Atopic dermatitis (AD) is one of the most common inflammatory skin conditions. The pathogenesis of AD involves skin barrier disruption and immune activation of T-helper (Th)2 and Th22, as well as varying degrees of Th1 and Th17 activation in various patient subtypes. Although AD is mainly driven by Th2, the molecular and clinical heterogeneity of AD underscores the need for more efficacious treatments that target multiple immune axes. Janus kinase (JAK) inhibitors are novel therapeutics that broadly block many AD-related proinflammatory cytokines (IL-4, IL-5, IL-13, IL-31, thymic stromal lymphopoietin [TSLP], IFN [interferon]-γ, IL-12, IL-23, IL-17) across different immune pathways. Oral JAK inhibitors have been shown to be efficacious in AD, with two (abrocitinib and upadacitinib) recently gaining FDA-approval and several others under investigation in clinical trials with promising results. These systemic agents have surpassed conventional thresholds of treatment response, with many patients achieving complete/almost complete skin clearance, and provide a fast-acting alternative therapy for patients who are not responsive to biologics or other conventional therapies. However, systemic JAK inhibitors come with health concerns, requiring additional long-term clinical trials to characterize their safety profile in patients with AD. This review summarizes the current literature on the safety and efficacy of oral JAK inhibitors in AD and discusses future directions for research.

The role of NLRP1 inflammasome activation and subsequent production of IL-1 family cytokines in the development of atopic dermatitis (AD) is not clearly understood. S. aureus is known to be associated with increased mRNA levels of IL-1 family cytokines in the skin and more severe AD. In this study, the altered expression of IL-1 family cytokines and inflammasome-related genes was confirmed and positive relationship between mRNA levels of inflammasome sensor NLRP1 and IL1B or IL18 was determined. Enhanced expression of the NLRP1 and PYCARD proteins, and increased caspase-1 activity were detected in the skin of AD patients. The genetic association of IL18R1 and IL18RAP with AD was confirmed and the involvement of various immune cell types was predicted using published GWAS and eQTL datasets. In keratinocytes, the inoculation with S. aureus led to the increased secretion of IL-1β and IL-18, while siRNA silencing of NLRP1 inhibited the production of these cytokines. Our results together suggest that skin colonization with S. aureus may cause the activation of the NLRP1 inflammasome in keratinocytes, which leads to the secretion of IL-1β and IL-18 and thereby may contribute to the pathogenesis of AD, particularly in the presence of genetic variations in the IL-18 pathway.

Janus kinase (JAK) inhibitors represent one of the newest and most promising additions to the available treatments of atopic dermatitis (AD). Janus kinase inhibitors offer several key benefits over injectable biologics to include more predictable pharmacokinetics, nonimmunogenicity, and flexible dosing, in addition to their oral and topical bioavailability. Recommended laboratory assessments before and during treatment in addition to medication side effects may limit the scope of use in the active-duty military population and specifically within special-duty populations. In this article, we review approved and emerging JAK inhibitors for the treatment of AD as well as important considerations for both military and nonmilitary patient populations.

Atopic dermatitis (AD) is a common chronic, multisystem inflammatory skin disease in pediatric patients. There has been an increase in the incidence of AD in the pediatric population of the Asia-Pacific region. Studies have shown that genetic, epigenetic, environmental and cultural factors may lead to differences in the clinical manifestation and prevalence of AD between races. Early treatment of AD is necessary to prevent the atopic march leading to comorbidities such as asthma and allergic rhinitis. Topical corticosteroids (TCS) are used as first-line therapy for the treatment of AD, but their long-term usage poses a risk to the patient's health. Pimecrolimus (1%) is a topical calcineurin inhibitor (TCI) that is indicated for the treatment of mild to moderate AD. Pimecrolimus has no apparent increase in adverse events compared to TCS, and it causes less of a burning sensation than tacrolimus. The safety and efficacy of pimecrolimus has been established through various clinical trials; yet, in many Asian countries, the use of pimecrolimus in infants is still restricted due to safety concerns. Based on the available evidence, the expert panel recommends pimecrolimus in infants between 3 months and 2 years of age in the Asian population.

Hochuekkito (HET) is a Kampo prescription, used for the clinical treatment of skin diseases such as atopic dermatitis (AD), in Japan. Oral administration of HET exerts anti-allergic effects in an experimental dermatitis mice model and in patients with atopic dermatitis; however, the mechanism underlying the anti-allergic effects of HET is still unclear. Therefore, we investigated the immunopharmacological properties of the anti-allergic actions of HET using a 2,4,6-trinitrochlorobenzene (TNCB)-induced murine contact hypersensitivity (CHS) model and adoptive cell transfer experiments. Oral administration of HET (1.4 g/kg) exhibited anti-allergic effects in a TNCB-induced CHS model via activation of Tregs; this activation was observed even without antigen sensitization in donor mice. Activation was dependent on the duration of HET administration and required at least 4 days of dosing. In addition, the anti-allergic effects of HET through the activation of Tregs were not antigen specific. Flow cytometry results indicated that the proportion of CD4+CD25+Foxp3+ cells in the splenic lymphocytes increased after oral administration of HET. Therefore, oral administration of HET induced both inducible regulatory T cells (iTregs) and thymus-derived naturally occurring regulatory T cells (nTregs). Ginseng radix and Bupleuri radix were involved in the anti-allergic actions of HET through the induction and/or activation of Tregs; Bupleuri radix participated in the activation of nTregs. In conclusion, our findings suggest that HET exerts the anti-allergic effects through the induction and/or activation of Tregs. These findings elucidate the usefulness of HET as an immunomodulator.

