimetría y pérdida transepidérmica de agua.De los jabones analizados, 37 % demostró ser tóxico para los queratinocitos in vitro. El jabón con mayor toxicidad indujo el mayor índice de eritema y pérdida transepidérmica de agua, en comparación con el jabón menos tóxico y el vehículo empleado como solución control.Los jabones comercializados para el aseo cutáneo pueden incluir ingredientes químicos que dañan los queratinocitos humanos y causan irritación subclínica de la barrera cutánea. Su utilización puede agravar dermatosis preexistentes, generar dermatitis xerósica o de contacto irritativa y causar atrofia y dermatoporosis.

Batik, a resist-dyeing technique to decorate a special cotton fabric, has been practiced for centuries in Indonesia. Unfortunately, as an informal enterprise, batik industry activities lack work safety and health regulations. This study aimed to identify potential health hazards, including inventorying the chemicals to which the workers are exposed, the PPE profile, and investigating the prevalence of occupational skin diseases (OSD) in the batik industry. A cross-sectional study and an inventory of exposure to the chemicals were done in traditional batik workplaces in 5 districts in Yogyakarta province, Indonesia. The chemicals were classified as potential sensitizers/irritants, and the workers were examined and interviewed using the Nordic Occupational Skin Questionnaire-2002/LONG. Of 222 traditional batik workers, OSD were diagnosed in 61 (27.5%) workers, with occupational contact dermatitis was the most common OSD encountered (n = 23/61; 37.7%) (allergic contact dermatitis n = 7/23; irritant contact dermatitis n = 16/23). A smaller portion of other OSD was also encountered including callus, miliaria, and nail disorder (9%, 6.3%, and 5.9%, respectively). During each step of the traditional batik manufacturing process, the workers are exposed to substances that act as irritants and/or as potential contact allergens. However, only one-fourth of the workers used PPE regularly, particularly during the coloring process and wax removal (wet processes). Traditional batik manufacturing process exposes the worker to various physical and chemical hazards, resulting in a high prevalence of occupational skin diseases, especially contact dermatitis among the employees.

Irritant contact dermatitis (ICD) is a localized, nonimmune-induced inflammatory skin reaction, characterized by multiform skin lesions, including erythema, scaling, edema, blisters, and erosion. Mercury and its related compounds are highly allergic agents that can induce allergic contact dermatitis.This article aims to clarify the skin damage caused by irritant contact dermatitis caused by the addition of high doses of mercury to skin care products.A 30-year-old female patient sought treatment at our Institute for contact dermatitis.Through the patch test of the patients and the component detection of the skin care products her use. A large amount of mercury was found in skin care products, and the patient had no apparent allergic reaction to mercury.We considered irritant contact dermatitis caused by excess mercury, and the patient's condition improved with treatment.

Contact dermatitis is a common disease that is caused by repeated skin contact with contact allergens or irritants, resulting in allergic contact dermatitis (ACD) and/or irritant contact dermatitis. Attempts have been made to identify biomarkers to distinguish irritant and allergic patch test reactions, which could aid diagnosis. Some promising candidates have recently been identified, but verification and validation in clinical cases still need to be done. New causes of ACD are constantly being recognized. In this review, 10 new contact allergens from recent years, several relating to anti-aging products, have been identified. Frequent allergens causing considerable morbidity in the population, such as the preservative methylisothiazolinone, have been regulated in the European Union. A significant drop in the number of cases has been seen, whereas high rates are still occurring in other areas such as North America. Other frequent causes are fragrance allergens, especially the widely used terpenes and acrylates found in medical devices for control of diabetes. These represent unsolved problems. Recent advances in immunology have opened the way for a better understanding of the complexity of contact dermatitis, especially ACD-a disease that may be more heterogenous that previous understood, with several subtypes. With the rapidly evolving molecular understanding of ACD, the potential for development of new drugs for personalized treatment of contact dermatitis is considerable.

Foot eczema in children is a commonly encountered condition but is associated with diverse etiology, thereby posing a diagnostic challenge. These include atopic eczema, juvenile plantar dermatoses, irritant contact dermatitis, and allergic contact dermatitis. Because of the diverse etiology, it is often difficult to distinguish between the conditions clinically, thereby warranting patch testing for the correct diagnosis.The study was conducted to determine the frequency of positive patch tests among children with foot eczema and to compare them with children with and without atopy.This was a prospective observational study done on 86 children aged 4 to 17 years presenting with foot eczema in whom patch testing was done using Indian standard series and footwear series and patients' own footwear.The clinical diagnosis of foot eczema in our study was allergic contact dermatitis (37%), followed by atopic eczema (30%), juvenile plantar dermatoses (17%), and lichen simplex chronicus (15%). Patch test positivity was present in 36% of the cases with clinical relevance in 65% of the cases. The common allergens were rubber allergens and disperse dyes. Of the children who were patch tested, highest patch test positivity rates were seen in allergic contact dermatitis (50%) and juvenile plantar dermatoses (53%). No significant differences were observed with regard to patch test positivity or relevance between children with and without atopy.The diagnosis of foot eczema in children cannot be made on clinical grounds alone, and patch testing should be recommended in children with any morphological pattern of foot eczema irrespective of presence or absence of atopy, especially in those with long-standing and recalcitrant disease with frequent exacerbations.

