Materiały źródłowe

• #1 Hidradenitis suppurativa: from pathogenesis to diagnosis and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5402905/

  Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease primarily affecting apocrine gland-rich areas of the body and presenting with painful nodules, abscesses, sinus tracts, and scarring. HS is a multifactorial disease in which genetic and environmental factors play a key role. The primary defect in HS pathophysiology involves follicular occlusion of the folliculopilosebaceous unit, followed by follicular rupture, and immune responses (perifollicular lympho-histiocytic inflammation), finally leading to the development of clinical HS lesions. […] The primary defect in HS pathophysiology involves occlusion and subsequent inflammation of the hair follicle; these conditions, together with both innate and adaptive immune dysregulation, are necessary to initiate the development of clinical HS.

• #2 The Pathogenesis and Treatment of Hidradenitis Suppurativa

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10749691/

  Hidradenitis suppurativa (HS) is a multifactorial disease involving the skin and subcutaneous tissues characterized by deep-seated, painful nodules and abscesses with draining sinus tracts. […] Its pathogenesis is multifactorial and as such requires a multimodal approach to treatment, which subsequently is reviewed here. Moreover, the pathogenesis of HS is complex and only partially understood. Autoinflammation is the key driver of disease development and is linked with dysregulated inflammasome activation with the subsequent production of inflammatory cytokines. Genetics and cutaneous microbiome play a role in the development of chronic inflammation and lesion formation. […] The pathogenesis of HS involves not only systemic autoinflammation, which is exacerbated by numerous risk factors, but it is also characterized by cutaneous microbiome dysregulation and genetic contributions.

• #3 Hidradenitis Suppurativa: Molecular Etiology, Pathophysiology, and Management—A Systematic Review

  https://www.mdpi.com/1467-3045/45/5/280

  Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory skin disorder characterized by the development of persistent or recurrent double-headed comedones, painful, firm papules and nodules, draining sinuses linking inflammatory lesions, and residual hypertrophic and atrophic scarring. […] The exact cause of HS is unknown. However, it is thought to be a multifaceted disease caused by genetic, environmental, and immune system components. […] HS may be linked to abnormal immune activation that results in persistent inflammation and skin barrier malfunction, with obesity, smoking, and hormone abnormalities being significant risk factors. […] The pathophysiology of HS involves a complicated interplay of various processes, including follicular hyperkeratosis, sweat gland dysfunction, immune dysregulation, bacterial infection, and chronic inflammation.

• #4 Hidradenitis suppurativa: Pathogenesis, clinical features, and diagnosis – UpToDate

  https://www.uptodate.com/contents/hidradenitis-suppurativa-pathogenesis-clinical-features-and-diagnosis

  Hidradenitis suppurativa (HS; from the Greek hidros = sweat, and aden = glands) is a chronic inflammatory skin condition that is also known as acne inversa and, historically, as Verneuil’s disease. […] Although the name „hidradenitis suppurativa” implies a suppurative disorder that primarily involves sweat glands, increasing knowledge of the pathogenesis of the condition has led to the prevailing theory that HS is a chronic follicular occlusive disease involving the follicular portion of folliculopilosebaceous units (FPSUs). […] The pathogenesis, clinical manifestations, and diagnosis of HS will be discussed here.

• #5 The Pathophysiology of Hidradenitis Suppurativa | Consultant360

  https://www.consultant360.com/exclusives/pathophysiology-hidradenitis-suppurativa

  Research into the pathogenesis of hidradenitis suppurativa (HS) is ongoing. […] However, research has disproved this theory and instead has demonstrated that occlusion of the terminal hair follicle is the key event in disease pathogenesis. […] In HS, hyperplasia of the follicular epithelium causes follicular hyperkeratosis and follicle plugging. The follicle dilates and expands, releasing antigens that stimulate the immune system, causing a lymphocytic perifolliculitis. […] If repair does not occur, the follicle may rupture secondary to mechanical stress on the skin. […] Rupture of the follicle releases bacteria, sebum, and hair follicles into the connective tissue, which results in further inflammation. […] Bacterial infection does not cause the formation of HS lesions but is instead a secondary feature of the disease.

• #6 Hidradenitis suppurativa: from pathogenesis to diagnosis and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5402905/

  The basis for follicular occlusion in HS is yet to be fully defined. Melnik and Plewig recently proposed the concept of HS as an auto-inflammatory disease characterized by dysregulation of the gamma-secretase/Notch pathway. […] In support of this hypothesis, elevated levels of several pro-inflammatory cytokines, most notably tumor necrosis factor (TNF)-, interleukin (IL)-1, and IL-17, have been observed in HS lesions. […] Hence, it is clear that HS is a follicular disease showing some defect in keratin clearance, with resultant follicular occlusion, where defective innate cellular immunity plays an important role. […] Although HS is not primarily an infectious disease, the role of bacteria seems to be very important in HS pathophysiology. Follicular hyperkeratinization and occlusion result in the rupture of pilosebaceous units, releasing bacteria within the dermis and triggering a local inflammatory response and thereby sustaining chronic inflammation.

