{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:34:33Z","timestamp":1787160873413,"version":"build-2736575974"},"reference-count":95,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,26]],"date-time":"2021-12-26T00:00:00Z","timestamp":1640476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Chronic inflammation and dysregulated epithelial differentiation, especially of hair follicle keratinocytes, have been suggested as the major pathogenetic pathways of hidradenitis suppurativa\/acne inversa (HS). On the other hand, obesity and metabolic syndrome have additionally been considered as an important risk factor. With adalimumab, a drug has already been approved and numerous other compounds are in advanced-stage clinical studies. A systematic review was conducted to detect and corroborate HS pathogenetic mechanisms at the molecular level and identify HS molecular markers. The obtained data were used to confirm studied and off-label administered drugs and to identify additional compounds for drug repurposing. A robust, strongly associated group of HS biomarkers was detected. The triad of HS pathogenesis, namely upregulated inflammation, altered epithelial differentiation and dysregulated metabolism\/hormone signaling was confirmed, the molecular association of HS with certain comorbid disorders, such as inflammatory bowel disease, arthritis, type I diabetes mellitus and lipids\/atherosclerosis\/adipogenesis was verified and common biomarkers were identified. The molecular suitability of compounds in clinical studies was confirmed and 31 potential HS repurposing drugs, among them 10 drugs already launched for other disorders, were detected. This systematic review provides evidence for the importance of molecular studies to advance the knowledge regarding pathogenesis, future treatment and biomarker-supported clinical course follow-up in HS.<\/jats:p>","DOI":"10.3390\/pharmaceutics14010044","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:06:54Z","timestamp":1640567214000},"page":"44","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Hidradenitis Suppurativa and Comorbid Disorder Biomarkers, Druggable Genes, New Drugs and Drug Repurposing\u2014A Molecular Meta-Analysis"],"prefix":"10.3390","volume":"14","author":[{"given":"Viktor A.","family":"Zouboulis","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Universitaetsklinikum Hamburg-Eppendorf (UKE), 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin C.","family":"Zouboulis","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH) Zurich, 8092 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1646-2608","authenticated-orcid":false,"given":"Christos C.","family":"Zouboulis","sequence":"additional","affiliation":[{"name":"Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, 06847 Dessau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1159\/000431175","article-title":"Hidradenitis suppurativa\/acne inversa: Criteria for diagnosis, severity assessment, classification and disease evaluation","volume":"231","author":"Zouboulis","year":"2015","journal-title":"Dermatology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Del Duca, E., Morelli, P., Bennardo, L., Di Raimondo, C., and Nistic\u00f2, S.P. (2020). Cytokine pathways and investigational target therapies in hidradenitis suppurativa. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228436"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1111\/jdv.16147","article-title":"Alterations in innate immunity and epithelial cell differentiation are the molecular pillars of hidradenitis suppurativa","volume":"34","author":"Zouboulis","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kaleta, K.P., Nikolakis, G., Hossini, A.M., Balthasar, O., Almansouri, D., Vaiopoulos, A., Knolle, J., Boguslawska, A., Wojas-Pelc, A., and Zouboulis, C.C. (2021). Metabolic disorders\/obesity is a primary risk factor in hidradenitis suppurativa: An immunohistochemical real-world approach. Dermatology.","DOI":"10.1159\/000517017"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1111\/jdv.12966","article-title":"European S1 guideline for the treatment of hidradenitis suppurativa\/acne inversa","volume":"29","author":"Zouboulis","year":"2015","journal-title":"J Eur. Acad. Dermatol. Venereol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/jdv.15233","article-title":"Hidradenitis suppurativa\/acne inversa: A practical framework for treatment optimization\u2014Systematic review and recommendations from the HS ALLIANCE working group","volume":"33","author":"Zouboulis","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1111\/exd.14214","article-title":"What causes hidradenitis suppurativa? 15 years after","volume":"29","author":"Zouboulis","year":"2020","journal-title":"Exp. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/exd.14338","article-title":"Target molecules for future hidradenitis suppurativa treatment","volume":"30","author":"Zouboulis","year":"2021","journal-title":"Exp. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1056\/NEJMoa1504370","article-title":"Two phase 3 trials of adalimumab treatment of hidradenitis suppurativa","volume":"375","author":"Kimball","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1001\/jamadermatol.2021.2905","article-title":"Bimekizumab in moderate-to-severe hidradenitis suppurativa: A phase 2, double-blind, placebo-controlled randomized clinical trial","volume":"157","author":"Glatt","year":"2021","journal-title":"JAMA Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e251","DOI":"10.1111\/jdv.16976","article-title":"Drug repurposing through drug-gene interaction profiles for hidradenitis suppurativa\/acne inversa treatment","volume":"35","author":"Zouboulis","year":"2021","journal-title":"J Eur Acad Dermatol Venereol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1111\/bjd.19627","article-title":"An additional drug repurposing study for hidradenitis suppurativa\/acne inversa","volume":"184","author":"Zouboulis","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.ejmech.2018.04.018","article-title":"Discovery of new erbB4 inhibitors: Repositioning an orphan chemical library by inverse virtual screening","volume":"152","author":"Giordano","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yu, J.L., Dai, Q.Q., and Li, G.B. (2021). Deep learning in target prediction and drug repositioning: Recent advances and challenges. Drug Discov. Today.","DOI":"10.1016\/j.drudis.2021.10.010"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"Bmj"},{"key":"ref_16","unstructured":"(2021, November 15). Gene Expression Omnibus, Available online: https:\/\/www.ncbi.nlm.nih.gov\/geo\/."},{"key":"ref_17","unstructured":"(2021, November 15). HUGO Gene Nomenclature Committee. Available online: https:\/\/www.genenames.org\/tools\/multi-symbol-checker\/."},{"key":"ref_18","unstructured":"(2021, November 15). Biological DataBase network, Available online: https:\/\/biodbnet-abcc.ncifcrf.gov\/db\/db2db.php."},{"key":"ref_19","unstructured":"(2021, November 15). g:Profiler. Available online: https:\/\/biit.cs.ut.ee\/gprofiler\/gost."},{"key":"ref_20","unstructured":"(2021, November 15). Kyoto Encyclopedia of Genes and Genomes. Available online: https:\/\/www.genome.jp\/kegg\/."},{"key":"ref_21","unstructured":"(2021, November 15). Reactome. Available online: https:\/\/reactome.org\/."},{"key":"ref_22","unstructured":"(2021, November 15). WikiPathways. Available online: https:\/\/www.wikipathways.org\/."},{"key":"ref_23","unstructured":"(2021, November 15). Human Phenotype Ontology. Available online: https:\/\/hpo.jax.org\/app\/."},{"key":"ref_24","unstructured":"(2021, November 15). The Drug Repurposing Hub. Available online: https:\/\/s3.amazonaws.com\/data.clue.io\/repurposing\/downloads\/repurposing_drugs_20200324.txt."},{"key":"ref_25","unstructured":"(2021, November 15). Gene Cards, The Human Gene Database. Available online: https:\/\/www.genecards.org\/."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e139932","DOI":"10.1172\/jci.insight.139932","article-title":"Immunopathogenesis of hidradenitis suppurativa and response to anti-TNF-alpha therapy","volume":"5","author":"Lowe","year":"2020","journal-title":"JCI Insight"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hoffman, L.K., Tomalin, L.E., Schultz, G., Howell, M.D., Anandasabapathy, D., Alavi, A., Su\u00e1rez-Fari\u00f1as, M., and Lowes, M.A. (2018). Integrating the skin and blood transcriptomes and serum proteome in hidradenitis suppurativa reveals complement dysregulation and a plasma cell signature. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0203672"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s00403-019-02018-4","article-title":"Circulating levels of adiponectin, leptin, resistin and visfatin in non-diabetics patients with hidradenitis suppurativa","volume":"312","author":"Vilanova","year":"2020","journal-title":"Arch. Dermatol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s00403-017-1752-1","article-title":"The microRNA effector RNA-induced silencing complex in hidradenitis suppurativa: A significant dysregulation within active inflammatory lesions","volume":"309","author":"Hessam","year":"2017","journal-title":"Arch. Dermatol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1007\/s00011-020-01381-7","article-title":"Transcriptomic analysis of hidradenitis suppurativa skin suggests roles for multiple inflammatory pathways in disease pathogenesis","volume":"69","author":"Rumberger","year":"2020","journal-title":"Inflamm. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1016\/j.jid.2020.04.011","article-title":"Lipidomics profiling of hidradenitis suppurativa skin lesions reveals lipoxygenase pathway dysregulation and accumulation of proinflammatory leukotriene B4","volume":"140","author":"Penno","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Coates, M., Mariottoni, P., Corcoran, D.L., Kirshner, H.F., Jaleel, T., Brown, D.A., Brooks, S.R., Murray, J., Morasso, M.I., and MacLeod, A.S. (2019). The skin transcriptome in hidradenitis suppurativa uncovers an antimicrobial and sweat gland gene signature which has distinct overlap with wounded skin. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0216249"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1111\/ced.13959","article-title":"Transcriptome patterns in hidradenitis suppurativa: Support for the role of antimicrobial peptides and interferon pathways in disease pathogenesis","volume":"44","author":"Shanmugam","year":"2019","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1111\/bjd.14371","article-title":"Gene expression profiling of skin and blood in hidradenitis suppurativa","volume":"174","author":"Blok","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1097\/DAD.0000000000000206","article-title":"Immunohistochemical analysis of steroid hormone receptors in hidradenitis suppurativa","volume":"37","author":"Buimer","year":"2015","journal-title":"Am. J. Dermatopathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1111\/jdv.15354","article-title":"Apremilast for moderate hidradenitis suppurativa: No significant change in lesional skin inflammatory biomarkers","volume":"33","author":"Vossen","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_37","first-page":"413","article-title":"Complement activation in hidradenitis suppurativa: A new pathway of pathogenesis?","volume":"179","author":"Kanni","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1111\/bjd.14075","article-title":"Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa","volume":"173","author":"Kelly","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S193","DOI":"10.1016\/j.jid.2016.06.206","article-title":"Profiling of the transcriptome in hidradenitis suppurativa: A case-control sample","volume":"136","author":"Vossen","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1016\/j.jid.2018.11.018","article-title":"The IL-1 pathway is hyperactive in hidradenitis suppurativa and contributes to skin infiltration and destruction","volume":"139","author":"Wolk","year":"2019","journal-title":"J. Investig. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1111\/all.13665","article-title":"Novel cytokine and chemokine markers of hidradenitis suppurativa reflect chronic inflammation and itch","volume":"74","author":"Vossen","year":"2019","journal-title":"Allergy"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1016\/j.jid.2020.03.064","article-title":"Hidradenitis suppurativa RNA-seq skin transcriptome overlaps with psoriasis vulgaris and reveals a marked upregulation of multiple targetable cytokines","volume":"140","author":"Garcet","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1111\/bjd.16600","article-title":"Collagen deposition in chronic hidradenitis suppurativa: Potential role for CD163(+) macrophages","volume":"179","author":"Byrd","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1016\/j.jid.2016.04.036","article-title":"Intrinsic defect in keratinocyte function leads to inflammation in hidradenitis suppurativa","volume":"136","author":"Hotz","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e139930","DOI":"10.1172\/jci.insight.139930","article-title":"Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis","volume":"5","author":"Gudjonsson","year":"2020","journal-title":"JCI Insight"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.4049\/jimmunol.0903907","article-title":"Deficiency of IL-22 contributes to a chronic inflammatory disease: Pathogenetic mechanisms in acne inversa","volume":"186","author":"Wolk","year":"2011","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1111\/exd.13973","article-title":"E-cadherin and p120ctn protein expression are lost in hidradenitis suppurativa lesions","volume":"28","author":"Nelson","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jaad.2017.03.016","article-title":"Gene expression of sphingolipid metabolism pathways is altered in hidradenitis suppurativa","volume":"77","author":"Dany","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_49","first-page":"736","article-title":"Chitinase-3-like protein 1 (YKL-40): Novel biomarker of hidradenitis suppurativa disease activity?","volume":"95","author":"Matusiak","year":"2015","journal-title":"Acta Dermatovenereol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"141","DOI":"10.21873\/invivo.11450","article-title":"Chitinase-3-like protein 1 (YKL-40) Is expressed in lesional skin in hidradenitis suppurativa","volume":"33","author":"Salomon","year":"2019","journal-title":"Vivo"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/bjd.19795","article-title":"Activity and components of the granulocyte colony-stimulating factor pathway in hidradenitis suppurativa","volume":"185","author":"Wolk","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.jaad.2011.07.020","article-title":"Expression of innate defense antimicrobial peptides in hidradenitis suppurativa","volume":"66","author":"Hofmann","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1001\/archdermatol.2011.315","article-title":"Hidradenitis suppurativa: The role of deficient cutaneous innate immunity","volume":"148","author":"Khammari","year":"2012","journal-title":"Arch. Dermatol."},{"key":"ref_54","first-page":"18","article-title":"A composite biomarker score for the diagnosis of hidradenitis suppurativa","volume":"28","author":"Argyropoulou","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jdermsci.2016.02.009","article-title":"Inflammation induced changes in the expression levels of components of the microRNA maturation machinery Drosha, Dicer, Drosha co-factor DGRC8 and Exportin-5 in inflammatory lesions of hidradenitis suppurativa patients","volume":"82","author":"Hessam","year":"2016","journal-title":"J. Dermatol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1111\/j.1365-2133.2011.10254.x","article-title":"Elevated levels of tumour necrosis factor (TNF)-\u03b1, interleukin (IL)-1\u03b2 and IL-10 in hidradenitis suppurativa skin: A rationale for targeting TNF-\u03b1 and IL-1\u03b2","volume":"164","author":"Dik","year":"2011","journal-title":"Br. J. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1111\/bjd.12234","article-title":"Myeloid marker S100A8\/A9 and lymphocyte marker, soluble interleukin 2 receptor: Biomarkers of hidradenitis suppurativa disease activity?","volume":"168","author":"Wieland","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jaad.2016.08.036","article-title":"Interleukin 6 and high-sensitivity C-reactive protein are potential predictive markers of response to infliximab in hidradenitis suppurativa","volume":"76","author":"Cornille","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.jaad.2016.10.042","article-title":"Increased interleukin (IL)-17 serum levels in patients with hidradenitis suppurativa: Implications for treatment with anti-IL-17 agents","volume":"76","author":"Matusiak","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.jaad.2010.07.010","article-title":"Expression of the IL-23\/Th17 pathway in lesions of hidradenitis suppurativa","volume":"65","author":"Schlapbach","year":"2011","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1111\/jdv.14389","article-title":"Increased expression of the interleukin-36 cytokines in lesions of hidradenitis suppurativa","volume":"31","author":"Thomi","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00403-019-02012-w","article-title":"Serum IL-36alpha, IL-36beta, and IL-36gamma levels in patients with hidradenitis suppurativa: Association with disease characteristics, smoking, obesity, and metabolic syndrome","volume":"312","author":"Hayran","year":"2020","journal-title":"Arch. Dermatol. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s00403-018-1867-z","article-title":"Visfatin and insulin levels and cigarette smoking are independent risk factors for hidradenitis suppurativa: A case-control study","volume":"310","author":"Akdogan","year":"2018","journal-title":"Arch. Dermatol. Res."},{"key":"ref_64","first-page":"S235","article-title":"Lipocalin-2 as a novel biomarker in acne inversa","volume":"136","author":"Wolk","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1111\/bjd.14338","article-title":"Ustekinumab in hidradenitis suppurativa: Clin-ical results and a search for potential biomarkers in serum","volume":"174","author":"Blok","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4097574","DOI":"10.1155\/2016\/4097574","article-title":"MMP8 is increased in lesions and blood of acne inversa patients: A potential link to skin destruction and metabolic alterations","volume":"2016","author":"Tsaousi","year":"2016","journal-title":"Mediators Inflamm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1126\/science.1196284","article-title":"Gamma-secretase gene mutations in familial acne inversa","volume":"330","author":"Wang","year":"2010","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1111\/j.1365-2133.2007.08425.x","article-title":"Toll-like receptor 2 is highly expressed in lesions of acne inversa and colocalizes with C-type lectin receptor","volume":"158","author":"Hunger","year":"2008","journal-title":"Br. J. Dermatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00403-010-1028-5","article-title":"Cutaneous PGP 9.5 distribution patterns in hidradenitis suppurativa","volume":"302","author":"Sartorius","year":"2010","journal-title":"Arch. Dermatol. Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Fabregat, A., Sidiropoulos, K., Viteri, G., Forner, O., Marin-Garcia, P., Arnau, V., D\u2019Eustachio, P., Stein, L., and Hermjakob, H. (2017). Reactome pathway analysis: A high-performance in-memory approach. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1559-2"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.12688\/f1000research.17268.1","article-title":"A systematic review and critical evaluation of immunohistochemical associations in hidradenitis suppurativa","volume":"7","author":"Frew","year":"2018","journal-title":"F1000Research"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.3389\/fimmu.2018.02965","article-title":"Hidradenitis suppurativa: A systematic review integrating inflammatory pathways into a cohesive pathogenic model","volume":"9","author":"Vossen","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.jid.2018.10.020","article-title":"Apocrine gland-rich skin has a non-inflammatory IL-17 related immune milieu, which turns to inflammatory IL-17 mediated disease in hidradenitis suppurativa","volume":"139","author":"Jenei","year":"2019","journal-title":"J. Investig. Dermatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrd4518","article-title":"Targeting the IL-17-T(H)17 pathway","volume":"14","author":"Bartlett","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3575","DOI":"10.1128\/IAI.00596-16","article-title":"Interleukin-17A (IL-17A) and IL-17F are critical for antimicrobial peptide production and clearance of Staphylococcus aureus nasal colonization","volume":"84","author":"Archer","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1001\/jamadermatol.2015.3903","article-title":"Safety and efficacy of anakinra in severe hidradenitis suppurativa: A randomized clinical trial","volume":"152","author":"Tzanetakou","year":"2016","journal-title":"JAMA Dermatol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Mintoff, D., Benhadou, F., Pace, N.P., and Frew, J.W. (2021). Metabolic syndrome and hidradenitis suppurativa: Epidemiological, molecular, and therapeutic aspects. Int. J. Dermatol.","DOI":"10.1111\/ijd.15910"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"718929","DOI":"10.3389\/fphar.2021.718929","article-title":"Adiponectin inhibits the production of TNF-alpha, IL-6 and chemokines by human lung macrophages","volume":"12","author":"Salvator","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"934","DOI":"10.5187\/jast.2021.e87","article-title":"Effect of ciglitazone on adipogenic transdifferentiation of bovine skeletal muscle satellite cells","volume":"63","author":"Zhang","year":"2021","journal-title":"J. Anim. Sci. Technol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4161\/derm.2.1.12490","article-title":"Comorbidities of hidradenitis suppurativa (acne inversa)","volume":"2","author":"Fimmel","year":"2010","journal-title":"Derm.-Endocrinol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s13555-020-00354-2","article-title":"Review of comorbidities of hidradenitis suppurativa: Implications for daily clinical practice","volume":"10","author":"Tzellos","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jaad.2018.05.040","article-title":"Long-term adalimumab efficacy in patients with moderate-to-severe hidradenitis suppurativa\/acne inversa: 3-year results of a phase 3 open-label extention study","volume":"80","author":"Zouboulis","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1080\/1744666X.2016.1221762","article-title":"Adalimumab for the treatment of hidradenitis suppurativa\/acne inversa","volume":"12","author":"Zouboulis","year":"2016","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/bjd.12884","article-title":"Acitretin treatment for hidradenitis suppurativa: A prospective series of 17 patients","volume":"171","author":"Matusiak","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.jaad.2020.05.007","article-title":"The effect of subcutaneous brodalumab on clinical disease activity in hidradenitis suppurativa: An open-label cohort study","volume":"83","author":"Frew","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/j.1365-2133.1986.tb05740.x","article-title":"A double-blind controlled cross-over trial of cyproterone acetate in females with hidradenitis suppurativa","volume":"115","author":"Mortimer","year":"1986","journal-title":"Br. J. Dermatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s40257-019-00442-w","article-title":"Is there a role for antiandrogen therapy for hidradenitis suppurativa? A systematic review of published data","volume":"20","author":"Nikolakis","year":"2019","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.jaad.2020.12.089","article-title":"The efficacy and tolerability of tetracyclines and clindamycin plus rifampicin for the treatment of hidradenitis suppurativa: Results of a prospective European cohort study","volume":"85","author":"Tzellos","year":"2021","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jaad.2008.11.898","article-title":"A prospective clinical trial of open-label etanercept for the treatment of hidradenitis suppurativa","volume":"60","author":"Lee","year":"2009","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1001\/archdermatol.2010.72","article-title":"Treatment of hidradenitis suppurativa with etanercept injection","volume":"146","author":"Adams","year":"2010","journal-title":"Arch. Dermatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1016\/j.jid.2021.04.026","article-title":"Golimumab for the treatment of hidradenitis suppurativa in patients with previous TNF-alpha treatment failure","volume":"141","author":"Hamad","year":"2021","journal-title":"J. Investig. Dermatol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jaad.2009.06.050","article-title":"Infliximab therapy for patients with moderate to severe hidradenitis suppurativa: A randomized, double-blind, placebo-controlled crossover trial","volume":"62","author":"Grant","year":"2010","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1111\/j.1468-3083.2012.04668.x","article-title":"Metformin for the treatment of hidradenitis suppurativa: A little help along the way","volume":"27","author":"Verdolini","year":"2013","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/bjd.17822","article-title":"Open-label, investigator-initiated, single-site exploratory trial evaluating secukinumab, an anti-interleukin-17A monoclonal antibody, for patients with moderate-to-severe hidradenitis suppurativa","volume":"181","author":"Prussick","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/bjd.18877","article-title":"Clinical efficacy of complement C5a inhibition by IFX-1 in hidradenitis suppurativa: An open-label single-arm trial in patients not eligible for adalimumab","volume":"183","author":"Argyropoulou","year":"2020","journal-title":"Br. J. Dermatol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/1\/44\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:53:46Z","timestamp":1760169226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/1\/44"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,26]]},"references-count":95,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["pharmaceutics14010044"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14010044","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.741491784.793591186","asserted-by":"object"}]},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,26]]}}}