Abstract
Hidradenitis suppurativa tunnels represent treatment-resistant disease compartment that perpetuates inflammation, microbial dysbiosis, and relapse. Surgical deroofing remains the standard intervention, yet optimal postoperative wound management strategies are lacking. Objectives: We aimed to evaluate the efficacy of a wireless bioelectric wound dressing compared with that of standard of care in modulating tunnel-associated microbiota and preventing surgical site recurrence after hidradenitis suppurativa deroofing. Methods: In this randomized, single-center, split-body trial, patients with bilateral Hurley stages II–III axillary disease underwent tunnel deroofing, with 1 side randomized to bioelectric wound dressing or standard of care (petrolatum and gauze dressing). Subjects (n = 12) were followed for 8 weeks to assess primary outcomes: healing rates. Secondary outcomes included disease recurrence at week 8, change in bacterial load, microbiome composition, and QOL. Results: Bioelectric wound dressing–treated sites showed a significant reduction in bacterial load at weeks 2 and 4 after excision, with enrichment of commensals and a shift away from anaerobic taxa, which were not observed in standard of care–treated sites. Minimal recurrences were observed on bioelectric wound dressing–treated sides alone compared with multiple recurrences on standard of care–treated sites, with trends of improved healing trajectories. Conclusions: Optimized wound care holds a potential to reduce surgical site recurrence and reverse hidradenitis suppurativa dysbiosis. Our data emphasize the importance of postsurgical care to improve outcomes in patients with hidradenitis suppurativa. This trial was registered at ClinicalTrials.gov with NCT05057429. Study registration was submitted on September 15, 2021.
Keywords: Dermatologic surgery, Deroofing, Hidradenitis suppurativa, Microbiome, Wound healing
Introduction
Hidradenitis suppurativa (HS) is a debilitating, chronic inflammatory skin disease characterized by painful nodules, abscesses, and epithelialized tunnels in intertriginous areas. Disease management necessitates a comprehensive approach that integrates both medical and surgical modalities, particularly in instances of severe disease stages (Aarts et al, 2023; Goldburg et al, 2020; Maskan Bermudez et al, 2023). A widely used surgical technique is tunnel deroofing with excision, which can be typically performed in an outpatient setting under local anesthesia (Danby et al, 2015; van der Zee et al, 2010; Vossen et al, 2017). Surgical wounds can be repaired or are left to heal by secondary intention (Alikhan et al, 2019). The primary closure of postderoofing surgical wounds harbors a risk of epidermal appendages entrapment and retention of remaining active disease foci and, consequently, an increased risk of recurrence compared with healing by secondary intention (Danby et al, 2015). Therefore, healing by secondary intention is favored, but the complexity of wound care, pain, extended healing time, and disease recurrence are challenging for patients (Dahmen et al, 2019; Danby, 2010; Danby et al, 2015; Ravi et al, 2022; van der Zee et al, 2010). Despite the widely used surgical interventions for advanced HS, management of postsurgical HS wounds has not been standardized and remains challenging. Thus, optimizing postderoofing wound care remains critical.
During physiological wound healing, an endogenous electrical field guides the migration of individual keratinocytes and large epithelial sheets (Jonkman et al, 1991; Kaur et al, 2011; Nishimura, 1996; Zhao, 2009; Zhao et al, 2022, 2006, 1996), facilitating successful wound re-epithelialization and complete healing (Pastar et al, 2014). In addition, electrical fields can be bactericidal and disrupt bacterial biofilms (Banerjee et al, 2015; Kim et al, 2014). The role of electrical field in wound healing prompted the creation of a wireless bioelectric wound dressing (BEWD) that produces a 1-volt electric potential and superoxide radicals through a silver–zinc reduction–oxidation reaction (Banerjee et al, 2014). BEWDs facilitate healing by promoting cell migration into the wound bed and superoxide anion generation, which inhibit bacterial biofilm formation in burns, surgical wounds, and diabetic foot ulcers (Chan et al, 2023; Cole, 2016; Evans and Sen, 2023; Harding et al, 2012; Khona et al, 2021; Miller et al, 2023; Sen et al, 2021, 2020). In addition, BEWDs demonstrated an anti-inflammatory effect within wound tissue mediated through a TNF-α– and IL-1–dependent pathway, 2 key cytokines involved in the pathogenesis of HS (Kaur et al, 2011; Wolk et al, 2020).
