Atopic Manifestations Research Articles

Human body resistance dynamics in the post-covid period

The issue of the state of specific and nonspecific resistance in the post-COVID period and the possible consequences of COVID-19 remains poorly understood. A clinical and laboratory examination of 124 patients was conducted at various time points after COVID-19 infection. 62 patients recovered completely and 62 had post-COVID syndrome. The leukocyte count and leukogram were evaluated in all patients. Immunogram parameters were additionally evaluated in patients with post-COVID syndrome. The results showed that, regardless of post-COVID syndrome, leukocyte count is lower in all patients within six months after COVID-19 infection than in unaffected subjects. The absolute neutrophil count is restored only 12 months later. In the presence of post-COVID syndrome, the absolute number of CD3+, CD4+and CD19+lymphocytes was lower than in healthy people. At the same time, 3 to 15 months after that, IgA titer in patients with PCS was significantly lower and that of for total IgM and IgG was higher without any clinical or laboratory signs of inflammation. The total blood IgE level was significantly higher and increased by the end of the observation period. A decreased activity of nonspecific protection, as well as indicators of cellular and humoral immunity in patients with post-COVID syndrome is accompanied by higher rate of viral and bacterial infections of various localization. Whereas during the first period an increase in total blood ID is not accompanied by clinical signs of atopy, then 6 months later the frequency of allergy increases. During the same period, cases of a joint syndrome revealed as arthralgia or progressive joint destruction become more frequent. Atopic manifestations are often combined with joint syndrome. Thus, after a COVID-19 infection, a low long-term level of nonspecific protection remains in vivo. In patients with post-COVID syndrome, low nonspecific and specific body resistance is manifested by viral and bacterial infections of the mucous membranes and skin. An imbalance in the immune system contributes to developing allergic and autoimmune processes.

Experience of abrocitinib in atopic dermatitis

Atopic dermatitis is an autoinflammatory, genetically determined, itchy disease characterized by a long, relapsing course and a sharp decrease in the patient’s quality of life. Atopic dermatitis is caused by a complex interaction of immune dysregulation, epidermal gene mutations, and multi-environmental factors that affect the skin, causing intense itchy rashes. The disease often occurs among young children and subsequently has age-related clinical features. Currently, the treatment of atopic dermatitis has a wide range of options, including drugs from the group of small molecules recently registered in the Russian Federation. The drugs are intended for patients with moderate to severe atopic dermatitis. Baricitinib, abrocitinib and upadacitinib as Janus kinase inhibitors from the small molecule group have already demonstrated good tolerability, safety and a pronounced clinical effect in the vast majority of patients with atopic dermatitis in available clinical trials. The first clinical experience with the use of abrocitinib in adult patients with atopic dermatitis is presented. The interest of the presented clinical cases lies in the demonstration of high clinical efficacy and safety of mono- and combination therapy with the Janus kinase inhibitor abrocitinib. Despite the short period of treatment and observation (4 weeks), objective severity of atopic dermatitis manifestations (SCORAD index 60 points) and sharp decrease in the patients' quality of life (DLQI index 20 points), a reduction of clinical parameters exceeding 60% was achieved at a dose of 200 mg daily. During the whole observation period no adverse clinical reactions or changes in laboratory parameters were registered against the background of abrocitinib administration. The pilot results of abrocitinib use are encouraging and provide grounds for conducting longer and larger-scale studies to investigate the efficacy of the drug for its inclusion in the combination therapy of patients with moderate to severe atopic dermatitis.

Impaired calcium influx underlies skewed T helper cell differentiation in children with IgE-mediated food allergies.