• #7 Hidradenitis Suppurativa: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1073117-overview

  The earliest inflammatory event in hidradenitis suppurativa is the rupture of the follicular epithelium. […] The apocrine glands may play a role in hidradenitis suppurativa since an abnormal secretion (either the excess or absence) could be influencing an effect on the acroinfundibulum, distal from the gland itself. […] Although the inciting influences for the follicular occlusion and sinus tract formation have not been fully elucidated, genetic factors may play a role. […] Heterozygous mutations were have been reported in the gamma-secretase genes PSENEN, PSEN1, and NCSTN in some patients with hidradenitis suppurativa. […] Gamma-secretase appears integral to normal skin function, through effects on notch signaling, such as the biological role in the hair follicle. […] The pattern of mutations suggests that loss of function of components of the gamma-secretase complex underlies the disease: follicular keratinization, follicular atrophy, the formation of epidermal cysts, absence of sebaceous glands, and epidermal hyperplasia.

• #8 Hidradenitis suppurativa – Wikipedia

  https://en.wikipedia.org/wiki/Hidradenitis_suppurativa

  The exact cause of hidradenitis suppurativa remains unknown, and there has, in the recent past, been notable disagreement among experts in this regard. The condition, however, likely stems from both genetic and environmental causes. Specifically, an immune-mediated pathology has been proposed, although environmental factors have not been ruled out. […] The historical understanding of the disease suggests dysfunctional apocrine glands or dysfunctional hair follicles, possibly triggered by a blocked gland, which creates inflammation, pain, and a swollen lesion. […] Some cases have been found to result from mutations in the NCSTN, PSEN1, or PSENEN genes. The genes produce proteins that are all components of a complex called gamma- (-) secretase. This complex cuts apart (cleaves) many different proteins, which is a crucial step in several chemical signaling pathways. One of these pathways, known as notch signaling, is essential for the normal maturation and division of hair follicle cells and other types of skin cells. Notch signaling influences normal immune system function. Studies suggest mutations in the NCSTN, PSEN1, or PSENEN genes impair notch signaling in hair follicles. Although little is known about the mechanism, abnormal notch signaling appears to promote the development of nodules and lead to skin inflammation.

• #9 New Insight into the Molecular Pathomechanism and Immunomodulatory Treatments of Hidradenitis Suppurativa

  https://www.mdpi.com/1422-0067/24/9/8428

  Hidradenitis suppurativa (HS) is an immune-mediated inflammatory disorder characterized by deep-seated nodules, abscesses, sinus tracts and scars localized in the intertriginous areas. […] Although the pathogenesis has not been entirely elucidated, the primary event is follicular hyperkeratosis of the pilosebaceous apocrine unit. […] It has been speculated that the dysregulation of the gamma-secretase/Notch pathway is implicated in the basis of follicular occlusion in HS. […] Deficiency in the Notch signaling pathway, which has a pivotal role in maintaining the inner and outer root sheath of the hair follicle and skin appendages, results in the conversion of hair follicles to keratin-enriched epidermal cysts, compromises the apocrine gland homoeostasis and leads to the stimulation of toll-like receptor (TLR)-mediated innate immunity, which supports and maintains chronic inflammation.

• #10 Hidradenitis suppurativa: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/hidradenitis-suppurativa/

  Hidradenitis suppurativa, also known as acne inversa, is a chronic skin disease characterized by recurrent boil-like lumps (nodules) under the skin. […] The condition probably results from a combination of genetic and environmental factors. Originally, researchers believed that the disorder was caused by the blockage (occlusion) of specialized sweat glands called apocrine glands. However, recent studies have shown that the condition actually begins with a blockage of hair follicles in areas of the body that also contain a high concentration of apocrine glands (such as the armpits and groin). The hair follicles have a buildup of a fibrous protein called keratin (hyperkeratosis). The blocked hair follicles trap bacteria, leading to inflammation and rupture. […] Genetic factors clearly play a role in causing hidradenitis suppurativa. Some cases have been found to result from variants (also known as mutations) in the NCSTN, PSEN1, or PSENEN gene. The proteins produced from these genes are all components of a complex called gamma- (γ-) secretase. This complex cuts apart (cleaves) many different proteins, which is an important step in several chemical signaling pathways. One of these pathways, known as Notch signaling, is essential for the normal growth and maturation (differentiation) of hair follicle cells and other types of skin cells. Notch signaling is also involved in normal immune system function. Studies suggest that variants in the NCSTN, PSEN1, or PSENEN gene impair Notch signaling in hair follicles. Although little is known about the mechanism, abnormal Notch signaling appears to promote the development of nodules and lead to inflammation in the skin.

