Medical and Surgical Management of Hidradenitis Suppurativa

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

Thank you for your  very well-written and insightful review manuscript. The paper is well-structured, easy to follow, and provides a highly useful contribution to the field. I find the synthesis of data to be comprehensive and valuable.

More detailed comments:

1.The manuscript provides a comprehensive and up-to-date review of the current literature regarding Medical and Surgical Management of Hidradenitis Suppurativa, successfully synthesizing existing data to provide an organized clinical framework.

2. The topic is highly relevant and timely. It addresses a specific gap in the literature by consolidating recent clinical data into a single, high-level review, bridging the gap between clinical research and practical bedside application.

3. Compared to existing literature, this review offers a much-needed, updated synthesis of the latest evidence. It stands out by integrating recent guidelines and clinical trends into an exceptionally structured and clinically actionable overview.

4. As a review manuscript, the literature search and data synthesis strategies are already comprehensive, objective, and sound. The authors have done an excellent job, and no improvements are required.

5. The conclusions are entirely consistent with the evidence presented. The authors ground their final summary strictly in the reviewed data, directly answering the main objective of the paper and accurately highlighting areas for future research.

6.I think that  the references are highly appropriate, comprehensive, and up-to-date. The bibliography correctly includes all the landmark trials, diagnostic criteria, and international guidelines essential to this topic.

7. Even though table 1 is too busy, The tables are well-designed and serve as a major strength of the manuscript/ They summarize complex data efficiently, making it easy for the reader to grasp key points at a glance. 

Author Response

Thankyou for the supportive comments. As no suggestions were made for alterations- no changes are addressed in this reply.

 

 

Reviewer 2 Report

Comments and Suggestions for Authors

Dear authors,

thank you for your submission, please find my comments below

1-your introduction clearly articulates why “medicine versus surgery” is the wrong question for HS, but consider adding a short paragraph that explicitly defines what you mean by “inflammatory” versus “structural” disease in clinical terms (for example do you mean predominant nodules/abscesses vs established tunnels/scarred fields?), and how this maps onto common scoring systems such as IHS4, Hurley stage, and ultrasound findings. this would help readers translate the conceptual model into bedside phenotyping.

2-the methods are appropriately described as a structured narrative review rather than a registered systematic review, which is honest and appropriate given the heterogeneity of endpoints. that said, I would still add the date ranges searched, whether language restrictions were applied, and a brief statement on how you handled overlapping evidence (e.g., when multiple meta-analyses cover the same surgical cohorts).

3-I liked the evidence synthesis section summarizing the major biologic trials and the message that biologics improve inflammatory endpoints but cannot remove tunnels. 1 improvement i would sugges is to more explicitly teach readers what these effect sizes mean clinically by adding a short note on baseline disease severity in the pivotal trials and the proportion of “non-responders,” since HiSCR50 rates in the 48-54% range still imply a large unmet need and reinforces the rationale for combined pathways.

4-When you recommend phenotype-driven selection, what specific clinical or ultrasound criteria do you consider sufficient to label disease as “structural-dominant” and justify early surgery?

5-The surgical evidence summary you need clarify the heterogeneity in the definition of “recurrence,” which you flag later as a major limitation. since you mention recurrence estimates ranging from single-digit pooled recurrence after wide excision to much higher recurrence in long follow-up cohorts, it would be helpful to explicitly distinguish tunnel recurrence (true surgical failure) from inflammatory flares in adjacent/nearby tissue, and to recommend that future studies report these separately, your own text already gestures toward this distinction and it deserves to be elevated.

6-In your discussion of combined therapy add a practical peri-operative decision framework, basically showing which patients should continue biologics through surgery, what infection screening/optimization is needed, what wound-closure strategies may be more sensitive to delayed healing, and how to counsel patients about the trade-off suggested by cohort data (potentially lower recurrence signal but longer healing time). from a clinician's POV, this will probably matter the most.

7-In your discussion something important that's missing is talking about AI. As medicine increasingly moves toward AI-supported diagnosis, AI may help move HS towards a more individualized approach. In my hospital, I already see patients using image-recognizing large language models as informal adjuncts when evaluating their lesions, and recent studies have shown promising potential for such systems in dermatologic image interpretation (see PMID: 40668105 and PMID: 40064599). In the context of this review, this future direction is very important because HS is not a purely inflammatory disease or a purely surgical disease, but a mixed disorder in which nodules and abscesses coexist with tunnels, fibrosis, and scarring, requiring clinicians to decide when medical therapy, surgery, or combined treatment is most appropriate. In your future directions, write a sentence saying that image recognizing AI has shown strong diagnostic capabilities for diagnosis of skin conditions and references the two provided studies to support the statement. Then acknowledge that image-recognizing artificial intelligence could help clinicians flag visual patterns of inflammatory activity, fixed tunnel burden, scarring... that are difficult to standardize by routine examination alone, and that future multimodal systems could integrate clinical photographs and disease severity scores to better identify which patients are most likely to benefit from early biologic escalation, lesion-directed surgery.... 

