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Ethnopharmacological Relevance: The leaves of Artemisia argyi Levl.et Vant. have a long history of being used to treat skin diseases such as pruritus and dermatitis in China, but the therapeutic effect on allergic contact dermatitis (ACD) is still unclear., Aim of the Study: To investigate the effect and molecular mechanisms of the volatile oil of A. argyi leaves (abbreviated as 'AO') in the treatment of ACD., Materials and Methods: The main components in AO were analyzed using GC-MS. The effect of AO on channel currents in hTRPA1-transfected HEK293T cells was studied by whole-cell patch clamp. Subsequently, chloroquine-evoked acute itch and squaraine dibutyl ester (SADBE)-induced ACD chronic itch model was established to evaluate the antipruritic effect through counting scratching behavior, and the anti-inflammatory effects on ACD mice were measured using histological analysis. Meanwhile, the changes of CGRP, the infiltration of nerve fibers and the recruitment of dendritic cells, the expression of Il-23 and Il-17 mRNA in skin lesions, the phosphorylation of ERK and p38 in dorsal root ganglion (DRG), were evaluated by molecular biological methods. Then the inhibitory effect of AO on AITC- or SADBE-activated TRPA1 channels in primary DRG neurons of C57BL/6, Trpa1 -/- or Trpv1 -/- mice was elucidated by Ca 2+ imaging and immunofluorescence., Results: AO treatment inhibited the activation of TRPA1 in HEK293T cells and alleviated acute itch caused by chloroquine, but this effect was lacking in Trpa1 -/- mice. Furthermore, administration of AO attenuated scratching behavior in SADBE-induced ACD mice. AO also inhibited the increase of nerve fibers and recruitment of dendritic cells, and down-regulated the expression of CGRP and the levels of Il-23 and Il-17 mRNA. Meanwhile, AO reduced the expression of p-p38 and p-ERK in the lesioned skin and DRG of SADBE-induced ACD mice. Additionally, AO blocked the activation of TRPA1 channels and decreased the levels of CGRP, p-p38, and p-ERK in DRG neurons., Conclusion: AO could inhibit TRPA1 channels in sensory neurons, thereby reducing the release of CGRP and exerting anti-pruritic and anti-inflammatory effect. These findings also provide a new strategy for exploring the role of A. argyi in treating ACD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Allergic contact dermatitis (ACD) is a common inflammatory skin disease that accounts for approximately 20% of all occupational skin diseases. As an adverse and recurrent inflammatory dermatological agent, ACD shows insufficient response to current therapies largely owing to abnormal inflammatory activation and accompanying bacterial infection in lesions. Cold atmospheric plasma is a noninvasive fledgling reactive oxygen and nitrogen species (RONS)-based therapeutic technique for ACD treatment; however, its clinical adoption has been hindered due to the risk of electrical burns and insufficient delivery of the plasma-generated RONS. To address these limitations, we constructed plasma-activated AVC (PA-AVC) hydrogels loaded with plasma-generated RONS for ACD treatment as an alternative to the common direct plasma irradiation treatment. The proposed PA-AVC hydrogels were produced on a biodegradable acryloyldimethylammonium taurate/VP copolymer (AVC) with the aid of a novel air discharge plasma without the involvement of any catalyst. In vitro data showed that abundant RONS were produced and incorporated into the PA-AVC hydrogels via complex gas-liquid reactions between the air discharge plasma and hydrosolvent; additionally, the PA-AVC hydrogels exhibited excellent storage, slow release and transdermal delivery of RONS as well as good antibacterial effects. Moreover, in vivo experiments demonstrated that PA-AVC hydrogels effectively alleviated the ACD symptoms, such as skin redness and swelling, reduced epidermal thickening and inhibited mast cell infiltration and IL-9, TNF-α, and TSLP expression with no evident systemic toxicity. Our results revealed that long-acting plasma-activated AVC hydrogels could be effective therapeutic agents for local ACD treatment.

Background: Ferroptosis is considered as an immunogenic type of regulated cell death and associated with the pathogenesis of inflammatory skin diseases. However, the involvement and function of ferroptosis in allergic contact dermatitis (ACD) remains unknown., Objective: To explore the role of ferroptosis in ACD. To reveal which type of cells develops ferroptosis in ACD., Methods: We detected the key markers of ferroptosis in 1-Chloro-2,4-dinitrochlorobenzene (DNCB)-induced ACD mice model. We applicated ferrostatin-1 (Fer-1) to restrain ferroptosis in ACD mice and then compared the severity of dermatitis and the level of inflammation and ferroptosis in dermis and epidermis, respectively. Keratinocyte-specific Gpx4 conditional knockout (cKO) mice were used to investigate the function of keratinocyte ferroptosis in the development of ACD. Single-cell RNA sequencing was conducted to analyze the affection of Fer-1 on different type of cells in ACD., Results: Ferroptosis was involved in DNCB-induced ACD mice. Ferroptosis activation was more remarkable in dermis rather than in epidermis. Gpx4 cKO mice showed similar severity of skin dermatitis as control mice. Fer-1 alleviated skin inflammation in mice and reduced ferroptosis in neutrophils and CD8 + T cells both of which contribute to development of ACD., Conclusion: Ferroptosis was activated in immune cells, especially neutrophils and CD8 + T cells in DNCB-induced ACD mice. Fer-1 treatment inhibited ferroptosis of neutrophils and CD8 + T cells and relieved skin damage in ACD mice., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Contact dermatitis (CD) is a common and burdensome condition divided into irritant contact dermatitis and allergic contact dermatitis. Treatment relies on accurate diagnosis and identification of the trigger, because definitive treatment is irritant or allergen avoidance. However, avoidance is not always possible, such as when the patient is reacting to a necessary medical device, when the trigger is integral to the patient's occupation, and when avoidance is practically untenable. In these cases, treatment is particularly challenging, especially because the literature on treatments in this clinical scenario is limited. In addition, CD has a complex pathophysiology that varies according to the trigger type, leading to variable treatment efficacy. This article reviews the current literature on treatments for CD with a focus on treatments when trigger avoidance is not feasible., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

