Therapy Of Atopic Dermatitis Research Articles

Translated article] BIOBADATOP Spanish Atopic Dermatitis Registry: Description and Early Findings

BackgroundIn recent years, remarkable improvements in our understanding of atopic dermatitis (AD) have revolutionized treatment perspectives, but access to reliable data from clinical practice is essential. Materials and methodThe Spanish Atopic Dermatitis Registry, BIOBADATOP, is a prospective, multicenter database that collects information on patients of all ages with AD requiring systemic therapy with conventional or novel drugs. We analyzed the registry to describe patient characteristics, diagnoses, treatments, and adverse events (AEs). ResultsWe studied data entries for 258 patients who had received 347 systemic treatments for AD. Treatment was discontinued in 29.4% of cases, mostly due to a lack of effectiveness (in 10.7% of cases). A total of 132 AEs were described during follow-up. Eighty-six AEs (65%) were linked to a systemic treatment, most commonly dupilumab (39 AEs) and cyclosporine (38 AEs). The most common AEs were conjunctivitis (11 patients), headache (6), hypertrichosis (5), and nausea (4). There was 1 severe AE (acute mastoiditis) associated with cyclosporine. ConclusionsInitial findings on AEs from the Spanish BIOBADATOP registry are limited by short follow-up times precluding comparisons or calculation of crude and adjusted incidence rates. At the time of our analysis, no severe AEs had been reported for novel systemic therapies. BIOBADATOP will help answer questions on the effectiveness and safety of conventional and novel systemic therapies in AD.

Probiotic-fermented Portulaca oleracea L. alleviated DNFB-induced atopic dermatitis by inhibiting the NF-κB signaling pathway

Ethnopharmacological relevanceProbiotic fermentation is a mild and safe biological method to boost the performance of herbs. Portulaca oleracea L. (PO), with folklore records of purgative, anti-dermatological and anti-epidemic effects, has been demonstrated to possess anti-inflammatory, immunomodulatory, and antioxidant properties. However, the potential of PO for the treatment of atopic dermatitis (AD) has not been sufficiently explored. Aim of studyThis study aimed to evaluate the therapeutic benefits of PO and fermented Portulaca oleracea L. (FPO) and explore their intrinsic mechanisms. MethodsBy utilizing 2,4-dinitrofluorobenzene-induced AD mice as a model, the histopathology of the lesions was observed using H&E and toluidine blue staining methods; the levels of immunoglobulin E (Ig E), histamine (HIS), and thymic stromal lymphopoietin (TSLP) in serum were measured using ELISA, whereas, the expression of inflammatory cytokines in skin lesion was measured using ELISA and immunohistochemistry experiments. The expression of tumor necrosis factor-α (TNF-α), IKKα, NF-κB mRNA was measured using qPCR; and the expression of TNF-α、p-IKKα, p-IκBα, p-NF-κB was measured using western blotting. ResultsBoth 20 mg/mL PO and FPO alleviated mast cell infiltration and lesion pathology, reduced serum levels of Ig E, HIS and TSLP, down-regulated the expression of AD-related inflammatory cytokines, such as, TNF-α, interferon-γ, and interleukin-4, and increased filaggrin expression. Furthermore, they inhibited the expression of TNF-α, IKKα, and NF-κB genes and TNF-α, p-IKKα, p-NF-κB and p-IκBα proteins associated with the NF-κB signaling pathway. ConclusionsPO and FPO has a positive therapeutic potential on AD, indicating that it may be employed as alternative therapies for AD.

Evaluation of effectiveness of complex therapy for atopic dermatitis in children and adolescents using transcranial magnetic therapy

Today, the development and implementation of modern physiotherapeutic treatment options, including those safe for home use by patients, is promising.Purpose of the study. Studying the safety and effectiveness of transcranial magnetotherapy with mild and moderate severity of atopic dermatitis.Material and methods. The study was attended by 104 patients, aged 5 to 16 years, with a prescription of the disease from 2 months to 16 years. Patients were divided into groups: the 1st group received standard therapy, in the 2nd group they combined standard therapy and placebo in physiotherapeutic treatment, patients of the 3rd groups used transcranial therapy in monotherapy, participants of the 4th group were on combined therapy – transcranial magnetotherapy and standard.Results. According to the study, the effectiveness of transcranial magnetotherapy is based on a positive effect on the state of the central nervous system and its autonomic department, which is accompanied by the relief of clinical symptoms, itching and helps to improve psychoemotional status.Conclusions. The use of transcranial magnetotherapy in a complex with standard therapy helps to relieve clinical symptoms of atopic dermatitis and the quality of life of patients.

