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Review

Safety and Efficacy of Pemphigus Treatments: A Subtype-Specific Review of Conventional and Emerging Therapies

by
Pokphazz Christjaroon
1,2,3,
Orli Wagon
1,2 and
Artiene H. Tatian
1,2,3,*
1
Department of Dermatology, Sydney Children’s Hospital, Randwick, NSW 2031, Australia
2
Faculty of Medicine and Health, University of New South Wales, Kensington, Sydney, NSW 2033, Australia
3
Department of Dermatology, Liverpool Hospital, Liverpool, NSW 2170, Australia
*
Author to whom correspondence should be addressed.
BioChem 2025, 5(3), 28; https://doi.org/10.3390/biochem5030028
Submission received: 29 June 2025 / Revised: 6 August 2025 / Accepted: 28 August 2025 / Published: 2 September 2025
Browse Figure
Versions Notes

Abstract

Background/Objectives: Pemphigus is a rare blistering disease characterized by a chronic course, associated with significant mortality and morbidity. This review article aims to delve into three Pemphigus subtypes: Pemphigus Vulgaris, Pemphigus Foliaceus and Paraneoplastic Pemphigus, including the safety and efficacy of their treatment options. Methods: A thorough literature search was conducted using PubMed, EMBASE, Medline and Cochrane Library to collate data on pharmaceutical treatments of Pemphigus. Studies were selected based on predefined inclusion criteria, which included English language, peer-reviewed articles published in the date range January 2000 to May 2025. Eligible studies involved adults diagnosed with Pemphigus Vulgaris, Pemphigus Foliaceus or Paraneoplastic Pemphigus who were treated with Glucocorticoids, Mycophenolate mofetil, azathioprine or rituximab. The focus was on identifying adverse effects, complete remission and relapse rates. Results: The analysis revealed that glucocorticoid is the first-line treatment for Pemphigus. However, low remission rates of 34% along with steroid-related adverse effects indicate the use of Mycophenolate and azathioprine as steroid-sparing adjuvant therapies. Emerging treatments with rituximab have demonstrated 90% remission rates, indicating promising results with a comparatively mild side effect profile. Conclusions: The findings highlight the importance of ongoing evaluation of treatment modalities for Pemphigus subtypes to optimise remission rates and minimise adverse effects. Ultimately, studies often fail to isolate specific Pemphigus subtypes owing to the scarcity of literature. There is also a crucial need to address the lack of a standardised grading system for the side effects of glucocorticoids and long-term safety data for rituximab in further longitudinal research.

1. Introduction

Pemphigus encompasses a group of chronic autoimmune diseases that affect the skin and mucous membranes, etymologically derived from the Greek word ‘pemphix’, meaning blister. The two major subtypes are Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF), while Paraneoplastic Pemphigus (PNP) is a rare, non-classical form [1]. Pemphigus has an incidence rate of 0.6–0.8 per million people per year, with the highest prevalence occurring in Iran and Korea for PV, and Brazil for PF [2,3]. The epidemiological distribution shows female predominance, primarily affecting individuals aged 45–65 [4,5].
Early intervention is crucial in mitigating the significant mortality rate of approximately 5% and the impaired quality of life, as measured by the Dermatology Life Quality Index [6,7]. It prevents life-threatening complications like sepsis, while also curbing disease progression that exacerbates pain, disfigurement and psychological distress [8,9]. Pemphigus treatment focuses on increasing remission rates and decreasing relapse rates while minimising adverse effects [10]. Currently, glucocorticoids remain the first-line therapy in the consolidation phase, but approximately 50% of patients relapse during tapering [11]. Due to the adverse effects of long-term steroid use, adjuvant steroid-sparing immunosuppressive drugs are often required. Mycophenolate mofetil or azathioprine are frequently added historically, which decreases relapse rates to 21.7% and 28.6%, respectively [12].
However, no standardised dosing protocol has been agreed upon for Pemphigus treatment [13]. Additionally, the relationship between PV and hematological neoplasm sparked controversy regarding the use of immunosuppressive therapy for treating PV, due to the potential increased risk of cancer development [14]. Recent advancements in therapies, particularly rituximab, have shown promising results from a meta-analysis, demonstrating that 59–100% of patients achieve complete clinical remission within 3–6 months. However, evidence related to their long-term safety and efficacy is still lacking [11]. Due to its rare incidence rate, large-scale RCTs are limited, and most studies group Pemphigus subtypes together, overlooking key differences in prognosis and management. This literature review synthesises the current evidence on the safety and efficacy of treatments for three subtypes of Pemphigus, which is critical for guiding clinical decisions and improving patient outcomes.

2. Pathophysiology

Pemphigus is an autoimmune condition characterised by autoantibodies that target key adhesion molecules in the skin and mucous membranes. The pathogenesis involves a complex interplay between predisposing genetic and inducing environmental factors [15]. Patients with human leukocyte antigen (HLA) class II alleles, particularly HLA-DRB1 and HLA-DQB1, have an increased susceptibility to produce autoantibodies [16]. Environmental factors, such as ultraviolet radiation, viral infections, and certain thiol-containing medications, can trigger the immune system’s production of autoantibodies [17].
The underlying mechanism of PF involves auto-antibodies targeting Desmoglein 1, which is predominantly expressed in the epidermis. To maintain skin integrity, Desmoglein 3 partially compensates by providing adhesion in deeper layers, thereby limiting its involvement to the superficial skin, which can cause pruritus and burning sensations [18]. Contrarily, in PV, auto-antibodies against Desmoglein 3 found in the deeper layers cause only mucosal involvement as Desmoglein 1 compensates for the loss in superficial layers [19]. Positivity for both auto-antibodies leads to mucocutaneous PV due to the lack of compensation of their Desmoglein protein function [20]. Their dysfunction causes acantholysis, the loss of cellular cohesion and subsequent blistering and erosions [21]. These mechanisms of Desmoglein compensation and antibody targeting are illustrated in Figure 1.
Oral, genital and conjunctival erosions cause dysphagia, dyspareunia and ocular irritation, which cause weight loss and global functional impairment [22]. PNP arises from cross-reactivity between IgG tumour antigens from underlying neoplasms and epithelial antigens, including Plakin family proteins, Desmoglein 1 and 3, and A2ML1 [23]. The humoral and T-cell mediated lichenoid inflammation may cause multi-organ complications, including in the respiratory tract, progressing to Bronchiolitis Obliterans, contributing to the 90% mortality rate [24].
Biochem 05 00028 g001
Figure 1. Pathophysiologic mechanisms in Pemphigus [25]. (a,b) The phenotypes of PV and PF correspond with the presence of anti-Dsg1 and/or anti-Dsg3 antibodies. Blue triangle = anti-Dsg 3 antibodies; Brown triangle = anti-Dsg1 antibodies; X= functional loss of adhesion by corresponding desmoglein. Compensation of Dsg1/Dsg2 determines mucosal/skin blistering. (c) The binding of autoantibodies to Dsg leads to the steric hindrance and signal-independent loss of adhesion, amplifying acantholysis. After the loss of adhesion, signalling-dependant processes occur. Cis-cross linking of Dsg may cause signal-dependant endocytosis. Anti-Dsg3 = Anti-Desmoglein3, Anti-Dsg1 = Anti-Desmoglein1, PV = Pemphigus Vulgaris, PF = Pemphigus Foliaceus, abs = antibodies.
Figure 1. Pathophysiologic mechanisms in Pemphigus [25]. (a,b) The phenotypes of PV and PF correspond with the presence of anti-Dsg1 and/or anti-Dsg3 antibodies. Blue triangle = anti-Dsg 3 antibodies; Brown triangle = anti-Dsg1 antibodies; X= functional loss of adhesion by corresponding desmoglein. Compensation of Dsg1/Dsg2 determines mucosal/skin blistering. (c) The binding of autoantibodies to Dsg leads to the steric hindrance and signal-independent loss of adhesion, amplifying acantholysis. After the loss of adhesion, signalling-dependant processes occur. Cis-cross linking of Dsg may cause signal-dependant endocytosis. Anti-Dsg3 = Anti-Desmoglein3, Anti-Dsg1 = Anti-Desmoglein1, PV = Pemphigus Vulgaris, PF = Pemphigus Foliaceus, abs = antibodies.
Biochem 05 00028 g001

