New Insight into the Molecular Pathomechanism and Immunomodulatory Treatments of Hidradenitis Suppurativa

Molinelli, Elisa; Gioacchini, Helena; Sapigni, Claudia; Diotallevi, Federico; Brisigotti, Valerio; Rizzetto, Giulio; Offidani, Annamaria; Simonetti, Oriana

doi:10.3390/ijms24098428

Cited by 13 publications

(2 citation statements)

References 216 publications

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“…Furthermore, TNF and IL-1β can stimulate endothelial cells and strengthen the expression of chemokines, such as CXCL1, CXCL6, CXCL8, CXCL11, CCL20, and CCL22, favoring the recruitment of neutrophils, T-cells, and monocytes into the skin [30].…”

Section: Hidradenitis Suppurativa Pathogenesismentioning

confidence: 99%

Therapeutic Potential of IL-1 Antagonism in Hidradenitis Suppurativa

Calabrese,

Malvaso,

Coscarella

et al. 2024

Biomolecules

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The immunopathogenesis of HS is partially understood and exhibits features of an autoinflammatory disease; it is associated with the potential involvement of B cells and the contribution of Th1 or Th17 cell subsets. Recently, the pathogenic role of both innate immunity and IL-1 family cytokines in HS has been deeply investigated. Several agents targeting the IL-1 family pathway at different levels are currently available and under investigation for the treatment of HS. HS is still characterized by unmet clinical needs and represents an expanding field in the current scientific research. The aim of this narrative review is to describe the pathological dysregulation of IL-1 family members in HS and to provide an update on therapeutic strategies targeting IL-1 family cytokine signaling. Further clinical and preclinical data may likely lead to the enrichment of the therapeutic armamentarium of HS with IL-1 family cytokine antagonists.

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Section: Hidradenitis Suppurativa Pathogenesismentioning

confidence: 99%

Therapeutic Potential of IL-1 Antagonism in Hidradenitis Suppurativa

Calabrese,

Malvaso,

Coscarella

et al. 2024

Biomolecules

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show abstract

“…Despite the relatively high prevalence and severe impact on quality of life, the pathophysiology of HS remains poorly understood, hindering advances in therapeutics [3]. It has been proposed that follicular occlusion, progressing to follicle rupture releasing hair keratins and microbes into the dermis, elicits an aberrant immune response leading to the lesions implicated in HS [4,5]. In contrast to other inflammatory skin disorders such as psoriasis, recent drug development has not enabled highly efficacious therapies for HS [6].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic Analysis of Hidradenitis Suppurativa: A Unique Molecular Signature with Broad Immune Activation

Ben Abdallah,

Bregnhøj,

Iversen

et al. 2023

IJMS

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Hidradenitis suppurativa is a chronic inflammatory skin disease with limited treatment options. The poorly understood pathogenesis hinders the development of effective treatments; therefore, a pressing need exists to further elucidate the molecular mechanisms in hidradenitis suppurativa. This study investigated the underlying inflammatory pathways and cell types in hidradenitis suppurativa using transcriptomic approaches with RNA sequencing of lesional and non-lesional skin biopsies from hidradenitis suppurativa, which was jointly analyzed with previously published transcriptomic data from atopic dermatitis and psoriasis patients. The differential expression and pathway enrichment analyses demonstrated the activation of multiple inflammatory processes, including the innate and adaptive immune systems, implicated in the hidradenitis suppurativa pathogenesis. In agreement, hidradenitis suppurativa exhibited a unique and heterogeneous cell type signature involving lymphoid and myeloid cells such as B cells and macrophages. Furthermore, hidradenitis suppurativa displayed increased expression of TH1/2/17 signatures with no predominant TH signatures unlike psoriasis (TH1/17) and atopic dermatitis (TH2). In summary, our study provides molecular insights into the pathomechanisms in hidradenitis suppurativa, revealing a strong and widespread immune activation, which may benefit from treatment strategies offering a broad immunomodulation of various key inflammatory pathways. Our data not only corroborate previously reported findings but also enhance our understanding of the immune dysregulation in hidradenitis suppurativa, uncovering novel and potential therapeutic targets.

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Topical and Systemic Retinoids in the Management of Hidradenitis Suppurativa: A Comprehensive Literature Review

Molinelli,

Gioacchini,

Marani

et al. 2024

Dermatol Ther (Heidelb)

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Hidradenitis suppurativa (HS) is a debilitating chronic skin disorder characterized by painful inflammatory nodules, abscesses and sinus tracts involving intertriginous areas and has an adverse impact on patient quality of life. Over the past decade, the therapeutic options of HS have increased significantly to comprise multiple modalities, including topical medication, systemic therapies (mainly antibiotics, retinoids, and biologics), surgical approaches, and lifestyle modifications. Biologics alone or in combination with surgery remain the treatment of choice for moderate to severe disease. However, non-biologic therapies (including retinoids) may be used as monotherapy for mild disease and in combination with biologics and surgical treatment in moderate to severe disease. Retinoids, specifically isotretinoin, acitretin, and alitretinoin, are historically used in the management of HS, supported by anecdotal evidence and with variable treatment response. Although the current American and European guidelines offer different recommendations on the use of retinoids in HS, retinoids remain a valuable ally in HS management. This review provides a comprehensive analysis of the current scientific literature on retinoid therapy (topical and systemic) in HS, highlighting disparities in mechanisms of action, efficacy, and safety to clarify their role in HS treatment.

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New Insight into the Molecular Pathomechanism and Immunomodulatory Treatments of Hidradenitis Suppurativa

Cited by 13 publications

References 216 publications

Therapeutic Potential of IL-1 Antagonism in Hidradenitis Suppurativa

Therapeutic Potential of IL-1 Antagonism in Hidradenitis Suppurativa

Transcriptomic Analysis of Hidradenitis Suppurativa: A Unique Molecular Signature with Broad Immune Activation

Topical and Systemic Retinoids in the Management of Hidradenitis Suppurativa: A Comprehensive Literature Review

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