John Frew
The University of New South Wales, Dermatology, Graduate Student
- Dermatologist and Dermatological Researcheredit
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SUMMARY Background Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient’s treatment journey leading to biologic therapy is... more
SUMMARY Background Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient’s treatment journey leading to biologic therapy is unclear. Objectives To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy. Methods We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients’ treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variab...
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Hidradenitis suppurativa is a complex inflammatory skin disease with the molecular pathogenesis of disease incompletely understood. Recent observational and experimental insights into disease pathogenesis are challenging long‐held beliefs... more
Hidradenitis suppurativa is a complex inflammatory skin disease with the molecular pathogenesis of disease incompletely understood. Recent observational and experimental insights into disease pathogenesis are challenging long‐held beliefs regarding the causes and mechanisms of disease. The most effective treatments to date are anti‐inflammatory in nature suggesting inflammation is the major driver of disease activity. This study critically evaluates the existing literature regarding the mechanisms of disease pathogenesis. Specifically, it questions the role of follicular occlusion as the central driver of disease activity and reframes hidradenitis suppurativa as a complex autoinflammatory and autoimmune disorder. Ongoing efforts to understand the mechanisms of disease will no doubt lead to more efficacious therapeutics to control this burdensome disabling disease.
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BACKGROUND While hidradenitis suppurativa (HS) shares some transcriptomic and cellular infiltrate features with psoriasis, their skin proteome remains unknown. OBJECTIVE To define and compare inflammatory protein biomarkers of HS and... more
BACKGROUND While hidradenitis suppurativa (HS) shares some transcriptomic and cellular infiltrate features with psoriasis, their skin proteome remains unknown. OBJECTIVE To define and compare inflammatory protein biomarkers of HS and psoriasis skin. METHODS We assessed 92 inflammatory biomarkers in HS (n=13), psoriasis (n=11) and control skin (n=11) using Olink high-throughput proteomics. We also correlated HS skin and blood biomarkers using proteomics and RNA-sequencing. RESULTS We identified 57 differentially expressed proteins (DEPs) in lesional psoriasis and 64 DEPs in lesional HS skin, compared to healthy controls. Both HS and psoriasis lesional skin demonstrated a significant upregulation of Th1 and Th17 proteins. Healthy-appearing perilesional HS skin had 63 DEPs compared to healthy controls. Nonlesional HS and psoriasis skin had 24 and 7 DEPs, respectively, compared to healthy controls. TNF and 8 other proteins were significantly correlated with clinical severity in perilesional skin (2cm from a nodule). LIMITATIONS Inclusion of only moderate-to-severe patients and the cohort size. CONCLUSION HS has a higher inflammatory profile and is more diffusely distributed versus psoriasis. Proteins correlated with disease severity are potential disease mediators. Perilesional skin is comparably inflamed to lesional skin, suggesting the need to treat beyond skin nodules.
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Introduction: Hidradenitis suppurativa (HS) patients may be at increased risk of COVID-19 infection and complications from their medications and comorbidities. There is a lack of expert consensus on recommendations for the COVID-19... more
Introduction: Hidradenitis suppurativa (HS) patients may be at increased risk of COVID-19 infection and complications from their medications and comorbidities. There is a lack of expert consensus on recommendations for the COVID-19 vaccine for HS patients. Herein, we aim to provide expert-driven consensus recommendations regarding COVID-19 vaccinations in HS patients. Methods: A modified Delphi consensus survey developed by a core committee of 7 dermatologist HS experts consisting of 4 demographic questions and 12 practice statements was distributed to the US HS Foundation-sponsored provider listserv. Participants were attending physician HS experts. Survey results were to be reviewed by the core group and revised and resubmitted until consensus (≥70% agreement) was achieved. Results: Among the 33 survey participants, there were 30 (87%) dermatologists, 1 general surgeon, 1 plastic surgeon, and 1 rheumatologist. Consensus for all 12 statements on vaccine counseling and HS treatment ...