3. Conventional Treatments

3.1. Glucocorticoids

3.1.1. Efficacy

Pemphigus Vulgaris
Glucocorticoids are vital in PV treatment, reducing mortality from 75% to 30% by suppressing auto-antibody-mediated blister formation [26]. Prednisone monotherapy has a high relapse rate of 60% at 9 weeks, potentially linked to glucocorticoid resistance due to NR3C1 polymorphism [27,28]. Almugairen et al. reported 58.7% of 80 patients achieving complete remission off treatment (CRoffT) after 36 ± 39 months, likely due to combination therapy [29]. Glucocorticoids ensure quick control before introducing steroid-sparing immunotherapy [30]. This gap underscores the need for predictive genetic and immune biomarkers for clinicians to move beyond a trial-and-error approach to precise regimens maximising efficacy and minimising toxicity [31]. Critical limitations arise in the evidence base: most studies utilise a retrospective design with a small cohort and inconsistent outcome measures. A summary of clinical studies evaluating glucocorticoid efficacy in Pemphigus is presented in Table 1.
Pemphigus Foliaceus
In Almugairen et al., 21 out of 47 PF patients treated with prednisone achieved CRoffT [29]. As the current literature on PF is largely discussed in conjunction with PV, the remainder of this review will primarily discuss outcomes related to a combined PV/PF section.
The lack of PF-specific treatment outcomes is a significant deficit in Pemphigus research and existing treatment guidelines. This could be due to the overlap in characteristics and the potential of co-existence and evolution between types. Nonetheless, more PF-focused studies are required to make definitive conclusions.
Pemphigus Vulgaris/Pemphigus Foliaceus
In Schmidt et al. (n = 90), only 34% of patients in the prednisolone group achieved complete remission (p < 0.0001). This suggests the inefficacy of glucocorticoid monotherapy in achieving sustained disease control [32]. However, no combination therapies were superior in complete response rate. The limited sample size, particularly of PF patients, however, limits the generalizability of these findings to the broader PF population [33,34].
Paraneoplastic Pemphigus
PNP treatment focuses on the underlying neoplasm. While excisions for benign tumours such as Castleman’s disease can help, malignant neoplasms like B-cell lymphoma, Chronic Lymphocytic Leukaemia and Thymoma often remain uncontrolled, with a poor prognosis (75–90% mortality) [35,36]. Glucocorticoid efficacy in PNP is variable and typically suboptimal in monotherapy [37]. According to Lee et al., only two reports of PNP showed good response with steroids alone [38].
Furthermore, out of the 37 patients Leger et al. treated with glucocorticoids, 70% did not achieve complete epithelisation [37]. These studies were derived from small case series rather than from controlled trials, and there were no standardized steroid tapering protocols or guidelines for duration as a controlled measure in treatment outcomes.
Table 1. Comparison of Glucocorticoid efficacy in Pemphigus.
Table 1. Comparison of Glucocorticoid efficacy in Pemphigus.
First Author
(Year)		Study DesignStudy Population Results/Conclusion
Sharma et al. (2013) [27]Non-blinded, prospective RCT60 PV60% relapse rate after 9 weeks
71% relapse rate after 1 year
Almugairen et al. (2013) [29]Multi-centre retrospective study80 PV
47 PF		47 out of 80 (58.7%) of patients achieved CRoffT after 36 ± 39 months
21 out 47 (44.7%) of patients achieved CRoffT after 36 ± 39 months
Schmidt et al. (2020) [32]Controlled prospective trial90 PV/PF34% of patients achieved CRoffT after 2 years
Leger et al. (2012) [37]Multi-centre retrospective cohort study37 PNP26 out of 37 (70%) did not achieve complete epithelisation

3.1.2. Safety

Pemphigus Vulgaris
Long-term glucocorticoid safety is still a prevalent issue due to numerous adverse effects (AEs). Prolonged use of glucocorticoids (>4 months) is associated with complications of hypertension, diabetes mellitus, infection and osteoporosis [30]. The introduction of early adjuvant therapy has proven to minimize steroid exposure [13]. Chen et al. (n = 36) showed 67% of candidates on prednisone alone experienced grade 3–4 Corticosteroid-related AEs on the Common Terminology Criteria for Adverse Events (CTCAE) grading system initially developed for cancer clinical trials which is summarised in Table 2 [39]. However, a systematic review from 1978 to 2020 identified only 12 trials with a “steroid-only” arm that lacked a standardised grading system for side effects, which highlights the inadequacy of the literature on standalone safety profiles. The development of an index like the Glucocorticoid Toxicity index would allow for the quantification of AEs [40].
Pemphigus Foliaceus
Methylprednisolone is frequently used because it has less mineralocorticoid activity, possibly leading to less polyuria and polydipsia [42]. However, short and long-term side effects are still prevalent, such as polyphagia, increased risk of infection, alopecia, cutaneous atrophy, and steroid hepatopathy [42]. These side effects have a considerable effect on the quality of life of patients and may result in discontinuation of treatment, which underscores the importance of steroid-sparing drugs and other treatments.
Paraneoplastic Pemphigus
The glucocorticoid safety profile in PNP is concerning as these patients are already immunocompromised due to their underlying cancer. Long-term use of high-dose glucocorticoids can cause severe infections, osteoporosis, and other toxicities, which can hasten the already poor prognosis of PNP [43]. More studies must be conducted on the specific AEs in PNP patients.

