-
Biological Research Sep 2022Atopic dermatitis (AD) is highly comorbid with negative emotions such as anxiety and depression. Although acupuncture has demonstrated efficacy in AD, its influence on...
Atopic dermatitis (AD) is highly comorbid with negative emotions such as anxiety and depression. Although acupuncture has demonstrated efficacy in AD, its influence on comorbid anxiety and depression remains unclear. We sought to explore the impact and mechanisms of action of acupuncture on comorbid anxiety and depression of AD. AD-like skin lesions were induced by the topical application of MC903 to the mouse cheek. Acupuncture was performed at Gok-Ji (LI11) acupoints. AD-like phenotypes were quantified by lesion scores, scratching behavior, and histopathological changes. The effects of acupuncture on comorbid anxiety and depression-like behaviors were assessed using the elevated plus-maze (EPM), open-field tests (OFT), and tail-suspension test (TST). In addition, biochemical changes in the brain reward regions were investigated by immunoblotting for the expression of tyrosine hydroxylase (TH), dopamine D1 receptor (D1R), phospho-dopamine and cAMP-regulated phosphoprotein-32 kDa (pDARPP-32), phospho-cAMP response element binding protein (pCREB), ΔFosB, and brain-derived neurotrophic factor (BDNF) in the nucleus accumbens, dorsolateral striatum, and ventral tegmental area. Acupuncture effectively improved the chronic itching and robust AD-like skin lesions with epidermal thickening. Additionally, it considerably reduced comorbid anxiety- and depression-like symptoms, as indicated by more time spent in the open arms of the EPM and in the center of the open field and less time spent immobile in the TST. Higher pCREB, ΔFosB, BDNF, and pDARPP-32 levels, and reduced TH and D1R protein expression in the brain reward regions of AD mice were reversed by acupuncture treatment. The beneficial effects of acupuncture on clinical symptoms (scratching behavior) and comorbid psychological distress in AD strongly correlated with dorsal striatal ΔFosB levels. Collectively, these data indicate that acupuncture had a significant, positive impact on comorbid anxiety- and depression-like behaviors by modulating neuroadaptation in the brain reward circuit in mice with AD, providing a novel perspective for the non-pharmacological management of psychiatric comorbidities of AD.
Topics: Acupuncture Therapy; Animals; Anxiety; Brain; Brain-Derived Neurotrophic Factor; Dermatitis, Atopic; Disease Models, Animal; Mice; Reward
PubMed: 36088447
DOI: 10.1186/s40659-022-00396-0 -
Actas Dermo-sifiliograficas Apr 2023Atopic dermatitis is a chronic inflammatory disease that is multifactorial in nature. Allergic contact dermatitis and protein contact dermatitis are allergic conditions... (Review)
Review
Atopic dermatitis is a chronic inflammatory disease that is multifactorial in nature. Allergic contact dermatitis and protein contact dermatitis are allergic conditions that may occur in the context of atopic dermatitis and be the cause of exacerbations. Although the prevalence of allergic contact dermatitis is similar in atopic patients and the general population, these 2 conditions are frequently associated because atopic inflammation disrupts the skin barrier. Skin tests are therefore recommended in atopic individuals. Dupilumab could be useful for treating allergic contact dermatitis if it is mediated by type 2 helper T cells but could exacerbate inflammation if mediated by T1 cells: further study is needed before conclusions can be drawn. Although the mechanism by which exposure to environmental proteins exacerbates atopic dermatitis remains under discussion, such exacerbations are routinely seen in clinical practice. Prick testing is recommended in symptomatic atopic dermatitis. When prick-test findings are positive, patients should be advised to avoid the culprit substances.
Topics: Humans; Dermatitis, Atopic; Haptens; Patch Tests; Dermatitis, Allergic Contact; Inflammation; Allergens
PubMed: 36529271
DOI: 10.1016/j.ad.2022.11.009 -
The Journal of Allergy and Clinical... Aug 2023Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype.
BACKGROUND
Atopic dermatitis (AD) is a chronic inflammatory skin condition with a highly variable clinical phenotype.
OBJECTIVE
This study aimed to identify historical and clinical features and biomarkers associated with AD severity.
METHODS
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.
RESULTS
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).
CONCLUSIONS
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.
