{"doi":"10.1073/pnas.2319797121","title":"Molecular chaos under the skin: Epigenetic reprogramming in hidradenitis suppurativa","abstract":"Hidradenitis suppurativa (HS) is a human autoinflammatory disorder that primarily involves hair follicles in intertriginous skin areas of the groin, axillary, perineal, perianal, and inframammary regions (1).The clinical manifestations of HS are recurrent painful nodules and abscesses in sweaty areas of the body, fistulas, and severe scarring.With an early onset (in the early 20s), HS appears to have a female predominance (with a 3:1 sex ratio) and significant gender differences in epidemiology and disease manifestations (2).Although HS isn't a contagious disease, it significantly compromises the quality of life caused by physical and psychological distress including intense pain, work disability, sexual dysfunction, social isolation, and depression (3).Unfortunately, HS is often associated with long diagnostic delays, due to disease unawareness among physicians.Further, HS has complex and heterogeneous histopathologic features and, in some cases, it is difficult to distinguish HS from other inflammatory skin diseases.The clinical features of HS appear to cover a broad histologic spectrum, which needs to be carefully considered.Smith et al. performed a comprehensive and systematic review of the histopathology of HS and confirmed a high prevalence of follicular occlusion, follicular hyperkeratosis, and hyperplasia of the follicular epithelium (4).Unfortunately, the medical treatment of HS is challenging due to the recurrent nature of this disease and the lack of detailed understanding of the pathogenesis of HS, which was originally thought to be an infectious condition of the apocrine sweat gland as suggested by its name (hidros meaning \"sweat\" and aden meaning \"gland\") (3).In fact, there is no currently available curative therapy for HS.The existing treatments for HS are limited to only managing its symptoms, and surgical removal of affected skin areas remains the decisive option for nonresponder patients.Hence, HS presents an unmet medical need for which additional mechanistic understanding and therapeutic options are required.Based on current literature, inflammatory pathways have been considered the key factors in HS pathogenesis.Thus, the available therapies for the management of HS symptoms target various signaling molecules responsible for an exaggerated inflammatory response such as tumor necrosis factor alpha (TNF), and interleukins (IL) including and IL12/23 (5,6).However, so far, the US Food and Drug Administration has only approved Adalimumab, a humanized monoclonal antibody against TNF, for the treatment of moderate-to-severe HS (5).Indeed, one of the main hurdles in the development of effective therapeutics is due to the lack of proper understanding of pathophysiological mechanisms of HS.Further, the interplay among genetics, hormonal status, inflammatory, and immune regulations remains unclear.The involvement of epigenetics in the pathophysiology of HS is not well understood.In addition, a detailed understanding of epithelial cell reprogramming in the context of chronic inflammation in HS is required.Moreover, studies focusing on immune dysregulation in HS are urgently needed to identify novel and specific pathways that may provide clues toward generating more effective treatments.In this issue of PNAS, Jin et al. ( 7) present clinically relevant findings defining altered transcriptional states of the skin lesions at single-cell resolution in the human inflammatory disorder HS and determined the epigenetic reprogramming","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":415397,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9695,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":406491,"name":"Nihal Ahmad","orcid":"0000-0002-4239-9887","position":1,"is_corresponding":false},{"id":413407,"name":"Gagan Chhabra","orcid":"0000-0001-5205-7218","position":0,"is_corresponding":true}],"reference_count":21,"raw_metadata":null,"created_at":"2026-07-19T01:22:12.933438Z","pmid":"38147564","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}