Global consensus process to establish a core dataset for hidradenitis suppurativa registries.

BACKGROUND: Several registries for hidradenitis suppurativa (HS) already exist in Europe and the USA. There is currently no global consensus on a core dataset (CDS) for these registries. Creating a global HS registry is challenging, owing to logistical and regulatory constraints, which could limit opportunities for global collaboration as a result of differences in the dataset collected. The solution is to encourage all HS registries to collect the same CDS of information, allowing registries to collaborate. OBJECTIVES: To establish a core set of items to be collected by all HS registries globally. The core set will cover demographic details, comorbidities, clinical examination findings, patient-reported outcome measures and treatments. METHODS: Beginning in September 2022, 20 participants - including both clinicians with expertise in HS and patient advocates - from eight countries across three continents participated in a Delphi process consisting of four rounds of voting, with all participants completing each round. A list of potential items for inclusion in the core set was generated from the relevant published literature, including systematic reviews of comorbidities in HS, clinical and examination findings, and epidemiology. For disease severity and progression items, the Hidradenitis SuppuraTiva Core outcome set International Collaboration (HiSTORIC) core set and other relevant instruments were considered for inclusion. This resulted in 47 initial items. Participants were invited to suggest additional items to include during the first round. Anonymous feedback was provided to inform each subsequent round of voting to encourage consensus. RESULTS: The eDelphi process established a CDS of 48 items recommended for inclusion in all HS registries globally. CONCLUSIONS: The routine adoption of this CDS in current and future HS registries should allow registries in different parts of the world to collaborate, enabling research requiring large numbers of participants.

Outcome Measures for the Evaluation of Treatment Response in Hidradenitis Suppurativa for Clinical Practice: A HiSTORIC Consensus Statement.

Importance: Although several clinician- and patient-reported outcome measures have been developed for trials in hidradenitis suppurativa (HS), there is currently no consensus on which measures are best suited for use in clinical practice. Identifying validated and feasible measures applicable to the practice setting has the potential to optimize treatment strategies and generate generalizable evidence that may inform treatment guidelines. Objective: To establish consensus on a core set of clinician- and patient-reported outcome measures recommended for use in clinical practice and to establish the appropriate interval within which these measures should be applied. Evidence Review: Clinician- and patient-reported HS measures and studies describing their psychometric properties were identified through literature reviews. Identified measures comprised an item reduction survey and subsequent electronic Delphi (e-Delphi) consensus rounds. In each consensus round, a summary of outcome measure components and scoring methods was provided to participants. Experts were provided with feasibility characteristics of clinician measures to aid selection. Consensus was achieved if at least 67% of respondents agreed with use of a measure in clinical practice. Findings: Among HS experts, response rates for item reduction, e-Delphi round 1, and e-Delphi round 2 surveys were 76.4% (42 of 55), 90.5% (38 of 42), and 92.9% (39 of 42), respectively; among patient research partners (PRPs), response rates were 70.8% (17 of 24), 100% (17 of 17), and 82.4% (14 of 17), respectively. The majority of experts across rounds were practicing dermatologists with 18 to 19 years of clinical experience. In the final e-Delphi round, most PRPs were female (12 [85.7%] vs 2 males [11.8%]) and aged 30 to 49 years. In the final e-Delphi round, HS experts and PRPs agreed with the use of the HS Investigator Global Assessment (28 [71.8%]) and HS Quality of Life score (13 [92.9%]), respectively. The most expert-preferred assessment interval in which to apply these measures was 3 months (27 [69.2%]). Conclusions and Relevance: An international group of HS experts and PRPs achieved consensus on a core set of HS measures suitable for use in clinical practice. Consistent use of these measures may lead to more accurate assessments of HS disease activity and life outcomes, facilitating shared treatment decision-making in the practice setting.

Credibility of clinical research depends on consensus on outcomes.

In clinical studies, beneficial and harmful effects of interventions are investigated by measuring predefined outcomes. The uncontrolled choice of these outcomes carries a risk of outcome reporting bias, large heterogeneity of outcomes with reduced options for evidence synthesis. Furthermore, such outcomes may not be important for stakeholders including patients. A potential solution to these problems is to develop a core outcome set (COS) - a list of outcomes which have been estimated to be important to include in all future studies in a given setting by all relevant stakeholders. This review summarises the benefits of defining a COS.