In addition to inflammation, microbial dysbiosis is a hallmark feature of HS, with the increased abundance of anaerobic Gram-negative bacteria associated with severe disease stage and HS tunnels (Pardo et al, 2023; Ring et al, 2019, 2017). The dominance of anaerobic pathogens is preceded by reduction of common cutaneous commensal microorganisms. Although the mechanistic effects of the skin’s microbiome on HS tunnel formation remain mostly unknown, microbial dysbiosis is suspected to contribute to inflammation even before tunnels are clinically appreciated (Riverain-Gillet et al., 2020, Riverain-Gillet et al., 2020). The BEWD-mediated reduction of bacterial load observed in chronic wounds has yet to be explored in the setting of HS wound management (Cooke et al, 2018; Kim et al, 2014). Given the positive effect of BEWDs on epithelialization and its electricidal benefit, we hypothesized that the BEWD will improve healing in postderoofing wounds by targeting HS microbial dysbiosis. We evaluated BEWD effects in a randomized, split-body pilot clinical trial, enrolling patients with bilateral Hurley stages II–III axillary disease who underwent deroofing, with 1 side randomized to either BEWD or standard of care (SOC) (petrolatum and gauze dressing). Our data demonstrate that postderoofing wound care with the BEWD results in reduction of bacterial load and reduced abundance of anaerobic pathogens compared with SOC. Importantly, BEWD application after deroofing has shown potential to reduce disease recurrence at the surgical site, emphasizing the need for standardization of wound care protocols for patients with HS.
Results
Patient disposition, baseline demographics, and disease characteristics
A total of 12 participants with bilateral axillary HS were recruited, all of whom completed the study (Figure 1). Baseline participant characteristics were as follows: 75.0% (9) female, 25.0% (3) Black, 66.7% (8) Hispanic, median age 31.5 (range = 19–52), and 83.3% (10) overweight/obese. Regarding HS characteristics, 50.0% (6) of participants were classified as Hurley stage II, and 50.0% (6) were classified as stage III (Table 1), with no differences in Hurley stage between treated sides of a single patient. Assessing HS severity using the Hidradenitis Suppurativa Physician’s Global Assessment score, 75.0% (9) of participants scored 3 (moderate severity), whereas 16.7% (2) and 8.3% (1) scored 4 (severe) and 5 (very severe), respectively (Table 1).
Figure 1.
CONSORT chart. Consort flow chart for same person trials (following the 2010 consort reporting guidelines). BEWD, bioelectric wound dressing; SOC, standard of care.
Table 1.
Baseline Population Demographic and Clinical Data
| Characteristics | Value |
|---|---|
| Female sex, n (%) | 9 (75.0%) |
| Race N (%) | |
| Black | 3 (25.0%) |
| White | 9 (75.0%) |
| Hispanic ethnicity, n (%) | |
| Hispanic | 8 (66.7%) |
| Patient age, median (range) | 31.5 (19–52) |
| Age at diagnosis, median (range) | 25 (15–41) |
| Years of diagnosis, median (range) | 4 (1–15) |
| Positive family history, n (%) | 2 (16.7%) |
| Positive smoking history, n (%) | 4 (33.3%) |
| BMI category, n (%) | |
| Normal (18–24.9) | 2 (16.7%) |
| Overweight (25–29.9) | 3 (25.0%) |
| Class I obese (30–34.9) | 2 (16.7%) |
| Class III obese (>40) | 5 (41.7%) |
| Number of anatomical areas involved, n (%) | |
| 1 | 2 (16.7%) |
| 2 | 2 (16.7%) |
| 3 | 5 (41.7%) |
| 4 | 2 (16.7%) |
| Hurley Stage N (%) | |
| 2 | 6 (50.0%) |
| 3 | 6 (50.0%) |
| HS-PGA score, n (%) | |
| 3 | 9 (75.0%) |
| 4 | 2 (16.7%) |
| 5 | 1 (8.3%) |
| Co-morbidities N (%) | |
| Diabetes | 3 (25.0%) |
| Hypertension | 1 (8.3%) |
| Hyperlipidemia | 0 |
| Inflammatory Bowel Disease | 0 |
| Anemia | 1 (8.3%) |
| HIV | 1 (8.3%) |
| Asthma | 2 (16.7%) |
| Gynecologic | 2 (16.7%) |
| Atopic Dermatitis | 1 (8.3%) |
| Systemic antibiotics | 4 (33.3%) |
| Topical antibiotics | 6 (50.0%) |
| Concurrent Medications N (%) | |
| Adalimumab | 4 (33.3%) |
| Oral Contraceptive Pills | 5 (41.7%) |
| Spironolactone | 7 (58.3%) |
Abbreviations: BMI, body mass index; HS-PGA, Hidradenitis Suppurativa Physician’s Global Assessment.
