Hidradenitis suppurativa (HS) is a chronic, recurrent, auto-inflammatory skin disease originating from the hair follicles. The typical inflammatory nodules, abscesses, and draining sinus tracts (tunnels) are characterized by a massive influx of neutrophils, macrophages, B-cells, plasma cells, T helper (Th)1, Th17 cells and upregulation of pro-inflammatory cytokines such as IL-1, IL-17, IL-12/23, and TNF-α. Over the last decades, several clinical trials evaluated the clinical efficacy of different biologics targeting these pro-inflammatory cytokines, in particular TNF-α and IL-1. However, adalimumab is still the only registered drug for HS. This review discusses biologics and small molecules with high level of evidence for their clinical application, provides guidance on when and how to use these biologics and small molecules in clinical practice, and elaborates on the combination with medical and surgical treatment options beyond the current guidelines. Furthermore this review provides an overview of potential biologics and small molecules currently under investigation for novel targets in HS such as IL-36, C5a, Janus kinase family members, CD-40, LTA4 and CXCR1/2.

I 2 ¼ 69.16%; P ¼ .001) compared to nail 2 (ER, 5%; 95% CI, 3-8; I 2 ¼ 65.22%; P ¼ .002), nail 3 (ER, 5%; 95% CI, 3-8; I 2 ¼ 0.00%; P ¼ .83), nail 4 (ER, 5%; 95% CI, 3-8; I 2 ¼ 0.00%; P ¼ .74), and nail 5 (ER, 7%; 95% CI, 3-17; I 2 ¼ 73.02%; P ¼ .001) (Supplemental Fig 4; available via Mendeley at https://doi.org/10.17632/ y6kxmmz9x9.1). Regarding melanomas of individual toes, the distributions were as follows: hallux: ER, 40%; 95% CI, 25-57; I 2 ¼ 0.00%; P ¼ .53); second toe: ER, 17%; 95% CI, 8-33; I 2 ¼ .00%; P ¼ .83); third toe: ER, 24%; 95% CI, 13-38; I 2 ¼ 0.00%; P ¼ .91); fourth toe: ER, 16%; 95% CI, 7-33; I 2 ¼ 0.00%; P ¼ .65); and fifth toe: ER, 21%; 95% CI, 9-41; I 2 ¼ 9.39%; P ¼ .36). Egger's regression analysis showed no evidence of publication bias.Studies suggest that inflammation is a contributing factor to the development of several malignancies. 3 A 2020 meta-analysis exclusively in the Asian population found that areas of plantar pressure were associated with a higher number of melanomas. 4 Previous research suggests that the first toe, including the subungual surface, also has a greater tendency for trauma and repetitive sheer force. 5 Our systematic review and meta-analysis included study populations from all ethnic background and supports the hypothesis of repetitive mechanical stress as a risk factor for plantar melanoma carcinogenesis, with melanoma locations correlating with pressure areas of the feet. Future research exploring distributions of plantar melanoma and biomechanical stress patterns within the same patient population may provide further evidence for this hypothesis.

B.H. reports fees from Janssen-Cilag (for advisory boards, educational grants, consultations, investigator initiative studies), AbbVie (for advisory boards, educational grants, consultations, investigator initiative studies), Novartis Pharma (for advisory boards, consultations, investigator initiative studies), UCB Pharma (for advisory boards, consultations), Leo Pharma (for consultations), Solenne B.V. (for investigator initiative studies), Celgene (for consultations and investigator initiative studies), Akari Therapeutics (for consultations and investigator initiative studies), Philips (for consultation), Roche (for consultation), Regeneron (for consultation) and Sanofi (for consultation); the fees were payed to the institution. E.P.P. has received honoraria from AbbVie, Amgen, Celgene, Janssen, Galderma, Novartis and Pfizer for participation as a speaker and for serving on advisory boards; E.P.P. also received investigator-initiated grants (paid to Erasmus MC) from AbbVie, AstraZeneca, Janssen and Pfizer.

