Guidelines of care for the management of atopic dermatitis

Sidbury, Robert; Davis, Dawn M.; Cohen, David E.; Cordoro, Kelly M.; Berger, Timothy G.; Bergman, James N.; Chamlin, Sarah L.; Cooper, Kevin D.; Feldman, Steven R.; Hanifin, Jon M.; Krol, Alfons; Margolis, David J.; Paller, Amy S.; Schwarzenberger, Kathryn; Silverman, Robert A.; Simpson, Eric L.; Tom, Wynnis L.; Williams, Hywel C; Elmets, Craig A.; Block, Julie; Harrod, Christopher G.; Begolka, Wendy Smith; Eichenfield, Lawrence F.

doi:10.1016/j.jaad.2014.03.030

Cited by 730 publications

(364 citation statements)

References 70 publications

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“…AD affects an estimated 15% to 30% of children and 2% to 10% of adults in industrialized countries and causes significant difficulties in health‐related quality of life from disease symptoms and the stigma associated with a highly visible skin condition 1, 3. Most patients with AD have mild to moderate disease and are often treated with topical therapies; systemic modalities are recommended only for patients with moderate to severe disease 4. Patients with mild to moderate AD are typically treated with topical emollients, corticosteroids, and calcineurin inhibitors 2.…”

mentioning

confidence: 99%

Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open‐Label, Maximal‐Use Systemic Exposure Study

Zane¹,

Kircik

Call³

et al. 2016

Pediatric Dermatology

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BackgroundPhosphodiesterase‐4 (PDE4) is a promising target in atopic dermatitis (AD) treatment. The pharmacokinetics (PK), safety, and efficacy of crisaborole topical ointment, 2% (formerly AN2728) (Anacor Pharmaceuticals, Palo Alto, CA), a boron‐based benzoxaborole PDE4 inhibitor, were evaluated in children with mild to moderate AD.MethodsThis phase 1b, open‐label, maximal‐use study of crisaborole topical ointment, 2% applied twice daily (dose 3 mg/cm2) for 28 days enrolled patients ages 2 to 17 years with extensive AD involving 25% or more or 35% or more treatable body surface area, depending on age. Primary PK and safety assessments included systemic exposure to crisaborole and its metabolites after 7 days of treatment and the incidence of treatment‐emergent adverse events (TEAEs). Secondary efficacy assessments included change from baseline in Investigator Static Global Assessment (ISGA), treatment success (ISGA score ≤1 with a two‐grade or greater improvement from baseline), and improvement in five AD signs and symptoms.ResultsOf 34 patients enrolled, 31 completed the study. Crisaborole was rapidly absorbed, with limited systemic exposure between days 1 and 8. Twenty‐three of 34 patients reported one or more TEAEs; 95% were mild or moderate and one patient discontinued because of a TEAE. Mean ISGA scores declined from 2.65 at baseline to 1.15 at day 29, 47.1% of patients achieved treatment success, and 64.7% of patients achieved ISGA scores of clear (0) or almost clear 1. Mean severity scores for AD signs and symptoms declined throughout the study.ConclusionsThis open‐label study provides evidence that crisaborole topical ointment, 2% was well tolerated, with limited systemic exposure under maximal‐use conditions in patients ages 2 years and older.

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confidence: 99%

Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open‐Label, Maximal‐Use Systemic Exposure Study

Zane¹,

Kircik

Call³

et al. 2016

Pediatric Dermatology

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“…However, because AD patients often gradually acquire drug resistance, there is documented risk, particularly with systemic corticosteroid use. For patients with severe AD, particularly in adults, phototherapy, methotrexate, azathioprine, cyclosporine, and mycophenolate mofetil have been successfully used instead of corticosteroids [31]. A drug that can be safely used as a systemic immunosuppressant is sought for the treatment of severe AD.…”

Section: Discussionmentioning

confidence: 99%

The Role of Proteasome Inhibitor MG132 in 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis in NC/Nga Mice