Attempted treatment of primary axillary hyperhidrosis with one session of either Neodymium YAG laser or Intense Pulsed Light: A within patient randomized trial of treated versus untreated contralateral axilla.

BACKGROUND: Primary axillary hyperhidrosis (PAH) affects 1-5% of the world's population who has an unmet need for improved treatments. The heating of sweat glands with specific microwave therapy has shown promising results, yet, treatment with widely available devices such as long-pulsed Neodymium Yttrium Aluminum Garnet (Nd:YAG) lasers, diode lasers or Intense Pulsed Light (IPL) may serve as pragmatic alternatives. OBJECTIVES: To compare sweat secretion of treated versus untreated contralateral control axilla 1-3 months after one session of Nd:YAG laser or IPL in patients with PAH. METHODS: A within-person randomized controlled trial. Patients were randomized to receive either one session of Nd:YAG laser or IPL in one axilla with the contra-lateral serving as control. Sweat production was assessed by gravimetry, trans-epidermal water loss, hyperhidrosis disease severity scale and dynamic optical coherence tomography. Mixed-effects models were used to handle the within-person design, containing both fixed effect factors (side, group, and subgroup), and random effects (patients), while also adjusting for the level at baseline. RESULTS: A total of 20 patients were enrolled. At follow-up 1-3 months after treatment, sweat secretion was not affected in the treated axilla when compared to the control axillae (0.01 [95%CI: -0.04 to 0.05]; p = 0.68). In the Nd:YAG subgroup (10 patients), least squares means for sweat secretion was 0.18 mg/5 min in the treated versus 0.15 mg/5 min in the control axilla, respectively, corresponding to a statistically insignificant mean difference of 0.02 mg/5 min (95% CI: -0.06 to 0.11; p = 0.54). In the IPL subgroup (10 patients), sweat secretion was 0.06 mg/5 min in the treated axilla versus 0.07 mg/5 min in the control axilla with a statistically insignificant difference of -0.01 points (95% CI: -0.03 to 0.02; p = 0.46). Likewise, none of the secondary outcomes were significantly affected by treatment. However, both treatments appeared safe and well tolerated with no adverse effects reported at follow-up. CONCLUSIONS: One treatment with external 1064 nm Nd:YAG laser or 640 nm IPL at commercially available settings, failed to demonstrate clinical benefit in treating PAH, with narrow confidence intervals implying that this was not due to a type-2 error.

Validation of the Hidradenitis Suppurativa Investigator Global Assessment: A Novel Hidradenitis Suppurativa-Specific Investigator Global Assessment for Use in Interventional Trials.

Importance: Few simplified instruments exist for use in hidradenitis suppurativa (HS) trials. Objective: To assess psychometric properties of the Hidradenitis Suppurativa Investigator Global Assessment (HS-IGA) score using a clinical trial data set. Design, Setting, and Participants: This retrospective analysis of a phase 2 randomized double-blind, placebo-controlled, active-reference arm trial (UCB HS0001) included adults with moderate-to-severe HS. Exposures: Trial participants were randomized at baseline to receive bimekizumab, adalimumab, or placebo. Main Outcomes and Measures: The HS-IGA score at prespecified time points up to 12 weeks after randomization. Results: The HS-IGA score showed strong convergent validity with IHS4 and HS-PhGA scores at baseline (Spearman correlation, 0.86 [P < .001] and 0.74 [P < .001], respectively) and at week 12 (Spearman correlation, 0.73 [P < .001] and 0.64 [P < .001], respectively). The HS-IGA scores assessed during predosing visits at screening and baseline showed good test-retest reliability (intraclass correlation coefficient [ICC] = 0.92). At week 12, HS-IGA responders were significantly associated with HiSCR-(50/75/90) responders (χ2 = 18.45; P < .001; χ2 = 18.11; P < .001; and χ2 = 20.83; P < .001, respectively). The HS-IGA score was predictive of HiSCR-50/75/90 and HS-PhGA response at week 12 (AUC, 0.69, 0.73, 0.85, and 0.71, respectively). However, the HS-IGA as a measure of disease activity showed low predictive validity with patient-reported outcomes at week 12. Conclusions and Relevance: The HS-IGA score demonstrated good psychometric properties compared with existing measures and may be considered for use as an end point in clinical trials for HS.