Atopic dermatitis in skin of colour. Part 2: considerations in clinical presentation and treatment options.

Recent advances in atopic dermatitis (AD) present the condition as a heterogeneous disease of distinct endotypes across ethnic groups. AD in people with skin of colour may appear psoriasiform, lichenoid, scaly or papular, with a violaceous colour and there is a higher prevalence of post-inflammatory dyspigmentation compared with affected individuals of White ethnicity. These differences in clinical presentation may limit the use of AD assessment tools in people with skin of colour, leading to the potential for misdiagnosis and underestimation of severity, particularly in relation to assessment of erythema. Recent targeted therapies for AD have been studied in multiple ethnic groups; however, ethnicity-based subgroup analysis is often not performed. Further research is required to understand whether treatment responses or safety may differ among ethnic groups.

Efficacy of short-term combination of intralymphatic allergen immunotherapy and lokivetmab treatment in canine atopic dermatitis: A double-blinded, controlled, randomised study.

Allergen-specific immunotherapy (ASIT) is an effective therapy for canine atopic dermatitis (cAD). Intralymphatic immunotherapy (ILIT) is potentially beneficial in decreasing time to clinical effectiveness. To compare clinical efficacy of six monthly ILIT injections combined with three monthly injections of lokivetmab (LVM) with monthly LVM monotherapy at Day (D)168. To monitor dogs treated with ILIT for an additional six months of subcutaneous immunotherapy (SCIT). Thirty-six client-owned dogs with cAD. In this double-blinded, randomised study, dogs received either six monthly injections of ILIT combined with three monthly LVM injections (ILIT group) or six monthly LVM injections (LVM group). Monthly evaluations with pruritus Visual Analogue Scale (pVAS), Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) and medication scores (MS) were undertaken. Owners completed a Quality of Life (QoL) questionnaire. Treatment success was predefined as ≥50% reduction in pVAS and CADESI-04 score ≤ 10. After D168, the ILIT group continued with SCIT until subjective assessment at 12 months. The treatment benchmark at D168 was achieved by 11.1% of the ILIT group and 11.8% of LVM group. A significant decrease in mean pVAS and CADESI scores was observed in both groups (p < 0.001). The ILIT group had a trend towards higher MS compared to LVM. QoL was better in LVM (p = 0.01). At 12 months subjective good-to-excellent response in 77.8% of dogs in the ILIT/SCIT group was seen. The efficacy of this ILIT protocol was comparable with LVM monotherapy at six months. When ILIT was continued with SCIT, a favourable response was seen.

MiRNAs' Cross-Involvement in Skin Allergies: A New Horizon for the Pathogenesis, Diagnosis and Therapy of Atopic Dermatitis, Allergic Contact Dermatitis and Chronic Spontaneous Urticaria.

Skin inflammation is a common underlying feature of atopic dermatitis, allergic contact dermatitis and chronic spontaneous urticaria. The pathogenetic mechanisms have not been fully elucidated. The purpose of this study was to examine whether miRNA, by regulating inflammatory mechanisms through the modulation of innate and adaptive immune responses, could play a major role in the pathogenesis of these skin conditions. We conducted a narrative review using the Pubmed and Embase scientific databases and search engines to find the most relevant miRNAs related to the pathophysiology, severity and prognosis of skin conditions. The studies show that miRNAs are involved in the pathogenesis and regulation of atopic dermatitis and can reveal an atopic predisposition or indicate disease severity. In chronic spontaneous urticaria, different miRNAs which are over-expressed during urticaria exacerbations not only play a role in the possible response to therapy or remission, but also serve as a marker of chronic autoimmune urticaria and indicate associations with other autoimmune diseases. In allergic contact dermatitis, miRNAs are upregulated in inflammatory lesions and expressed during the sensitization phase of allergic response. Several miRNAs have been identified as potential biomarkers of these chronic skin conditions, but they are also possible therapeutic targets.