Postderoofing treatment with BEWD resulted in reduction of bacterial load and reversal of microbial dysbiosis
The bacterial load and skin microbiome composition was assessed at BEWD and SOC sites using 16S ribosomal RNA (rRNA) qPCR and amplicon sequencing from the collected tissue samples at baseline (week 0) and week 4 (Figure 2). Bacterial load in the SOC control group showed no significant change between week 0 and week 2 or week 4 time points (P = .89 and P = .97) (Figure 2). Axillae randomized to BEWD treatment showed a significant decrease in bacterial load by week 2 compared with that at baseline (P = .0164). The decrease in bacterial load remained significant at week 4 compared with that at baseline (week 0) (P = .0124) (Figure 2).
Figure 2.
Post-deroofing wound care of HS with a bioelectric wound dressing (BEWD) reduces bacterial load. Average LogCFU were calculated at Week 0, Week 2, and Week 4 in both axillae (n = 12 each). There were no significant differences in bacterial load at each timepoint in the group treated with SOC (P = .89, P = .97). Statistically significant reduction in bacterial load was noted between week 0 and week 2 (P = .0164) and between week 0 and week 4 (P = .0124) in the group treated with the BEWD; data presented as mean ± standard deviation. Repeated measures one-way ANOVA was used to compare LogCFU change within the treatment. Statistical significance was defined as P < .05.
Next, we assessed potential shifts in the skin microbiome composition in BEWD- and SOC-treated axillae utilizing a 16S rRNA amplicon sequencing. No significant changes in microbial composition of the anaerobic genera associated with HS pathogenesis were observed in the SOC-treated sites (Figure 3). The Shannon diversity index indicated a lack of significant diversity variation (P = .073), and beta diversity, assessed through the Bray–Curtis dissimilarity index, showed no substantial differences in SOC-treated sites after 4 weeks of postsurgical wound care (Figure 4). Opposed to lack of microbiome changes in SOC-treated sites, marked difference in the microbiome composition was revealed at both the genus (Figure 5a) and species (Figure 5b) level at BEWD-treated postderoofing sites. Alpha diversity, a measurement of intrasample diversity (Willis, 2019), was not significant (P = .862). However, beta diversity or intersample variability was statistically significant when comparing samples at initial visit and after 4 weeks of postderoofing wound care with the BEWD (P = .018) (Figure 5c). Specifically, multiple anaerobes characteristic for HS tunnels and abundant at baseline, including Peptinophilus, Prevotella, Porphyromonas, and Peptostreptococcus, were reduced by week 4 in BEWD-treated sites only, with statistically significant reduction of Peptinophilus (P = .008), Parvimonas (P = .038), and Clostridium (P = .001) (Figure 6). In addition to reduction of pathogenic anaerobes, we observed increased abundance of genera known as skin commensals (Almoughrabie et al, 2023; Kim et al, 2020; Lukic et al, 2017; Piewngam et al, 2023), particularly Cutibacterium (P = .023), Lactobacillus (P = .018), and Bacillus (P = .006) in BEWD-treated sites (Figure 6). In contrast to observed increased abundance of commensal genera in BEWD-treated postderoofing wounds, no significant variation over 4 weeks of SOC after surgery was observed for Cutibacterium, whereas abundance of Corynebacterium was significantly increased by week 4 in SOC-treated wounds only (Figure 3).
Figure 3.
Post-deroofing SOC does not reduce levels of anaerobic pathogens and increases Corynebacterium. Relative abundance (%) of genera from BEWD treated sites at week 0 and week 4 is shown. The genera associated with HS pathogenesis, Prevotella (P = .951), Finegoldia (P = .108), and Porphyromonas (P = .151), demonstrated an insignificant difference between Week 0 and Week 4. Additionally, the genera known to be commensals, Cutibacterium (P = .477), were shown to remain unchanged between week 0 and week 4 while Corynebacterium was significantly increased by week 4 (P = .013). Boxes represent the interquartile range, the central line denotes the median, and whiskers indicate the minimum and maximum values. Paired-sample t-test was conducted; statistical significance was defined as P < .05.
Figure 4.