Wound drainage measurements: a narrative review.

Drainage from chronic wounds can significantly negatively impact a patient's quality of life. Change in severity of wound drainage is an important measure of treatment efficacy for wounds. This study reviews existing tools used to assess wound drainage. Qualitative drainage tools are overall less burdensome, and however, differences in user interpretation may reduce inter-rater reliability. Quantitative drainage tools enable more reliable comparisons of drainage severity and treatment response between patients but sometimes require equipment to administer, increasing responder burden. Gaps in the current wound drainage measurement landscape are highlighted. Many of the existing scales have not been validated in robust studies. There is also a lack of validated global drainage measurement tools for patients with chronic inflammatory skin disorders with drainage, such as hidradenitis suppurativa or pyoderma gangrenosum. Development of a succinct drainage measurement tool for inflammatory skin diseases where drainage is a prominent symptom will improve monitoring of meaningful treatment response.

Factors associated with treatment satisfaction in patients with hidradenitis suppurativa: results from the Global VOICE project.

BACKGROUND: Nearly half of patients with hidradenitis suppurativa (HS) report dissatisfaction with their treatment. However, factors related to treatment satisfaction have not been explored. OBJECTIVES: To measure associations between treatment satisfaction and clinical and treatment-related characteristics among patients with HS. METHODS: Treatment satisfaction was evaluated utilizing data from a cross-sectional global survey of patients with HS recruited from 27 institutions, mainly HS referral centres, in 14 different countries from October 2017 to July 2018. The primary outcome was patients' self-reported overall satisfaction with their current treatments for HS, rated on a five-point scale from 'very dissatisfied' to 'very satisfied'. RESULTS: The final analysis cohort comprised 1418 patients with HS, most of whom were European (55%, 780 of 1418) or North American (38%, 542 of 1418), and female (85%, 1210 of 1418). Overall, 45% (640 of 1418) of participants were either dissatisfied or very dissatisfied with their current medical treatment. In adjusted analysis, patients primarily treated by a dermatologist for HS had 1·99 [95% confidence interval (CI) 1·62-2·44, P < 0·001] times the odds of being satisfied with current treatment than participants not primarily treated by a dermatologist. Treatment with biologics was associated with higher satisfaction [odds ratio (OR) 2·36, 95% CI 1·74-3·19, P < 0·001] relative to treatment with nonbiologic systemic medications. Factors associated with lower treatment satisfaction included smoking (OR 0·78, 95% CI 0·62-0·99; active vs. never), depression (OR 0·69, 95% CI 0·54-0·87), increasing number of comorbidities (OR 0·88 per comorbidity, 95% CI 0·81-0·96) and increasing flare frequency. CONCLUSIONS: There are several factors that appear to positively influence satisfaction with treatment among patients with HS, including treatment by a dermatologist and treatment with a biologic medication. Factors that appear to lower treatment satisfaction include active smoking, depression, accumulation of comorbid conditions and increasing flare frequency. Awareness of these factors may support partnered decision making with the goal of improving treatment outcomes. What is already known about this topic? Nearly half of patients with hidradenitis suppurativa report dissatisfaction with their treatments. What does this study add? Satisfaction with treatment is increased by receiving care from a dermatologist and treatment with biologics. Satisfaction with treatment is decreased by tobacco smoking, accumulation of comorbid conditions including depression, and higher flare frequency. What are the clinical implications of this work? Awareness of the identified factors associated with poor treatment satisfaction may support partnered decision making and improve treatment outcomes.

Development and initial validation of the HS-IGA: a novel hidradenitis suppurativa-specific investigator global assessment for use in interventional trials.

