Decreased skin colonization with Malassezia spp. and increased skin colonization with Candida spp. in patients with severe atopic dermatitis

Background: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease in which patients are sensitized towards a plethora of allergens. The hosts fungal microbiota, the mycobiota, that is believed to be altered in patients suffering from AD acts as such an allergen. The correlation context of specific sensitization, changes in mycobiota and its impact on disease severity however remains poorly understood. Objectives: We aim to enhance the understanding of the specific sensitization towards the mycobiota in AD patients in relation to their fungal skin colonization. Methods: Sensitization pattern towards the Malassezia spp. and Candida albicans of 16 AD patients and 14 healthy controls (HC) were analyzed with the newly developed multiplex-assay ALEX2® and the established singleplex-assay ImmunoCAP®. We compared these findings with the fungal skin colonization analyzed by DNA sequencing of the internal transcribed spacer region 1 (ITS1). Results: Sensitization in general and towards Malassezia spp. and C. albicans is increased in AD patients compared to HC with a quantitative difference in severe AD when compared to mild to moderate AD. Further we saw an association between sensitization towards and skin colonization with Candida spp. yet a negative correlation between sensitization towards and skin colonization with Malassezia spp. Conclusion: We conclude that AD in general and severe AD in particular is associated with increased sensitization towards the hosts own mycobiota. There is positive correlation in Candida spp. skin colonization and negative in Malassezia spp. skin colonization when compared to AD, AD severity as well as to specific sensitization patterns

Comorbidities of atopic dermatitis—what does the evidence say?

Atopic dermatitis (AD) is a common disease that is associated with atopic and nonatopic comorbidities. There has been a growing interest in this area of AD, because presence or risk of comorbidities can in many ways impact the management of patients with AD. Thus, some treatments for AD may improve its comorbidities as well, whereas others may increase their risk. In this review article, we discuss various comorbidities of AD mostly on the basis of the results of recent multiple systematic reviews and meta-analyses to update readers about this rapidly developing area of dermatology. We emphasize the important information provided by studies presenting both relative risk and absolute risk, and show that AD is associated with, among others, atopic comorbidities such as asthma, rhinitis, and food allergy, nonatopic comorbidities such as ocular, psychiatric, infectious, endocrine, autoimmune, and cardiovascular diseases, and certain cancers. Clinicians need to be aware of these and be cognizant about positive and negative effects of existing and new treatments for AD

IgE-mediated sensitization to malassezia in atopic dermatitis: More common in male patients and in head and neck type

BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Malassezia, the predominant skin microbiota fungus, is considered to exacerbate AD, especially in a subset of patients with head and neck type AD (HNAD). In the present study, the relationship between AD and sensitization to Malassezia antigens was investigated. METHODS: We assessed 173 patients with AD. The severity of eczema was determined with Eczema Area and Severity Index (EASI); the type of AD, namely, head and neck type, was reported as well. The total serum IgE and specific IgE to Malassezia were determined and correlated with clinical picture of AD, sex, age, and the EASI. RESULTS: Total IgE was elevated in 77.7% of patients. Specific IgE to Malassezia was positive (≥0.35 kU/L) in 49.1% of patients. Men were significantly more often sensitized to Malassezia antigen (58% of men vs 42% of women; P value, 0.04). Concurrently, 58% of patients with HNAD versus 42% non-HNAD patients had higher levels of specific IgE to Malassezia, this difference being nearly significant (P value, 0.06). Patients with atopy were also more frequently sensitized to Malassezia. No significant relationship between EASI and the level of total IgE or specific IgE to Malassezia was observed. CONCLUSIONS: In our population, IgE-mediated sensitization was found in up to 49% of all patients with AD, most common in men and in head and neck type

Efficacy and safety of abrocitinib in patients with moderate‐to‐severe atopic dermatitis and comorbid allergies

Background: Abrocitinib efficacy by comorbidity status in patients with moderate‐to‐severe atopic dermatitis (AD) has not been previously assessed. This post hoc analysis evaluated the efficacy and safety of abrocitinib in patients with AD and allergic comorbidities. Methods: Data were pooled from patients who received abrocitinib 200 mg, 100 mg, or placebo in phase 2b (NCT02780167) and phase 3 (NCT03349060, NCT03575871) monotherapy trials. Patients with and without allergic comorbidities (allergic asthma, rhinitis, conjunctivitis, or food allergy) were evaluated for Investigator's Global Assessment (IGA) response (clear [0] or almost clear [1]), ≥75% improvement in the Eczema Area and Severity Index (EASI‐75), ≥4‐point improvement in Peak Pruritus Numerical Rating Scale (PP‐NRS4), and Dermatology Life Quality Index (DLQI) response (<2 with baseline score ≥2). Other outcomes were Patient‐Oriented Eczema Measure (POEM), SCORing Atopic Dermatitis (SCORAD), Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD), and treatment‐emergent adverse events (TEAEs). Results: Of 942 patients, 498 (53%) reported at least one allergic comorbidity (asthma only, 33%; conjunctivitis only or rhinitis only or both, 17%; food allergies only, 15%; >1 allergic comorbidity, 34%). Regardless of comorbidity status, from Week 2 to Week 12, higher percentages of patients treated with either abrocitinib dose achieved IGA 0/1, EASI‐75, PP‐NRS4, or DLQI 0/1 versus placebo‐treated patients. Changes from baseline in POEM, SCORAD, and PSAAD were greater with abrocitinib than with placebo in patients with and without allergic comorbidities. Most TEAEs were mild or moderate. Conclusions: Efficacy and safety data support abrocitinib use to manage AD in patients with or without allergic comorbidities

