Hidradenitis Suppurativa: An Exploration of Genetic Perturbations and Immune Dysregulation

Abstract

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition that poses a significant diagnostic and therapeutic challenge for clinicians, as the underlying etiology and pathogenesis remains unclear. The host of genetic mutations and immune dysfunction has been identified to be involved in the pathogenesis of HS during recent years. These genetic defects, including monogenetic mutations altering subunits of g-secretase, a protease that functions through Notch signaling to maintain skin appendages, promote epithelial stability, suppress/terminate innate immune responses (ie, Toll-receptors), further have the propensity to induce aberrant cytokine responses that create to a proinflammatory environment, consequently induce hyperkeratosis and promote expression of pro-inflammatory, locally destructive matrix metalloproteinases. Cytokine-driven inflammation propagates the disease state of HS and contributes to the formation of painful subcutaneous nodules, abscesses, and eventually, fistulas and draining sinus tracts. A closer look at genetic mutations linked to the disease may explain the immune perturbations seen in HS. An understanding of the immune cells and inflammatory markers expressed in affected individuals provides insight into disease pathogenesis and can help identify therapeutic targets.

The Composition of Subgingival Microbiome in Hidradenitis Suppurativa and Periodontitis Patients

“…Studies revealed increased serum IL-6 levels in Hurley II and III HS individuals, indicating that IL-6 may participate in the development of HS [ 85 , 86 ]. Moreover, TLRs and NLRP3 inflammasome, which are involved in periodontal bacteria pathogenicity, play also a role in the pathogenesis of HS [ 87 , 88 ].…”

New treatment of pyoderma gangrenosum and hidradenitis suppurativa: A review

“…The signature abscesses and deep lesions of HS frequently evolve into draining sinus tracts. Over time, due to dermal fibrosis and subsequent healing, these tracts can induce skin deformities and contractures 16,17 HS has a notable prevalence, with estimates suggesting it affects 1%-4% of the Western population. 18 The exact pathogenesis of HS remains elusive.…”

“…Through inhibiting the actions of TNF-α, ADA enhances the innate immune response by diminishing the concentrations of pro-inflammatory cytokines and inflammatory white blood cells. 17,24 Notably, ADA stands out as the sole treatment for HS endorsed by the US Food and Drug Administration (FDA). A recent review revealed that 75% of patients on adalimumab experienced full resolution of PG.…”

Hidradenitis Suppurativa in the United States: Insights From the National Inpatient Sample (2008-2017) on Contemporary Trends in Demographics, Hospitalization Rates, Chronic Comorbid Conditions, and Mortality

“…Follicular occlusion followed by bacterial infection is believed to be the most likely inciting event [ 2 ]. Various genetic, hormonal, and environmental factors have been implicated in the development of HS [ 3 , 4 ]. These include smoking, obesity, high serum levels of certain interleukins, presence of gamma-secretase mutations, and alterations in progesterone and estrogen levels [ 5 - 7 ].…”