ПРОФИЛАКТИЧЕСКОЕ ПРИМЕНЕНИЕ ЭМОЛЕНТОВ У ДЕТЕЙ С АТОПИЧЕСКИМ ДЕРМАТИТОМ И ПЫЛЬЦЕВОЙ СЕНСИБИЛИЗАЦИЕЙ В СЕЗОН ЦВЕТЕНИЯ РАЗЛИЧНЫХ РАСТЕНИЙ: ОДНОЦЕНТРОВОЕ ПРОСТОЕ ОТКРЫТОЕ ПРОСПЕКТИВНОЕ СРАВНИТЕЛЬНОЕ ИССЛЕДОВАНИЕ

Penetration of pollen allergens through the damaged skin barrier in patients with atopic dermatitis (AD) can lead to a worsening of the severity of the disease in sensibilized patients during the flowering season, however, the preventive effect of agents that restore the structure of the epidermal barrier has not been studied enough as yet. The purpose of this research was to study the clinical efficacy and safety of the La Roche-Posay Lipikar Syndet AP+ and Lipikar AP+M cosmetic products for the prevention of AD exacerbations in children during the flowering season. Materials and methods used: a single-center prospective experimental randomized comparative open study was conducted in Apr. 22-Jul. 11, 2022. The study included 19 children aged 6 to 15 y/o with AD sensibilized to pollen allergens. The two groups were formed: patients in the main group used Lipikar for 28 days and received standard AD therapy during the flowering period; patients in the control group received the standard AD therapy only. The severity of AD was evaluated with the SCORAD as well as the quality of life, pruritus intensity and corneometry were assessed during each of the three visits to pediatric allergologists. Changes in SCORAD were considered the primary endpoint of the research. Results: a statistically significant decrease in SCORAD were revealed by the 14th day of the study (p=0.007) in the main group; whilst at the same time there were no statistically significant decrease in SCORAD in the control group. It was also found that the quality of life improved statistically significantly by the 28th day of the study (p=0.001) in patients of the main group when evaluated the secondary endpoints of the study. The pruritus intensity decreased statistically significantly (p=0.002) by the 14th day of the study; the skin hydration increased (p=0.001) as well (compared to the control group). Conclusion: the use of the Lipikar Syndet AP+ and Lipikar AP+M in children in the complex therapy of AD during the flowering season of causally significant allergens statistically significantly reduced the severity of AD, reduced the pruritus intensity, improved skin hydration and quality of life.

643 Incidence of conjunctivitis adverse event with biological therapies in atopic dermatitis: A systematic review and meta-analysis

643 Incidence of conjunctivitis adverse event with biological therapies in atopic dermatitis: A systematic review and meta-analysis

Influence of the cream with filaggrin activity modulator for dry and sensitive skin in children with mild to moderate severity atopic dermatitis on objective indicators of skin barrier function and disease severity indices