SOC wound dressing did not influence microbiome composition in HS tissue post-deroofing. 16S ribosomal RNA sequencing was performed on excised axillary tissue that received SOC wound dressing. Stacked bar charts show microbial composition between week 0 and 4 in individual subjects at the level of a genus and b species. (c) Alpha diversity as measured by Shannon Diversity Index between Week 0 and Week 4 of SOC treated axillae showed no significant change in diversity between time points (P = .073). (d) Beta diversity as measured by Bray Curtis Dissimilarity Index demonstrates no significant differences between week 0 and week 4 (P = .864). Statistical significance was defined as P < .05.
Figure 5.
Post-deroofing wound care of HS with a BEWD shifts microbiome composition in lesional tissue. Relative abundance (%) of genera a and species b from BEWD sites before and after treatment with overall most abundant genera displayed. (c) Beta diversity demonstrated a significant difference between BEWD sites at week 0 and week 4. Beta diversity of microbiome composition at weeks 0 and 4 was measured by Bray-Curtis index. Statistical significance was defined as P < .05.
Figure 6.
Post-deroofing wound care with BEWD results in reduced abundance of HS pathogens and increased abundance of commensal genera. Relative abundance (%) of genera from BEWD treated sites at week 0 and week 4. Multiple genera demonstrated differences between week 0 and week 4. Genera that decreased with BEWD application includes Peptinophilus (P = .008), Parvimonas (P = .038), and Clostridium (P = .001). The genera shown to increase after BEWD application included Cutibacterium (P = .023), Lactobacillus (P = .018), and Bacillus (P = .006). Boxes represent the interquartile range, the central line denotes the median, and whiskers indicate the minimum and maximum values. Paired-sample t-test was conducted; statistical significance was defined as P < .05.
Postderoofing sites treated with BEWD demonstrated trend of improved healing and reduction of recurrence
At week 8, the BEWD-treated side demonstrated a trend toward faster rate of healing (0.45 ± 0.28 cm2/day) compared with SOC-treated side (0.39 ± 0.28 cm2/day) (Figure 7a). Similar results were observed looking at percentage wound area reduction. A high percentage closed wound area was observed on the BEWD-treated side (88.00 ± 15.69) compared with that on SOC-treated sites (80.90 ± 24.28), but results did not reach statistical significance (Figure 7b). Clinical photographs from 2 participants showcasing patient baseline bilateral axillary disease burden, immediate postoperative wounds, and wound-healing progression at weeks 4 and 8 indicate improvement with BEWD compared with SOC (Figure 8a and b). We followed patients for additional 4 weeks to evaluate recurrence rate, a common issue in patients with HS undergoing surgical excision (Mehdizadeh et al, 2015). At week 8, none of the subjects exhibited unilateral recurrence at the site treated with BEWD (Figure 8c). Overall, recurrence was observed in 50.0% of participants, with 4 exhibiting unilateral recurrence in the SOC-treated site and 2 exhibiting recurrence bilaterally (Figure 8c and d). Sex, race, ethnicity, number of sites, Hidradenitis Suppurativa Physician’s Global Assessment scores, smoking status, and treatment agents were similar across participant who exhibited recurrence on bivariate and multivariable analysis.
Figure 7.
BEWD demonstrates trend of improved healing of HS post-deroofing wounds compared to SOC wound care.(a) Decrease in wound area for each patient at individual timepoint. Wound area closure at individual timepoints in post-deroofing excision axillary wounds treated with bioelectric wound dressing (BEWD; red) when compared to standard of care (SOC, green). (b) Bar graph dot plot showcasing remaining percent wound area open at week 8 in wounds treated with BEWD (red) as compared to those treated with SOC (green); Data are presented as mean, error bars represent standard error of mean. Statistical significance was defined as a 2-sided α-level of 0.05.
Figure 8.
Short-term hidradenitis suppurativa (HS) localized recurrence is reduced in post-deroofing excision axillary wounds treated with BEWD when compared to SOC.(a) and (b) Photographs of study sites from 2 participants, detailing pre-operative HS lesions and burden, immediate post-operative wounds, and wounds at weeks 4 and 8 post-surgery treated with either BEWD or SOC. Clinical images in panels a demonstrate successful healing regardless of the dressing used. Written patient consent for the publication of photographs was obtained. (c) Venn diagram showing surgical site recurrence per treatment. By week 8, 4 patients showed signs of HS recurrence on the site treated with SOC only and 2 patients showed recurrence in the bilateral axillae. No patient experienced HS recurrence only on the side treated with the BEWD. (d) Close-up images showcasing HS recurrence in a representative participant on the surgical site treated with SOC. Recurrence was diagnosed due to the presence of new onset drainage (white arrows) not present at the initial assessment or at the time of deroofing. Physical examination revealed erythema consistent with irritant contact dermatitis, likely caused by the inflammatory exudate. Overall and surgical site-specific recurrence rates were computed for surgical site-specific recurrence rates. Bivariate analysis was performed using chi-square for categorical variables and Fischer exact tests for site-specific disease recurrence at the surgical sites were used.
