Presence of draining tunnels denotes a distinct hidradenitis suppurativa phenotype

Abstract

The cross-sectional survey with retrospective data collection by Ingram et al. published in this issue targets the characterization of the clinical profile of patients with moderate-to-severe hidradenitis suppurativa (HS) with and without draining tunnels.¹ It came to the expected result that patients with draining tunnels had more inflammatory nodules, abscesses and scarring. Furthermore, the presence of draining tunnels was associated with significantly more inflammation/redness, drainage from lesions, pain on sitting, low mood/depression, sleep disturbance and fatigue. Physicians agreed that patients with draining tunnels experienced a negative impact of disease on their daily life, mental health, and sexual function compared to those without.

This evidence further enhances the notion that the presence of draining tunnels denotes a distinct HS phenotype with more severe disease, which depicts disease progression and exhibits a poorer response to many current HS treatments. Dermal tunnels are structures unique to HS and are associated with a more severe disease, cause significant pain and morbidity via chronic, malodorous discharge and have a detrimental impact on quality of life.² It has been suggested that the presence of tunnels is associated with a more aggressive course of Hurley stage 3 disease.²

Furthermore, individual patient data analysis from the PIONEERs phase 3 adalimumab trials employing time-to-event analyses was performed to estimate time to achieve HiSCR and time to loss of HiSCR, whereas the presence of dermal tunnels significantly negatively influenced the odds of achieving HiSCR and the time to achieve HiSCR with adalimumab.³ It was proven that integrating draining tunnel status [using the International Hidradenitis Severity Score System (IHS4)] reduced placebo response rates in both PIONEER studies regardless of if a binary or continuous variable was used. Effective treatments against draining tunnels are still an unmet need in the HS treatment.

HS samples with tunnels have a distinct molecular profile compared to HS samples without tunnels.² HS tunnels were at least in part dependent on IL-17 signalling. It is suggested that the response of the subcutaneous nodules to TNFα blockade and not the tunnels suggests that the cellular migration to and across tunnel epithelium is more dependent on IL-17 signalling rather than TNF-α signalling. Taken together, these data demonstrate a novel avenue for the development of therapeutics for this devastating disease and treatment with the newly developed and approved drugs bimekizumab and secukinumab, which target different subunits of IL-17 and seem promising in decreasing dermal tunnel drainage and in the resolution of sinus tracts.

All this evidence clearly suggests that the presence of draining tunnels should be considered a potential marker of disease progression that should be taken into account when treating and evaluating patients in the daily clinical practice. Furthermore, assessing disease severity in a validated manner in an effort to capture the ‘window of opportunity’ concept is a critical step. That is why the recently published European guidelines suggest that severity assessment should be performed with IHS4, which quantifies draining tunnels in a validated manner and also allows characterization of a non-mild HS case without the presence of draining tunnels.^{2, 4} Using such outcomes in clinical trials is of utmost importance as well, as the authors suggest. The impact on draining tunnels maybe overlooked when using the common measure of treatment efficacy, that is, the Hidradenitis Suppurativa Clinical Response (HiSCR). Future clinical trials should incorporate endpoints that can measure improvements in draining tunnels. The use of specific and validated measures that quantify draining tunnels will help to this direction. That is why the recently published European guidelines suggest IHS4-55, a validated dichotomous outcome which represents the 55 reduction of IHS4 compared to baseline, as an important outcome to assess the anti-inflammatory effect of treatments.^{2, 5}

Thrasyvoulos Tzellos has received honoraria from UCB, Novartis, Abbvie, Merck, Boehringer Ingelheim. He is co-copyright holder of IHS4 on behalf of the EHSF e.V. Christos C. Zouboulis has received honoraria as a consultant for AccureAcne, Almirall, Biogen, Boehringer Ingelheim, CLS Behring, Eli Lilly and Company, Estée Lauder, Idorsia, Incyte, L'Oréal, MSD, NAOS-BIODERMA, Novartis, PPM, Sanofi, ShiRhom, Takeda, UCB and ZuraBio and lecture honoraria from Almirall, Amgen, NAOS-BIODERMA, Biogen, BMS, L'Oréal, Novartis, Pfizer and UCB. His departments have received grants from his participation as a clinical and research investigator for AstraZeneca, Boehringer Ingelheim, BMS, Brandenburg Medical School Theodor Fontane, EADV, European Union, German Federal Ministry of Education and Research, GSK, Incyte, InflaRx, MSD, Novartis, Relaxera, Sanofi and UCB. He is President of the EHSF e.V., President of the Deutsches Register Morbus Adamantiades-Behçet e.V., Board member of the International Society for Behçet's Disease, coordinator of the ALLOCATE Skin group of the ERN Skin and chair of the ARHS Task Force group of the EADV. He is Editor of the EADV News and co-copyright holder of IHS4 on behalf of the EHSF e.V.