Objective: The aim of this study was to identify which types of skin reactions are associated with slime toys and which of their ingredients are most frequently involved in cases of poisoning. Data source: Between January and July 2021, articles were selected using PubMed, SciELO, and LILACS databases. The following descriptors were used: (dermatitis OR rash OR eczema OR inflammation) AND slime. Inclusion criteria were articles available in full, in either Portuguese, English, or Spanish, published between January 2000 and July 31, 2021, and articles reporting cases of contact dermatitis or eczema potentially or directly attributed to slime toys. Articles not meeting these criteria and duplicate texts in the databases were excluded. Data synthesis: In total, 65 publications were identified, of which 16 were included in this review. This resulted in a total of 22 children (2 males, 20 females), aged between 4 and 13 years, who were reportedly intoxicated by slime toys, most of these being linked to homemade preparations. Studies reported the occurrence of contact or allergic dermatitis on hands, fingers, nails, forearms, and cheeks. The most allergenic and/or irritant ingredients included liquid detergent and soap. Additionally, patch tests identified positive reactions to methylisothiazolinone and methylchloroisothiazolinone, the preservatives used by chemical industries on preparation of glue, soap, detergents, etc. Conclusions: Although slime toys might be important for improving motor development and parental relationships, homemade slime toy recipes include several allergenic and irritant ingredients which might be exposed to vulnerable children and cause intoxications. Therefore, homemade slime toys preparations should be used cautiously and under the supervision of adults. Resumo Objetivo: Identificar quais tipos de reações de pele e ingredientes do brinquedo slime estão frequentemente envolvidos em relatos de intoxicação. Fontes de dados: Entre janeiro e julho de 2021, ocorreu a seleção dos artigos, utilizando-se as bases de dados: United States National Library of Medicine (PubMed), Scientific Electronic Library Online (SciELO) e Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS). Foram utilizados os seguintes descritores: (dermatitis OR rash OR eczema OR inflammation) AND slime. Incluíram-se artigos disponíveis na íntegra, em português, inglês ou espanhol, publicados entre janeiro de 2000 e 31 julho de 2021, que relatassem casos de crianças e adolescentes que apresentaram reação cutânea após a manipulação do brinquedo slime. Foram excluídos artigos sem aderência ao tema e textos duplicados nas bases de dados. Síntese dos dados: Identificaram-se 65 publicações, sendo 16 utilizadas para a elaboração desta revisão. Isso resultou no total de 22 crianças (duas do sexo masculino, 20 do feminino), com idades entre quatro e 13 anos, que teriam sido intoxicadas por slime, a maioria dos casos ligado a preparações caseiras. Estudos relataram a ocorrência de dermatite de contato ou alérgica nas mãos, dedos, unhas, antebraços e bochechas. Os ingredientes mais alergênicos e/ou irritantes foram detergentes líquidos e sabão. Ademais, o patch test identificou reações positivas para metilisotiazolinona e metilcloroisotiazolinona, que são conservantes utilizados em produtos como cola, sabão, detergente, etc. Conclusões: Ainda que o brinquedo slime seja importante para o desenvolvimento motor e das relações parentais, receitas caseiras incluem vários ingredientes alergênicos e irritantes, que podem ser expostos a crianças vulneráveis e causar intoxicações. Sendo assim, as preparações do slime devem ser feitas com cautela e sob supervisão de adultos.

In the present study, a comparative human toxicity assessment between newly developed Mn3O4 nanoparticles with enhanced electrochemical properties (GNA35) and their precursor material (Mn3O4) was performed, employing different in vitro cellular models representing main exposure routes (inhalation, intestinal and dermal contact), namely the human alveolar carcinoma epithelial cell line (A549), the human colorectal adenocarcinoma cell line (HT29), and the reconstructed 3D human epidermal model EpiDerm. The obtained results showed that Mn3O4 and GNA35 harbour similar morphological characteristics, whereas differences were observed in relation to their surface area and electrochemical properties. In regard to their toxicological properties, both nanomaterials induced ROS in the A549 and HT29 cell lines, while cell viability reduction was only observed in the A549 cells. Concerning their skin irritation potential, the studied nanomaterials did not cause a reduction of the skin tissue viability in the test conditions nor interleukin 1 alpha (IL- 1 α) release. Therefore, they can be considered as not irritant nanomaterials according to EU and Globally Harmonized System of Classification and Labelling Chemicals. Our findings provide new insights about the potential harmful effects of Mn3O4 nanomaterials with different properties, demonstrating that the hazard assessment using different human in vitro models is a critical aspect to increase the knowledge on their potential impact upon different exposure routes.

Polymyxin B (PMB) is an essential antibiotic active against multidrug-resistant bacteria, such as multidrug-resistant Pseudomonas aeruginosa (MDRP). However, the clinical use of PMB is limited, because PMB causes serious side effects, such as nephrotoxicity and neurotoxicity, probably due to its cytotoxic activity. However, cytotoxic mechanisms of PMB are poorly understood. In this study, we found that macrophages are particularly sensitive to PMB, when compared with other types of cells, including fibroblasts and proximal tubule (PT) cells. Of note, PMB-induced necrosis of macrophages allowed passive release of high mobility group box 1 (HMGB1). Moreover, upon exposure of PMB to macrophages, the innate immune system mediated by the NLR family pyrin domain containing 3 (NLRP3) inflammasome that promotes the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β) was stimulated. Interestingly, PMB-induced IL-1β release occurred in the absence of the pore-forming protein gasdermin D (GSDMD), which supports the idea that PMB causes plasma membrane rupture accompanying necrosis. Emerging evidence has suggested that both HMGB1 and IL-1β released from macrophages contribute to excessive inflammation that promote pathogenesis of various diseases, including nephrotoxicity and neurotoxicity. Therefore, these biochemical properties of PMB in macrophages may be associated with the induction of the adverse organ toxicity, which provides novel insights into the mechanisms of PMB-related side effects.

BACKGROUND Many nail cosmetics have components that are considered irritants or allergens. Due to the current clinical assessment limitations, it is often too late to identify nail enamel hazards until they cause disease. Thus, it is essential to investigate effective methods of detecting minor changes and early lesions in nails before they worsen. OBJECTIVES To provide a reliable method to investigate and evaluate nail enamel hazards on nails earlier using ultrasonic equipment. METHODS Eighty-three volunteers with smooth, lustrous nails were enrolled after being clinically examined. The thumbnails and middle nails were evaluated before and after using nail enamel for 2 weeks. Nail health was then assessed using three methods: clinical evaluation, nail surface image analysis, and an ultrasonic device. RESULTS Using clinical diagnostic and imaging methods for analyzing the nail surface showed no visible differences before and after using nail enamel for 2 weeks. However, there was a significant difference in the nails' depth and density (p