The QOL improved for all subjects
Although the split-body study design limited opportunity to evaluate QOL per treatment arm, we assessed QOL, pain, and wound-associated parameters prior to surgery and at 8-week follow-up visit. A significant decrease of 5.3 ± 4.7 (P = .0034) in mean Dermatology Quality of Life Index scores 8 weeks after surgery was observed (Figure 9a). This change represents an average decrease from “moderate effect” to “small effect” of HS on participants’ QOL regardless of the treatment arm. Changes in Dermatology Quality of Life Index per individual participant revealed an improvement in QOL in 11 (91.7%) of participants. None of the 12 participants reported Dermatology Quality of Life Index worsening (Figure 9b). Overall, the mean pain score as per Visual Analog Scale was 0.8 ± 1.5 at week 8, and wound erythema and exudation improved for all subjects.
Figure 9.
Changes in Dermatology Quality of Life Index (DLQI) before and after deroofing excision surgery.(a) Mean DLQI score prior to de-reroofing (week 0) and at week 8 post-deroofing. (b) Individual DLQI Score Change between week 0 and week 8. Data are presented as mean, error bars represent standard error of mean. Paired-sample t-test was conducted; statistical significance was defined as a 2-sided α-level of 0.05.
Discussion
There is a recognized need for surgical care for patients with severe HS (Aarts et al, 2023); however, postsurgical care in HS remains challenging with no current consensus (Alikhan et al, 2019). In this study, we introduce the prospect of an enhanced healing process coupled with lower recurrence rates with a BEWD as a compelling postderoofing wound care regimen that can target microbial dysbiosis and alleviate the burden on patients with HS who have severe diseases.
Postsurgical disease recurrence is challenging for patients living with HS, their caregivers, and providers (Mehdizadeh et al, 2015). Our participants experienced an overall low short-term surgical site recurrence rate compared with current literature (Bouazzi et al, 2020; Mehdizadeh et al, 2015; van Hattem et al, 2012). Interestingly, we noted the absence of unilateral disease recurrence in the sites treated with BEWD, suggesting that BEWD can mitigate local recurrence. This effect may be mediated through the observed effects on HS microbiome characterized by reduction of tunnel-associated anaerobic pathogens and increased abundance of skin commensals. In addition to its antimicrobial effect, future evaluation of the dressing’s immunomodulatory effect may uncover whether it exerts its documented effect on TNF-α and IL-1 (Kaur et al, 2011; Wolk et al, 2020) within postderoofing excisional wounds or acts through a different immunomodulatory pathway.
The BEWD was noninferior to the SOC (gauze with petroleum) considering pain levels, wound exudation, and erythema. Furthermore, the trend of higher rate of wound closure in the BEWD-treated sites at week 8 suggests a tangible clinical benefit in terms of expediting the healing process. The BEWD appears to foster an environment conducive to efficient tissue repair and re-epithelialization, further supporting the notion that the BEWD offers a superior alternative to traditional SOC postsurgical wound care method.
BEWD was additionally well-tolerated by all participants, as reported subjectively, which aligns with the effect of BEWD on chronic wound care (Roy et al, 2019). Our study validates the findings of previous HS microbiome data, demonstrating prevalence of Gram-negative anaerobes and a loss of skin commensals in HS tunnels prior to surgical intervention (Naik et al, 2020; Pardo et al, 2023; Ring et al, 2019, 2017; Świerczewska et al, 2022; Williams et al, 2024), yet warranting confirmation in larger clinical studies. The HS tunnel microenvironment is highly anaerobic, providing a unique niche for fastidious Gram-negative anaerobic pathogens; however, little is known of the effects of these anaerobes on HS pathogenesis or response to treatment, including surgical procedures. Importantly, our microbiome data are strengthened by the split-body design, avoiding interpersonal variability in microbiome composition and supporting the overall beneficial effect of BEWD demonstrated through modulation of HS microbiome and reduction of tunnel-associated anaerobic pathogens and increased abundance of skin commensals (Figure 3), which were not observed with SOC postderoofing wound care. The recent study demonstrated ability of Gram-negative anaerobes characteristic for HS to provoke significant inflammation in human keratinocytes (Williams et al, 2024), implying potential effect on BEWD on tissue inflammation during wound-healing process. To the best of our knowledge, this controlled study demonstrates previously unreported microbiome characterization in HS wounds after surgical deroofing. The control arm of our study suggests that deroofing alone with SOC wound care—petrolatum and gauze dressing—does not correct the disease-associated dysbiosis, imposing the risk of recurrence. Our findings further emphasize the critical importance of standardizing procedural therapeutic strategies for HS and highlight the necessity for development of innovative therapies targeting microbial dysbiosis in patients affected with HS.