BACKGROUND: Atopic dermatitis is a chronic, relapsing and severely itchy dermatitis that usually occurs in childhood and has a characteristic age-related distribution. Atopic dermatitis is relatively frequent, affecting 1020% of children in developed countries. Atopic dermatitis in children associated with poor school performance, low self-esteem and family problems. Recent studies show importance in atopic dermatitis pathogenesis of protein filaggrin and modulation of its activity may be a promising direction in the pathogenic therapy of atopic dermatitis.&#x0D; AIM: to study the effect of a cream for dry, sensitive and atopic skin with a modulator of filaggrin activity on the course of mild and moderate atopic dermatitis.&#x0D; MATERIAL AND METHODS: An open, prospective, multicentre, non-comparative, single-group clinical trial was organized to test the effectiveness of a cream with a filaggrin activity modulator. The study was on outpatients in the participated centers and included 5 visits with a screening visit 1, and 5th visit ― therapy completion. Cream was used for 12 weeks. In total, the study involved 60 children aged 3 to 18 years with diagnoses of atopic dermatitis of mild and moderate severity. The severity of atopic dermatitis was measured with the SCORAD, EASI, IGA scales, also measured was skin pH and transepidermal water loss (TEWL), as well as the severity of xerosis according to visual analogue scale.&#x0D; RESULTS: The severity of atopic dermatitis in children whose therapy regimens included Admera cream decreased by 19.6 points according to the SCORAD index, including in children who did not receive mometasone furoate in the therapy schemes, the SCORAD index decreased statistically significantly compared to the baseline data (p 0.001). The overall decline in the EASI index ― by 3.0 points, the IGA global assessment index ― by 2.0 points, the severity of xerosis decreased by 3 points (in all cases, p 0.001). Transepidermal water loss decreased (by 4.5 g/m2 per hour, p 0.001); Skin pH did not change (difference 0.02, p=0.34). The smell was rated as "excellent" by 86.7% (95% CI 75.494.1), the consistency ― by 83.3% (95% CI 71.591.7) of the respondents, and overall satisfaction was noted by ― 88.3% (95% CI 77.495.2) of the respondents.&#x0D; CONCLUSION: Сream for dry and sensitive skin with a modulator of filaggrin activity during the study showed good efficacy and tolerability and can be used in atopic dermatitis treatment regimens as a basic care product, both during exacerbation and remission.

The role of modern emollients in prophylaxis of atopic dermatitis exacerbation during pollination season

BACKGROUND: Skin epidermal barrier impairment in patients with atopic dermatitis facilitates percutaneous penetration of allergens and leads to persistent skin inflammation in sensitized patients and even primary sensitization to the allergens. We hypothesized that the use of skincare products that restore the structure of the skin barrier may positively affect the disease course in patients with atopic dermatitis and pollen sensitization during the pollen season.&#x0D; AIMS: This study aimed to investigate the clinical efficacy and safety of La Roche Posay formulas, i.e., Lipikar Syndet and Lipikar Baume AP+M, in the prevention of atopic dermatitis exacerbations in children and adults sensitized to different pollen allergens during the pollination season.&#x0D; MATERIALS AND METHODS: Sixty patients aged 560 years with a clinical history of mild-to-moderate atopic dermatitis sensitized to different pollen allergens were enrolled in a single-center, simple, open, prospective comparative study, and they were divided into two groups. The main group used Lipikar Syndet and Baume AP+M daily together with standard atopic dermatitis treatment for 28 days during the pollen season of their clinically significant allergens. The control group received only standard therapy without any use of moisturizers. The study required three visits. At each visit, the severity of atopic dermatitis (SCORing atopic dermatitis [SCORAD] index), quality of life (Dermatology Life Quality Index/and Childrens Dermatology Life Quality Index), pruritus intensity (numerical rating scale), and corneometry were assessed. SCORAD changes were considered the primary endpoint of the study.&#x0D; RESULTS: A significant decrease in SCORAD in the main group was registered by day 14 of the study (p 0.0001), whereas no significant changes in the SCORAD index were noted in the control group even by day 28. The SCORAD index in the main group was significantly lower than that in the control group (p=0.005) by day 28. For the secondary endpoints, the quality of life significantly improved by day 28 (p=0.0005), the intensity of pruritus significantly decreased (p 0.0001), and the level of skin hydration increased (p 0.0001) by day 14 in the main group compared with those in the control group. No adverse events were reported during the study.&#x0D; CONCLUSIONS: Daily use of Lipikar Syndet and Lipikar Baume AP+M by patients with atopic dermatitis and pollen allergy during the pollen season significantly improved the atopic dermatitis course, reducing skin itching and improving skin hydration and patients quality of life. The use of these skincare products together with atopic dermatitis therapy helped reduce atopic dermatitis severity associated with direct skin contact with pollen allergens. This indicates a protective effect of Lipikar skincare products on the epidermal barrier function.

In vitro and in vivo exploration of the anti-atopic dermatitis mechanism of action of Tibetan medicine Qi-Sai-Er-Sang-Dang-Song decoction.

