Proteomic, miRNA and bacterial biomarker patterns in atopic dermatitis patients and their course upon anti-IL-4Rα therapy.

BACKGROUND: Identification of biomarkers is required for a systems medicine approach and personalized treatment in atopic dermatitis (AD). These biomarkers may not only aid in diagnosing but also might be suitable to predict the effectiveness of targeted treatment. OBJECTIVE: We aimed to identify proteomic, microbial and miRNA biomarkers in AD patients and investigated their course in relation to the clinical response upon anti-IL-4Rα therapy. METHODS: Proteomic and miRNA screening was performed in AD patients in comparison to healthy controls. Differentially regulated serum proteins, miRNA and selected skin microbiota were measured consecutively in 50 AD patients before and upon systemic dupilumab treatment. A random forest classifier was used to predict the outcome of dupilumab therapy based on the initial biomarker patterns. RESULTS: We identified 27 proteomic candidates, miRNA and three microbial strains to be dysregulated in AD. CCL17, CCL13, CCL22, E-selectin and BDNF were differently regulated and significantly associated with treatment response. In contrast, neither the microbial composition nor the miRNA pattern was associated with treatment response upon dupilumab treatment. CONCLUSION: AD patients display defined dysregulations regarding their systemic proteomic serum profile, miRNA patterns and their skin microbiome. The proteomic profile and selected skin bacteria changed profoundly upon anti-IL-4Rα therapy which was associated with an overall clinical response. This was not seen in miRNA-related biomarkers. Our findings support the hypothesis that biomarker profiles reflect treatment responses and may in the future be used to develop a personalized medicine approach for the treatment of AD patients.

Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.

Short-course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy.

BACKGROUND: A modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid-A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short-course treatment of grass-pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial. METHODS: In this exploratory, randomized, double-blind, placebo-controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre-seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18-65 years) with moderate-to-severe SAR with or without asthma that was well-controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ-S) and allergen-specific IgG4 response. RESULTS: The mean CSMS compared to placebo was 33.1% (p = .0325) and 39.5% (p = .0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p < .01) as well as an improvement in total RQLQ-S for the extended regimen (mean change -0.72, p = .02). Both regimens were well-tolerated. CONCLUSIONS: This trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well-tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial.

Acquired Brain Injury Among Adolescents and Young Adults: A Nationwide Study of Labor Market Attachment.

Purpose Young patients represent a particularly vulnerable group regarding vocational prognosis after an acquired brain injury (ABI). We aimed to investigate how sequelae and rehabilitation needs are associated with vocational prognosis up to 3 years after an ABI in 15-30-year-old patients. Methods An incidence cohort of 285 patients with ABI completed a questionnaire on sequelae and rehabilitation interventions and needs 3 months after the index hospital contact. They were followed-up for up to 3 years with respect to the primary outcome "stable return to education/work (sRTW)", which was defined using a national register of public transfer payments. Data were analyzed using cumulative incidence curves and cause-specific hazard ratios. Results Young individuals reported a high frequency of mainly pain-related (52%) and cognitive sequelae (46%) at 3 months. Motor problems were less frequent (18%), but negatively associated with sRTW within 3 years (adjusted HR 0.57, 95% CI 0.39-0.84). Rehabilitation interventions were received by 28% while 21% reported unmet rehabilitation needs, and both factors were negatively associated with sRTW (adjusted HR 0.66, 95% CI 0.48-0.91 and adjusted HR 0.72, 95% CI 0.51-1.01). Conclusions Young patients frequently experienced sequelae and rehabilitation needs 3 months post ABI, which was negatively associated with long-term labor market attachment. The low rate of sRTW among patients with sequelae and unmet rehabilitation needs indicates an untapped potential for ameliorated vocational and rehabilitating initiatives targeted at young patients.

Tralokinumab plus topical corticosteroids in adults with severe atopic dermatitis and inadequate response to or intolerance of ciclosporin A: a placebo-controlled, randomized, phase III clinical trial (ECZTRA 7).