This study evaluated the therapeutic efficacy and underlying mechanisms of crisaborole combined with vitamin D in the treatment of allergic contact dermatitis. While crisaborole, a phosphodiesterase 4 inhibitor, and vitamin D analogs are commonly used in the treatment of atopic dermatitis, their combined therapeutic potential in allergic contact dermatitis (ACD) remains unexplored. Given their anti-inflammatory properties, we hypothesized that the combination of crisaborole and vitamin D could offer superior efficacy in mitigating the symptoms and underlying mechanisms of allergic contact dermatitis. In vitro, HaCaT cells stimulated with tumor necrosis factor-α and interferon-γ were treated with a combination of crisaborole and vitamin D, followed by cytokine expression analysis. In vivo, male C57BL/6 mice were divided into five groups and treated accordingly: blank control, dinitrochlorobenzene-induced model, crisaborole alone, vitamin D alone, and a combination of crisaborole and vitamin D. On day 14, dorsal skin and ear thickness were measured, followed by comprehensive pathological evaluations. In vivo and in vitro experiments showed that the expression levels of inflammatory factors were significantly lower in the DNCB + VD + Cri group than in the DNCB group. Histological analyses revealed that, compared with the DNCB group, the combined treatment group significantly reduced epidermal hyperkeratosis, improved epidermal transdermal water loss, decreased dermatitis scores, and diminished mast cell infiltration. Moreover, it lowered the expression levels of IL-6, IL-4, TNF-α, iNOS, IL-17, CC chemokine ligand 2 (CCL2), and CC chemokine receptor 2 (CCR2). CCL2 recognizes CCR2 and stimulates inflammatory cells, enhancing the inflammatory response. Increased CCL2 expression correlates with heightened inflammation and dendritic cell infiltration in ACD, while downregulation of CCL2 attenuates inflammation. Thus, the combined use of crisaborole and vitamin D demonstrates superior therapeutic efficacy over monotherapy in a mouse model of ACD. The combination of vitamin D and crisaborole significantly reduces inflammation and epidermal hyperkeratosis in a mouse model of allergic contact dermatitis, demonstrating superior therapeutic efficacy compared to either treatment alone. This suggests that the combined therapy could be a promising approach for the prevention and treatment of allergic contact dermatitis., (© 2024. The Author(s).)

Background: Chronic Hand Eczema (CHE) is a heterogeneous fluctuating inflammatory disease that represents a significant burden. Effective treatment options for moderate to severe CHE are limited., Objectives: To assess how patients with moderate to severe CHE are treated in clinical practice., Methods: A retrospective, physician-led patient record review assessed the demographic, clinical and treatment characteristics of patients aged ≥18 years with CHE across seven countries. Each participating physician was requested to review records for their three most recent patients with moderate to severe CHE treated with a topical or systemic therapy., Results: A total of 264 physicians, of whom 88.6% were dermatologists and 70.1% were predominantly or partly hospital-based, reviewed the records of 792 patients. Signs were present on hands only in 56.4% of patients and the mean time on current treatment was 16.7 months. Overall, 62.9% of patients received systemic therapy and almost one-quarter (23.4%) were treated with a biologic; 28.6% of patients were only treated with topical corticosteroids and/or topical calcineurin inhibitors., Conclusion: In patients with moderate to severe CHE, most received systemic therapy with one-quarter on biologic therapy. However, given that many of these treatments have limited evidence of efficacy in CHE, there is a need for studies specifically in patients with CHE as well as new therapeutic options., (© 2024 LEO Pharma. Contact Dermatitis published by John Wiley & Sons Ltd.)

Topical corticosteroids are commonly used to treat inflammatory skin conditions due to their anti-inflammatory properties. However, patients with long-lasting, non-responsive eczema have to be evaluated for a complicating contact allergy to the topical product. Clinical management of allergic contact dermatitis to corticosteroids can be challenging. The preventive measures should be tailored according to the sensitization patterns and supported by currently available classification systems to avoid cross-reactivity, as argued in this review., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Background: Overall adherence in the treatment of chronic dermatoses is poor. Textbooks state an adherence dependence on galenics., Trial Design: Prospective, randomized, parallel-grouped, single-blinded (investigator), monocentric clinical trial (phase IV) on the adherence to treatment of chronic mild to moderate hand eczema with topical methylprednisolone aceponate (MPA, Advantan®) in different vehicles., Objectives and Endpoints: Primary objective was the assessment of the adherence depending on vehicle type in patients with chronic hand eczema. Secondary objective was improvement after a 4-week treatment period. Primary Endpoint Adherence is defined as the percentage of patients applying at least aimed daily dose. Prescribed daily dose was defined as the planned number of applications per day (1) * surface (measured) * aimed amount per application (mg/cm 2 ). Truly applicated daily dose was evaluated as individual mean amount per dose * individual mean number of applications per day. Adherence was assumed, if truly applicated daily dose is at least 75% of the prescribed daily dose and the individual mean number of applications per day is at least 0.85. Secondary Endpoint Efficacy was measured by improvement of Hand Eczema Severity Index (HECSI) and Investigator's Global Assessment (IGA) after a 4-week treatment period and in addition to Quality of Life in Hand Eczema Questionnaire (QOLHEQ) and Visual Analogue Scale (VAS) to assess pruritus., Methods: Number of participants randomized to each group 40, 80 total. Group 1 MPA-C: Methylprednisolone aceponate 0.1% cream and barrier repair emollient (Bepanthen® Sensiderm). Group 2 MPA-FO: Methylprednisolone aceponate 0.1% fatty ointment and barrier repair emollient (Bepanthen® Sensiderm). Adherence to treatment was compared via Fisher's exact test., Results: Of the patients, 48% were adherent