The most common complication in individuals with ostomies is irritant contact dermatitis from the acidic stoma effluent coming into contact with the peristomal skin. Although protective powders are widely used for the treatment of peristomal skin, there is little scientific evidence to justify their use. The combined use of sodium carboxymethylcellulose cellulose fibers (SCCFs) together with a hydrocolloid dressing for fixation is an effective alternative in the management of these wounds. Here, the authors report a case series of three patients presenting at a stoma therapy clinic with peristomal skin lesions because of severe irritant contact dermatitis. Patients were men aged between 70 and 81 years, had been diagnosed with colon cancer (n = 2) or bladder cancer (n = 1), and had undergone a colostomy (n = 1), ileostomy (n = 1), or Bricker-type ureteroileostomy (n = 1). A semiocclusive care protocol was applied in a moist environment using SCCF and an extrathin hydrocolloid adhesive dressing, and the collection device was secured using adhesive resin and an ostomy belt. The combined use of SCCF and hydrocolloid dressings provided beneficial results to treat the dermatitis, with reduced discomfort after 7 days and lesions healing within 4 weeks.

The skin is an important barrier that protects against invasion by foreign substances, including irritants and harmful microorganisms, and holds water in the body. Washing the skin with cleansers and shampoos containing anionic surfactants, for example sodium dodecyl sulfate (SDS), is important for maintaining skin homeostasis. However, surfactants can cause dermatitis, cutaneous hypersensitivity (e.g., alloknesis), and pruritus in humans. Our previous studies revealed an alloknesis response in the skin with SDS-induced dermatitis in C57BL/6 mice. In addition, we found that alloknesis responses and afterdischarge responses following stimulation with light touch are related because they are observed contemporaneously. In this study, we used Hos:HR-1 hairless mice to establish a mouse model to evaluate long-term drug application for alloknesis responses. Alloknesis was observed in HR-1 mice with SDS-induced dermatitis. The mean number of c-Fos (a marker of neural activity) immunopositive neurons was increased in the lamina 1-2 (L1-2) spinal dorsal horn, but not in L3-4, of SDS-treated HR-1 mice compared to vehicle-treated mice. We also discovered that afterdischarge responses were observed in neurons in L1-2. There was also a correlation between the intensity of the afterdischarge responses and depth of the recording site. Thus, the following were suggested: 1) neurons that mediate these afterdischarge responses are located on the superficial layer of the spinal cord; 2) afterdischarge responses can be an index of alloknesis responses, and 3) the mouse model of SDS-induced dermatitis is an appropriate alloknesis model.

International audience; Chemotherapy is almost exclusively administered via the intravenous (IV) route, which has serious limitations (e.g., patient discomfort, long hospital stays, need for trained staff, high cost, catheter failures, infections). Therefore, the development of effective and less costly chemotherapy that is more comfortable for the patient would revolutionize cancer therapy. While subcutaneous (SC) administration has the potential to meet these criteria, it is extremely restrictive as it cannot be applied to most anticancer drugs, such as irritant or vesicant ones, for local toxicity reasons. Herein, we report a facile, general, and scalable approach for the SC administration of anticancer drugs through the design of well-defined hydrophilic polymer prodrugs. This was applied to the anticancer drug paclitaxel (Ptx) as a worst-case scenario due to its high hydrophobicity and vesicant properties (two factors promoting necrosis at the injection site). After a preliminary screening of well-established polymers used in nanomedicine, polyacrylamide (PAAm) was chosen as a hydrophilic polymer owing to its greater physicochemical, pharmacokinetic, and tumor accumulation properties. A small library of Ptx-based polymer prodrugs was designed by adjusting the nature of the linker (ester, diglycolate, and carbonate) and then evaluated in terms of rheological/viscosity properties in aqueous solutions, drug release kinetics in PBS and in murine plasma, cytotoxicity on two different cancer cell lines, acute local and systemic toxicity, pharmacokinetics and biodistribution, and finally their anticancer efficacy. We demonstrated that Ptx-PAAm polymer prodrugs could be safely injected subcutaneously without inducing local toxicity while outperforming Taxol, the commercial formulation of Ptx, thus opening the door to the safe transposition from IV to SC chemotherapy.

BackgroundEvery evening, chimpanzees (Pan troglodytes) build a sleeping platform so called “nest” by intertwining branches of tree. Most of chimpanzees’ communities studied have a preference for tree species in which they nest. As female mosquitoes are feeding on the blood of their host at nighttime, chimpanzees may prevent being disturbed and bitten by mosquitoes by selecting tree species having properties to repel them.MethodsTo test the hypothesis that chimpanzees choose tree species for their aromatic properties, data related to 1,081 nesting trees built between 2017 and 2019 in the Sebitoli community of Kibale National Park (Uganda) were analysed. The 10 most used trees were compared to the 10 most common trees in the habitat that were not preferred for nesting. Leaves from the 20 trees species were collected and hydro-distillated to obtain essential oils and one of the by-products for behavioural bioassays against females of the African mosquito,Anopheles gambiae.ResultsSebitoli chimpanzees showed tree preferences: 10 species correspond to more than 80% of the nesting trees. Out of the essential oil obtained from the 10 nesting trees, 7 extracts for at least one concentration tested showed spatial repellency, 7 were irritant by contact and none were toxic. In the other hand, for the abundant trees in their habitat not used by chimpanzees, only 3 were repellent and 5 irritants.Discussion and conclusionThis study contributes to evidence that chimpanzees, to avoid annoying mosquitoes, may select their nesting trees according to their repellent properties (linked to chemical parameters), a potential inspiration for human health.

