Topographic Expression of IL-1β and Inflammasome-Associated Proteins in Lesional, Perilesional, and Distant Hidradenitis Suppurativa Skin

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent nodules, abscesses, draining tunnels, and scarring. Dysregulated IL-1 and inflammasome-associated pathways have been implicated in its pathogenesis, but their spatial distribution beyond clinically apparent lesions remains incompletely characterized. To assess topographic expression of NLRP3, caspase-1, IL-1β, and IL-18 across lesional, perilesional, and distant HS skin. Skin samples were obtained from eight biologic-untreated patients with HS, six patients receiving adalimumab, and five healthy controls. In HS, matched 6 mm full-thickness biopsies were obtained from the same axilla at an active inflammatory lesion (0 cm), clinically normal-appearing skin 2 cm from the visible lesion edge, and clinically uninvolved skin 10 cm from the lesion edge. Protein abundance was assessed by Western blot. Primary topographic effects were evaluated using mixed-design ANOVA with Benjamini–Hochberg FDR correction, supplemented by non-parametric and exploratory contrast analyses. No protein showed an FDR (false discovery rate)-significant overall site effect or cohort × site interaction in the primary analysis. In biologic-untreated HS, IL-18 showed an FDR-significant topographic effect (q = 0.0444), with higher expression at 0 cm than at 10 cm (q = 0.0469). An exploratory post hoc 2-versus-10 cm analysis identified a highly concordant IL-1β pattern: expression was higher at 2 cm in 7/8 biologic-untreated and 6/6 adalimumab-treated patients. Fisher’s combined probability remained significant after BH correction across the four proteins evaluated for this contrast (p = 0.00421, q4 = 0.0168), whereas comprehensive correction across all 12 protein × contrast combinations yielded q12 = 0.0505 and did not meet q < 0.05. Overall, 13/14 patients showed the same direction (92.9%; exact 95% CI 66.1–99.8%). IL-18 provided the clearest FDR-supported secondary topographic finding. IL-1β showed a highly concordant but hypothesis-generating perilesional-to-distant spatial pattern, whereas total NLRP3 and caspase-1 did not show robust FDR-adjusted spatial variation.