• #11

  https://link.springer.com/article/10.1007/s00403-025-04016-1

  Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterised by an aberrant activation of innate immunity and increased production of pro-inflammatory mediators such as interleukin 17 (IL-17). […] IL-17 has been shown to play a key role in the pathogenesis of HS and evidence highlights the potential of IL-17-targeted therapies. […] HS is characterised by aberrant activation of innate immunity and a large inflow of pro-inflammatory mediators (i.e. interferon [IFN]-, tumour necrosis factor [TNF]-, interleukin [IL]6, 8, 17 and 12/23). […] Three main events occur in HS pathogenesis, namely (i) follicular occlusion, (ii) rupture of the dilated follicle and (iii) chronic inflammation with sinus tract formation, each of which is characterised by a cascade of events. […] Follicular occlusion is defined by hyperkeratosis and hyperplasia of the follicular epithelium, causing the formation of a keratin plug due to the accumulation of cellular debris.

• #12

  https://journals.lww.com/ijd/fulltext/2023/68030/pathogenesis_of_hidradenitis_suppurativa__an.10.aspx

  Hidradenitis suppurativa, HS (syn: acne inversa) is a cicatrizing, aberrantly keratinizing, follicular-occlusive systemic inflammatory disorder predominantly affecting (pilosebaceous units of apocrine gland rich) intertriginous areas of the body which have hypoxic, hyperthermic, and moist environment/background. It has recently been recognized as a chronic immune-mediated auto-inflammatory keratinizing disease. The underlying pathogenic mechanisms of this chronic debilitating disease are complex and heterogeneous and are, as yet, incompletely understood. A dynamic interplay of the individual’s genetic landscape, tissue-specific immune micro-environment, host-microbial interactions, metabolic stressors, and associated risk factors and co-morbidities have been implicated in the pathophysiology of this multi-factorial disease. The immunopathogenesis of HS represents a complex and poorly delineated interaction of the neutrophil-dominant, an inflammasome-driven innate component of the immune system, T helper (Th) 1 and Th17 (but not Th22) cells of the adaptive immune system, as well as non-immune cells including fibroblasts, keratinocytes, and endothelial cells, leading to the production of enormous amounts of pro-inflammatory cytokines (along with a significant anti-inflammatory interleukin (IL)-10 mediated element) that, in turn, create, sustain, and amplify numerous reverberating immunological circuits.

• #13

  https://journals.lww.com/ijd/fulltext/2023/68030/pathogenesis_of_hidradenitis_suppurativa__an.10.aspx

  The traditional pathologic model describes HS pathophysiology initiating with follicular occlusion/plugging/dilatation of the follicular-pilosebaceous unit (as a primary event) resulting from inflammation-driven infundibular hyperkeratosis, acanthosis, and perifolliculitis that is worsened by impaired Notch signaling and smoking. This is followed by a follicular rupture with spillage of intrafollicular contents (cell-damage associated molecules and bacteria) inciting innate immune responses, seen histologically as a neutrophil-rich reaction further ensuring a continued influx of macrophages and other immune cells. […] Recently there has been a paradigmatic shift from follicular-occlusion focussed understanding to a greater appreciation of the role of auto-inflammatory mechanisms in HS pathogenesis. Autoinflammatory etiological frameworks are underpinned by a massive involvement of innate immunity involving both structural and cellular innate immune sensors. Upregulation of IL-1 signifies an important autoinflammatory component in the pathogenesis of this disease. Dysregulated Toll-like receptor (TLR) signaling (potentiated by defective Notch signaling), inappropriate AMP production, abnormal systemic complement activation (anaphylatoxins C5a and C5b-9), upregulated type I interferon (INF) signaling, raised leukotriene B4 levels (recruiting innate inflammatory cells), massive tissue infiltrates of neutrophils, macrophages and dendritic cells (DCs) with a few mast cells and natural killer (NK) cells along with their proinflammatory cytokines (tumor necrosis factor (TNF)-), all potentiate HS pathophysiology.

• #14 Unlocking the Mechanisms of Hidradenitis Suppurativa: Inflammation and | CCID

  https://www.dovepress.com/unlocking-the-mechanisms-of-hidradenitis-suppurativa-inflammation-and–peer-reviewed-fulltext-article-CCID

  Understanding the complexity of HSs disease mechanisms is essential, as current research converges on three key pathways: TNF-, IL-1, and the IL-17/IL-23 axis, which are crucial in driving the inflammatory processes underlying HS. Understanding these pathways further elucidates the mechanisms behind these therapeutic strategies, highlighting their critical involvement in HS pathology. […] Impact of microRNA Dysregulation on HS Pathophysiology […] MicroRNAs (miRNAs) have emerged as regulators in the pathogenesis of hidradenitis suppurativa, specifically influencing key inflammatory mediators within the TNF-, IL-1, and IL-17/IL-23 pathways and contributing significantly to the complex clinical manifestations of the disease. Recent studies have found significant overexpression of miRNA-155-5p, miRNA-223-5p, miRNA-31-5p, miRNA-21-5p, and miRNA-146a-5p in lesional HS skin compared to healthy controls, suggesting their involvement in the inflammatory processes of HS. These miRNAs have regulatory roles in the inflammatory pathway; miRNA-155-5p promotes pro-inflammatory cytokine production, and miRNA-146a-5p is a negative regulator of TNF- production.