Recently, consensus panel recommendations suggested that HS postsurgical wound dressing choice should take into consideration the wound bioburden (Chopra et al, 2023). Understanding how BEWD influences the skin microbiome at postderoofing excision surgical sites, including shifts in bacterial diversity and abundance, suggests yet unexplored microbiome component contributing to reduction of recurrence. In addition, the increased abundance of commensal bacterial genera, known to promote cutaneous barrier restoration (Almoughrabie et al, 2023; Mohammedsaeed et al, 2015; Pastar et al, 2020), in response to BEWD underscores the importance of healthy microbiome for successful healing and suggests the restoration of the normal microbial composition as a potentially novel strategy to prevent recurrence. Subsequent investigations employing shotgun sequencing and metagenomic analysis of viable bacterial populations, in conjunction with assessments of host immune response, may delineate the species-specific alterations in microbial communities and reduction of inflammation associated with BEWD application.
After deroofing, participants experienced clinically meaningful improvement in QOL, aligning with current literature (Kohorst et al, 2017; van der Zee et al, 2010). BEWD was well-tolerated by all participants and was noninferior to SOC considering pain levels, wound exudation, and erythema. The trend of higher rate of wound closure in the BEWD-treated sites at week 8 suggests a notable clinical benefit, especially considering that BEWDs have been shown to foster an environment conducive to efficient tissue repair and re- epithelialization (Pastar et al, 2014). These findings align with the broader trends observed in the faster healing rates, further supporting the notion that the BEWD offers a superior alternative to traditional SOC wound care method (Chan et al, 2023; Cole, 2016; Harding et al, 2012; Kaur et al, 2011; Miller et al, 2023), warranting confirmation in larger clinical studies. BEWD was additionally well-tolerated by our participants, a finding that aligns with the literature (Roy et al, 2019).
Our study was strengthened by its split-body design, which eliminates interindividual variability and enhances internal validity. In addition, our study population reflected the demographics of patients with HS, in terms of sex ratio, and skin of color representation (Garg et al, 2017a, 2017b; Ingram et al, 2018). The inclusion of participants receiving various HS systemic and topical treatments increases generalizability, capturing management heterogeneity in HS management. However, acknowledging the limitations of our study is crucial for a nuanced interpretation of the results. In addition to the small number of subjects, the split-body design imposes a constraint on identifying the differential impacts of BEWD and SOC on QOL. Furthermore, 16S rRNA sequencing detects both live and dead organisms indiscernibly (Acosta et al, 2023). Further discernment among bacterial species will require characterizing the viable microbiome and combining metagenomics with culture techniques, providing a more comprehensive understanding of the HS microbiome dynamics in response to deroofing. In addition, the short duration of follow-up limited our ability to assess long-term comparative outcomes between the dressing types. Finally, both clinical investigators and patients were unblinded to treatment allocation, which could introduce bias in patient-reported and physician-assessed outcomes. However, laboratory-based investigators analyzing bacterial load and microbiome were blinded to treatment allocation, ensuring objective assessment of these data.
In summary, the results of our study emphasize the importance of postderoofing wound care for patients affected by HS and highlight the benefits of BEWD. The BEWD not only addresses the critical clinical concern of disease recurrence but also offers a window into the underlying microbiome-mediated pathogenesis of advanced HS. Furthermore, our data imply that interventions targeting the postsurgical wound microenvironment can have far-reaching effects on the chronicity and recurrence patterns of HS, emphasizing the need for standardized wound care protocols.
Materials and Methods
Trial design, ethics, and registration
This randomized, open label, split-body, single-center clinical trial is a pilot study evaluating the healing outcomes of a BEWD for postderoofing care in patients with HS. The study protocol was approved by all relevant ethics committees and institutional review board. The trial was conducted according to the principles of the Declaration of Helsinki and the International Council on Harmonization Guidelines for Good Clinical Practice and preregistered in ClinicalTrials.gov. Written informed consent was provided by patients prior to enrollment.