3.2. Mycophenolate Mofetil

Mycophenolate mofetil (MMF) and azathioprine are most broadly used and recommended as first-line steroid-sparing treatments adjuvant to glucocorticoids, in both European guidelines and international recommendations, as these agents serve to lessen the consequences of prolonged glucocorticoid exposure, while maintaining remission [41].

3.2.1. Efficacy

Pemphigus Vulgaris
MMF is effective as an adjuvant therapy for PV, reducing disease activity and antibody titres even in azathioprine-resistant cases [44]. In Beissert et al., MMF led to a faster response, longer remission, and lower relapse rates (21.8% MMF vs. 44.5% placebo at 24 weeks [45]. However, the lack of a lesion ring and photographic assessment introduces subjectivity and observer’s bias. Without visual documentation, it is difficult to reproduce findings across different time points, affecting the reliability of study results [38]. These results conflict with Chams-Davatchi et al., who evaluated that treatment with glucocorticoids and MMF (3 g/day) offered no advantage over monotherapy with glucocorticoids [46]. This is further supported by a meta-analysis of 154 patients which concluded that MMF had no steroid-sparing effect compared to oral glucocorticoids alone [33,45,47].
Pemphigus Foliaceus
MMF shows inconsistent results in PF treatment. In one study, it achieved earlier sustained remission than placebo but lacked a steroid-sparing effect or improved remission rates [33]. Mimouni et al. reported 45% complete and 36% partial remission [48]; however, the study’s age (2003) limits its relevance to current guidelines.
Pemphigus Vulgaris/Pemphigus Foliaceus
MMF reduces cumulative glucocorticoid doses to control disease activity [49]. A meta-analysis of 201 patients found no improvement in response rate than with glucocorticoid monotherapy [33,45,46,47]. Ioannides et al.’s open-label design may have introduced performance bias, with short follow up periods limiting evidence reliability due to the chronic nature of the condition [46]. Sukanjanapong et al. found MMF superior to azathioprine for disease control (n = 40; RR 0.72; 95% CI 0.52 to 0.99, NNT 3.7) [50].
Paraneoplastic Pemphigus
MMF shows partial success in PNP treatment. Two studies with single patients demonstrated therapeutic efficacy, including prednisone dose reduction (from 25 mg to 10 mg) and lesion quiescence [51,52]. However, the low generalizability of the studies due to the small number of cases and lack of a control group lowers the strength of the evidence. Taken together, these clinical studies assessing the variable efficacy of MMF across Pemphigus subtypes are illustrated in Table 3.

3.2.2. Safety

MMF has a more favourable safety profile compared to other immunosuppressants, but it is not without risk. The most frequent side effects are mild gastrointestinal disturbances such as nausea and diarrhea [42].
Pemphigus Vulgaris
In Beissert et al., 3 out of 58 patients (5%) with mild-to-moderate PV experienced grade 3 adverse effects [45]. Dose-related haematological effects with few lymphoproliferative disorders have been reported [53]. Regular blood tests are recommended to monitor for cytopenia and further investigations on long-term safety [54].
Pemphigus Vulgaris/Pemphigus Foliaceus
Mimouni et al. showed that there was no statistically significant difference in clinical response to MMF or incidence of AE between PV and PF [48]. Out of 42 Pemphigus patients (31 PV, 11 PF), 77% experienced no AE [48]. However, there were rare serious side effects, including one case of symptomatic neutropenia and refractory nausea, both leading to treatment discontinuation [48]. MMF theoretically carries malignancy risk due to long-term immunosuppression; however, this has not been specifically documented in PF patients [55].
Paraneoplastic Pemphigus
Due to the background of malignancy, patients are prone to infections and will require strict monitoring if placed on immunosuppressants. Treatment should be discontinued if leukocyte count is below 3500–4000 cells/mm3 [55]. Other safety considerations are non-specific to PNP and apply to other Pemphigus subtypes, as mentioned in the above sections.

3.3. Azathioprine

3.3.1. Efficacy

Pemphigus Vulgaris
The European Dermatology Forum considers azathioprine a first-line adjuvant in PV, reducing the cumulative glucocorticoid dose required compared to MMF [30]. Mignogna et al. tracked 37 oropharyngeal Pemphigus Vulgaris patients over 2–13 years, with 34 achieving complete lesion healing in 4.70  ±  2.57 months [56]. Similarly, Davarmanesh et al. observed complete remission in 46/47 patients in 150  ±  224 days, with 36 patients relapsing, 55% of them due to self-discontinuation [57].
Pemphigus Foliaceus
The efficacy of azathioprine has been evaluated in various studies and yielded mixed outcomes. It did not show superiority regarding remission rates, disease control duration, withdrawal or death rates when compared to glucocorticoids monotherapy [33]. In Goodale et al., there was no difference in the course of treatment between glucocorticoids monotherapy and combination therapy with azathioprine and prednisone [42]. In Pathak et al., azathioprine had a lower relapse rate of 39.3% compared to the glucocorticoid-only group with 64.3% [31]. However, limitations persist as it does not account for confounding factors such as disease severity or patient adherence to therapy.
Paraneoplastic Pemphigus
Azathioprine (AZA) has been attempted as a supplementary treatment for PNP, but with weak evidence of efficacy. Morshedi et al. exhibited a patient who was resistant to azathioprine treatment but stabilised with prednisone and rituximab [58]. Current case reports lack robustness, highlighting the need for larger case series to establish efficacy.
Details of published studies investigating the efficacy of azathioprine across Pemphigus subtypes are compiled in Table 4.

3.3.2. Safety

Pemphigus Vulgaris
Compared to MMF, azathioprine has less well-tolerated AEs owing to greater risks for leukopenia, thrombocytopenia, anaemia and hepatotoxicity, which increases the occurrence of infections and neoplasms [59]. Patients with thiopurine methyltransferase enzyme deficiency are contraindicated for azathioprine due to their inability to metabolise the drug, leading to myelotoxicity warranting pharmacogenetic screening. Pregnant and lactating women are contraindicated for azathioprine [60]. Zeng et al. (n = 21) reported 14% of patients experienced grade 2 and 5% with grade 3 AE [40]. Nevertheless, the cost-effective adoption of universal screening remains debated, and prospective registries on malignancy risks and screening guidelines are understudied.
Pemphigus Foliaceus
Azathioprine proved to have a steroid-sparing effect on Pemphigus treatment based on a meta-analysis of 116 patients [33]. Ten trials involving 592 patients were analysed, suggesting that azathioprine pulse therapy can reduce cumulative steroid dosage compared to glucocorticoids alone by a mean difference of −3032.48 mg [61]. Due to indirect comparisons, effect estimates may be imprecise, and the retrospective design combined with a small number of studies are confounding factors limiting the generalizability of these conclusions. The adverse effects include pancreatitis, suppression of the bone marrow, and hepatotoxicity, which necessitate baseline and ongoing monitoring of the blood count and liver enzymes [42].
Paraneoplastic Pemphigus
Due to the background of malignancy, patients are prone to infections and will require strict monitoring if placed on immunosuppressants. Treatment should be discontinued if leukocyte count is below 3500–4000 cells/mm3 [55]. After-safety considerations are non-specific to PNP and apply to other Pemphigus subtypes, as mentioned in the above sections.

