Pemphigus vulgaris is a potentially life-threatening autoimmune blistering disorder driven by pathogenic IgG autoantibodies targeting desmoglein 3 and 1. While rituximab has transformed management-achieving complete remission off-therapy in 70-90% of patients-approximately 20-30% of patients relapse or fail to respond, defining a critical unmet need. The key drivers of rituximab-refractory disease include post-depletion B-cell repopulation fuelled by elevated BAFF and APRIL, persistence of long-lived plasma cells in bone marrow niches that evade anti-CD20 depletion, IgG4-dominant autoantibodies requiring high complement-dependent cytotoxicity, innate immune amplification via Fcγ-receptor signalling and human anti-chimeric antibody formation neutralizing the drug itself. This review critically evaluates five emerging targeted therapeutic classes addressing these mechanisms. Next-generation anti-CD20 monoclonal antibodies-ofatumumab, ocrelizumab, obinutuzumab and veltuzumab-offer enhanced effector functions, reduced immunogenicity and subcutaneous delivery for rituximab-intolerant or HACA-positive patients, though evidence remains at case and cohort level. BAFF/APRIL pathway inhibitors, principally telitacicept and ianalumab, target the B-cell survival axis elevated post-rituximab and show promise in pemphigus case reports and extrapolated phase 2/3 systemic lupus erythematosus data. Bruton tyrosine kinase inhibitors, particularly rilzabrutinib, demonstrated rapid disease control and meaningful steroid-sparing effects in phase 2 trials, though the pivotal PEGASUS phase 3 trial did not meet its primary endpoint. FcRn antagonists, led by efgartigimod, achieve 60-70% reduction in circulating IgG within weeks without broad immunosuppression; the phase 3 ADDRESS trial missed its primary endpoint, likely due to corticosteroid confounding rather than biological inefficacy. Finally, DSG3-CAAR T-cell therapy represents the most transformative approach-antigen-specific elimination of pathogenic anti-Dsg3 B cells while preserving normal humoral immunity-with early phase 1 data awaited. Rational combination strategies and refined trial designs will be essential to translate the biological promise of these next-generation agents into clinical practice for patients with refractory pemphigus.

Bullous pemphigoid is the most common autoimmune subepidermal blistering disease, typically diagnosed through a combination of clinical features, histopathology, and direct immunofluorescence (DIF). However, histopathological findings can be misleading when re-epithelialization shifts the blister plane from subepidermal to suprabasal, mimicking pemphigus vulgaris. We present the case of a 58-year-old woman with type 2 diabetes mellitus, diabetic neuropathy, and a sacral pressure ulcer admitted with a three-week history of generalized tense bullae in a symmetric distribution across the trunk and extremities, with subsequent oral mucosal involvement. The disease was classified as severe bullous pemphigoid. Skin biopsy revealed a suprabasal blister with eosinophilic infiltrate, a pattern classically associated with pemphigus vulgaris; however, DIF demonstrated linear immunoglobulin G and complement C3c deposition at the dermoepidermal junction, confirming bullous pemphigoid and categorically ruling out pemphigus. Initial treatment with systemic corticosteroids and immunosuppressants was complicated by septic shock secondary to a catheter-related bloodstream infection, hospital-acquired pneumonia, and urinary tract infection, requiring vasopressor support, adjustment of the immunosuppressive regimen, and antimicrobial escalation. The patient also developed progressive multifactorial anemia, sepsis-associated coagulopathy, and upper gastrointestinal bleeding. Following multidisciplinary management, she achieved near-complete resolution of skin lesions and clinical recovery, and was discharged with plans for rituximab as definitive steroid-sparing therapy. This case highlights two critical lessons: first, a suprabasal blister on histopathology does not exclude bullous pemphigoid, as re-epithelialization can alter the apparent cleavage plane, making DIF indispensable for an accurate diagnosis; second, severe bullous pemphigoid requiring intensive immunosuppression carries a substantial risk of sequential nosocomial infections warranting close microbiological surveillance, early source control, and timely modulation of immunosuppressive regimens.

Subdural empyema (SDE) is a life-threatening condition. Reports on SDE are scarce. We report the case of a 96-year-old immunocompromised patient on steroids for pemphigus who received repeat burrhole trephination and antibiotics to treat SDE. We identified Citrobacter koseri as the causative pathogen. Our patient made a good recovery at 2 months. We conclude that surgical treatment may yield a favorable outcome after cranial SDE, even in an elderly immunocompromised patient.