More than 400 single gene defects have been identified as inborn errors of immunity, including many arising from genes encoding proteins that affect NF-κB activity. We summarise the skin phenotypes in this subset of disorders and provide an overview of pathogenic mechanisms. NF-κB acts cell-intrinsically in basal epithelial cells during differentiation of skin appendages, influences keratinocyte proliferation and survival, and both responses to and amplification of inflammation, particularly TNF. Skin phenotypes include ectodermal dysplasia, reduction and hyperproliferation of keratinocytes, and aberrant recruitment of inflammatory cells, which often occur in combination. Phenotypes conferred by these rare monogenic syndromes often resemble those observed with more common defects. This includes oral and perineal ulceration and pustular skin disease as occurs with Behcet's disease, hyperkeratosis with microabscess formation similar to psoriasis, and atopic dermatitis. Thus, these genotype-phenotype relations provide diagnostic clues for this subset of IEIs, and also provide insights into mechanisms of more common forms of skin disease.

Examining the genetics of peanut allergy (PA) in the context of clinical trial interventions and outcomes provides an opportunity to not only understand gene-environment interactions for PA risk but to also understand the benefit of allergen immunotherapy. A consistent theme in the genetics of food allergy is that in keeping with the dual allergen exposure hypothesis, barrier- and immune-related genes are most commonly implicated in food allergy and tolerance. With a focus on PA, we review how genetic risk factors across 3 genes (FLG, MALT1, and HLA-DQA1) have helped delineate distinct allergic characteristics and outcomes in the context of environmental interventions in the Learning Early about Peanut Allergy (LEAP) study and other clinical trials. We specifically consider and present a framework for genetic risk prediction for the development of PA and discuss how genetics, age, and oral consumption intertwine to predict PA outcome. Although there is some promise in this proposed framework, a better understanding of the mechanistic pathways by which PA develops and persists is needed to develop targeted therapeutics for established disease. Only by understanding the mechanisms by which PA develops, persists, and resolves can we identify adjuvants to oral immunotherapy to make older children and adults immunologically similar to their younger, more malleable counterparts and thus more likely to achieve long-term tolerance.

Allergic contact dermatitis is one of the most common recorded occupational diseases. There are many different substances that the skin comes into contact with on a daily basis and that can cause ACD, e.g., preservatives, surfactants, and antimicrobial agents. The development of a mouse model of ACD has provided insight into the immune mechanisms involved. Drugs used in the treatment of skin diseases have many side effects. Therefore, alternative methods of suppressing the immune response to reduce the symptoms of skin diseases are being sought. In recent years, high hopes have been placed on dietary modulation and supplementation to affect the intestinal microbial composition and promote anti-inflammatory responses. In addition, other studies have shown the crucial role of intestinal microbiota in many immune-mediated diseases. Recognition and characterization of pro- and anti-inflammatory nutrients and supplements may be crucial to support the treatment of diseases such as atopic dermatitis, acne vulgaris, psoriasis, and allergic contact dermatitis.

Capping protein regulator and myosin 1 linker 2 (CARMIL2) is necessary for invadopodia formation, cell polarity, lamellipodial assembly, membrane ruffling, acropinocytosis, and collective cell migration. CARMIL2 deficiency is a rare autosomal recessive disease characterized by dysfunction in naïve T-cell activation, proliferation, differentiation, and effector function and insufficient responses in T-cell memory. In this paper, we report a 9-year-old female patient with a novel pathogenic variant in CARMIL2 (c.2063C > G:p.Thr688Arg) who presented with various symptoms of primary immunodeficiencies including recurrent upper and lower respiratory infections, perioral and perineum papules, reddish impetiginized atopic dermatitis, oral ulcer, painful urination and vaginitis, otitis media, and failure to thrive. A missense mutation leading to insufficient CARMIL2 protein expression, reduced absolute T-cell and natural killer cell (NK cell) counts, and marked skewing to the naïve T-cell form was identified and indicated defective maturation of T cells and B cells. Following 1 year of multitargeted treatment with corticosteroids, hydroxychloroquine, mycophenolate mofetil, and thymosin, the patient presented with significant regression in rashes. CD4+ T-cell, CD8+ T-cell, and NK cell counts were significantly improved.

