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Cytokines involved in hidradenitis suppurativa (HS) pathogenesis include interleukin (IL)-1β, IL-17, IL-10 and to a lesser extent TNF-α, therefore representing potential therapeutic targets.
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An overzealous toll-like receptor response to commensal bacteria may be an initiating factor in the the pathogenesis of this disease. In advanced stages, characterised by sinus tract formation and scarring, superinfection with bacterial strains known to induce soft tissue infection may occur, which
Inflammatory Mechanisms in Hidradenitis Suppurativa
Section snippets
Key points
Cytokines in hidradenitis suppurativa
There is a lack of consensus as to which cytokines and immune pathways drive the inflammation in HS. TNF-α is a pivotal proinflammatory cytokine, produced by innate and adaptive immune cells, and it has an established role in many inflammatory conditions such as psoriasis, Crohn disease, rheumatoid arthritis, sarcoidosis, and uveitis.7 Because clinical improvement in HS is frequently observed with infliximab8 and adalimumab treatment,9 it is hypothesized that TNF-α expression is enhanced in
Antimicrobial peptides
Constitutively produced antimicrobial peptides (AMPs), released as part of the body’s innate immune response to microbial threat, are secreted by keratinocytes in large quantities in the presence of invasive pathogens.24 In addition to antimicrobial properties, they also have immunomodulatory effects such as cytokine production, antigen presentation, recruitment of immune cells, and wound healing.24 AMPs are particularly important where the skin barrier function is disrupted as a means of
Proposed involved signaling pathways in hidradenitis suppurativa
Pathogen recognition receptors (PRRs) are germline-encoded, nonclonal binding sites for the recognition of microbes/infectious agents by the innate immune system. PRRs may be found in the cytoplasm or cell surface of immunocytes, or be secreted into the local and circulating fluids.26 PRRs include toll-like receptors (TLRs), the nucleotide oligomerization domain (NOD) proteins, the RIG-like helicases, and the C type lectins.27 The main functions of PRRs include proinflammatory signaling,
Effects of smoking on keratinocytes and skin immunity: facilitating skin inflammation?
HS has been linked epidemiologically to cigarette smoking.39 Tobacco smoke is composed of thousands of chemicals, some of which may have proinflammatory and oxidative properties.40 These components (along with nicotine) activate keratinocytes (KCs) via at least 2 types of receptors: nicotinic acetylcholine receptors (nAChRs) and the aryl hydrocarbon receptors (AHRs).41, 42 Nicotine signals in an agonistic manner via the nAChR, expressed in the peripheral and central nervous system, as well as
Inflammatory pathways in hidradenitis suppurativa
A subclinical inflammatory state may arise in the skin prior to the onset of a visibly active HS lesion. It is suggested that the process begins with an aberrant keratinocyte response to commensal bacteria, which results in inappropriate cytokine and AMP production.4 This results in a mild influx of immune cells, such as innate cells and T cells, which go on to secrete further proinflammatory cytokines and chemokines. The follicular epithelium responds by becoming hyperplastic with keratosis of
Summary
HS was once regarded a disease of primary infectious etiology.41 This is understandable given the clinical presentation of recurrent painful nodules and abscesses, associated systemic malaise, elevated inflammatory markers, suppuration, exudation of serosanguineous material, and response to antimicrobials, at least in the short term. HS does not behave like a typical infection, however. Many cases do not ultimately respond to antibiotics, particularly more advanced, established chronic disease.
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Conflict of interest: None declared.