Reasons for Th2 skewing in IgE-mediated food allergies remains unclear. Clinical observations suggest impaired T cell activation may drive Th2 responses evidenced by increased atopic manifestations in liver transplant patients on tacrolimus (a calcineurin inhibitor). We aimed to assess differentiation potential, T cell activation and calcium influx of naïve CD4+ T cells in children with IgE-mediated food allergies. Peripheral blood mononuclear cells from infants in the Starting Time for Egg Protein (STEP) Trial were analyzed by flow cytometry to assess Th1/Th2/Treg development. Naïve CD4+ T cells from children with and without food allergies were stimulated for 7 days to assess Th1/Th2/Treg transcriptional factors and cytokines. Store operated calcium entry (SOCE) was measured in children with and without food allergies. The effect of tacrolimus on CD4+ T cell differentiation was assessed by treating stimulated naïve CD4+ T cells from healthy volunteers with tacrolimus for 7 days. Egg allergic infants had impaired development of IFNγ+ Th1 cells and FoxP3+ transitional CD4+ T cells compared with non-allergic infants. This parallels reduced T-bet, IFNγ and FoxP3 expression in naïve CD4+ T cells from food allergic children after invitro culture. SOCE of naïve CD4+ T cells was impaired in food allergic children. Naïve CD4+ T cells treated with tacrolimus had reduced IFNγ, T-bet, and FoxP3, but preserved IL-4 expression. In children with IgE-mediated food allergies, dysregulation of T helper cell development is associated with impaired SOCE, which underlies an intrinsic impairment in Th1 and Treg differentiation. Along with tacrolimus-induced Th2 skewing, this highlights an important role of SOCE/calcineurin pathway in T helper cell differentiation.

PLCG2 variants in cherubism

BackgroundCherubism is most commonly caused by rare heterozygous gain-of-function (GOF) missense variants in SH3BP2, which appear to signal through Phospholipase C Gamma 2 (PLCG2) to cause excessive osteoclast activity leading to expansile lesions in facial bones in childhood. GOF variants in PLCG2 lead to autoinflammatory PLCG2-associated antibody deficiency and immune dysregulation (autoinflammatory PLAID, or PLAID-GOF), characterized by variably penetrant autoinflammatory, autoimmune, infectious, and atopic manifestations. Cherubism has not been reported in PLAID to date. ObjectiveTo determine whether GOF PLCG2 variants may be associated with cherubism. MethodsClinical, laboratory, and genomic data from two patients with cherubism and other clinical symptoms observed in patients with PLCG2 variants were reviewed. Primary B-cell receptor (BCR)-induced calcium flux was assessed by flow cytometry. ResultsTwo patients with lesions consistent with cherubism but no SH3BP2 variants were found to have rare PLCG2 variants previously shown to be GOF in vitro, leading to increased BCR-induced calcium flux in one patient’s B cells. Variable humoral defects, autoinflammatory rash, and other clinical and laboratory findings consistent with PLAID were observed as well. ConclusionGOF PLCG2 variants likely represent a novel genetic driver of cherubism and should be assessed in SH3BP2-negative cases. Expansile bony lesions expand the phenotypic landscape of autoinflammatory PLAID, and bone imaging should be considered in PLAID patients.

The journey toward disease modification in cow milk protein allergy.

Cow milk protein allergy (CMPA) is one of the most common food allergies in the pediatric age worldwide. Prevalence, persistence, and severity of this condition are on the rise, with a negative impact on the health-related quality of life of the patients and families and on the costs related to its management. Another relevant issue is that CMPA in early life may be the first stage of the "allergic march," leading to the occurrence of other atopic manifestations later in life, especially asthma, atopic eczema, urticaria, and rhinoconjunctivitis. Thus, "disease modification" options that are able to modulate the disease course of pediatric patients affected by CMPA would be very welcomed by affected families and healthcare systems. In this review, we report the most relevant progress on this topic.

IKZF1 and UBR4 gene variants drive autoimmunity and Th2 polarization in IgG4-related disease.

IgG4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease whose pathomechanisms remain poorly understood. Here, we identified gene variants in familial IgG4-RD and determined their functional consequences. All 3 affected members of the family shared variants of the transcription factor IKAROS, encoded by IKZF1, and the E3 ubiquitin ligase UBR4. The IKAROS variant increased binding to the FYN promoter, resulting in higher transcription of FYN in T cells. The UBR4 variant prevented the lysosomal degradation of the phosphatase CD45. In the presence of elevated FYN, CD45 functioned as a positive regulatory loop, lowering the threshold for T cell activation. Consequently, T cells from the affected family members were hyperresponsive to stimulation. When transduced with a low-avidity, autoreactive T cell receptor, their T cells responded to the autoantigenic peptide. In parallel, high expression of FYN in T cells biased their differentiation toward Th2 polarization by stabilizing the transcription factor JunB. This bias was consistent with the frequent atopic manifestations in patients with IgG4-RD, including the affected family members in the present study. Building on the functional consequences of these 2 variants, we propose a disease model that is not only instructive for IgG4-RD but also for atopic diseases and autoimmune diseases associated with an IKZF1 risk haplotype.

