RARE DISEASE
Pemphigus vulgaris
Pemphigus vulgaris
Pemphigus vulgaris
Drug discovery
15
drugs
With orphan designations
Overview
Pemphigus vulgaris is a rare, chronic autoimmune blistering disorder characterized by painful flaccid blisters and erosions affecting mucous membranes (oral/ocular/genital) and skin. Pathogenesis involves IgG autoantibodies targeting desmoglein 1/3, disrupting epidermal adhesion (acantholysis). Diagnosis requires histopathology with suprabasal clefting and direct immunofluorescence showing intercellular IgG/C3 deposits. Untreated cases risk sepsis and dehydration, with mortality historically >90% pre-corticosteroids [1][6][12].
Burden
Morbidity: 89% report impaired eating; 63% have depression/anxiety [6][17]
Mortality: 5-15% with treatment (vs 90% untreated); 3× increased mortality vs general population [6][7][12]
Economic: Median hospitalization cost $26,800 (US); 30% require ICU care for sepsis/fluid loss [14][16]
Critical complications include secondary infections (22.6× sepsis risk) and steroid-related adverse effects (diabetes/osteoporosis). Maintenance therapy achieves remission in 75% at 5 years with rituximab [3][18].
Therapies
First-line: High-dose systemic corticosteroids (0.5-1.5 mg/kg/day prednisone) + rituximab (anti-CD20 monoclonal antibody) [3][6][18]
Adjuvants: Immunosuppressants (azathioprine/mycophenolate), IVIG, plasmapheresis [3][16][18]
Supportive: Antiseptic/analgesic mouthwashes, topical tacrolimus, nutritional support [1][3][16]
Categories: rare skin diseases
Research Papers
1,467 drug discovery papers about Pemphigus vulgaris, with 1 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,467 drug discovery papers about Pemphigus vulgaris, with 1 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-22 | Unraveling the autoimmune architecture of pemphigus: from B-cell depletion to network-based immune engineering.
Pemphigus encompasses autoimmune blistering diseases driven by autoantibodies to desmosomal proteins. Disruption of keratinocyte adhesion produces acantholysis and epidermal fragility. Anti-CD20 B-cell depletion and IgG lowering strategies have transformed care, but many patients relapse, some variants respond incompletely, and durable drug-independent tolerance remains uncommon across variants. These gaps highlight that pemphigus is not a simple linear B-cell disorder, but an autoantibody disease sustained by a network linking the innate immunity, the adaptive lymphocytes, and the stromal niches. In this review, we focus on pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome, and IgA pemphigus as representative variants within this network. We place these entities within a conceptual type 1, type 2, and type 3 immunity framework and summarize how central and peripheral B-cell tolerance can fail. We further consider current and emerging therapies as partial interventions within this network and outline next-generation strategies that modulate innate circuits, rewire survival pathways, restore antigen-specific regulation, and shift the adaptive autoimmune response toward a more tolerogenic state. Framing pemphigus in this way may help move the field from empiric immunosuppression toward precise immune engineering with the goal of durable immune reset and long-term drug-independent remission.
2026-07-11 | Case Report: Dupilumab as a corticosteroid-sparing adjunct in severe mucocutaneous pemphigus vulgaris with prior avascular necrosis and chronic kidney disease.
Pemphigus vulgaris is a potentially life-threatening autoimmune blistering disease for which corticosteroid minimization can be difficult when prior steroid toxicity has already occurred. We report a 60-year-old woman with severe mucocutaneous pemphigus vulgaris confirmed by clinical, immunopathologic, and serologic findings, who had previously developed femoral head avascular necrosis during high-dose prednisone therapy and also had advanced chronic kidney disease, hypoalbuminemia, and anemia. Rituximab was discussed as a guideline-supported first-line option; however, after counseling regarding its expected benefits and potential adverse effects, the patient declined rituximab. Therefore, dupilumab was introduced off-label as an adjunctive corticosteroid-minimizing approach together with oral prednisone 30 mg/day and supportive care. The Pemphigus Disease Area Index was 111 during the first treatment week and decreased to 22 by week 6, when disease control was achieved with cessation of new lesions and marked healing of pre-existing erosions. Prednisone was then tapered gradually. Complete re-epithelialization was achieved by approximately month 4 while the patient was receiving oral prednisone 7.5 mg/day, and clinical stability was maintained through month 6 after dupilumab discontinuation at month 4. No adverse events were observed. This case supports the clinical feasibility of dupilumab-assisted corticosteroid minimization in selected patients with pemphigus vulgaris and major treatment-related constraints, while further evidence is needed regarding patient selection, duration of therapy, and long-term relapse risk.
