Topical glucocorticoid or pimecrolimus treatment suppresses thymic stromal lymphopoietin-related allergic inflammatory mechanism in an oxazolone-induced atopic dermatitis murine model

Yoon

et al. 2016

Ann Dermatol

Self Cite

BackgroundThe acidic pH of the stratum corneum (SC) is important for epidermal permeability barrier homeostasis. Acidification of the skin surface has been suggested as a therapeutic strategy for skin disorders such as atopic dermatitis (AD).ObjectiveWe performed an animal study to evaluate the usefulness of acidification of SC for inhibition of AD lesions and to find out if the therapeutic effect of vinegar is attributable to its herbal contents, rather than its acidity.MethodsFive groups of six oxazolone-treated (Ox)-AD mice were treated for three weeks with creams of different acidity: vehicle cream alone (pH 5.5), neutralized vinegar cream (pH 7.4), pH 5.0 vinegar cream, pH 3.5 vinegar cream, and pH 3.5 hydrogen chloride (HCl) cream. Also, we have compared two groups of Ox-AD mice treated with pH 5.5 vehicle cream or pH 5.5 vinegar cream.ResultsOx-AD mice treated with acidic creams exhibited fewer AD-like lesions, had significantly lower eczema scores, decreased basal by transepidermal water loss (TEWL), and increased SC hydration compared to the groups given only vehicle and neutral cream. There was no significant difference between the acidic vinegar and HCl groups. Between the groups treated with vehicle and pH 5.5 vinegar cream, there was no difference in eczema score, basal TEWL and SC hydration.ConclusionApplication of topical acids, regardless of their source materials, inhibits the development of AD lesions by maintenance of skin surface pH and skin barrier function in murine model.

Section: Discussionmentioning

confidence: 75%

Application of Topical Acids Improves Atopic Dermatitis in Murine Model by Enhancement of Skin Barrier Functions Regardless of the Origin of Acids

Yoon

et al. 2016

Ann Dermatol

Self Cite

“…Tacrolimus is a calcineurin antagonist that inhibits the transcription of inflammatory cytokines released from T‐cells and mast cells via binding to FK‐binding protein and blocking calcineurin phosphatase activity. Tacrolimus also suppresses the expression of cytokines such as proteinase‐activated receptor‐2 and thymic stromal lymphopoietin, both of which are involved in allergic Th2 responses and itch sensation (Grassberger et al, ; Hanifin & Chan, ; Reynolds & Al‐Daraji, ; Yoon, Jung, Kim, Lee, & Choi, ). In a prospective, open, multicenter, investigator‐driven trial of 29 adult patients with occupationally induced hand dermatitis (OHD) due to irritant exposure, application of tacrolimus 0.1% ointment twice daily for 4 weeks resulted in 44% of patients with complete clearance, and additional 67% of the patients attaining at least 50% improvement, based on the Jena HE Score, which calculates severity based on area affected by vesicles, erythema, scaling, infiltration, lichenification, and fissuring (Schliemann et al, ).…”

Section: Topical Agentsmentioning

confidence: 99%

Current and emerging therapies for hand eczema

Maarouf

Hendricks

et al. 2019

Dermatologic Therapy

Although hand eczema (HE) and chronic hand eczema (CHE) are common conditions with significant disease burden, they traditionally have had limited treatment options beyond topical and short‐term systemic corticosteroids. We reviewed published and preliminary evidence on the current and emerging topical and systemic therapeutic agents for HE and CHE. The etiologies of various HE subtypes are discussed, and remaining knowledge and practice gaps are highlighted to encourage further investigations. A comprehensive search of http://clinicaltrials.gov and PubMed was completed for clinical trials that utilized known and emerging treatment options for HE and CHE. Several agents that target IL‐4 and IL‐13 signaling, keratinocyte proliferation, inflammatory cytokine production, bacterial protein synthesis, and inflammatory mediator (TNF‐α, JAK1, JAK2, and JAK3) proliferation are shown to be involved in the pathogenesis of CHE. Systemic agents include dupilumab, alitretinoin, acitretin, cyclosporine, azathioprine, and probiotics. Topical agents include delgocitinib, retapamulin, halometasone/triclosan, calcipotriol/betamethasone, tacrolimus, and pimecrolimus. These modalities have demonstrated varying degrees of clinical efficacy, evaluated by subjective assessments and scoring indexes. Targeted therapies are emerging for HE, but options are still limited, partially due to our narrow understanding of this heterogeneous condition. Additional and targeted therapeutic options are needed to match the rising prevalence and burden of HE. Keypoints Hand eczema (HE) is a heterogenous dermatosis with limited therapeutic options due to a lack of international guidelines regarding classification of HE subtypes and treatment. This review discusses current and emerging topical and systemic agents and their efficacies in the treatment of different types of hand eczema.

“…Topical treatment with mid-potent GC has been shown to improve the AD-like skin lesion and barrier impairment by suppressing inflammation [33]. In line with this, Chiba et al [4] demonstrated that topical GC could reverse PPARa expression in NC/Nga AD-like mice skin, accompanied with amelioration of inflammation.…”

Section: Discussionmentioning

confidence: 92%

Pseudoceramide stimulates peroxisome proliferator-activated receptor-α expression in a murine model of atopic dermatitis: molecular basis underlying the anti-inflammatory effect and the preventive effect against steroid-induced barrier impairment

Jung

et al. 2015

Arch Dermatol Res

Topical pseudoceramides are successfully used in skin barrier repair therapy for atopic dermatitis (AD) and demonstrated to reduce the adverse effects of topical glucocorticoids (GC). However, the molecular mechanisms involved are not fully understood. We investigated whether PC-9S (myristoyl/palmitoyloxostearamide/arachamide MEA, Neopharm, Daejeon, Korea), one of the synthetic pseudoceramides, could stimulate peroxisome proliferator-activated receptor (PPAR)α expression in a hapten [oxazolone (oxa)]-induced AD murine model (oxa-AD mice) and subsequently improved permeability barrier, reduced inflammation, and increased antimicrobial peptides (AMPs) expression. Normal hairless mice and oxa-AD mice were topically treated twice daily with either PC-9S-containing physiologic lipid mixture (PLM), vehicle (PLM), or PPARα agonist for 4 days. Topical PC-9S significantly increased PPARα expression in mouse epidermis in vivo and in oxa-AD mice skin comparable with PPARα agonist. Topical PC-9S-containing PLM significantly reduced basal trans-epidermal water loss (TEWL), surface pH, and mast cell infiltrates and prevented the decline of AMPs expression in oxa-AD mice, which were abrogated by PPARα antagonist. Then, oxa-AD mice were treated with super-potent topical GC twice daily for 4 days with or without PC-9S co-applications. Co-treatment with PC-9S-containing PLM suppressed GC-induced increase in basal TEWL, epidermal thinning, reduced loricrin expression, and impaired barrier recovery and these effects were attenuated by PPARα antagonist. Collectively, our findings suggest that pseudoceramide PC-9S-induced stimulation of PPARα expression provides a new mechanism by which pseudoceramides show anti-inflammatory property, improve the permeability and antimicrobial barrier function, and prevent the negative effects of topical GC.