BACKGROUND: Few validated instruments exist for use in hidradenitis suppurativa (HS) trials. OBJECTIVES: To develop a novel HS Investigator Global Assessment (HS-IGA) and to validate its psychometric properties. METHODS: Development of HS-IGA involved discussion among stakeholders, including patients, within HISTORIC. Data from replicate phase III randomized controlled trials evaluating HS treatment were utilized. Multivariate models identified lesion type and body region as variables of importance. Classification and regression trees for ordinal responses were built. Validation included assessment of test-retest reliability, predictive validity, responsiveness and clinical meaningfulness. RESULTS: There were 3024 unique measurements available in PIONEER I. Mean and median lesion counts by region were largely <10 and were highest in axillary and inguinal regions. The mean and median number of regions involved were ≤ 3 for individual lesions and combinations. Regardless of lesion type, axillary and inguinal regions most influenced the HS-IGA score. Accordingly, regions were combined into a six-point IGA based on the maximum lesion number in either upper or lower body regions with a score of 0 (0-1 lesions), 1 (2-5), 2 (6-10), 3 (11-15), 4 (16-20) and 5 (≥ 20 lesions). The intraclass correlation coefficient for test-retest reliability was 0·91 (95% confidence interval 0·87-0·94). Spearman's rank order correlations (SROCs) with HS-PGA and Hidradenitis Suppurativa Clinical Response (HiSCR) were 0·73 and 0·51, respectively (P < 0·001 for both comparisons). SROCs with Dermatology Life Quality Index (DLQI), pain numerical rating scale and HS-QoL were 0·42, 0·34 and -0·25, respectively (P < 0·001 for all comparisons). HS-IGA was responsive at weeks 12 and 36. Predictive convergent validity was very good with HS-PGA (area under the curve = 0·89) and with HiSCR (area under the curve = 0·82). Predictive divergent validity was low with DLQI and HS-QoL. CONCLUSIONS: HS-IGA has moderate-to-strong psychometric properties and is simple to calculate.

Sub-classification of Hidradenitis suppurativa: a cross-sectional study.

The typical Hidradenitis Suppurativa (HS) patient is a young woman with axillary and groin involvement, but the spectrum of the disease presentation is broad and no internationally acknowledged sub-classification of the disease exists to date. It is however speculated that different, yet unidentified, subtypes may respond differently to different treatments or carry a different prognosis. Classification according to self-reported clinically meaningful outcomes for patients offer practical advantages. Our objective was to build an empirical framework for sub-classification of HS patients based on the frequency of HS flares in various anatomic locations, using a cross-sectional questionnaire-based design. All patients with a clinically confirmed diagnosis of HS registered at our department until March 1, 2017 were invited to participate. The frequency of HS flares in various anatomic locations was used for identification of possible HS subtypes using Principal Component Analysis (PCA) and cluster analysis. A total of 524 (62%) of 845 invited patients answered the questionnaire; 402 (76.7%) were female. From the cluster analysis, we identified two possible subtypes of HS, labeled the "upper type" and the "lower type". The "upper type" was characterized by repeated outbreaks in axillary and mammary regions. Meanwhile, the "lower type" was characterized by outbreaks in the inguinal, genital, perianal, and gluteal regions. Our findings support the notion that HS can be sub-classified and imply that the pattern of where lesions are located may be an important element in future HS sub-classification systems.

How to diagnose and measure primary hyperhidrosis: a systematic review of the literature.