2026-07-07 | RITUXIMAB THERAPY IN PEMPHIGUS VULGARIS: CLINICAL OUTCOMES, SAFETY, AND QUALITY-OF-LIFE ASSESSMENT
Objectives: Pemphigus vulgaris is a chronic autoimmune blistering disorder that affects the skin and mucous membranes, often requiring prolonged immunosuppressive treatment. Although systemic corticosteroids remain effective in controlling disease activity, their long-term use is frequently limited by infections, metabolic adverse effects, steroid dependence, and relapse during dose reduction. Rituximab, an anti-CD20 monoclonal antibody, has emerged as a valuable treatment option, particularly in patients with moderate-to-severe disease, recurrent flares, or poor response to conventional therapy. Methods: The present work was a prospective single-arm interventional study. Sixty patients with clinically, histopathologically, and immunologically confirmed pemphigus vulgaris were enrolled. Rituximab was administered using the rheumatoid arthritis (RA) protocol, 1 g intravenously on Day 1 and Day 14, with standard pre-medication and short-term bridging corticosteroids. Patients were followed at 1, 3, 6, 9, and 12 months. Disease activity was assessed by the pemphigus disease area index (PDAI), and quality of life was assessed by the dermatology life quality index (DLQI). Clinical response definitions were aligned with the 2008 pemphigus consensus statement. Adverse events were graded using Common Terminology Criteria for Adverse Events v5.0, and causality was assessed clinically using the World Health Organization-Uppsala Monitoring Centre approach. Results: The mean age was 40.6±11.8 years. There were 38 females (63.3%) and 22 males (36.7%). Oral mucosal involvement was present in all 60 patients (100.0%), cutaneous lesions in 52 patients (86.7%), and genital mucosal involvement in 18 patients (30.0%). At baseline, 8 patients (13.3%) had mild disease, 20 patients (33.3%) had moderate disease, and 32 patients (53.3%) had severe disease according to PDAI-based severity grouping. The mean PDAI score decreased from 78.6±31.4 at baseline to 8.9±6.2 at 12 months. Mean DLQI score improved from 19.2±5.7 to 3.1±2.6. Disease control was achieved in 6.4±2.1 weeks. Complete remission on minimal therapy was seen in 51 patients (85.0%). Relapse occurred in 12 patients (20.0%), and 10 patients (16.7%) required booster rituximab. Mild infusion reactions occurred in 8 patients (13.3%). Serious infection requiring hospital-based care occurred in 2 patients (3.3%), and no mortality was observed. Conclusion: Rituximab administered by the RA protocol was effective and generally well tolerated in this single-arm cohort. The treatment reduced disease activity, improved quality of life, and supported corticosteroid tapering. Because there was no control group, no prospective trial registration, and limited immunological monitoring, the findings should be interpreted as real-world evidence rather than proof of superiority over other regimens.
2026-06-01 | Severe Pemphigus Vulgaris with Oral and Cutaneous Involvement: A Case Report
Pemphigus vulgaris (PV) is a rare, chronic, and potentially life-threatening autoimmune vesiculobullous disorder characterized by intraepithelial blister formation involving the skin and mucous membranes. It commonly affects individuals in the fifth to seventh decades of life and is associated with significant morbidity due to fluid and protein loss, metabolic disturbances, and secondary infections if left untreated. This report presents the case of a 50-year-old female patient with severe PV who presented with persistent painful oral ulcerations and recurrent cutaneous blisters over a period of three years. The patient had shown an inadequate clinical response to conventional systemic corticosteroid therapy. Due to the chronicity and severity of the condition, the treatment regimen was modified to include combination immunomodulatory therapy along with systemic corticosteroids, which resulted in marked clinical improvement in both oral and cutaneous lesions. This case highlights the importance of early diagnosis, prompt intervention, and individualized therapeutic strategies in the successful management of pemphigus vulgaris. Timely initiation of appropriate treatment can significantly reduce disease-related morbidity and improve the overall quality of life of affected patients.
