Update on the Pathogenesis and Therapy of Atopic Dermatitis

Li, Huaguo; Zhang, Zhen; Zhang, Hui; Guo, Yuxin; Yao, Zhirong

doi:10.1007/s12016-021-08880-3

Cited by 117 publications

(90 citation statements)

References 137 publications

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“…88 The janus kinase-signal transducer and activator (JAK STAT) pathway upregulates CD4 T cells as well as numerous inflammatory cytokines and has been recognized for immune pathogenesis in other skin conditions such as atopic dermatitis. 89 Although there is less available information on the use of tyrosine kinase inhibitors and JAK inhibitors, they may serve as good treatment choices for PN. One study evaluated the JAK STAT pathway in prurigo nodules to determine if this inflammatory pathway may be prevalent in the disease.…”

Section: Current Immunotherapeutics Used For Pnmentioning

confidence: 99%

Immunotargets and Therapy for Prurigo Nodularis

Labib¹,

Ju²,

Does³

et al. 2022

ITT

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Prurigo nodularis is a chronic inflammatory skin disease consisting of severely pruritic nodules that can be very debilitating for patients. The basis of this skin condition is immunological dysregulation and neural amplification, driven by T-lymphocytes, mast cells, eosinophilic granulocytes, macrophages, and cytokines mediating itchy processes. Further complicating this already taxing diagnosis is the lack of approved treatment and consensus on management; although there are off-label treatments utilized as therapy. Immunomodulators are the cornerstone of treatment for PN, and additional novel therapies targeting key players in the immunological cascade are currently undergoing investigation. In this review, we will highlight targets of the immune cascade and explore current immunomodulating treatments as well as immunotherapies on the horizon for the management of prurigo nodularis.

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Section: Current Immunotherapeutics Used For Pnmentioning

confidence: 99%

Immunotargets and Therapy for Prurigo Nodularis

Labib¹,

Ju²,

Does³

et al. 2022

ITT

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“…Elevated levels of inflammatory cytokines and inflammatory cell infiltration are a typical characteristic in AD [ 30 ]. Thus, we estimated the cytokines level in the serum of DNFB-sensitized mice.…”

Section: Resultsmentioning

confidence: 99%

Ta-Xi-San Suppresses Atopic Dermatitis Involved in Multitarget Mechanism Using Experimental and Network Pharmacology Analysis

Zhi

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Atopic dermatitis (AD) is a relapsing and chronic skin inflammation with a common incidence worldwide. Ta-Xi-San (TXS) is a Chinese herbal formula usually used for atopic dermatitis in clinic; however, its active compounds and mechanisms of action are still unclear. Our study was designed to reveal the pharmacological activities, the active compounds, and the pharmacological mechanisms of TXS for atopic dermatitis. Mice were induced by 2,4-dinitrocluorobenzene (DNCB) to build atopic dermatitis model. The pathological evaluation, enzyme-linked immunosorbent assay (ELISA), and hematoxylin and eosin (H&E) assay were performed. The UPLC-Q-Exactive-MSE and network pharmacology analysis were performed to explore active ingredients and therapeutic mechanisms of TXS. TXS treatment decreased levels of immunoglobulin E (IgE), interleukin-4 (IL-4), and tumor necrosis factor-α (TNF-α) in serum induced by DNCB. TXS reduced scratching behavior and alleviated inflammatory pathology of skin and ear. Meanwhile, TXS decreased the spleen index and increased spleen index. The UPLC-Q-Exactive-MSE results showed that 65 compounds of TXS were detected and 337 targets were fished. We collected 1371 AD disease targets, and the compound-target gene network reveled that the top 3 active ingredients were (−)-epigallocatechin gallate, apigenin, and esculetin, and the core target genes were PTGS2, PTGS1, and HSP90AA1. The KEGG pathway and GO analysis showed that TXS remedied atopic dermatitis via PI3K-Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and Toll-like receptor (TLR) signaling pathway with the regulation of inflammatory response and transcription. Further, we found that the targets of PTGS2 and HSP90AA1 were both elevated in ears and skin of AD model mouse; however, TXS decreased the elevated expressions of PTGS2 and HSP90AA1. Our study revealed that TXS ameliorated AD based on (−)-epigallocatechin gallate, apigenin, and esculetin via targeting PTGS2 and HSP90AA1.

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“…The cytokines, IL‐4, IL‐10, IL‐13 and IL‐31, are considered important markers of enhanced T helper (Th)2 inflammation seen in AD 33 . Recent studies have highlighted the importance of an immunological Th2 shift and its relation with the skin immune system, epidermal barrier and the cutaneous microbiome in the pathogenesis of AD in infants and children 34 .…”

Section: Discussionmentioning

confidence: 99%

Safety of tacrolimus 0.03% and 0.1% ointments in young children with atopic dermatitis: a 36‐month follow‐up study

Salava

Perälä

Pelkonen

et al. 2022

Clin Experimental Derm

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Background. Topical tacrolimus is used off-label in young children, but data are limited on its use in children under 2 years of age and for long-term treatment. Aim. To compare safety differences between topical tacrolimus (0.03% and 0.1% ointments) and topical corticosteroids (mild and moderate potency) in young children with atopic dermatitis (AD). Methods. We conducted a 36-month follow-up study with 152 young children aged 1-3 years with moderate to severe AD. The children were followed up prospectively, and data were collected on infections, disease severity, growth parameters, vaccination responses and other relevant laboratory tests were gathered. Results. There were no significant differences between the treatment groups for skin-related infections (SRIs) (P = 0.20), non-SRIs (P = 0.20), growth parameters height (P = 0.60), body weight (P = 0.81), Eczema Area and Severity Index (EASI) (P = 0.19), vaccination responses (P = 0.62), serum cortisone levels (P = 0.23) or serum levels of interleukin (IL)-4, IL-10, IL-12, IL-31 and interferon-c. EASI decreased significantly in both groups (P < 0.001). In the tacrolimus group, nine patients (11.68%) had detectable tacrolimus blood concentrations at the 1-week visit. There were no malignancies or severe infections during the study, and blood eosinophil counts were similar in both groups. Conclusions. Topical tacrolimus (0.03% and 0.1%) and topical corticosteroids (mild and moderate potency) are safe to use in young children with moderate to severe AD, and have comparable efficacy and safety profiles.

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Update on the Pathogenesis and Therapy of Atopic Dermatitis

Cited by 117 publications

References 137 publications

Immunotargets and Therapy for Prurigo Nodularis

Immunotargets and Therapy for Prurigo Nodularis

Ta-Xi-San Suppresses Atopic Dermatitis Involved in Multitarget Mechanism Using Experimental and Network Pharmacology Analysis

Safety of tacrolimus 0.03% and 0.1% ointments in young children with atopic dermatitis: a 36‐month follow‐up study

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