BACKGROUND: Patients with severe atopic dermatitis (AD) not controlled with topical therapy have limited treatment options. Ciclosporin A (CSA) is a commonly used, broad immunosuppressant in AD, but treatment with CSA requires monitoring for potentially serious adverse effects. In a previous phase III trial, tralokinumab plus topical corticosteroids (TCS) as needed provided early and sustained improvements in AD signs and symptoms. OBJECTIVES: To evaluate the efficacy and safety of tralokinumab plus TCS in adult patients with severe AD whose disease was not adequately controlled with CSA or who had contraindications to oral CSA. METHODS: In this 26-week, multicentre, parallel, randomized, double-blind, placebo-controlled, phase III trial, European adults with severe AD were randomized 1 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks plus TCS as needed. The primary endpoint was a 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. RESULTS: In total, 277 patients were randomized. At week 16, more patients treated with tralokinumab plus TCS vs. placebo plus TCS achieved EASI 75 [64·2% vs. 50·5%; difference 14·1% (95% confidence interval 2·5-25·7); P = 0·018], which increased further up to week 26. Improvements in AD severity were accompanied by early improvements in patient-reported outcomes, including Dermatology Life Quality Index, Patient-Oriented Eczema Measure, pruritus and sleep interference. Tralokinumab plus TCS also showed a higher EASI75 response at week 16 among patients who had previously failed CSA therapy vs. placebo plus TCS (57% vs. 41%). The overall incidence of adverse events was similar between treatment arms. CONCLUSIONS: Tralokinumab 300 mg plus TCS as needed was effective and well tolerated in patients with severe AD whose disease was not adequately controlled with CSA or who had contraindications to oral CSA.

Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study.

BACKGROUND: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. OBJECTIVE: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. METHODS: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. RESULTS: An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine. CONCLUSION: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.

Vocational/educational prognosis in adolescents and young adults with acquired brain injury: a nationwide cohort study.

OBJECTIVE: To determine prognostic factors for work ability and employment/educational status among young patients referred to outpatient neurorehabilitation clinics after an acquired brain injury. METHODS: A nationwide cohort study of 471 15-30-year-old patients who attended an interdisciplinary clinical assessment and provided questionnaire data at baseline and after one year. The outcomes were the Work Ability Score (WAS, 0-10 (best)) and employment/educational status after one year. Prognostic performance was analyzed using univariable regression and multivariable Ridge regression in a five-fold cross-validated procedure. RESULTS: Preinjury, 86% of the patients were employed, while the percentage had decreased to 55% at baseline and 52% at follow-up. The model, which included clinical measures of function, showed moderate prognostic performance with respect to WAS (R2=0.29) and employment/educational status (area under the curve (AUC)=0.77). Glasgow Outcome Scale Extended (R2=0.15, AUC=0.68) and the cognitive subscale of the Functional Independence Measure (R2=0.09, AUC=0.64), along with fatigue measured with the Multidimensional Fatigue Inventory (R2=0.15, AUC=0.60) were the single predictors with the highest predictive performance. CONCLUSION: Despite generally high scores in motor and cognitive tests, only about half of the patients were employed at baseline and this proportion remained stable. Global disability, cognitive sequelae and fatigue had the highest prognostic performance.

[Role of vegan diets in food allergies-risk of developing food anaphylaxis?] / Bedeutung veganer Ernährung für die Nahrungsmittelanaphylaxie.

We report about a 28-year-old woman with an anaphylactic reaction to falafel. The diagnosis of type 1 allergy to peas was made based on the detailed medical history, the sensitization profile and an oral food challenge. Pea (Pisum sativum) is a legume that is increasing used, for example, as protein flour in vegetarian and vegan food products. In addition to the case report, we discuss the anaphylaxis risk of food used in the vegan diet.

[Loss of tolerance : Anaphylaxis after milk protein shake consumption in an adult sportsman]. / "Loss of tolerance" : Anaphylaxie nach Milcheiweißshake bei einem erwachsenen Sportler.