2026-05-27 | CD19 CAR T Therapy Is Feasible in Patients with Pemphigus Vulgaris Treated Without Lymphodepletion in the RESET-PV Trial.
Lymphodepleting pre-conditioning (LD) is essential for the efficacy of CAR T therapy in hematologic malignancies. However, in the setting of autoimmune diseases (ADs), the contribution of LD for efficacy is unclear. Here, we report on the early safety, efficacy, and correlative data of the first four pemphigus vulgaris (PV) subjects who received resecabtagene autoleucel (rese-cel) a fully human CD19-CAR T cell therapy, without LD in the RESET-PV® trial (NCT04422912), a sub-study of the DesCAARTes trial. Following infusion, pemphigus disease area index (PDAI) scores improved significantly in all subjects. A favorable safety profile was observed with a single episode of grade 1 cytokine release syndrome. Immune-effector-cell-associated neurotoxicity was not observed. Rese-cel expansion was similar in PV subjects as compared to other rese-cel treated AD subjects who received LD. B cell depletion was observed in all PV subjects, with 3 of 4 subjects achieving B cell aplasia. Elevations in serum BAFF were observed, with 3 of 4 subjects achieving levels within the lowest end of the range exhibited in rese-cel treated AD subjects who received LD. Pathogenic PV autoantibodies decreased in 2 of 4 subjects. Together, these preliminary data suggest that LD may not be required for humanized CAR T efficacy in patients with AD.
2026-07-22 | Unraveling the autoimmune architecture of pemphigus: from B-cell depletion to network-based immune engineering.
Pemphigus encompasses autoimmune blistering diseases driven by autoantibodies to desmosomal proteins. Disruption of keratinocyte adhesion produces acantholysis and epidermal fragility. Anti-CD20 B-cell depletion and IgG lowering strategies have transformed care, but many patients relapse, some variants respond incompletely, and durable drug-independent tolerance remains uncommon across variants. These gaps highlight that pemphigus is not a simple linear B-cell disorder, but an autoantibody disease sustained by a network linking the innate immunity, the adaptive lymphocytes, and the stromal niches. In this review, we focus on pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome, and IgA pemphigus as representative variants within this network. We place these entities within a conceptual type 1, type 2, and type 3 immunity framework and summarize how central and peripheral B-cell tolerance can fail. We further consider current and emerging therapies as partial interventions within this network and outline next-generation strategies that modulate innate circuits, rewire survival pathways, restore antigen-specific regulation, and shift the adaptive autoimmune response toward a more tolerogenic state. Framing pemphigus in this way may help move the field from empiric immunosuppression toward precise immune engineering with the goal of durable immune reset and long-term drug-independent remission.
2026-07-11 | Case Report: Dupilumab as a corticosteroid-sparing adjunct in severe mucocutaneous pemphigus vulgaris with prior avascular necrosis and chronic kidney disease.
Pemphigus vulgaris is a potentially life-threatening autoimmune blistering disease for which corticosteroid minimization can be difficult when prior steroid toxicity has already occurred. We report a 60-year-old woman with severe mucocutaneous pemphigus vulgaris confirmed by clinical, immunopathologic, and serologic findings, who had previously developed femoral head avascular necrosis during high-dose prednisone therapy and also had advanced chronic kidney disease, hypoalbuminemia, and anemia. Rituximab was discussed as a guideline-supported first-line option; however, after counseling regarding its expected benefits and potential adverse effects, the patient declined rituximab. Therefore, dupilumab was introduced off-label as an adjunctive corticosteroid-minimizing approach together with oral prednisone 30 mg/day and supportive care. The Pemphigus Disease Area Index was 111 during the first treatment week and decreased to 22 by week 6, when disease control was achieved with cessation of new lesions and marked healing of pre-existing erosions. Prednisone was then tapered gradually. Complete re-epithelialization was achieved by approximately month 4 while the patient was receiving oral prednisone 7.5 mg/day, and clinical stability was maintained through month 6 after dupilumab discontinuation at month 4. No adverse events were observed. This case supports the clinical feasibility of dupilumab-assisted corticosteroid minimization in selected patients with pemphigus vulgaris and major treatment-related constraints, while further evidence is needed regarding patient selection, duration of therapy, and long-term relapse risk.
