John W Frew

UNSW Sydney | UNSW · School of clinical medicine

Background: Several registries for hidradenitis suppurativa (HS) already exist in Europe and USA. There is currently no global consensus on a core dataset (CDS) for these registries.Creating a global HS registry is challenging due to logistical and regulatory constraints, which could limit opportunities for global collaboration due to differences...

Background: Current infectious disease screening recommendations for hidradenitis suppurativa (HS) are adopted from recommendations in chronic plaque psoriasis. No HS-specific guidelines for infectious disease screening prior to immunomodulatory therapy have been developed. Objectives: To establish an expert Delphi consensus of recommendations rega...

Hidradenitis Suppurativa is a chronic inflammatory disease of which the pathogenesis is incompletely understood. Dermal fibroblasts have been previously identified as a major source of inflammatory cytokines, however information pertaining to the characteristics of subpopulations of fibroblasts in HS remains unexplored. Using in silico-deconvolutio...

Melanoma accounts for the majority of skin cancer‐related mortality, highlighting the need to better understand melanoma initiation and progression. In‐depth molecular analysis of neoplastic melanocytes in whole tissue biopsies may be diluted by inflammatory infiltration, which may obscure gene signatures specific to neoplastic cells. Thus, a metho...

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic disabling and debilitating inflammatory disease with high unmet medical need. The prevalence of HS is 1-2% in most studies, although it is likely underreported and estimates vary globally due to variance in data collection methods, ethnicity, geographical location, and underdia...

Resident memory T-cells (T-RMs) remain in epithelial barrier tissues after antigen exposure and the initial effector phase. These T-RMs provide effective antimicrobial and anticancer immunity, however pathogenic T-RMs have been shown to mediate various chronic inflammatory disorders in a variety of tissue types. In the skin, T-RMs are referred to a...

Mast cells have traditionally been associated with allergic inflammatory responses; however, they play important roles in cutaneous innate immunity and wound healing. The Hidradenitis Suppurativa tissue transcriptome is associated with alterations in innate immunity and wound healing-associated pathways; however, the role of mast cells in the disea...

Background: Hidradenitis Suppurativa is an autoinflammatory disorder of keratinization with a prominence of B cells and plasma cells. Fostamatinib is a spleen tyrosine kinase inhibitor targeting B cells and plasma cells. Objectives: To assess the safety, tolerability and clinical response at week 4 and week 12 of fostamatinib in moderate to seve...

Hidradenitis Suppurativa (HS) is a chronic, suppurative condition of the pilosebaceous unit. The typical HS patient is characterized as obese, smoker, manifesting nodules, abscesses and/or draining tunnels predominantly distributed in intertriginous skin. It is established that lifestyle and genetic factors are the main pathophysiological drivers o...

Mast cells have traditionally been associated with allergic inflammatory responses; however they play important roles in cutaneous innate immunity and wound healing. The Hidradenitis Suppurativa tissue transcriptome is associated with alterations in innate immunity and wound healing associated pathways, however the role of Mast cells in the disease...

Background: The prevalence of hidradenitis suppurativa (HS) is 0.00033% to 4.10% globally. Few epidemiological studies derive from Asia, with social stigmatisation postulated to result in under-diagnosis. Objective: This study aimed to assess the self-reported prevalence of HS, and the knowledge, attitudes, and perceptions towards HS among Singapo...

Introduction Academic dermatologists in Australia and New Zealand provide high-quality and meaningful contributions to the understanding of disease and therapeutic translational research. Concerns have been raised by the Australian Medical Association regarding the decline of clinical academics in Australia as a whole, however, such trends in scho...

Hidradenitis suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. IL-23 interacts with sex hormones but the relationships between the two in HS remains uninvestigated. To assess whether baseline clinical, hormonal or molecular markers are associated with clinical response to IL-23 antagonism wi...

Background: Psoriasis is a chronic immune-mediated inflammatory disorder that also occurs in the setting of human immunodeficiency virus (HIV). Biological therapy has transformed the treatment landscape for psoriasis; however, individuals with HIV are excluded from clinical trials. The impact of biological therapy on blood parameters in HIV is unc...

Background: Hidradenitis Suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. IL-23 interacts with sex hormones but the relationships between the two in HS remains uninvestigated. Objectives: To assess whether baseline clinical, hormonal, or molecular markers are associated with clinical respon...