Effect of Bifidobacterium bifidum Supplementation in Newborns Born from Cesarean Section on Atopy, Respiratory Tract Infections, and Dyspeptic Syndromes: A Multicenter, Randomized, and Controlled Clinical Trial.

Cesarean section is considered a possible trigger of atopy and gut dysbiosis in newborns. Bifidobacteria, and specifically B. bifidum, are thought to play a central role in reducing the risk of atopy and in favoring gut eubiosis in children. Nonetheless, no trial has ever prospectively investigated the role played by this single bacterial species in preventing atopic manifestations in children born by cesarean section, and all the results published so far refer to mixtures of probiotics. We have therefore evaluated the impact of 6 months of supplementation with B. bifidum PRL2010 on the incidence, in the first year of life, of atopy, respiratory tract infections, and dyspeptic syndromes in 164 children born by cesarean (versus 249 untreated controls). The results of our multicenter, randomized, and controlled trial have shown that the probiotic supplementation significantly reduced the incidence of atopic dermatitis, upper and lower respiratory tract infections, and signs and symptoms of dyspeptic syndromes. Concerning the gut microbiota, B. bifidum supplementation significantly increased α-biodiversity and the relative values of the phyla Bacteroidota and Actinomycetota, of the genus Bacteroides, Bifidobacterium and of the species B. bifidum and reduced the relative content of Escherichia/Shigella and Haemophilus. A 6-month supplementation with B. bifidum in children born by cesarean section reduces the risk of gut dysbiosis and has a positive clinical impact that remains observable in the following 6 months of follow-up.

Eosinophilic esophagitis and comorbid pathology: current state of the problem

Eosinophilic esophagitis and asthma are often found as part of comorbid pathology in children and adults, along with other manifestations of atopy. The two diseases share similar pathophysiology due to T-helper type 2 responses, common treatment approaches such as the use of glucocorticosteroids and targeted anti-cytokine biologic therapy. Patients with eosinophilic esophagitis, as with asthma, often have elevated serum markers of atopy, including IgE levels, peripheral eosinophil counts, and T-helper type 2-associated cytokines. A review of the literature shows that the true incidence of eosinophilic esophagitis remains poorly understood due to the difficulty of diagnosing this pathology, which has a mask of gastroesophageal reflux disease. Gastroesophageal reflux disease has been shown to influence asthma through microaspiration, airway hyperresponsiveness, and increased vagal tone. Understanding the relationship between gastroesophageal reflux and eosinophilic esophagitis is also being actively explored. Many works show the high efficacy of PPIs in the initial treatment of eosinophilic esophagitis and gastroesophageal reflux disease. The development of new clinical diagnostic criteria for eosinophilic esophagitis will improve the differential diagnosis of this disease and the improvement of therapeutic strategies for managing this pathology, especially in combination with asthma.

Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study

ObjectiveTo examine the association between early-life atopic manifestations and later risk of inflammatory bowel disease (IBD), for which prospective data are scarce. Study designThe population-based All Babies in Southeast Sweden (ABIS) and Norwegian Mother, Father, and Child (MoBa) cohorts follow children from birth (ABIS 1997–1999; MoBa 2000–2009) to the end of 2021. Based on validated questionnaires, parents prospectively reported information on asthma, food-related allergic symptoms, atopic dermatitis, and allergic rhinitis by age 3. IBD was defined by ≥2 diagnostic records in the national health registries. Cox regression estimated hazard ratios adjusted (aHR) for parental IBD, atopy, education level, smoking habits, and national origin. Cohort-specific estimates were pooled using a random-effects model. ResultsWe compiled data on 83,311 children (ABIS, n=9,041; MoBa, n=74,270). In over 1,174,756 person-years of follow-up, 301 participants were diagnosed with IBD. Children with atopic dermatitis at age 3 had an increased risk of IBD (pooled aHR=1.46 [95% confidence interval [CI]=1.13-1.88]), Crohn’s disease (pooled aHR=1.53 [95%CI=1.04-2.26]), and ulcerative colitis (pooled aHR=1.78 [95%CI=1.15-2.75]). Conversely, any atopic manifestation by age 3 was not associated with IBD (pooled aHR=1.20 [95%CI=0.95-1.52]), nor were analyses specifically focused on early-life food-related allergic symptoms, asthma, and allergic rhinitis. ConclusionWhile atopic manifestations in early childhood were overall not associated with IBD, children with atopic dermatitis specifically were at increased risk of developing IBD, suggesting shared etiological traits; these findings might be useful in identifying at-risk individuals for IBD.