We describe the case of a man who developed an acute allergic reaction for the first time in his life directly after drinking a protein shake after a workout session. Allergy diagnostics, including skin prick testing and the determination of specific IgE antibodies revealed sensitizations to cow's milk and hen's egg. Due to the association between the onset of symptoms after ingestion of a milk protein shake, a type-1-allergic reaction to milk protein was suggested. The patient denied a provocation test, although this could have been an opportunity to elucidate the role of physical exercise in this case. We suspect in the present case a loss of tolerance of early childhood sensitization due to repetitive high protein exposure in the context of physical activity. The patient was provided information regarding dietary and emergency management.

Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2).

BACKGROUND: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms. OBJECTIVES: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments. METHODS: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885. RESULTS: At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 [difference 8·6%, 95% confidence interval (CI) 4·1-13·1; P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8-16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5-17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8-27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient-Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16-week initial period. CONCLUSIONS: Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.

Predictors of disability in adolescents and young adults with acquired brain injury after the acute phase.

AIM: To develop and validate a prediction model for disability among young patients with acquired brain injury (ABI) after the acute phase. METHODS: Within a nationwide cohort of 446 15-30-year-old ABI-patients, we predicted disability in terms of Glasgow Outcome Scale - Extended (GOS-E) <7 12 months after baseline assessment in outpatient neurorehabilitation clinics. We studied 22 potential predictors covering demographic and medical factors, clinical tests, and self-reported fatigue and alcohol/drug consumption. The model was developed using multivariable logistic regression analysis and validated by 5-fold cross-validation and geographical validation. The model's performance was assessed by receiver operating characteristic curves and calibration plots. RESULTS: Baseline assessment took place a median of 12 months post-ABI. Low GOS-E (range 1-8 (best)) and Functional Independence Measure (range 18-126 (best)) along with high mental fatigue (range 4-20 (worst)) predicted disability. The model showed high validity and performance with an area under the curve of 0.82 (95% confidence interval (CI) 0.77, 0.87) in the cross-validation and 0.81 (95% CI 0.73, 0.88) in the geographical validation. CONCLUSION: We developed and validated a parsimonious model which effectively predicted disability. The model may be useful to guide decision-making in outpatient neurorehabilitation clinics treating young patients with ABI.

Thymic stromal lymphopoietin production induced by skin irritation results from concomitant activation of protease-activated receptor 2 and interleukin 1 pathways.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) mediates proallergic T helper 2-type responses by acting on leucocytes. Endogenous pathways regulating TSLP production are poorly defined. OBJECTIVES: To uncover the mechanisms by which skin barrier disruption elicits TSLP production and to delineate the level at which individual mechanistic components may converge. METHODS: A combination of primary keratinocytes, skin explants and in vivo strategies was employed. Murine skin was tape stripped in the presence of neutralizing antibodies or antagonists. Cells and explants were stimulated with interleukin (IL)-1 and protease-activated receptor 2 agonist (PAR-2-Ag). TSLP levels were quantified by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. Chromatin immunoprecipitation and promoter reporter assays were used to examine recruitment and functional activity of nuclear factor kappa B (NF-κB) at the TSLP promoter. RESULTS: TSLP induction in mouse skin occurred in a PAR-2- and IL-1-dependent manner. This scenario was duplicated by exogenous IL-1 plus PAR-2-Ag vs. each stimulus alone. Joint activity of PAR-2 and IL-1 was also observed in human keratinocytes. The TSLP promoter was identified as the target of PAR-2/IL-1, whereby PAR-2 activation augmented the recruitment of NF-κB and transcriptional activation over IL-1 alone. Combined treatment showed activity at concentrations of IL-1 unable to elicit NF-κB activity on their own. CONCLUSIONS: Skin barrier disruption activates the IL-1 and the PAR-2 pathways, which act in concert to activate the TSLP promoter and possibly other inflammatory genes. Awareness of this combined activity may permit a more flexible clinical management by selective targeting of either pathway individually or collectively. What's already known about this topic? Thymic stromal lymphopoietin (TSLP) is rapidly induced upon skin perturbation and mediates proallergic T helper 2-type responses by acting on leucocytes. Endogenous control of TSLP expression is poorly understood, but interleukin (IL)-1 is one regulator in the cutaneous environment In addition to IL-1, protease-activated receptor 2 (PAR-2) organizes central inflammatory pathways in the skin. What does this study add? IL-1 and PAR-2 pathways cooperate in driving TSLP production in mice and humans. Pathway integration occurs at the level of the TSLP promoter through enhanced recruitment and transcriptional activation of nuclear factor kappa B. When PAR-2 is co-stimulated, very low IL-1 levels (inactive by themselves) can induce biologically meaningful responses in the skin environment. What is the translational message? Physical skin irritation results in robust TSLP production by simultaneous activation of PAR-2 and IL-1 pathways.

