NOD/Scid IL2Rγnull Mice Reconstituted with PBMCs from Patients with Atopic Dermatitis or Psoriasis Vulgaris Reflect the Respective Phenotype.

NSG (NOD/Scid IL2Rγnull) mice reconstituted with PBMCs donated by patients with ulcerative colitis or Crohn's disease highly reflect the respective pathological phenotype. To determine whether these findings could be applicable to atopic dermatitis (AD) and psoriasis vulgaris (PV), PBMCs isolated from patients with AD and PV were first subjected to immunological profiling. Subsequently, NSG mice were reconstituted with these PBMCs. Hierarchical clustering and network analysis revealed a distinct profile of patients with AD and PV with activated CD4+ T cells (CD69, CD25) occupying a central position in the AD network and CD4+ CD134+ cells acting as the main hub in the PV network. After dermal application of DMSO, both NSG mice reconstituted with PBMCs from donors with AD (ie, NSG-AD mice) and NSG mice reconstituted with PBMCs from donors with PV (ie, NSG-PV mice) exhibited increased clinical, skin, and histological scores. Immunohistochemical analysis, frequencies of splenic human leukocytes, and cytokine expression levels indicated that CD4+ CD69+ cells, M1 and TSLP receptor-expressing monocytes, switched B cells, and monocyte chemoattractant protein 3 were the driving factors of inflammation in NSG-AD mice. In contrast, inflammation in NSG-PV mice was characterized by an increase in fibroblasts in the epidermis, frequencies of CD1a-expressing monocytes, and IL-17 levels. Therefore, the pathological phenotypes of NSG-AD mice and NSG-PV mice differ and partially reflect the respective human diseases.

Italian S3-Guideline on the treatment of atopic eczema - First Update, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

The evidence- and consensus-based guideline on atopic eczema, published in JEADV on 18 August 2022 (part 1) and 3 September 2022 (part 2) was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. To reflect the most recent evidence on novel systemic medications, an update was published in October 2022. According to the purpose of the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA) to adapt the EuroGuiDerm guideline on the treatment of atopic eczema into the Italian Healthcare setting, the original update has been supplemented by inserting notes, well highlighted by the original text, to emphasize the laws, rules, procedures and suggestions of the Italian Ministry of Health and regional Health authorities.

Italian S3-Guideline on the treatment of atopic eczema Part 2: non-systemic treatments and treatment recommendations for special AE patient populations, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for pediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

Italian S3-Guideline on the treatment of Atopic Eczema - Part 1: Systemic therapy, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for pediatric, adolescent, pregnant and breastfeeding patients.

Real-world effectiveness and tolerability of a cream containing postbiotic Aquaphilus dolomiae extract-G3 in subjects with sensitive facial skin.

Previous studies indicate that a postbiotic extract from Aquaphilus dolomiae (ADE-G3) improves skin barrier function and relieves neuroinflammation. Evaluation of an ADE-G3-based soothing cream for managing sensitive facial skin. This real-world, international, pre-post comparative study involved adults with sensitive facial skin who used the study product once or twice daily for two to three months according to usual practice. Subjects reported changes in perceived clinical symptoms using self-administered questionnaires. Physicians assessed changes in xerosis severity, overall product effectiveness and tolerability. User satisfaction and quality of life (QoL) assessments, and subgroup analyses according to the factors triggering sensitive skin were also conducted. In total, 2,382 subjects with sensitive facial skin (female: 79%; median age: 40 years) were included. An immediate skin soothing effect after the first ADE-G3-based cream application was reported by 93% of subjects, and improvements in symptoms were reported in 94% after a mean of nine days of product use. After several months of use (mean: 71±21 days), xerosis severity and dermatological-related QoL significantly improved in the whole study population and in the subgroups (p<0.001). At the end of the study, 92% of users were satisfied with the product and 95% reported improvements in their overall skin condition. Physicians found the cream to be effective and well tolerated in 92% and 98% of subjects, respectively. Regular use of the ADE-G3-based cream was shown to be effective in real-world management of sensitive facial skin, regardless of the factors involved in triggering skin sensitivity.

