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Background: Atopic dermatitis (AD) is associated with an increased risk for viral infections including those caused by herpes simplex virus and varicella zoster virus. Objectives: This study examined treatment‐emergent (TE) herpes simplex infection including eczema herpeticum (EH), and herpes zoster (HZ), in adult patients with AD receiving ≥1 dose of baricitinib (BARI), an oral selective inhibitor of Janus kinase 1/2. Methods: We evaluated data from six double‐blinded, randomized, placebo‐controlled (PC) trials and two long‐term extension studies, within three analysis sets: PC, 2–4‐mg BARI extended and All‐BARI‐AD. Frequency, incidence rate (IR)/100 person‐years (PYs) and clinical characteristics of TE‐herpes simplex, EH and HZ were reported. Results: In the All‐BARI‐AD dataset (n = 2531; 2247 PYs), herpes simplex was reported in 8.9% of patients (n = 224; IR = 10.3). Most herpes simplex events were rated as mild or moderate (93.3%), rarely led to permanent discontinuation (2.2%) and presented mostly as oral/perioral herpes simplex (51.3%). TE‐EH occurred at a low frequency (All‐BARI‐AD 1.7% n = 43; IR = 2.0) and were reported in 0.5%, 0.2% and 1.4% of patients receiving placebo, 2‐mg or 4‐mg BARI respectively. In the All‐BARI‐AD dataset, most events were investigator‐rated as mild/moderate (79.1%), affected ≤2% of the body surface area (74.2%) and occurred as single events (88.4%). Serious TE‐EH (n = 11) occurred exclusively in patients with poor disease control (vIGA‐AD™ score ≥3) at infection onset. TE‐HZ was reported in 2.1% of BARI patients (n = 53; IR = 2.3), without a dose relationship during the PC period (IR = 2.7 and IR = 0.0) or the extended dataset (IR = 3.7 and IR = 1.7) for 2‐ or 4‐mg BARI respectively. Conclusions: TE‐herpes simplex was common, while occurrence of EH was uncommon. Most events of EH were localized with involvement of a small BSA and were linked to poor disease control. Events of HZ were rare in the PC dataset and without a dose dependent increase in frequency. [ABSTRACT FROM AUTHOR]

The pathogenesis of atopic dermatitis ( AD) is multifactorial and complex. Consequently, clinical signs and symptoms vary strongly depending on individually relevant trigger factors and the stage of the disease. So far, treatment of AD was commonly limited to topical treatment or, in more severe cases, to systemic drugs mostly approved for other indications than AD. However, emerging data on new anti-inflammatory agents have been published in the recent years. As these new substances specifically focus on immune responses in AD, these are partially considered as possible 'breakthrough' in the treatment of AD. Therapeutic strategies of the future appear to be 'customized' for inflammation in AD as they target pro-inflammatory, highly relevant cytokines and cytokine receptors, such as IL-4Rα, IL-13, IL-31, and IL-17. Further innovative therapeutic approaches aim to block the function of relevant molecules such as thymic stromal lymphopoietin, chemoattractant-receptor homologous molecule expressed on Th2 lymphocytes ( CRTh2), and phosphodiesterase ( PDE)-4 inhibitors. Recently, anti-inflammatory effects in AD by antagonizing the histamine (H)-4 receptor have also been detected. Finally, specific immunotherapy is under further investigation as treatment option for AD patients with clinically relevant sensitization. [ABSTRACT FROM AUTHOR]

In older children, adolescents, and adults, a substantial part of all IgE-mediated food allergies is caused by cross-reacting allergenic structures shared by inhalants and foods. IgE stimulated by a cross-reactive inhalant allergen can result in diverse patterns of allergic reactions to various foods. Local, mild, or severe systemic reactions may occur already after the first consumption of a food containing a cross-reactive allergen. In clinical practice, clinically relevant sensitizations are elucidated by skin prick testing or by the determination of specific IgE in vitro. Component-resolved diagnosis may help to reach a diagnosis and may predict the risk of a systemic reaction. Allergy needs to be confirmed in cases of unclear history by oral challenge tests. The therapeutic potential of allergen immunotherapy with inhalant allergens in pollen-related food allergy is not clear, and more placebo-controlled studies are needed. As we are facing an increasing incidence of pollen allergies, a shift in sensitization patterns and changes in nutritional habits, and the occurrence of new, so far unknown allergies due to cross-reactions are expected. [ABSTRACT FROM AUTHOR]

Background 8-Methoxypsoralen- UVA ( PUVA) and narrowband ultraviolet B ( NB- UVB) are well-established treatments for chronic plaque-type psoriasis vulgaris. However, long-term risks of PUVA therapy include premature skin ageing and squamous cell carcinoma. Objectives To develop a device for targeted UV therapy of psoriatic plaques with protection of the healthy adjacent skin to reduce the risk for premature skin ageing and squamous cell carcinoma. Methods In total 28 patients with exacerbated psoriasis vulgaris were treated with the digital phototherapy device skintrek® [cream PUVA ( n = 8), bath PUVA ( n = 11) and UVB ( n = 9)] or with conventional bath PUVA ( n = 9) or NB- UVB ( n = 4). Results The local Psoriasis Area and Severity Index ( PASI) score was significantly reduced from a mean of 6·25 at baseline to 2·75 at the end of therapy in the skintrek cream PUVA group, from 6·4 to 3·0 in the skintrek bath PUVA group and from 5·5 to 2·0 in the skintrek UVB group. Treatment with skintrek cream PUVA reduced the mean local PASI by 54%, while skintrek bath PUVA did so by 51% and skintrek UVB by 63%. Targeted skintrek PUVA and skintrek UVB of inflamed psoriatic skin avoided skin pigmentation and were not inferior to conventional bath PUVA and NB- UVB therapy regimens. Conclusions Targeted UV therapy of psoriatic plaques with the digital phototherapy device skintrek is as effective as conventional cream and bath PUVA, as well as NB- UVB, while simultaneously sparing the healthy adjacent skin. It therefore potentially reduces the carcinogenic risk, reduces premature skin ageing and avoids tanning of healthy surrounding skin. [ABSTRACT FROM AUTHOR]

Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology's ( EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence-based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non-life-threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines. [ABSTRACT FROM AUTHOR]

