{
  "abstract": "Chronic spontaneous urticaria (CSU) and atopic dermatitis (AD) are pruritic inflammatory skin diseases that share partly overlapping mast-cell-related pathways, including IgE/FcεRI signaling, type 2 inflammation, neuroimmune signaling, and lipid mediator pathways. Yet they usually produce distinct phenotypes: transient wheals and angioedema in CSU and persistent eczematous lesions with inflammation in AD. Whether disease activity in the two conditions fluctuates concordantly or independently within the same patient has not been directly tested. This Perspective proposes that phenotypic divergence reflects the tissue-response network in which mast cell activation is embedded rather than mediator identity alone. In CSU, autoimmune and autoallergic FcεRI-dependent activation, MRGPRX2-related neuropeptide pathways, coagulation/fibrinolysis-C5a signaling, and platelet-activating factor (PAF)/lipid mediators may preferentially converge on mast cells and basophils poised for rapid degranulation within the dermal vascular/perivascular unit. This network favors histamine bursts, endothelial hyperpermeability, neurovascular itch, and feedback-limited wheal formation. In AD, mast cells are embedded in a barrier-disrupted, alarmin-rich neuroepidermal niche, producing a multicellular inflammatory network involving keratinocyte activation, cytokine and chemokine production, neuronal sensitization, itch-scratch cycling, and tissue remodeling, although degranulation and vascular effects may also occur. Neuropeptides and PAF illustrate how shared mediators may be preferentially routed toward vascular leakage in CSU or neuroepidermal inflammatory amplification in AD. This tissue-addressed mast cell output model is proposed as a testable hypothesis for how overlapping inflammatory mediators may generate feedback-limited vascular whealing in CSU but sustained neuroepidermal inflammation in AD. The model emphasizes that shared pathways are preferentially weighted toward different tissue-level outcomes in CSU and AD.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea",
    "Department of Dermatology, Hiroshima City Hiroshima Citizens Hospital, Hiroshima City Hospital Organization, Hiroshima, Japan",
    "Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan"
  ],
  "article_type": "brief report",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Young-Min Ye"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Michihiro Hide"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9gsg3yvzvwwet.bib",
  "cited_by": 0,
  "doi": "10.3389/falgy.2026.1976519",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696231/",
  "id": "9gsg3yvzvwwet",
  "issns": [
    "2673-6101"
  ],
  "landing_url": "https://doi.org/10.3389/falgy.2026.1976519",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Perspective"
    ],
    [
      "openalex",
      "2745|Urticaria and Related Conditions"
    ]
  ],
  "openalex": "W7221450222",
  "pdf_url": "https://europepmc.org/articles/PMC13696231?pdf=render",
  "pmcid": "PMC13696231",
  "pmid": "42935749",
  "published": "2026-10-12",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/9gsg3yvzvwwet.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "PMC13696231",
      "source": "pmc",
      "url": "https://doi.org/10.3389/falgy.2026.1976519"
    },
    {
      "first_seen": "2026-10-30T12:22:24Z",
      "native_id": "MED:42935749",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42935749"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Urticaria and Related Conditions",
      "subfield": "general"
    }
  ],
  "title": "Shared mediators, divergent networks: a tissue-response hypothesis for discordant phenotypes in chronic spontaneous urticaria and atopic dermatitis",
  "title_text": "Shared mediators, divergent networks: a tissue-response hypothesis for discordant phenotypes in chronic spontaneous urticaria and atopic dermatitis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:36Z",
  "url": "https://research.draconitic.com/paper/9gsg3yvzvwwet",
  "venue": "Frontiers in Allergy",
  "versions": []
}