• #15 An Update on Current Clinical Management and Emerging Treatments in Hidradenitis Suppurativa

  https://www.skintherapyletter.com/hidradenitis-suppurativa/emerging-treatments-update/

  Elevated levels of many pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-10, IL-17, and IL-23 have been observed in blood and skin biopsy samples of HS patients, further implicating immune dysregulation. […] It should be noted that while the primary driver of HS is not infectious, bacterial colonization of lesions can complicate acute flares and worsen symptoms. […] The management of HS is a challenge, in part due to its chronic and variable nature with a poorly understood pathophysiology. […] An improved understanding of the disease mechanisms and wider range of biologic therapies aimed at these underlying inflammatory pathways and specific pathophysiology of HS is poised to create a major shift in this management conundrum.

• #16 The Pathogenesis and Treatment of Hidradenitis Suppurativa

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10749691/

  The hyperkeratosis seems to be driven by the excessive activation of inflammatory pathways and aberrant cytokine signaling. Activation of the inflammasome, which is a group of proteins that responds to stimuli, triggers the production and release of pro-inflammatory cytokines. The cytokines, in turn, contribute to both the primary inflammation and the perpetuating inflammation in HS. […] The cellular infiltrate of HS lesional tissue in moderate to severe disease shows high levels of inflammatory cells especially Th1 and Th17 cells and neutrophils. […] Inflammasome activation can be in response to endogenous or exogenous stimuli. Endogenous sources include gamma secretase dysfunction, impaired Notch signaling, excess TNF-alpha, endogenous hormones, insulin resistance, and metabolic stress. Exogenous sources include smoking, visceral adipose deposition, and dysregulation of the microbiome.

• #17

  https://link.springer.com/article/10.1007/s00403-025-04016-1

  Rupture of the dilated follicle follows, with dispersion of keratin fibres, bacteria and pathogen- and damage-associated molecular patterns (PAMPs/DAMPs) into the dermis, triggering an acute and severe immune response that induces a large inflow of immune cells and the release of cytokines including IL-1 and TNF-. […] This can lead to the formation of nodules, abscesses or fistulas. […] Importantly, at this stage, activated dendritic cells produce IL-12, inducing T helper (Th) 1 polarisation, and IL-23, which maintains the Th17 phenotype. […] Lastly, chronic inflammation is characterised by the formation of epithelialised tunnels, sinus tracts and keloid scars, further triggering inflammation and the production of IFN- (which recruits more inflammatory cells) and TNF- (which supports Th17 polarisation), among others.

• #18

  https://link.springer.com/article/10.1007/s00403-025-04016-1

  Th17 cells are characterised by the production of IL-17 that, in turn, stimulates neutrophil- and macrophage-induced production of IL-1, IL-6, TNF- and matrix metalloproteinases, and, consequently, the formation of fibrosis and sinus tracts. […] Despite recent advances, and the fact that HS was first described in the mid-1800s, the pathogenesis is not fully understood, and the main challenges remain disease management and treatment. […] Several lines of evidence have pinpointed IL-17 as a key player in the pathogenesis of HS, paving the way for a number of targeted therapies against IL-17 in the clinical setting, including human immunoglobulin (Ig) G1/ monoclonal antibodies (secukinumab and CJM112), a humanised IgG1 antibody (bimekizumab), a human IgG2 monoclonal antibody (brodalumab), ligand trap using Affibody molecules (Izokibep, a novel subcutaneous inhibitor with a small molecular size), and a novel trivalent nanobody (sonelokimab, neutralises IL-17A and IL17F).

• #19

  https://insight.jci.org/articles/view/139932

  Rupture of follicular cysts in HS patients results in a heterogenous immune cell infiltrate composed initially of predominantly myeloid cells followed by T cells and B cells. […] Our data are consistent with these findings and further suggest that type 1 T cell responses dominate over IL-17 responses in HS skin. […] We also show that specific myeloid cell subsets that are normally regulatory in nature adopt a proinflammatory phenotype in inflamed HS lesions, with dysregulation of the IL-1 pathway perhaps lying at the center of this phenomenon. […] In addition, we found that regulatory T cells are relatively reduced, as percentages of these cells within the CD4+ T cell compartment were equivalent to that of normal skin, despite the fact that HS skin is highly inflamed. […] This is in stark contrast to psoriatic skin and other highly inflamed tissues, suggesting that a defective compensatory Treg response may contribute to the ongoing and chronic dysregulated skin inflammation observed in this disease. […] Interestingly, Tregs localize to hair follicles in skin and have recently been reported to play a major role in suppressing dermal fibrosis, a prominent feature of late-stage HS lesions.