Participants
Eligible patients were adults diagnosed with HS, classified as moderate-to-severe HS as per Hurley staging, with at least 1 tunnel in each axilla (Hurley, 1996). Demographic information and HS disease clinical data were collected, including current and past HS therapeutics, medical comorbidities, and antimicrobial treatments (Table 1). Race and ethnicity categories were collected because it is recognized that certain populations are disproportionately affected by HS and self-reported through a selection of choices. The study followed the Consolidated Standards of Reporting Trials guideline (Figure 1).
Interventions
Twelve patients underwent bilateral same-day axillary tunnel deroofing procedures at the baseline visit (week 0). Preoperative tunnel mapping was conducted using a handheld, low-frequency (1–10 MHz) ultrasound device (ButterflyIQ+, Butterfly Network). Anesthesia was administered through tumescent lidocaine injections. Intraoperatively, tunnel identification was facilitated using a blunt probe, followed by postexcision curettage of the tunnel base. Excised tissue samples were collected for DNA isolation and microbiome analysis.
Subsequently, each patient’s surgical sites were randomly assigned in a 1:1 ratio to receive either the study device, a BEWD (Procellera, Vomaris Innovations, Inc.), on one side or the SOC, petrolatum with nonadherent gauze, on the other side, as primary wound coverings until complete wound healing (Figure 1). The BEWD dressing, powered by a Silver-Zinc reduction–oxidation–coupled reaction that generates a low electric field (∼1 V), was coated with the wound hydrogel provided in the kit for conductivity. Bilateral secondary foam dressings (Mepilex, Mölnlycke Health Care) were applied to SOC- and BEWD-treated sites. Patients were then scheduled for follow-up on day 3 and weeks 1, 2, 4, and 8 for a total of 6 visits. Wound debridement was performed at weeks 2 and 4, and discarded tissue was collected for DNA isolation and microbiome analysis.
Outcomes
The primary endpoint was rate of healing, reported as area reduction in cm2/per day and percentage wound area reduction at every time point. Key secondary endpoints reported included disease recurrence defined as surgical-site recurrence, wound exudate qualification, periwound erythema, postprocedural pain, surgical-site tenderness, and change in QOL. Safety was assessed as treatment-emergent adverse events in all patients, defined as any adverse event that began or worsened in severity after the intervention. Wound size was evaluated at each visit utilizing the eKare inSight Advanced Wound Care software (eKare, Fairfax, VA). Additional wound-related outcomes were documented, including wound exudate quantification using a 5-point Likert scale and periwound erythema using the 5-point clinician erythema assessment (Tan et al, 2014). Data on missed work or school days, pain medication usage, and dressing changes were also collected. Pain levels were assessed using the Visual Analog Scale (Haefeli and Elfering, 2006), and surgical-site tenderness was recorded. HS disease activity was assessed using the Hurley staging system, Hidradenitis Suppurativa Physician’s Global Assessment scale, and a body map for HS lesions (Kimball et al, 2012; Revuz, 2015). Disease recurrence at the surgical sites, defined as the emergence of a nodule or tunnel either within the wound itself or within a distance <1.0 cm from the wound’s outer margin, was assessed. QOL was surveyed using the Dermatology Quality of Life Index questionnaire at both week 0 and week 8 (Finlay and Khan, 1994; Kirby et al, 2020). An additional secondary endpoint included bacterial colony forming unit count from tissue samples, quantified using a logarithmic equation determined by the standard curve.
Bacterial DNA isolation and 16S rRNA real-time qPCR
DNA was extracted from the collected tissue samples (weeks 0, 2, and 4) with the Quick- DNA Fungal/Bacterial Microprep Kit (Zymo Research, Irvine, CA). The concentration of the isolated DNA was determined using a DeNovix Spectrophotometer (DeNovix, Wilmington, DE) and subsequently diluted to 10 ng/μl using microbial DNA-free water (Qiagen, Hilden, Germany). Absolute quantification of the bacterial load was performed using 16S rRNA real-time qPCR with the following V1–V3 16s rDNA primers: 27F (5′-GCTGCCTCCCGTAGGAGT-3′) and 338R (5′-AGAGTTTGATCCTGGCTCAG-3′). Standard curve was generated as previously described (Kim et al, 2023). The PCR reactions were conducted in a final volume of 20 μl, employing PowerUp SYBR Green Mastermix (Applied Biosystems, Waltham, MA), and carried out in a Biorad CFx Connect Real-time System (Bio-Rad Laboratories, Hercules, CA). As a negative control, a no-template reaction was included, consisting of microbial DNA-free water (Qiagen).