2026-07-07 | RITUXIMAB THERAPY IN PEMPHIGUS VULGARIS: CLINICAL OUTCOMES, SAFETY, AND QUALITY-OF-LIFE ASSESSMENT
Objectives: Pemphigus vulgaris is a chronic autoimmune blistering disorder that affects the skin and mucous membranes, often requiring prolonged immunosuppressive treatment. Although systemic corticosteroids remain effective in controlling disease activity, their long-term use is frequently limited by infections, metabolic adverse effects, steroid dependence, and relapse during dose reduction. Rituximab, an anti-CD20 monoclonal antibody, has emerged as a valuable treatment option, particularly in patients with moderate-to-severe disease, recurrent flares, or poor response to conventional therapy. Methods: The present work was a prospective single-arm interventional study. Sixty patients with clinically, histopathologically, and immunologically confirmed pemphigus vulgaris were enrolled. Rituximab was administered using the rheumatoid arthritis (RA) protocol, 1 g intravenously on Day 1 and Day 14, with standard pre-medication and short-term bridging corticosteroids. Patients were followed at 1, 3, 6, 9, and 12 months. Disease activity was assessed by the pemphigus disease area index (PDAI), and quality of life was assessed by the dermatology life quality index (DLQI). Clinical response definitions were aligned with the 2008 pemphigus consensus statement. Adverse events were graded using Common Terminology Criteria for Adverse Events v5.0, and causality was assessed clinically using the World Health Organization-Uppsala Monitoring Centre approach. Results: The mean age was 40.6±11.8 years. There were 38 females (63.3%) and 22 males (36.7%). Oral mucosal involvement was present in all 60 patients (100.0%), cutaneous lesions in 52 patients (86.7%), and genital mucosal involvement in 18 patients (30.0%). At baseline, 8 patients (13.3%) had mild disease, 20 patients (33.3%) had moderate disease, and 32 patients (53.3%) had severe disease according to PDAI-based severity grouping. The mean PDAI score decreased from 78.6±31.4 at baseline to 8.9±6.2 at 12 months. Mean DLQI score improved from 19.2±5.7 to 3.1±2.6. Disease control was achieved in 6.4±2.1 weeks. Complete remission on minimal therapy was seen in 51 patients (85.0%). Relapse occurred in 12 patients (20.0%), and 10 patients (16.7%) required booster rituximab. Mild infusion reactions occurred in 8 patients (13.3%). Serious infection requiring hospital-based care occurred in 2 patients (3.3%), and no mortality was observed. Conclusion: Rituximab administered by the RA protocol was effective and generally well tolerated in this single-arm cohort. The treatment reduced disease activity, improved quality of life, and supported corticosteroid tapering. Because there was no control group, no prospective trial registration, and limited immunological monitoring, the findings should be interpreted as real-world evidence rather than proof of superiority over other regimens.
2026-06-01 | Severe Pemphigus Vulgaris with Oral and Cutaneous Involvement: A Case Report
Pemphigus vulgaris (PV) is a rare, chronic, and potentially life-threatening autoimmune vesiculobullous disorder characterized by intraepithelial blister formation involving the skin and mucous membranes. It commonly affects individuals in the fifth to seventh decades of life and is associated with significant morbidity due to fluid and protein loss, metabolic disturbances, and secondary infections if left untreated. This report presents the case of a 50-year-old female patient with severe PV who presented with persistent painful oral ulcerations and recurrent cutaneous blisters over a period of three years. The patient had shown an inadequate clinical response to conventional systemic corticosteroid therapy. Due to the chronicity and severity of the condition, the treatment regimen was modified to include combination immunomodulatory therapy along with systemic corticosteroids, which resulted in marked clinical improvement in both oral and cutaneous lesions. This case highlights the importance of early diagnosis, prompt intervention, and individualized therapeutic strategies in the successful management of pemphigus vulgaris. Timely initiation of appropriate treatment can significantly reduce disease-related morbidity and improve the overall quality of life of affected patients.
