Retrospective assessment of immunologic and histologic heterogeneity in granuloma annulare by cytokine staining

Int J Dermatol. 2024 May;63(5):655-659. doi: 10.1111/ijd.16998. Epub 2023 Dec 22.

Abstract

Background: Type 1 (Th1) and Type 2 (Th2) immunity have both been implicated in granuloma annulare (GA). To what extent these pathways contribute to clinical/histologic heterogeneity and/or distinct disease endotypes remains unexplored.

Methods: We retrospectively analyzed 30 GA biopsies with either palisaded or interstitial histology with and without eosinophils. We performed RNA in situ hybridization to assess how markers of Type 1 (interferon gamma), Type 2 (interleukin [IL]4, IL13, IL5), and Type 3 (IL17A) immunity in GA compared with canonical inflammatory disorders and whether markers correlated with histology. We analyzed another cohort of 14 patients who had multiple biopsies across anatomic space and time for individual conservation of histologic features.

Results: Interferon (IFN)G staining is highest in GA relative to other cytokines. Type 2 cytokine staining is less prominent, with IL4 increased in interstitial pattern cases. Eosinophils did not correlate with Type 2 markers. Patients with multiple biopsies display intrapatient variability in histology.

Conclusion: Type 1 inflammation predominates over Type 2 inflammation in GA irrespective of histologic pattern. Distinct disease endotypes were not detected.

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Cytokines / metabolism
  • Eosinophils* / immunology
  • Eosinophils* / pathology
  • Female
  • Granuloma Annulare* / diagnosis
  • Granuloma Annulare* / immunology
  • Granuloma Annulare* / pathology
  • Humans
  • In Situ Hybridization
  • Interferon-gamma
  • Interleukin-17 / metabolism
  • Interleukin-4
  • Interleukin-5
  • Male
  • Middle Aged
  • Retrospective Studies
  • Skin / immunology
  • Skin / pathology
  • Staining and Labeling
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Young Adult

Substances

  • Interferon-gamma
  • Interleukin-4
  • Interleukin-17
  • Interleukin-5
  • IL4 protein, human
  • IL5 protein, human
  • IL17A protein, human
  • Cytokines
  • IFNG protein, human