according to our definition. There was no significant difference between MPA-C (42.1%) and MPA-FO (54.1%; p = 0.36; group difference-12.0%, 95% CI-34.3%-11.5%). Generalized-linear-model-analysis of adherence to study treatment with factors emollient use, treatment, time and treatment-time interaction showed a parallel between adherence and amount of emollient use (odds ratio 1.74, p = 0.0038; 95% CI-1.22-2.52). Improvement of hand eczema was seen according to clinical scores without remarkable differences between the groups., Conclusions: No dependence of adherence on galenics of topical treatment of chronic hand eczema could be proved. Patients who use more emollient tend to be more adherent to the topical treatment., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Topical corticosteroids under occlusion have been used to enhance the treatment of eczema. However, no study has investigated the efficacy of a steroid-containing transdermal patch for the treatment of chronic hand eczema., Methods: We conducted a randomized, controlled, assessor-blinded trial to determine the efficacy of a transdermal patch containing betamethasone dipropionate compared to topical betamethasone dipropionate ointment in the treatment of mild to moderate chronic hand eczema. The patients were included and assigned to receive either the transdermal patch once daily at night or the ointment twice daily for a period of 8 weeks. The outcomes were assessed using the Hand Eczema Severity Index (HECSI), Physical Global Assessment (PGA) score, self-reported compliance, level of patient satisfaction, quality of life, and side effects., Results: Fifty-six patients completed this study. At 8 weeks, there was a significant reduction in the HECSI scores in both the transdermal patch and topical ointment groups compared to those measured at baseline (14.61 to 1.86, p < 0.001; 18.46 to 3.43, p < 0.001, respectively) without a statistically significant difference between the two groups. Similarly, the two groups did not show any significant difference in the PGA scores, quality of life and side effects. However, the transdermal patch group reported better compliance and a higher level of patient satisfaction than the topical ointment group., Conclusion: The transdermal corticosteroid patch has proven to be a safe and effective treatment, comparable to topical corticosteroids, after 8 weeks of use. Its sustained-release properties, along with once-daily use, can improve patient satisfaction and promote greater adherence to the treatment., Trial Registration: This study was registered with the Thai Clinical Trials Registry (www., Clinicaltrials: in.th) under registration number TCTR20220413003., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Endothelial protein C receptor (EPCR) is a receptor for the natural anti-coagulant activated protein C (aPC). It mediates the anti-inflammatory and barrier-protective functions of aPC through the cleavage of protease-activated receptor (PAR)1/2. Allergic contact dermatitis is a common skin disease characterized by inflammation and defective skin barrier. This study investigated the effect of EPCR and 3K3A-aPC on allergic contact dermatitis using a contact hypersensitivity (CHS) model. CHS was induced using 1-Fluoro-2,4-dinitrobenzene in EPCR-deficient (KO) and matched wild-type mice and mice treated with 3K3A-aPC, a mutant form of aPC with diminished anti-coagulant activity. Changes in clinical and histological features, cytokines, and immune cells were examined. EPCRKO mice displayed more severe CHS, with increased immune cell infiltration in the skin and higher levels of inflammatory cytokines and IgE than wild-type mice. EPCR, aPC, and PAR1/2 were expressed by the skin epidermis, with EPCR presenting almost exclusively in the basal layer. EPCRKO increased the epidermal expression of aPC and PAR1, whereas in CHS, their expression was reduced compared to wild-type mice. 3K3A-aPC reduced CHS severity in wild-type and EPCRKO mice by suppressing immune cell infiltration/activation and inflammatory cytokines. In summary, EPCRKO exacerbated CHS, whereas 3K3A-aPC could reduce the severity of CHS in both EPCRKO and wild-type mice.

Background: Allergic contact dermatitis (ACD) is prevalent among pediatric population, adolescent and young adults. Patients with ACD experience a lot of sociopsychological and qualityof- life (QoL) difficulties. Children and their caregivers alike are vulnerable to the burden of ACD., Objectives: We have, in this paper, provided an overview of ACD and discussed common and unusual causes of ACD., Methods: We performed an up-to-date literature review in the English language on "allergic contact dermatitis" via PubMed Clinical Queries, using the keywords "allergic contact dermatitis" in August 2022. The search included meta-analyses, randomized controlled trials, clinical trials, casecontrol studies, cohort studies, observational studies, clinical guidelines, case series, case reports, and reviews. The search was restricted to English literature and children., Results: ACD may be acute or chronic and it affects more than 20% of children and adults with significant quality-of-life impairments. ACD is manifested by varying degrees of cutaneous edema, vesiculation, and erythema. The hypersensitivity reaction is one of the most prevalent forms of immunotoxicity in humans. Localized acute ACD lesions can be managed with high-potency topical steroids; if ACD is severe or extensive, systemic corticosteroid therapy is often required to provide relief within 24 hours. In patients with more severe dermatitis, oral prednisone should be tapered over 2-3 weeks. Rapid discontinuation of corticosteroids can result in rebound dermatitis. Patch testing should be performed if treatment fails and the specific allergen or diagnosis remains unknown., Conclusion: ACD is common and can be a physically, psychologically, and economically burdensome disease. Diagnosis of ACD is primarily based on history (exposure to an allergen) and physical examination (morphology and location of the eruption). Skin patch test can help determine the causative allergen. Allergen avoidance is the cornerstone of management. Topical mid- or highpotency corticosteroids are the mainstay of treatment for lesions on less than 20% of the body area. Severe cases of ACD may require treatment with systemic corticosteroids., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Tissue-resident memory T (T RM ) cells are detrimental in allergic contact dermatitis (ACD), in which they contribute to the chronicity