{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T16:19:47Z","timestamp":1778602787854,"version":"3.51.4"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease. Topical or systemic corticosteroids are often used as the first-line treatment. However, long-term corticosteroid use may lead to significant side effects. Therefore, various adjuvant immunosuppressant therapies are used as steroid-sparing agents, with accumulating reports of biological treatments for severely recalcitrant BP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To describe the clinical and immunological features of a series of patients with recalcitrant BP treated with immunobiological therapies. To assess the efficacy and safety of their therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients receiving biological treatment for BP from two centers were assessed. Here, we described the clinical, immunopathological, and immunofluorescence findings of adult patients with BP and analyzed the clinical response and adverse events associated with various biological therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified nine eligible patients treated with rituximab (seven), omalizumab (three), or dupilumab (one). The mean age at diagnosis was 60.4 years, the average BP duration before biologic initiation was 1.9 years, and the average previous treatment failure was 2.11 therapies. The mean follow-up period from the first biological treatment to the last visit was 29.3 months. Satisfactory response, defined as clinical improvement, was achieved in 78% (7) of the patients, and total BP clearance was achieved in 55% (5) of the patients at the last follow-up visit. Additional rituximab courses improved the disease outcomes. No adverse events were reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Efficient and safe novel therapies can be considered in recalcitrant steroid-dependent BP non-responsive to conventional immunosuppressant therapies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1157250","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T05:09:02Z","timestamp":1682572142000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Biological treatment for bullous pemphigoid"],"prefix":"10.3389","volume":"14","author":[{"given":"Meital","family":"Oren-Shabtai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Mimouni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adi","family":"Nosrati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihi","family":"Atzmony","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baruch","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aviv","family":"Barzilai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Baum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61140-4","article-title":"Pemphigoid diseases","volume":"381","author":"Schmidt","year":"2013","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.det.2011.03.010","article-title":"Clinical features and practical diagnosis of bullous pemphigoid","volume":"29","author":"Schmidt","year":"2011","journal-title":"Dermatol Clin"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s0190-9622(99)70061-7","article-title":"Increased risk of bullous pemphigoid in male and very old patients: a population-based study on incidence","volume":"41","author":"Jung","year":"1999","journal-title":"J Am Acad Dermatol"},{"key":"B4","article-title":"Evaluation of histological criteria for bullous pemphigoid. correlation with antigens recognized by immunoblotting of anti-epidermal autoantibodies","volume":"20","author":"Courville","year":"2000","journal-title":"Ann Pathol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/0190-9622(90)70094-x","article-title":"Direct immunofluorescence studies of sodium chloride-separated skin in the differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita","volume":"22","author":"Gammon","year":"1990","journal-title":"J Am Acad Dermatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114812","article-title":"Isolation of a human epidermal cDNA corresponding to the 180-kD autoantigen recognized by bullous pemphigoid and herpes gestationis sera. immunolocalization of this protein to the hemidesmosome","volume":"86","author":"Diaz","year":"1990","journal-title":"J Clin Invest"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12072","article-title":"British Association of dermatologists\u2019 guidelines for the management of bullous pemphigoid 2012","volume":"167","author":"Venning","year":"2012","journal-title":"Br J Dermatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2012.04.008","article-title":"Corticosteroid use in autoimmune blistering diseases","volume":"32","author":"Frew","year":"2012","journal-title":"Immunol Allergy Clin North Am"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011592","article-title":"A comparison of oral and topical corticosteroids in patients with bullous pemphigoid","volume":"346","author":"Joly","year":"2002","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.412","article-title":"A comparison of two regimens of topical corticosteroids in the treatment of patients with bullous pemphigoid: a multicenter randomized study","volume":"129","author":"Joly","year":"2009","journal-title":"J Invest Dermatol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13717","article-title":"Management of bullous pemphigoid: the European dermatology forum consensus in collaboration with the European academy of dermatology and venereology","volume":"172","author":"Feliciani","year":"2015","journal-title":"Br J Dermatol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD002292.pub3","article-title":"Interventions for bullous pemphigoid","volume":"2010","author":"Kirtschig","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2011.06.003","article-title":"Evidence-based management of bullous pemphigoid","volume":"29","author":"Daniel","year":"2011","journal-title":"Dermatol Clin"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4103\/0378-6323.82400","article-title":"Evidence-based treatments for pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid: a systematic review","volume":"77","author":"Singh","year":"2011","journal-title":"Indian J Dermatol Venereol Leprol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-018-0401-6","article-title":"Rituximab and omalizumab for the treatment of bullous pemphigoid: a systematic review of the literature","volume":"20","author":"Kremer","year":"2019","journal-title":"Am J Clin Dermatol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.jaad.2020.01.089","article-title":"Dupilumab as a novel therapy for bullous pemphigoid: a multicenter case series","volume":"83","author":"Abdat","year":"2020","journal-title":"J Am Acad Dermatol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.738907","article-title":"Efficacy and safety of dupilumab in moderate-to-severe bullous pemphigoid","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.240","article-title":"B cells and immunological tolerance","volume":"129","author":"Manjarrez-Ordu\u00f1o","year":"2009","journal-title":"J Invest