Tissue necrosis is a serious but rare complication of sclerotherapy. Early detection and targeted management are essential to prevent progression and minimise serious complications. In the first instalment of this paper, we reviewed the pathogenic mechanisms of post-sclerotherapy necrosis. Here, we describe risk minimisation and management strategies. Risk factors must be addressed to reduce the chance of necrosis following sclerotherapy. These may be treatment-related including poor choice of sclerosant type, concentration, volume or format, poor injection technique, suboptimal ultrasound visualisation and treatment of vessels in high-risk anatomical areas. Risk factors specific to individual patients should be identified and optimised pre-operatively. Tissue necrosis is more likely to occur with extravasation of irritant sclerosants such as absolute alcohol, sodium iodide, bleomycin and hypertonic saline, whereas extravasation of foam detergent sclerosants rarely results in tissue loss. Proposed treatments for extravasation of irritant sclerosants include infiltration of an isotonic fluid and hyaluronidase. Management of inadvertent intra-arterial injections may require admission for neurovascular observation and monitoring for ischaemia, intravenous systemic steroids, anticoagulation, thrombolysis and prostanoids infusion when required. Treatment of veno-arteriolar reflex vasospasm (VAR-VAS) necrosis follows the same protocol involving systemic steroids but rarely requires hospital admission and may not require anticoagulation. In general, treatment of post-sclerotherapy necrosis is challenging and most proposed treatment measures are not evidence-based and only supported by anecdotal personal experience of clinicians. Despite all measures, once the necrosis has set in, it is very difficult to reverse the process and all measures described here may only be useful in prevention of progression and extension of the ulceration. Mid to long-term measures include addressing exacerbating factors, management of medical and psychosocial comorbidities, treatment of secondary infections and referrals to relevant specialists. All ulcers should be managed with compression and prescribed dressing regimes in line with the healing stage of the ulcer.

Background Contact sensitizers may interfere with correct protein folding. Generation of un-/misfolded proteins can activate the IRE-1 or PERK signaling pathways initiating the unfolded protein response (UPR) and thereby determine inflammatory immune responses. We have analyzed the effect of sensitizers with different potencies on the induction of UPR activation/inhibition and the subsequent generation of a pro-inflammatory micromilieu in vitro as well as the effect of UPR modulation on the inflammatory response in the murine contact hypersensitivity (CHS) in vivo. Methods Semi-quantitative and quantitative PCR, fluorescence microscopy, ELISA, NF-κB activation and translocation assays, DC/keratinocyte co-culture assay, FACS, and in vivo CHS experiments were performed. Results Sensitizers and irritants activate IRE-1 and PERK in murine and human keratinocytes. Synergistic effects occur after combination of different weak sensitizers / addition of irritants. Moreover, tolerogenic dinitrothiocyanobenzene can be converted into a strong sensitizer by pre-activation of the UPR. Blocking UPR signaling results in decreased NF-κB activation and cytokine production in keratinocytes and in activation marker downregulation in a HaCaT/THP-1 co-culture. Interestingly, not only systemic but also topical application of UPR inhibitors abrogates CHS responses in vivo. Conclusion These observations highlight an important role of the UPR in determination of the inflammatory response in vitro and in vivo further underlining the importance of tissue stress and damage responses in the development of ACD and provide mechanistically based concepts as a basis for the development of new therapeutic approaches to treat allergic contact dermatitis.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 5 acyl sarcosines and 9 sarcosinate salts as used in cosmetics; all of these ingredients are reported to function in cosmetics as hair conditioning agents and most also can function as surfactants—cleansing agents. The ingredients reviewed in this assessment are composed of an amide comprising a fatty acyl residue and sarcosine and are either free acids or simple salts thereof. The Panel relied on relevant new data, including concentration of use, and considered data from the previous Panel report, such as the reaction of sarcosine with oxidizing materials possibly resulting in nitrosation and the formation of N-nitrososarcosine. The Panel concluded that these ingredients are safe as used in cosmetics when formulated to be non-irritating, but these ingredients should not be used in cosmetic products in which N-nitroso compounds may be formed.

Caffeine has long been vilified as a cause for urinary urgency incontinence (UUI) along with other potential bladder irritants such as carbonation, alcohol, and acidic juices. The objective of this study was to assess the fluid intake behavior of people with urgency, UUI, and those with lower urinary tract symptoms (LUTS) without UUI or urgency to assess if they avoided certain potential bladder irritants or had different fluid intake. We hypothesized that patients with UUI would avoid caffeine as a self-management method more so than these other two groups.Treatment-seeking men and women with LUTS in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Observational Cohort study completed a baseline 3-day voiding and intake diary. "Complete" diaries had 3 days of data and no missing intake or voided volumes. Beverages with any caffeine, alcohol, carbonation, or acidic juice were identified and the total volume was recorded as well as the type of beverage containing caffeine to calculate the daily caffeine dose.Four hundred and ninety-one participants (277 men and 214 women) with a median age of 63 had complete diaries. Urinary urgency was more prevalent in women than men (79% vs. 55%, p 0.0001) as was UUI (84% vs. 47%, p 0.0001). Total fluid intake over 3 days was lower among the urgency group versus the nonurgency group (median [interquartile range] 5.2 [4.0-6.8] L vs. 5.7 [4.3-7.0] L, p = 0.028) and the UUI group compared to the urgency without incontinence group were less likely to consume alcohol (26% vs. 37%, p = 0.04). After adjusting for sex, BMI, age, and total intake volume, UUI participants had 54% lower odds of consuming any caffeine (odds ratio = 0.46, 95% confidence interval = 0.22-0.96, p = 0.04) than those without incontinence, but among those that did consume caffeine, no difference in the volume of caffeinated beverages or milligrams of caffeine consumed was detected between those with UUI and those with urgency without incontinence. No difference in carbonation or acidic juice intake was detected between groups.Individuals with urgency consume a lower volume of fluid than those without urgency. UUI participants more often abstain from caffeine, but among those that consume caffeine, the dose is similar to those without UUI. One explanation for these results is that only a subset of individuals with urgency or UUI are caffeine sensitive.

Sensitive skin is a widespread dermatologic condition, and no optimal treatments have been established so far.To investigated the efficacy and safety of the combined therapy of short-wave radiofrequency (SWRF) and intense pulsed light (IPL) in improving transepidermal water loss (TEWL) and facial erythema in sensitive skin patients.Twenty-two patients with sensitive skin received the SWRF treatment once per week for 4 weeks and IPL treatment once. Digital photographs and three-dimensional images were taken at each follow-up. The clinical efficacy was evaluated by the improvement of sensitive scale-10 including irritant symptoms and facial erythema. In addition, erythema area and TEWL values were measured.All patients showed subjective and objective improvement in irritant sensations and facial erythema after treatment. The TEWL values decreased from 20.29 ± 5.97 g·hThe combination of SWRF with IPL was effective in relieving skin irritant sensations and facial erythema of sensitive skin by repairing skin barrier function.