Food allergy and atopic eczema (AE) may occur in the same patient. Besides typical immediate types of allergic reactions (i.e. noneczematous reactions) which are observed in patients suffering from AE, it is clear that foods, such as cow’s milk and hen’s eggs, can directly provoke flares of AE, particularly in sensitized infants. In general, inhaled allergens and pollen-related foods are of greater importance in older children, adolescents and adults. Clinical studies have revealed that more than 50% of affected children with AE that can be exacerbated by certain foods will react with a worsening of skin eczema either alone or in addition to immediate symptoms. Adolescents and adults may also react to foods, but reactions to ‘classical’ food allergens, such as hen’s eggs and cow’s milk, are not as common as in childhood. Some patients with AE do react to pollen-associated foods. Food-induced eczema should not be neglected by the allergologist: On the one hand, food can be a relevant trigger factor of persistent moderate-to-severe AE; on the other hand, unnecessary diets which are not based on a proper diagnosis may lead to malnutrition and additional psychological stress on patients suffering from AE. Eczematous reactions to food can only be diagnosed by a thorough diagnostic procedure, taking into account the patient’s history, the degree of sensitization and the clinical relevance of the sensitization. The latter has often to be proven by oral food challenges. Upon oral food challenge it is most important to evaluate the status of the skin with an established score (e.g. SCORAD, EASI) after 24 h and later because otherwise worsening of eczema will be missed. [ABSTRACT FROM AUTHOR]

Background: The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi-centre, randomized dose–response trial, double-blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed. Methods: Eighty-nine adults with a chronic course of atopic dermatitis, SCORAD ≥40 and allergic sensitization to house dust mites [CAP-FEIA ≥3] were included, of whom 51 completed the study. Subcutaneous SIT with a house dust mite preparation ( Dermatophagoides pteronyssinus/ D. farinae) applying maintenance doses of 20, 2000 and 20 000 SQ-U in weekly intervals for 1 year. The main outcome measures addressed the change of the SCORAD as average of the values after 9 and 12 months of SIT in comparison with the value at baseline. Results: The SCORAD declined in the three dose groups in a dose-dependent manner ( P = 0.0368, Jonckheere–Terpstra test) and was significantly lower in the two high-dose groups (2000, 20000 SQ-U) compared with the low-dose group of 20 SQ-U ( P = 0.0379, U-test) after 1 year of SIT. The use of topical corticosteroids was significantly reduced with higher doses ( P = 0.0007, Mantel–Haenszel chi-square test). Conclusions: Allergen-SIT for 1 year with a house dust mite preparation is able to improve the eczema in patients with atopic dermatitis who are sensitized to house dust mite allergens and reduces the need for topical corticosteroids. SIT may be valuable in the treatment of this chronic skin disease. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a common chronic inflammatory disease characterized by severe pruritus with its symptoms occurring in phases. Conjunctivitis occurring in atopic dermatitis patients treated with dupilumab-clinical characteristics and treatment. Goblet cell scarcity and conjunctival inflammation during treatment with dupilumab in patients with atopic dermatitis. [Extracted from the article]

Background: Bovine casein leads to an expansion of lymphocytes expressing the cutaneous lymphocyte antigen and to specific lymphocyte proliferation in a subgroup of patients with milk-responsive atopic dermatitis (AD). The casein fraction is composed of different proteins with defined and completely different sequences. Objective To define the stimulatory capacity of the major casein protein (n.Β and N) in lymphocyte proliferation assays with cells from milk-allergic and non-allergic individuals. Methods :Proliferative responses of peripheral blood mononuclear cells to lipopoly saccharide-depleted casein subfractions were measured by thymidine incorporation. Lymphocytes from milk-responsive patients with AD were compared with cells from non-responsive patients with AD and to non-atopic individuals. Atopic individuals with immediate symptoms following consumption of COW'S milk were included as positive controls. Casein-specific T-cell clones (TCC) from four patients with milk- responsive Al) were restimulated with unfractioned casein and t-casein. Results Higher proliferative responses to unfractionated casein and a-Β and &-kappa;casein were observed in milk-responsive patients compared with non-responders. Unfractionated casein and κcasein discriminated best between the milk-responsive patients with Al) and non-responders. Twenty-five of 31 TCC from patients with milk- responsive AD reacted to the mixed casein preparation and casein. Conclusion:A pronounced κ-casein -specific T-cell-mediated immune response is Found in the blood of many patients with a history of milk-related exacerbation of AD. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shed light on the complex regulation of genetic, environmental, immunologic and pharmacologic factors, which contribute to the development of atopic dermatitis (AD). However, it is still unclear to which extent neuroimmune mediators have a role in AD. Aims of the study: To assess peripheral neurotrophin levels and their correlation with scoring atopic dermatitis (SCORAD) scores in both the intrinsic and extrinsic types of AD compared with patients with psoriasis and nonatopic healthy subjects. Methods: Levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were assessed in peripheral blood with enzyme-linked immunosorbent assay. Based on IgE-mediated sensitization, AD was divided into the extrinsic and intrinsic type. Severity of AD was assessed with SCORAD score and with psoriasis area and severity index (PASI) in patients with psoriasis. Results: Brain-derived neurotrophic factor and NGF were detectable in all the subjects studied. However, the levels of both neurotrophins were significantly higher in patients with extrinsic and intrinsic types of AD compared with patients with psoriasis and nonatopic healthy subjects (NGF: P < 0.001, BDNF: P < 0.001). NGF and BDNF levels were similar in the intrinsic and extrinsic type of AD. There was a significant correlation between BDNF and SCORAD score only in patients with the intrinsic type of AD ( r = 0.57, P < 0.05). Conclusions: This study shows for the first time that NGF and BDNF are increased in both, the extrinsic type and the intrinsic type of AD. This finding points to a similar pathophysiologic background implicating a neuroimmune network in both variants of this chronic inflammatory skin disease. Future studies are needed to show the direct mechanisms of neurotrophin action in chronic inflammatory skin. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor on the successful treatment with oral isotretinoin of acneiform skin lesions associated with cetuximab therapy.

Background: The German S2k guideline is the first to include a checklist that captures atopic dermatitis (AD) signs and symptoms as well as the lack of treatment response to identify patients eligible for systemic therapy. Objectives: Identifying candidates for a start/switch of systemic therapy in adult AD patients in Germany by applying the S2k guideline's checklist. Methods: In this German multicentre, cross‐sectional, non‐interventional study (German Clinical Trials Register number: DRKS00023296), adult patients with mild to severe AD were enrolled at dermatological outpatient clinics and offices between April and October 2021. Demographics, clinical characteristics and quality of life were collected using questionnaires during one single visit. Eligibility for a start/switch of systemic AD therapy was evaluated according to the criteria of the German S2k guideline's checklist. Results: Atopic dermatitis patients (575) were included in the analysis. One hundred and sixty‐four patients (28.5%) received systemic (SYS) AD therapy and 411 patients (71.5%) did not (TOP). Of the TOP therapy patients, 38.7% were eligible to start systemic AD therapy, and about half of those (49.1%), were scheduled to start systemic AD therapy. The most frequent reason deciding against a systemic therapy was the patient's wish. Although 29.3% of SYS patients were eligible for a switch according to the criteria of the German S2k guideline's checklist, the majority (81.3%) did not switch AD therapy. Conclusions: This is the first study on the implementation of the German S2k guideline's checklist in everyday care of AD patients in Germany. More than one‐third of the TOP patients were identified as eligible for systemic treatment. By applying the guideline's checklist criteria, another one‐third of SYS patients may have benefited from a change of current systemic therapy. The use of the German S2k guideline's checklist in routine care represents an important tool to ensure effective patient care and identify inadequately treated patients. [ABSTRACT FROM AUTHOR]