The 16S rRNA sequencing and analyses
We utilized CosmosID (Germantown, MD) 16S rRNA sequencing and bioinformatic pipeline services. Isolated genomic DNA from tissue samples collected at weeks 0 and 4 were sequenced. Raw reads were processed using DADA2 algorithm, trimming was achieved using Cutadapt, and human-aligned reads were excluded from analysis (Martin, 2011). Relative abundance calculated from total reads per individual sample was used for composition and diversity analysis. Alpha diversity was determined using Shannon diversity index, and beta diversity was determined using Bray–Curtis dissimilarity index. Individual genera and species were compared between weeks 0 and 4 using Wilcoxon rank-sum test.
Statistical methods
Baseline characteristics of the study participants were described using univariate frequency statistics. Paired-sample t-tests were conducted to assess the changes in mean rate of healing, mean percentage wound area reduction was calculated for each treatment group, and paired-sample t-tests were conducted to assess the changes in these outcomes from week 0 to week 8. Considering a total of 24 surgical sites, overall and surgical-site–specific recurrence rates were computed for surgical site–specific recurrence rates. Bivariate analysis was performed using chi-square for categorical variables and Fischer exact tests for continuous variables to compare baseline demographic and clinical characteristics across cohorts, on the basis of stratifying for site-specific disease recurrence in surgical sites. This was followed by a multivariable analysis to identify the characteristics associated with surgical recurrence at surgical sites. Statistical analyses were carried out using Statistical Package for the Social Sciences, version 28.0 (IBM, Armonk, NY).
Average log colony forming units were determined for the BEWD and SOC groups at weeks 0, 2, and 4, and repeated-measures 1-way ANOVA was performed using GraphPad Prism (GraphPad Software, San Diego, CA). Statistical significance was defined as a 2-sided α-level of 0.05.
Ethics Statement
All aspects of this study, including written informed consent, data collection, and photo acquisition, have been approved by the University of Miami Institutional Review Board under the following approval identification for research on human subjects: 20210621. The authors attest to obtaining written patient consent for the publication of recognizable patient photographs or other identifiable material, with the understanding that this information may be publicly available.
Data Availability Statement
HL-T, IP, MY, and TG have access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Individual participant data that underly the results reported in this article after deidentification will be shared upon reasonable request after signing a data-access agreement. Original sequences are available through Sequence Read Archive under accession number and BioProject PRJNA1055075. Sequencing data are publicly available at https://www.ncbi.nlm.nih.gov/sra/PRJNA1055075.
ORCIDs
Marita Yaghi: http://orcid.org/0000-0001-5818-7558
Tammy Gonzalez: http://orcid.org/0000-0003-0013-6429
Nicole Vecin: http://orcid.org/0009-0007-6223-6202
Irena Pastar: http://orcid.org/0000-0003-0197-6198
Hadar Lev-Tov: http://orcid.org/0000-0001-6223-7001
Conflict of Interest
The authors state no conflict of interest.
Acknowledgments
We are grateful to all our patients affected by hidradenitis suppurativa who trust us to care for them. We are also thankful to Jelena Marjanovic and Rebecca Verpile for their technical support. This work was supported by Vomaris Innovations grant to HL-T and IP; IP and HLT are supported by National Institutes of Health AR083385; TG is supported by National Institutes of Health P50MD017347. This trial was registered at ClinicalTrials.gov with NCT05057429. Study registration was first submitted on September 15, 2021.
Author Contributions
Conceptualization: HL-T, IP; Formal Analysis: TG, MY, NV, HL-T, IP; Funding Acquisition: HL-T, IP; Investigation: TG, MY, NV, HL-T, IP; Methodology: HL-T, IP TG; Project Administration: HL-T, IP; Supervision: HL-T, IP; Validation: TG, MY, NV, HL-T, IP; Writing – Original Draft Preparation: TG, MY, IP; Writing - Review and Editing: TG, MY, HL-T, IP
Declaration of Generative Artificial Intelligence (AI) or Large Language Models (LLMs)
The author(s) did not use AI/LLM in any part of the research process and/or manuscript preparation.
accepted manuscript published online XXX; corrected proof published online XXX
Footnotes
Cite this article as: JID Innovations 2026.100461
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
HL-T, IP, MY, and TG have access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Individual participant data that underly the results reported in this article after deidentification will be shared upon reasonable request after signing a data-access agreement. Original sequences are available through Sequence Read Archive under accession number and BioProject PRJNA1055075. Sequencing data are publicly available at https://www.ncbi.nlm.nih.gov/sra/PRJNA1055075.









