Summary Background Current insight into the histopathological course of events during disease progression in hidradenitis suppurativa (HS) is fragmentary.

Objectives To identify histological alterations and leucocyte subsets in normal‐appearing perilesional skin, and early and chronic HS lesions.

Methods In this observational study we examined eight perilesional skin samples, and six early and 10 chronic prototypic HS lesions, as well as skin samples from four healthy donors using in situ immunostaining.

Results Perilesional skin showed mild psoriasiform hyperplasia and follicular plugging as well as a low‐grade influx of tryptase‐positive mast cells, CD3+ T cells, CD138+ plasma cells and factor XIIIa+ dendritic cells. In early HS lesions, neutrophilic abscess formation and influx of mainly macrophages, monocytes and dendritic cells predominated. In chronic disease, the infiltrate expanded with markedly increased frequencies of CD20+ and CD79a+ B cells and CD138+ plasma cells. As in early lesions, free keratin fibres were detected in the dermis and within giant cells. Single detached keratinocytes and strands of follicular epithelium were observed in the dermis, the latter frequently expressing Ki67, indicative of active proliferation.

Conclusions Psoriasiform hyperplasia, follicular plugging and low‐grade leucocytic infiltration are already present in normal‐appearing perilesional skin. Keratin fibres in the dermis are associated with clinical disease. Early lesions are characterized by neutrophilic abscess formation and influx of mainly histiocytes, and chronic lesions mainly by expansion of B cells and plasma cells in ‘pseudo’ follicles. Proliferating strands of follicular epithelium may initiate fistula formation. Mast cells are increased in all stages of HS including perilesional skin.