Infliximab reduces activated myeloid dendritic cells, different macrophage subsets and CXCR3-positive cells in granuloma annulare

J Dermatol. 2019 Sep;46(9):808-811. doi: 10.1111/1346-8138.14981. Epub 2019 Jul 10.

Abstract

Disseminated granuloma annulare (GA) is a rare granulomatous dermatitis of unknown etiology. Treatment is often challenging and lack of a uniformly effective treatment, adds to the disease morbidity. Tumor necrosis factor (TNF)-α is an important cytokine in granuloma formation and previous reports have shown improvement of disseminated GA with anti-TNF-α therapy. Nevertheless, the underlying mechanism of actions of TNF-α inhibitors in GA remains unclear. Our aim was to evaluate alterations in the inflammatory infiltrate in a patient who experienced complete clearance of GA after treatment with infliximab. A skin biopsy was obtained before and 24 weeks after treatment with infliximab 5 mg/kg at weeks 0, 2, 6, 14 and 24. Immunohistochemical stains were performed in pre- and post-treatment biopsy specimens using CD1a, CD4, CD8, CD11c, CD32, CD68, CD69, CD163, CD183 and human leukocyte antigen (HLA)-DR to characterize alterations of the infiltrates. Parallel with clinical improvement, we observed a marked decrease in myeloid (CD11c) dendritic cells, different macrophage subsets (CD68, CD32, CD163) and T cells. In addition, a marked reduction of activation markers (HLA-DR, CD69) and CD183+ (CXCR3) cells was observed in post-treatment biopsy specimens. In conclusion, the clinical improvement of disseminated GA by infliximab is paralleled by inhibition of activated myeloid dendritic cells, different macrophage subsets and type 1 T cells.

Keywords: T cells; dendritic cells; granuloma annulare; infliximab; macrophages.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Biopsy
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dermatologic Agents / pharmacology*
  • Dermatologic Agents / therapeutic use
  • Granuloma Annulare / drug therapy*
  • Granuloma Annulare / immunology
  • Granuloma Annulare / pathology
  • Humans
  • Infliximab / pharmacology*
  • Infliximab / therapeutic use
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Receptors, CXCR3 / immunology
  • Receptors, CXCR3 / metabolism
  • Skin / cytology
  • Skin / drug effects
  • Skin / pathology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • CXCR3 protein, human
  • Dermatologic Agents
  • Receptors, CXCR3
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Infliximab