Hailey-Hailey disease (HHD), also known as benign familial pemphigus, is a rare autosomal dominant genodermatosis characterized by recurrent erosive lesions in intertriginous areas. Previous case reports have described clinical improvement with upadacitinib, but post-response maintenance strategies remain poorly defined. We report a 62-year-old woman with a 7-year history of refractory HHD who showed marked improvement after 2 months of upadacitinib 15 mg once daily. After 6 months of daily treatment, the lesions had completely cleared and disease control was stable. The regimen was then changed to 15 mg every other day after discussion with the patient. The change was based on sustained clinical control, concern about the financial burden of continued daily treatment, and a preference to limit prolonged systemic exposure; it was not prompted by an adverse event. The patient adhered to the alternate-day schedule, did not resume daily treatment, and required no rescue or additional therapy. During the subsequent 3 months, no new or recurrent lesions were observed and no apparent adverse events occurred. This case therefore documents short-term disease control after transition to an alternate-day maintenance schedule. Given the relapsing and fluctuating course of HHD and the limited follow-up after dose reduction, the observation should not be interpreted as evidence of durable remission or long-term efficacy.

Pemphigus is an autoimmune bullous disease. PNP/PAMS represents a rare subtype of autoimmune bullous disease, and typically associated with an underlying neoplasm, particularly lymphoproliferative disorders. Current management of PNP primarily involves glucocorticoids, immunosuppressants, and rituximab. This article reports a 67-year-old male who presented with generalized erythema, blisters, and oral erosions with pain for one month. Initially diagnosed with pemphigus, he received methylprednisolone treatment, which led to slight improvement in skin lesions but minimal resolution of oral ulcers. Based on the available clinical, histopathological, immunofluorescence, and serological findings, the patient was initially diagnosed with pemphigus vulgaris in the setting of CLL. However, the refractory oral mucositis, dual positivity for Dsg1 and Dsg3, and the underlying B-cell malignancy raised the concern for paraneoplastic pemphigus (PNP). Given that PNP-specific tests-including anti-plakin antibodies, indirect immunofluorescence on rat bladder, and immunoblotting-were not performed, a definitive diagnosis of PNP could not be established. Therefore, the condition was managed as "suspected CLL-associated PNP" Following the initiation of zanubrutinib in combination with ongoing corticosteroid therapy and CLL treatment, significant improvement of oral erosions was observed. In this case, the clinical improvement may be potentially related to zanubrutinib, but the concurrent corticosteroid therapy and the control of CLL likely contributed as well. If zanubrutinib did play a role, the mechanism might involve enhanced disease control or immune modulation. However, the current evidence is insufficient to draw a firm conclusion, and its true efficacy needs to be evaluated in further studies.

Pemphigus vegetans is a rare variant of pemphigus vulgaris characterized by vegetating plaques predominantly involving intertriginous areas. A 34-year-old woman presented with persistent painful oral lesions followed by progressive flexural, palmoplantar, and pan-ungual involvement. Examination revealed exuberant erosive vegetating plaques of the major folds, associated with oral erosions, palmoplantar pustules, and diffuse nail involvement. Histopathology showed papillomatosis, acanthosis, suprabasal cleavage, and acantholysis. Direct immunofluorescence demonstrated intercellular immunoglobulin G and complement C3 deposits, while indirect immunofluorescence detected circulating anti-intercellular substance antibodies, confirming Hallopeau-type pemphigus vegetans. Treatment with systemic corticosteroids and rituximab resulted in progressive healing of the cutaneous and mucosal lesions, with subsequent nail regrowth. This case highlights the importance of considering pemphigus vegetans in patients with vegetating lesions of the folds associated with mucosal involvement and extensive pan-ungual involvement, a rare but clinically distinctive feature of this disease.