This paper aims to develop an amperometric, non-enzymatic sensor for detecting and quantifying UA as an alert signal induced by allergens with protease activity in human cell lines (HEK293 and HeLa). Uric acid (UA) has been classified as a damage-associated molecular pattern (DAMP) molecule that serves a physiological purpose inside the cell, while outside the cell it can be an indicator of cell damage. Cell damage or stress can be caused by different health problems or by environmental irritants, such as allergens. We can act and prevent the events that generate stress by determining the extent to which cells are under stress. Amperometric calibration measurements were performed with a carbon paste electrode modified with La(OH)

Introduction:Occupational hand dermatitis is common among healthcare workers, with increased incidence during the COVID-19 pandemic. Irritant contact dermatitis accounts for the majority of occupational hand dermatitis and is largely due to frequent contact with hand hygiene products. Long-term prognosis of occupational contact dermatitis is often very poor. This study aims to identify and implement suitable workplace interventions to aid in the recovery of occupational irritant hand dermatitis among healthcare workers during the COVID-19 pandemic.MethodsA quality improvement (QI) project was performed in a tertiary hospital using the Plan-Do-Study-Act model. Healthcare workers seen at the Occupational Dermatology Clinic from March 2020 to May 2021 for the first time for likely occupational irritant dermatitis were targeted for the project. Four workplace interventions were implemented: (a) substitute current alcohol-based hand rub (ABHR) with a different, gentler ABHR, (b) alternate ABHR with gentle hand wash products, (c) temporary job modification with less clinical work (d) switch latex gloves to nitrile gloves. The improvement was assessed after 2 months of workplace intervention using a visual analogue scale, based on changes seen on photographs taken at the baseline and monthly review. The target improvement was set at 70% after 2 months of workplace interventions.ResultsA total of 21 participants were included in the QI project. All participants were found to have significant improvement in their hand condition. The estimated mean reduction of signs and symptoms was 80% in comparison to their baseline hand condition before intervention.ConclusionWorkplace interventions such as substituting irritant hand hygiene products with gentler alternatives and temporary reduction in clinical duties may be useful in improving the recovery rate of irritant hand dermatitis among healthcare workers. Areas with high hand hygiene workload or high incidences of hand dermatitis may opt to implement systemic workplace changes.

International audience; While exposure to irritant and sprayed cleaning products at home is known to have a harmful role in asthma, the potential health effect of other categories or forms has not been investigated. We studied the associations of household use of cleaning products, including green, home-made products and disinfecting wipes, with asthma based on data from the large French populationbased Constances cohort. Participants completed standardized questionnaires on respiratory health and household use of cleaning products. Cross-sectional associations of cleaning products with current asthma, adjusted for gender, age, smoking status, BMI and educational level, were evaluated by logistic regressions. Analyses were conducted in 41,570 participants (mean age: 47 years, 56% women, weekly use of the six specific products/forms studied varied from 11% to 37%). Weekly use of irritants (OR=1.23[1.13-1.35]), scented (OR=1.15[1.06-1.26]), green (OR=1.09[1.00-1.20]) and homemade products (OR=1.19[1.06-1.34]), as well as sprays (OR=1.18[1.08-1.29]), disinfecting wipes (OR=1.21[1.09-1.34]) were significantly associated with asthma, with significant trends according to the frequency of use. When they were not co-used with irritants/sprays, associations were reduced and persisted only for disinfecting wipes. Weekly use of disinfecting wipes at home was associated with current asthma, but fewer risks were observed for the use of green and home-made products.

The nipple region is characterized by special anatomical conditions and from a dermatological perspective can be divided into breast skin, skin of the areola and the skin of the nipple. In a clinical context the nipples are often altered during lactation by mechanical alteration, changes in the environment with maceration by the milk flow and by microbial pathogens. In addition, there is a risk of developing puerperal mastitis. Outside of pregnancy and lactation, eczema diseases are occasionally found on the mammary skin, often with atopic disposition (atopic nipple eczema) or as irritant contact eczema ("joggers nipple"). More rarely, allergic contact eczema is observed from preservatives in topical preparations or metals (piercings). Also, in the context of a scabies infestation involvement of the nipples, especially in women, is regularly observed. Of great clinical importance are rare preinvasive lesions of breast cancer or Paget's disease of the mamilla of the extramammary type. Due to the special anatomical conditions, it is obvious that specific penetration conditions are also derived from the application of topical substances. Experimental studies on human skin ex vivo suggest that depending on the molecular weight and solubility of the drug as well as the vehicle system used, a significant increase in cutaneous bioavailability, especially on the nipple itself through the transpapillary diffusion pathway, may occur. This should be considered in particular in the topical application of drugs with known potential of dose-dependent side effects (e.g. glucocorticoids); however, there is still no clinical evidence for this.Die Mamillenregion ist durch besondere anatomische Verhältnisse charakterisiert und lässt sich aus dermatologischer Perspektive in Brusthaut, Haut des Brustwarzenhofes (Areola) und Haut der Brustwarze (Papilla mammae) unterteilen. Im klinischen Zusammenhang sind die Brustwarzen häufig während der Stillzeit durch mechanische Beanspruchung, Milieuänderung mit Mazeration durch den Milchfluss sowie durch mikrobielle Erreger alteriert. Zudem besteht hier die Gefahr der Entwicklung einer Mastitis puerperalis. Außerhalb der Schwangerschaft und Stillzeit finden sich gelegentlich an der Mamillenhaut Ekzemerkrankungen, häufig bei atopischer Disposition (atopisches Mamillenekzem) oder als irritatives Kontaktekzem („joggers nipple“). Seltener werden allergische Kontaktekzeme auf Konservierungsstoffe von Topika oder Metallen (Piercings) beobachtet. Auch im Rahmen einer Skabiesinfestation wird eine Beteiligung der Mamillen, insbesondere bei Frauen, regelmäßig beobachtet. Von großer klinischer Bedeutung sind seltene, präinvasive Läsionen eines Mammakarzinoms oder der Morbus Paget der Mamille vom extramammären Typ. Durch die besonderen anatomischen Gegebenheiten ist es naheliegend, dass bei der Anwendung von Topika sich auch spezifische Penetrationsbedingungen ableiten. Experimentelle Untersuchungen an Humanhaut ex vivo legen nahe, dass in Abhängigkeit von der Molmasse und der Löslichkeit des Arzneistoffs sowie des eingesetzten Vehikelsystems eine deutliche Zunahme der kutanen Bioverfügbarkeit, insbesondere an der Brustwarze selbst durch den transpapillären Diffusionsweg, auftreten kann. Dies sollte insbesondere bei der topischen Anwendung von Arzneistoffen mit bekanntem dosisabhängigem Nebenwirkungspotenzial (z. B. Glukokortikoiden) beachtet werden. Allerdings fehlt dafür bisher eine klinische Evidenz.

