Atopic Research Articles

Evaluating the Efficacy and Safety of Mepolizumab in Elderly Patients with Severe Asthma: Insights from the REDES Study

Objective Asthma and severe asthma are problems affecting all age groups, but asthma is frequently undiagnosed in the elderly, due to the poor perception of airflow limitation, lack of fitness, and presence of multiple comorbidities. Even so, the proportion of patients with severe asthma aged ≥65 is significant, and data on efficacy of asthma medications in the elderly are sometimes limited. We report here the effectiveness and safety of mepolizumab (an IL-5 inhibitor) in elderly (≥ 65 years) patients. Methods The REDES study was an observational, multicenter study of the effectiveness and safety of mepolizumab 100mg SC every 4 weeks in 318 severe asthma patients in Spain. This post-hoc analysis compares the effectiveness and safety of patients ≥65 years old to patients <65 years after 12 months of mepolizumab treatment. Results 27% of patients were ≥65 years old, compared with 73% of patients <65 years. Elderly patients showed a trend towards less frequent comorbid nasal polyps (p = 0.06) and a lower proportion of atopic sensitization (as detected by prick test or specific IgE) (p = 0.02). Similar improvements were noted in ACT score (p < 0.0001), comparable exacerbation reductions (p < 0.0001) and lung function parameters (p < 0.04 in elder group and p < 0.0001 in younger elder group), although an apparent greater reduction of OCS daily dose was observed in elder patients (p = 0.0002). No new safety signals were reported in the elderly population. Conclusions This study further supports mepolizumab as an effective and well tolerated therapy in the difficult to treat population of elderly patients with severe asthma.

Immunohistochemical investigation of transient receptor potential melastatin-2 and spexin immunoreactivity in atopic dermatitis and mycosis fungoides.

Atopic dermatitis (AD) is a chronic, pruritic, and inflammatory dermatosis seen in individuals with an atopic predisposition. This study aimed to examine the immunoreactivity of spexin and TRPM2 in skin samples from patients with AD and MF lesions using immunohistochemical methods. The study utilized a total of 60 skin samples, comprising 20 from AD patients, 20 from MF patients, and 20 from control subjects. Skin samples from patients diagnosed with other dermatological diseases, malignancies, and diabetes mellitus were excluded from the study. During staining, the prevalence (0.1: <25%, 0.4: 26-50%, 0.6: 51-75%, 0.9: 76-100%) and intensity (0: none, + 0.5: very low, + 1: low, + 2: moderate, + 3: intense) of immunoreactivity were used as criteria to establish a histo-score. Calculations employed the formula histo-score = prevalence x intensity. Statistically significant higher spexin histoscores were observed in both the AD and MF patient groups compared to the control group (1.30 ± 0.46, 1.04 ± 0.29, and 0.20 ± 0.07, respectively; p = 0.000). Similarly, TRPM2 histoscores were significantly higher in the AD and MF patient groups compared to the control group (1.12 ± 0.28, 1.02 ± 0.30, and 0.20 ± 0.07, respectively; p = 0.000). It is hypothesized that the increase in the neuropeptide spexin in both AD and MF is triggered by inflammation and contributes to itching mechanisms via galanin receptors. TRPM2, an ion channel, is speculated to be a marker of Reactive Oxygen Species (ROS) in chronic inflammatory dermatoses like AD, but it may not serve as a potential biomarker for distinguishing chronic inflammatory dermatoses from MF.

Unveiling the Effect of Age and IgE Level on Alopecia Areata: Insights from Comparative RNAseq Analysis.

Alopecia areata (AA) is a common autoimmune disease, causes sudden hair loss on the scalp, face, and sometimes other areas of the body. Previous studies have suggested more severe manifestations and higher recurrence rates in children than in adults. Moreover, pediatric AA patients with atopic predisposition often exhibit elevated IgE levels, early onset, and a poor prognosis. This study aimed to investigate the impact of age and IgE levels on AA by conducting RNA sequencing on scalp samples from AA patients with atopic predisposition, age-matched healthy controls, and AA samples with varying IgE levels. We employed the single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm in conjunction with gene expression analysis to assess immune infiltration. Differential gene expression analysis was performed using the DESeq package in R. Immunohistochemical staining and qPCR was performed to validate these findings. Our results revealed a more pronounced inflammatory immune infiltration in AA patients across all age groups compared to healthy controls. Pediatric AA was characterized by an upregulation of genes controlling inflammatory responses, such as the IFN-γ pathway and JAK-STAT cascade, contrasting to adult AA. Compared to age-matched healthy controls, pediatric AA patients exhibited a significant increase in the infiltration of B cell subtypes, mast cells, and regulatory T cells. Additionally, high IgE levels in AA patients led to the upregulation of IFN-γ pathway genes, compared to AA patients with normal IgE levels. In summary, the heightened immune and inflammatory responses, along with the more significant infiltration of immune cells in pediatric AA with atopic predisposition, may explain the increased clinical severity and recurrence rates. Dissecting these molecular mechanisms sheds some light on the contributions of age and IgE to the pathogenesis and progression of AA, revealing potential age-specific and allergy-related therapeutic targets.