Hidradenitis Suppurativa is a chronic inflammatory disease of which the pathogenesis is incompletely understood. Dermal fibroblasts have been previously identified as a major source of inflammatory cytokines, however information pertaining to the characteristics of subpopulations of fibroblasts in HS remains unexplored. Using in silico-deconvolutio...

https://doi.org/10.1093/bjd/ljad027 Hidradenitis suppurativa (HS) is a debilitating inflammatory disease in desperate need of novel therapeutics.¹ Only by understanding the pathogenesis of disease can we reliably identify novel therapeutic targets.¹ In this edition of the BJD, Dudink et al.² present insightful work demonstrating that T-helper (Th)1...

This chapter explores the role of epigenetic modifications in atopic dermatitis. It draws its data from various translational studies performed over the last two decades to define the role of three epigenetic mediators (DNA methylation, microRNAs, and histone modifications) in the immune dysfunction and breakdown of epidermal integrity associated w...

The utility of Strongyloidiasis screening in the setting of Dupilumab therapy is unknown. Our retrospective cohort study identifies a low prevalence of Strongyloidiasis with no cases of disseminated disease in the setting of Dupilumab therapy. Baseline IgE and Eosinophil levels were not associated with Strongyloidiasis and screening is likely of lo...

Altered gut microbiota composition has been observed in individuals with hidradenitis suppurutiva (HS) and many other inflammatory diseases, including obesity, type 1 and type 2 diabetes. Here we addressed whether Adalimumab, a systemic anti‐inflammatory therapy, may impact the microbiota biochemical profile, particularly on beneficial metabolites...

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 vaccina...

Background: Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). While 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 HS patients preceding biologic...

Dear Editor, Adalimumab is currently the only biologic approved for moderate to severe hidradenitis suppurativa (HS).¹ Although the treatment may initially reduce the number of flares, patients with HS may often discontinue the treatment due to insufficient disease control. This was recently exemplified by the observation that time to discontinuati...

Background: Hidradenitis suppurativa (HS) is an inflammatory skin disease with dysregulation of the IL-17 axis. Recently we reported clinical benefit of brodalumab, a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody, in moderate-to-severe HS. Objectives: To characterize the molecular response to brodalumab in HS skin and serum, and to i...

Pyoderma Gangrenosum is a painful recurrent ulcerative neutrophilic dermatosis in which the pathogenesis is incompletely defined. Current evidence suggests that PG is associated with dysregulation of components of both the innate and adaptive immune system with dysregulation of neutrophil function and contribution of the Th17 immune axis. PG can pr...

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...

Dupilumab associated head and neck dermatitis is incompletely understood. This prospective multicentre prospective study identified baseline Malassezia‐specific IgE as associated with the development of Dupilumab associated head and neck dermatitis.

Importance: The identification and validation of biomarkers in hidradenitis suppurativa (HS) has potential to improve the understanding and management of this chronic, burdensome disease. Objective: To systematically identify all known HS biomarkers, categorize them by biomarker type, and critically evaluate their validity according to establish...

The pathogenic model of hidradenitis suppurativa (HS) is in the midst of a paradigm shift away from a disorder of primary follicular occlusion to an autoinflammatory keratinization disease. Observational, experimental, and therapeutic evidence supports the concept of HS as a primarily inflammatory disorder and/or a disorder of autoimmunity, in cont...

Hidradenitis suppurativa is considered to be a T helper 17–mediated inflammatory disorder. However, the role of prominent B-cell and plasma cell infiltrates has not been incorporated into pathogenic understanding of the disease. In their new article in the Journal of Investigative Dermatology, Carmona-Rivera et al. (2021) present new insights regar...

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...

Hidradenitis suppurativa (HS) is a chronic, suppurative condition of the pilosebaceous unit. Patients suffering from HS demonstrate a molecular profile in keeping with a state of systemic inflammation and are often found to fit the criteria for a diagnosis of metabolic syndrome (MetS). In this paper, we review the literature with regards to establi...

Hidradenitis suppurativa is a chronic, inflammatory skin disease of the hair follicle defined by recurrent nodules, tunnels and scarring involving the intertriginous regions. HS is associated with microbial dysbiosis and immune dysregulation. In HS, an increasing number of studies have investigated antimicrobial peptides (AMPs). A systematic litera...

In Reply We thank Lipsker for his feedback about our article that proposes harmonized morphological definitions for hidradenitis suppurativa (HS) assessment.¹ We congratulate our colleagues for their first clinical definition for tunnels. Given the clinical and pathophysiological importance of these structures,² the consistent and accurate assessme...

In Hidradenitis Suppurativa (HS), the identification of disease activity biomarkers is a key priority¹. Sonographic-based imaging biomarkers have been established as valid measurements of baseline disease activity2,3, however the response of epidermal thickness, tunnel diameter and power Doppler intensity³ in the setting of pharmacologic therapy is...