Topics: Humans; Dermatitis, Atopic; Ectropion; Respiratory Sounds; Phenotype; Biomarkers; Allergens; Conjunctivitis; Immunoglobulin E; Blepharitis; Severity of Illness Index
PubMed: 37182563
DOI: 10.1016/j.jaip.2023.04.052 -
Clinical Interventions in Aging 2023Atopic dermatitis (AD) in the elderly has recently emerged as a distinct subgroup of AD, garnering widespread concern due to its increasing global incidence rate.... (Review)
Review
Atopic dermatitis (AD) in the elderly has recently emerged as a distinct subgroup of AD, garnering widespread concern due to its increasing global incidence rate. Epidermal barrier dysfunction, inflammatory response, and chronic pruritus interact with each other, contributing to the pathogenesis and pathophysiology of AD in the elderly. Although fundamental medications are essential for managing AD in the elderly, older adults often struggle with regular usage of moisturizing emollients, topical medications, and avoidance of environmental triggers, leading to recurrent or even exacerbated disease progression. Therefore, a systematic medication approach is necessary to control pruritus and skin lesions. Traditional systemic treatments may not adequately meet the treatment needs of moderate and severe AD in the elderly and may even pose certain safety risks. Biologics and Janus kinase (JAK) inhibitors, exhibiting excellent clinical efficacy, have made significant breakthroughs in AD treatment. Existing evidence suggests that dupilumab, a human monoclonal IgG4 antibody, has been confirmed as an effective and safe first-line systematic treatment for moderate to severe AD in the elderly, with no notable differences between adults and the elderly. However, the limited inclusion of elderly patients in related clinical studies hinders the generalizability of these findings. As older patients face a higher risk of adverse events with JAK inhibitors, JAK inhibitors are recommended when no other suitable treatment options are available. Obtaining population-specific data is crucial for making evidence-based treatment choices when managing AD in older adults with JAK inhibitors.
Topics: Humans; Aged; Dermatitis, Atopic; Antibodies, Monoclonal; Administration, Cutaneous; Pruritus; Treatment Outcome
PubMed: 37810952
DOI: 10.2147/CIA.S426044 -
Acta Dermato-venereologica Jun 2023Atopic dermatitis is a chronic, relapsing and inflammatory skin disease. The impact of atopic dermatitis on the partners living with patients has been poorly...
Atopic dermatitis is a chronic, relapsing and inflammatory skin disease. The impact of atopic dermatitis on the partners living with patients has been poorly investigated. The objective of this study was to evaluate the impact of atopic dermatitis in the daily lives of adult patients and to assess the burden of the disease on their partners. A population-based study was conducted on a representative sample of the general population of French adults aged 18 years of age using stratified, proportional sampling with a replacement design. Data were collected on 1,266 atopic dermatitis patient-partner dyads (mean age of patients 41.6 years, 723 (57.1%) women). The mean age of partners was 41.8 years. Patient burden, measured by the Atopic Dermatitis Burden Scale for Adults (ABS-A) score, was closely related to the objective atopic dermatitis severity: the mean score in the mild group (29.5) was significantly lower than in the moderate (43.9) and severe groups (48.6) (p < 0.0001). Partner burden, measured by the EczemaPartner score, was highly related to atopic dermatitis severity (p < 0.0001). Daytime sleepiness, measured by the Epworth Sleepiness Scale, showed a mean score of 9.24 in patients and 9.01 in their partners, indicating impaired sleep. Atopic dermatitis was found to decrease sexual desire in 39% and 26% of partners and patients respectively.
Topics: Adult; Humans; Female; Adolescent; Male; Dermatitis, Atopic; Quality of Life; Severity of Illness Index; Libido; Patients
PubMed: 37358393
DOI: 10.2340/actadv.v103.5285 -
Acta Bio-medica : Atenei Parmensis Sep 2020Atopic dermatitis (AD) is a common inflammatory skin disease, clinically characterized by recurrent eczematous lesions and intense itching, leading to excoriations and...
Atopic dermatitis (AD) is a common inflammatory skin disease, clinically characterized by recurrent eczematous lesions and intense itching, leading to excoriations and susceptibility to cutaneous infections. Although it is considered a pediatric disorder, mainly starting in infancy, it is also very common in adults. Etiology of AD is complex and multifactorial: interaction between genetic susceptibility and environment, but also cutaneous barrier impairment, change in microbiome composition and innate and adaptive immune dysregulation are the main factors involved in the pathogenesis of the disease. Originally, the disorder was considered mediated by an imbalance towards a T-helper 2 response and excessive IgE production to allergens, but now it is recognized as a lifelong disposition with variable clinical expressivity, where dysfunctions of the epidermal barrier, immune system and microbiome play a central role. AD leads to a substantial psycho-social burden on patients and their relatives and increases the risk of other allergic and non allergic disorders. The real economic impact of AD is difficult to measure due to the broad spectrum of disease severity and the multiple direct and indirect costs, but the overall medical expenses seem to be very high and similar to those of other diseases such as diabetes. Currently, a multiple therapeutic approach is aimed only at improving the skin state, reducing itching and keeping a stable condition. New safety and curative treatments may be developed only after enhancing our understanding on the pathogenesis of AD and the heterogeneity of its clinical manifestations.
Topics: Adult; Allergens; Child; Dermatitis, Atopic; Humans; Immune System; Severity of Illness Index; Skin
PubMed: 33004781
DOI: 10.23750/abm.v91i11-S.10313 -
Acta Dermato-venereologica Feb 2021Currently no treat-to-target framework to guide systemic treatment in adults with moderate-to-severe atopic dermatitis exists. We sought to reach international consensus...