No Evidence of Interaction Between FADS2 Genotype and Breastfeeding on Cognitive or Other Traits in the UK Biobank.

Breastfeeding is hypothesised to benefit child health and cognitive functioning by providing long-chain polyunsaturated fatty acids, which are essential for brain development. In 2007, Caspi et al. found evidence in two cohorts for an interaction between genetic variation in the FADS2 gene (a gene involved in fatty acid metabolism) and breastfeeding on IQ. However, subsequent studies have provided mixed evidence for the existence of an interaction. We investigated the relationship between genetic variation in the FADS2 region, breastfeeding, and their interaction in up to 335,650 individuals from the UK Biobank. We tested for the interaction over a range of cognitive functioning tests, as well as educational attainment and other traits thought to be influenced by breastfeeding, including cardiometabolic traits, number of offspring, and atopic allergy. FADS2 alleles associated with an increase in docosahexaenoic acid in blood serum (the C allele of rs174575) were associated with decreased verbal-numerical reasoning ( ) and triglycerides ( ), increased number of offspring ( ), total cholesterol ( ), HDL ( ), and LDL cholesterol ( ). We observed no evidence of an interaction in any of the traits, regardless of the modelling strategy on any cognitive or non-cognitive traits. We postulate that the previous positive findings are likely to be spurious, perhaps due to lack of appropriate control for latent population structure.

Success of Immunopathogenetic Therapy for Management of Congenital Ichthyosis, Combined Form, in a Child: Rare Clinical Case

Background. Congenital ichthyosis (CI) is relating to the group of clinical and genetically heterogeneous severe genodermatoses. SAM syndrome is included in classification of CI syndromic forms. Defects in the desmoplakin (DSP) and desmoglein 1 (DSG1) genes are the prime cause of disease. Impaired function of encoded proteins leads to desmosomal anomalies and disease symptoms. Comorbid atopic syndrome becomes the major cause of diagnostic mistakes. Patients are observed continuously with diagnosis “Atopic dermatitis (AD) torpid to standard treatment methods”. Clinical case description. This article describes a rare case of a boy with severe AD. Despite the chronic dermatosis several systemic disorders were revealed during examination: short stature, protein-energy malnutrition, adrenal insufficiency, juvenile polyarthritis, vitamin D deficiency, onychodystrophy, dysmorphic disorders. Molecular genetic study conducted via high-throughput sequencing followed by validation with Sanger sequencing has revealed two genetic variants: novel variant chr18:28934543G&gt;T in the DSG1 gene in the heterozygous state and pathogenic variant chr5:157468728C&gt;A in the NIPAL4 gene in the homozygous state. As a result, the final diagnosis was established: “SAM syndrome. Congenital ichthyosiform erythroderma”. Flow cytometry immunology study has shown dominant immunological profile of Th17-, and Thact-lymphocyte proliferation. The immunobiological therapy with IL-17A inhibitor, secukinumab, was initiated. Clinical efficacy was evaluated via ISS (Ichthyosis Severity Index), CDLQI (Children’s Dermatology Life Quality Index), pruritus numerical rating scale. ISS was 5.8 points, pruritus scale — 9, CDLQI — 24 at therapy initiation. Improvement in the skin condition was observed after a month of therapy. ISS was 1.2 points, pruritus scale — 2, CDLQI — 4 6 months after the therapy initiation. Conclusion. The diagnosis of a child with combined form of CI made it possible to change the management strategy, to prescribe pathogenetically justified targeted immunobiological therapy, and to achieve significant improvement in the child's health and quality of life, which does not differ from healthy peers.