The high prevalence of allergic diseases warrants for sufficient health care provisions available to patients with allergic diseases. Allergy care should be delivered by well-trained specialists. However, the current status of allergy care is not well documented. For this reason a survey among European and a few non-European countries was launched by the National Allergy Society Committee from the European Academy of Allergy and Clinical Immunology and the Union Européenne des Médecins Spécialistes section and board of Allergology. The survey shows that in the vast majority of countries allergy care services are available. However, a substantial heterogeneity is reported regarding recognition of the full specialty, the number of practicing specialists or subspecialists, and training aspects. Growth but also decline of specialty and subspecialties is reported. In addition, the survey gives insight in strengths, weaknesses, opportunities and threats in this field. It appears that the recognition of the full specialty determines strength as well as weakness. Aging of specialists combined with a decline in the number of trainees form a major threat. Opportunities are seen in creating awareness for allergy, focus on attracting young physicians. The conclusion is that harmonization of allergy services across Europe is needed. Investment in young doctors, creating new opportunities and lobbying for the full specialty is required. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib improved signs and symptoms of moderate‐to‐severe atopic dermatitis (AD) at Weeks 12 and 16 in phase 3 studies, with a manageable safety profile. Patient‐reported outcomes with long‐term abrocitinib treatment were not reported. Objective: To evaluate patient‐reported outcomes with long‐term abrocitinib treatment in patients with moderate‐to‐severe AD. Methods: JADE EXTEND (NCT03422822) is an ongoing, phase 3, long‐term extension study that enrolled patients from previous abrocitinib AD trials. This analysis includes patients from the phase 3 trials JADE MONO‐1 (NCT03349060), JADE MONO‐2 (NCT03575871) and JADE COMPARE (NCT03720470) who completed the full treatment period of placebo or abrocitinib (200 or 100 mg once daily) and subsequently entered JADE EXTEND and were randomised to receive once‐daily abrocitinib 200 or 100 mg. Patient‐reported endpoints to Week 48 included the proportion of patients who achieved Dermatology Life Quality Index (DLQI) scores of 0/1 (no effect of AD on quality of life [QoL]) and a ≥4‐point improvement in Patient‐Oriented Eczema Measure (POEM) score (clinically meaningful improvement). Data cut‐off: April 22, 2020. Results: Baseline DLQI mean scores were 15.4 and 15.3 in the abrocitinib 200‐ and 100‐mg groups, respectively, which corresponded to a 'very large effect' on QoL; at Week 48, mean DLQI scores were lower with abrocitinib 200 mg (4.6; 'small effect' on QoL) and abrocitinib 100 mg (5.9; 'moderate effect' on QoL). Baseline POEM mean scores were 20.4 and 20.5 in the abrocitinib 200‐ and 100‐mg groups, respectively; at Week 48, mean POEM scores were 8.2 and 11.0. Week 48 patient‐reported responses with abrocitinib 200 mg and abrocitinib 100 mg were 44% and 34% for DLQI 0/1, and 90% and 77% for a ≥4‐point reduction in POEM score. Conclusion: In patients with moderate‐to‐severe AD, long‐term abrocitinib treatment resulted in clinically meaningful improvement in patient‐reported symptoms of AD, including QoL. [ABSTRACT FROM AUTHOR]

Background: Eczema herpeticum (EH) is a disseminated viral infection of eczematous skin disease with the herpes simplex virus. Knowledge on clinical characteristics, risk factors and recurrent disease is limited. Our aim was to better define clinical characteristics and risk factors for EH and especially for recurrent EH. Methods: A retrospective analysis of EH cases assessed the history, clinical signs, prior treatment and laboratory results using a predefined questionnaire. Results: A total of 224 EH cases from eight European centres were included. Extrinsic AD was identified as risk factor for EH, and only one patient suffered from intrinsic AD. Early onset of AD was identified as risk factor for recurrent EH. Pretreatment with topical steroids, systemic steroids, topical calcineurin inhibitors or plain emollients reflected standard therapy. Many patients showed AD lesions without EH, but skin without AD lesions was never affected by herpetic lesions. Conclusion: Patients with clinically active, extrinsic AD are at risk of EH. Recurrent EH is associated with confounders of severe atopic distortion and requires active AD lesions for clinical manifestation. Recurrent eczema herpeticum mainly affects patients with early onset of AD. [ABSTRACT FROM AUTHOR]

A letter to the editor that discusses vitamin D deficiency among patients with cutaneous lupus erythemathosus is presented.

Focuses on the causes of allergic inflammation in skin. Stimulation of T cells from allergic contact dermatitis; Association of pathogenic factors with chronic skin diseases; Role of T-cell responses to propagation of atopic dermatitis.

Background and objectives: The economic burden of atopic dermatitis (AD) is of particular interest. The present study aims to analyse the association of disease‐related characteristics, annual costs and treatment benefits in AD. Methods: Between August 2017 and June 2019, a cross‐sectional observational study in patients with AD was conducted in Germany. Cost‐of‐illness data were assessed from the societal perspective. Disease characteristics included severity, time since diagnosis and therapy, as well as atopic comorbidity and the implementation of prevention measures. Subgroup analyses of the total costs were conducted for these characteristics. A linear regression model was applied to analyse the impact of disease characteristics on the costs. Furthermore, associations of biologic treatment with outcome parameters were analysed. Results: A total of 1291 patients from 111 centres were included in the analyses. The total costs amounted on average to € 3660 ± € 6428 per patient and year. Higher costs were shown in various patient groups, for example, in patients using biologics (€ 20 983 vs. € 2470). In a regression analysis, gender, education and the number of implemented prevention measures were identified as significant predictors of costs. Patients treated with biologics showed consistently better outcome parameters and were more often satisfied with their treatment. Conclusions: Gender, education and implemented prevention measures are significant cost determinants in AD. The results confirm that treatment with biologics is the main cost driver in AD. However, incremental patient‐relevant benefits of high‐priced therapy are reflected by the significantly better clinical outcomes in the group treated with biologics. [ABSTRACT FROM AUTHOR]