Tibetan medicine Qi-Sai-Er-Sang-Dang-Song Decoction(QSD, ཆུ་སེར་སེང་ལྡེང་སུམ་ཐང་།)is a traditional Tibetan medical formulation with demonstrated clinical benefits in atopic dermatitis (AD). However, its potential mechanism and molecular targets remain to be elucidated. This study aims to explore the activity and mechanism of QSD on AD in multiple dimensions by combining in vitro and in vivo experiments with network pharmacology. The AD effect of QSD was investigated by evaluating the levels of nitric oxide (NO) and interleukin-6 (IL-6) in the lipopolysaccharide (LPS) stimulated RAW264.7cells. AD-like skin lesions in female BALB/c mice were induced by 2,4-dinitrochlorobenzene (DNCB). QSD or dexamethasone (positive control) were gavagely administered daily for 15 consecutive days. The body weight and skin lesion severity were recorded throughout the study. Enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) analysis were used to illuminate the molecular targets associated with the anti-AD effects of QSD. Meanwhile, the ingredients of QSD in the blood were revealed and analyzed by Ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method. Network pharmacology was used to predict the targets and mechanism of active ingredient therapy for AD. In addition, the network pharmacology outcomes were further verified by molecular docking. After treatment with QSD, the levels of NO and IL-6 were decreased in the cell supernatant. Herein, QSD markedly decreased the eosinophil and mast cells infiltration in the dorsal skin of the 2,4-dinitrochlorobenzene. Moreover, QSD reconstructed the epidermal barrier by increasing the content of collagen fibers and changing the arrangement of DNCB-treated mice. QSD not only inhibited the levels of tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) but also inhibited phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) proteins in the dorsal skin. Four active ingredients were identified through UPLC-Q-TOF/MS, including (-)-epicatechin, kaempferol-7-O-glucoside, cassiaside, and questin. After the network pharmacological analysis, six core targets of QSD closely related to AD were obtained, including TNF-α, IL-6, Caspase-3 (CASP3), Epidermal growth factor (EGFR), Peroxisome proliferator-activated receptor gamma (PPARG), and Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1). Meanwhile, through Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, the Mitogen-activated protein kinase (MAPK) signaling pathway occupies an important position in the QSD treatment of AD. The molecular docking results showed that the six core targets are stable in binding to the four active ingredients as indicated by the molecular docking results. The anti-AD effect of QSD might be related to the reconstruction of the epidermal barrier and inhibition of inflammation, which regulated the MAPK pathway. Hence, it provided a promising idea for the study of Tibetan medicine prescriptions for the treatment of AD.

Exosome therapy in atopic dermatitis – A way to look forward

Exosome therapy in atopic dermatitis – A way to look forward

Detection and treatment of skin infection with Staphylococcus aureus in children with atopic dermatitis

Introduction. Atopic dermatitis is a common chronic relapsing inflammatory multifactorial skin disease. Staphylococcus aureus skin colonization increases during disease outbreaks and correlates with the severity of skin symptoms. Purpose - to evaluate the effectiveness of thyrothricin gel as an adjuvant therapy in the treatment of atopic dermatitis and the influence of polymorphisms of pattern recognition receptors on the achieving a therapeutic effect. Materials and methods. This study included patients with atopic dermatitis (n=37) aged 2-18 years from the Allergy Department of the Kyiv City Children’s Clinical Hospital No. 2. Patients were devided into two groups: a group that received thyrothricin gel on the affected skin areas 2 times a day for 7 days (the Group A) and a control group (the Group B) that received only basic symptomatic therapy. SCORAD (SCORing AD) and CDLQI (Children’s Quality of Life Index in Dermatology) scores were recorded before and after treatment, side effects were recorded during the study. Skin swabs were taken in the Group A before and after treatment. Genotyping of polymorphisms rs4696480 in the TLR2 gene, rs7309123 in the Dectin-1 gene were performed using polymerase chain reaction. Results. In both groups of children, improvement was observed in 7 days after treatment (p&lt;0.001). In the Group A, the improvement in ΔSCORAD was 16.6±5.9 points, in the Group B - 8.1±4.5 points. The difference in ΔSCORAD scores between the Groups A and B was statistically significant (W=225.0, p&lt;0.001). The decrease in CDLQI score after treatment was 3.8±1.8 points in the Group A and 2.3±1.25 points in the Group B. A significant decrease in CDLQI score was demonstrated in the intervention group than in the control group after treatment (W=275.5, p=0.004). After treatment, a bacteriological examination of the skin demonstrated the eradication of Staphylococcus aureus: in the Group A, 94.4% of patients were Staphylococcus aureus-negative. Polymorphisms rs4696480 in the TLR2 gene and rs7309123 in the Dectin-1 gene did not affect the speed of achieving the therapeutic effect. Conclusions. The addition of thyrothricin to standard therapy for atopic dermatitis in children with Staphylococcus aureus infection of affected skin may provide significant clinical benefit in SCORAD and CDLQI scores. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patients was obtained for conducting the studies. No conflict of interests was declared by the author.