Increasing prevalence of galactose-α-1,3-galactose sensitization in the Danish general adult population.

Alpha-gal syndrome is a novel food allergy to the oligosaccharide galactose-α-1,3-galactose (alpha-gal) present in mammalian meat. Tick bites are considered an important route of sensitization to alpha-gal. Data on alpha-gal sensitization in the general population is scant. We utilized a unique data source of repeated population-based health examination studies to assess prevalence, time trends, risk factors, and characteristics of alpha-gal sensitization. Alpha-gal sensitization was assessed in >11.000 adults from four health examination studies of randomly invited residents in the Copenhagen region conducted in 1990-1991, 2011-2012, 2012-2015, and 2016-2017. Alpha-gal sensitization was defined as serum specific IgE (sIgE) to alpha-gal ≥0.1 kUA/L; ≥0.35 kUA/L; ≥0.7 kUA/L; ≥3.5 kUA/L. The population was characterized according to genetically determined ABO blood group, aeroallergen sensitization, and pets at home. The prevalence of sIgE to alpha-gal ≥0.1 kUA/L was 1.3% in 1990-1991, 3.7% in 2012-2015 and 3.2% in 2016-2017. Of those sensitized to alpha-gal >97% reported to consume red meat at least once a week, even for sIgE to alpha-gal ≥3.5 kUA/L. Male sex, older age, aeroallergen sensitization, cat at home, and blood group A were associated with increased odds of alpha-gal sensitization. The known protective effect of blood group B was confirmed. In this general adult population, the prevalence of alpha-gal sensitization had doubled from 1990-1991 to 2016-2017. This could potentially be due to increased tick exposure and an increased atopic predisposition.

Early-pregnancy BMI, maternal gestational weight gain, and asthma and allergic diseases in children.

Association of early pregnancy body mass index (BMI) and maternal gestational weight gain (GWG), and asthma and allergic disease in children is unclear. We analyzed data from 3176 mother-child pairs in a prospective birth cohort study. Maternal anthropometric measurements in the first and last antenatal clinic visits were obtained through post-delivery questionnaires to calculate early pregnancy BMI and maternal GWG. Asthma and allergic diseases in children by the age of 5 years was assessed using a validated questionnaire. Furthermore, serum samples were analyzed for IgE antibodies to eight allergens. We applied Cox proportional hazards and logistic regression analyses to estimate the association of early pregnancy BMI and maternal GWG (as continuous variables and categorized into quarters), and asthma, atopic eczema, atopic sensitization, and allergic rhinitis in children. Neither early pregnancy BMI nor maternal GWG was associated with asthma and allergic disease in children when analyzed as continuous variables. However, compared to the first quarter of GWG (a rate <0.32 kg/week), mothers in the third quarter (rate 0.42-0.52 kg/week) had children with significantly higher odds of developing atopic eczema (adjusted OR 1.49, 95% CI [1.13-1.96]) by 5 years of age. Association of early pregnancy BMI and maternal GWG, and asthma and allergic disease in children, is inconsistent. High maternal GWG may be associated with increased odds of atopic eczema.

Performance of applications of Ophytrium-containing mousse with or without shampoo in cats with pruritic and irritated skin: a multicentre prospective field trial.

This study aimed to evaluate the performance of a protocol in which topical products (DOUXO S3 CALM Shampoo and Mousse; Ceva Santé Animale) containing Ophytrium were applied to cats to help manage feline atopic syndrome (FAS). A total of 23 client-owned cats with a history of FAS and presenting irritated skin and pruritus were recruited for this study. The cats were either shampooed or moussed on day 0 (D0) and then moussed every 48-72 h for 3 weeks. On D0, D7 and D21, clinical signs were assessed using the validated scoring system, Scoring Feline Allergic Dermatitis (SCORFAD). Pruritus was graded by the owner using an adapted dual visual analogue scale (Pruritus Visual Analog Scale for Cats [VAScat]). Veterinarians also assessed pruritus intensity and frequency, and provided a subjective assessment of global skin condition and of improvements in each cat's condition. On D21, all questionnaires were collected from both veterinarians and owners. Among the 19 cats that completed the study, the SCORFAD and VASmax (maximum value of VAScat, either scratching or licking) scores improved by ⩾50% in 63.2% and 38.9% of animals, respectively. Mean SCORFAD values decreased significantly between D0 and D21 (from 6.2 to 2.8, P <0.05). Similarly, mean VASmax values decreased significantly between D0 and D21 (from 7.4 to 4.3, P <0.05). Overall, veterinarians assessed the improvement as satisfactory, good or excellent in 18/19 (94.7%) cases. The protocol was considered efficient and practical by 18/19 (94.7%) and 19/19 (100%) owners, respectively, and the resulting good condition of skin and coat was emphasised by 15/19 (78.9%) owners. This topical protocol with Ophytrium-containing mousse and shampoo was well tolerated. The products were effective in reducing skin irritation and discomfort quickly and significantly in cats with skin irritation and pruritus, yielding high satisfaction levels among both veterinarians and owners.