The safety assessment of cosmetics considers the exposure of a ‘common consumer’, not the occupational exposure of hairdressers. This review aims to compile and appraise evidence regarding the skin toxicity of cysteamine hydrochloride (cysteamine HCl; CAS no. 156-57-0), polyvinylpyrrolidone (PVP; CAS no. 9003-39-8), PVP copolymers (CAS no. 28211-18-9), sodium laureth sulfate (SLES; CAS no. 9004-82-4), cocamide diethanolamine (cocamide DEA; CAS no. 68603-42-9), and cocamidopropyl betaine (CAPB; CAS no. 61789-40-0). A total of 298 articles were identified, of which 70 were included. Meta-analysis revealed that hairdressers have a 1.7-fold increased risk of developing a contact allergy to CAPB compared to controls who are not hairdressers. Hairdressers might have a higher risk of acquiring quantum sensitization against cysteamine HCl compared to a consumer because of their job responsibilities. Regarding cocamide DEA, the irritant potential of this surfactant should not be overlooked. Original articles for PVP, PVP copolymers, and SLES are lacking. This systematic review indicates that the current standards do not effectively address the occupational risks associated with hairdressers’ usage of hair cosmetics. The considerable irritant and/or allergenic potential of substances used in hair cosmetics should prompt a reassessment of current risk assessment practices.

Silicosis is a worldwide serious occupational disease that is caused by inhalation of silica crystals. However, little is known about the pathogenesis mechanism of silicosis. We performed single-cell sequencing in bronchoalveolar lavage fluid (BALF) from mine workers with silicosis and their co-workers who did not develop silicosis, and found that the RAB20 deficiency in monocytes/macrophages was strongly linked to the development of silicosis. In the silicosis murine model, RAB20 knockout markedly enhanced the silica crystal-induced pulmonary interstitial fibrosis and respiratory dysfunction. Moreover, this process is strongly accompanied by IL-1β release and NLRP3 activation.

Allergic rhinitis and asthma are common airway allergic diseases, the incidence of which has increased annually in recent years. The human body is frequently exposed to allergens and environmental irritants that trigger immune and inflammatory responses, resulting in altered gene expression. Mounting evidence suggested that epigenetic alterations were strongly associated with the progression and severity of allergic diseases. Noncoding RNAs (ncRNAs) are a class of transcribed RNA molecules that cannot be translated into polypeptides and consist of three major categories, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Previous studies showed that ncRNAs were involved in the physiopathological mechanisms of airway allergic diseases and contributed to their occurrence and development. This article reviews the current state of understanding of the role of noncoding RNAs in airway allergic diseases, highlights the limitations of recent studies, and outlines the prospects for further research to facilitate the clinical translation of noncoding RNAs as therapeutic targets and biomarkers.

BACKGROUND: Work is a substantial contributing factor of adult-onset asthma. A subtype of occupational asthma (OA) is caused by irritant agents, but knowledge of the clinical outcomes of irritant-induced asthma (HA) is incomplete. OBJECTIVES: To evaluate whether the clinical picture of IIA differs from that of sensitizer-induced OA. METHODS: This retrospective study analyzed acute and subacute IIA patients diagnosed in an occupational medicine clinic during 2004 to 2018. Sixty-nine patients fulfilled the inclusion criteria, and their characteristics were analyzed at the time of the diagnosis and 6 months later. The results were compared with those of 2 subgroups of sensitizer-induced OA: 69 high-molecular-weight (HMW) and 89 low-molecular-weight (LMW) agent-induced OA patients. RESULTS: Six months after the diagnosis, 30% of the patients with IIA needed daily short-acting beta-agonists (SABA), 68% were treated with Global Initiative for Asthma, 2020 report (GINA) step 4-5 medication, and 24% of the patients had asthma exacerbation after the first appointment. HA depicted inferiority to LMW-induced OA in daily need for SABA (odds ratio [OR]: 3.80, 95% confidence interval [CI]: 1.38-10.46), treatment with GINA step 4-5 medication (OR: 2.22, 95% CI: 1.08-4.57), and exacerbation (OR: 3.85, 95% CI: 1.35-11.04). HA showed poorer results than HMW-induced OA in the latter 2 of these features (OR: 2.49, 95% CI: 1.07-5.79 and OR: 6.29, 95% CI: 1.53-25.83, respectively). CONCLUSIONS: Six months after the OA diagnosis, a significant proportion of the patients with IIA remain symptomatic and the majority of these patients use asthma medications extensively suggesting uncontrolled asthma. The short-term outcomes of IIA appear poorer than that of sensitizer-induced OA. (C) 2022 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.

