The pathogenesis of hidradenitis suppurativa: Evolving paradigms in a complex disease

Kozera, Emily; Frew, John W.

doi:10.1002/der2.113

Cited by 6 publications

(1 citation statement)

References 128 publications

(344 reference statements)

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“…Hidradenitis suppurativa (HS) is a chronic disabling inflammatory skin disease characterized by painful, deeply seated nodules, abscesses, sinuses, and scars with yet uncertain etiopathogenesis [ 1 , 2 ]. The majority of HS patients are sporadic cases, whereas familial HS has accounted for 3.2–35.8% of HS patients, respectively [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of hypoxia-inducible factor-1α in hidradenitis suppurativa: the link between deviated immunity and metabolism

et al. 2023

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Hypoxia-inducible factor-1α (HIF-1α) is the master transcription factor of glycolysis, Th17 cell differentiation and suppression of regulatory T cells. In the skin and serum of patients with psoriasis vulgaris, increased expression of HIF-1α has been reported, whereas HIF-1α expression in the skin and serum of patients with hidradenitis suppurativa (HS) has not yet been studied. The objective of the study is to demonstrate is there a role for HIF-1α in the pathogenesis of hidradenitis suppurativa, and its relation to HS severity. Twenty patients suffering from hidradenitis suppurativa were included in the study. Punch biopsies were taken from lesional skin for the determination of HIF-1α expression by immunohistochemical staining, and HIF-1α gene expression by quantitative reverse transcription real time PCR. Quantification of HIF-1α protein concentration was done by enzyme-linked immunosorbent assay. Twenty socio-demographically cross-matched healthy volunteers served as controls. We found increased serum levels of HIF-1α. Literature-derived evidence indicates that the major clinical triggering factors of HS, obesity, and smoking are associated with hypoxia and enhanced HIF-1α expression. Pro-inflammatory cytokines such as tumor necrosis factor-$$a$$ a via upregulation of nuclear factor $$\kappa$$ κ B enhance HIF-1α expression. HIF-1α plays an important role for keratinocyte proliferation, especially for keratinocytes of the anagen hair follicle, which requires abundant glycolysis providing sufficient precursors molecules for biosynthetic pathways. Metformin via inhibition of mTORC1 as well as adalimumab attenuate HIF-1α expression, the key mediator between Th17-driven deviated immunity and keratinocyte hyperproliferation. In accordance with psoriasis, our study identifies HS as an HIF-1α-driven inflammatory skin disease and offers a new rationale for the prevention and treatment of HS by targeting HIF-1$$a$$ a overexpression.

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Section: Introductionmentioning

confidence: 99%

Overexpression of hypoxia-inducible factor-1α in hidradenitis suppurativa: the link between deviated immunity and metabolism

et al. 2023

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Hidradenitis Suppurativa

Jenkins

Isaac

Edwards

et al. 2023

Dermatologic Clinics

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Response to adalimumab in Caucasian and Asian patients with hidradenitis suppurativa: A retrospective cohort study of an Australian cohort stratified by patient‐reported ethnicity

Pham,

Flora,

Guttman

et al. 2024

Aust J Dermatology

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Background/ObjectivesCaucasian and Asian patients with hidradenitis suppurativa demonstrate significant differences with regard to age, gender and body mass index. Demographic characteristics are known to influence the efficacy and drug survival of hidradenitis suppurativa therapeutics including biologic therapies. What remains unknown is the impact of ethnicity upon the efficacy of therapeutics once demographic and disease characteristics have been taken into account. This is an important question given the expansion of biologic therapies for HS into the global patient community.MethodsWe assessed 170 patients from a single HS specialist centre in Australia stratified by patient‐identified ethnicity including those identifying as either Caucasian or Asian.ResultsAsian patients demonstrated lower BMI, higher rates of smoking and greater odds of Hurley stage 3 disease with tunnels than Caucasian patients in line with the reported literature. There was no significant difference between percentage of individuals achieving HiSCR50 or IHS4‐55 at Week 16. Significant differences were seen in median time to secondary loss of response, and Kaplan–Meier curve analysis showed a significant difference between curves when stratified by patient‐reported ethnicity. Cox regression analysis demonstrated after accounting for age, gender, BMI, smoking and Hurley stage, the significance of ethnicity in influencing time to secondary loss of response disappears.ConclusionsCaucasian or Asian ethnicity does not influence response to adalimumab treatment on patients with hidradenitis suppurativa.

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The pathogenesis of hidradenitis suppurativa: Evolving paradigms in a complex disease

Cited by 6 publications

References 128 publications

Overexpression of hypoxia-inducible factor-1α in hidradenitis suppurativa: the link between deviated immunity and metabolism

Overexpression of hypoxia-inducible factor-1α in hidradenitis suppurativa: the link between deviated immunity and metabolism

Hidradenitis Suppurativa

Response to adalimumab in Caucasian and Asian patients with hidradenitis suppurativa: A retrospective cohort study of an Australian cohort stratified by patient‐reported ethnicity

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