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BACKGROUND Hidradenitis Suppurativa (HS) is a chronic inflammatory disease with diverse manifestations ranging from nodules and abscesses to draining tunnels. Whether the underlying inflammation from lesions extends to relatively... more
BACKGROUND Hidradenitis Suppurativa (HS) is a chronic inflammatory disease with diverse manifestations ranging from nodules and abscesses to draining tunnels. Whether the underlying inflammation from lesions extends to relatively healthy-appearing adjacent perilesional and distant nonlesional skin has not been systematically evaluated. OBJECTIVE We sought to characterize lesional, perilesional and nonlesional skin in HS patients. METHODS Skin biopsy samples were collected under ultrasound guidance from active, untreated moderate-to-severe HS patients. Site-matched healthy volunteer control biopsies were used for comparison. RESULTS RNA-sequencing demonstrated that HS skin clustered separately from healthy controls, with perilesional and lesion skin clustering together and away from nonlesional skin. Immunohistochemistry analysis identified psoriasiform hyperplasia with keratin 16 positivity in both perilesional and lesional skin, with comparable levels of CD3+, CD11c+ and Neutrophil Elastase+ cellular infiltration. There was a marked up-regulation of IL-17 signaling in perilesional and lesional skin. HS samples clustered based on the expression of Lipocalin-2 (LCN2), with samples with high LCN2 expression in the skin exhibiting a differing transcriptomic profile with significantly higher overall inflammation compared to those with low LCN2 levels. CONCLUSIONS Perilesional HS skin has a comparable transcriptomic and molecular profile as the lesional skin. HS can be grouped into two distinct subtypes based on molecular levels of LCN2 in the skin, with the LCN2-high subtype exhibiting a higher overall inflammatory burden and an upregulation of targetable cytokines. This is the first study to characterize a unique HS subtype (and a potential endotype) which may guide future therapeutic targets.
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Abstract Hidradenitis Suppurativa is a chronic inflammatory disease often confused with an immune deficiency due to the chronic draining sinus tracts. Related conditions affect additional regions of skin. The pathophysiologic basis is... more
Abstract Hidradenitis Suppurativa is a chronic inflammatory disease often confused with an immune deficiency due to the chronic draining sinus tracts. Related conditions affect additional regions of skin. The pathophysiologic basis is over production of inflammatory mediators and the treatments are usually directed at restoring the balance of inflammatory pathways. Typically sporadic and episodic in nature, features of these syndromes can occur in association with inborn errors of immunity.
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There is a paucity of high-quality, randomized,double-blind, control clinical trials to accuratelyassess interventions in pemphigus. The recentdevelopment of consensus statements withcommon definitions and end points will aid in thefuture... more
There is a paucity of high-quality, randomized,double-blind, control clinical trials to accuratelyassess interventions in pemphigus. The recentdevelopment of consensus statements withcommon definitions and end points will aid in thefuture by enabling the inclusion of smaller studies,which would otherwise have been underpoweredinto larger meta-analyses.
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Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of the skin with a predilection for women. The role of sex hormones, including estrogen and progesterone, is incompletely understood, but alterations in hormone levels may... more
Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of the skin with a predilection for women. The role of sex hormones, including estrogen and progesterone, is incompletely understood, but alterations in hormone levels may play a role in disease activity for many patients. Specific clinical considerations should be made for women with HS, particularly in the setting of pregnancy, childbirth, breastfeeding, and menopause. Current knowledge gaps regarding HS include the cumulative impact of disease across an individual’s lifespan, as well as the mechanistic role of sex hormones in the disease. An improved understanding of the pathophysiologic role of hormones in HS would optimize our ability to use targeted therapies for hormonally driven disease. Psychological and psychosexual support for women with HS is an important facet of any holistic management strategy for the disease. This article integrates up-to-date pathogenic and mechanistic insights with evidence-based clinical management to optimize care for women with HS. © 2021 The Author(s). Published by Elsevier Inc. on behalf of Women’s Dermatologic Society. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )
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targeted therapies for vascular malformations. Am J Clin Dermatol 2020; 21:657–68. 3 Fereydooni A, Dardik A, Nassiri N. Molecular changes associated with vascular malformations. J Vasc Surg 2019; 70:314–26. 4 Wouters OJ, McKee M, Luyten... more
targeted therapies for vascular malformations. Am J Clin Dermatol 2020; 21:657–68. 3 Fereydooni A, Dardik A, Nassiri N. Molecular changes associated with vascular malformations. J Vasc Surg 2019; 70:314–26. 4 Wouters OJ, McKee M, Luyten J. Estimated research and development investment needed to bring a new medicine to market, 2009–2018. JAMA 2020; 323:844–53. 5 Schmitt J, Lange T, Kottner J et al. Cochrane reviews and dermatological trials outcome concordance: why core outcome sets could make trial results more usable. J Invest Dermatol 2019; 139:1045–53. 6 COSMIN. Find the right tool. Available at: https://www.cosmin.nl/ finding-right-tool/developing-core-outcome-set (last accessed 7 July 2021). 7 Horbach SER, van der Horst CMAM, Blei F et al. Development of an international core outcome set for peripheral vascular malformations: the OVAMA project. Br J Dermatol 2018; 178:473–81.