The Clinical Features of Vernal Conjunctivitis in Cicendo National Eye Hospital

Introduction: Vernal conjunctivitis is a chronic, recurrent form of allergic conjunctivitis that occurs mainly in children and is commonly found in warm and humid climates or tropical countries, including Indonesia. Although vernal conjunctivitis is a self-limiting disease, it often leads to visual impairment and significantly affects the patient's quality of life. Methods: This retrospective descriptive study was conducted in Cicendo National Eye Hospital from March to April 2023 using the total sampling method to obtain the clinical features of vernal conjunctivitis patients. Result: This study took 117 patients (234 eyes) registered in electronic medical records from January to December 2022 with an age range of 7-18 years. The mean age of the patients was 10.73 ± 3.02 years, with total of 78 patients (66.67%) being male. A total of 30 patients (25.64%) had a history of atopic allergies. All patients in this study had a bilateral condition. The palpebral type was diagnosed in 85 patients (72.64%). Red eyes were the most prominent symptom experienced in 89 eyes (76.06%). Papillary signs were seen in 203 eyes (86.75%), with an uncorrected visual acuity of 6/6 to 6/18 were found in 163 eyes (69.66%). A small proportion of patients experienced complications in 93 eyes (39.74%). Conclusion: The clinical features of vernal conjunctivitis patients in Cicendo National Eye Hospital are similar to those in other tropical countries. Most patients were male and complained of itching and red eyes. The palpebral type is the most common type. Few distinct features were noted indicating a low association with atopy.

Cord blood methylation at TNFRSF17 is associated with early allergic phenotypes

Food allergy and eczema are the earliest allergic phenotypes in childhood. These diseases could be related to either IgE-mediated or non-IgE-mediated reactions to the allergen. TNFRSF17 is a key molecule in B cell maturation and is important in both types of responses.We conducted a study comparing the relative expression and the methylation status at the TNFRSF17 in regard to the child’s early atopic sensitisation and allergic phenotypes.In the recruited population of 200 women and 174 children with available clinical data (physical examination by allergist and antigen-specific IgE measurements), 78 cord blood samples were included in the gene expression analysis (relative gene expression with GAPDH as reference by RT-PCR) and 96 samples with microarray DNA methylation data (whole genome methylation profile Infinium MethylationEPIC).The altered TNFRSF17 methylation pattern in the cord blood at both single cg04453550 and mean methylation at upstream of TNFRSF17 was observed in children who developed food allergy and/or eczema in early childhood. The change in methylation profile was mirrored by the relative expression. The profile of IgE sensitisation to food and/or inhalant allergens was not significantly associated with either methylation or expression of TNFRSF17.In conclusion, methylation at the upstream sites at TNFRSF17 in the cord blood at birth is associated with food allergy and eczema early in childhood.

Neonatal BCG Vaccination for Prevention of Allergy in Infants: The MIS BAIR Randomised Controlled Trial.

The beneficial off-target effects of Bacille Calmette-Guérin (BCG) vaccination potentially include protection against allergy. In the MIS BAIR trial, we aimed to determine whether neonatal BCG vaccination reduces atopic sensitisation and clinical food allergy in infants. In this randomised controlled trial, 1272 neonates were allocated to BCG-Denmark vaccine (0.05 mL intradermal dose) or no BCG at birth. Randomisation was stratified by recruitment site, mode of delivery and plurality of birth. The primary outcome was the incidence of atopic sensitisation determined by skin prick test at 1 year of age. Food allergy was determined by 3-monthly online questionnaires and oral food challenges. Data were analysed by intention-to-treat using binary regression. gov (NCT01906853). Atopic sensitisation during the first year of life was 22.9% among infants in the BCG group and 18.9% in the control group (adjusted risk difference (aRD) 3.8% (95% CI -1.5 to 9.1) after multiple imputation). Clinical food allergy was similar between infants in the BCG and control groups (9.8% vs. 9.6%; aRD 0.2, 95% CI -3.4 to 3.8). An interaction was observed between the primary outcome and maternal history of BCG vaccination. No interaction was observed for the additional prespecified potential effect modifiers tested (sex, delivery mode, family history of any allergy, season of birth, hepatitis B vaccination at randomisation, BCG scar and age at BCG administration). Neonatal BCG-Denmark vaccination does not protect against atopic sensitisation or clinical food allergy in the first year of life.