Skin Barrier Function Assessment: Electrical Impedance Spectroscopy Is Less Influenced by Daily Routine Activities Than Transepidermal Water Loss.

BACKGROUND: Skin barrier function assessment is commonly done by measuring transepidermal water loss (TEWL). An important limitation of this method is the influence of intrinsic and extrinsic factors. Electrical impedance spectroscopy (EIS) is a lesser-established method for skin barrier function assessment. Some influential factors have been described, but no guidelines exist regarding the standardization of these measurements. OBJECTIVE: To evaluate the effect size of daily routine activities on TEWL and EIS, as well as their correlation with age and anatomical differences. METHODS: Healthy participants (n=31) were stratified into three age groups (18-29, 30-49, and ≥50 years). In a climate-controlled room, EIS and TEWL measurements were performed on the left and right volar forearm and abdomen. RESULTS: Body cream application decreased TEWL and EIS values after 15 and 90 minutes. Skin washing decreased TEWL for 15 minutes and EIS values for at least 90 minutes. TEWL was increased 5 minutes after moderate to intense exercise. Coffee intake increased TEWL on the abdomen after 60 minutes. TEWL and EIS values did not correlate with participants' age and no anatomical differences were observed. No correlation was observed between TEWL and EIS. CONCLUSION: Body cream application and skin washing should be avoided at least 90 minutes prior to measurements of TEWL and EIS. Exercise and coffee intake should also be avoided prior to TEWL measurements. EIS may be a promising tool for skin barrier function assessment as it is less affected by daily routine activities than TEWL.

Obesity is linked to disease severity in moderate to severe atopic dermatitis-Data from the prospective observational TREATgermany registry.

BACKGROUND: There are conflicting data on a potential association between obesity and atopic dermatitis (AD). The purpose of this study was to investigate the relationship between obesity and AD disease severity. METHODS: Patients from the TREATgermany registry cohort were divided into three groups according to their body mass index (BMI). Due to low numbers, underweight patients (BMI <18.5 kg/m2) were excluded from the analysis. Physician- and patient-reported disease severity scores as well as additional phenotypic characteristics were evaluated for association with BMI. Generalized linear mixed models and multinomial logit models, respectively, were applied to investigate the association of BMI, age, sex and current systemic AD treatment with disease severity. RESULTS: This study encompassed 1416 patients, of which 234 (16.5%) were obese (BMI ≥30 kg/m2). Obesity was associated with lower educational background and smoking. Otherwise, obese and non-obese AD patients had similar baseline characteristics. Increased BMI was associated with higher oSCORAD (adjusted ß: 1.24, 95% CI: 1.05-1.46, p = 0.013) and Patient-oriented eczema measure (POEM) (adjusted ß: 1.09, 95% CI: 1.01-1.17, p = 0.038). However, the absolute difference in the overall oSCORAD was small between obese and non-obese AD patients (Δ oSCORAD = 2.5). Allergic comorbidity was comparable between all three groups, with the exception of asthma which was more pronounced in obese patients (p < 0.001). DISCUSSION: In this large and well-characterized AD patient cohort, obesity is significantly associated with physician- and patient-assessed measures of AD disease severity. However, the corresponding effect sizes were low and of questionable clinical relevance. The overall prevalence of obesity among the German AD patients was lower than in studies on other AD cohorts from different countries, which confirms previous research on the German population and suggests regional differences in the interdependence of AD and obesity prevalence.

The Burden of Pediatric Atopic Dermatitis: Quality of Life of Patients and Their Families.

