Hidradenitis suppurativa: A folliculotropic disease of innate immune barrier dysfunction?

Abstract

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease affecting the axillae, perineum and inframammary regions, among other body sites. Accumulating evidence indicates a hair follicle (HF) focus to this disease, as it is characterized by an early occlusion, followed by rupture of the HF and more generalized skin inflammation. 1 HS is part of the follicular occlusion tetrad of disorders (HS, acne conglobata, dissecting cellulitis of the scalp and pilonidal sinus).It results in painful local nodules and abscesses that can develop into pus-filled malodorous sinus tracts, also known as tunnels, that may result in extensive scarring. 2,3 In addition to cutaneous inflammation, patients with moderate-to-severe HS have evidence of systemic inflammation, as measured by C-reactive protein (CRP) and highsensitivity CRP. 1,4-8 Thus, it is unsurprising that HS is associated with significant psychosocial morbidity and profoundly impaired patient quality of life, when compared to other inflammatory skin diseases such as psoriasis. [9][10][11][12] Aside from the obvious pain and discomfort of HS lesions, patients commonly experience mood disorders (eg depression), altered body image, stigmatization, social isolation and sexual dysfunction. 9,[12][13][14][15][16] Approximately 35% of HS cases in northwestern European cohorts display a positive family history which suggests a genetic component. 17 This is less in some Asian populations at approximately 5% of patients. 18,19 Environmental factors,

Hidradenitis suppurativa (HS)

“…Neutrophils make up half of the white blood cells in humans and phagocytose invading microbes [20]. The activation of neutrophils appears to be an important factor in the development of HS, as a high level of neutrophils is often observed in the blood of HS patients [21], [22]. Macrophages are phagocytic cells capable of ingesting and destroying microbes.…”

“…APCs are necessary for early HS inflammation due to their expression of Toll-like receptors (TLRs), their ability to phagocytose free-keratin in the dermis, and their secretion of multiple cytokines. However, the relevance of this remains unclear [20], [22], [24], [25].…”

Hydra and the hair follicle – An unconventional comparative biology approach to exploring the human holobiont

“…[3] These imbalances are often associated with changes in the immune and metabolic landscape of the HF microenvironment, including AMP dysregulation, reactive oxygen species (ROS) production and inflammatory cytokine and immune cell induction, which result in induction or exacerbation of inflammatory processes. [4][5][6][7][8] However, whether this HF dysbiosis plays a primary pathogenic role or represents a secondary consequence of diseaserelated environmental and/or intra-tissue changes remains to be clarified. For example, in AA, the initial stimulus recognised by the immune cells that triggers the accumulation of a dense perifollicular inflammatory cell infiltrate remains unknown.…”

Cell‐free DNA is elevated in the serum of patients with hidradenitis suppurativa

“…Cell-free DNA levels positively correlated with CRP (Figure 1c), a disease marker in HS. 1 Cell-free DNA did not correlate with age or BMI (Figure 1d).…”