Клінічний ефект застосування персикової олії з вітамінами А, Е, D зовнішньо на шкіру в дітей з атопічним дерматитом

Vitamins A, E, D play an extremely important role in ensuring the normal functioning of the skin and mucous membranes, an adequate immune response, and maintaining resistance to various adverse external factors. The impact of vitamins A, E, D, and the relationship between their availability and the susceptibility to skin allergies continues to be studied. Peach oil is widely used in medicinal ointments and creams for dermatitis, and vitamins are successfully used in the systemic treatment of atopic dermatitis in children. The possibility of combined external application of peach oil and vitamins A, E, D to the skin in atopic dermatitis in children is of scientific interest. Purpose - to study, evaluate and analyze the clinical effect of combined external application of peach oil and vitamins A, E, D on the skin in atopic dermatitis in children. Materials and methods. During the research, 64 children with atopic dermatitis and 32 children of the control group aged from 1 to 17 years were examined. Сomparative assessment of the clinical effect of traditional and improved complex therapy of 64 children with atopic dermatitis. Improved complex therapy included the external application on the skin of peach oil with vitamins A, E, D twice a day during four weeks. General clinical, immunological, questionnaires and statistical research methods were used. Results. The research of different variants for the treatment of atopic dermatitis in children showed better clinical effect of improved complex therapy with the external application on the skin of peach oil with vitamins A, E, D, which was accompanied by a decrease in the prevalence and intensity of skin manifestations, itching, normalization of sleep and it was confirmed by a decrease in the SCORAD index, a decrease markers of allergic inflammation - concentrations of leukocytes, eosinophils and histamine in the blood. The significant improvement in the course of the disease was noted under the influence of improved complex treatment compared to traditional therapy. Conclusions. The combined external application on the skin of peach oil and vitamins A, E, D with atopic dermatitis in children contributes to a significantly faster reduction of the skin signs such as dryness / flaking, xerosis/hyperkeratosis, lichenization/lichenification, erythema/hyperemia, edema/papules, excoriations/scratches, microvesiculation, exudation/wetting, hemorrhagic and serous crusts, hyperpigmentation, compared to traditional therapy of atopic dermatitis in children. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Autologous Th2-polarized lymphocytes induce atopic dermatitis lesions in non-atopic human skin xenotransplants.

The key signals that suffice to induce atopic dermatitis (AD) in human skin remain incompletely understood. Also, current mouse models reflect human AD only unsatisfactorily. Therefore, we have asked whether a humanized AD mouse model can be developed that reflects human AD more faithfully and permit to identify key signals that suffice to induce AD lesions in previously healthy human skin in vivo. Healthy human skin from non-atopic donors was transplanted onto SCID/beige mice. After xenotransplant reinnervation by mouse sensory nerve fibers had occurred, mixed autologous human Th2 CD4+ and Tc2 CD8+ T cells that had been pretreated in vitro with IL-2, IL-4, and LPS were injected intradermally into the xenotransplants without skin barrier disruption. Injected non-atopic xenotransplants rapidly developed a morphological, functional, and immunological phenocopy of human AD lesions regarding skin barrier defects, immunopathology including intraepidermal eosinophils, mast cell activation, increase of thymic stromal lymphopoietin, eotaxin-1 and type 2 cytokine circuits, and even showed characteristic neuroimmunological abnormalities such as ß2-adrenergic receptor downregulation. The experimentally induced AD lesions in human skin responded to standard AD therapy (topical dexamethasone or tacrolimus; systemic anti-IL-4Rα antibody [dupilumab]), and relapsed when neurogenic skin inflammation was induced by exposing mice to perceived stress. This new animal model uniquely mimics the complexity of human AD and its clinical response to standard therapy and psychoemotional stressors in vivo, and shows that Th2-polarized lymphocytes associated with excessive IL-4Rα-mediated signaling suffice to induce human AD skin lesions, while atopy and epidermal barrier disruption are dispensable.