Background Hidradenitis Suppurativa (HS) is now recognized as a systemic inflammatory disease, sharing molecular similarities with psoriasis. Direct comparison of the systemic inflammation in HS with psoriasis is lacking. Objectives To evaluate the serum proteome of HS and psoriasis, and to identify biomarkers associated with disease severity. Me...

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=...

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 W...

The registration of the tumour necrosis factor‐α inhibitor adalimumab in 2015 was a major step forward in the treatment of hidradenitis suppurativa/acne inversa (HS). However, it soon became evident that the effectiveness of adalimumab in daily practice was highly variable. A significant unmet medical need of HS patients remained, and the search fo...

Linked Article: Cao et al. Br J Dermatol 2021; 185:804–814.

Elevated BMI in Hidradenitis Suppurativa is associated with decreased response to Adalimumab therapy. BMI is proposed to segregate distinct disease subtypes. It remains unresolved whether a threshold BMI exists above which increased dosages may provide clinical benefit. Individual patient data from 578 PIONEER Phase 3 participants were analyzed. De...

https://doi.org/10.1007/978-3-030-54779-0_18

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,...

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...

Hidradenitis Suppurativa (HS) is a chronic inflammatory dermatosis with presentations ranging from painful nodules and abscesses to draining tunnels. Using an unbiased proteomics approach, we assessed 368 cardiovascular, cardiometabolic and inflammation-related biomarkers in serum of moderate to severe HS patients. HS serum clustered separately fro...

The cover image is based on the Original Article The erythema Q‐score, an imaging biomarker for redness in skin inflammation by John Frew et al., https://doi.org/10.1111/exd.14224.

Diabetes mellitus is associated with numerous dermatological conditions. As diabetes is a powerful risk factor for cardiovascular disease, recognition of these conditions is important both for treatment of the cutaneous disorder and the prevention of long-term cardiovascular sequelae. Dermatological manifestations may be the first indicator of diab...

Background Hidradenitis Suppurativa (HS), also known as acne inversa, is a chronic, painful, burdensome inflammatory disease manifesting in nodules and abscesses with progression to chronically draining tunnels in later-stage disease. Objective We sought to determine whether HS tunnels are immunologically active participants in disease activity....

Hidradenitis Suppurativa (HS) is a chronic inflammatory dermatosis in which a subset of patients display genetic variants in components of the gamma secretase complex¹ proposed to result in dysregulation of Notch signaling². This pathogenic paradigm has been highly influential in providing a succinct explanation for the pathogenesis of HS, however...

Over the last two decades, tremendous advances have been made in the treatment of psoriatic disease. Our understanding of the complex immunopathogenesis of this chronic inflammatory condition has led to the development of highly effective, safe, targeted monoclonal antibodies that result in clearance in the vast majority of treated patients. Howeve...

Background Physician rating of cutaneous erythema is central to clinical dermatological assessment as well as quantification of outcome measures in clinical trials in a number of dermatologic conditions. However, issues with interrater reliability and variability in the setting of higher Fitzpatrick skin types makes visual erythema assessment unrel...

The 14 authors of the first review article on hidradenitis suppurativa (HS) pathogenesis published 2008 in EXPERIMENTAL DERMATOLOGY cumulating from the 1st International Hidradenitis Suppurativa Research Symposium held March 30–April 2, 2006 in Dessau, Germany with 33 participants were prophetic when they wrote “Hopefully, this heralds a welcome ne...

Background Hidradenitis suppurativa (HS) demonstrates high placebo response rates in clinical trials, possibly due to the natural variability of the disease. No quantification of variability in lesion counts of untreated disease has been undertaken. Objective To quantify the variability of untreated HS. Methods Deidentified individual patient dat...

This systematic review identifies and critically evaluates the mechanistic and clinical evidence of new promising therapeutic targets in hidradenitis suppurativa (HS). Evidence for these targets is largely based on observational data with limited ex vivo and translational data from clinical trials. A number of placebo-controlled studies have been c...

Background: Clinical response in hidradenitis suppurativa (HS) is most commonly assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR). Dermal tunnels, increased BMI, smoking and antibiotic use significantly decrease the odds of achieving HISCR. However, there is little data exploring if clinical features are also associated with le...

Brodalumab1 is an IL‐17RA antagonist previously used in an open‐label cohort study every 2 weeks (E2W) in HS2. Brodalumab E2W demonstrated high clinical efficacy (10/10 HiSCR at Week12), however participants with draining tunnels were observed to demonstrate cyclical response2 (rapid reduction in acute symptoms, with slow re‐emergence of tunnel dra...