4. Emerging Treatment

4.1. Rituximab

4.1.1. Efficacy

Pemphigus Vulgaris
Rituximab, a monoclonal anti-CD20 antibody, has recently emerged as an effective option, especially in non-responders to conventional therapies [62]. In Chen et al., 90% of participants treated with rituximab and prednisone achieved CRoffT at month 24, compared to 28% in the prednisone-only group [39]. Relapse rates were also lower (24% vs. 50%) [39]. Few studies have investigated the effectiveness of rituximab monotherapy in mild, moderate and severe PV. In Nili et al., complete remission was achieved in 50% of severe, 40% of moderate and 97% of mild PV cases [63]. Early prescription has been shown to reduce the duration of treatment and dosage required but limitations of the study remain, owing to its low sample size and lack of control groups.
Pemphigus Foliaceus
In Palacios-Álvarez et al., the relapse rate of PF on rituximab was 50% after 12 months, 50% of patients showed CRoffT, and 42% achieved a partial response on/off minimal therapy; however, no correlation between CR and additional cycles was observed [64].
Pemphigus
In Joly et al., 89% of patients treated with rituximab achieved remission compared to 34% in the prednisolone group [65]. A meta-analysis found remission rates up to 91% [33]. Despite its success, according to Colliou et al. [66], rituximab has a 25% relapse rate within 2 years and 81% relapse rate by 7 years. These findings stress the importance of follow-up and repeated therapy. Prophylactic rituximab infusions for patients in remission were not beneficial, bringing to question the efficacy of maintenance therapy [67]. The heterogeneity of relapse rates among studies underscores the necessity for standard definitions of relapse/remission in Pemphigus studies.
Paraneoplastic Pemphigus
Rituximab has emerged as a promising therapeutic intervention for PNP. Long-term remission and prompt healing of mucosal lesions have occurred in approximately 60–100% of patients [38]. Contrastingly, Kappius et al. mentions that cutaneous involvement improves within 12 weeks, while mucosal lesions respond poorly. It is also efficacious in PNP with underlying lymphoproliferative malignancies [24].
An overview of studies examining Rituximab efficacy in Pemphigus is provided in Table 5.

4.1.2. Safety

Pemphigus Vulgaris
Rituximab is safer than high-dose steroids, reducing CS exposure and steroid-related AEs. In Chen et al., rituximab-treated patients had fewer grade 3/4 glucocorticoid AEs (Cushing syndrome, muscle disorder, myopathy at 34% and 67%, respectively) than those on prednisone alone [39]. Prolonged B-cell depleting therapy is linked to infections, hypogammaglobulinemia and malignancies, though mild side effects resolve after infusion cessation [69,70]. Low-dose rituximab showed no severe side effects, and long-term maintenance protocols remain undefined.
Pemphigus Foliaceus
Severe AEs from rituximab are rare but potentially life-threatening, often involving infections like hepatitis or herpes reactivation [67]. Kasperkiewicz et al. reported that AEs manifested in 23.7% of patients, with a 19.7% infection and 3.9% mortality rate [12]. Hence, careful patient selection and monitoring are essential. However, the power is insufficiently powered; utilising unsuitable statistical methods to analyse time-to-event-outcomes decrease validity, leaving dosing and long-term safety inconclusive [33].
Paraneoplastic Pemphigus
Rituximab generally shows good safety in PNP treatment, with mostly transient infusion-related side effects (headache, fever, chills, rash, hypotension). Severe AEs like opportunistic infections are rare but possible [38]. More case-control studies are needed to determine optimal dosing, combination therapy, and risk-benefit ratios.
Despite available PNP treatments, the evidence is limited to small case series and expert opinions [71]. The literature on PNP is weaker compared to PV and PF due to rarity, diagnostic complexity, and clinical heterogeneity [72].

5. Conclusions

This literature review explores the role of steroid-sparing drugs and glucocorticoids in Pemphigus treatment, particularly on adverse effects, remission and relapse rates. Although steroid-sparing drugs are known to have better safety profiles, glucocorticoids appear to be fundamental in treatment, showing higher efficacy even in conjunction with rituximab. The introduction of rituximab is seen as a breakthrough in patient outcomes, but gaps in the understanding of its long-term safety and dosing remain. Further exploration into predictable biomarkers such as HLA subtype and antibody titres could provide insights and enable personalised treatment. In addition to rituximab, other pharmacological agents such as rilzabrutinib, a Bruton’s tyrosine kinase inhibitor, and efgartigimod, a neonatal Fc receptor, have shown encouraging preliminary clinical results. Thus, these other novel treatments are also expected to be available for Pemphigus patients in the near future [73].
Ultimately, longitudinal studies should be conducted with an established Pemphigus-specific toxicity. There is also a critical need for randomised controlled trials with well-defined endpoints, including subtype-specific studies and comparative clinical trials directly evaluating between treatment options for better tailored strategies in Pemphigus treatment.

Author Contributions

Conceptualization, P.C. and A.H.T.; methodology, P.C.; software, P.C.; validation, P.C., A.H.T. and O.W.; formal analysis, P.C.; investigation, P.C.; resources, P.C.; writing—original draft preparation, P.C.; writing—review and editing, P.C., A.H.T. and O.W.; visualization, P.C.; supervision, A.H.T. and O.W.; project administration, A.H.T.; funding acquisition, A.H.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