Ohkusu-Tsukada¹,

Ito²,

Takahashi³

2018

Int Arch Allergy Immunol

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Background: Although immunosuppressants for therapy of atopic dermatitis (AD) are still being sought, proteasome inhibitors are also potential candidates for the treatment of AD. Proteasome inhibitors exert various effects by blocking proteasomal degradation and help regulate processes such as apoptosis induction via caspase-9, cell cycle progression via cyclins, NF-κB inactivation via IκB, and downregulation of antigen cross-presentation. The cells targeted by proteasome inhibitors are therefore activated cells undergoing proliferation or differentiation, and antigen-presenting cells carrying out protein degradation. Objectives: This study investigated the therapeutic effects and side effects of a proteasome inhibitor, MG132, on the treatment of AD. Methods: AD-like disease in NC/Nga mice housed under specific pathogen-free conditions was induced by repeated application of 2,4-dinitrofluorobenzene (DNFB). Disease progression was evaluated by inflammation score, histopathology, and serum IgE level, and the effects of systemic MG132 administration were investigated. The percentages and absolute numbers for each population of Th1, Th2, and Th17 cells in the axillary lymph nodes were analyzed by flow cytometry. Results: DNFB application increased the expression of a unique major histocompatibility complex class I mutant molecule D/L^dm7 in dendritic cells (DCs), and increased Th1 and Th17 cells in NC/Nga mice. In vivo MG132 administration to NC/Nga mice with DNFB-induced dermatitis reduced Th17 cells but maintained the level of Th1 cells, resulting in the alleviation of dermatitis lesions by decreasing both serum IgE hyperproduction and mast cell migration. To understand the mechanisms maintaining Th1 cell levels following in vivo MG132-administration, we focused on the role of proteasomes regulating D/L^dm7 expression. Interestingly, 20S proteasome activity was higher in NC/Nga DCs than in BALB/c DCs. In vitro MG132 administration partially increased D/L^dm7 expression in a dose-dependent manner during DC maturation, and induced IFN-γ production from autoreactive CD8+ T cells but not from CD4+ T cells following coculturing with D/L^dm7-upregulated DCs. Conclusion: Although MG132 administration temporarily alleviated AD pathogenesis in NC/Nga mice, prolonged MG132 treatment may result in immunopathogenesis leading to chronic AD due to its side effect of maintaining Th1 levels via autoreactive CD8+ T cells.

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“…AD-relevant medications were also included as a single, grouped category and represented as a binary variable. These medications include topical corticosteroids, topical calcineurin inhibitors, prescription emollients, antihistamines, oral corticosteroids, phototherapy, cyclosporine A, interferon gamma, doxepin, azathioprine, methotrexate, and mycophenolate mofetil [14], [16]. Patient ages were calculated by subtracting date of birth from March 15, 2017.…”

Section: Methodsmentioning

confidence: 99%

A Machine Learning Algorithm for Identifying Atopic Dermatitis in Adults from Electronic Health Records

Gustafson

Pacheco

Wehbe

et al. 2017

2017 IEEE International Conference on Healthcare Informatics (ICHI)

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The current work aims to identify patients with atopic dermatitis for inclusion in genome-wide association studies (GWAS). Here we describe a machine learning-based phenotype algorithm. Using the electronic health record (EHR), we combined coded information with information extracted from encounter notes as features in a lasso logistic regression. Our algorithm achieves high positive predictive value (PPV) and sensitivity, improving on previous algorithms with low sensitivity. These results demonstrate the utility of natural language processing (NLP) and machine learning for EHR-based phenotyping.

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Guidelines of care for the management of atopic dermatitis

Cited by 730 publications

References 70 publications

Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open‐Label, Maximal‐Use Systemic Exposure Study

Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open‐Label, Maximal‐Use Systemic Exposure Study

The Role of Proteasome Inhibitor MG132 in 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis in NC/Nga Mice

A Machine Learning Algorithm for Identifying Atopic Dermatitis in Adults from Electronic Health Records

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