Introduction and Context
Hidradenitis suppurativa (HS) is a chronic, painful inflammatory disease of the hair-bearing, intertriginous skin. Clinical trials in HS depend fundamentally on accurate lesion identification and counting by investigators: endpoint definitions such as the Hidradenitis Suppurativa Clinical Response (HiSCR) and severity scores like the International Hidradenitis Suppurativa Severity Score System (IHS4) use lesion counts as part of responder definitions and disease staging. Inconsistent interpretation of what constitutes an inflammatory nodule vs an abscess, a draining tunnel vs a scar, or how to count lesions that have multiple openings can introduce measurement error, reduce interrater reliability, and undermine trial conclusions.
In response to these challenges, Garg et al. convened an international expert and rater group and performed a modified Delphi consensus exercise to produce standardized morphological definitions and guidance statements for HS lesion assessment intended for use in clinical trials (Garg A et al., JAMA Dermatol. 2025). This article summarizes their methods, main recommendations, areas of strong consensus and persistent disagreement, and practical implications for clinicians, trialists and regulators.
Why this consensus was needed now
– Clinical gaps: Prior trials and routine clinical practice showed variability in lesion identification and counting, especially for complex lesions such as tunnels (sinus tracts), tunneled plaques with multiple openings, or healed but scarred areas. That variability contributes to inconsistent endpoint measurement across studies.
– Newer therapies and tighter trial endpoints: As targeted biologic and small-molecule therapies proliferate, trials increasingly require precise lesion-based endpoints and consistent rater training to detect modest but clinically meaningful treatment effects.
– Preparedness for multicenter global trials: Standardized definitions facilitate cross-site consistency, regulatory confidence, and meta-analyses.
Methods in brief
– Participants: An international cohort of health professionals (primarily dermatologists experienced in HS measurement) plus novice raters participated.
– Process: A preliminary questionnaire with image-based lesion assessments and qualitative feedback informed the draft definitions and guidance. Two rounds of electronic Delphi surveys followed; a virtual group discussion after round 1 helped clarify contentious points before round 2.
– Consensus threshold: Definitions or guidance statements reaching ≥70% agreement were considered to have achieved consensus.
New Guideline Highlights
– Scope: The exercise provided morphologic definitions for 11 lesion types commonly encountered in HS and 18 practical guidance statements to standardize assessment practices in clinical trials.
– High agreement: All 11 lesion definitions reached the prespecified consensus threshold; 9 of the 11 exceeded 90% agreement. Sixteen of 18 guidance statements met consensus, with 13 supported by >80% of participants.
– Remaining controversies: Two guidance statements failed to reach consensus—assessment of tunneled plaques with multiple openings, and assessment of scalp lesions—highlighting areas needing further study or tailored protocols.
Consensus outputs — What investigators should use
Below are the key takeaways distilled for use in trial protocols and rater training programs. (The original paper provides detailed wording and photo examples; trialists should incorporate those materials into training.)
1) Standardized lesion types (consensus definitions achieved for 11 lesions):
– Inflammatory nodule: a firm, tender, dome-shaped lesion in the dermis or subcutis without a clearly fluctuant center or overt purulent drainage. Count as inflammatory lesion when active.
– Abscess: a fluctuant, painful collection with central softening or expressed purulent drainage; typically larger than nodules and may require incision/drainage in clinical care.
– Inflammatory papule: small, raised, erythematous lesion without fluctuation or purulence.
– Pustule: raised lesion with visible purulent material localized to the surface.
– Comedo/open comedo: a follicular plug, often blackhead-like, without overt inflammation (differentiated from inflammatory lesions).
– Plaque: a well-demarcated, raised, flat-topped lesion — inflammatory plaques characterized by tenderness/induration and active inflammation; distinguishing from chronic noninflammatory scar is critical.
– Tunnel/sinus tract (draining tunnel): a subcutaneous tract that may have visible external openings with active drainage or that can be probed clinically.
– Scar/fibrotic band: noninflamed, flattened, hypopigmented/atrophic tissue or thick fibrotic bands consistent with healed disease activity rather than active inflammation.
– Hypertrophic scar/keloid: raised fibrotic scar tissue distinct from active inflammatory lesions.
– Cyst: encapsulated structure, may be inflamed, typically well circumscribed.
– Draining opening: an external ostium with visible drainage; guidance emphasizes distinguishing a single draining opening associated with a tunnel vs multiple separate openings.
2) Key practical guidance statements (16/18 reached consensus):
– Count lesions based on morphology and activity, not on presumed pathogenesis. For example, count a tender, fluctuant lesion as an abscess irrespective of how it formed.
– Define and count a single tunnel/sinus tract as one lesion even if it has multiple adjacent openings, except where a tunneled plaque with many separate openings is present (no consensus here — see below).
– Count only active inflammatory lesions (e.g., nodules, abscesses, draining tunnels) for endpoints like HiSCR; chronic scars and noninflammatory comedones should not be counted as active inflammatory lesions.
– Use standardized palpation and clinical maneuvers to assess fluctuation, induration, and tenderness; palpation should be part of on-site rater training.
– Document lesion counts with standardized photography and annotation whenever possible to enable remote review and adjudication.
– When in doubt, default to conservative counting rules specified in the protocol and trigger central adjudication.
– Provide novice raters with photo atlases, hands-on exercises, and periodic calibration sessions to maintain reliability over a trial’s duration.
– Explicitly instruct raters how to handle lesions in anatomically challenging areas (e.g., groin, axilla), including how to identify multiple distinct lesions vs extensions of a single lesion.