I Dear Editor i , This mono-centre, randomized, open-label, observer-blinded parallel-group study (clinicaltrials.gov; NCT03315611) was initiated to study effects of emollients on skin inflammation in atopic dermatitis (AD) upon grass pollen exposure in moderately to highly grass pollen IgE-sensitized patients (approved by the Ethics committee MHH, no. 7586). Taken together, this is the first study to elucidate effects of basic therapy on allergen-induced skin inflammatory immune responses and on the skin microbiome in AD. [Extracted from the article]

Comparing the CESD-score's symptom categories, registry patients scored highest on sleep, fatigue and agitation. This is in line with previous results.7,8 Patients' reportings on symptom frequency was markedly higher for AD patients having depression as comorbidity compared to patients reporting no depression comorbidity. The presented issue highlight the relevant role of depressive symptoms for a high proportion of adult patients with moderate-to-severe AD. [Extracted from the article]

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial genesis including genetic predispositions and environmental risk and trigger factors. One of the latter possibly is smoking, indicated by an increased prevalence of AD in adults and children that are actively or passively exposed to cigarette smoke. Objectives: In this study, AD characteristics and its atopic comorbidities are compared in smoking and non‐smoking AD patients. Methods: TREATgermany is a non‐interventional clinical registry which includes patients with moderate to severe AD in Germany. Baseline data of patients included in TREATgermany from inception in June 2016 to April 2020 in 39 sites across Germany was analysed comparing AD disease characteristics and comorbidities in smokers vs. non‐smokers. Results: Of 921 patients, 908 (male: 58.7%) with a mean age of 41.9 ± 14.4 reported their smoking status. The objective Scoring of Atopic Dermatitis (oSCORAD) did not differ between smokers (n = 352; 38.8%) and non‐smokers, however, lesions' intensity of oozing/crusts and excoriations as well as patient global assessment scores (PGA) of AD severity were higher in smoking as opposed to non‐smoking patients. Smokers reported a lower number of weeks with well‐controlled AD and more severe pruritus than non‐smokers. Total IgE levels were more elevated in smokers and they displayed a younger age at the initial diagnosis of bronchial asthma. After adjustment for potential confounders, the increased intensity of oozing/crusts, the reduced number of weeks with well‐controlled AD and the greater pruritus remained different in smokers compared to non‐smokers. In addition, smoking patients with adult‐onset AD showed a 2.5 times higher chance of involvement of the feet. Conclusions: German registry data indicate that AD patients who smoke have a higher disease burden with a different distribution pattern of lesions in adult‐onset AD. Linked Commentary Valeria Aoki and Raquel Leão Orfali J Eur Acad Dermatol Venereol 2022; 36: 324–325. https://doi.org/10.1111/jdv.17901. [ABSTRACT FROM AUTHOR]

Background and Purpose: Since the identification of the histamine H₄ receptor, several ligands activating this receptor have been described and more compounds are in development. These ligands are well characterized in pharmacological assays, including radioligand competition binding studies, GTPγS and GTPase assays. In most cases, these experiments are performed in transfected cell lines, expressing unnaturally high levels of target receptors and G-protein signalling components. In this study we investigated the specific properties of H₄ receptor ligands in native cells.Experimental Approach: Histamine and five different H₄ receptor agonists - 4-methylhistamine, UR-PI376, clobenpropit, VUF8430 and ST-1006 - were characterized in freshly isolated human monocytes. The ligands (10 nM-10 μM) were tested as inhibitors of IL-12p70 secretion from human monocytes and the effects of the H₂ receptor antagonist ranitidine and the H₄ receptor antagonist JNJ7777120 on their action was investigated.Key Results: Histamine and all the tested agonists reduced IL-12p70 secretion into monocyte supernatants by 40-70%. The potencies varied with pEC50 values ranging from 5.7 to 6.9, depending on the agonist used. All potencies were lower than those determined in the original investigations of the compounds. Pretreatment of monocytes with H₂ or H₄ receptor antagonists showed that some H₄ receptor ligands also had low activity at the H₂ receptor.Conclusions and Implications: Our study demonstrates discrepancies between the potencies obtained from assays in transfected cell lines and assays in native human cells, indicating the importance of evaluating H₄ receptor ligands in native cells. [ABSTRACT FROM AUTHOR]

Background and Purpose Since the identification of the histamine H4 receptor, several ligands activating this receptor have been described and more compounds are in development. These ligands are well characterized in pharmacological assays, including radioligand competition binding studies, GTPγS and GTPase assays. In most cases, these experiments are performed in transfected cell lines, expressing unnaturally high levels of target receptors and G-protein signalling components. In this study we investigated the specific properties of H4 receptor ligands in native cells. Experimental Approach Histamine and five different H4 receptor agonists - 4-methylhistamine, UR- PI376, clobenpropit, VUF8430 and ST-1006 - were characterized in freshly isolated human monocytes. The ligands (10 n M-10 μM) were tested as inhibitors of IL-12p70 secretion from human monocytes and the effects of the H2 receptor antagonist ranitidine and the H4 receptor antagonist JNJ7777120 on their action was investigated. Key Results Histamine and all the tested agonists reduced IL-12p70 secretion into monocyte supernatants by 40-70%. The potencies varied with pEC50 values ranging from 5.7 to 6.9, depending on the agonist used. All potencies were lower than those determined in the original investigations of the compounds. Pretreatment of monocytes with H2 or H4 receptor antagonists showed that some H4 receptor ligands also had low activity at the H2 receptor. Conclusions and Implications Our study demonstrates discrepancies between the potencies obtained from assays in transfected cell lines and assays in native human cells, indicating the importance of evaluating H4 receptor ligands in native cells. Linked Articles This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 [ABSTRACT FROM AUTHOR]

The patients in this manuscript have given written informed consent to the publication of their case details. In conclusion, this study is the first to suggest beneficial effects of TLA in HDM-sensitized adult AD patients regarding objective, subjective and in vitro parameters. Atopic dermatitis (AD) patients are commonly sensitized to house dust mites (HDM). [Extracted from the article]

While the hearing loss recovered completely in the high frequencies from 2 kHz on, moderate sensorineural hearing loss remained in the low and medium frequencies of up to 65 dB. (c) Syphilis was diagnosed due to a positive TPPA, RPR, and positive IgG as well as IgM immunoblot. The patient in this manuscript has given written informed consent to publication of their case details. Interestingly, in up to 90% of patients with otosyphilis CSF reveals no abnormalities.4 Unfortunately, randomized controlled studies regarding the treatment of otosyphilis are not available. [Extracted from the article]