Atopic diseases-Diagnostics, mechanisms, and exposures.

Epidemiological data suggest that atopic diseases begin in early life and that most cases present clinically during early childhood. The diseases are highly prevalent and increase as communities adopt western lifestyles. Disentangling the pathophysiological mechanisms leading to disease debut is necessary to identify beneficial/harmful exposures so that successful prevention and treatment can be generated. The objective of this review is to explore the definition of atopy and mechanisms of atopic diseases, and to investigate the importance of environmental factors in early life, prior to disease development. First, the distribution of sIgE levels in children is investigated, as this is one of the main criteria for the definition of atopy. Thereafter, it is explored how studies of parental atopic status, sensitization patterns, and early debut and severity of atopic dermatitis have substantiated the theory of an early-life window of opportunity for intervention that precedes the development of atopic diseases in childhood. Then, it is examined whether early-life exposures such as breastfeeding, dogs, cats, and house dust mites in the home perinatally constitute important influencers in this crucial time of life. Finally, it is discussed how these findings could be validated in randomized controlled trials, which might prepare the ground for improved diagnostics and prevention strategies to mitigate the current atopic pandemic.

The prevalence of hand dermatitis among intensive care unit nurses.

Healthcare workers are at high risk of developing occupational hand dermatitis (HD) due to their frequent exposure to wet-work and use of gloves. Complaints of HD may interfere with work and cause loss of work productivity, or sick leave, and may have impact on job pleasure and performing daily activities. The prevalence of HD among intensive care unit (ICU) nurses is unknown. To investigate the point prevalence and the 1-year prevalence of HD among ICU nurses, and to determine the impact of HD on work and daily activities. A questionnaire-based cross-sectional study was performed among ICU nurses. Participants were recruited in the Amsterdam University Medical Centre. A symptom-based questionnaire was used to determine HD and atopic predisposition, and an additional questionnaire was used concerning the influence of HD. ICU nurses with an atopic predisposition or symptoms suiting HD were invited for the hand dermatitis consultation hour (HDCH). Data were analysed with logistic regression. A total of 184 ICU nurses were included. The point prevalence of HD was 9.8% (95% CI: 5.9-15.0) and the 1-year prevalence was 26.6% (95% CI: 20.4-33.6). Sick leave was reported by 0.5%. HD seemed to have more impact on job pleasure than on work productivity. The high prevalence rate of HD resulting from our study highlights the need for the prevention of occupational HD among healthcare workers.

Diagnosis and treatment of atopic skin syndrome in cats

Background: Feline allergic skin disease presents a diagnostic challenge due to the potentially subtle and widely variable clinical presentations known as feline reaction patterns. Cats are often secretive in their pruritic behaviours and so, unlike with canine disease, the clinical history for a cat may not give insight into the presence of pruritus. Once a diagnosis of feline allergic disease is achieved, there are several treatment options available; however, the majority have not been studied extensively in cats and many represent off‐license use.Aim of the article: This article outlines the relevant steps in making a diagnosis of feline atopic skin syndrome and reviews the treatment options available.

OSBPL2 compound heterozygous variants cause dyschromatosis, ichthyosis, deafness and atopic disease syndrome

In this study, we identified and diagnosed a novel inherited condition called Dyschromatosis, Ichthyosis, Deafness, and Atopic Disease (DIDA) syndrome. We present a series of studies to clarify the pathogenic variants and specific mechanism. Exome sequencing and Sanger sequencing was conducted in affected and unaffected family members. A variety of human and cell studies were performed to explore the pathogenic process of keratosis. Our finding indicated that DIDA syndrome was caused by compound heterozygous variants in the oxysterol-binding protein-related protein 2 (OSBPL2) gene. Furthermore, our findings revealed a direct interaction between OSBPL2 and Phosphoinositide phospholipase C-beta-3 (PLCB3), a key player in hyperkeratosis. OSBPL2 effectively inhibits the ubiquitylation of PLCB3, thereby stabilizing PLCB3. Conversely, OSBPL2 variants lead to enhanced ubiquitination and subsequent degradation of PLCB3, leading to epidermal hyperkeratosis, characterized by aberrant proliferation and delayed terminal differentiation of keratinocytes. Our study not only unveiled the association between OSBPL2 variants and the newly identified DIDA syndrome but also shed light on the underlying mechanism.