and severity of the disease., Methods: We assessed the impact of a standard topical corticosteroid (TCS) treatment, triamcinolone acetonide (TA), on the formation, maintenance and reactivation of epidermal T RM cells in a preclinical model of ACD to 2,4-dinitrofluorobenzene. TA 0.01% was applied at different time points of ACD response and we monitored skin inflammation and tracked CD8+ CD69+ CD103+ T RM by flow cytometry and RNA sequencing., Results: The impact of TA on T RM formation depended on treatment regimen: (i) in a preventive mode, that is, in sensitized mice before challenge, TA transiently inhibited the infiltration of effector T cells and the accumulation of T RM upon hapten challenge. In contrast, (ii) in a curative mode, that is, at the peak of the ACD response, TA blocked skin inflammation but failed to prevent the formation of T RM . Finally, (iii) in a proactive mode, that is, on previous eczema lesions, TA had no effect on the survival of skin T RM , but transiently inhibited their reactivation program upon allergen reexposure. Indeed, specific T RM progressively regained proliferative functions upon TA discontinuation and expanded in the tissue, leading to exaggerated iterative responses. Interestingly, T RM re-expansion correlated with the decreased clearance of hapten moieties from the skin induced by repeated TA applications., Conclusions: Our results demonstrate that TCS successfully treat ACD inflammation, but are mostly ineffective in impeding the formation and expansion of allergen-specific T RM , which certainly restricts the induction of lasting tolerance in patients with chronic dermatitis., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Programmed cell death receptor/ligand 1 (PD-1/PD-L1) blockade therapy for various cancers induces itch. However, few studies have evaluated the mechanism underlying PD-1/PD-L1 inhibitor-induced itch. This study aimed to establish and evaluate a mouse model of acute itch induced by PD-1/PD-L1 inhibitors and to explore the role of the PD-1/PD-L1 pathway in chronic itch. The intradermal injection of the PD-1/PD-L1 small molecule inhibitors, or anti-PD-1/PD-L1 antibodies in the nape of the neck in the mice elicited intense spontaneous scratches. The model was evaluated using pharmacological methods. The number of scratches was reduced by naloxone but not by antihistamines or the transient receptor potential (TRP) channel inhibitor. Moreover, the PD-1 receptor was detected in the spinal cord of the mouse models of chronic itch that exhibited acetone, diethyl ether, and water (AEW)-induced dry skin, imiquimod-induced psoriasis, and 1-fluoro-2,4-dinitrobenzene (DNFB)-induced allergic contact dermatitis. Intrathecal PD-L1 (1 μg, 4 times a week for 1 week) suppressed the activation of the microglia in the spinal dorsal horn to relieve the chronic itch that was elicited by imiquimod-induced psoriasis and DNFB-induced allergic contact dermatitis. Although the activation of the microglia in the spinal dorsal horn was not detected in the AEW-treated mice, intrathecal PD-L1 still reduced the number of scratches that were elicited by AEW. Our findings suggest that histamine receptor inhibitors or TRP channel inhibitors have limited effects on PD-1/PD-L1 inhibitor-induced itch and that spinal PD-1 is important for the spinal activation of the microglia, which may underlie chronic itch., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Parthenium dermatitis is the commonest form of plant dermatitis in India, caused by the plant Parthenium hysterophorus. Systemic immunosuppressives are commonly employed in its treatment. However, there is a relative lack of comparative head-to-head trials. This study was done to assess the relative efficacy and safety of systemic treatments in Parthenium dermatitis. We systematically reviewed all the published studies investigating the safety and efficacy of systemic treatments for Parthenium dermatitis in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and clinical trial registries. Treatment benefit data were tabulated based on outcome measures of scoring systems. The quality of evidence for each outcome was assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria for meta-analysis. The pooled Standardized mean difference (SMD) for case series and comparative studies based on clinical severity score (CSS) for azathioprine was 4.007 (95% CI (Confidence interval): 3.141, 4.873) and 0.746 (95% CI: 0.139, 1.352), respectively. About 88.8% (95% CI: 76.8%, 100.8%, p = 0.076) of the patients had excellent or a good response to azathioprine. Our meta-analysis shows that azathioprine has the highest level of evidence in the treatment of Parthenium dermatitis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objectives: Allergic contact dermatitis is a common type IV hypersensitivity reaction characterised by redness, itching, oedema and thickening of the skin. It occurs in about 7% of the population and its incidence is increasing. It has been observed that the preconditioning of tissues by exposing them to transient ischemia increases resistance to subsequent permanent ischemia, and this phenomenon is called ischemic preconditioning. It has been shown that conditioning in one organ can also protect other organs. The protective effect of remote ischemic preconditioning is thought to be based on the induction of anti-inflammatory responses. The aim of this project was to investigate the anti-inflammatory and antipruritic effects of remote ischemic postconditioning in a mouse model of experimental allergic contact dermatitis. Methods: Experimental allergic contact dermatitis was induced with 1-fluoro-2,4-dinitrobenzene. Remote ischemic postconditioning was performed at 3 and 25 h after the challenge. Ear thickness and number of scratches 24 and 48 h after challenge, as well as cytokine levels and the infiltration of mast cells, neutrophils, CD4 + and CD8 + T lymphocytes in serum and ear tissue at 48 h were measured to determine the effect of RIPsC. Results: Remote ischemic postconditioning decreased ear thickness, one of the symptoms of allergic contact dermatitis ( p < 0.0001). It had no significant effect on the number of scratches. It reduced serum IL-17 levels ( p < 0.01). It alleviated local inflammation by suppressing CD8 + T lymphocyte and neutrophil infiltration. Conclusions: It was concluded that remote ischemic postconditioning may alleviate the symptoms of allergic contact dermatitis by suppressing CD8 + T lymphocyte and neutrophil infiltration and reducing IL-17 secretion.