Background Interleukin-31 is a cytokine expressed by activated T cells. A major function of IL-31 in atopic dermatitis ( AD) is the induction of pruritus in the skin. We recently showed that IL-31 induces pro-inflammatory cytokines following staphylococcal exotoxins' stimulation in human macrophages. However, signalling pathways of IL-31 in activated human macrophages still remain unclear. The aim of the study was to investigate the signalling pathways of IL-31 receptor as well as functional effects of IL-31 in activated macrophages. Methods Human macrophages were prestimulated with staphylococcal exotoxins ( SEB, α-toxin) to up-regulate the IL-31 receptor with and without IL-31. Phospho-signal transducer and activator of transcription ( pSTAT) 1/3/5, phospho-extracellular signal-regulated kinase ( ERK 1/2), β-actin as well as p21/WAF/Cip1 levels were determined by means of Western blot analysis. Interleukin-12p40, IL-12p70 and IL-23 secretions were assessed by using an enzyme-linked immunosorbent assay. Results Interleukin-31 strongly activated STAT-1 and 5 but not STAT-3 in human macrophages after up-regulation of IL-31 receptor with staphylococcal exotoxins. p21/ WAF/ Cip1 expression was induced by IL-31 in activated human macrophages. Furthermore, IL-31 down-regulated. IL-12p40 secretion via ERK 1/2 phosphorylation in human macrophages following up-regulation of IL-31 receptor with staphylococcal exotoxins. Conclusions The T helper ( Th) 2 cytokine IL-31 induces pro-inflammatory effects in activated human macrophages via STAT-1 and 5 phosphorylation. Interleukin-31-induced ERK 1/2 activation contributes to the underlying mechanism of Th1 cytokine IL-12 suppression in macrophages. This mechanism may be relevant in Th2 inflammatory responses and may help to develop therapeutic strategies in IL-31-associated diseases such as AD. [ABSTRACT FROM AUTHOR]

Background Interleukin (IL)-33 is a member of the IL-1 family and has been implicated in Th2-driven allergic diseases such as atopic dermatitis (AD) and asthma. The principal Th2 cytokine IL-4, found highly expressed in acute allergic eczema, is known to downregulate human β-defensin 2 (hBD2) expression in human keratinocytes and this is associated with superinfection in patients with AD. Objectives To investigate the effect of IL-33 on the expression of hBD2 in human keratinocytes. Methods hBD2 production by stimulated keratinocytes was measured by enzyme-linked immunosorbent assay. Results Our results showed that serum is a very potent inducer of hBD2 and 2·5% human serum was much more potent in inducing hBD2 than 20 ng mL−1 of tumour necrosis factor-α. Interestingly, serum from patients with AD showed an impaired ability to induce hBD2 in normal keratinocytes. IL-33 significantly downregulated serum-induced hBD2. The downregulatory capacity of IL-33 was found to be 1·5- to 2-fold weaker compared with IL-4. Conclusions Our data suggest that IL-33 can significantly contribute to the decreased expression of hBD2 in acute eczematous reaction clinically characterized by spongiosis and oozing - thus indicative for contact of the epidermis with serum components. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% children and 9% adults world-wide. AD patients are often sensitized against a broad variety of allergens and more than 90% of them suffer from skin superinfections with Staphylococcus aureus. Objective In this study, we searched for the presence of specific IgE antibodies against S. aureus and Escherichia coli antigens in AD patients. Methods Sera from AD patients (n = 79), patients suffering only from allergic rhinoconjunctivitis (n = 41) or allergic asthma (n = 37) were tested for IgE reactivity to nitrocellulose-blotted S. aureus, E. coli and gut bacterial antigens. IgE-reactive bacterial antigens were affinity purified and identified by mass spectrometry.Results More than 30% of AD patients but not patients suffering only from allergic rhinoconjunctivitis and asthma or non-allergic persons exhibited IgE binding to several protein antigens among them DNA-binding and ribosomal proteins and flagellin. Patients with severe skin manifestations showed more frequently IgE reactivity to S. aureus compared with AD patients with mild symptoms. Positive immediate and late skin test reactions could be induced in sensitized AD patients with S. aureus extract. Conclusion and Clinical Relevance Specific IgE reactivities against a variety of bacterial antigens were observed in a subgroup comprising a third of AD patients and may contribute to allergic inflammation. [ABSTRACT FROM AUTHOR]

Background Chronic inflammatory skin diseases such as atopic dermatitis and psoriasis are characterized by the infiltration of lymphocytes into the epidermal compartment. Several studies point to an active role of skin epithelial cells in the pathophysiology of such diseases. Objectives In this study we addressed the regulatory function of primary human keratinocytes in the interaction with autologous T cells and monocytes. Methods We used a human coculture model with keratinocytes grown from epidermal stem cells of the outer root sheath of human hair follicles and autologous T cells. Results In our coculture system we observed a high production of interferon (IFN)-γ, but not Th2 cytokines, in the presence of superantigen or antigen-pulsed autologous monocytes. Critical parameters for this effect were: (i) T-cell receptor activation, (ii) an intercellular adhesion molecule-1/lymphocyte function-associated antigen (LFA)-1-dependent interaction between keratinocytes and T cells, and (iii) secretion of interleukin (IL)-1β. Remarkably, in the presence of activated T cells, epithelial cells seemed to be a more significant source of IL-1β than monocytes. Application of the LFA-1 blocker efalizumab or IL-1 receptor antagonist anakinra enabled us to suppress completely the production of IFN-γ by T cells in the coculture. Conclusions IL-1 secretion and the physical contact between keratinocytes and activated, infiltrating T cells may be central for the development of chronic inflammatory skin conditions. [ABSTRACT FROM AUTHOR]

To cite this article: Kasraie S, Niebuhr M, Werfel T. Interleukin (IL)-31 induces pro-inflammatory cytokines in human monocytes and macrophages following stimulation with staphylococcal exotoxins. Allergy 2010; 65: 712–721. Background: IL-31 is a cytokine expressed by T cells following activation with cytokines or staphylococcal exotoxins. A major function of IL-31 in atopic dermatitis (AD) is the induction of pruritus in the skin via the IL-31 receptor on sensory nerve cells. However, the regulation of the IL-31 receptor and pro-inflammatory functions of IL-31 in human monocytes and monocyte-derived cells are yet to be studied in detail. Objective:  To investigate the regulation and function of IL-31 receptors in resting and activated human monocytes, macrophages and dendritic cells. Methods: Human monocytes, macrophages and dendritic cells were stimulated with staphylococcal exotoxins (SEB, α-toxin) or cytokines (IFN-γ, IL-13). IL-31RA expression and regulation were then investigated at both the mRNA and the protein level. Subsequently, functional effects of IL-31 stimulation on cytokine secretion were measured at the protein level. Results: Staphylococcal exotoxins significantly up-regulated IL-31RA expression on monocytes and macrophages but not on dendritic cells at both the mRNA and the protein level. IL-31 enhanced the secretion of IL-1β, IL-6 and IL-18 and up-regulated CD86 expression. In patients with AD, functional IL-31RA was also detected following stimulation of PBMC with IFN-γ. However, this was not observed in healthy individuals. Conclusion: IL-31 induces pro-inflammatory effects in activated human monocytes and macrophages. This may have implications for cutaneous inflammation in eczema where an over-expression of IL-31 has been described previously. Moreover, our findings provide a new link between staphylococcal colonization and the worsening of inflammation via IL-31. Further therapeutic considerations may include IL-31 as a target in AD. [ABSTRACT FROM AUTHOR]