8-since many clinicians use guidelines as “permission structures,” I would add a short sentence in the narrative emphasizing that the newest guidelines are less sequential and more parallel, and that procedural interventions (deroofing/local excision) are not “failure states” but appropriate early choices for recurrent fixed lesions even when systemic burden is mild.

9-the clinical recommendations section is clear I would just add one or two concrete “red flags” that should prompt early surgical referral (e.g., recurrent drainage from the same tract, ultrasound-confirmed tunnels, regionally destructive Hurley III fields) and one or two “red flags” that should prompt early systemic escalation (diffuse inflammatory burden, rapid relapse after antibiotics, major QOL impairment).

10-One additional limitation worth emphasizing is that much of the surgical literature is observational and likely confounded by referral patterns, surgical expertise, and varying definitions of disease extent and margin.

11-Just for my own info, for peri-operative biologics, do you recommend continuing only adalimumab based on HS-specific evidence?

Comments on the Quality of English Language

english is ok

Author Response

1-your introduction clearly articulates why “medicine versus surgery” is the wrong question for HS, but consider adding a short paragraph that explicitly defines what you mean by “inflammatory” versus “structural” disease in clinical terms (for example do you mean predominant nodules/abscesses vs established tunnels/scarred fields?), and how this maps onto common scoring systems such as IHS4, Hurley stage, and ultrasound findings. this would help readers translate the conceptual model into bedside phenotyping.

 

Thankyou- yes the reviewer is correct in assuming the inflammatory lesions pertain to nodules and abscesses whilst the structural lesions refer to draining tunnels. This has been amended in the manuscript.

2-the methods are appropriately described as a structured narrative review rather than a registered systematic review, which is honest and appropriate given the heterogeneity of endpoints. that said, I would still add the date ranges searched, whether language restrictions were applied, and a brief statement on how you handled overlapping evidence (e.g., when multiple meta-analyses cover the same surgical cohorts).

 

Thankyou this has been inserted into the methods which now read: “Any overlapping cohorts present in more than one meta analysis were included in only the larger of the overlapping analyses.” “No language restrictions or date restrictions were put in place for the search strategy.”

3-I liked the evidence synthesis section summarizing the major biologic trials and the message that biologics improve inflammatory endpoints but cannot remove tunnels. 1 improvement i would sugges is to more explicitly teach readers what these effect sizes mean clinically by adding a short note on baseline disease severity in the pivotal trials and the proportion of “non-responders,” since HiSCR50 rates in the 48-54% range still imply a large unmet need and reinforces the rationale for combined pathways.

Thankyou the following has been added: “Importantly, participants enrolled in the pivotal biologic trials generally had moderate-to-severe disease with substantial baseline inflammatory burden, including multiple abscesses and inflammatory nodules and frequent prior exposure to systemic therapies. Consequently, even the reported HiSCR50 rates of approximately 42–59% imply that 40–60% of patients remained classified as non-responders at primary endpoints, highlighting a persistent unmet need and supporting interest in multimodal strategies that combine inflammatory control with procedural management of structural disease.”

 

4-When you recommend phenotype-driven selection, what specific clinical or ultrasound criteria do you consider sufficient to label disease as “structural-dominant” and justify early surgery?

The following has been added to the discussion: “In practice, a structural-dominant phenotype is suggested by persistent draining tunnels, fixed fibrotic cords, extensive scarring, recurrent drainage arising from the same anatomical tract, ultrasound-confirmed subclinical tunnel networks, or regionally destructive Hurley III disease. In such patients, repeated escalation of anti-inflammatory therapy alone is unlikely to eliminate established tissue damage, and early referral for deroofing, local excision, or wide excision should be considered. Conversely, patients with predominantly inflammatory nodules and abscesses but limited tunnel burden may derive greater benefit from early systemic escalation.”

5-The surgical evidence summary you need clarify the heterogeneity in the definition of “recurrence,” which you flag later as a major limitation. since you mention recurrence estimates ranging from single-digit pooled recurrence after wide excision to much higher recurrence in long follow-up cohorts, it would be helpful to explicitly distinguish tunnel recurrence (true surgical failure) from inflammatory flares in adjacent/nearby tissue, and to recommend that future studies report these separately, your own text already gestures toward this distinction and it deserves to be elevated.

Thankyou the following has been added: ““More recent studies suggest this apparent heterogeneity largely reflects inconsistent definitions of recurrence. Many studies report any subsequent inflammatory activity within an operated region as recurrence, whereas others distinguish true tunnel recurrence (reflecting failure to eradicate structurally diseased tissue) from inflammatory nodules or abscesses arising adjacent to the original surgical field. This distinction is clinically important because tunnel recurrence may represent surgical failure, whereas inflammatory relapse may instead reflect ongoing systemic disease activity”

 

6-In your discussion of combined therapy add a practical peri-operative decision framework, basically showing which patients should continue biologics through surgery, what infection screening/optimization is needed, what wound-closure strategies may be more sensitive to delayed healing, and how to counsel patients about the trade-off suggested by cohort data (potentially lower recurrence signal but longer healing time). from a clinician's POV, this will probably matter the most.