Management of Atopy with Dupilumab and Omalizumab in CADINS Disease.

The caspase activation and recruitment domain 11 (CARD11) gene encodes a scaffold protein required for lymphocyte antigen receptor signaling. Dominant-negative, loss-of-function (LOF) pathogenic variants in CARD11 result in CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease. Patients with CADINS suffer with severe atopic manifestations including atopic dermatitis, food allergy, and chronic spontaneous urticaria in addition to recurrent infections and autoimmunity. We assessed the response of dupilumab in five patients and omalizumab in one patient with CADINS for the treatment of severe atopic symptoms. CARD11 mutations were validated for pathogenicity using a T cell transfection assay to assess the impact on activation-induced signaling to NF-κB. Three children and three adults with dominant-negative CARD11 LOF mutations were included. All developed atopic disease in infancy or early childhood. In five patients, atopic dermatitis was severe and recalcitrant to standard topical and systemic medications; one adult suffered from chronic spontaneous urticaria. Subcutaneous dupilumab was initiated to treat atopic dermatitis and omalizumab to treat chronic spontaneous urticaria. All six patients had rapid and sustained improvement in atopic symptoms with no complications during the follow-up period. Previous medications used to treat atopy were able to be decreased or discontinued. In conclusion, treatment with dupilumab and omalizumab for severe, refractory atopic disease in patients with CADINS appears to be effective and well tolerated in patients with CADINS with severe atopy.

The similar characteristics of IgG4-related disease and allergic diseases

IgG4-related disease (IgG4-RD) is a chronic inflammation with fibrosis. About 30% to 40% of patients with IgG4-RD are complicated with atopic manifestations as allergic rhinitis and asthma, usually with elevated serum total immunoglobulin E and peripheral blood eosinophils, which are also of some value for predicting disease activity and relapse. Similar to allergic diseases, activation of type 2 inflammation is also observed in the pathogenesis of IgG4-RD, and eosinophils, basophils, mast cells, thymic stromal lymphopoietin, IL-33, IL-4, IL-5, and IL-13 all participate in the pathogenesis of IgG4-RD. Studies of susceptible genes showed that IgG4-RD and allergic disease shared the same susceptible genes. Monoclonal antibodies targeting type 2 inflammation pathway may become a novel choice for IgG4-RD treatment.

Phenotypic and Endotypic Determinants of Atopic Dermatitis Severity From the Atopic Dermatitis Research Network (ADRN) Registry.

Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype. This study aimed to identify historical and clinical features and biomarkers associated with AD severity. A US registry of extensively phenotyped AD participants (aged 0.73-80 years) were enrolled at 9 academic centers. Information on family and personal medical history, examination, skin swabs (culture), and serum biomarkers was collected to evaluate their association with AD severity. Participants with AD (N= 2862) whose disease was categorized as mild (11.6%), moderate (58.0%), or severe (30.4%) based on Rajka-Langeland scoring were enrolled. The trend test, when adjusting for gender, race, and age, demonstrated that severity was strongly (P ≤ .04) associated with a personal/family history of allergic disorders, history of alopecia, exposure to passive smoke, ocular herpes infection, skin bacterial and viral infections, and history of arrhythmia. Features observed more frequently (P ≤ .002), as a function of severity, included skin infections (impetigo, human papillomavirus, and molluscum contagiosum virus), Staphylococcus aureus colonization, excoriations, hyperlinear palms, ichthyosis, blepharitis, conjunctivitis, ectropion, and wheezing. Serum IgE, allergen and food (≤6 years) Phadiatop, and eosinophilia were strongly linked to severity (P < .001). In a diverse US AD population, severity was associated with a history of atopic disorders, skin and extracutaneous bacterial and viral infections (by history and physical examination), higher IgE, eosinophilia and allergen sensitization, atopic skin manifestations (ie, excoriation, hyperlinear palms, and ichthyosis), and atopic ocular features (ie, blepharitis, conjunctivitis, and ectropion) as well as asthma findings (ie, wheezing). Data from our prospective registry significantly advance our understanding of AD phenotypes and endotypes, which is critical to achieve optimal management.