Maternal use of snus as smokeless tobacco in pregnancy and infant lung function.

Smoking in pregnancy has detrimental effects on infant respiratory health, while the effects of other nicotine-containing products on infant lung function are unclear. We aimed to explore if smokeless tobacco such as snus used in pregnancy increased the risk of lower lung function in infancy and if the associations differed by sex. From the Scandinavian population-based Preventing Atopic Dermatitis and ALLergies in Children birth cohort, we included 1163 infants with available tidal flow-volume measurements at 3 months of age and maternal self-reported use of nicotine-containing products in pregnancy. The risk of a ratio of time to peak tidal expiratory flow to total expiratory time <25th percentile by any nicotine exposure, snus exclusively and cigarette smoking with or without other nicotine-containing products was explored by regression analyses adjusting for maternal age, education and asthma. Overall 120 out of 1163 (10.3%) infants were exposed to any nicotine in utero, 71 out of 120 by snus exclusively and 49 out of 120 by smoking, with six also exposed to snus. By pregnancy week 6, 85.8% of mothers reported stopping nicotine use. The risk of lower lung function was higher in children exposed in utero to nicotine-containing products with an odds ratio (OR) of 1.63 (95% confidence interval (CI) 1.02-2.59) with a similar tendency for snus exclusively (OR 1.55, 95% CI 0.88-2.71) and smoking (OR 1.79, 0.84-3.84). Effect estimates were similar after adjusting for covariates. No differences of the effect by sex were observed. Our study suggests that in utero exposure to not only cigarettes, but also snus, may negatively affect infant lung function.

Rare FLG mutation associated with severe atopy

Background: The prevalence of atopic disease, which consists of conditions such as atopic dermatitis, allergies, and asthma, has been on the rise in recent decades. In children, atopic dermatitis often acts as an initial manifestation of atopic disease and frequently precedes the development of food allergies, asthma, and allergic rhinitis. Mutations in the FLG gene, encoding the fillagrin precursor profillagrin, serve as a genetic risk factor for these diseases. Approximately 25%–50% of individuals with atopic dermatitis carry FLG mutations. It has been proposed that FLG mutations exhibit variations specific to different populations, indicating distinct patterns within each population. Severe allergic symptoms could indicate the presence of an underlying immunodeficiency or immune dysregulation and in patients with severe, early-onset, or simultaneous allergic conditions, these could be suggestive of an underlying Primary Atopic Disorder. Specifically, the allergic triad characterized by elevated IgE levels, eosinophilia, and eczema is a common feature in various inborn errors of immunity that could be mistakenly diagnosed as severe allergic conditions. Method: Our patient’s medical record was analyzed retrospectively, including her medical history, as well as results from immune laboratory tests and genetic analyses. Results: We present a 9-year-old female of mixed ethnicity with a history severe eczematous rash diagnosed with atopic dermatitis. Whole exome sequencing analysis revealed an initially novel heterozygous variant in the FLG gene (NM_002016: EXON3:c.C2218T: p.R740X). Conclusion: Healthcare providers caring for patients with atopic dermatitis and recurrent staphlococcus infections should be aware of the significant link between filaggrin gene mutations and the development of severe, persistent atopic dermatitis that begins in childhood, as well as its association with recurring staphlococcus infections. Additionally, they should keep in mind that certain inborn errors of immunity may predominantly manifest as severe and treatment-resistant atopic disorders. Statement of novelty: We have identified a rare variant in the FLG gene associated with severe atopic dermatitis and allergies.

Ciclosporin oral solution in cats: a retrospective survey of compliance with treatment and adverse effects.

