Epithelialized Tunnels are a Source of Inflammation in Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis Suppurativa (HS), also known as acne inversa, is a chronic, painful, burdensome inflammatory disease manifesting in nodules and abscesses with progression to chronically draining tunnels in later-stage disease.

OBJECTIVE: We sought to determine whether HS tunnels are immunologically active participants in disease activity.

METHODS: Skin biopsy specimens were obtained using ultrasound guidance in untreated HS patients and those enrolled in an open-label study of Brodalumab, NCT03960268, for patients with moderate to severe HS.

RESULTS: Immunohistochemistry of HS biopsies demonstrated that the epithelialized HS tunnels recapitulate the psoriasiform epidermal hyperplasia morphology of the overlying epidermis, displaying molecular inflammation including S100A7 (psoriasin) positivity, as well as features of epidermal skin including loricrin, filaggrin, lipocalin-2 and Melan-A positive cells. Tunnels were associated with increased infiltration of T cells, dendritic cells and neutrophils, formation of neutrophil extracellular traps (NETs), and increased expression of psoriasiform pro-inflammatory cytokines. Unsupervised hierarchical clustering demonstrated a separation of HS samples based on the presence or absence of tunnels. Tunnels isolated by microdissection had higher levels of epithelial-derived inflammatory cytokines compared to the overlying epidermis and healthy controls. Clinically, the size and draining of the tunnels were decreased with treatment with IL-17RA antagonist Brodalumab.

CONCLUSION: This data suggests that tunnels are a source of inflammation in HS.