Background: The atopy patch test (APT) is an in vivo model to study the induction of eczema by inhalant allergens in atopic dermatitis (AD) patients. Mepolizumab is a monoclonal antibody to interleukin-5, which reduces peripheral blood eosinophils. Previously, we reported that mepolizumab treatment did not result in clinical improvement in AD. The current study investigates the effect of mepolizumab therapy on the APT in the same patients. Methods: Mepolizumab treatment was given at days 0 and 7 in a double-blind placebo-controlled design. The APT was applied at days –2, 0, 14 and 28. Clinical evaluation of each APT was conducted 48 h after application at days 0, 2, 16 and 30. Skin biopsies were taken at days 0, 2 and 16 for eosinophil counts. Results: The mepolizumab-treated group showed no significant reduction in macroscopic outcome of the APT. Tissue eosinophils were reduced in the mepolizumab-treated group at day 16 compared with placebo; however, this was not significant. Conclusion: Mepolizumab therapy cannot prevent the eczematous reaction induced by the APT. Furthermore, the influx of tissue eosinophil numbers in the APT is not significantly inhibited after mepolizumab treatment compared with placebo, despite a significant reduction in peripheral blood eosinophils. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Eosinophils may play an important role in the pathogenesis of atopic dermatitis (AD). Interleukin-5 is essential for eosinophil growth, differentiation and migration. A monoclonal antibody to human interleukin-5 (mepolizumab) was developed for atopic diseases. This study was designed to study the effect of mepolizumab in AD.Two single doses of 750 mg mepolizumab, given 1 week apart, were studied in patients with moderate to severe AD using a randomized, placebo-controlled parallel group design. The primary endpoint of‘success’ to treatment was defined as the percentage of patients with at least‘marked improvement’ after 2 weeks as assessed by the Physician's Global Assessment of Improvement (PGA). Furthermore, SCORing AD (SCORAD), pruritus scoring, number of blood eosinophils and serum thymus and activation-regulated chemokine (TARC) values served as secondary endpoints. Fluticason propionate cream 0.05%, once daily could be used as rescue medication from day 16 if no improvement was recorded.Eighteen patients received mepolizumab and 22 placebo treatment. Peripheral blood eosinophil numbers were significantly reduced in the treatment group compared with placebo (P < 0.05). No clinical success was reached by PGA assessment (P = 0.115), SCORAD (P = 0.293), pruritus scoring and TARC values in the mepolizumab-treated group compared with placebo. However, modest improvement (<50% improvement) assessed by PGA was scored significantly more in the mepolizumab-treated group compared with placebo (P < 0.05).Two single doses of 750 mg mepolizumab did not result in clinical success in patients with AD, despite a significant decrease in peripheral blood eosinophils. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic and relapsing, inflammatory skin disease characterized by impaired skin barrier function and immune system dysregulation that results in dryness, skin microbiome dysbiosis and intense pruritus. It is highly heterogeneous, and its management is demanding. Patients with AD are at greater risk of comorbidities such as attention‐deficit hyperactivity disorder as well as other atopic diseases. Early‐onset AD cases typically improve or resolve in late childhood; however, it is proposed that the prevalence of persistent or adult‐onset AD is higher than previously thought. Basic therapy consists of emollient application and trigger avoidance, and when insufficient, topical corticosteroids (TCS) are the first‐line treatment. However, corticophobia/steroid aversion and TCS side‐effects, particularly on sensitive skin areas, lead to low compliance and insufficient disease control. Several long‐ and short‐term randomized controlled and daily practice studies have demonstrated that topical calcineurin inhibitors, such as pimecrolimus, have similar anti‐inflammatory effects to low‐to‐medium strength TCS, reduce pruritus and improve the quality of life of patients. In addition, pimecrolimus does not cause skin atrophy, is steroid‐sparing and has a good safety profile, with no evidence for an increased risk of malignancies or skin infections. In general, pimecrolimus cream is well‐accepted and well‐tolerated, encouraging patient adherence and leading to its use by many physicians as a preferred therapy for children and sensitive skin areas. [ABSTRACT FROM AUTHOR]

Evaluates the cause of complications of atopic dermatitis (AD). Definition and origin of AD; Characterization of AD compared to chronic lesions; Identification of environmental allergen and food allergen as common cause of AD complication.

Background: Eosinophils are important effector cells in several atopic diseases. The levels of eosinophil granule-derived mediators (ECP, EPX) in serum and body fluids have been proven to be correlated with disease activity in atopic respiratory diseases and atopic dermatitis. The study aimed to demonstrate an interrelationship between urine EPX and disease activity in adult patients with atopic dermatitis. Methods: We determined urine EPX concentration, serum ECP concentration, and peripheral blood eosinophil count in 40 adult patients with mild to severe atopic dermatitis and compared it with the disease activity as assessed with the SCORAD index. Results: Urine EPX and serum ECP concentrations were significantly higher in patients with severe atopic dermatitis than in patients with mild or moderate disease (median values 123.5 vs 78.3 µg/mmol creatinine, P<0.0001; 25.4 vs 14.9 µg/l, P<0.0001, respectively). We found a significant correlation between urine EPX levels, serum ECP levels, and the SCORAD (r=0.36, P<0.0001 and 0.34, P<0.0001, respectively). Conclusions: Urine EPX is a useful in vitro parameter of inflammation in atopic dermatitis of the adult age. [ABSTRACT FROM AUTHOR]