• #20 Hidradenitis Suppurativa (HS) Causes and Inflammation

  https://www.hsdiseasesource.com/hs-causes

  Anti-inflammatory cytokines, such as IL-10, are increased as a compensatory response to inflammation, attempting to limit the immune response. […] In one study, the expression of two antimicrobial peptides was shown to be significantly altered in HS lesional skin. […] Subclinical inflammation results in epidermal hyperplasia and hyperkeratosis in the upper part of the follicle, leading to follicle occlusion and cyst formation, further accumulating commensal bacteria and propagating a chronic inflammatory response cycle. […] Clinical HS begins with the dilation and eventual rupture of the fragile epithelial lining of the hair follicle. […] The rupture induces massive tissue inflammation and infiltration of neutrophils, dendritic cells, macrophages, T and B cells, plasma cells, and secondary bacterial colonization, which may produce purulent discharge.

• #21 Hidradenitis suppurativa: from pathogenesis to diagnosis and treatment | CCID

  https://www.dovepress.com/hidradenitis-suppurativa-from-pathogenesis-to-diagnosis-and-treatment-peer-reviewed-fulltext-article-CCID

  In support of this hypothesis, elevated levels of several pro-inflammatory cytokines, most notably tumor necrosis factor (TNF)-, interleukin (IL)-1, and IL-17, have been observed in HS lesions. […] Hence, it is clear that HS is a follicular disease showing some defect in keratin clearance, with resultant follicular occlusion, where defective innate cellular immunity plays an important role. […] Although HS is not primarily an infectious disease, the role of bacteria seems to be very important in HS pathophysiology. […] Follicular hyperkeratinization and occlusion result in the rupture of pilosebaceous units, releasing bacteria within the dermis and triggering a local inflammatory response and thereby sustaining chronic inflammation. […] A microbiological study of 102 HS lesions from 82 patients showed Staphylococcus lugdunensis to be the most prevalent species, found as a unique or predominant isolate in 58% of HS nodules and abscesses.

• #22 The Pathogenesis and Treatment of Hidradenitis Suppurativa

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10749691/

  Risk factors for HS contribute to the overall systemic pro-inflammatory state associated with the disease. The most common risk factors include obesity, hyperlipidemia, cardiovascular disease, metabolic syndrome, diabetes mellitus, genetics, and smoking. […] Dysbiosis of the cutaneous microbiome is implicated in contributing to the inflammation driving HS. Samples of HS lesional tissue showed increased Prevotella and Porphyromonas compared to a predominance of Cutibacterium in normal tissue. […] Biofilm formation was also found to be common in HS lesions, but not in samples of non-lesional tissue. Biofilm formation is driven by Staphylococcus epidermidis. The microbiome is thought to contribute to the pathogenesis of HS by inciting an aberrant immune response rather than a response to an infectious process.

• #23 Hidradenitis suppurativa: an up-to-date review of clinical features, pathogenesis and therapeutic approaches :: Cambridge Media Journals

  https://journals.cambridgemedia.com.au/wpr/volume-30-number-1/hidradenitis-suppurativa-date-review-clinical-features-pathogenesis-and-therapeutic-approaches

  Approximately 30-40% of HS patients report a family history of disease in a first-degree relative, suggesting a hereditary component with a mostly autosomal dominant transmission pattern. Mutations in the gamma-secretase Notch signalling pathway have been implicated in a subset of patients with severe HS phenotypes. […] The role of bacteria in HS pathogenesis remains cryptogenic. While a polymorphic flora may be observed at HS-affected sites, superficial and deep bacterial cultures from early unruptured lesions are often sterile. […] It has been theorised that bacteria are implicated in HS pathogenesis by promoting an inflammatory response. Furthermore, biofilm formation is associated with chronic HS lesion, which likely aggregates as a secondary event and contributes to the persistence of inflammation seen in HS.

• #24 Hidradenitis suppurativa. What’s new in pathogenesis and management | Medicine Today

  https://medicinetoday.com.au/mt/2020/july/supplements/feature-article/hidradenitis-suppurativa-what%E2%80%99s-new-pathogenesis-and-management

  Hidradenitis suppurativa (HS) is an autoinflammatory skin condition involving the innate immune system. […] The pathogenesis of HS is not fully understood; inflammation has been regarded as secondary to follicular occlusion but is now considered the likely initial event. […] Genetics, the skin and gut microbiome and biofilms are also likely to play significant roles in HS pathogenesis. […] The pathogenesis of HS is not fully understood. Classically, it has been considered an inflammatory skin disease triggered by occlusion of hair follicles, with secondary inflammation. New evidence suggest that HS should be considered a disease with multifactorial causes including genetic factors, the skin and gut microbiome, skin biofilms and dysregulation of the innate immune system. […] Biofilms, composed of bacteria and the extracellular matrix that they produce, have been identified in both chronic HS lesions and perilesional skin and are often associated with treatment resistance.

