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      Paradoxical Hidradenitis Suppurativa during Biologic Therapy, an Emerging Challenge: A Systematic Review

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      Biomedicines
      MDPI AG

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          Abstract

          Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease usually occurring after puberty with painful, deep-seated, inflammatory lesions in the apocrine gland-bearing areas of the body. Although HS pathogenesis is still unproven, recent major research advantages have increased our knowledge of the mechanisms behind HS lesions. Particularly, follicular occlusion followed by follicular rupture has been shown to be crucial to HS development, leading to immune response activation, and resulting in typical clinical HS lesions. Moreover, an increased and imbalanced cytokine production, such as interleukin (IL) 17 and tumor necrosis factor (TNF) α, may play a role in HS. In recent years, paradoxical adverse events have been described during treatment. Since the recent increased use of biologic treatments in HS, an increased number of paradoxical HS occurrences have been reported. In this review, we analyzed all current data on paradoxical HS triggered by biological drugs.

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          Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum.

          Treatment of hidradenitis suppurativa (HS) is difficult and the search for effective therapies continues.
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            Hidradenitis suppurativa/acne inversa: a practical framework for treatment optimization – systematic review and recommendations from the HS ALLIANCE working group

            Abstract Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and there is a need for international, evidence‐based and easily applicable consensus on HS management. We report here the findings of a systematic literature review, which were subsequently used as a basis for the development of international consensus recommendations for the management of patients with HS. A systematic literature review was performed for each of nine clinical questions in HS (defined by an expert steering committee), covering comorbidity assessment, therapy (medical, surgical and combinations) and response to treatment. Included articles underwent data extraction and were graded according to the Oxford Centre for Evidence‐based Medicine criteria. Evidence‐based recommendations were then drafted, refined and voted upon, using a modified Delphi process. Overall, 5310 articles were screened, 171 articles were analysed, and 65 were used to derive recommendations. These articles included six randomized controlled trials plus cohort studies and case series. The highest level of evidence concerned dosing recommendations for topical clindamycin in mild disease (with systemic tetracyclines for more frequent/widespread lesions) and biologic therapy (especially adalimumab) as second‐line agents (following conventional therapy failure). Good‐quality evidence was available for the hidradenitis suppurativa clinical response (HiSCR) as a dichotomous outcome measure in inflammatory areas under treatment. Lower‐level evidence supported recommendations for topical triclosan and oral zinc in mild‐to‐moderate HS, systemic clindamycin and rifampicin in moderate HS and intravenous ertapenem in selected patients with more severe disease. Intralesional or systemic steroids may also be considered. Local surgical excision is suggested for mild‐to‐moderate HS, with wide excision for more extensive disease. Despite a paucity of good‐quality data on management decisions in HS, this systematic review has enabled the development of robust and easily applicable clinical recommendations for international physicians based on graded evidence.
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              Elevated levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-α and IL-1β.

              The pathogenesis of hidradenitis suppurativa (HS) is largely unknown and the disease is difficult to treat. Patients are in high need of an effective treatment. Although it is not known whether the levels of tumour necrosis factor (TNF)-α are aberrant in HS skin, anti-TNF-α biologics are used, with variable clinical efficacy. To determine the cytokine profile in lesional and perilesional HS skin. We cultured 20 lesional and 10 normal-appearing perilesional HS skin samples, seven psoriasis and six healthy control skin samples in a transwell culture system. Two distinct cytokine bead arrays were used to measure the spectrum of inflammatory cytokines in the culture supernatant. Results from HS skin samples were compared with those of healthy and psoriasis skin. The proinflammatory cytokines interleukin (IL)-1β and TNF-α as well as the anti-inflammatory cytokine IL-10 were significantly elevated in HS skin. Elevated levels of these cytokines were also found in perilesional HS skin. Fold increases relative to control skin of IL-1β, TNF-α and IL-10 in HS were 31, 5 and 34, compared with psoriasis: 4, 1 and 2, respectively. Levels of all three cytokines showed a trend towards a positive correlation with disease severity. IL-2, IL-4, IL-5 and interferon-γ were hardly detectable in HS or healthy control skin. This study shows for the first time that IL-1β, TNF-α and IL-10 levels are elevated in HS skin. These data provide a rationale for therapies with biologics targeting cytokines such as TNF-α and IL-1. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.
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                Author and article information

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                Journal
                BIOMID
                Biomedicines
                Biomedicines
                MDPI AG
                2227-9059
                February 2022
                February 16 2022
                : 10
                : 2
                : 455
                Article
                10.3390/biomedicines10020455
                35203664
                bbfb35e7-9831-4b7d-9784-fdeb24dba9bd
                © 2022

                https://creativecommons.org/licenses/by/4.0/

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