Summary C5a, a 74 amino acid peptide cleaved from the complement protein C5, is an extremely potent anaphylatoxin. Expression of the receptor for the anaphylatoxin C5a (C5aR) has been thought to be restricted to cells of myeloid origin. However, recent evidence suggests that the C5aR is also expressed in hepatocytes as well as in pulmonary epithelial, endothelial and smooth muscle cells. In the present study, we investigated the tissue distribution of C5aR by immunohistochemistry in normal human lung, liver, intestine and kidney using well‐defined monoclonal antibodies (mAbs) directed against the extracellular N‐terminus of the receptor. In all tissues examined, macrophages displayed an abundant expression of C5aR protein. However, in the normal human lung, C5aR expression was not detectable in bronchial and alveolar epithelial cells or in vascular smooth muscle or endothelial cells. In the normal human liver, no C5aR protein was detected in hepatocytes, whereas Kupffer cells strongly expressed the C5aR. In normal human kidney, the C5aR was detectable only in proximal tubular cells. C5aR gene transcription in Kupffer cells and proximal tubular cells was confirmed by in situ hybridization. Thus, our results point to an as yet unknown role of the C5aR in normal renal physiology. In the normal lung and liver, however, previous evidence for the ubiquitous expression of C5aR in epithelial, endothelial and smooth muscle cells in situ should be re‐evaluated. [ABSTRACT FROM AUTHOR]

Background: Progress in the management of atopic dermatitis (AD) and the recent introduction of the first biologic have raised interest in the costs of treating AD. Objectives: Since there is a lack of recent data, the objective of this study was to determine the annual costs of adults with AD from the societal perspective. Methods: A nationwide cross‐sectional study was conducted in 111 dermatological offices under routine conditions. Cost parameters were collected with a standardised questionnaire on disease‐related costs. This questionnaire allows the determination of costs for systemic and topical treatment, outpatient and inpatient visits, rehabilitation stays and travel costs. Direct costs were determined for the statutory health insurance (SHI) and for the patients (out‐of‐pocket costs). Societal costs also included the indirect costs due to incapacity to work. Costs were calculated for all severity grades and further stratified by mild and moderate‐to‐severe AD. Results: From August 2017 to June 2019, N = 1291 adult patients from all over Germany were included. The total annual costs in the group with all severity grades (n = 706) amounted to € 3616 ± € 6452 (median € 874) per patient. For patients with mild AD (n = 367), the annual costs were € 1466 ± € 3029 (median € 551) per patient, while they were € 5229 ± € 7538 (median € 1791) for patients with moderate‐to‐severe AD (n = 682). The total economic burden for treating adult patients with AD in Germany is estimated at more than € 2.2 billion. Conclusions: In total, the data from this study show that compared to for example psoriasis, AD has a moderate level of costs‐of‐illness in Germany. The approval of new therapies is expected to lead to markedly more resource utilisation in the next years. [ABSTRACT FROM AUTHOR]

Dr. Chernyshov, Dr. Stalder, Dr. Svensson, Dr. Kunz reports no conflict of interest. At least 3 weeks are recommended between the two COVID-19 vaccine doses, which increases the risk of AD flares and loss of AD control if the systemic AD medication is paused or reduced in dose for longer periods. European Task Force on Atopic Dermatitis: position on vaccination of adult patients with atopic dermatitis against COVID-19 (SARS-CoV-2) being treated with systemic medication and biologics. [Extracted from the article]

Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier‐stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti‐inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid‐potency corticosteroids are proven agents for proactive therapy, which is defined as the long‐term intermittent anti‐inflammatory therapy of frequently relapsing skin areas. Systemic anti‐inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit–risk ratio. The IL‐4R‐blocker dupilumab is a safe, effective and licensed, but expensive, treatment option with potential ocular side‐effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R‐blockers) only have limited effects on AD‐related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient‐specific, and elimination diets should only be advised in case of proven food allergy. Allergen‐specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress‐induced exacerbations. Efficacy‐proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults. [ABSTRACT FROM AUTHOR]

Editor Atopic dermatitis (AD), a common inflammatory skin condition characterized by chronic or relapsing episodes of eczema, itch and sleep disturbance,1 is associated with psychiatric, infectious and allergic comorbidities. Dr. Hijnen has been investigator, speaker or consultant for Abbvie, Eli Lilly, Incyte, LeoPharma, MedImmune/Astrazeneca, Pfizer, Sanofi and ThermoFisher. Dr. Ring has been an advisor or speaker for AbbVie, Allergika, Sanofi-Genzyme, Pfizer, Bencard, LEO Pharma and Mylan. [Extracted from the article]

Summary: Patients with atopic dermatitis (AD) have an increased risk of bacterial skin infections, which cause significant morbidity and, if untreated, may become systemic. Staphylococcus aureus colonizes the skin of most patients with AD and is the most common organism to cause infections. Overt bacterial infection is easily recognized by the appearance of weeping lesions, honey‐coloured crusts and pustules. However, the wide variability in clinical presentation of bacterial infection in AD and the inherent features of AD – cutaneous erythema and warmth, oozing associated with oedema, and regional lymphadenopathy – overlap with those of infection, making clinical diagnosis challenging. Furthermore, some features may be masked because of anatomical site‐ and skin‐type‐specific features, and the high frequency of S. aureus colonization in AD makes positive skin swab culture of suspected infection unreliable as a diagnostic tool. The host mechanisms and microbial virulence factors that underlie S. aureus colonization and infection in AD are incompletely understood. The aim of this article is to present the latest evidence from animal and human studies, including recent microbiome research, to define the clinical features of bacterial infections in AD, and to summarize our current understanding of the host and bacterial factors that influence microbial colonization and virulence. [ABSTRACT FROM AUTHOR]

Background: Cross‐sectional data on patient burden in adults with atopic dermatitis (AD) from real‐world clinical practice are limited. Objective: This study compared patient‐reported burden associated with adult AD across severity levels from clinical practices in Canada and Europe. Methods: This study included adults (18–65 years) diagnosed with AD by dermatologists, general practitioners or allergists. Participants categorized as mild (n = 547; 37.3%), moderate (n = 520; 35.4%) or severe (n = 400; 27.3%) based on Investigator's Global Assessment completed a questionnaire that included pruritus and pain numerical rating scales, Patient‐Oriented‐Scoring of Atopic Dermatitis (PO‐SCORAD) itch and sleep visual analogue scales, Dermatology Life Quality Index (DLQI), and the Hospital Anxiety and Depression Scale (HADS). Participants were also stratified by inadequate efficacy/intolerance/contraindication to cyclosporine [Cyclo; n = 62 (4 mild, 18 moderate, 40 severe)] and any systemic immunomodulatory agent [IMM; n = 104 (13 mild, 31 moderate, 60 severe)] and compared with the severe group excluding participants identified as Cyclo/IMM. Results: Age was similar across severity groups; the proportion of women was higher in the mild group relative to severe (61.2% vs. 50.5%; P < 0.001). Compared with moderate and mild, participants with severe AD had more comorbidities, higher itch and pain severity, worse sleep and higher levels of anxiety and depression (all P < 0.001). Mean ± SD DLQI score among participants with severe AD (16.2 ± 6.9) showed a large effect on quality of life that was higher than those with moderate (10.2 ± 6.3) and mild (5.5 ± 4.9) (both P < 0.001). The burden among Cyclo and IMM subgroups was generally similar to that of participants with severe AD. Conclusions: Adults with AD reported a substantial burden across multiple domains that was significantly higher in those with severe disease. The burden among participants in the Cyclo/IMM subgroups was similar to those with severe AD. [ABSTRACT FROM AUTHOR]

