Tunnels in Hidradenitis Suppurativa: Active Inflammatory Entities with Specific Molecular and Genetic Profiles – A Narrative Review

Abstract

Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating disorder of the pilosebaceous unit. Dermal tunnels, sinus tracts, or fistulas are unique features of HS. One may hypothesize that HS tunnels remain active and may contribute to inflammation and disease severity. Summary: Increased inflammatory infiltrate with an increased number and densities of immune cells was reported in HS tunnels. Moreover, significantly higher levels of IL-36, Il-17A, IL-17C, IL-17F, and CXCL8 mRNA compared to non-tunnel HS skin were found. Furthermore, in the lumen, a proliferative gelatinous mass consisting of inflammatory cells with similar cytokine levels as inflammatory HS lesions was found. It was also proven that HS sinus tracts are often colonized by Porphyromonas spp. and Prevotella spp. with a tendency to biofilm creation. The genetic profile of HS tunnels varies from non-tunnel HS skin, with upregulation of proinflammatory and down-regulation of anti-inflammatory genes. Lastly, treatment with newly developed drugs targeting different subunits of IL-17 seem promising in decreasing dermal tunnel drainage and in the resolution of sinus tracts. Moreover, a higher percentage of patients treated with these drugs achieved HiSCR75 and HiSCR90. Key message: All these data support the hypothesis that dermal tunnels are active, inflammatory entities with different molecular and genetic profiles.

Risk of cardiovascular disorders in hidradenitis suppurativa patients: a large‐scale, propensity‐matched global retrospective cohort study

“…9 The expression of pro-inflammatory cytokines, including IL-1b, IL-6, IL-8, IL-12, IL-17, IL-23, IL-36, and TNF-a, chemokines (CXCL1, CXCL6, CXCL8), danger-associated molecular patterns (DAMPs), and epidermal antimicrobial proteins (AMPs) are significantly higher in the lesional and perilesional skin of HS patients in comparison to HC. 9,38 Some of the cytokines mentioned above are so abundant that they reach the circulation, promoting systemic inflammation and contributing to certain comorbidities. Serum levels of IL-1b, IL-6, and serum amyloid A (SAA) have been found to be statistically increased in patients with HS.…”

“…The pathogenesis is not fully understood; however, local and systemic inflammation seem to play an important role in the development and exacerbation of HS 9 . The expression of pro‐inflammatory cytokines, including IL‐1β, IL‐6, IL‐8, IL‐12, IL‐17, IL‐23, IL‐36, and TNF‐α, chemokines (CXCL1, CXCL6, CXCL8), danger‐associated molecular patterns (DAMPs), and epidermal antimicrobial proteins (AMPs) are significantly higher in the lesional and perilesional skin of HS patients in comparison to HC 9,38 …”

The NLRP3 Inflammasome Gene Is Overexpressed in Hidradenitis Suppurativa Lesions: A Preliminary Study on the Role of Pyroptosis in Disease Pathogenesis

“…The exact prevalence of the disease is unknown, yet according to the latest epidemiological studies, it may vary between 0.6–2.2% [ 14 , 15 , 16 ], with almost two-fold higher prevalence among women [ 17 ]. The disease is characterized by the appearance of recurrent, slowly healing, deeply seated inflammatory nodules or abscesses, which subsequently progress into purulent inflammatory tunnels and mutilating scarring [ 1 , 18 ]. HS has been widely related to a very high psychosocial burden for the patients and their families [ 19 , 20 , 21 ] and is frequently referred to as the worst dermatosis [ 22 ].…”

An Atlas of the Hidradenitis Suppurativa Transcriptome

“…It is worth underlining that there has been a shift in the understanding of HS lesions as a source of inflammation. While scarring tissues and non-draining tunnels are primarily considered to be static lesions that did not influence the further deterioration of the tissue [ 32 ], the genetic, epigenetic, and cytokine profile of HS tunnels, as well as the influence of the presence of proinflammatory gelatinous mass and microbiota, highlights their possible implications in further skin deterioration due to the disease.…”