{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:05:56Z","timestamp":1790132756900,"version":"4.0.1"},"reference-count":44,"publisher":"PAGEPress Publications","issue":"4","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dermatol Reports"],"abstract":"<jats:p>Pemphigus is a severe autoimmune blistering disorder that significantly affects patients\u2019 quality of life. While corticosteroids and immunosuppressive agents are commonly used, they have substantial side effects, highlighting the need for safer alternatives. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, has shown efficacy in treating other autoimmune diseases and may offer promise for pemphigus. This systematic review evaluated the clinical outcomes, safety, and potential role of apremilast in the treatment of pemphigus by synthesizing available case reports and series. A literature search was conducted across multiple databases (PubMed, EMBASE, Cochrane, Web of Science, ScienceDirect, and Google Scholar) for case reports and series involving apremilast in pemphigus. Inclusion criteria were a confirmed pemphigus diagnosis and apremilast treatment. Five studies (four case reports and one case series) involving 7 patients were included. Apremilast led to significant clinical improvement in 4 patients, with reductions in disease activity, lesion severity, and symptom scores (Pemphigus Disease Area Index [PDAI], Autoimmune Bullous Skin Disorder Intensity Score [ABSIS], Visual Analog Scale [VAS], and Numerical Rating Score [NRS]). Increases in regulatory T cells and decreases in anti-desmoglein antibodies were observed. No serious adverse events were reported, although one study noted treatment failure, possibly due to short follow-up or concurrent infections. Apremilast appears to be a promising treatment for therapy-resistant or corticosteroid-intolerant pemphigus patients. Although the evidence is limited, it supports apremilast\u2019s efficacy and favorable safety profile. Further research with larger sample sizes and randomized controlled trials is necessary to confirm these findings.<\/jats:p>","DOI":"10.4081\/dr.2025.10245","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T08:07:40Z","timestamp":1746605260000},"source":"Crossref","is-referenced-by-count":5,"title":["The efficacy of apremilast in pemphigus: a systematic review of case reports"],"prefix":"10.4081","volume":"17","author":[{"given":"Roudin H.","family":"Alhasawi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esraa A.","family":"Shaheen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura M.","family":"Alshabanat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9455-4586","authenticated-orcid":false,"given":"Reem","family":"Brashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7037-2537","authenticated-orcid":false,"given":"Walaa Abdu","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1742-7540","authenticated-orcid":false,"given":"Shumukh H.","family":"Alqahtani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1340-7515","authenticated-orcid":false,"given":"Ethar G.","family":"Alharbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazin","family":"Aljabri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2549","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"key":"34600","doi-asserted-by":"crossref","unstructured":"1. 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J Dermatol 2023;50:212-21.","DOI":"10.1111\/1346-8138.16641"},{"key":"34604","doi-asserted-by":"crossref","unstructured":"5. Brodszky V, Tam\u00e1si B, Hajdu K, et al. Disease burden of patients with pemphigus from a societal perspective. Expert Rev Pharmacoecon Outcomes Res 2021;21:77-86.","DOI":"10.1080\/14737167.2020.1722104"},{"key":"34605","doi-asserted-by":"crossref","unstructured":"6. Kridin K, Schmidt E. Epidemiology of Pemphigus. JID Innov 2021;1:100004.","DOI":"10.1016\/j.xjidi.2021.100004"},{"key":"34606","doi-asserted-by":"crossref","unstructured":"7. Hasanaj A, Zaki F, Harman KE, et al. Cause\u2010specific mortality in people with bullous pemphigoid and pemphigus vulgaris: a systematic review and meta\u2010analysis. Br J Dermatol 