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Despite their similar pathogenesis featuring impaired adhesion of suprabasal keratinocytes as a result of defective ATPases in epidermal calcium channels, the two diseases differ considerably in clinical presentation and therapeutic options. Darier disease is characterized by reddish brown, keratotic papules in seborrheic and intertriginous areas, which may coalesce into extensive lesions. Individuals affected with Hailey\u2010Hailey disease primarily develop intertriginous papulovesicles and small blisters, which often evolve into erythematous plaques with erosions and painful fissures. Quality of life is significantly reduced because of complaints (itch, burning sensation, pain), body malodor and chronicity. Therapeutic options remain limited. Antiseptics and intermittent topical corticosteroids are a cornerstone of therapy, and systemic anti\u2010infective treatment is often required in cases of superinfection. Ablative surgical interventions such as dermabrasion and CO<jats:sub>2<\/jats:sub> laser surgery can lead to long\u2010term remissions in intertriginous Hailey\u2010Hailey disease, while temporary relief may also be achieved by intralesional injections of botulinum toxin. Of the systemic medications available for Darier disease, acitretin, which is approved for this purpose, has the best supporting evidence. The efficacy of immunosuppressants and immune modulators is inconsistent. Low\u2010dose naltrexone produces more satisfactory results in Hailey\u2010Hailey than Darier disease. The present CME article summarizes current knowledge of the two dermatoses, taking recent developments into account.<\/jats:p>","DOI":"10.1111\/ddg.14619","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T07:06:14Z","timestamp":1634799974000},"page":"1478-1501","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Darier and Hailey\u2010Hailey disease: update 2021"],"prefix":"10.1111","volume":"19","author":[{"given":"Danielle Franziska","family":"Rogner","sequence":"first","affiliation":[{"name":"Hospital and Clinic for Dermatology and Allergology Klinikum Rechts der Isar Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Lammer","sequence":"additional","affiliation":[{"name":"Hospital and Clinic for Dermatology and Allergology Klinikum Rechts der Isar Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Zink","sequence":"additional","affiliation":[{"name":"Hospital and Clinic for Dermatology and Allergology Klinikum Rechts der Isar Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Hamm","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology University W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"e_1_2_29_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-019-00477-z"},{"key":"e_1_2_29_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00128071-200304020-00003"},{"key":"e_1_2_29_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.12082"},{"key":"e_1_2_29_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601966200"},{"key":"e_1_2_29_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23164"},{"key":"e_1_2_29_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2004.05904.x"},{"key":"e_1_2_29_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.8"},{"key":"e_1_2_29_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32679"},{"key":"e_1_2_29_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-8343(00)00050-5"},{"key":"e_1_2_29_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.12111"},{"key":"e_1_2_29_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2011.04355.x"},{"key":"e_1_2_29_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjps.2008.06.060"},{"key":"e_1_2_29_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0190-9622(92)70154-8"},{"key":"e_1_2_29_15_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2004.45.5.956"},{"key":"e_1_2_29_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2010.09876.x"},{"key":"e_1_2_29_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.t01-1-12045.x"},{"key":"e_1_2_29_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.15457"},{"key":"e_1_2_29_19_1","volume-title":"6: The Nail in Dermatological Disease","author":"Holzberg M BR","year":"2012"},{"key":"e_1_2_29_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jobcr.2018.05.001"},{"key":"e_1_2_29_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/IOP.0b013e31820cd645"},{"key":"e_1_2_29_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1982.01650160068028"},{"key":"e_1_2_29_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ad.2017.02.012"},{"key":"e_1_2_29_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/ddg.14179_g"},{"issue":"6","key":"e_1_2_29_25_1","first-page":"449","article-title":"Brun AM. 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