ain is one of the most prominent and debilitating symptoms of hidradenitis suppurativa (HS) and has been incorporated as a domain in the newly developed core outcome set for HS. 1 The chronic, inflammatory, and painful nature of HS has been postulated to induce a process known as central sensitization (CS). 2 Central sensitization is an increased responsiveness of the pain perception pathway in the central nervous system to normal or subthreshold stimuli, altering and amplifying pain perception. 2 Symptoms of CS are not confined to pain and can include fatigue, memory loss, and sleep disturbances. 2 Moreover, several syndromes have been associated with CS. For example, fibromyalgia and irritable bowel syndrome are considered to share a common pathophysiological pathway, implicating neuronal hyperexcitability as the central mechanism. 2 The presence of CS in HS-associated inflammatory diseases, such as inflammatory bowel disease and rheumatic diseases, has been well established. 3,4 Therefore, the aim of this study was to assess the prevalence of central sensitization in patients with HS compared with age-and sex-matched controls. Methods Study DesignThis cross-sectional, survey-based, case-control study was performed at the Department of Dermatology of the Erasmus University Medical Center Rotterdam, in Rotterdam, the Netherlands, from February to November 2020. All consecutive, adult patients IMPORTANCE Chronic pain is one of the most prominent symptoms of hidradenitis suppurativa (HS) and an independent domain in the core outcome set for HS. Previously, the chronic, recurrent, inflammatory nature of HS was hypothesized to induce central sensitization (CS; alteration and amplification of pain perception). However, evidence for this hypothesis is currently lacking.OBJECTIVE To determine the prevalence of CS in patients with HS compared with sex-and age-matched controls. DESIGN, SETTING, AND PARTICIPANTSThis was a cross-sectional, survey-based, case-control study conducted from February to November 2020 that included all consecutive adult patients with HS attending the outpatient clinic of the Department of Dermatology of the Erasmus University Medical Center Rotterdam, in Rotterdam, the Netherlands. Age-and sex-matched controls without chronic inflammatory dermatologic diseases were recruited from the same department. MAIN OUTCOMES AND MEASURESThe main outcome was the Central Sensitization Inventory (CSI) score (ranging from 0-100) as a screening tool for presence of CS. Based on current literature, a score of 40 or higher was deemed to indicate the presence of CS. RESULTSOverall, 100 patients with HS (median [IQR] age, 34.5 [27.3-47.0] years; 71 [71%] female) and 100 controls (median [IQR] age, 33.5 [27.0-48.8] years; 71 [71%] female) were included, of which 36% and 12%, respectively, had a CSI score of 40 or higher (P < .001). Multivariate logistic regression showed that patients with HS had 4.46 (95% CI, 1.89-10.52; P = .001) times the odds of having a positive CSI compared with controls. In addition, CS ...

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Background Effectiveness of available biologics for the treatment of hidradenitis suppurativa (HS) is limited. Additional therapeutic options are highly needed. Objective To investigate the efficacy and mode of action of guselkumab (an anti-IL-23p19 monoclonal antibody) 200 mg s.c., every four weeks for 16 weeks in HS patients. Methods An open label, multicenter, phase IIa trial in patients with moderate-to-severe HS. The pharmacodynamic response in skin and blood was measured after 16 weeks of treatment. Clinical efficacy was assessed using the HS clinical response (HiSCR), the International Hidradenitis Suppurativa Severity Score System (IHS4), and the abscess and inflammatory nodule (AN) count. Results Thirteen out of 20 patients (65%) achieved HiSCR with also a significant decrease in the median IHS4-score (8.5 to 5.0, p=.002) and the median AN-count (6.5 to 4.0, p=0.002). The overall patient reported outcomes did not show a similar trend. One SAE, likely unrelated to guselkumab treatment was observed. Transcriptomic analysis revealed, in lesional skin, upregulation of various genes associated with inflammation such as immunoglobulin, S100, MMP, keratin, B cell and complement genes, which decreased after treatment in clinical responders. Immunohistochemistry revealed a marked decrease in inflammatory markers in clinical responders at week 16. Conclusions Sixty five (65) percent of moderate-to-severe HS patients achieved HiSCR after 16 weeks of treatment with guselkumab. We could not demonstrate a consistent correlation between gene and protein expression and clinical responses. The main limitations of this study are the small sample size and the absence of a placebo arm. The large placebo-controlled phase IIb NOVA-trial for guselkumab in HS patients, reported a lower HiSCR response of 45.0 to 50.8%, and 38.7% for the placebo group. Guselkumab seems of benefit to only a subgroup of HS patients, indicating that the IL-23/Th17-axis is not central to the pathophysiology of HS.

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Introduction Cohort studies on the use of retinoids for hidradenitis suppurativa (HS) have yielded contradicting results. As the clinical presentation of HS is heterogeneous, with different predilection sites and hallmark features, it can be hypothesized that HS phenotypes are associated with the effectiveness of specific retinoid treatments. Objectives The aim of this study was to evaluate the drug survival of oral retinoids in the treatment of HS and to establish predictors for longer treatment duration. Methods A retrospective, dual-center study was conducted in the Netherlands in adult HS patients treated with oral retinoids between 2011 and 2021. Drug survival analyses were performed through Kaplan-Meier survival curves. Additionally, Cox regression models were used to determine predictors for a longer drug survival. Results In total, 102 patients were included. Overall drug survival of (low-dose) isotretinoin ( n = 66) at 12 and 24 months was 44.2% and 15.5%, respectively. Termination of treatment was mostly due to ineffectiveness (26%). Presence of widespread comedones ( p = 0.03) and the use of concomitant systemic medication ( p = 0.04) were associated with a prolonged treatment duration. For acitretin ( n = 36), the overall drug survival was 42.0% at 12 months and 37.4% at 24 months, and was also predominantly determined by ineffectiveness (28%). Interestingly, the scarring folliculitis phenotype ( p < 0.05) was associated with prolonged drug survival time for acitretin treatment relative to the regular phenotype. Conclusion Comparable drug survival rates at 12 months for isotretinoin and acitretin were found. HS patients with widespread comedones and the scarring folliculitis phenotype could benefit from treatment with isotretinoin or acitretin, respectively. Supplementary Information The online version contains supplementary material available at 10.1007/s40257-022-00725-9.