Identification of clinical predictors for dupilumab dose spacing in adults with atopic dermatitis: a real-world study

BackgroundDupilumab is a monoclonal antibody against the IL-4/IL-13 receptor-subunit approved for the treatment of moderate-severe atopic dermatitis (AD). Some attempts to increase dose interval have been described in both trial and real-world settings.ObjectiveThis study aimed to identify predictive clinical and demographic factors affecting patient selection for dose spacing or treatment withdrawal due to satisfactory response.Materials and methodsThis retrospective study included adult patients with moderate-to-severe AD treated with dupilumab for at least 16 weeks. Descriptive statistics were performed to analyze demographic and clinical variables. Logistic regression models were used to identify predictor variables.ResultsA total of 818 adult patients with moderate-to-severe AD was included in the study and 12% (97/818) of them performed dose spacing to 3–4 weeks or treatment withdrawal (8%, 67/818). The presence of non-cutaneous atopic manifestations (OR = 1.59, 95%CI = 1.06–2.38, p = 0.024), prurigo nodularis phenotype (OR = 4.5, 95%CI = 1.87–10.9, p = 0.001) and the age at treatment initiation (OR = 1.82, 95%CI = 1.12–2.94, p = 0.015) were confirmed as the strongest predictors of dose spacing or treatment withdrawal while maintaining dupilumab effectiveness.ConclusionOur findings contribute to define the patient profile that could maintain the therapeutic response after dose spacing or treatment withdrawal.

Atopic Manifestations Are Underestimated Clinical Features in Various Primary Immunodeficiency Disease Phenotypes.

Atopic manifestations are described as a clinical feature of various primary immunodeficiency disease (PID) phenotypes and are frequently reported in combined immunodeficiencies. The prevalence of atopic manifestations in other PIDs remains largely unknown. Objective: To evaluate the prevalence of atopic manifestations in PIDs other than combined immunodeficiencies and to identify in which PIDs atopic manifestations are most common with the aim of improving patient care. A partner-controlled, questionnaire-based study was performed in pediatric and adult PID patients. Data from diagnostic tests to assess atopic manifestations (ie, diagnostic criteria for atopic dermatitis, spirometry, specific IgE against food and inhalant allergens) were collected from adult patients to confirm patient-reported atopic manifestations. Forty-seven children and 206 adults with PIDs and 56 partner-controls completed the questionnaire. Thirty-five pediatric patients (74.5%) and 164 adult patients (79.6%) reported having experienced 1 or more atopic manifestations compared with 28 partner-controls (50.0%). In the comparison of adult patients with partner-controls, prevalence values were as follows: atopic dermatitis, 49.5% vs 27.3% (P=.003); food allergy, 10.7% vs 1.9% (P=.031); asthma, 55.7% vs 14.8% (P<.001); and allergic rhinitis, 49.8% vs 21.8% (P<.001). The frequency of current atopic manifestations reported by patients was higher than the prevalence based on diagnostic tests (atopic dermatitis, 11.2%; food allergy, 1.9%; asthma 16.4%; and allergic rhinitis, 11.5%). Atopic manifestations are prevalent clinical features across a broad spectrum of PIDs and, in our cohort, frequently present in patients with combined immunodeficiencies and predominant antibody deficiencies. Atopic manifestations should be evaluated in patients with PIDs.

Epidemiological Profile and Associated Allergic Conditions of Atopic Dermatitis: Data from a Referral Service in Southeastern Brazil