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Hidradenitis Suppurativa is a chronic inflammatory disease manifesting in painful nodules, abscesses and malodorous draining tunnels with a pre‐disposition to flexural regions of skin. Traditional surgical interventions include excision... more
Hidradenitis Suppurativa is a chronic inflammatory disease manifesting in painful nodules, abscesses and malodorous draining tunnels with a pre‐disposition to flexural regions of skin. Traditional surgical interventions include excision of clinically visible lesions and in severe cases – excision down to fascia of entire anatomical regions (axilla, groin) and repair with split‐thickness grafting or skin substitutes. However, such techniques are plagued by long healing times (up to several months), extensive tissue loss and high recurrence rates given that a large proportion of disease is not clinically visible. Deroofing is a tissue‐saving surgical technique, ideal for Hurley Stage 2 disease, which when combined with bedside pre‐operative sonography can allow for the accurate identification and removal of occult dermal tunnels whilst minimising the risks of pain, infection, minimising healing times and can be safely conducted in the setting of immunomodulatory therapy.
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Importance Standard morphological terminology and definitions are vital for identification of lesion types in the clinical trial setting and communication about the condition. For hidradenitis suppurativa (HS), morphological definitions... more
Importance Standard morphological terminology and definitions are vital for identification of lesion types in the clinical trial setting and communication about the condition. For hidradenitis suppurativa (HS), morphological definitions have been proposed by different groups, representing various regions of the world, but no international consensus has been reached regarding such definitions. A lack of globally harmonized terminology and definitions may contribute to poor-quality data collection in clinical trials as well as poor communication among clinicians, investigators, and patients. Objective To establish and validate consensus definitions for typical morphological findings for HS lesions. Methods This study was conducted from August 2019 to August 2020. A Delphi study technique was used to assess agreement and then resolve disagreement on HS terminology among international experts. After an initial preparation phase, the process consisted of 3 rounds. In each round, participants reviewed preliminary definitions and rated them as "keep, with no changes," "keep, with changes," or "remove." Eight HS primary lesions, including papule, pustule, nodule, plaque, ulcer, abscess, comedo, and tunnel, were selected because they are most frequently used in HS clinician-reported outcome measures. The initial definitions were based on extant literature, and modifications were made between rounds based on qualitative thematic analysis of open-ended responses or discussion. Consensus was defined as greater than 70% to accept a definition. Consensus stability across rounds was defined as less than 15% change in agreement. Reliability was evaluated using the Gwet agreement coefficient. Validation was based on assessment of face validity and stability across rounds. Results A total of 31 experts participated. All 8 HS primary lesion definitions achieved greater than 70% consensus by Delphi round 3. Stability was achieved for papule, pustule, and abscess. The Gwet agreement coefficient increased from 0.49 (95% CI, 0.26-0.71) in round 1 to 0.78 (95% CI, 0.64-0.92) in round 3. Face validity was supported by expert endorsement to keep terms in survey responses. Previously unmeasured variation among clinicians' definition of tunnels was identified, and consensus was achieved. Conclusions and Relevance An international group of experts agreed on definitions for morphological features of HS lesions frequently included in HS clinical trials. These international consensus terms and definitions are needed to support consistency of lesion identification and quantification in clinical trials.
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Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin, manifesting in chronic, recurrent painful pustules, nodules, boils and purulent draining abscesses. Our current understanding of the pathogenesis of the disease... more
Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin, manifesting in chronic, recurrent painful pustules, nodules, boils and purulent draining abscesses. Our current understanding of the pathogenesis of the disease is incomplete. This review aims to identify available treatment options in HS and discuss the pharmacological mechanisms through which such agents function. Identifying common pathways may inform our understanding of the pathogenesis of HS as well as identify future therapeutic targets. The pharmacological mechanisms implicated in topical therapies, antibiotic, hormonal, systemic immunomodulatory and biologic therapies for HS are discussed. Significant differences exist between agents and implicated pathways in therapy for mild and severe disease. This is an expression of the possible dichotomy in inflammatory pathways (and treatment responses) in HS. Studies involving monoclonal antibodies provide the greatest insight into what these specific mecha...
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A: Grouped violaceous papules on the dorsolateral aspect of the foot with associated oedema. B: Significant improvement in foot oedema with healing blisters and erosions after 3 days of oral prednisolone (25mg). C: Low-power image of... more
A: Grouped violaceous papules on the dorsolateral aspect of the foot with associated oedema. B: Significant improvement in foot oedema with healing blisters and erosions after 3 days of oral prednisolone (25mg). C: Low-power image of upper dermis and epidermis with marked subepidermal oedema and spongiosis responsible for the bullous clinical appearance (pseudobullous change) (objective magnification, 4; haematoxylineeosin stain). D: High-power image showing prominent interstitial dermal infiltrate of eosinophils with flame figure (arrow) at top of image (objective magnification, 20; haematoxylineeosin stain). Clinical record