• #25 Hidradenitis suppurativa: what’s new in pathogenesis and management | Medicine Today

  https://medicinetoday.com.au/mt/2020/february/feature-article/hidradenitis-suppurativa-whats-new-pathogenesis-and-management

  The development of a biofilm may partly explain the chronicity and treatment resistance of lesions, as well as disease recurrence after surgical excision. […] Classically, HS has been considered a cutaneous disease characterised by follicular occlusion with a secondary inflammatory response. However, some evidence suggests that follicular occlusion is secondary to the underlying inflammatory process, thought to be driven by interleukin (IL)-1. […] Additionally, the interleukins IL-12, IL-17 and IL-23 and tumour necrosis factor-alfa (TNF-alfa) have all been identified in active HS lesions. […] The evolving skin-gut-brain axis model of skin disease may be applicable to HS. […] Ongoing research examining pathways of disease pathogenesis in HS is required, particularly to identify the inciting causes of HS and determine why it progresses in severity.

• #26 Unlocking the Mechanisms of Hidradenitis Suppurativa: Inflammation and | CCID

  https://www.dovepress.com/unlocking-the-mechanisms-of-hidradenitis-suppurativa-inflammation-and–peer-reviewed-fulltext-article-CCID

  HS is currently divided into familial, sporadic, and syndromic forms to understand the genetic influences further. In the familial form, more than one-third of patients with HS report a family history of the disease, which may follow an autosomal dominant inheritance pattern with incomplete penetrance. Genetic factors that contribute to HSs pathogenesis include mutations in genes encoding -secretase components (NCSTN, PSENEN, and PSEN1). These mutations result in dysregulated hair follicle differentiation, hyperkeratosis, and cyst formation due to aberrant Notch signaling, further complicating the disease mechanism. Recent studies, however, present varying results regarding the prevalence and impact of these mutations. For instance, Orobets Karamyshev (2023) extended Nomuras work, relying heavily on familial case studies. They analyzed familial and sporadic cases, uncovering a broader spectrum of genetic variations. Their study suggests that while -secretase mutations are prevalent in many HS cases, their pathogenic impact might differ based on additional genetic and environmental factors not fully explored in earlier studies.

• #27 The Pathophysiology of Hidradenitis Suppurativa | Consultant360

  https://www.consultant360.com/exclusives/pathophysiology-hidradenitis-suppurativa

  A familial form of HS has been described with an autosomal dominant mode of transmission. […] A single culprit gene has not been identified. […] Obesity is not causative but contributes to and exacerbates the disease through several mechanisms, including increased areas of friction between body folds, relative androgen excess, and irritation from sweat retention. […] It has been proposed that nicotine may release toxins into sweat and alter neutrophilic granulocytes and sweat gland activity, contributing to follicular plugging and inflammation. […] There is conflicting evidence about the role of sex hormones in HS. […] Further research is needed to clarify the role of hormones in HS.

• #28 An overview of hidradenitis suppurativa – Dermatology Republic

  https://www.dermatologyrepublic.com.au/an-overview-of-hidradenitis-suppurativa/1942

  Smoking is a lifestyle factor that is highly correlated with disease severity, and with active smokers being 13 times more likely to have HS compared to non-smokers (Acharya Mathur, 2020; Revuz et al., 2008). […] This association might be explained by follicular shearing via mechanical friction between skin folds, the promotion of bacterial growth due to perspiration retention, and increased circulatory levels of pro-inflammatory adipokines (Krajewski et al., 2023). […] Finally, although their role remains unclear, sex hormones are implicated in the progression of HS, since patients most commonly develop symptoms only after the onset of puberty, and disease severity can vary according cycles of menstruation and pregnancy (Clark et al., 2017).

• #29 Hidradenitis Suppurativa: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1073117-overview

  Host-defense defects in patients with hidradenitis suppurativa are suspected but not proven. […] Hyperreactive neutrophils have been proposed to be of pathophysiologic importance in many chronic inflammatory diseases involving the destruction of the surrounding tissue by the simultaneous release of reactive oxygen species and active proteases. […] The release of oxygen radicals from peripheral neutrophils that are activated in vitro was studied in patients with inactive hidradenitis suppurativa. […] The following evidence supports the association of androgens and hidradenitis suppurativa: the disease is rarely present until after puberty begins, […] An abnormal end-organ response to normal circulating levels of androgens is proposed. […] Cigarette smoking may be among the major triggering factors in hidradenitis suppurativa, and its cessation should be encouraged, although whether cessation improves the course of disease is unknown.