(1) Background: Atopic dermatitis (AD) is one of the most common inflammatory skin conditions, thus having a significant impact on the quality of life (QoL) of patients and their families. We performed a survey to gather more data to help describe the burden of AD in Lithuania and to help expand the treatment plan to this important aspect of the disease. (2) Methods: A cross-sectional study was conducted involving healthy and AD pediatric patients. The assessment instruments used were the Patient-Oriented Eczema Measure (POEM), QoL, and original questionnaires (the original questionnaire was designed by the authors to determine the demographics, medical history, and treatment methods of the respondents). (3) Results: This study included 302 participants in total: 247 AD patients (51% boys) and 55 non-AD patients (51% boys). The mean age for AD patients was 6.8 ± 4.4. years, and this was 10.5 ± 3.1 years for the control patients. A significant difference was found between the QoL questionnaire scores and the Family Dermatology Life Quality Index (FDLQI) score for the atopic dermatitis group (QoL: 6.3 ± 5.6; FDLQI: 7.1 ± 6.9) and controls (QoL 0.5 ± 1.1; FDLQI 2.1 ± 5.9) (p = 0.000). The mean QoL questionnaire score for severe AD was 14.3 ± 6.2 (very large effect), that for moderate AD was 6.9 ± 4.4 (moderate effect), and that for mild AD was 4.4 ± 4.2 (small effect) (p = 0.000). (4) Conclusions: Our study revealed a moderate effect of AD on dermatology-related QoL in patients and their families. It has been shown that increased disease severity was associated with a greater impairment of QoL in both patients and patient's parents. The burden of AD in children and their parents is considerable and should be taken into account in the management of atopic dermatitis.

OX40 in the Pathogenesis of Atopic Dermatitis-A New Therapeutic Target.

Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities and secondary complications, which can result in significant clinical burden that impacts the patient's overall quality of life. The complex interplay of immune dysregulation and skin barrier disruption drives AD pathogenesis, of which T-cell-dependent inflammation plays a critical role in patients with AD. Despite new targeted therapies, many patients with moderate-to-severe AD fail to achieve or sustain their individual treatment goals and/or may not be suitable for or tolerate these therapies. There remains a need for a novel, efficacious, well-tolerated therapeutic option that can deliver durable benefits across a heterogeneous AD patient population. Expression of OX40 [tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], a prominent T-cell co-stimulatory molecule, and its ligand [OX40L; tumor necrosis factor superfamily, member 4 (TNFSF4)] is increased in AD. As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD.

S3 Guideline Atopic dermatitis: Part 1 - General aspects, topical and non-drug therapies, special patient groups.

This S3 guideline was created based on the European S3 guideline, with special consideration of the medical conditions in the German-speaking region and incorporating additions from the previous German-language version. The interdisciplinary guideline commission consisted of representatives from the German Dermatological Society, the Professional Association of German Dermatologists, the Austrian Society of Dermatology and Venereology, the Swiss Society of Dermatology and Venereology, the German Society for Allergology and Clinical Immunology, the German Society for Pediatric and Adolescent Medicine, the Professional Association of Pediatricians and Adolescent Medicine, the Society for Pediatric Allergology and Environmental Medicine, the German Society for Pediatric Rehabilitation and Prevention, the German Society for Psychosomatic Medicine and Medical Psychotherapy, the German Network for Health Services Research, the German Eczema Association and the German Allergy and Asthma Association. This first part of the guideline focuses on the definition and diagnostic aspects of atopic dermatitis (AD), addressing topical therapy as well as non-pharmacological treatment approaches such as UV therapy, psychoeducational therapy, dietary interventions for AD, allergen immunotherapy for AD, and complementary medicine. This part of the guideline also covers specific aspects of AD in children and adolescents, during pregnancy and lactation, and in the context of family planning. Additionally, it addresses occupational aspects of AD and highlights the perspective of the patients. The second part of the guideline, published separately, addresses the systemic therapy of AD.

Tralokinumab Provides Clinically Meaningful Responses at Week 16 in Adults with Moderate-to-Severe Atopic Dermatitis Who Do Not Achieve IGA 0/1.