Currently no treat-to-target framework to guide systemic treatment in adults with moderate-to-severe atopic dermatitis exists. We sought to reach international consensus through an eDelphi process on a core set of recommendations for such an approach. Recommendations were developed by an international Steering Committee, spanning 3 areas (Guiding Principles, Decision Making, and Outcome Thresholds) and 2 specific time-points; an initial acceptable target at 3 months and an optimal target at 6 months, each based on improvements in patient global assessment plus at least one specific outcome domain. These treat-to-target- orientated recommendations were evaluated by an extended international panel of physicians, nurses and patients. Proposed recommendations were rated using a 9-point Likert scale; for each recommendation, consensus agreement was reached if ≥ 75% of all respondents rated agreement as ≥ 7. Consensus on 16 core recommendations was reached over 2 eDelphi rounds. These provide a framework for shared decision-making on systemic treatment continuation, modification, or discontinuation.
Topics: Adult; Consensus; Delphi Technique; Dermatitis, Atopic; Eczema; Humans
PubMed: 33491094
DOI: 10.2340/00015555-3751 -
Dermatitis : Contact, Atopic,...The management required for atopic dermatitis (AD) may worsen patient burden, thereby resulting in iatrogenic burden, that is, morbidity caused by medical treatment. We... (Review)
Review
The management required for atopic dermatitis (AD) may worsen patient burden, thereby resulting in iatrogenic burden, that is, morbidity caused by medical treatment. We sought to describe the iatrogenic burden of AD and conducted a narrative review of key areas that clinicians can address to minimize it. Clinicians should think strategically about itch trigger avoidance, encourage slow incorporation of lifestyle changes, and emphasize step-up therapy when avoidance becomes too burdensome. Out-of-pocket treatment costs should be incorporated into shared decision making to balance affordability, preference, efficacy, and safety. Polypharmacy should be minimized by eliminating ineffective, nonevidence-based, and redundant therapies while appropriately stepping up to advanced therapy. Clinicians should take adequate time to communicate, the impact of AD on quality of life, and incorporate evidence-based guidelines. The multidimensional nature of AD requires a dynamic approach. Future guidelines should incorporate step-up, step-down, and maintenance approaches to reduce treatment burden and improve quality of life.
Topics: Humans; Dermatitis, Atopic; Quality of Life; Pruritus; Iatrogenic Disease
PubMed: 34570733
DOI: 10.1097/DER.0000000000000799 -
Ugeskrift For Laeger Jan 2018Atopic dermatitis is a chronic and relapsing inflammatory skin disease. The clinical features vary among different age and ethnic groups, but pruritus is a hallmark. The... (Review)
Review
Atopic dermatitis is a chronic and relapsing inflammatory skin disease. The clinical features vary among different age and ethnic groups, but pruritus is a hallmark. The treatment of atopic dermatitis includes skin barrier restoration with daily application of moisturizers. Topical corticosteroids and calcineurin inhibitors are first-line treatment for acute flares. In severe cases, immunosuppressive drugs are indicated. Targeted biological drugs are being tested in clinical trials.
Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Calcineurin Inhibitors; Comorbidity; Dermatitis, Atopic; Dermatologic Agents; Humans; Immunosuppressive Agents; Risk Factors
PubMed: 29393034
DOI: No ID Found -
Journal of the American Academy of... Mar 2022Difamilast is a selective phosphodiesterase 4 inhibitor. Phosphodiesterase 4 is involved in cytokine production linked with inflammatory disorders, including atopic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Difamilast is a selective phosphodiesterase 4 inhibitor. Phosphodiesterase 4 is involved in cytokine production linked with inflammatory disorders, including atopic dermatitis.
OBJECTIVE
To demonstrate the superiority of difamilast ointment 1% to vehicle in adult Japanese patients with atopic dermatitis.
METHODS
In this phase 3, randomized, double-blind trial, patients aged 15-70 years with an investigator global assessment score of 2 or 3 received topical difamilast ointment 1% (n = 182) or a vehicle (n = 182) twice daily for 4 weeks.
RESULTS
The success rate in investigator global assessment score at week 4 (primary endpoint)-the percentage of patients achieving an investigator global assessment score of 0 or 1 with ≥2-grade improvement-was significantly higher with 1% difamilast than with the vehicle (38.46% vs 12.64%, respectively, P < .0001). The success rates in ≥50%, ≥75%, and ≥90% improvement in overall eczema area and severity index score at week 4 followed the same trend. Difamilast at 1% provided significant mean percent improvement from baseline in overall eczema area and severity index score versus vehicle from week 1 to 4. Treatment-emergent adverse events were mostly mild or moderate and less frequent with difamilast.
LIMITATIONS
Study treatment was limited to 4 weeks.
CONCLUSION
Difamilast ointment 1% demonstrated superiority to the vehicle and favorable safety in adult Japanese patients with atopic dermatitis.
Topics: Adult; Benzamides; Dermatitis, Atopic; Double-Blind Method; Eczema; Emollients; Humans; Hyperplasia; Ointments; Phosphodiesterase 4 Inhibitors; Severity of Illness Index; Treatment Outcome
PubMed: 34710557
DOI: 10.1016/j.jaad.2021.10.027