Hidradenitis suppurativa: pathogenesis.

Hidradenitis suppurativa (HS) is a complex immune-mediated disorder, initially presenting as folliculitis, and progressively worsening in some patients to advanced lesions, such as fistulas, that may require extensive surgical interventions. In a subset of HS patients, genetic mutations affecting the gamma-secretase complex or keratinocyte dysfunction (pro-inflammatory and hyperproliferative keratinocytes) are implicated. The microbiota is thought to play a crucial role in the development of HS lesions, with dysbiosis observed in both lesional and non-lesional skin, suggesting preclinical alterations. However, the precise role of bacteria in HS remains unclear: Are they contaminants, co-inflammatory agents, or potential disease triggers? A mixed inflammatory response has been observed in lesional skin, involving both innate (macrophages, neutrophils, unconventional lymphocytes) and adaptive (T-and B-cell) immune pathways. However, the dynamics of this immune response remain poorly understood. Because of the unclear nature of HS inflammation, current treatments primarily are based on TNF or IL-17 inhibition. A better understanding of the complexity of HS is critical for the development of more effective treatments.