PDE4 inhibitors are expected to be anti-inflammatory agents based on their mechanism of action, but the application of this drug class is limited by a narrow therapeutic window due to adverse effects associated with gastrointestinal function. Difamilast, a novel selective phosphodiesterase 4 (PDE4) inhibitor, demonstrated significant efficacy without adverse reactions such as nausea and diarrhea in patients with atopic dermatitis (AD) and was recently approved in Japan. In this study, we investigated the pharmacological and pharmacokinetic properties of difamilast to provide nonclinical data to help understand the clinical effects. Difamilast selectively inhibited recombinant human PDE4 activity in assays. The IC 50 of difamilast against PDE4B, a PDE4 subtype that plays an important role in the inflammatory response, was 0.0112 μ M, representing a 6.6-fold decrease compared with the IC 50 against PDE4D (0.0738 μ M), a subtype that can trigger emesis. Difamilast inhibited TNF- α production in human (IC 50 = 0.0109 μ M) and mouse (IC 50 = 0.0035 μ M) peripheral blood mononuclear cells and improved skin inflammation in a mouse model of chronic allergic contact dermatitis. These effects of difamilast on TNF- α production and dermatitis were superior to those of other topical PDE4 inhibitors: CP-80633, cipamfylline, and crisaborole. In pharmacokinetic studies using miniature pigs and rats, the concentrations of difamilast in the blood and brain after topical application were not sufficient to support pharmacological activity. This nonclinical study contributes to explain the efficacy and safety of difamilast with a sufficient therapeutic window in the clinical trials. SIGNIFICANCE STATEMENT: This is the first report on the nonclinical pharmacological profile of difamilast ointment, a novel topical PDE4 inhibitor that demonstrated utility in clinical trials in patients with atopic dermatitis. Difamilast, which has high PDE4 selectivity (especially for the PDE4B subtype), ameliorated chronic allergic contact dermatitis in mice after topical application, with a pharmacokinetic profile in animals that suggests few systemic side effects; thus, difamilast is a promising new therapeutic treatment for atopic dermatitis., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

Allergic contact dermatitis (ACD) is a common skin disorder caused by contact with allergens. The optimal treatment for ACD is to avoid contact with allergens. However, in some cases, avoiding exposure is not possible when the allergens are unknown. Therefore, establishing treatment methods other than allergen avoidance is important. We previously reported that the continuous administration of methionine, an essential amino acid, in a mouse model of atopic dermatitis alleviated its symptoms. In the present study, we investigated the effect of methionine on a mouse model of ACD caused by 1-fluoro-2,4-dinitrobenzene (DNFB). Differences in the effect of methionine were observed in DNFB-induced ACD model mice based on the mouse strain used. This difference was attributed to the suppression of hepatic dimethylglycine (DMG) production, which is associated with the suppression of hepatic betaine-homocysteine methyltransferase (Bhmt) expression by ACD. Although we did not reveal the mechanism underlying DMG suppression, our study suggests the presence of interactions between the liver and skin in dermatitis, such as the regulation of hepatic metabolic enzyme expression in dermatitis and the alleviation of dermatitis symptoms by the hepatic metabolism status of DMG.

Ethnopharmacological Relevance: The seeds of Entada phaseoloides (Linn.) Merr. commonly named "Ke-teng-zi" is a traditional Chinese folk medicine and reported to treat dermatitis, spasm, and headache. However, the exact effect and the mechanism of Ke-teng-zi on the treatment of dermatitis is unclear., Aim of the Study: To elucidate the antipruritic effect and molecular mechanisms of Ke-teng-zi on the treatment of allergic contact dermatitis (ACD)., Materials and Methods: The main components of the n-butanol fraction of 70% ethanol extract from Ke-teng-zi (abbreviated as KB) were analyzed by HPLC. The chloroquine (CQ)-induced acute itch and squaraine dibutyl ester (SADBE)-induced ACD chronic itch in mice was established, and the TNF-α/IFN-γ stimulated Human keratinocytes (HaCaT) were used to evaluate the antipruritic and anti-inflammatory effects of KB. Behavioral tests, lesion scoring, and histology were also examined. The expression levels of molecules in MAPK and JAK/STAT3 pathways, the mRNA levels of chemokines and cytokines in both the skin of ACD mice and the HaCaT cells were detected by western blot and qPCR. Furthermore, whole-cell patch-clamp recordings in TRPA1-tranfected HEK293T cells were used to elucidate the effect of KB on TRPA1 channels. TRPA1 siRNA was used to evaluate the role of TRPA1 in the anti-inflammatory effect of KB in keratinocytes., Results: The main compounds in KB could bind to the active sites of TRPA1 mainly through hydrogen bond and hydrophobic bond interactions. KB could inhibit the scratching behavior in CQ-induced acute itch, and the inhibitory effect of KB was blocked by TRPA1 inhibitor HC-030031. In addition, KB significantly decreased the scratching bouts of ACD mice, reduced the skin lesion scores, mast cells degranulation, and epidermal thickening, inhibited the production of inflammatory chemokines/cytokines and CGRP, and down-regulated the levels of p-ERK1/2, p-p38, and p-STAT3, compared to the ACD mice. Moreover, continuous application of KB induced the desensitization of TRPA1 channels. Also, KB inhibited the expression of p-ERK1/2, p-p38, and p-STAT3, and down-regulated the expression of inflammatory chemokines and cytokines in vitro, which were reversed by the TRPA1 siRNA., Conclusions: KB alleviated the pruritus and skin inflammation in ACD mice through TRPA1 channels desensitization and down-regulation of intracellular MAPK and JAK/STAT3 signaling pathways. Our results suggested that Ke-teng-zi is a potential drug for the treatment of inflammatory skin diseases such as ACD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Allergic contact dermatitis (ACD) is a common allergic inflammatory disease that is concomitant with skin swelling, redness, dry itching, and relapses. Prinsepia utilis Royle, a Chinese and Indian folk medicine, is rich in polyphenols with potential anti-inflammatory and skin-protective activities. However, the underlying mechanism of P. utilis leaf (PUL) in the treatment of ACD and its functional basis remains unclear., Aim of the Study: This study is aimed to explore and reveal the active substances and mechanism of PUL against ACD., Materials and Methods: Hyaluronidase inhibitory assay and fluorescein isothiocyanate (FITC)-induced ACD mouse model were performed to assess the antiallergic effects of PUL in vitro and in vivo. Different solvents were applied to obtain multiple PUL extracts. The extracts were further tested for total phenolic content (TPC) and total flavonoid content (TFC) by using spectrophotometric assays. Polyphenolic profiles were analyzed by using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), and a simultaneous quantification method was established using UPLC-QTrap-MS/MS through multiple reaction monitoring (MRM) and applied to analyze the pharmacokinetics of the multiple major polyphenols of PUL in mice., Results: The water extract of PUL with the highest TPC/TFC exhibited the strongest antihyaluronidase effect (IC 50  = 231.93 μg/mL). In vivo assays indicated that the oral administration of PUL water extract dose-dependently attenuated ACD-like symptoms by decreased interleukin (IL)-4, IL-5, IL-13, IL-33, thymic stromal lymphopoietin, and IgE production, suppressed eosinophil and basophil secretion, and increasing the expression of tight junction (TJ) proteins (claudin-1 [CLDN-1] and occludin). Concomitantly, UPLC-QTOF-MS/MS analysis enabled the identification of 60 polyphenols and the pharmacokinetic parameters of seven quantified constituents of PUL were characterized. Four compounds, trans-p-coumaric acid 4-O-β-D-glucopyranoside (11), vicenin-2 (21), isoschaftoside (31), and kaempferol 3-O-(2″,6″-di-O-α-L-rhamnopyransoyl)-β-D-glucopyranoside (38) which displayed satisfactory pharmacokinetic features, were considered as potential effective substances in PUL., Conclusions: PUL water extract ameliorated the allergic inflammation of ACD by repairing the epithelial barrier and alleviating Th2-type allergic inflammation. The anti-allergic effect of PUL is closely related to its phenolic substances, and compounds 11, 21, 31, and 38 were the active substances of PUL. It revealed that P. utilis could be developed as a new source of antiallergic agents for ACD therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Allergic contact dermatitis is one of the most common recorded occupational diseases. There are many different substances that the skin comes into contact with on a daily basis and that can cause ACD, e.g., preservatives, surfactants, and antimicrobial agents. The development of a mouse model of ACD has provided insight into the immune mechanisms involved. Drugs used in the treatment of skin diseases have many side effects. Therefore, alternative methods of suppressing the immune response to reduce the symptoms of skin diseases are being sought. In recent years, high hopes have been placed on dietary modulation and supplementation to affect the intestinal microbial composition and promote anti-inflammatory responses. In addition, other studies have shown the crucial role of intestinal microbiota in many immune-mediated diseases. Recognition and characterization of pro- and anti-inflammatory nutrients and supplements may be crucial to support the treatment of diseases such as atopic dermatitis, acne vulgaris, psoriasis, and allergic contact dermatitis., (© 2023. The Author(s).)