• #30 Beyond the skin: endocrine, psychological and nutritional aspects in women with hidradenitis suppurativa | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06175-1

  Following the initial pathogenic events, macrophages and dendritic cells (DCs) detect keratin fibers and other debris through TLRs. This detection leads to an increase in the production of tumour necrosis factor alpha (TNF-), which recruits numerous immune cells into the skin. […] Specifically, T helper (Th)1 and Th17 cells, which locally produce interferon gamma (IFN-) and interleukin (IL)-17 respectively, mainly contribute to hallmarks of HS. […] Furthermore, IL-17 promotes the production of IL-1 by keratinocytes through the activation of the inflammasome and caspase-1. […] Hormonal fluctuations during the menstrual cycle, pregnancy or menopause can further exacerbate these cascades and trigger HS flares. […] Although HS is not an infectious or contagious disease, bacterial colonization in skin lesions is considered a secondary pathogenic event.

• #31 Beyond the skin: endocrine, psychological and nutritional aspects in women with hidradenitis suppurativa | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06175-1

  Notably, sex-related differences in the skin microbiome have been observed, which are associated with variations in sweating rates, skin pH, and hormone fluctuations. […] Bacteria can also sustain the inflammation in hair follicles, once they are already blocked and damaged due to the condition. […] Moreover, the presence of the anti-inflammatory mediator IL-10 in HS lesions, along with limited Th22 activity, may contribute to the reduction of antimicrobial peptides (AMPs), and thereby increase susceptibility to infections. […] Indeed, HS lesions are often colonized by a wide range of opportunistic pathogens. […] These strains can form biofilms that exacerbate chronic inflammation and complicate the management of HS lesions. […] In parallel, the gut microbiome of HS patients exhibits a reduced diversity compared to healthy subjects.

• #32 NK and NKT cells in the pathogenesis of Hidradenitis suppurativa: Novel therapeutic strategy through targeting of CD2 | bioRxiv

  https://www.biorxiv.org/content/10.1101/2023.10.31.565057v1

  Hidradenitis suppurativa (HS) is a chronic debilitating inflammatory skin disease with poorly understood pathogenesis. […] Single-cell RNAseq analysis of HS lesional and healthy individual skins revealed that NKT and NK cell populations were greatly expanded in HS, and they expressed elevated CD2, an activation receptor. […] Immunohistochemistry analyses confirmed significantly expanded numbers of CD2+ cells distributed throughout HS lesional tissue, and many co-expressed the NK marker, CD56. […] In summary, we show that a cellular network of heterogenous NKT and NK cell populations drives inflammation, tunnel formation and fibrosis in the pathogenesis of HS. […] Furthermore, CD2 blockade is a viable immunotherapeutic approach for the management of HS.

• #33 Study reveals the disruption of interaction between proteins CD2:CD58 is a potential new treatment option for people with hidradenitis suppurativa – UAB News

  https://www.uab.edu/news/research-innovation/study-reveals-the-disruption-of-interaction-between-proteins-cd2-cd58-is-a-potential-new-treatment-option-for-people-with-hidradenitis-suppurativa

  Study reveals the disruption of interaction between proteins CD2:CD58 is a potential new treatment option for people with hidradenitis suppurativa. […] Stream HSUAB researchers uncover that interaction between proteins CD2:CD58 can be disrupted to mitigate the expression of genes and proteins that trigger HS pathogenesis. […] The Raman and Athar teams study uncovered that the lymphocyte cell surface protein CD2 is expressed at elevated levels on T lymphocytes and innate lymphocytes, including natural killer cells (NK), natural killer T cells (NKT) and mucosal-associated invariant T cells (MAIT) in HS lesions. […] The understanding that innate lymphocyte populations, specifically NKT cells and natural killer cells, express high levels of CD2 and are the predominant lymphocyte population in HS lesions helped this study to demonstrate that the blockade of cognate interaction between CD2 and CD58 had profound effects in mitigating gene expression and secretion of proteins (cytokines, chemokines, growth factors) which are highly relevant to the pathogenesis of HS.

• #34 Study reveals the disruption of interaction between proteins CD2:CD58 is a potential new treatment option for people with hidradenitis suppurativa – UAB News

  https://www.uab.edu/news/research-innovation/study-reveals-the-disruption-of-interaction-between-proteins-cd2-cd58-is-a-potential-new-treatment-option-for-people-with-hidradenitis-suppurativa

  CD2 through its interaction with the cell surface protein, CD58, has critical functions for the activation of T cells and innate lymphocytes leading to the perpetuation of the inflammatory response, which remains poorly understood and is current focus of this groups research. […] Our study identifies CD2:CD58 interaction along with NKT and NK cells as major drivers of HS pathogenesis, Raman said. […] Targeting of CD2:CD58 therapeutically offers an opportunity to treat HS, an incurable debilitating skin disease impacting quality of life among young patient populations, particularly women. […] Defining the immune cell landscape of HS, particularly at different stages of the disease, and their molecular signatures along with interacting epithelial cell populations will provide us the tools to understand disease progression and develop therapies that arrest and potentially cure the disease, Athar said.