3) Areas without consensus:
– Tunneled plaques with multiple openings: the group did not reach agreement on whether to count such a lesion as a single lesion (the tunneled plaque) or as multiple distinct lesions (one per opening). Because treatment effect signals and endpoint definitions may be sensitive to counting rules here, the authors recommend that protocols prespecify a counting convention and use central adjudication for ambiguous cases.
– Scalp lesions: lack of agreement likely reflects low prevalence and limited clinical familiarity among raters; trials including scalp disease should build in explicit instructions and training examples.
Updated Recommendations and What Changed
This consensus differs from prior practice in three important ways:
– Greater specificity: prior trial protocols often used broad and variably interpreted terms (e.g., “abscess” or “nodule”) without uniform morphological criteria. The consensus delivers precise, image-supported definitions to reduce ambiguity.
– Explicit counting rules: the guidance clarifies which lesions are to be counted for inflammatory endpoints and provides principles for grouping lesions (e.g., tunnels) that prior studies left vague.
– Focus on rater training and calibration: while previous guidelines recommended training, the consensus emphasizes structured, image-based calibration, documented photography and centralized adjudication options to preserve data quality.
Topic-by-Topic Recommendations
– Diagnostic criteria and lesion identification: Use the morphological definitions above. Distinguish active inflammatory lesions (counted for endpoints) from chronic scars and noninflammatory features (not counted).
– Grading/staging: Routine staging systems (Hurley stage; IHS4 scoring) remain relevant. This consensus does not replace staging systems but provides standardized inputs (lesion counts) that feed those systems.
– Treatment strategies in trials: Not a treatment guideline per se; however, accurate lesion counting supports fair assessment of efficacy for systemic therapies (e.g., biologics) and should be part of protocols that define rescue treatments or criteria for treatment discontinuation.
– Follow-up and monitoring: Raters should use the same standardized definitions at each visit; photographic documentation is encouraged at baseline and key assessment time points.
– Special populations: For scalp disease, children, or unusual anatomic distributions, protocols must include tailored training and clear counting rules because the Delphi exercise did not fully resolve those scenarios.
Expert Commentary, Consensus Strengths and Controversies
– Strengths: The modified Delphi process drew on both experienced and novice raters, used real clinical images with qualitative feedback, and included a virtual group discussion to deepen shared understanding. High response rates across rounds strengthen the validity of the consensus.
– Expert viewpoints: Panelists emphasized that small definitional differences can materially affect responder rates in trials, especially when baseline lesion counts are low. Many experts stressed that a single, consistently applied rule—documented in the protocol and enforced through training—is more valuable than attempting to resolve every clinical nuance globally.
– Controversies and research needs: The lack of consensus on tunneled plaques with multiple openings underlines a research need: empirical evaluation of how alternative counting rules affect trial endpoints, sample size, and clinical interpretation. Scalp lesions, relatively rare in many cohorts, also require specific study and photo references.
Practical Implications for Clinical Trials and Practice
– For trial designers: Adopt the consensus definitions in protocols, include the full photo atlas and verbatim guidance statements for raters, and prespecify handling of ambiguous scenarios (e.g., tunneled plaques) and adjudication procedures.
– For site investigators and raters: Implement structured rater training, calibration exercises, and use photography to reduce drift over time.
– For regulators and sponsors: The availability of consensus-based, widely endorsed definitions should increase confidence in lesion-based endpoints and make cross-trial comparisons more meaningful.
– For clinicians: Although the guidance was created for trials, many elements (clear lesion definitions, use of photography and structured assessments) can improve routine care documentation and longitudinal disease tracking.
Patient vignette: Applying the guidance
Maria, a 32-year-old woman with Hurley stage II HS, presents for a baseline trial visit. On exam: two tender, nonfluctuant nodules in the left axilla, one fluctuant painful lesion in the right groin (abscess), a tunneled area on the left perineum with three small external openings and intermittent drainage, and multiple atrophic scars on the lower abdomen. Using the consensus guidance: count 2 inflammatory nodules + 1 abscess + 1 tunnel (the tunneled area is counted as one tunnel lesion per the trial’s prespecified rule) = 4 active inflammatory lesions. Scars and noninflamed comedones are not counted. Photos and annotated lesion maps are taken for central review.
Conclusions
The modified Delphi consensus led by Garg et al. provides practical, high-agreement morphological definitions and guidance to standardize HS lesion assessment in clinical trials. By reducing ambiguity in lesion identification and counting, these recommendations can improve interrater reliability, data quality, and the interpretability of efficacy signals for new and existing therapies. Remaining areas of disagreement—most notably tunneled plaques with multiple openings and scalp lesions—should be prioritized for empirical study and protocol-specified handling in future trials.
References
1. Garg A, Strunk A, Midgette B, et al. Standardization of Lesion Classification and Assessment by Investigators in Clinical Trials for Hidradenitis Suppurativa: A Consensus Exercise Using a Modified Delphi Approach. JAMA Dermatol. 2025 Nov 26. doi:10.1001/jamadermatol.2025.4652. Epub ahead of print. PMID: 41296358.
2. Kimball AB, Okun MM, Williams DA, et al. Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa. N Engl J Med. 2016;375(5):422–434.
3. Zouboulis CC, Desai N, Emtestam L, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol. 2015;29(4):619–644.
(Note: Trialists and clinicians implementing these recommendations should consult the full Garg et al. JAMA Dermatology 2025 paper for precise wording, photographic atlases and the full set of guidance statements recommended for inclusion in protocols and rater training.)