 

 

The following discussion paragraph has been added: “A practical peri-operative approach includes assessment of active infection, smoking status, glycaemic control, nutritional status, obesity-related risk factors, and wound-healing capacity. Patients receiving effective biologic therapy for active inflammatory disease may often continue treatment through surgery, particularly when extensive interruption risks inflammatory rebound. Preoperative ultrasound can assist surgical planning and margin definition. Closure strategy should also be considered carefully because flap and graft reconstruction may have different recurrence and healing profiles than primary closure. Patients should be counselled that available cohort data suggest a potential trade-off between reduced inflammatory recurrence and prolonged wound-healing time when biologics are combined with surgery.”

7-In your discussion something important that's missing is talking about AI. As medicine increasingly moves toward AI-supported diagnosis, AI may help move HS towards a more individualized approach. In my hospital, I already see patients using image-recognizing large language models as informal adjuncts when evaluating their lesions, and recent studies have shown promising potential for such systems in dermatologic image interpretation (see PMID: 40668105 and PMID: 40064599). In the context of this review, this future direction is very important because HS is not a purely inflammatory disease or a purely surgical disease, but a mixed disorder in which nodules and abscesses coexist with tunnels, fibrosis, and scarring, requiring clinicians to decide when medical therapy, surgery, or combined treatment is most appropriate. In your future directions, write a sentence saying that image recognizing AI has shown strong diagnostic capabilities for diagnosis of skin conditions and references the two provided studies to support the statement. Then acknowledge that image-recognizing artificial intelligence could help clinicians flag visual patterns of inflammatory activity, fixed tunnel burden, scarring... that are difficult to standardize by routine examination alone, and that future multimodal systems could integrate clinical photographs and disease severity scores to better identify which patients are most likely to benefit from early biologic escalation, lesion-directed surgery.... 

8-since many clinicians use guidelines as “permission structures,” I would add a short sentence in the narrative emphasizing that the newest guidelines are less sequential and more parallel, and that procedural interventions (deroofing/local excision) are not “failure states” but appropriate early choices for recurrent fixed lesions even when systemic burden is mild.

The following has been added: “Importantly, modern guidelines increasingly view procedural interventions as complementary treatment modalities rather than as markers of therapeutic failure, supporting early deroofing or local excision for recurrent fixed lesions even when overall inflammatory burden remains relatively limited.”

 

9-the clinical recommendations section is clear I would just add one or two concrete “red flags” that should prompt early surgical referral (e.g., recurrent drainage from the same tract, ultrasound-confirmed tunnels, regionally destructive Hurley III fields) and one or two “red flags” that should prompt early systemic escalation (diffuse inflammatory burden, rapid relapse after antibiotics, major QOL impairment).

Thankyou- red flags have been added so the paragraphs now read: “For moderate-to-severe inflammatory HS without dominant fixed tunnel burden, early biologic-centred therapy is justified. The strongest direct RCT evidence still exists for adalimumab, but secukinumab and bimekizumab now provide robust phase 3 alternatives. Response should be re-evaluated at clinically relevant intervals, and biologic failure should trigger reconsideration of phenotype, adherence, comorbidity, and the presence of occult structural disease rather than simply prolonging ineffective monotherapy. [5,7,10,13,14] Red flags supporting early systemic escalation include diffuse inflammatory involvement across multiple anatomical regions, rapid relapse following antibiotic withdrawal, frequent inflammatory flares, and major quality-of-life impairment disproportionate to visible disease extent.

 

 

For persistent tunnels, fibrosis, and scarred regional disease, surgical referral should be early rather than deferred indefinitely. Deroofing or local excision is well suited to discrete recurrent tunnels or nodules. Wide excision remains the best-supported option for extensive localised Hurley III disease or long-standing anatomically destructive disease, especially where chronic structural change dominates the clinical picture. Reconstruction strategy should be planned, not improvised, because recurrence differs by wound closure method. [8,16-23] Practical red flags prompting early surgical referral include recurrent drainage from the same anatomical tract, ultrasound-confirmed tunnel networks, persistent fibrotic cords despite medical therapy, and regionally destructive Hurley III disease.”

 

10-One additional limitation worth emphasizing is that much of the surgical literature is observational and likely confounded by referral patterns, surgical expertise, and varying definitions of disease extent and margin.

 

Thankyou the following has been added:” In addition, much of the surgical literature remains observational and is susceptible to referral bias, centre-specific expertise effects, variation in operative technique, differences in disease extent at baseline, and inconsistent definitions of surgical margins. These factors complicate direct comparison between studies and may contribute substantially to variability in reported recurrence rates.”

11-Just for my own info, for peri-operative biologics, do you recommend continuing only adalimumab based on HS-specific evidence?

At present Adalimumab has the clearest HS Specific peri-operative evidence base.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Revisions are appropriate, I have no further comments

Comments on the Quality of English Language

english is ok

Author Response

Revisions are appropriate, I have no further comments:

 

Thankyou