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by a compromised skin barrier due to a variety of reasons, such as hereditary predisposition, immunological overactivity, and skin microbiome disruption. There is strong evidence linking food allergies (FA) with AD in some children, and many children with AD develop asymptomatic food sensitivity. FA and AD are two frequent childhood illnesses that are closely related. Food allergies affect 30% of kids suffering from moderate and severe eczema and can cause a variety of symptoms, including dry, cracked skin, rash, itchiness, oozing, and crusted skin. While preteens and teens with AD are commonly sensitive to environmental allergens including house dust mites, mold, pollen, or dander of animals, younger kids with AD typically exhibit sensitivity to food items like peanuts, milk, or eggs. A food challenge test (FC) should be used to confirm allergies before recommending a stringent diet that could be hazardous to the patient. While elimination diets continue to be the cornerstone of the management of FA, they should only be carried out under the guidance of a specialist. Topical treatments are crucial for all individuals with AD. Early skin care with emollients, topical steroid treatment, and early introduction of highly allergenic foods are promising methods of alleviating symptoms of AD.

Atopic dermatitis (AD) is an allergic disease with extreme itching that bothers patients. However, diagnosing AD depends on clinicians' subjective judgment, which may be missed or misdiagnosed sometimes.

Background: There is currently limited insight into the broader impact of atopic dermatitis (AD) on mental health. Although studies indicate that AD patients may experience fatigue, no study has so far examined fatigue in more granular detail, for example, occurrence of general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue, or correlated fatigue measures with AD severity and symptoms intensity. Objectives: To examine fatigue subtypes and their prevalence in adults with AD, as well as their possible association with AD severity. Methods: A survey was conducted in adults with AD who had been managed in a hospital setting. The Patient-Oriented SCORing Atopic Dermatitis was used to determine AD severity. Patient reported outcomes, including multidimensional fatigue inventory, were included. Results: Data from 2729 adults with AD were analyzed. The total and individual fatigue scores increased consistently with lower socioeconomic scores, higher AD severity, Dermatology Life Quality Index, itch, pain, and sleep scores. Increased fatigue scores were associated with AD severity in adjusted analyses. Conclusions: Among adults with AD, fatigue scores increased with disease severity as well as intensity of AD symptoms. Fatigue is a hitherto underappreciated symptom of AD that clinicians should be cognizant about.

Background: Atopic dermatitis (AD) induces alterations of external appearance and self-esteem, with impact on the personal development of the children. However, tools for estimating such suffering are lacking. We aimed to assess how children with AD represent themselves through their drawings. Methods: In this retrospective study, we included children (<18 years) suffering from AD who followed the instruction "draw yourself with and without eczema" at the end of a routine follow-up consultation. Drawings were interpreted with the child and then classified in different analysis groups by 5 independent evaluators. Results: A total of 64 children (41 [64.1%] girls and 23 [35.9%] boys, median [range] age 8 [3-7] years) made 64 drawings. Five groups of drawing were identified: "amputee" (n = 8, 12.5%), "identical" (n = 18, 28.1%), "sad" (n = 19, 29.7%), "complex" (n = 11, 17.2%), and "other" (n = 8, 12.5%). Univariate analysis found that age was differently distributed among the different drawing groups (P = 0.0047), as was the predominance of light colors (P = 0.038). The distribution of the other variables (gender, investigator global assessment score, active AD, and duration of activity) was not different among drawing groups. Conclusions: The drawing allows a majority of the AD children to express their self-image with and without eczema, as well as their feelings and their interactions with the environment and with their entourage. The visual tool proposed herein could be used during consultations, to (a) become aware of the need to treat AD, (b) better evaluate the impact of AD burden in childhood, and (c) adjust appropriately AD treatment.

To compare the quality of life (QoL) of children with and without atopic dermatitis (AD) and that of their caregivers and to assess their QoL according to different degrees of AD. This is a cross-sectional, case-control study conducted with patients aged between 4 and 12 years with and without AD and their caregivers. Patients were treated at the Pediatric Dermatology Outpatient Center and the Childcare Center of the Joana de Gusmão Children's Hospital, respectively, from June 2021 to March 2022. The QoL Assessment Scale Autoquestionnaire Qualité de Vie Infant Imagé (AUQEI) was applied to children and adolescents with AD and the control group while the World Health Organization Quality of Life assessment instrument was administered to their caregivers. Fifty cases and fifty controls were included in this study. When assessing the QoL of the case and control groups, statistically significant differences were found in the domains of the AUQUEI instrument. Regarding QoL and AD severity, a statistically significant difference was seen (p = 0.027) when comparing moderate and severe SCORAD scores. When comparing the QoL of children with and without AD, a difference was seen between the two groups. The QoL of AD patients was worse and related to the severity of the disease. A better QoL was found among the caregivers in the control group. In the case group, the higher the SCORAD score, the worse the QoL. No relationship was found between AD severity and the QoL of the caregivers in the case group.

Nagashima-type palmoplantar keratoderma (PPK) is an autosomal recessive PPK. We report four patients, highlight two new genetic variants, and emphasize the possibility of misdiagnosing the condition. Concomitant atopic dermatitis, specifically, may make correct diagnosis challenging. Clinicians should consider the diagnosis of Nagashima-type PPK in patients presenting with mild PPK with transgrediens and understand the importance of individualized multimodal treatment regimens.