Keywords
Rituximab
Biological therapy
Clinical efficacy
Immunosuppression
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Abstract
Objective: To assess, based on updated evidence, the efficacy, safety, and emerging therapeutic strategies for the treatment of pemphigus vulgaris in adults. Methods: Integrative review based on the PVO strategy, including adult patients diagnosed with pemphigus vulgaris. Primary open-access studies were selected from PubMed Central, published between 2020 and 2025, addressing therapeutic interventions and clinical outcomes. After screening and eligibility, 18 studies were included. Results: The analyzed studies included 1,433 patients, mostly evaluating rituximab and its biosimilars, along with adjuvant therapies such as metformin, L-carnitine, and DFPP. Complete clinical remission rates ranged from 40% to 79%, and most adverse events were mild. Early use of biologics, maintenance regimens, and personalized approaches showed positive effects in relapse prevention and disease control. Final considerations: Rituximab stands out as an effective and safe therapeutic option for moderate to severe pemphigus vulgaris, with growing evidence supporting the use of adjuvant strategies. However, challenges remain regarding vaccine responsiveness, paradoxical flares, and the lack of prognostic biomarkers.
References
ABRAMOVA TV, et al. A new solid-phase immunosorbent for selective binding of desmoglein 3 autoantibodies in patients with pemphigus vulgaris. Acta Naturae, 2020; 12(2): 63-69.
AIDI S, et al. Adverse electrocardiographic effects of rituximab infusion in pemphigus patients. Dermatology and Therapy, 2020; 33(6): 14299.
AMONCHAISAKDA N, et al. Hospitalization and mortality in Asian autoimmune bullous dermatosis patients: A 17-year retrospective study. Experimental Dermatology, 2024; 33(5): 15095.
ARYANIAN Z, et al. Rituximab exhibits a better safety profile when used as a first line of treatment for pemphigus vulgaris: A retrospective study. International Immunopharmacology, 2021; 96: 107755.
BHATTACHARJEE R, et al. Assessment of the effects of rituximab monotherapy on different subsets of circulating T-regulatory cells and clinical disease severity in severe pemphigus vulgaris. Dermatology, 2016; 232(5): 572–577.
CHEN S, et al. A novel combined use of dupilumab for treatment of aggressive refractory pemphigus vulgaris complicated with pulmonary tuberculosis: A case report and the RNA-seq analysis. Frontiers in Immunology, 2022; 13: 825796.
CURA MJ, et al. Pemphigus vulgaris: A retrospective cohort study of clinical features, treatments, and outcomes. Actas Dermosifiliogr, 2020; 111(5): 398-407.
DIDONA D, et al. Pemphigus: Current and future therapeutic strategies. Frontiers in Immunology, 2023; 14: 1188-1209.
FELDMAN RJ. Paradoxical worsening of pemphigus vulgaris following rituximab therapy. British Journal of Dermatology, 2015; 173(3): 858–859.
FORTUNA G, et al. Immunocytometric analysis of oral pemphigus vulgaris patients after treatment with rituximab as adjuvant. Biomolecules, 2021; 11(11): 1634.
GUPTA V, et al. Clinical and immunological predictors of post-rituximab paradoxical pemphigus flare: A prospective cohort study. Indian Journal of Dermatology, Venereology and Leprology, 2025; 91(1): 3-8.
KAKUTA R, et al. Results of the guideline-based treatment for pemphigus: a single-centre experience with 84 cases. Journal of the European Academy of Dermatology and Venereology, 2020; 34(6): 1324-1330.
KANOKRUNGSEE S, et al. Rituximab therapy for treatment of pemphigus in Southeast Asians. Drug Design, Development and Therapy, 2021; 15: 1677-1690.
LIU Y, et al. Double-filtration plasmapheresis combined with immunosuppressive treatment for severe pemphigus: 10 years’ experience of a single center in China. Journal of Clinical Apheresis, 2021; 36(1): 20-27.
LOUCHEZ A, et al. Maintenance treatment of pemphigus with rituximab in real life: A single-center study of 50 patients. Annales de Dermatologie et de Vénéréologie, 2024; 151(2): 103264.
LU KL, et al. Immunosuppressants in dermatology on vaccine immunogenicity: a prospective cohort study of pemphigus patients in the pandemic. Frontiers in Immunology, 2024; 15: 1506962.
MAGLIE R, et al. Dramatic exacerbation of bullous pemphigoid following rituximab and successful treatment with omalizumab. European Journal of Dermatology; 2019, 29(2): 213–215.