2022;186:359-61.","DOI":"10.1111\/bjd.20759"},{"key":"34607","doi-asserted-by":"crossref","unstructured":"8. Kridin K, Mruwat N, Ludwig RJ. Association of Rituximab With Risk of Long-term Cardiovascular and Metabolic Outcomes in Patients With Pemphigus. JAMA Dermatol 2023;159:56-61.","DOI":"10.1001\/jamadermatol.2022.5182"},{"key":"34608","doi-asserted-by":"crossref","unstructured":"9. Zhao W, Wang J, Zhu H, Pan M. Comparison of Guidelines for Management of Pemphigus: a Review of Systemic Corticosteroids, Rituximab, and Other Immunosuppressive Therapies. Clin Rev Allergy Immunol 2021;61:351-62.","DOI":"10.1007\/s12016-021-08882-1"},{"key":"34609","doi-asserted-by":"crossref","unstructured":"10. Sparling K, Butler DC. Oral Corticosteroids for Skin Disease in the Older Population: Minimizing Potential Adverse Effects. Drugs Aging 2024;41:795-808.","DOI":"10.1007\/s40266-024-01143-8"},{"key":"34610","doi-asserted-by":"crossref","unstructured":"11. Zhang Q, Yu L, Wan L, et al. Case report: Managing pemphigus foliaceus using apremilast without systemic glucocorticosteroids or immunosuppressive agents. 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Nat Commun 2023;14:116.","DOI":"10.1038\/s41467-022-35741-0"},{"key":"34614","doi-asserted-by":"crossref","unstructured":"15. Meier K, Holstein J, Solimani F, et al. Case Report: Apremilast for Therapy-Resistant Pemphigus Vulgaris. Front Immunol 2020;11:588315.","DOI":"10.3389\/fimmu.2020.588315"},{"key":"34615","doi-asserted-by":"crossref","unstructured":"16. Zhang Q, Yu L, Wan L, et al. Ineffectiveness of apremilast in moderate-to-severe pemphigus: A case series of three patients. Australas J Dermatol 2024;65:e121-2.","DOI":"10.1111\/ajd.14312"},{"key":"34616","doi-asserted-by":"crossref","unstructured":"17. Zhou Y, Xiao Y, Wang Y, Li W. Refractory atypical IgA pemphigus successfully treated with apremilast. J Dermatol 2024;51:e86-7.","DOI":"10.1111\/1346-8138.17007"},{"key":"34617","doi-asserted-by":"crossref","unstructured":"18. Delvaux C, Bohelay G, Sitbon IY, et al. Activity of apremilast in a patient with severe pemphigus vulgaris: case report. Front Immunol 2024;15:1404185.","DOI":"10.3389\/fimmu.2024.1404185"},{"key":"34618","doi-asserted-by":"crossref","unstructured":"19. Mease PJ, Hatemi G, Paris M, et al. Apremilast Long-Term Safety Up to 5 Years from 15 Pooled Randomized, Placebo-Controlled Studies of Psoriasis, Psoriatic Arthritis, and Beh\u00e7et\u2019s Syndrome. Am J Clin Dermatol 2023;24:809-20.","DOI":"10.1007\/s40257-023-00783-7"},{"key":"34619","doi-asserted-by":"crossref","unstructured":"20. Joly P, Maho-Vaillant M, Prost-Squarcioni C, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet 2017;389:2031-40.","DOI":"10.1016\/S0140-6736(17)30070-3"},{"key":"34620","unstructured":"21. DrugBank. DB05676: Uses, interactions, mechanism of action [Internet]. DrugBank Online; [cited 2025 Apr 3]. Available from: https:\/\/go.drugbank.com\/drugs\/DB05676"},{"key":"34621","unstructured":"22. DrugBank. Rituximab: Uses, interactions, mechanism of action [Internet]. DrugBank Online; [cited 2025 Apr 3]. Available from: https:\/\/go.drugbank.com\/drugs\/DB00073"},{"key":"34622","doi-asserted-by":"crossref","unstructured":"23. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009;62:e1-34.","DOI":"10.1016\/j.jclinepi.2009.06.006"},{"key":"34623","doi-asserted-by":"crossref","unstructured":"24. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan\u2014a web and mobile app for systematic reviews. Syst Rev 2016;5:210.","DOI":"10.1186\/s13643-016-0384-4"},{"key":"34624","doi-asserted-by":"crossref","unstructured":"25. Murad MH, Sultan S, Haffar S, Bazerbachi F. Methodological quality and synthesis of case series and case reports. BMJ Evid Based Med 2018;23:60-3.","DOI":"10.1136\/bmjebm-2017-110853"},{"key":"34625","doi-asserted-by":"crossref","unstructured":"26. Burns PB, Rohrich RJ, Chung KC. The levels of evidence and their role in evidence-based medicine. Plast Reconstr Surg 2011;128:305-10.","DOI":"10.1097\/PRS.0b013e318219c171"},{"key":"34626","doi-asserted-by":"crossref","unstructured":"27. Liu Y, Li Y, Du H. Efficacy of apremilast for psoriasis: a meta-analysis of randomized controlled studies. Postepy Dermatol Alergol 2023;40:165-70.","DOI":"10.5114\/ada.2022.119081"},{"key":"34627","unstructured":"28. Alharthy RF, Alharthy JM, Bawazir RO, et al. The Efficacy and Safety of Apremilast in the Management of Psoriatic Arthritis: A Systematic Review and Meta-Analysis. Cureus 16:e55773."