PURPOSE: Hyperhidrosis (i.e. excessive sweating) is diagnosed from patient medical history and physical examination. In addition, focal sweat measurements can substantiate the hyperhidrosis diagnosis. Likewise, the impact of living with hyperhidrosis can be assessed with patient-reported outcome measures. However, no consensus exists on how to diagnose hyperhidrosis, how to quantify the disease, or how to measure the impact hyperhidrosis has on patients. Therefore, the objective of this review was to summarize the literature on diagnostic criteria, focal sweat measurement methods, and patient-reported outcome measures of hyperhidrosis. METHODS: A literature search of Cochrane Library, Embase, and PubMed was conducted. Studies that included and aimed at developing or validating hyperhidrosis diagnostic criteria, focal sweat measurement methods, or patient-reported outcome measures for individuals with hyperhidrosis were eligible for inclusion. The methodological quality of diagnostic accuracy studies about focal sweat measurement methods was determined using the Quality Assessment of Diagnostic Accuracy Studies-2. RESULTS: Overall, 33 studies were included. We identified two sets of hyperhidrosis diagnostic criteria, one scale for assessment of severity of hyperhidrosis sweating, four focal sweat measurement methods, and 15 patient-reported outcome measures. CONCLUSION: The algorithm for diagnosing hyperhidrosis and focal sweat measurement methods needs validation in large cohorts. Most patient-reported outcome measures for hyperhidrosis are not adequately validated. A potential solution is to develop a core outcome set that can standardize outcomes reported in clinical trials.

[Intense pulsed light treatment for hidradenitis suppurativa: a within-person randomized controlled trial]. / Intense pulsed light treatment for hidradenitis suppurativa: a within-person randomized controlled trial.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the intertriginous areas. HS affects hair follicles causing perifollicular inflammation, resulting in the formation of nodules and painful abscesses. Intense pulsed light (IPL) uses selective photothermolysis to destroy the hair follicles. OBJECTIVES: To evaluate the effect of IPL hair removal as treatment for mild-to-moderate HS. MATERIALS & METHODS: We conducted a single-blinded, clinical randomized trial with patients with Hurley Stage I-II. Patients with symmetrical disease were randomized to monthly unilateral treatment of the axilla or groin. The contralateral side served as internal control. Concomitant treatment modalities for HS were not permitted throughout the study. Efficacy was assessed using Hidradenitis Suppurativa Clinical Response (HiSCR), modified Sartorius score (MSS) and patient-reported outcomes. RESULTS: A total of 17 patients completed the trial and were included in the analysis. HiSCR was not evaluated in patients without abscesses or inflammatory nodules pre-treatment. HiSCR was insignificantly different between the intervention side (8/12) and control side (4/10), P=0.467. There was, however, a significant reduction in regional MSS on the intervention side with a median score decreasing from 8.5 (IQR: 6.3-13.5) to 4.5 (IQR 1.8-8.0) post-treatment, P=0.006, and an insignificant score reduction in the control side from 6.0 (IQR: 4.5-8.3) to 5.0 (IQR: 2.5-9.0), post-treatment P=0.492. CONCLUSION: IPL hair removal resulted in a significant reduction on MSS on the treated area with no significant reduction on the control side. Our study suggests that IPL may be an effective treatment for mild-to-moderate HS.

Proposed Definitions of Typical Lesions in Hidradenitis Suppurativa.

BACKGROUND: Although not rare, hidradenitis suppurativa (HS) is often under-recognized by physicians. The diagnosis of HS is clinical via the recognition of lesions typical of the disease, but universally accepted definitions of these latter are currently lacking, which means that certain severity scores employed for HS classification/management are used differently by different physicians. Our aim was to develop a set of descriptive definitions and associated images of HS lesions, in order to enable doctors to better recognize and evaluate the disease. METHODS: MEDLINE-available literature and dermatological textbooks on HS morphology were retrieved (January 1996 to February 2016). A preliminary set of definitions of HS typical lesions was created, including 10 terms. Each term was associated with a pathophysiological classification and an image. This preliminary set was shown during the 5th Conference of the European HS Foundation (EHSF). The physicians attending the event were invited to vote on each term and make comments via a voting sheet. RESULTS: A total of 81 physicians answered the questionnaire. Their agreement/disagreement rates and comments were used to obtain a revised set of definitions and images. Pathophysiological classifications were dropped. CONCLUSION: A user-friendly set of definitions/images of HS typical lesions was proposed and will need to be validated by further studies. This set could ultimately serve as a tool to better recognize, score, and assess treatment efficacy.

Evaluating patients' unmet needs in hidradenitis suppurativa: Results from the Global Survey Of Impact and Healthcare Needs (VOICE) Project.