No new data were generated as part of this review.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Didona, D.; Maglie, R.; Eming, R.; Hertl, M. Pemphigus: Current and Future Therapeutic Strategies. Front. Immunol. 2019, 10, 1418. [Google Scholar] [CrossRef] [PubMed]
  2. Prüßmann, W.; Prüßmann, J.; Koga, H.; Recke, A.; Iwata, H.; Juhl, D.; Görg, S.; Henschler, R.; Hashimoto, T.; Schmidt, E.; et al. Prevalence of pemphigus and pemphigoid autoantibodies in the general population. Orphanet J. Rare Dis. 2015, 10, 63. [Google Scholar] [CrossRef]
  3. Timóteo, R.P.; Pessoa-Gonçalves, Y.M.; do Carmo Neto, J.R.; Rodrigues, W.F.; da Silva, M.V.; Oliveira, C.J.F. A Global View of Pemphigus: Geographical Variations. Clin. Rev. Allergy Immunol. 2024, 66, 14–29. [Google Scholar] [CrossRef]
  4. Kridin, K.; Schmidt, E. Epidemiology of Pemphigus. JID Innov. 2021, 1, 100004. [Google Scholar] [CrossRef] [PubMed]
  5. Aryanian, Z.; Balighi, K.; Esmaeli, N.; Daneshpazhooh, M.; Mazloomi Tootoonchi, N.; Razavi, Z.; Beigmohammadi, F.; Gul, U.; Khayyat, A.; Hatami, P. A Comparative Study of Demographic and Clinical Criteria Between Male and Female Patients with Pemphigus Referred to a Referral Hospital in Iran. Dermatol. Res. Pract. 2024, 2024, 9572303. [Google Scholar] [CrossRef]
  6. Padniewski, J.J.; Shaver, R.L.; Schultz, B.; Pearson, D.R. Patient Quality of Life Improvement in Bullous Disease: A Review of Primary Literature and Considerations for the Clinician. Clin. Cosmet. Investig. Dermatol. 2022, 15, 27–42. [Google Scholar] [CrossRef]
  7. Quintarelli, L.; Coi, A.; Maglie, R.; Corrà, A.; Mariotti, E.B.; Aimo, C.; Ruffo di Calabria, V.; Verdelli, A.; Bianchi, B.; Del Bianco, E.; et al. Clinical Patterns, Survival, Comorbidities, and Treatment Regimens in 149 Patients With Pemphigus in Tuscany (Italy): A 12-Year Hospital-Based Study. Front. Immunol. 2022, 13, 895490. [Google Scholar] [CrossRef] [PubMed]
  8. Kiran, K.C.; Madhukara, J.; Abraham, A.; Muralidharan, S. Cutaneous Bacteriological Profile in Patients with Pemphigus. Indian J. Dermatol. 2018, 63, 301–304. [Google Scholar] [CrossRef]
  9. Wang, J.; Wu, H.; Cong, W.; Zhu, H.; Zheng, J.; Li, X.; Pan, M. Psychological morbidity in patients with pemphigus and its clinicodemographic risk factor: A comparative study. J. Dermatol. 2023, 50, 1237–1245. [Google Scholar] [CrossRef]
  10. DiMarco, C. Pemphigus: Pathogenesis to Treatment. Rhode Isl. Med. J. 2016, 99, 28–31. [Google Scholar]
  11. Kasperkiewicz, M.; Ellebrecht, C.T.; Takahashi, H.; Yamagami, J.; Zillikens, D.; Payne, A.S.; Amagai, M. Pemphigus. Nat. Rev. Dis. Primers 2017, 3, 17026. [Google Scholar] [CrossRef] [PubMed]
  12. Carver, C.A.; Kalesinskas, M.; Ahmed, A.R. Current biologics in treatment of pemphigus foliaceus: A systematic review. Front. Immunol. 2023, 14, 1267668. [Google Scholar] [CrossRef]
  13. Cholera, M.; Chainani-Wu, N. Management of Pemphigus Vulgaris. Adv. Ther. 2016, 33, 910–958. [Google Scholar] [CrossRef]
  14. Luo, Y.; Fei, X.; Wang, M.; Yang, H.; Zhang, Y.; Chen, Y.; Luo, Y.; Ding, X.; Gao, C.; Shen, F.; et al. Epidemiology of malignant tumors in patients with pemphigus: An analysis of trends from 1955 to 2021. Clin. Exp. Med. 2024, 24, 100. [Google Scholar] [CrossRef]
  15. Moro, F.; Sinagra, J.L.M.; Salemme, A.; Fania, L.; Mariotti, F.; Pira, A.; Didona, B.; Di Zenzo, G. Pemphigus: Trigger and predisposing factors. Front. Med. 2023, 10, 1326359. [Google Scholar] [CrossRef]
  16. Vuong, T.B.T.; Do, D.M.; Ong, P.T.; Thanh Le, T.V. HLA-DRB1 and DQB1 genetic susceptibility to pemphigus vulgaris and pemphigus foliaceus in Vietnamese patients. Dermatol. Rep. 2022, 14, 9286. [Google Scholar] [CrossRef] [PubMed]
  17. Stone, C.; Bak, G.; Oh, D.; Zhao, C.; Venugopal, S.; Kumar, K.; Murrell, D.F. Environmental triggers of pemphigus vulgaris and bullous pemphigoid: A case control study. Front. Med. 2024, 11, 1441369. [Google Scholar] [CrossRef]
  18. Lepe, K.; Yarrarapu, S.N.S.; Zito, P.M. Pemphigus Foliaceus. In StatPearls (StatPearls Publishing Copyright © 2025); StatPearls Publishing LLC.: Treasure Island, FL, USA, 2025. [Google Scholar]
  19. Sardana, K.; Garg, V.K.; Agarwal, P. Is there an emergent need to modify the desmoglein compensation theory in pemphigus on the basis of Dsg ELISA data and alternative pathogenic mechanisms? Br. J. Dermatol. 2013, 168, 669–674. [Google Scholar] [CrossRef]
  20. Malik, V.S.; Hu, F.B. Obesity Prevention. In Cardiovascular, Respiratory, and Related Disorders; Prabhakaran, D., Anand, S., Gaziano, T.A., Mbanya, J.C., Wu, Y.F., Nugent, R., Eds.; The International Bank for Reconstruction and Development/The World Bank © 2017 International Bank for Reconstruction and Development/The World Bank: Washington, DC, USA, 2017. [Google Scholar]
  21. Zhao, L.; Chen, Y.; Wang, M. The Global Incidence Rate of Pemphigus Vulgaris: A Systematic Review and Meta-Analysis. Dermatology 2023, 239, 514–522. [Google Scholar] [CrossRef]
  22. Lim, Y.L.; Bohelay, G.; Hanakawa, S.; Musette, P.; Janela, B. Autoimmune Pemphigus: Latest Advances and Emerging Therapies. Front. Mol. Biosci. 2021, 8, 808536. [Google Scholar] [CrossRef] [PubMed]
  23. Maruta, C.W.; Miyamoto, D.; Aoki, V.; Carvalho, R.G.R.D.; Cunha, B.M.; Santi, C.G. Paraneoplastic pemphigus: A clinical, laboratorial, and therapeutic overview. An. Bras. Dermatol. 2019, 94, 388–398. [Google Scholar] [CrossRef]
  24. Kappius, R.H.; Ufkes, N.A.; Thiers, B.H. Paraneoplastic Pemphigus. In StatPearls (StatPearls Publishing Copyright © 2025); StatPearls Publishing LLC.: Treasure Island, FL, USA, 2025. [Google Scholar]
