Profiling the human hair follicle immune system in lichen planopilaris and frontal fibrosing alopecia: Can macrophage polarization differentiate these two conditions microscopically?

BACKGROUND: Frontal fibrosing alopecia (FFA) is traditionally regarded as a variant of lichen planopilaris (LPP) based on histological features. Distinct clinical presentation, demographics and epidemiology suggest differing pathogenic factors determine the final phenotype.

OBJECTIVES: To map the hair follicle immune system (HIS) in LPP and FFA by systematically comparing key inflammatory markers in defined hair follicle compartments.

METHODS: Lesional scalp biopsies from LPP, FFA and healthy controls were stained with the following immunohistochemical markers: CD1a and CD209, CD4, CD8, CD56, CD68, CD123, CXCR3, FOXP3, mast cell tryptase and cKit. Macrophage polarization was explored using CD206, CD163, CD86, RAGE, IL-4 and IL-13 on paired lesional and non-lesional LPP and FFA samples.

RESULTS: Increased numbers of CD8+, CXCR3+ and FOXP3+ T-cells and CD68+ macrophages were identified in the distal HF epithelium and peri-follicular mesenchyme in both LPP and FFA compared with controls. In both LPP and FFA, total and degranulated mast cells and CD123+ plasmacytoid dendritic cells were increased in the perifollicular mesenchyme adjacent to the bulge and infundibulum, whereas numbers of CD1a+ and CD209+ dendritic cells were significantly reduced in the infundibulum CTS. However, only with CD68 staining was a significantly difference between LPP and FFA identified, with greater numbers CD68+ cell in LPP samples. Further, macrophage polarization markers identifed down regulated CD86 and up regulated CD163 and IL-4 expression in lesional LPP compared with FFA samples.

CONCLUSIONS: This comparative immunopathology analysis is the first to systematically profile the HIS in LPP and FFA. Our analysis highlights a potential role of macrophages in disease pathobiology and suggests that macrophage polarization may differ between LPP and FFA allowing microscopic differentiation.