Allergic contact dermatitis (ACD) and atopic dermatitis (AD) are the most common human skin disorders. Although corticosteroids have been widely used to treat ACD and AD, the side effects of corticosteroids encourage researchers to explore new immunoregulatory treatments. Here, an immunomodulatory approach based on lipid nanoparticles carrying α-helical configurational melittin (α-melittin-NP) is developed to overcome T cell-mediated inflammatory reactions in an oxazolone (OXA)-induced contact hypersensitivity mouse model and OXA-induced AD-like mouse model. Intradermal injection of low-dose α-melittin-NPs prevents the skin damage caused by melittin administration alone and efficiently targeted lymph nodes. Importantly, melittin and α-melittin-NPs restrain RelB activity in dendritic cells (DCs) and further suppresses dendritic cell activation and maturation in lymph nodes. Furthermore, low-dose α-melittin-NPs leads to relief of antigen recognition-induced effector T cell arrest in the dermis and inhibited allergen-specific T cell proliferation and activation. Significantly, this approach successfully controls Th1-type cytokine release in the ACD model and restricts Th2-type cytokine and IgE release in the AD-like model. Overall, intradermal delivery of low-dose α-melittin-NPs efficiently elicits immunosuppression against T cell-mediated immune reactions, providing a promising therapeutic strategy for treating skin disorders not restricted to the lesion region., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Janus kinase (JAK) inhibitors represent a promising class of small molecule inhibitors that treat a range of inflammatory skin diseases, such as atopic dermatitis (AD), psoriasis, and alopecia areata. Although the evidence for their use in allergic contact dermatitis (ACD) remains limited, early results from animal studies and case reports are promising. Herein, we provide an overview of JAK inhibitors and the evidence for their use in ACD.

Objectives: Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms., Methods: Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions., Results: Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1β, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1β, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05)., Conclusions: Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.

Ethnopharmacological Relevance: In treating atopic dermatitis, multi-mode management is adopted, including trying to avoid the allergens, controlling and preventing secondary infections, and using drugs to control itching. At present, most of the commonly used anti-pruritic drugs in the clinic are single-target and lead to serious side effects. Many studies have shown that a variety of traditional Chinese medicines have significant anti-inflammatory and anti-pruritic effects, and have the characteristics of multiple components, multiple targets, and multiple effects., Aim of the Study: The study aimed to explore the anti-inflammatory and anti-pruritic effects of the Chi-Huang Solution in a murine model of Allergic contact dermatitis (ACD). This study considers the effectiveness of the Chi-Huang Solution for external use on skin to provide an experimental basis for the clinical development and application of Chinese medicine and related preparations for Canine atopic dermatitis (CAD)., Materials and Methods: Forty-two male SPF C57BL/6 mice were randomly divided into control group (n = 6), ACD model group (n = 6), HAC control group (n = 6), and 4 Chi-Huang Solution groups (n = 6 in each group). With SADBE induce the murine model of ACD chronic pruritus, and initially evaluate whether the model is successful by counting scratching behavior, measuring the skin fold thickness and skin lesion score within 1 h. After treating the ACD model mice with deionized water, HAC, 1CH, 2CH, 3CH, and 4CH for 7 days, behavioral changes were used to evaluate the anti-pruritic effect. The skin fold thickness, skin lesion score, and spleen index were used to evaluate the anti-inflammatory effect of the Chi-Huang Solution. H.E. staining was used for the epidermal thickness measurement and pathological evaluation. RT-qPCR was used to analyze the mRNA expression of related inflammatory factors such as IL-1β, TNF-α, IL-33, IL-4, IL-17A, CXCL10, and its receptor CXCR3 in the skin of the lesion site, as well as to detect the mRNA expression of pruritus-related genes such as TRPV1, TRPA1, and GRP in DRG., Results: After the treatment of low-dose (0.1 g/mL) and medium-dose (0.2 g/mL) Chi-Huang Solution, the scratching times both decreased significantly (P < 0.05), meanwhile the medium-dose Chi-Huang Solution had an obvious effect on reducing scratches/scab score (P < 0.05). Moreover, no matter what dose it takes, all Chi-Huang Solution can alleviate the epidermal thickening (P < 0.05) and the infiltration of mast cells in the ACD murine model of ACD. It is worth mentioning that the count of mast cells in the dermis was significantly down-regulated after the treatment of medium-dose Chi-Huang Solution (P < 0.005). Furthermore, Chi-Huang Solution can significantly down-regulate the mRNA expression of related inflammatory factors in the skin, and reduce the mRNA expression of pruritus-related genes, such as TRPA1, TRPV1, and GRP in the spinal cord., Conclusions: The results indicated that Chi-Huang Solution for external use exhibits significant anti-inflammatory and anti-pruritic effects on SADBE-induced ACD chronic pruritus murine models. Chi-Huang Solution might emerge as an effective drug for the treatment of CAD and high-dose Chi-Huang Solution (0.4 g/ml) has better comprehensive effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Ocular allergies to brimonidine are frequent in patients treated for glaucoma. There is variability in reporting due to the lack of diagnostic criteria and the absence of cutaneous testing. Many false-negative patch tests (PT) have been described. Alternative methods, such as strip and scratch PT, have been used without a standardized method., Objectives: The primary objective is to identify the best method of cutaneous testing and brimonidine concentration for patch testing. The secondary objective is to identify clinical signs and symptoms suggestive of ocular allergy., Patients and Methods: A retrospective review of patient files suspected of brimonidine ocular allergy was performed. Patch testing method, brimonidine concentration and clinical symptoms were reviewed., Results: Of the 36 patients identified, half tested positive for brimonidine for at least one of the testing methods. The scratch PT demonstrated 17 positive reactions (94% detection rate). Three patients reacted with strip PT. No positive results were found with standard PT. The 5% brimonidine concentration demonstrated the highest sensitivity. The absence of eyelid pruritus was associated with negative testing., Conclusion: In the investigation of ocular allergy to brimonidine, scratch PT proved to be an essential tool. Brimonidine 5% pet. appeared as the most sensitive concentration for scratch PT., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: The present study aimed to investigate the potential of epimedin A to ameliorate DNFB-induced allergic contact dermatitis (CD) and reveal its potential underlying mechanisms of action, emphasizing its role in modulating NF-κB/NLRP3, Nrf2/HO-1 pathways, and inflammation., Main Methods: Seven-week-old BALB/c mice received epimedin A orally for 11 days at doses of 5, 10, or 20 mg/kg/day, starting from the seventh day of DNFB-inducing CD., Key Findings: Epimedin A dose-dependently ameliorated DNFB-induced CD, as revealed by the repression of the mice's scratching behavior, dermatitis score, ear thickness and weight, and ear tissue's histopathological changes, and area percent of collagen fibers induced by DNFB. These potentials were due to the NF-κB/NLRP3 pathway suppression and the Nrf2 pathway enhancement, as demonstrated by the reduction of NF-κB, NLRP3, ASC, caspase-1, and 8 mRNA expression, and NF-κBp65, IL-1β, MDA levels, and NF-κBp65 binding activity, along with the enhancement of the Nrf2, HO-1, IκB-α, GSH levels, SOD activity, and Nrf2 binding activity. Besides, it suppressed ear tissues' NLRP3 and caspase-8 induced pyroptosis by suppressing the ear tissues' caspase-1, 8, GSDMD upregulation, and LDH activity. Additionally, it repressed the local inflammatory reaction of ear tissue, as evidenced by the reduction of the elevated inflammatory cytokines (IL-1β, IL-6, Il-4, TNF-α, and IFN-γ), the serum level of t-IgE, DNFB s-IgE, s-IgE/t-IgE ratio, and the abrogation of the ear tissues histopathological changes., Significance: Epimedin A is a novel, hopeful, natural therapeutic agent for CD by modulating NF-κB/NLRP3, Nrf2 pathways, and inflammation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Allergic contact dermatitis (CD) is a chronic inflammatory skin disease caused by type 1 biased adaptive immunity for which there is an unmet need for antigen (Ag)-specific immunotherapies. Exposure to skin sensitizers stimulates secretion of the proinflammatory neuropeptides substance P and hemokinin 1, which signal via the neurokinin-1 receptor (NK1R) to promote the innate and adaptive immune responses of CD. Accordingly, mice lacking the NK1R develop impaired CD. Nonetheless, the role and therapeutic opportunities of targeting the NK1R in CD remain to be elucidated., Objective: We sought to develop an Ag-specific immunosuppressive approach to treat CD by skin codelivery of hapten and NK1R antagonists integrated in dissolvable microneedle arrays (MNA)., Methods: In vivo mouse models of contact hypersensitivity and ex vivo models of human skin were used to delineate the effects and mechanisms of NK1R signaling and the immunosuppressive effects of the contact sensitizer NK1R antagonist MNA in CD., Results: We demonstrated in mice that CD requires NK1R signaling by substance P and hemokinin 1. Specific deletion of the NK1R in keratinocytes and dendritic cells, but not in mast cells, prevented CD. Skin codelivery of hapten or Ag MNA inhibited neuropeptide-mediated skin inflammation in mouse and human skin, promoted deletion of Ag-specific effector T cells, and increased regulatory T cells, which prevented CD onset and relapses locally and systemically in an Ag-specific manner., Conclusions: Immunoregulation by engineering localized skin neuroimmune networks can be used to treat cutaneous diseases that like CD are caused by type 1 immunity., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Allergic contact dermatitis (ACD) has been estimated to affect up to 20% of the general population. Patch testing is the gold standard for identification of causative allergens. When allergen avoidance fails, current treatment options include topical and oral corticosteroids, systemic immunosuppressants, and phototherapy. Dupilumab, a monoclonal antibody targeting IL-4/IL-13, is approved by the US Food and Drug Administration for the treatment of moderate to severe atopic dermatitis. It also has been used off label with some success in the treatment of ACD. This article discusses the evidence for using dupilumab to treat ACD as well as considerations for patch testing in patients who are taking this medication.