  25. Hammers, C.M.; Stanley, J.R. Recent Advances in Understanding Pemphigus and Bullous Pemphigoid. J. Investig. Dermatol. 2020, 140, 733–741. [Google Scholar] [CrossRef]
  26. Kridin, K. Emerging treatment options for the management of pemphigus vulgaris. Ther. Clin. Risk Manag. 2018, 14, 757–778. [Google Scholar] [CrossRef] [PubMed]
  27. Sharma, V.K.; Khandpur, S. Evaluation of cyclophosphamide pulse therapy as an adjuvant to oral corticosteroid in the management of pemphigus vulgaris. Clin. Exp. Dermatol. 2013, 38, 659–664. [Google Scholar] [CrossRef]
  28. Fang, S.Y.; Li, C.L.; Liu, X.S.; Chen, F.; Hua, H. Correlation between polymorphisms of the NR3C1 gene and glucocorticoid effectiveness in patients with pemphigus vulgaris. Sci. Rep. 2017, 7, 11890. [Google Scholar] [CrossRef]
  29. Almugairen, N.; Hospital, V.; Bedane, C.; Duvert-Lehembre, S.; Picard, D.; Tronquoy, A.F.; Houivet, E.; D’incan, M.; Joly, P. Assessment of the rate of long-term complete remission off therapy in patients with pemphigus treated with different regimens including medium- and high-dose corticosteroids. J. Am. Acad. Dermatol. 2013, 69, 583–588. [Google Scholar] [CrossRef]
  30. Gregoriou, S.; Efthymiou, O.; Stefanaki, C.; Rigopoulos, D. Management of pemphigus vulgaris: Challenges and solutions. Clin. Cosmet. Investig. Dermatol. 2015, 8, 521–527. [Google Scholar] [CrossRef]
  31. Pathak, G.N.; Agarwal, P.; Wolfe, S.M.; Patel, K.H.; Dhillon, J.; Rao, B.K. Pemphigus relapse: Mechanisms, risk factors, and agents associated with disease recurrence. J. Dermatol. 2024, 51, 1533–1546. [Google Scholar] [CrossRef] [PubMed]
  32. Schmidt, E.; Sticherling, M.; Sárdy, M.; Eming, R.; Goebeler, M.; Hertl, M.; Hofmann, S.C.; Hunzelmann, N.; Kern, J.S.; Kramer, H.; et al. S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid: 2019 update. J. Dtsch. Dermatol. Ges. 2020, 18, 516–526. [Google Scholar] [CrossRef] [PubMed]
  33. Atzmony, L.; Hodak, E.; Gdalevich, M.; Rosenbaum, O.; Mimouni, D. Treatment of pemphigus vulgaris and pemphigus foliaceus: A systematic review and meta-analysis. Am. J. Clin. Dermatol. 2014, 15, 503–515. [Google Scholar] [CrossRef]
  34. Ratnam, K.V.; Phay, K.L.; Tan, C.K. Pemphigus therapy with oral prednisolone regimens. A 5-year study. Int. J. Dermatol. 1990, 29, 363–367. [Google Scholar] [CrossRef]
  35. Porro, A.M.; Caetano Lde, V.; Maehara Lde, S.; Enokihara, M.M. Non-classical forms of pemphigus: Pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus. An. Bras. Dermatol. 2014, 89, 96–106. [Google Scholar] [CrossRef] [PubMed]
  36. Wieczorek, M.; Czernik, A. Paraneoplastic pemphigus: A short review. Clin. Cosmet. Investig. Dermatol. 2016, 9, 291–295. [Google Scholar] [CrossRef] [PubMed]
  37. Leger, S.; Picard, D.; Ingen-Housz-Oro, S.; Arnault, J.P.; Aubin, F.; Carsuzaa, F.; Chaumentin, G.; Chevrant-Breton, J.; Chosidow, O.; Crickx, B.; et al. Prognostic Factors of Paraneoplastic Pemphigus. Arch. Dermatol. 2012, 148, 1165–1172. [Google Scholar] [CrossRef]
  38. Lee, S.; Kim, S.C. Paraneoplastic pemphigus. Dermatol. Sin. 2010, 28, 1–14. [Google Scholar] [CrossRef]
  39. Chen, D.M.; Odueyungbo, A.; Csinady, E.; Gearhart, L.; Lehane, P.; Cheu, M.; Maho-Vaillant, M.; Prost-Squarcioni, C.; Hebert, V.; Houivet, E.; et al. Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect. Br. J. Dermatol. 2020, 182, 1111–1119. [Google Scholar] [CrossRef] [PubMed]
  40. Zeng, F.A.P.; Wilson, A.; Sheriff, T.; Murrell, D.F. Side effects of steroid-sparing agents in patients with bullous pemphigoid and pemphigus: A systematic review. JAAD Int. 2022, 9, 33–43. [Google Scholar] [CrossRef] [PubMed]
  41. Jiang, G.; Liu, H.; Solbrig, H. Mining Severe Drug-Drug Interaction Adverse Events Using Semantic Web Technologies: A Case Study. BioData Min. 2015, 8, 12. [Google Scholar] [CrossRef]
  42. Goodale, E. Pemphigus foliaceous. Can. Vet. J. 2019, 60, 311–313. [Google Scholar]
  43. Antiga, E.; Bech, R.; Maglie, R.; Genovese, G.; Borradori, L.; Bockle, B.; Caproni, M.; Caux, F.; Chandran, N.S.; Corrà, A.; et al. S2k guidelines on the management of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome initiated by the European Academy of Dermatology and Venereology (EADV). J. Eur. Acad. Dermatol. Venereol. 2023, 37, 1118–1134. [Google Scholar] [CrossRef]
  44. Sarma, N.; Ghosh, S. Mycophenolate mofetil as adjuvant in pemphigus vulgaris. Indian J. Dermatol. Venereol. Leprol. 2007, 73, 348–350. [Google Scholar] [CrossRef] [PubMed]
  45. Beissert, S.; Mimouni, D.; Kanwar, A.J.; Solomons, N.; Kalia, V.; Anhalt, G.J. Treating Pemphigus Vulgaris with Prednisone and Mycophenolate Mofetil: A Multicenter, Randomized, Placebo-Controlled Trial. J. Investig. Dermatol. 2010, 130, 2041–2048. [Google Scholar] [CrossRef]
  46. Ioannides, D.; Apalla, Z.; Lazaridou, E.; Rigopoulos, D. Evaluation of mycophenolate mofetil as a steroid-sparing agent in pemphigus: A randomized, prospective study. J. Eur. Acad. Dermatol. Venereol. 2012, 26, 855–860. [Google Scholar] [CrossRef]
  47. Chams-Davatchi, C.; Esmaili, N.; Daneshpazhooh, M.; Valikhani, M.; Balighi, K.; Hallaji, Z.; Barzegari, M.; Akhyani, M.; Ghodsi, S.Z.; Seirafi, H.; et al. Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris. J. Am. Acad. Dermatol. 2007, 57, 622–628. [Google Scholar] [CrossRef]
  48. Mimouni, D.; Anhalt, G.J.; Cummins, D.L.; Kouba, D.J.; Thorne, J.E.; Nousari, H.C. Treatment of pemphigus vulgaris and pemphigus foliaceus with mycophenolate mofetil. Arch. Dermatol. 2003, 139, 739–742. [Google Scholar] [CrossRef]