The aim of the study was to assess long-term ciclosporin oral solution compliance in cats treated for feline atopic skin syndrome (FASS). A survey was sent by email to 114 owners who had administered ciclosporin oral solution to their cats for FASS. In total, 42 owners completed the survey. The population was composed of 30 domestic shorthair cats and 12 pure breeds. There were 20 males and 22 females, and the median age was 5.5 years. Ciclosporin oral solution was administered directly into the mouth in 32/42 (76%) and with food/other in 10/42 (24%) cats. The administration was considered easy in 18/42 (43%) cats, difficult in 23/42 (55%) and impossible in 1/42 (2%). Treatment was stopped in 25/42 (60%) cats. The causes were as follows: administration difficulty (nine cats, 21%); complete resolution (four cats, 10%); treatment failure (four cats, 10%); price (two cats, 4%); and other causes (two deaths, two neoplasia, one adverse effect and one lack of compliance). Adverse effects involving clinical signs were reported in 25 (60%) cats: ptyalism (8/42); dysorexia/anorexia (6/42); vomiting (4/42); diarrhoea (4/42); gingival hyperplasia (1/42); and a combination of vomiting, diarrhoea and ptyalism (2/42). In addition, altered behaviour was reported in 27/42 (64%) cats: hiding in seven cats; scared of owner in 10 cats; modification of sleeping or playing activity in six cats; inappropriate urination/defecation in two cats; aggression in one cat; and all of the above in one cat. In total, 24 (57%) cats had adverse effects involving both clinical signs and altered behaviour, and only six cats had either adverse clinical signs or behavioural changes. This survey showed that behavioural changes appear to be underestimated in the cats treated with ciclosporin oral solution and this could cause treatment failure due to lack of compliance. Larger-scale studies are needed to confirm these preliminary results.

Phenotypes, endotypes and genotypes of atopic dermatitis and allergy in populations of African ancestry on the continent and diaspora.

Atopic dermatitis is a complex inflammatory condition characterized by synergist interactions between epidermal and immune related genotypes, skin barrier defects and immune dysregulation as well as microbial dysbiosis. Ethnicity-specific variations in clinical presentation, immune endotypes and genetic susceptibility have been described in diverse populations. We summarize available data with specific consideration of AD in populations of African ancestry. Some highlights include the observation of AD lesions on extensor surfaces, lichen planus-like AD, prurigo type AD and follicular AD in African populations. In addition, a consistent absence of dominant filaggrin gene defects has been reported. The detection of normal filaggrin protein content in AD skin implicates the contribution of alternative mechanisms in the pathogenesis of AD in African patients. Markedly high IgE has been described in paediatric and adult African AD. While Th2, Th22 and Th17 activation in African AD skin shares the same direction as with other populations, it has been noted that the magnitude of activation is dissimilar. Reduced Th17 cytokines have been observed in the circulation of moderate to severe paediatric AD.

English Cocker Spaniels under primary veterinary care in the UK: disorder predispositions and protections

BackgroundThe English Cocker Spaniel (ECS) is one of the most popular dog breeds in the UK but information on disorder predisposition and protection is limited. Using anonymised veterinary clinical data from the VetCompass™ Programme, this study aimed to compare disorder predisposition and protection between the ECS and the remaining dogs under primary veterinary care in the UK during 2016. Electronic patient records for random samples of ECS and non-ECS were reviewed. The most common disorders diagnosed during 2016 were extracted and compared using multivariable logistic regression, controlling for confounders.ResultsThe analysis included random samples of 2510/10,313 (24.3%) ECS and 7813/326,552 (2.39%) non-ECS. After accounting for confounding by age, sex, bodyweight within breed-sex, insurance status and veterinary practice group, the ECS had increased odds of 21/43 (48.85%) disorders at fine-level precision, with highest odds for aural discharge (odds ratio (OR) 14.66, 95% confidence interval (CI): 7.73–30.90, P < 0.001) and keratoconjunctivitis sicca (OR 7.64, 95% CI: 4.33–14.14, P < 0.001) and lowest odds for atopic dermatitis (OR 0.14, 95% CI: 0.05–0.31, P < 0.001) and allergy (OR 0.14, 95% CI: 0.06–0.28, P < 0.001).ConclusionsThis study provides evidence for strong predisposition to aural and ocular disorders and protection from hypersensitivity disorders in the ECS. These results can aid dog owners, breeders, and veterinarians to better monitor health in ECS, and promote earlier diagnosis with improved prognosis. Further, the results can help breeding organisations establish key priorities the health-based reforms of the ECS.