Background: Atopic eczema (AE) is a common and burdensome chronic skin disease. Clinical guidelines suggest an evidence‐based, personalized and stepwise treatment approach. Only few studies have so far focused on the specific patient needs in treatment. Objectives: To characterize therapeutic needs of patients with AE in routine care. Methods: Nationwide cross‐sectional study in 91 dermatology practices and outpatient clinics. Descriptive statistics were used for valuation. Comparisons of HRQoL and general health status were performed including subgroups (age, gender and disease duration). Group comparisons of patient needs were performed for age groups, gender and disease duration. Correlations between patients' needs (PNQ) and HRQoL, generic health status and severity were tested. In addition, a hierarchical regression analysis was performed to determine which variables contribute to explain the variance in patient needs. Results: Analysis of 1678 patients (60.5% female, mean age 38.35 ± 15.92 years) revealed a high disease burden with mean SCORAD of 42.26 ± 18.63, mean DLQI of 8.49 ± 6.45 and mean EQ VAS of 63.62 ± 21.98. Among the patient needs that were most frequently rated as 'quite important'/'very important' were as follows: 'to be free of itching' (96.0%), 'to get better skin quickly' (7.8%) and 'to be healed of all skin defects' (85.7%). In general, older people, women and patients who had been diagnosed with AE for 1 year or less rated the treatment needs as more important than younger patients, men and patients who had been diagnosed with AE for more than 1 year. Major determinants of higher needs were skin‐related quality of life impairments, higher disease severity and higher age. Conclusions: Patients with AE show a high number and variety of therapeutic needs related to disease signs and symptoms, which are associated with individual disease burden. The patient needs vary substantially according to patient characteristics. Identification of patient‐specific needs may support personalized, patient‐centred care and shared decision‐making. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up‐to‐date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine. [ABSTRACT FROM AUTHOR]

LCH can be subdivided into five different forms: single-system LCH, LCH with lung involvement, multiple-system LCH with or without risk organs affected and LCH associated with another myeloproliferative/myelodysplastic disorder. Despite a known variety of clinical manifestations of LCH, in this observation we report the first LCH manifestation with generalized pruritic nodules. Langerhans cell histiocytosis (LCH) depicts a rare disease belonging to the group of histiocytoses. [Extracted from the article]

Background: Quality indicators are essential tools for the assessment of health care, in particular for guideline‐based procedures. Objective: Development of a set of indicators for the evaluation of process and outcomes quality in atopic dermatitis (AD) care. Application of the indicators to a cross‐sectional study and creation of a global process quality index. Methods: An expert committee consisting of 10 members of the German guideline group on AD condensed potential quality indicators to a final set of 5 outcomes quality and 12 process quality indicators using a Delphi panel. The outcomes quality and 7 resp. 8 process quality indicators were retrospectively applied to a nationwide study on 1678 patients with atopic dermatitis (AtopicHealth). Each individual process quality indicator score was then summed up to a global index (ranges from 0 [no quality achieved] to 100 [full quality achieved]) displaying the quality of health care. Results: In total, the global process quality index revealed a median value of 62.5 and did not or only slightly correlate to outcomes quality indicators like the median SCORing Atopic Dermatitis (SCORAD; rp = 0.08), Dermatology Life Quality Index (DLQI; rp = 0.256) and Patient Benefit Index (PBI; rp = −0.151). Conclusion: Process quality of AD care is moderate to good. The healthcare process quality index does not substantially correlate to the health status of AD patients measured by 5 different outcomes quality indicators. Further research should include the investigation of reliability, responsiveness and feasibility of the proposed quality indicators for AD. [ABSTRACT FROM AUTHOR]

Background: Previous studies have indicated that in patients with atopic dermatitis (AD) and birch pollen allergy pollen‐related foods are able to cause late eczematous response. However, the relevance of AD worsening by ingestion of birch pollen‐related foods is still a matter of debate. Objective: The purpose of this retrospective study was to determine how frequently birch pollen‐related foods induce a deterioration of eczema. Additionally, the diagnostic value of specific IgE (sIgE) determination was evaluated. Methods: A total of 182 children and adults with AD and suspected birch pollen‐related food allergy underwent 261 double‐blind placebo‐controlled food challenges (DBPCFC). Total and sIgE levels were determined prior to DBPCFC. Results: Sixty‐five patients developed allergic reactions (responders) upon DBPCFC with birch pollen‐related foods (n = 103 DBPCFC). Of these, 32 patients exhibited significant deterioration of AD defined as a median increase of 15.4 severity scoring of atopic dermatitis index points (95% CI 12.4‐16.3) from baseline making up 37% of all positive reactions. Responders showed significantly higher sIgE levels to birch pollen and apple as well as a higher prevalence of allergic rhinoconjunctivitis compared to nonresponders (P < .05). However, patients with late eczematous response could not be differentiated from those with isolated immediate‐type reactions by sIgE levels. Conclusion: In a subpopulation of patients with AD and birch pollen sensitization, related foods should be considered as a trigger for an aggravation of eczema. As sufficient markers for prediction of late eczematous reactions are still lacking, DBPCFC cannot be replaced in diagnosis of birch pollen‐related foods in patients with AD. Clinical implications: In patients with AD and birch pollen allergy, birch pollen‐related foods should be considered as a provocation factor for an aggravation of disease signs and symptoms. Thirty‐seven percent of all positive reactions to birch pollen‐related foods were associated with a significant deterioration of atopic dermatitis (AD). Responders showed significantly higher sIgE levels to birch pollen and apple as well as a higher prevalence of allergic rhinoconjunctivitis compared to nonresponders (P < .05). In patients with AD and birch pollen allergy, birch pollen‐related foods should be considered as a provocation factor for an aggravation of dermatitis even in the absence of immediate‐type reaction to birch pollen‐related foods. [ABSTRACT FROM AUTHOR]

Abstract: This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus‐based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen‐specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease‐modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen‐specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress‐induced exacerbations. Therapeutic patient education (‘Eczema school’) is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline. [ABSTRACT FROM AUTHOR]

Abstract: This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus‐based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen‐specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti‐inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long‐term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long‐term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti‐inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline. [ABSTRACT FROM AUTHOR]