Background: Atopic dermatitis is a chronic, inflammatory, and pruritic dermatosis of high prevalence, especially in childhood. a relevant public health issue. Atopic dermatitis is associated with several factors, including genetic, psychological, infectious, food, and environmental, and may be associated with other manifestations of atopy, such as asthma and rhinitis. Objective: To determine the epidemiological profile and the prevalence of personal and family history of allergy in children with atopic dermatitis at a referral service, comparing it to existing literature. Methods: We conducted a cross-sectional and descriptive hospital-based study involving children of both genders under 18 years with clinical diagnosis of atopic dermatitis (Hanifin and Rajka criteria) seen at the Pediatric Dermatology Outpatient Clinic of Hospital Municipal Universitário de Taubaté (HMUT), SP-Brazil, from October 2018 to April 2019. Epidemiological data and data related to personal and family history of allergies were collected from the medical records. Microsoft Excel 2019 was used for compilation and data analysis. Results: Of the 440 consultations in that period, 35 (7.9%) were for atopic dermatitis, of which 23 of them were females (65.7%) and 15 were phototype IV (42.9%); their mean age was 7.7 (standard deviation = 4.3), and the duration of disease ranged from 2 months to 14 years (mean 5.3 years; standard deviation = 4.3). Among the 35 patients, 31 (88.6%) manifested the condition by the fifth year of life. Personal history of allergies was observed in 27 individuals (77.1%), with a predominance of allergic rhinitis and in older age groups. Conclusion: This study, as a pioneer in the region, contributes to the epidemiological profile of patients with atopic dermatitis from the Pediatric Dermatology Outpatient Clinic of HMUT, revealing an early onset and a higher prevalence in females and individuals with higher phototypes. In addition, this study also demonstrated the prevalence of personal and family history of allergies in these patients, consistent with literature.

A heterozygous CARD11 variant in a patient with infantile atopic disease, humoral deficiency and lymphocytosis

The etiology of a vast majority of allergic diseases is presumed to be multifactorial, with environmental and nutritional exposures playing a causal role in polygenically susceptible individuals. The expanding availability of sequencing has allowed the identification of monogenic causes in patients presenting with severe atopic disease with or without other co-morbidities. Here, we describe a case of severe atopic dermatitis and hypogammaglobinemia associated with a CARD11 loss-of-function. Patient is an otherwise healthy 7-month male who presented with severe atopic dermatitis and seborrheic dermatitis. Eczematous lesions developed at 3 months of age and progressed despite standard treatment with topical steroids. There was no history of immunodeficiency or atopy in the family. Physical exam was notable for extensive scaly and xerotic plaques with lichenification. Workup revealed hypereosinophilia, high IgE (179 kIU/L), normal IgA (10 mg/dL), low IgM (6 mg/dL) and IgG (41 mg/dL). Lymphocyte analysis was significant for mild B-cell lymphocytosis (1,063 cells/cm2) with appropriate subsets. Patient was initiated on subcutaneous replacement immunoglobulin. Whole exome trio sequencing identified a de novo CARD11 variant (c.221G>A, p.G74D). Confirmatory testing in a CARD11 deficient Jurkat T-cell line demonstrated loss-of-function and dominant interference of wild-type CARD11 signaling.CARD11 encodes a membrane-associated protein that partners with BCL10 and MALT1 to form the CBM complex responsible for integrating antigenreceptor engagement with downstream activation of NF-κB. Recently, heterozygous hypomorphic mutations in CARD11 have been discovered in patients with severe atopic manifestations, otherwise known as CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS). Our case highlights the need for genetic testing in the evaluation of patients with severe and/or unusual atopy. We discovered a novel CADINS variant (p.G74D) in an infant presenting with extensive atopic dermatitis, seborrheic dermatitis, and hypogammaglobulinemia. Curiously, our patient also developed B cell lymphocytosis in the first year of life which is typically associated with BENTA disease. However, no gain-of-function activity was detected on in vitro testing. Further studies are needed to elucidate if modulation of CARD11 signaling by this variant can explain both gain-of-function and loss-of-function phenotypic features, as noted in prior cases.

Efficacy and safety of abrocitinib monotherapy in adolescents and adults: a post hoc analysis of the phase 3 JAK1 atopic dermatitis efficacy and safety (JADE) REGIMEN clinical trial