MIYACHI H, et al. Clinical course and outcomes of pemphigus vulgaris and foliaceus: A retrospective study using a nationwide database in Japan. Journal of Dermatology, 2023; 50(2): 212-221.
MUSTIN DE, et al. Comparing clinical outcomes of steroid-sparing therapy with rituximab versus rituximab alone in pemphigus. Journal of Drugs in Dermatology, 2024; 23(3): 97-99.
NARAYANAN A, et al. A retrospective case-control study of clinical factors associated with paradoxical exacerbation of pemphigus vulgaris following rituximab infusion. International Journal of Dermatology, 2020; 59(12): 459–460.
NILI A, et al. Paradoxical reaction to rituximab in patients with pemphigus: A report of 10 cases. Immunopharmacology and Immunotoxicology, 2020; 42(1): 56–58.
NOORMOHAMMADI Z, et al. L-carnitine downregulate the muscle wasting effect of glucocorticoids in pemphigus patient: A randomized double-blind placebo-controlled study. Physiological Reports, 2023; 11(8): 15657.
PADHIYAR JK. Paradoxical disease flare, skin infection and hypogammaglobulinaemia in patients with pemphigus vulgaris treated with rituximab. Clinical and Experimental Dermatology, 2024; 49(2): 175–177.
PERUMAL JS, et al. Disease exacerbation after rituximab induction in neuromyelitis optica. Neurology® Neuroimmunology & Neuroinflammation, 2015; 2(5): 61.
PIRES CAA, et al. Therapeutic outcomes of pemphigus in a referral service in Northern Brazil: a retrospective study of 32 patients. Journal of Dermatological Treatment, 2021; 32(8): 1031-1034.
QUINTARELLI L, et al. Clinical patterns, survival, comorbidities, and treatment regimens in 149 patients with pemphigus in Tuscany (Italy): A 12-year hospital-based study. Frontiers in Immunology, 2022; 13: 895490.
RAHMATPOUR RG, et al. Effects of metformin on autoimmune immunoglobins and interferon-γ in patients with early diagnosed pemphigus vulgaris: a prospective clinical trial. Clinical and Experimental Dermatology, 2022; 47(1): 110-113.
RASHID H, et al. The effectiveness of rituximab in pemphigus and the benefit of additional maintenance infusions: Daily practice data from a retrospective study. Journal of the American Academy of Dermatology, 2020; 83(5): 1503-1505.
RAVIV T, et al. Prognostic factors predicting remission following rituximab therapy for pemphigus vulgaris. Acta Dermato-Venereologica, 2025; 105: 27140.
RUSSO I, et al. Ultra-low dose rituximab for refractory pemphigus vulgaris: a pilot study. Expert Opinion on Biological Therapy, 2020; 20(6): 673-678.
SHIN SH, et al. Comparative study of efficacy and safety: Biosimilar rituximab versus originator rituximab in the treatment of pemphigus. Journal of Dermatology, 2024; 51(8): 1104-1107.
SNAST I, et al. Treatment of pemphigus vulgaris and foliaceus with adjuvant rituximab compared to immunosuppression alone: Real-life experience. Dermatology, 2021; 237(2): 179-184.
SPAŁEK MM, et al. Dapsone as a current option for the treatment of autoimmune bullous diseases with autoimmunity to non-enzymes: A retrospective study from a single Central European referral center. Medicina (Kaunas), 2024; 60(8): 1324.
TOOSI R, et al. Efficacy and safety of biosimilar rituximab in patients with pemphigus vulgaris: a prospective observational study. Journal of Dermatological Treatment, 2021; 32(1): 33-40.
WANG X, et al. Focus on pemphigus treatment publications: A bibliometric and visual analysis (1992–2022). Heliyon, 2024; 10(7): 28462.
WERTH VP, et al. Rituximab versus mycophenolate mofetil in patients with pemphigus vulgaris. New England Journal of Medicine, 2021; 384(24): 2295-2305.
WIEDENMAYER N, et al. A novel high-dose intravenous immunoglobulin preparation for the treatment of severe pemphigus vulgaris failing standard therapy: A case report. Journal of Dermatology, 2024; 51(12): 1665-1668.
ZHANG W, et al. Short-term intravenous infusion of cyclophosphamide in the treatment of refractory pemphigus vulgaris: A retrospective study. Dermatology, 2021; 237(2): 185-190.