Efficacy and safety of topical delgocitinib in patients with chronic hand eczema: data from a randomized, double-blind, vehicle-controlled phase IIa study.

BACKGROUND: Management of chronic hand eczema (CHE) remains a challenge; effective topical treatment is limited to corticosteroids. OBJECTIVES: To assess the efficacy and safety of a novel, pan-Janus kinase inhibitor (delgocitinib) in patients with CHE. METHODS: In this randomized, double-blind, phase IIa study, patients with CHE received delgocitinib ointment 30 mg g-1 or vehicle ointment for 8 weeks. The primary end point was the proportion of patients achieving treatment success ['clear'/'almost clear' skin with ≥ 2-point improvement in the Physician's Global Assessment of disease severity (PGA)] at week 8. Secondary end points included Hand Eczema Severity Index (HECSI) score changes and the proportion of patients achieving treatment success on the Patient's Global Assessment of disease severity (PaGA). RESULTS: Ninety-one patients were randomized. More patients receiving delgocitinib (46%) than vehicle (15%) [odds ratio 4·89, 95% confidence interval (CI) 1·49-16·09; P = 0·009] achieved treatment success (PGA). Adjusted mean HECSI score at week 8 was lower with delgocitinib (13·0) than with vehicle (25·8) (adjusted mean difference -12·88, 95% CI -21·47 to -4·30; P = 0·003). More patients receiving delgocitinib than vehicle achieved treatment success by PaGA, but this did not reach statistical significance. The incidence of adverse events was similar with delgocitinib and vehicle; none led to discontinuation of delgocitinib. CONCLUSIONS: Delgocitinib ointment was efficacious and well tolerated. As a plateau of efficacy was not observed, a longer treatment period may lead to increased efficacy. Further clinical studies are warranted to confirm these findings in patients with CHE. What's already known about this topic? Chronic hand eczema (CHE) has a significant burden. Few randomized controlled studies have evaluated current treatments for CHE; only limited data are available to inform and guide clinical practice decisions. There is currently an unmet need for efficacious and well-tolerated topical treatment options for patients with CHE. What does this study add? Delgocitinib is a novel, pan-Janus kinase (JAK) inhibitor specific for JAK1, JAK2, JAK3 and tyrosine kinase 2. Topical use of delgocitinib ointment resulted in clearance of CHE after 8 weeks of treatment in a significantly greater number of patients than vehicle; delgocitinib was also well tolerated. Results from this proof-of-concept clinical study suggest that topical delgocitinib may provide therapeutic benefit to patients with CHE with inadequate responses to topical corticosteroids.

Recurrent eczema herpeticum - a retrospective European multicenter study evaluating the clinical characteristics of eczema herpeticum cases in atopic dermatitis patients.

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.

Atopy patch testing with aeroallergens in a large clinical population of dermatitis patients in Germany and Switzerland, 2000-2015: a retrospective multicentre study.