Atopic dermatitis – Perspectives and unmet medical needs

Atopic dermatitis (AD) is a chronic inflammatory skin disease for which many new insights have been gained in recent years through a better understanding of pathophysiology, concomitant diseases and therapeutics in particular. In this review, new and practice-relevant results from current research are presented. Many studies have been performed on the diagnosis of AD and on different subtypes, yet no diagnostic biomarker or clinical predictor of treatment response has been established. For topical treatment, some agents such as Janus kinase (JAK) inhibitors are in advanced stages of clinical trials or already approved in some countries, which will be available in Europe for the treatment of certain eczema subtypes in the foreseeable future. Current systemic therapies in Europe include two antibodies for inhibition of the interleukin (IL)-4/13 signaling cascades and three oral JAK inhibitors with somewhat different efficacy and safety profiles. Among the antibody therapies for AD already advanced in development, promising new targets include blockade of IL-31, of neurokinin-1 receptor on sensory neurons, and inhibition of the OX40/OX40L axis for cutaneous dendritic cell and T lymphocyte interaction. Primary prevention and modulation of sequential disease progression as well as effects on concomitant diseases by early therapeutic intervention will be important questions in future research on AD.

Anti-inflammatory and immunomodulatory effects of polysaccharide extracted from Wuguchong (maggot) on 2,4-dinitrochlorobenzene-induced atopic dermatitis in mice.

Atopic dermatitis (AD) is an inflammatory, heterogeneous, chronic skin disorder characterized by recurrent eczematous lesions and intense pruritus, and the pathophysiology mechanism of AD is known for immune dysregulation and inflammatory responses. Wuguchong (maggot) has been widely used in the wound field and found with pharmacological properties of the anti-inflammatory and immunomodulatory function. Recently, some polysaccharides were proven to have beneficial effects on AD skin lesions in mice and humans. However, the effect of the polysaccharide extracted from Wuguchong (PEW) on AD remains to be investigated. In the present study, we examined the anti-inflammatory and immunomodulatory effects of PEW on AD and explored the potential mechanisms. Balb/c mice were orally administrated with PEW to evaluate the therapeutic effect of PEW on 2,4-dinitrochlorobenzene (DNCB)-induced AD. Oral PEW administration significantly ameliorated the lesions and symptoms in AD mice, such as the ear thickness and ear swelling degree, epidermal and dermal thickness, and the infiltration of mast cells. In addition, PEW treatment decreased the levels of serum IgE and histamine, the frequencies of Th1 and Th17 cells, as well as the mRNA expression levels of Th1 and Th17 cytokines and nuclear transcript factors (IFN-γ, T-bet, IL-17A, and ROR-rt). Furthermore, the activation of the NF-κB pathway and the phosphorylation of MAPKs (p38, ERK, and JNK) were significantly suppressed by PEW treatment. Taken together, our study suggests that PEW exerts anti-inflammatory and immunomodulatory effects through inhibition of Th1 and Th17 responses and downregulation of NF-κB and MAPK pathways, PEW would be developed as a promising immune therapy for AD.