  49. Sukanjanapong, S.; Thongtan, D.; Kanokrungsee, S.; Suchonwanit, P.; Chanprapaph, K. A Comparison of Azathioprine and Mycophenolate Mofetil as Adjuvant Drugs in Patients with Pemphigus: A Retrospective Cohort Study. Dermatol. Ther. 2020, 10, 179–189. [Google Scholar] [CrossRef]
  50. Beissert, S.; Werfel, T.; Frieling, U.; Böhm, M.; Sticherling, M.; Stadler, R.; Zillikens, D.; Rzany, B.; Hunzelmann, N.; Meurer, M.; et al. A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of pemphigus. Arch. Dermatol. 2006, 142, 1447–1454. [Google Scholar] [CrossRef]
  51. Powell, A.M.; Albert, S.; Al Fares, S.; Harman, K.E.; Setterfield, J.; Bhogal, B.; Black, M.M. An evaluation of the usefulness of mycophenolate mofetil in pemphigus. Br. J. Dermatol. 2003, 149, 138–145. [Google Scholar] [CrossRef] [PubMed]
  52. Williams, J.V.; Marks, J.G., Jr.; Billingsley, E.M. Use of mycophenolate mofetil in the treatment of paraneoplastic pemphigus. Br. J. Dermatol. 2000, 142, 506–508. [Google Scholar] [CrossRef] [PubMed]
  53. Bredlich, R.O.; Grundmann-Kollmann, M.; Behrens, S.; Kerscher, M.; Peter, R.U. Mycophenolate mofetil monotherapy for pemphigus vulgaris. Br. J. Dermatol. 1999, 141, 934. [Google Scholar] [CrossRef]
  54. Doukaki, S.; Platamone, A.; Alaimo, R.; Bongiorno, M.R. Mycophenolate mofetil and enteric-coated mycophenolate sodium in the treatment of pemphigus vulgaris and pemphigus foliaceus. J. Dermatolog. Treat. 2015, 26, 67–72. [Google Scholar] [CrossRef] [PubMed]
  55. Surjushe, A.; Saple, D.G. Mycophenolate mofetil. Indian J. Dermatol. Venereol. Leprol. 2008, 74, 180–184. [Google Scholar] [CrossRef]
  56. Mignogna, M.D.; Fortuna, G.; Leuci, S.; Ruoppo, E. Oropharyngeal pemphigus vulgaris and clinical remission: A long-term, longitudinal study. Am. J. Clin. Dermatol. 2010, 11, 137–145. [Google Scholar] [CrossRef] [PubMed]
  57. Davarmanesh, M.; Zahed, M.; Sookhakian, A.; Jehbez, S. Oral Pemphigus Vulgaris Treatment with Corticosteroids and Azathioprine: A Long-Term Study in Shiraz, Iran. Evid. Based Complement. Alternat. Med. 2022, 2022, 7583691. [Google Scholar] [CrossRef]
  58. Morshedi, B.; Ring, K. Cutaneous paraneoplastic pemphigus syndrome associated with undifferentiated uterine sarcoma. Gynecol. Oncol. Rep. 2020, 32, 100534. [Google Scholar] [CrossRef]
  59. Ojaimi, S.; O’Connor, K.; Lin, M.; Schifter, M.; Fulcher, D. Treatment Outcomes in a Cohort of Patients with Mucosal-predominant Pemphigus Vulgaris. Intern. Med. J. 2014, 45, 284–292. [Google Scholar] [CrossRef] [PubMed]
  60. Porro, A.M.; Seque, C.A.; Ferreira, M.C.C.; Simões, M.M.; Enokihara, S. Pemphigus vulgaris. An. Bras. De Dermatol. 2019, 94, 264–278. [Google Scholar] [CrossRef]
  61. Lee, M.S.; Yeh, Y.C.; Tu, Y.K.; Chan, T.C. Network meta–analysis–based comparison of first-line steroid-sparing adjuvants in the treatment of pemphigus vulgaris and pemphigus foliaceus. J. Am. Acad. Dermatol. 2021, 85, 176–186. [Google Scholar] [CrossRef]
  62. Zakka, L.R.; Shetty, S.S.; Ahmed, A.R. Rituximab in the treatment of pemphigus vulgaris. Dermatol. Ther. 2012, 2, 17. [Google Scholar] [CrossRef]
  63. Nili, A.; Mahmoudi, H.; Heidari, N.; Tavakolpour, S.; Salehi Farid, A.; Balighi, K.; Daneshpazhooh, M. Rituximab monotherapy in mild pemphigus. J. Dermatol. Treat. 2022, 33, 1784–1786. [Google Scholar] [CrossRef]
  64. de Sena Nogueira Maehara, L.; Huizinga, J.; Jonkman, M.F. Rituximab therapy in pemphigus foliaceus: Report of 12 cases and review of recent literature. Br. J. Dermatol. 2015, 172, 1420–1423. [Google Scholar] [CrossRef]
  65. Joly, P.; Maho-Vaillant, M.; Prost-Squarcioni, C.; Hebert, V.; Houivet, E.; Calbo, S.; Caillot, F.; Golinski, M.L.; Labeille, B.; Picard-Dahan, 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, 2031–2040. [Google Scholar] [CrossRef]
  66. Colliou, N.; Picard, D.; Caillot, F.; Calbo, S.; Le Corre, S.; Lim, A.; Lemercier, B.; Le Mauff, B.; Maho-Vaillant, M.; Jacquot, S.; et al. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci. Transl. Med. 2013, 5, 175ra30. [Google Scholar] [CrossRef]
  67. Gregoriou, S.; Giatrakou, S.; Theodoropoulos, K.; Katoulis, A.; Loumou, P.; Toumbis-Ioannou, E.; Papadavid, E.; Avgerinou, G.; Stavrianeas, N.; Rigopoulos, D. Pilot study of 19 patients with severe pemphigus: Prophylactic treatment with rituximab does not appear to be beneficial. Dermatology 2014, 228, 158–165. [Google Scholar] [CrossRef]
  68. Palacios-Álvarez, I.; Riquelme-Mc Loughlin, C.; Curto-Barredo, L.; Iranzo, P.; García-Díez, I.; España, A. Rituximab treatment of pemphigus foliaceus: A retrospective study of 12 patients. J. Am. Acad. Dermatol. 2021, 85, 484–486. [Google Scholar] [CrossRef]
  69. Aryanian, Z.; Balighi, K.; Emadi, S.N.; Hatami, P. Rituximab as a maintenance treatment in patients with pemphigus vulgaris: When is the right time for discontinuation? J. Cosmet. Dermatol. 2024, 23, 406–408. [Google Scholar] [CrossRef]
  70. Zhou, X.; Zhan, T.; Xu, X.; Lan, T.; Hu, H.; Zhou, Y.; Xia, D.; Wang, J.; Wang, Y.; Xiao, Y.; et al. The efficacy and safety of low-dose rituximab in the treatment of pemphigus vulgaris: A cohort study. J. Dermatol. Treat. 2024, 35, 2302071. [Google Scholar] [CrossRef]
  71. Carranza, M.C. Paraneoplastic Pemphigus: A Comprehensive Review of Pathophysiology, Clinical Manifestations, Diagnostic Challenges, and Therapeutic Approaches. Int. J. Med. Sci. Clin. Res. Stud. 2024, 4, 1658–1665. [Google Scholar] [CrossRef]
  72. Rodriguez, R.; Sivesind, T.E.; Murrell, D.; Dellavalle, R.P. From the Cochrane Library: Interventions for Pemphigus Vulgaris and Pemphigus Foliaceus. JMIR Dermatol. 2023, 6, e46812. [Google Scholar] [CrossRef] [PubMed]