2026-05-27 | CD19 CAR T Therapy Is Feasible in Patients with Pemphigus Vulgaris Treated Without Lymphodepletion in the RESET-PV Trial.
Lymphodepleting pre-conditioning (LD) is essential for the efficacy of CAR T therapy in hematologic malignancies. However, in the setting of autoimmune diseases (ADs), the contribution of LD for efficacy is unclear. Here, we report on the early safety, efficacy, and correlative data of the first four pemphigus vulgaris (PV) subjects who received resecabtagene autoleucel (rese-cel) a fully human CD19-CAR T cell therapy, without LD in the RESET-PV® trial (NCT04422912), a sub-study of the DesCAARTes trial. Following infusion, pemphigus disease area index (PDAI) scores improved significantly in all subjects. A favorable safety profile was observed with a single episode of grade 1 cytokine release syndrome. Immune-effector-cell-associated neurotoxicity was not observed. Rese-cel expansion was similar in PV subjects as compared to other rese-cel treated AD subjects who received LD. B cell depletion was observed in all PV subjects, with 3 of 4 subjects achieving B cell aplasia. Elevations in serum BAFF were observed, with 3 of 4 subjects achieving levels within the lowest end of the range exhibited in rese-cel treated AD subjects who received LD. Pathogenic PV autoantibodies decreased in 2 of 4 subjects. Together, these preliminary data suggest that LD may not be required for humanized CAR T efficacy in patients with AD.
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Drug Discovery Landscape
15 orphan drug designations for Pemphigus vulgaris, including 1 approved therapy.
15 orphan drug designations for Pemphigus vulgaris, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
bispecific humanized IgG4 BCMA-directed CD3 T cell engager antibody | antibodies | FDA | 2026-08-20 | — | Ouro Medicines Ltd. |
resecabtagene autoleucel | cell therapies | FDA | 2026-03-14 | — | Cabaletta Bio, Inc. |
afamelanotide | peptides | FDA | 2025-10-16 | — | Wanbangde Pharmaceutical Group Co., Ltd. |
Efgartigimod alfa [Vyvgart] | antibodies | EMA | 2022-07-18 | — | Argenx |
Autologous Desmoglein 3 (DSG3) Chimeric Autoantibody Receptor-directed (CAAR) T cells | cell therapies | FDA | 2020-01-28 | — | Cabaletta Bio, Inc. |
orilanolimab | antibodies | FDA | 2018-09-10 | — | Alexion Pharmaceuticals, Inc. |
Rilzabrutinib [PRN1008] | small molecules | EMA | 2017-12-12 | — | Scendea (NL) B.V. |
Small Molecule Bruton's Agammaglobulinemia Tyrosine Kinase (BKT) Inhibitor | small molecules | FDA | 2017-06-29 | — | Principia Biopharma Inc. |
rituximab [Rituxan(r); MabThera(r)] | antibodies | FDA | 2015-02-23 | 2018-06-07 | Genentech, Inc. |
(S)-2-(1-((6-amino-5-cyanopyrimidin-4-yl)amino)ethyl)-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazine-5-carbonitrile | small molecules | FDA | 2015-01-26 | — | Almirall S.A. |
veltuzumab | antibodies | FDA | 2014-11-17 | — | Immunomedics, Inc. |
2-((1s)-1-((6-amino-5-cyano-4-pyrimidinyl)amino)ethyl)-3,4-dihydro-4-oxo-3-phenylpyrrolo(2,1-f)(1,2,4)triazine-5-carbonitrile [LAS191954] | small molecules | EMA | 2014-10-15 | — | Almirall S.A. |
Human monoclonal antibody against Fas ligand | antibodies | EMA | 2012-02-09 | — | PinCell S.r.l. |
Mycophenolate mofetil | small molecules | FDA | 2006-05-26 | — | Hoffman-La Roche, Inc. |
Desmoglein 3 synthetic peptide (PI-0824) | peptides | FDA | 2004-10-26 | — | Peptimmune, Inc. |
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