A Digital Self-help Intervention for Atopic Dermatitis: Analysis of Secondary Outcomes From a Feasibility Study.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by dry skin, eczematous lesions, and an often severe pruritus. The disease may have a negative effect on quality of life and is also associated with symptoms of anxiety and depression. Few individuals with AD receive any form of behavioral intervention. Behavioral interventions for AD are potentially efficacious but need to be constructed so that they are safe, credible, and user-friendly. We have previously reported on a feasibility study that demonstrated that a self-management version of a digital intervention based on cognitive behavioral therapy (CBT) for AD can potentially be effective in reducing AD symptoms. The aim of this secondary report was to further examine treatment feasibility and preliminary effects on dermatological quality of life, itching sensations, depressive symptoms, and perceived stress. This is a secondary report on intervention credibility, usability, adverse events, and preliminary effects on secondary measures of a self-management digital intervention for atopic dermatitis. In total, 21 adults with AD, recruited nationwide in Sweden, were assessed by telephone, and used the digital intervention for 8 weeks. Participants were also assessed directly afterward and 3 months after the end of the intervention. There was no therapist guidance. Feasibility indicators included intervention credibility, usability, and possible adverse effects. Other measures included preliminary effects on dermatological quality of life, itching sensations, depressive symptoms, and perceived stress. The intervention was regarded as credible and no serious adverse events were reported. System usability was, however, found to be below the predetermined cutoff for acceptable usability. Preliminary effects at 3-month follow-up were in the moderate to large range for dermatological quality of life (Cohen d=0.89, 95% CI 0.18-1.56), itching sensations (Cohen d=0.85, 95% CI 0.15-1.52), depressive symptoms (Cohen d=0.78, 95% CI 0.1-1.45), and perceived stress (Cohen d=0.75, 95% CI 0.01-1.36). This 8-week self-management digital CBT-based intervention was, together with telephone calls before and after, a feasible intervention for participants with AD. Preliminary effects were promising and should be explored further in a randomized controlled trial. Intervention usability was, however, rated below cutoff scores. Efforts should be made to improve written material to increase usability.

BIOBADATOP: Registro Español de Dermatitis Atópica. Descripción y primeros resultados

BackgroundIn recent years, remarkable improvements in our understanding of atopic dermatitis (AD) have revolutionized treatment perspectives, but access to reliable data from clinical practice is essential. Materials and methodThe Spanish Atopic Dermatitis Registry, BIOBADATOP, is a prospective, multicenter database that collects information on patients of all ages with AD requiring systemic therapy with conventional or novel drugs. We analyzed the registry to describe patient characteristics, diagnoses, treatments, and adverse events (AEs). ResultsWe studied data entries for 258 patients who had received 347 systemic treatments for AD. Treatment was discontinued in 29.4% of cases, mostly due to a lack of effectiveness (in 10.7% of cases). A total of 132 AEs were described during follow-up. Eighty-six AEs (65%) were linked to a systemic treatment, most commonly dupilumab (39AEs) and cyclosporine (38AEs). The most common AEs were conjunctivitis (11patients), headache (6), hypertrichosis (5), and nausea (4). There was 1severe AE (acute mastoiditis) associated with cyclosporine. ConclusionsInitial findings on AEs from the Spanish BIOBADATOP registry are limited by short follow-up times precluding comparisons or calculation of crude and adjusted incidence rates. At the time of our analysis, no severe AEs had been reported for novel systemic therapies. BIOBADATOP will help answer questions on the effectiveness and safety of conventional and novel systemic therapies in AD.

Experimental models of atopic dermatitis for preclinical researches

Introduction. The development of new methods and technologies for the treatment of atopic dermatitis (AtD) is an urgent medical task due to the growing incidence of the disease, increasing frequency of severe, continuously relapsing forms of dermatosis resistant to both external and systemic therapy. Appropriate experimental models of laboratory animals are needed to test new methods of AtD treatment. The purpose of the study is to describe the technologies of creating experimental models for AtD in laboratory animals to conduct preclinical studies to evaluate the effectiveness of AtD therapy, based on foreign and domestic literature data. Materials and methods. A search in the bibliographic databases PubMed, Scopus, Web of Science, scientific electronic library Elibrary was conducted, 58 sources were selected for the literary review. Search keywords: atopic dermatitis, animal models, mouse models, preclinical studies. Results and discussion. Mouse models are mainly used to reproduce AtD. Experimental mouse models of AtD can be divided into three groups: mice that spontaneously develop skin lesions similar to AtD; models using transgenic mice that either overexpress selective molecules or lack them; models induced cutaneous application of sensitizers. Typically, these models mimic various aspects of human AtD pathophysiology, such as defects in the skin barrier, Th2 predominance, with additional activation of Th1 and Th22 and, in some populations, Th17 immune response. Conclusion. Of the technologies for creating experimental models of AtD in laboratory animals, those with genetic predisposition and allergen-induced models are the closest to human AtD.