  73. Izumi, K.; Bieber, K.; Ludwig, R.J. Current Clinical Trials in Pemphigus and Pemphigoid. Front. Immunol. 2019, 10, 978. [Google Scholar] [CrossRef] [PubMed]
Table 2. CTCAE grading system [41].
Table 2. CTCAE grading system [41].
GradeDefinition
Grade 1Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
Grade 2Moderate; minimal, local or non-invasive intervention indicated; limiting age-appropriate instrumental ADL *.
Grade 3Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL **.
Grade 4Life-threatening consequences: urgent intervention indicated.
Grade 5Death related to AE.
Note: Activities of Daily Living (ADL); * Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.; ** Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications and not being bedridden.
Table 3. Comparison of MMF efficacy in Pemphigus.
Table 3. Comparison of MMF efficacy in Pemphigus.
First Author
(Year)		Study DesignStudy
Population		Results/Conclusion
Beissert et al. (2010) [45] Prospective,
multi-centre,
double-blinded RCT 		94 PV21.8% relapse rate in MMF vs. 44.5% relapse rate in placebo at 24 weeks.
Beissert et al. (2010) [45]
Chams-Davatchi et al. (2007) [47]		Prospective,
multi-centre,
double-blinded RCT
Randomised controlled
open-label trial 		94 PV
60 PV		MMF has no steroid-sparing effect compared to oral glucocorticoids alone.
Mimouni et al. (2003) [48] Historical
prospective study 		94 PF45% of patients achieved complete remission.
36% of patients achieved complete remission.
Beissert et al. (2006) [50]Prospective RCT19 PV/3 PFMMF had better results over azathioprine in maintaining disease in a trial (n = 40; RR 0.72; 95% CI 0.52 to 0.99, NNT 3.7).
Sukanjanapong et al. (2020) [49]Retrospective
cohort study		62 PV/PFMMF showed better results in disease control than azathioprine (n = 40; RR 0.72; 95% CI 0.52 to 0.99, NNT 3.7).
Beissert et al. (2010) [45]
Chams-Davatchi et al. (2007) [47]
Ioannides et al. (2012) [46]		Prospective,
multi-centre,
double-blinded RCT
Randomised controlled
open-label trial
Randomised, prospective,
non-blinded trial 		94 PV
60 PV
47 PV/PF		MMF does not have better response rate compared to glucocorticoid monotherapy.
Williams et al. (2000) [52]Case report1 PNPPrednisone, cyclosporin and azathioprine discontinued after 5 months with sustained resolution of skin and oral lesions.
Table 4. Comparison of azathioprine efficacy in Pemphigus.
Table 4. Comparison of azathioprine efficacy in Pemphigus.
First Author
(Year)		Study DesignStudy
Population		Results/Conclusion
Mignogna et al. (2010) [56]Longitudinal cohort study37 PVOver the course of 2–13 years, 34 were able to reach complete healing of lesions in 4.7  ±  2.57 months.
Davarmanesh et al. (2022) [57]Retrospective cohort study47 PV46/47 patients achieved complete remission in a mean time of 150  ±  224 days.
36 patients relapse at least once over the course of the treatment but 55% was due to self-discontinuation.
Pathak et al. (2024) [31]RCT56 PVAzathioprine had a lower relapse rate of 39.3% compared to glucocorticoid-only group with 64.3%.
Morshedi et al. (2020) [58]Case report1 PNPResistant to azathioprine,
but stabilised with prednisone and rituximab.
Table 5. Comparison of rituximab efficacy in Pemphigus.
Table 5. Comparison of rituximab efficacy in Pemphigus.
First Author
(Year)		Study DesignStudy
Population		Results/Conclusion
Chen et al. (2020) [39]Phase III,
open-label RCT		38 PV90% of participants treated with rituximab and prednisone demonstrated complete remission off glucocorticoids at month 24 compared to 28% in the prednisone-only group.
24% (9/38) of rituximab patients relapsed compared to 50% (18/36) of patients in the prednisone-only group.
Nili et al. (2020) [63]Retrospective cohort study16 severe Pemphigus
5 moderate PV
15 mild Pemphigus		50% achieved complete remission.
5 moderate PV patients had a 40% complete remission rate.
Majority of patients (87%, 13/15) achieved complete remission.
Palacios-Álvarez et al. (2021) [68]Retrospective case series 12 PF6/12 (50%) of patients showed CRoffT.
5/12 (42%) showed partial response on and off minimal therapy.
50% relapse rate after 12 months.
Joly et al. (2017) [65]Prospective RCT46 Pemphigus89% of patients treated with rituximab achieved remission compared to just 34% in the prednisolone group.
Colliou et al. (2020) [66]Prospective cohort study22 Pemphigus81% of patients relapse by 7 years.
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Christjaroon, P.; Wagon, O.; Tatian, A.H. Safety and Efficacy of Pemphigus Treatments: A Subtype-Specific Review of Conventional and Emerging Therapies. BioChem 2025, 5, 28. https://doi.org/10.3390/biochem5030028

AMA Style

Christjaroon P, Wagon O, Tatian AH. Safety and Efficacy of Pemphigus Treatments: A Subtype-Specific Review of Conventional and Emerging Therapies. BioChem. 2025; 5(3):28. https://doi.org/10.3390/biochem5030028

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Christjaroon, Pokphazz, Orli Wagon, and Artiene H. Tatian. 2025. "Safety and Efficacy of Pemphigus Treatments: A Subtype-Specific Review of Conventional and Emerging Therapies" BioChem 5, no. 3: 28. https://doi.org/10.3390/biochem5030028

APA Style

Christjaroon, P., Wagon, O., & Tatian, A. H. (2025). Safety and Efficacy of Pemphigus Treatments: A Subtype-Specific Review of Conventional and Emerging Therapies. BioChem, 5(3), 28. https://doi.org/10.3390/biochem5030028

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