Background: Although the Mas-related G-protein-coupled receptors (Mrgprs) play essential roles in itch detection, their contribution to allergic contact dermatitis (ACD)-associated itch remains unclear., Objectives: To investigate whether Mrgprs are involved in ACD and whether Mrgprs can be identified as potential therapeutic targets., Methods: Mrgpr-clusterΔ -/- mice and human MrgprX1 (hMrgprX1) transgenic mice were used to evaluate the function of Mrgprs in oxazolone-induced ACD., Results: Utilizing an ACD model, we found that Mrgpr-clusterΔ -/- mice display significantly reduced pruritus. Among 12 Mrgprs deleted in Mrgpr-clusterΔ -/- mice, the expression of MrgprC11 and MrgprA3 was significantly increased in the ACD model, which also innervated the skin and spinal cord at higher-than-normal densities. The proportions of dorsal root ganglia neurons responding to bovine adrenal medulla peptide 8-22 and chloroquine were also remarkably increased in the ACD model, resulting in enhanced itch behaviour. To study the function of human Mrgprs in ACD-induced itch, we used hMrgprX1 transgenic mice, which rescued the severe itch defect of Mrgpr-clusterΔ -/- mice in the ACD model. Remarkably, pharmacological blockade of hMrgprX1 significantly attenuates ACD itch in hMrgprX1 transgenic mouse., Conclusions: Our study provides the first evidence that Mrgprs are involved in ACD-induced chronic itch, which provides new avenues for itch management in ACD., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Juzentaihoto (JTT) is a Kampo prescription that has been used clinically for treating skin diseases such as atopic dermatitis in Japan. We have previously studied the anti-allergic effects of JTT on 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) in mice and demonstrated that it significantly suppresses ear swelling in a dose-dependent manner. However, the mechanism underlying the anti-allergic actions of JTT is obscure., Methods: We investigated the mechanism underlying the anti-allergic effects of JTT using a TNCB-induced murine CHS model and adoptive cell transfer experiments., Results: We showed that the anti-allergic effects of JTT are due to inhibition of effector T-cell activation and induction and/or activation of regulatory T cells. Furthermore, ex vivo experiments confirmed the effect of JTT on the activation of effector T cells and regulatory T cells, as interferon-γ production decreased, whereas interleukin (IL)-10 production increased, in the cultured lymphocytes obtained from 5% TNCB-sensitized mice treated with anti-CD3ε and anti-CD28 monoclonal antibodies. Flow cytometry showed that the CD4+CD25+Foxp3+, CD4+CD25+Foxp3-, and CD8+CD122+ cell population increased after oral administration of JTT. Finally, the anti-allergic effect of JTT by inducing and/or activating regulatory T cells (Tregs) was confirmed to be mediated by IL-10 through in vivo neutralization experiments with anti-IL-10 monoclonal antibodies., Conclusion: We suggested that JTT exerts anti-allergic effects by regulating the activation of effector T cells and Tregs involved in murine CHS model., (© 2021 S. Karger AG, Basel.)

Allergies are highly prevalent hypersensitivity responses to usually harmless substances. They are mediated by the immune system which causes pathologic responses such as type I (rhinoconjunctivitis, allergic asthma, atopy) or type IV hypersensitivity (allergic contact dermatitis). The different types of allergy are mediated by effector and memory T cells and, in the case of type I hypersensitivity, B cells. A prerequisite for the activation of these cells of the adaptive immune system is the activation of the innate immune system. The resulting inflammation is essential not only for the initiation but also for the elicitation and maintenance of allergies. Great progress has been made in the elucidation of the cellular and molecular pathomechanisms underlying allergen-induced inflammation. It is now recognized that the innate immune system in concert with tissue stress and damage responses orchestrates inflammation. This should enable the development of novel mechanism-based anti-inflammatory treatment strategies as well as of animal-free in vitro assays for the identification and potency classification of contact allergens., (© 2021. Springer Nature Switzerland AG.)

Thymic stromal lymphopoietin (TSLP), positioned at the top of the inflammatory cascade, is a key regulator that enhances allergic inflammatory responses by activating T helper type 2 cells, Group 2 innate lymphoid cells (ILC2), and myeloid dendritic cells (mDCs) via the TSLP receptor (TSLPR). We evaluated the inhibitory effects of ASP7266, a novel recombinant fully human IgG 1 monoclonal antibody against TSLPR, on TSLP signaling and inflammation. The inhibitory effects of ASP7266 and the control antibody tezepelumab on TSLP and TSLPR interactions were investigated using a proliferation assay with TSLP stimulation and a chemokine production assay. The pharmacological effects of ASP7266 were investigated by examining differentiation of naive CD4 + T cells, ILC2 cytokine production, and ascaris extract-induced skin allergic reaction in cynomolgus monkeys. ASP7266 potently inhibited TSLP-induced cell proliferation and C-C motif chemokine ligand 17 production. Furthermore, ASP7266 inhibited TSLP-stimulated mDC-mediated naive CD4 + T-cell differentiation and interleukin 5 production by lineage-negative peripheral blood mononuclear cells, which can be considered ILC2 in vitro. In sensitized monkeys, ASP7266 completely suppressed ascaris extract-induced allergic skin reactions. Based on these results, ASP7266, a novel human therapeutic antibody against TSLPR, is a potential therapy for patients with allergic diseases. SIGNIFICANCE STATEMENT: TSLP, positioned at the top of the inflammatory cascade, plays a key role in various allergic diseases, including asthma, chronic rhinosinusitis with nasal polyposis, and atopic dermatitis. Here we show that the anti-TSLPR antibody ASP7266 exhibited excellent pharmacological activity in preclinical studies. Therefore, ASP7266 has the potential to be a promising treatment option for patients with allergic disorders., (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: Occupational contact dermatitis may progress to a chronic course with an unfavorable prognosis. Dupilumab has been shown to be effective as a treatment for moderate-to-severe atopic dermatitis as well as other types of dermatitis., Objectives: The aim of the study was to describe cases of chronic recalcitrant occupational contact dermatitis treated with dupilumab and with long-term follow-up., Methods: A retrospective review of 6 patients treated with dupilumab for chronic occupational contact dermatitis for periods of up to 30 months was performed., Results: All 6 patients had a positive and sustainable response, with dermatitis clearance and the ability to sustain work tasks., Conclusions: We report a case series of atopic and nonatopic workers with occupational chronic contact dermatitis who failed to achieve remission under various systemic modalities but did so using dupilumab. We suggest considering dupilumab treatment for recalcitrant occupational contact dermatitis., (© 2022 The Author(s). Published by S. Karger AG, Basel.)