BACKGROUND: A needs assessment for patients with hidradenitis suppurativa (HS) will support advancements in multidisciplinary care, treatment, research, advocacy, and philanthropy. OBJECTIVE: To evaluate unmet needs from the perspective of HS patients. METHODS: Prospective multinational survey of patients between October 2017 and July 2018. RESULTS: Before receiving a formal HS diagnosis, 63.7% (n = 827) of patients visited a physician ≥5 times. Mean delay in diagnosis was 10.2 ± 8.9 years. Patients experienced flare daily, weekly, or monthly in 23.0%, 29.8%, and 31.1%, respectively. Most (61.4% [n = 798]) rated recent HS-related pain as moderate or higher, and 4.5% described recent pain to be the worst possible. Access to dermatology was rated as difficult by 37.0% (n = 481). Patients reported visiting the emergency department and hospital ≥5 times for symptoms in 18.3% and 12.5%, respectively. An extreme impact on life was reported by 43.3% (n = 563), and 14.5% were disabled due to disease. Patients reported a high frequency of comorbidities, most commonly mood disorders. Patients were dissatisfied with medical or procedural treatments in 45.9% and 34.6%, respectively. LIMITATIONS: Data were self-reported. Patients with more severe disease may have been selected. CONCLUSION: HS patients have identified several critical unmet needs that will require stakeholder collaboration to meaningfully address.

Development of HiSQOL: A Hidradenitis Suppurativa-Specific Quality of Life Instrument.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic and painful skin disease. In addition, HS lesions may be associated with pus and odour, potentially leading to significant stigma and, consequently, greatly affected quality of life (QOL). QOL is a multidimensional construct, which can be measured in various ways. However, generic or dermatologic QOL measures may not capture changes in QOL particularly affected in HS. Accordingly, patients and experts included in the HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) agreed that future clinical HS trials should measure HS-specific QOL. OBJECTIVES: To develop an HS-specific QOL instrument (HiSQOL, Hidradenitis Suppurativa Quality of life). METHOD: The initial phases of the questionnaire development, described in this study, included item generation by patient interviews, development of a pilot questionnaire, questionnaire refinement, and pilot testing. RESULTS: For item generation, 21 patients were interviewed individually or in focus groups. Analysis of the interviews identified 105 candidate items and, next, a pilot questionnaire was developed. Finally, item reduction and two rounds of pilot testing resulted in a 23-item questionnaire representing physical, psychological, and social QOL dimensions. CONCLUSIONS: We have comprehensively explored on HS's possible effect on the QOL of the affected individuals and identified a 23-item HS-specific QOL questionnaire. The questionnaire proved to be feasible, acceptable, and comprehensible in the second round of pilot testing. With HiSQOL, researchers can measure HS-specific QOL in future clinical trials, potentially enabling them to discover more effective treatment options. It is envisaged, that after thorough validation in a trial setting, a streamlined version of HISQOL may also become available for clinical use in daily practice.

Increased Suicide Risk in Patients with Hidradenitis Suppurativa.

Patients with skin disorders are considered at a higher risk of depression and anxiety than the background population. Patients with hidradenitis suppurativa (HS) may be particularly affected. We explored the association between HS and depression, anxiety, and completed suicides in the Danish national registries, expanding to include data on suicidal behavior, using both a cross-sectional and a cohort study design. Both designs included 7,732 patients with HS and a background population of 4,354,137. The cohort study revealed that HS patients had an increased risk of completed suicide after adjustment for confounding factors (11 per 7,732 vs. 2,904 per 4,354,137) (hazard ratio [95% confidence interval] = 2.42 [1.07-5.45]; P = 0.0334) and an increased risk of antidepressant drug use (1.30 [1.17-1.45]; P < 0.0001). In contrast to previous studies, the cross-sectional baseline data revealed nonsignificant association with depression (odds ratio [95% confidence interval] = 1.13; 0.87-1.47]; P = 0.36 and hospitalization due to depression (1.32 [0.94-1.85]; P = 0.1083). To the best of our knowledge, no previous studies have reported on the increased risk of completed suicide among HS patients. The increased risk of completed suicide is not solely explained by lifestyle and demographic differences and the results highlight the profound impact HS has on the lives of patients with this often devastating disease.