},{"key":"34628","doi-asserted-by":"crossref","unstructured":"29. Kridin K, Patel PM, Jones VA, et al. IgA pemphigus: A systematic review. J Am Acad Dermatol 2020;82:1386-92.","DOI":"10.1016\/j.jaad.2019.11.059"},{"key":"34629","doi-asserted-by":"crossref","unstructured":"30. Cho YT, Fu KT, Chen KL, et al. Clinical, Histopathologic, and Immunohistochemical Features of Patients with IgG\/IgA Pemphigus. Biomedicines 2022;10:1197.","DOI":"10.3390\/biomedicines10051197"},{"key":"34630","doi-asserted-by":"crossref","unstructured":"31. Gyldenl\u00f8ve M, Alinaghi F, Zachariae C, et al. Combination Therapy with Apremilast and Biologics for Psoriasis: A Systematic Review. Am J Clin Dermatol 2022;23:605-13.","DOI":"10.1007\/s40257-022-00703-1"},{"key":"34631","doi-asserted-by":"crossref","unstructured":"32. Hassanandani T, Panda M, Jena AK, Raj C. Methotrexate monotherapy versus methotrexate and apremilast combination therapy in the treatment of palmoplantar psoriasis: A prospective, randomised, assessor-blinded, comparative study. Indian J Dermatol Venereol Leprol 2023;89:213-20.","DOI":"10.25259\/IJDVL_843_2021"},{"key":"34632","doi-asserted-by":"crossref","unstructured":"33. Uchida H, Kamata M, Shimizu T, et al. Apremilast downregulates interleukin-17 production and induces splenic regulatory B cells and regulatory T cells in imiquimod-induced psoriasiform dermatitis. J Dermatol Sci 2021;104:55-62.","DOI":"10.1016\/j.jdermsci.2021.08.001"},{"key":"34633","doi-asserted-by":"crossref","unstructured":"34. Medvedeva IV, Stokes ME, Eisinger D, et al. Large-scale Analyses of Disease Biomarkers and Apremilast Pharmacodynamic Effects. Sci Rep 2020;10:605.","DOI":"10.1038\/s41598-020-57542-5"},{"key":"34634","doi-asserted-by":"crossref","unstructured":"35. Chen Y, Li Z, Li H, et al. Apremilast Regulates the Teff\/Treg Balance to Ameliorate Uveitis via PI3K\/AKT\/FoxO1 Signaling Pathway. Front Immunol 2020;11:581673.","DOI":"10.3389\/fimmu.2020.581673"},{"key":"34635","doi-asserted-by":"crossref","unstructured":"36. Megna M, Lauletta G, Tommasino N, et al. Management of Psoriasis Patients with Serious Infectious Diseases. Adv Ther 2024;41:2099-111.","DOI":"10.1007\/s12325-024-02873-2"},{"key":"34636","doi-asserted-by":"crossref","unstructured":"37. Mazzilli S, Lanna C, Chiaramonte C, et al. Real-life experience of apremilast in psoriasis and arthritis psoriatic patients: Preliminary results on metabolic biomarkers. J Dermatol 2020;47:578-82.","DOI":"10.1111\/1346-8138.15293"},{"key":"34637","doi-asserted-by":"crossref","unstructured":"38. Gelfand JM, Shin DB, Armstrong AW, et al. Association of Apremilast With Vascular Inflammation and Cardiometabolic Function in Patients With Psoriasis: The VIP-A Phase 4, Open-label, Nonrandomized Clinical Trial. JAMA Dermatol 2022;158:1394-403.","DOI":"10.1001\/jamadermatol.2022.3862"},{"key":"34638","doi-asserted-by":"crossref","unstructured":"39. Nassim D, Alajmi A, Jfri A, Pehr K. Apremilast in dermatology: A review of literature. Dermatol Ther 2020;33:e14261.","DOI":"10.1111\/dth.14261"},{"key":"34639","doi-asserted-by":"crossref","unstructured":"40. Varley CD, Winthrop KL. Long-Term Safety of Rituximab (Risks of Viral and Opportunistic Infections). Curr Rheumatol Rep 2021;23:74.","DOI":"10.1007\/s11926-021-01037-3"},{"key":"34640","doi-asserted-by":"crossref","unstructured":"41. Meneghini M, Bestard O, Grinyo JM. Immunosuppressive drugs modes of action. Best Pract Res Clin Gastroenterol 2021;54-55:101757.","DOI":"10.1016\/j.bpg.2021.101757"},{"key":"34641","doi-asserted-by":"crossref","unstructured":"42. Dehkordi AH, Mazaheri E, Ibrahim HA, et al. How to Write a Systematic Review: A Narrative Review. Int J Prev Med 2021;12:27.","DOI":"10.4103\/ijpvm.IJPVM_60_20"},{"key":"34642","unstructured":"43. Roukis TS. Case reports\/series & bias considerations. Foot Ankle Surg Tech Rep Cases [Internet] 2021[cited 2024 Nov 29];1. 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