BACKGROUND AND OBJECTIVE: Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) is a difficult endpoint to achieve after short-term treatment of chronic moderate-to-severe atopic dermatitis, and does not fully reflect clinically meaningful changes in other parameters. We assessed the impact of tralokinumab versus placebo on other clinically meaningful parameters in patients not achieving IGA 0/1 at week 16 using pooled data from two monotherapy phase III trials, ECZTRA 1 and 2. METHODS: This post hoc analysis included patients (n = 1328) from ECZTRA 1 and 2 who did not achieve the co-primary endpoint, IGA 0/1 at week 16 without rescue medication. Endpoints evaluating atopic dermatitis extent and severity included proportions of patients achieving IGA 0/1, 50%, 75%, and 90% improvement in Eczema Area and Severity Index (EASI-50/75/90); endpoints evaluating patient-reported outcomes included a ≥ 3-point improvement in worst daily pruritus Numerical Rating Scale (NRS), a ≥ 3-point improvement in eczema-related sleep interference (sleep) NRS, a ≥ 4-point improvement in Dermatology Life Quality Index (DLQI), and DLQI ≤ 5. Specifically, clinically meaningful responses were defined as EASI-50, a ≥ 3-point improvement in itch NRS, or a ≥ 4-point improvement in DLQI at week 16. RESULTS: Among ECZTRA 1 and 2 patients who did not achieve IGA 0/1 at week 16 without rescue medication, a significantly greater proportion of patients receiving tralokinumab versus placebo achieved EASI-50 (33.0% vs 13.0%), a ≥ 3-point improvement in itch NRS (22.6% vs 9.4%), or a ≥ 4-point improvement in DLQI (41.2% vs 24.5%) at week 16. In addition, compared with placebo, a numerically greater proportion of tralokinumab-treated patients achieved all three measures of clinically meaningful response (30% vs 18%) or a clinically meaningful change in at least one outcome (48.8% vs 28.5%). Significantly greater proportions of patients receiving tralokinumab versus placebo achieved additional clinician-reported and patient-reported outcomes, such as EASI-75 (13.5% vs 4.1%), EASI-90 (3.5% vs 1.1%), DLQI ≤ 5 (22.5% vs 12.5%), and a ≥ 3-point improvement in sleep NRS (24.5% vs 11.5%). CONCLUSIONS: Tralokinumab provided clinically meaningful responses in patients with moderate-to-severe atopic dermatitis who did not achieve IGA 0/1 at week 16 and/or used rescue medication. Using multiple validated outcome measures of both efficacy and quality of life, alongside IGA scores, can better characterize tralokinumab treatment responses in patients with moderate-to-severe atopic dermatitis. [Video abstract available] CLINICAL TRIAL REGISTRATION: NCT03131648 (ECZTRA 1); study start date: 30 May, 2017; primary completion date: 7 August, 2018; study completion date: 10 October, 2019. NCT03160885 (ECZTRA 2); study start date: 12 June, 2017; primary completion date: 4 September, 2019; study completion date: 14 August, 2019. Video abstract: Tralokinumab provides clinically meaningful responses at week 16 in adults with moderate-to-severe atopic dermatitis who do not achieve IGA 0/1 (MP4 362818 KB).

Treat-to-target in dermatology: A scoping review and International Eczema Council survey on the approach in atopic dermatitis.

Treat-to-target (T2T) is a pragmatic therapeutic strategy being gradually introduced into dermatology after adoption in several other clinical areas. Atopic dermatitis (AD), one of the most common inflammatory skin diseases, may also benefit from this structured and practical therapeutic approach. We aimed to evaluate existing data regarding the T2T approach in dermatology, with a specific focus on AD, as well as the views of International Eczema Council (IEC) members on the potential application of a T2T approach to AD management. To do so, we systematically searched for peer-reviewed publications on the T2T approach for any skin disease in the PubMed and Scopus databases up to February 2022 and conducted a survey among IEC members regarding various components to potentially include in a T2T approach in AD. We identified 21 relevant T2T-related reports in dermatology, of which 14 were related to psoriasis, five to AD, one for juvenile dermatomyositis and one for urticaria. In the IEC member survey, respondents proposed treatable traits (with itch, disease severity and sleep problems getting the highest scores), relevant comorbidities (with asthma being selected most commonly, followed by anxiety and depression in adults), recommended specialists that should define the approach in AD (dermatologists, allergists and primary care physicians were most commonly selected in adults), and applicable assessment tools (both physician- and patient-reported), in both adult and paediatric patients, for potential future utilization of the T2T approach in AD. In conclusion, while the T2T approach may become a useful tool to simplify therapeutic goals and AD management, its foundation in AD is only starting to build. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to further define the essential components needed to utilize T2T in AD.