BackgroundDifferences in atopic dermatitis (AD) disease course and manifestation with age may extend to treatment response.ObjectiveTo evaluate response maintenance with continuous-/reduced-dose abrocitinib or withdrawal and response to treatment reintroduction after flare in adolescent and adult participants in JADE REGIMEN (NCT03627767).MethodsAdolescents (12–17 years) and adults with moderate-to-severe AD responding to abrocitinib 200-mg induction were randomly assigned to 40-week maintenance with abrocitinib (200 mg/100 mg) or placebo. Patients who experienced flare during maintenance received rescue treatment.ResultsOf 246 adolescents and 981 adults, 145/246 (58.9%) and 655/981 (66.8%), respectively, responded to induction. Similar proportions of adolescents and adults experienced flare during maintenance with abrocitinib 200 mg (14.9%/16.9%), 100 mg (42.9%/38.9%), and placebo (75.5%/78.0%). From the abrocitinib 200-mg, 100-mg, and placebo arms, respectively, Eczema Area and Severity Index response was recaptured by 28.6%, 25.0%, and 52.9% of adolescents and 34.3%, 33.7%, and 58.0% of adults; Investigator’s Global Assessment response, by 42.9%, 50.0%, and 73.5% of adolescents and 34.3%, 50.6%, and 74.1% of adults. Abrocitinib had a similar safety profile regardless of age; nausea incidence was higher in adolescents.LimitationsAdolescents represented 20% of the trial population.ConclusionAbrocitinib was effective in preventing flare in adolescents and adults.Clinicaltrials.gov listing: NCT03627767.

Distinct healthy and atopic canine gut microbiota is influenced by diet and antibiotics.

The rising trend in non-communicable chronic inflammatory diseases coincides with changes in Western lifestyle. While changes in the human microbiota may play a central role in the development of chronic diseases, estimating the contribution of associated lifestyle factors remains challenging. We studied the influence of lifestyle-diet, antibiotic use, and residential environment with housing and family-on the gut microbiota of healthy and owner-reported atopic pet dogs, searching for associations between the lifestyle factors, atopy and microbiota. The results showed that atopic and healthy dogs had contrasting gut microbial composition. The gut microbiota also differed between two breeds, Labrador Retriever and Finnish Lapphund, selected for our study. Among all lifestyle factors studied, diet was most significantly associated with gut microbiota but only weakly with atopic symptoms. Thus, diet- and atopy-associated changes in the microbiota were not interrelated. Instead, the severity of symptoms was positively associated with the usage of antibiotics, which in turn was associated with the microbiota composition. Urban lifestyle was significantly associated with the increased prevalence of allergies but not with the gut microbiota. Our results from pet dogs supported previous evidence from humans, demonstrating that antibiotics, gut microbiota and atopic manifestation are interrelated. This congruence suggests that canine atopy might be a promising model for understanding the aetiology of human allergy.

Long-term dupilumab therapy in Netherton syndrome with severe atopic manifestations: Case report and review of the literature.

We herein present a unique patient of Netherton syndrome (NS) with ichthyosis linearis circumflexa (ILC) lesions associated with severe atopic manifestations since infancy, showing different responses of atopic and ILC lesions to a 2-year dupilumab therapy. The atopic eczematous lesions and pruritus healed remarkably, dramatically improving the patient's quality of life, whilst the scalp hair showed a clinical and light microscopic improvement. The additional recovery in axillary/pubic/extremity hair growth, sweating and nail growth in the presented case was not previously reported in NS patients treated with dupilumab. However, dupilumab had no therapeutic effect on ILC lesions which were not pruritic and showed a treatment-independent wax and waned course.

Eosinophilic Gastrointestinal Diseases in Inborn Errors of Immunity.

Inborn errors of immunity (IEI) are disorders mostly caused by mutations in genes involved in host defense and immune regulation. Different degrees of gastrointestinal (GI) involvement have been described in IEI, and for some IEI the GI manifestations represent the main and characteristic clinical feature. IEI also carry an increased risk for atopic manifestations. Eosinophilic gastrointestinal diseases (EGIDs) are emerging disorders characterized by a chronic/remittent and prevalent eosinophilic inflammation affecting the GI tract from the esophagus to the anus in the absence of secondary causes of intestinal eosinophilia. Data from the U.S. Immunodeficiency Network (USIDNET) reported that EGIDs are more commonly found in patients with IEI. Considering this element, it is reasonable to highlight the importance of an accurate differential diagnosis in patients with IEI associated with mucosal eosinophilia to avoid potential misdiagnosis. For this reason, we provide a potential algorithm to suspect an EGID in patients with IEI or an IEI in individuals with a diagnosis of primary EGID. The early diagnosis and detection of suspicious symptoms of both conditions are fundamental to prevent clinically relevant complications.