Dermatol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01919","article-title":"Effects of omalizumab on FcepsilonRI and IgE expression in lesional skin of bullous pemphigoid","volume":"10","author":"Seyed Jafari","year":"2019","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-014-8547-7","article-title":"Unraveling the significance of IgE autoantibodies in organ-specific autoimmunity: lessons learned from bullous pemphigoid","volume":"59","author":"Messingham","year":"2014","journal-title":"Immunol Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.800609","article-title":"Commentary: efficacy and safety of dupilumab in moderate-to-severe bullous pemphigoid","volume":"12","author":"Wang","year":"2021","journal-title":"Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/s12016-017-8633-4","article-title":"Autoimmune subepidermal bullous diseases of the skin and mucosae: clinical features, diagnosis, and management","volume":"54","author":"Amber","year":"2018","journal-title":"Clin Rev Allergy Immunol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.jaad.2018.02.021","article-title":"Diagnosis and management of pemphigus: recommendations of an international panel of experts","volume":"82","author":"Murrell","year":"2020","journal-title":"J Am Acad Dermatol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1016\/j.jaci.2015.12.1342","article-title":"Omalizumab for the treatment of chronic spontaneous urticaria: a meta-analysis of randomized clinical trials","volume":"137","author":"Zhao","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314768","article-title":"Dupilumab treatment in adults with moderate-to-severe atopic dermatitis","volume":"371","author":"Beck","year":"2014","journal-title":"N Engl J Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2011.06.032","article-title":"Definitions and outcome measures for bullous pemphigoid: recommendations by an international panel of experts","volume":"66","author":"Murrell","year":"2012","journal-title":"J Am Acad Dermatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051262","article-title":"Selective ablation of Ctip2\/Bcl11b in epidermal keratinocytes triggers atopic dermatitis-like skin inflammatory responses in adult mice","volume":"7","author":"Wang","year":"2012","journal-title":"PLoS One"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.788278","article-title":"A novel germline heterozygous BCL11B variant causing severe atopic disease and immune dysregulation","volume":"12","author":"Lu","year":"2021","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.928621","article-title":"Rituximab, omalizumab, and dupilumab treatment outcomes in bullous pemphigoid: a systematic review","volume":"13","author":"Cao","year":"2022","journal-title":"Front Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13633","article-title":"First-line combination therapy with rituximab and corticosteroids provides a high complete remission rate in moderate-to-severe bullous pemphigoid","volume":"173","author":"Cho","year":"2015","journal-title":"Br J Dermatol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-2116","article-title":"Efficacy of rituximab for pemphigus: a systematic review and meta-analysis of different regimens","volume":"95","author":"Wang","year":"2015","journal-title":"Acta Derm Venereol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2019.03.049","article-title":"Rituximab therapy in patients with bullous pemphigoid: a retrospective study of 20 patients","volume":"81","author":"Polansky","year":"2019","journal-title":"J Am Acad Dermatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.611549","article-title":"Case report: combination of omalizumab and dupilumab for recalcitrant bullous pemphigoid","volume":"11","author":"Seyed Jafari","year":"2020","journal-title":"Front Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.jaad.2019.07.060","article-title":"Pathophysiologic mechanisms of itch in bullous pemphigoid","volume":"83","author":"Hashimoto","year":"2020","journal-title":"J Am Acad Dermatol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.13984","article-title":"A review of bullous pemphigoid associated with PD-1 and PD-L1 inhibitors","volume":"57","author":"Lopez","year":"2018","journal-title":"Int J Dermatol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1177\/1203475420943260","article-title":"Cutaneous immune-related adverse events (irAEs) to immune checkpoint inhibitors: a dermatology perspective on management","volume":"25","author":"Muntyanu","year":"2021","journal-title":"J Cutan Med Surg"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1714","article-title":"PD-1 pathway inhibitors: immunooncology agents for restoring antitumor immune responses","volume":"36","author":"Medina","year":"2016","journal-title":"Pharmacotherapy"},{"key":"B38","doi-asserted-by":"publisher","first-page":"adv00377","DOI":"10.2340\/00015555-3740","article-title":"Bullous pemphigoid associated with anti-programmed cell death protein 1 and anti-programmed cell death ligand 1 therapy: a review of the literature","volume":"101","author":"Tsiogka","year":"2021","journal-title":"Acta Derm Venereol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1001\/jamaoncol.2019.2785","article-title":"Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer","volume":"5","author":"Pinato","year":"2019","journal-title":"JAMA Oncol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2017.0091","article-title":"Rituximab treatment of nivolumab-induced bullous pemphigoid","volume":"153","author":"Sowerby","year":"2017","journal-title":"JAMA Dermatol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/ajd.12987","article-title":"Nivolumab-induced bullous pemphigoid after radiotherapy and abscopal effect","volume":"60","author":"Grimaux","year":"2019","journal-title":"Australas J Dermatol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.13970","article-title":"Novel use of combination therapeutic plasma exchange and rituximab in the treatment of nivolumab-induced bullous pemphigoid","volume":"57","author":"Ridpath","year":"2018","journal-title":"Int J Dermatol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1186\/cc11304","article-title":"Clinical review: serious adverse events associated with the use of rituximab - a critical care perspective","volume":"16","author":"Kasi","year":"2012","journal-title":"Crit Care"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdcr.2016.05.009","article-title":"Development of bullous pemphigoid during nivolumab therapy","volume":"2","author":"Damsky","year":"2016","journal-title":"JAAD Case Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1157250\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T05:09:05Z","timestamp":1682572145000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1157250\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,27]]},"references-count":44,"alternative-id":["10.3389\/fimmu.2023.1157250"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1157250","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,27]]},"article-number":"1157250"}}