Clinical effectiveness of hymenoptera venom immunotherapy

Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors. Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase. In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models. 22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate. It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy

Eosinophils Play a Surprising Leading Role in Recurrent Urticaria in Horses

Urticaria, independent of or associated with allergies, is commonly seen in horses and often shows a high reoccurrence rate. Managing these horses is discouraging, and efficient treatment options are lacking. Due to an incidental finding in a study on horses affected by insect bite hypersensitivity using the eosinophil-targeting eIL-5-CuMV-TT vaccine, we observed the prevention of reoccurring seasonal urticaria in four subsequent years with re-vaccination. In an exploratory case series of horses affected with non-seasonal urticaria, we aimed to investigate the role of eosinophils in urticaria. Skin punch biopsies for histology and qPCR of eosinophil associated genes were performed. Further, two severe, non-seasonal, recurrent urticaria-affected horses were vaccinated using eIL-5-CuMV-TT, and urticaria flare-up was followed up with re-vaccination for several years. Eotaxin-2, eotaxin-3, IL-5, CCR5, and CXCL10 showed high sensitivity and specificity for urticarial lesions, while eosinophils were present in 50% of histological tissue sections. The eIL-5-CuMV-TT vaccine reduced eosinophil counts in blood, cleared clinical signs of urticaria, and even prevented new episodes of urticaria in horses with non-seasonal recurrent urticaria. This indicates that eosinophils play a leading role in urticaria in horses, and targeting eosinophils offers an attractive new treatment option, replacing the use of corticosteroids

Leukocyte redistribution as immunological biomarker of corticosteroid resistance in severe asthma

Background: Earlier studies have suggested that the leukocyte redistribution can be considered as an immunological marker of the clinical response to corticosteroids (CS), representing an easy measurable potential biomarker in severe asthma. Objective: The aim of this study was to determinate the utility of the leukocyte redistribution as a biomarker of disease heterogeneity in patients with severe asthma and as a bioindicator of potential CS resistance. Methods: We developed an unbiased clustering approach based on the clinical data and the flow cytometry results of peripheral blood leukocyte phenotypes of 142 patients with severe asthma before and after systemic CS administration. Results: Based on the differences in the blood count eosinophils, neutrophils and lymphocytes, together with the flow cytometry measurements of basic T cell, B cell and NK cell subpopulations before and after systemic CS administration, we identified two severe asthma clusters, which differed in the cell frequencies, response to CS and atopy status. Patients in cluster 1 had higher frequency of blood eosinophils at baseline, were sensitized to less allergens and had better steroid responsiveness, measured as the pronounced leukocyte redistribution after the administration of systemic CS. Patients in cluster 2 were determined by the higher frequency of B-cells and stronger IgE sensitization status to the multiple allergens. They also displayed higher steroid resistance, as the clinical correlate for the lower leukocyte redistribution after administration of systemic CS. Conclusion: The flow cytometry-based profiling of the basic populations of immune cells in the blood and its analysis before and after systemic corticosteroid administration could improve personalized treatment approaches in patients with severe asthma. Keywords: asthma phenotypes; biological therapy; corticosteroids resistance; leukocyte redistribution; severe asthma; treatment asthm

Association of endotoxin and allergens with respiratory and skin symptoms: a descriptive study in laboratory animal workers

In laboratory animal work, allergens are classically considered to play a prominent role in generation of respiratory and skin symptoms. However, recent development may have changed working conditions and require an updating of preventive measures. In workers exposed to a range of animals besides laboratory mice and rats the relative role of endotoxin, irritants, and allergens in symptom generation was assessed for updating preventative measures and health surveillance. Eligible workers were recruited from university units in which exposure to rats and/or mice, occurrence of respiratory and/or skin symptoms, and/or a history of animal bites had been reported. Exposure to endotoxin and rat and mouse allergen was assessed (71 half-day personal samples). 'Symptomatic' was defined by work-related ocular, nasal, respiratory, or skin symptoms. A concentration of specific IgE against rat or mouse (e87 and e88) ≥0.35 kU/l defined sensitization. Sensitivity analyses examined the effect of alternative exposure indicators and definitions of 'sensitized' and 'symptomatic'. From 302 eligible workers, 177 participated. There were 121 and 41 workers in the asymptomatic and non-sensitized and symptomatic but non-sensitized group, respectively. Eight subjects were symptomatic and sensitized. Six sensitized subjects were asymptomatic. One participant could not be assigned to a subgroup. Airborne endotoxin and allergen concentrations were mostly below 20 EU m-3 or the detection limit, respectively. Clinical history showed that irritants and sensitizers other than mouse/rat allergen or endotoxin were a major cause of symptoms. Results were sensitive to the selected exposure indicator and the definition of 'symptomatic'. Health surveillance programs need to be adapted to include a larger range of allergens and pay more attention to irritants