• #35 Hidradenitis suppurativa. What’s new in pathogenesis and management | Medicine Today

  https://medicinetoday.com.au/mt/2020/july/supplements/feature-article/hidradenitis-suppurativa-what%E2%80%99s-new-pathogenesis-and-management

  The inflammatory process is thought to be driven by cutaneous microbiome dysbiosis. […] Some evidence suggests that follicular occlusion is secondary to the underlying inflammatory process, thought to be driven by interleukin (IL)-1. […] Additionally, the interleukins IL-12, IL-17 and IL-23 and tumour necrosis factor-alfa (TNF-alfa) have all been identified in active HS lesions. […] The evolving skin-gut-brain axis model of skin disease may be applicable to HS. […] Further research is required to establish this relationship. […] HS belongs to the follicular occlusion tetrad, which also includes acne conglobata, dissecting cellulitis of the scalp and pilonidal sinus. […] It is likely that the local skin microbiome is involved. […] Precise correlation between HS phenotype and genotype is not currently possible. This probably reflects the multiple factors involved in HS pathogenesis. […] Ongoing research examining pathways of disease pathogenesis in HS is required, particularly to identify the inciting causes of HS and determine why it progresses in severity.

• #36 Beyond the skin: endocrine, psychological and nutritional aspects in women with hidradenitis suppurativa | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06175-1

  Specifically, it shows similarities to bacterial profiles linked to other inflammatory conditions, including Crohn’s disease and inflammatory arthritis. […] Interestingly, metabolites derived from this dysbiotic gut microbiota may contribute to the development of HS and its related comorbidities. […] Therefore, nutritional interventions play a crucial role in supporting the health and diversity of the gut microbiota. […] A balanced diet that includes prebiotics, probiotics, and essential nutrients can help improve gut dysbiosis and potentially reduce inflammation, which may also aid in managing the severity of HS.

• #37 Overview and Diagnosis of Hidradenitis Suppurativa (HS)

  https://www.hcplive.com/view/overview-and-diagnosis-of-hidradenitis-suppurativa-hs

  Hidradenitis suppurativa, which Im going to refer to as HS, is an inflammatory disorder that is characterized by chronic deep-seated nodules, abscesses, fistulas, sinus tracts, and scars in the axilla, inguinal region, inframammary folds, and the perianal area. […] The pathogenesis of HS is multifactorial, with genetic, environmental, and immunological factors included in both the onset and the maintenance of the condition. More specifically, geneticswe believe that up to about 42% of patients with HS do report a family history of the condition. […] Also, there are environmental factors such as mechanical stress, metabolic syndrome, obesity, diabetes, diet, smoking, the skin microbiome, and hormonal factors all involved, as well as in the development and the maintenance of HS. […] And then lastly, immunological, this cascade does start with the follicular occlusion that happens. This results from hyperkeratosis of the follicular epithelium. This accumulates cellular debris, and the formation of a keratin plug happens at that time.

• #38 An Update on Current Clinical Management and Emerging Treatments in Hidradenitis Suppurativa

  https://www.skintherapyletter.com/hidradenitis-suppurativa/emerging-treatments-update/

  Hidradenitis suppurativa (HS) is a severe, debilitating, chronic inflammatory skin disease characterized by recurrent painful nodules, abscesses and draining sinus tracts in intertriginous areas. […] While this condition appears to stem from follicular unit dysfunction, its cause is multifactorial and the exact pathogenesis has yet to be fully elucidated. […] Although the pathophysiology of HS has not been fully elucidated and is multifactorial, current evidence supports an inflammatory etiology with follicular unit dysfunction. […] The current driving theory suggests disease initiation is associated with a chronic subclinical inflammatory state and/or excess keratinocyte proliferation, which results in follicular occlusion and rupture with subsequent abnormal and diffuse inflammatory response.

• #39 An Update on Current Clinical Management and Emerging Treatments in Hidradenitis Suppurativa

  https://www.skintherapyletter.com/hidradenitis-suppurativa/emerging-treatments-update/

  Elevated levels of many pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-10, IL-17, and IL-23 have been observed in blood and skin biopsy samples of HS patients, further implicating immune dysregulation. […] It should be noted that while the primary driver of HS is not infectious, bacterial colonization of lesions can complicate acute flares and worsen symptoms. […] The management of HS is a challenge, in part due to its chronic and variable nature with a poorly understood pathophysiology. […] An improved understanding of the disease mechanisms and wider range of biologic therapies aimed at these underlying inflammatory pathways and specific pathophysiology of HS is poised to create a major shift in this management conundrum.

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