Eyelid dermatitis is a common dermatologic complaint.To characterize patients with eyelid dermatitis.Retrospective analysis (1994-2016) of North American Contact Dermatitis Group data.Of 50,795 patients, 2332 (4.6%) had eyelid dermatitis only, whereas 1623 (3.2%) also had dermatitis of the eyelids and head or neck. Compared with patients without eyelid involvement (n = 26,130), groups with eyelid dermatitis only and dermatitis of the eyelid and head or neck were significantly more likely to be female, white, and older than 40 years, and to have a history of hay fever, atopic dermatitis, or both (P .01). Final primary diagnoses included allergic contact dermatitis (eyelid dermatitis only: 43.4%; dermatitis of the eyelid and head or neck: 53.5%), irritant contact dermatitis (eyelid dermatitis only: 17.0%; dermatitis of the eyelid and head or neck: 9.8%), and atopic dermatitis (eyelid dermatitis only: 13.1%; dermatitis of the eyelid and head or neck: 13.8%). Top 5 currently relevant allergens included nickel sulfate (eyelid dermatitis only: 18.6%; dermatitis of the eyelid and head or neck: 22.5%), fragrance mix I (eyelid dermatitis only: 16.5%; dermatitis of the eyelid and head or neck: 18.3%), methylisothiazolinone (eyelid dermatitis only: 16.5%; dermatitis of the eyelid and head or neck: 17.7%), gold sodium thiosulfate (eyelid dermatitis only: 14.7%; dermatitis of the eyelid and head or neck: 11.4%), and balsam of Peru (eyelid dermatitis only: 11.9%; dermatitis of the eyelid and head or neck: 12.6%). Both eyelid-involvement groups were significantly more likely to react to gold sodium thiosulfate, carmine, shellac, dimethylaminopropylamine, oleamidopropyl dimethylamine, and thimerosal (P .05) compared with the no eyelid involvement group.Lack of specific distribution patterns of eyelid dermatitis and no long-term follow-up data.Patch testing remains a critical tool in evaluating patients with eyelid dermatitis.

Background Hand eczema (HE) is a heterogeneous and burdensome disorder. Objective To characterize the clinical characteristics, etiologies and allergen relevance in adults with HE referred for patch testing. Methods Retrospective analysis (2000-2016) of North American Contact Dermatitis Group data (n = 37,113). Results Overall, 10,034 patients had HE, with differences of overlap between allergic contact, irritant contact, and atopic dermatitis. Allergic contact HE fluctuated, whereas atopic HE steadily increased, and irritant HE decreased over time. HE was associated with higher proportions of positive patch tests (67.5% vs 63.8%; χ2, P Limitations No data on HE phenotype. Conclusion HE in adults was associated with higher proportions of positive patch tests, with a heterogeneous profile of allergens. Patch testing remains an important tool in the evaluation of patients with HE.

Background Scalp conditions are often multifactorial. Objective To characterize patients with scalp involvement and patch-testing outcomes. Methods Retrospective cross-sectional analysis of North American Contact Dermatitis Group data (1996-2016). Study groups included patients with scalp involvement (≤3 anatomic sites coded) with or without additional sites. Results A total of 4.8% of patients (2331/48,753) had scalp identified as 1 of up to 3 affected anatomic sites. Approximately one-third of "scalp-only" individuals had a specific primary diagnosis of allergic contact dermatitis (38.6%), followed by seborrheic dermatitis (17.2%) and irritant contact dermatitis (9.3%). When adjacent anatomic sites were affected, allergic contact dermatitis was more frequently identified as the primary diagnosis (>50%). The top 5 currently clinically relevant allergens in scalp-only patients were p-phenylenediamine, fragrance mix I, nickel sulfate, balsam of Peru, and cinnamic aldehyde. Methylisothiazolinone sensitivity was notable when adjacent anatomic sites were involved. The top 3 specifically identified sources for scalp-only allergens were hair dyes, shampoo/conditioners, and consumer items (eg, hair appliances, glasses). Limitations Tertiary referral population. Conclusion Isolated scalp involvement was less likely to be associated with allergic contact dermatitis than when adjacent anatomic sites were involved. Overlap with multiple diagnoses was frequent, including seborrheic dermatitis, irritant dermatitis, other dermatoses, or all 3. p-Phenylenediamine was the most common allergen.

Purpose Case series on respiratory features of Aerotoxic Syndrome (AS). The term AS has been coined to describe the spectrum of clinical manifestations after aircraft fume events. Among these manifestations, neurological and respiratory symptoms are the most frequently reported complaints. Methods Three cases of AS with relevant respiratory features are presented. Results Cough and shortness of breath for 6 to12 months were the predominant symptoms in the first two cases. The first case also developed neurological symptoms affecting his central nervous system. In the third case, the patient complained for nine years about an unbearable cough triggered by odors, smells, and a variety of indoor and outdoor irritants, among other symptoms of multiple chemical sensitivity. In all three cases, the respiratory symptoms resolved after appropriate treatment. Conclusion Our report aims at raising awareness on AS and calls for actions to improve the management of patients suffering from this syndrome.

None of the in vitro method are suitable for directly classifying of a substance as an eye irritant (category 2). They can classify substance as category 1 (serious eye damage) or as “no category” (not requiring classification). The aim of this study was to develop a new method for direct classification of a substance as category 2. Cytotoxicity Assay to Assess Eye Irritation (CEI) was performed on fibroblast - HDFn cell line with 36 substances. 5 concentrations of all substances and neat substances were applied directly to the cells. After 30 min, medium was added and cells were incubated at 37 °C. The next day, the cytotoxicity assay was performed (MTT assay in the first run and NRU assay in the second run). Based on viability and IC50 value (concentration with 50 % viability) a substance could be classified in category 2, category 1, and as “no category”. The results obtained were referred to ECHA database. This new method had high sensitivity (53.8–88.9 %), specificity (73.9–100.0 %) and accuracy (69.4–88.9 %) in the classification to all categories. It effectively classifies not only substances in category 2 but also in category 1 and substances that do not require classification.