Baricitinib treatment rapidly improves the four signs of atopic dermatitis assessed by Eczema Area and Severity Index (EASI) clinical subscores.

BACKGROUND: Baricitinib treatment in adults with moderate-to-severe atopic dermatitis (AD) has demonstrated rapid improvements in itch as well as AD sign severity and affected body surface area as assessed by the Eczema Area and Severity Index (EASI) total score, whether administered as monotherapy or in combination with topical corticosteroids (TCS). As EASI clinical signs differ in time course and associated antecedents, the effects of baricitinib on each individual clinical sign are of interest. OBJECTIVES: In this post hoc analysis, we aimed to investigate the effects of baricitinib on individual EASI subscores, namely excoriation, oedema/papulation, erythema and lichenification, in both monotherapy and TCS combination therapy trials. METHODS: We analysed the percent change from baseline in individual EASI subscores from three phase-III, double-blind, 16-week trials of baricitinib in monotherapy (BREEZE-AD1/BREEZE-AD2) and TCS combination therapy (BREEZE-AD7) cohorts via mixed model repeated measures (MMRM). RESULTS: Baricitinib 4 mg showed rapid and sustained improvements in all four clinical signs in both cohorts. Significant effects emerged at week 1 for excoriation, oedema/papulation and erythema scores in monotherapy (p < 0.001) and TCS combination therapy (p < 0.001, p < 0.01, p < 0.001), plateaued at week 4, and remained significant versus placebo through week 16. The effect on lichenification scores also emerged early, at week 1 in monotherapy (p < 0.05) and week 2 in combination therapy (p < 0.001), with scores continuously improving without a clear plateau. Effect magnitude was highest in excoriation scores, exhibiting near-maximal reduction in week 1 of monotherapy and remaining highest across all timepoints in combination therapy. CONCLUSIONS: Rapid and sustained improvements were observed across clinical signs of inflammation and particularly on excoriation following baricitinib treatment. Our findings suggest that selective inhibition of janus kinases 1 and 2 leads to rapid and sustained control of skin inflammation, and that rapid reductions in itch translate into early disruption of the itch-scratch cycle.

Atopic dermatitis: A global health perspective.

The International Society of AD (ISAD) organized a roundtable on global aspects of AD at the WCD 2023 in Singapore. According to the Global Burden of Disease (GBD) consortium, at least 171 million individuals were affected with AD in 2019, corresponding to 2.23% of the world population, with age-standardized prevalence and incidence rates that were relatively stable from 1990 to 2019. Based on the panel experience, most AD cases are mild-to-moderate. Without parallel data on disease prevalence and severity, the GBD data are difficult to interpret in many regions. This gap is particularly important in countries with limited medical infrastructure, but indirect evidence suggests a significant burden of AD in low-and-medium resource settings, especially urban areas. The Singapore roundtable was an opportunity to compare experiences in World Bank category 1 (Madagascar and Mali), 3 (Brazil, China) and 4 (Australia, Germany, Qatar, USA, Singapore, Japan) countries. The panel concluded that current AD guidelines are not adapted for low resource settings and a more pragmatic approach, as developed by WHO for skin NTDs, would be advisable for minimal access to moisturizers and topical corticosteroids. The panel also recommended prioritizing prevention studies, regardless of the level of existing resources. For disease long-term control in World Bank category 3 and most category 4 countries, the main problem is not access to drugs for most mild-to-moderate cases, but rather poor compliance due to insufficient time at visits. Collaboration with WHO, patient advocacy groups and industry may promote global change, improve capacity training and fight current inequalities. Finally, optimizing management of AD and its comorbidities needs more action at the primary care level, because reaching specialist care is merely aspirational in most settings. Primary care empowerment with store and forward telemedicine and algorithms based on augmented intelligence is a future goal.

S3 guideline Atopic dermatitis: Part 2 - Systemic treatment.

The present S3 guideline was created based on the European English-language S3 guideline, with special consideration given to the medical conditions in the German-speaking region, and with additions from the previous German-language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off-label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non-drug therapy approaches, and addresses aspects related to special patient groups.