BACKGROUND: The diagnostic significance of the atopy patch test for the management of dermatitis possibly triggered by aeroallergens is still controversial. However, sufficiently large studies with routinely tested standardized aeroallergen patch test preparations in dermatitis patients are lacking. OBJECTIVE: To evaluate the reaction frequency and the reaction profiles of 10 until mid-2015 commercially available, standardized aeroallergen patch test preparations of the 'Stallerpatch' test series (Stallergenes, Antony Cedex, France) in a large multicentre patient cohort. METHODS: A retrospective data analysis of patients with suspected aeroallergen-dependent eczematous skin lesions was performed, who were patch tested in 15 Information Network of Departments of Dermatology-associated clinics between 2000 and 2015. Patients were stratified according to their atopic dermatitis (AD) status. RESULTS: The study group included 3676 patients (median age 41 years, 34.8% males, 54.5% AD). The most common aeroallergens causing positive patch test reactions were Dermatophagoides pteronyssinus (19.6%), Dermatophagoides farinae (16.9%), birch (6.2%), timothy grass (6.0%), cat dander (5.4%), mugwort (4.9%) and dog dander (4.6%). Reactions to other pollen allergen preparations, that is 5 grasses (3.2%), cocksfoot (2.1%) and plantain (1.6%), were less common. Positive patch test reactions to aeroallergens were consistently more frequent in patients with AD. These patients showed proportionally less dubious, follicular, irritant and weak positive reactions. Independent of AD status, a patient history of past or present allergic rhinitis was associated with an increased chance of a positive aeroallergen patch test reaction to pollen allergens. CONCLUSION: The aeroallergen patch test is a useful add-on tool in clinical routine, especially in patients with AD and/or respiratory allergy. A patch test series comprising Dermatophagoides pteronyssinus, Dermatophagoides farinae, birch, timothy grass, cat dander and mugwort seems to be suitable. Controlled studies with specific provocation and elimination procedures are required to further evaluate the diagnostic significance of the proposed screening series.

Baseline characteristics, disease severity and treatment history of patients with atopic dermatitis included in the German AD Registry TREATgermany.

BACKGROUND: The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the 'real-life' situation of health care for patients with AD. OBJECTIVES: Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients. METHODS: Patients (≥18 years) with moderate-to-severe AD [objective (o)SCORAD > 20], or with current or previous anti-inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0-72), the oSCORAD (0-83) and the Investigator Global Assessment (IGA; 6-point scale) were used. The disease severity was globally scored by the patients [Patient Global Assessment (PGA); six-step Likert scale]. Disease symptoms were assessed by the patient-oriented eczema measure (POEM, 0-28) and numeric rating scales (NRS, 0-10). Health-related quality of life was measured using the dermatological life quality index (DLQI, 0-30). RESULTS: A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either 'current' (12.1%) or 'prescribed' (31.4%) at baseline. CONCLUSIONS: These 'real-life' data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order to achieve a perceptible improvement of quality of life of patients with moderate-to-severe AD.

[Reality of inpatient vasoactive treatment with prostacyclin derivatives in patients with acral circulation disorders due to systemic sclerosis in Germany]. / Versorgungsrealität der stationären vasoaktiven Therapie mit Prostazyklinderivaten bei Patienten mit akralen Durchblutungsstörungen bei systemischer Sklerose in Deutschland.