Objective This cross-sectional study determined whether acute sensory irritative or (sub)chronic inflammatory effects of the eyes, nose or respiratory tract are observed in employees who are exposed to naphthalene at the workplace. Methods Thirtynine healthy and non-smoking male employees with either moderate (n = 22) or high (n = 17) exposure to naphthalene were compared to 22 male employees from the same plants with no or only rare exposure to naphthalene. (Sub)clinical endpoint measures included nasal endoscopy, smell sensitivity, self-reported work-related complaints and the intensity of naphthalene odor and irritation. In addition, cellular and soluble mediators in blood, nasal lavage fluid (NALF) and induced sputum (IS) were analysed. All measurements were carried out pre-shift on Monday and post-shift on Thursday. Personal air monitoring revealed naphthalene shift concentrations up to 11.6 mg/m3 with short-term peak concentrations up to 145.8 mg/m3 and 1- and 2-naphthol levels (sum) in post-shift urine up to 10.1 mg/L. Results Acute sensory irritating effects at the eyes and upper airways were reported to occur when directly handling naphthalene (e.g., sieving pure naphthalene). Generally, naphthalene odor was described as intense and unpleasant. Habituation effects or olfactory fatigue were not observed. Endoscopic examination revealed mild inflammatory effects at the nasal mucosa of exposed employees in terms of reddening and swelling and abnormal mucus production. No consistent pattern of cellular and soluble mediators in blood, NALF or IS was observed which would indicate a chronic or acute inflammatory effect of naphthalene in exposed workers. Conclusions The results suggest that exposure to naphthalene induces acute sensory irritative effects in exposed workers. No (sub)chronic inflammatory effects on the nasal epithelium or the respiratory tract could be observed under the study conditions described here.

Atopic dermatitis (AD) is a chronic relapsing inflammatory cutaneous disease that is often associated with other atopic symptoms, such as food allergy, allergic rhinitis and asthma, leading to significant morbidity and health-care costs. The pathogenesis of AD is complicated and multifactorial. Although the etiology of AD remains incompletely understood, recent studies have provided further insight into AD pathophysiology, demonstrating that the interaction among genetic predisposition, immune dysfunction, and environmental provocation factors contributes to its development. However, the increasing prevalence of AD suggests that environmental factors such as irritation and cutaneous infection play a crucial role in triggering and/or aggravating the disease. Of note, AD skin is susceptible to bacterial, fungal, and viral infections, and microorganisms may colonize the skin and aggravate AD symptoms. Overall, understanding the mechanisms by which these risk factors affect the cutaneous immunity of patients with AD is of great importance for developing a precision medicine approach for treatment. This review summarizes recent developments in exogenous factors involved in the pathogenesis of AD, with special emphasis on irritants and microbial infections.

Background Intravenous drug administration is associated with potential complications, such as phlebitis. The physiochemical characteristics of the infusate play a very important role in some of these problems. Aim The aim of this study was to standardize the dilutions of intravenous drugs most commonly used in hospitalized adult patients and to characterize their pH, osmolarity and cytotoxic nature to better guide the selection of the most appropriate vascular access. Methods The project was conducted in three phases: (i) standardization of intravenous therapy, which was conducted using a modified double-round Delphi method; (ii) characterization of the dilutions agreed on in the previous phase by means of determining the osmolarity and pH of each of the agreed concentrations, and recording the vesicant nature based on the information in literature; and (iii) algorithm proposal for selecting the most appropriate vascular access, taking into account the information gathered in the previous phases. Results In total, 112 drugs were standardized and 307 different admixtures were assessed for pH, osmolarity and vesicant nature. Of these, 123 admixtures (40%), had osmolarity values >600 mOsm/L, pH < 4 or > 9, or were classified as vesicants. In these cases, selection of the most suitable route of infusion and vascular access device is crucial to minimize the risk of phlebitis-type complications. Conclusions Increasing safety of intravenous therapy should be a priority in the healthcare settings. Knowing the characteristics of drugs to assess the risk involved in their administration related to their physicochemical nature may be useful to guide decision making regarding the most appropriate vascular access and devices.

Background This Phase 2, open-label study evaluated the safety, efficacy, systemic exposure, and impact on quality of life (QoL) with treatment using VP-102, a drug-device combination containing cantharidin (0.7% w/v) in subjects with molluscum contagiosum (MC). Study design Pediatric subjects with MC (2n15 years of age) were eligible to enroll in this 12-week study. MC lesions were treated topically with VP-102 every 21 days until clearance (maximum of 4 treatments). Adverse events (AEs) and QoL outcomes (using the Children's Quality of Life Index, CDLQI) were documented at each visit. Rate of complete clearance and the percent reduction in lesions were measured at each visit on days 21, 42, 63, and 84 (end of study [EOS] visit). A group of 17 subjects with at least 21 MC lesions was evaluated for systemic cantharidin exposure via plasma samples obtained before the first application of VP-102, and at 2 hours, 6 hours, and 24 hours post-application. Results A total of 33 subjects enrolled in the study (n=17 systemic exposure group, n=16 standard group). There were an equal number of male and female subjects. Subject mean (SD, range) age was 6.7 (3.3, 2n15) years, with a mean lesion count of 30 (26.1, 3n113). Complete lesion clearance was achieved in 48.5% of subjects, with a 90.4% reduction in lesions from baseline to the EOS visit. Mean CDLQI score decreased from 2.6 at baseline to 0.38 at the EOS visit. AEs were mild to moderate in severity and expected due to the pharmacodynamic action of cantharidin. There were no serious treatment-related adverse events and no study discontinuations due to treatment. In the systemic exposure group plasma cantharidin levels were below the lower limit of quantitation (LLOQ, 2.5 ng/mL) in 65 of 66 samples. Conclusions VP-102 treatment resulted in a reduction in lesion counts and improved QoL. Treated subjects had a 48.5% rate of complete clearance of molluscum lesions. Negligible systemic cantharidin exposure was observed in the systemic exposure group. This data demonstrates safety and efficacy of treatment with VP-102 in MC; a widespread viral infection that does not have any current FDA-approved treatments. Significant Finding: Treatment of subjects with MC using VP-102 resulted in negligible systemic cantharidin exposure, as well as a reduction in lesion counts, improved QoL, and a demonstrated efficacy in clearance of new and baseline MC lesions. Meaning: Results of this Phase 2 study demonstrate efficacy and safety outcomes in using VP-102 in MC subjects, and large randomized clinical trials are warranted to compare topical VP-102 with a vehicle control in order to fully evaluate the use of the medication. ClinicalTrials.gov identifier: NCT03186378 J Drugs Dermatol. 2021;20(1):70-75. doi:10.36849/JDD.2021.5626.