BACKGROUND: Raynaud's phenomenon and the frequently ensuing digital ulcerations represent an early and very distressing symptom in patients with systemic sclerosis (scleroderma, SSc) causing significant limitations in the ability to work and quality of life. The use of vasoactive drugs (especially intravenous prostacyclin derivatives) is recommended to reduce the risk of hypoxic tissue damage up to the loss of fingers. METHODS: In order to obtain information about the current state of treatment of patients with prostacyclin derivatives in routine clinical life in Germany, a survey was conducted among the centers affiliated to the German Network for Systemic Scleroderma (DNSS). In addition, a separate patient survey was conducted by the schleroderma self-help group (Sklerodermie Selbsthilfe e. V.), which only covered the symptoms Raynaud's syndrome, digital ulcers and the use of intravenous prostacyclin derivatives. RESULTS: Of the 433 patients surveyed 56% stated that they had already been treated with prostacyclin derivatives (iloprost/alprostadil) because of their illness and symptoms. A total of 61% received the treatment for severe Raynaud's phenomenon and 39% for digital ulcerations. Most respondents not only experienced an improvement in Raynaud's phenomenon and digital ulcers but also a significant improvement of limitations in everyday life. They also needed significantly less outside help and absenteeism from work was much lower. CONCLUSION: Patients consistently reported a positive effect of treatment with prostacyclin derivatives on Raynaud's phenomenon, acral ulcerations, pain and daily restrictions and felt well and safely cared for during inpatient treatment. These positive effects in the patients' perceptions provide crucial information supporting and confirming the current European and international treatment recommendations.

The frequency of specific contact allergies is reduced in patients with psoriasis.

BACKGROUND: Earlier studies suggested an inverse association between contact allergy and psoriasis, although the results of clinical studies have been inconsistent. Gene expression studies in human contact allergy focusing on immune responses revealed nickel being an inducer of T helper (Th)1/Th17 and some Th22 immune polarization, whereas fragrances were found to promote a Th2-dominated immune activation. OBJECTIVES: To investigate the epidemiological association between contact allergy and psoriasis in a large multicentre cohort and to analyse the sensitization profile to specific allergens in these patients. METHODS: Retrospective analysis of patch-tested patients from 56 departments of dermatology (1996-2015), including 2387 patients with psoriasis and 161 989 control patients. All patients with atopic dermatitis were excluded from both groups. RESULTS: The odds ratio (OR) for contact allergy was calculated to be 0·55 in patients with psoriasis (95% confidence interval 0·50-0·59). Logistic regression analyses with several independent variables indicated a 'protective effect' of having psoriasis for most allergens, independently of age, sex, affected body site and patch test indication. Fragrance mix II (OR 0·36) and lanolin alcohols (OR 0·38) were found to be among the least common allergens in patients with psoriasis. In contrast, the frequency of contact dermatitis to nickel was only marginally affected in patients with psoriasis compared with controls (OR 0·75). CONCLUSIONS: The inverse association between psoriasis and allergic contact sensitization is likely to be not exclusively mediated by psoriasis itself. The polarization of the activated immune response by specific allergens may influence the occurrence and significance of contact allergies in underlying immune-mediated diseases, eventually even beyond the skin.

Clinical reactivity of celery cultivars in allergic patients: Role of Api g 1.

BACKGROUND: Celery (Apium graveolens L.) is a vegetable consumed world-wide. Celery stalks and celeriac roots are often ingredients in convenient food products like spice blends and soups. OBJECTIVE: In this study, we examined the allergenicity of distinct celeriac cultivars. METHODS: Sixteen celery-allergic patients were identified using a double-blind, placebo-controlled food challenge. Ten different celeriac cultivars were used for skin prick testing in the patients. Two cultivars were further applied for oral food challenges; their protein composition was analysed by immunoblotting, and contents of major allergen Api g 1 were quantified. RESULTS: From the 10 investigated celeriac cultivars, two cultivars elicited significantly different skin reactivity ("Anita": 5.0 [2.0-12.0] mm vs "Prinz": 7.0 [3.0-9.5] mm; P = .047). Moreover, "Anita" induced fewer symptoms after a controlled oral-celeriac challenge in 14 patient (P < .001). The protein profiles on 2DE protein gels showed distinct protein patterns and higher protein amounts of Api g 1 in "Prinz" than in "Anita." CONCLUSIONS AND CLINICAL RELEVANCE: Taken together, the data from this study suggest that cultivar Anita is better tolerated in celery-allergic patients than "Prinz." Differences in the protein expression profile between the cultivars, particularly the different content of Api g 1, could cause the different allergenicity.