Pemphigus vulgaris is a severe autoimmune blistering disease that occasionally develops lesions refractory to conventional systemic immunosuppressive therapy. We report the first documented case of successful treatment of therapy-resistant pemphigus vulgaris using cold atmospheric plasma. A 34-year-old woman presented with extensive oral and genital erosions that dramatically improved after initiating therapy with pulse corticosteroids in combination with cyclophosphamide. In the following weeks, she developed treatment-resistant facial erosions that persisted for 6 months despite aggressive systemic therapy consisting of intravenous immunoglobulin, azathioprine, and plasmapheresis. After 3 weekly cold atmospheric plasma treatments at 33 to 37 °C with a 2 cm torch gap for 3 min per treatment zone, the patient had remarkable clinical improvement, with an estimated > 80% epithelialization of facial erosions within 4 weeks, progressing to complete epithelialization by week 6. Disease activity assessment using the Pemphigus Disease Activity Index confirmed rapid improvement from a baseline of 14 to 0 within 6 weeks. Indirect immunofluorescence was negative throughout treatment. Sustained disease remission was achieved for 24 months. This novel application of cold atmospheric plasma is a promising therapeutic approach for recalcitrant lesions of pemphigus vulgaris.

Rituximab induces prolonged B-cell depletion and may alter protective antibody levels, but longitudinal antibody to hepatitis B surface antigen (anti-HBs) patterns in pemphigus vulgaris remain poorly characterized. This study evaluated anti-HBs levels and seroprotection after rituximab and explored associated factors. Methods: This retrospective cohort included 84 patients with pemphigus vulgaris treated with rituximab between 2010 and 2026 who had baseline and post-treatment anti-HBs measurements. Longitudinal changes in log-transformed anti-HBs levels were analyzed using a linear mixed-effects model with categorical time and a patient-specific random intercept. The probability of anti-HBs < 10 IU/L was assessed using a binomial generalized estimating equation model. Paired Wilcoxon signed-rank tests were performed as sensitivity analyses. Results: The median baseline anti-HBs level was 49.7 IU/L, and 34 patients (40.5%) had levels < 10 IU/L. Time was associated with longitudinal anti-HBs levels overall (p = 0.002). Compared with baseline, model-estimated levels were lower at month 6 (geometric mean ratio [GMR] 0.61, 95% CI 0.42-0.88), month 9 (GMR 0.64, 95% CI 0.45-0.89), and month 18 (GMR 0.50, 95% CI 0.32-0.78). Time was not significantly associated with the odds of anti-HBs < 10 IU/L (global p = 0.490). Positivity for antibody to hepatitis B core antigen (anti-HBc) IgG was associated with higher longitudinal anti-HBs levels (adjusted GMR 13.24, 95% CI 5.32-32.95; p < 0.001). No clinically or biochemically evident hepatitis B virus (HBV) reactivation was documented, although HBV DNA was not routinely monitored. Conclusions: Quantitative anti-HBs levels varied significantly during follow-up; whereas, the probability of crossing below the conventional seroprotection threshold did not increase significantly. These findings support HBV serological assessment and cautious interpretation of serial anti-HBs measurements in rituximab-treated patients with pemphigus vulgaris.

Background: Pemphigus is a rare group of autoimmune blistering diseases characterized by autoantibody-mediated loss of keratinocyte adhesion, resulting in intraepithelial blister formation involving the skin and mucous membranes. Pemphigus Vulgaris (PV) is the most common type of pemphigus, which usually presents in adulthood and has a prevalence rate of about 2.83 cases per million person years worldwide. The prevalence rate in children and adolescents is relatively uncommon; however, it accounts for about 1.4 to 3.7 percent of all cases of pemphigus vulgaris reported worldwide. The involvement of oral cavity is clinically significant since it can present prior to the disease or as its predominant feature. Hence, this narrative review seeks to review literature on pemphigus with involvement of oral cavity in children and adolescents. Objective: The objective of this study was to review the current literature regarding epidemiology, pathogenesis, clinical presentation, diagnosis, histopathological characteristics, treatment, and outcomes of pemphigus with oral involvement in children and adolescents. Materials and Methods: A literature search was conducted using the PubMed/MEDLINE, Scopus, and Cochrane Library databases to identify relevant studies published between 2015 and 2026. The search strategy included terms related to pemphigus, pediatric patients, and oral manifestations. Articles involving patients younger than 18 years of age with oral involvement were screened according to predefined inclusion criteria. Following database screening, duplicate removal, and full-text assessment, 25 studies comprising a total of 51 patients with documented oral or orofacial involvement were included in the final review. Results: Pemphigus vulgaris was the predominant subtype, with oral lesions representing the initial or sole manifestation in the majority of patients. The gingiva, mucosa, tongue, lip, and palate were the most common affected areas in the mouth. The lesions in these areas usually appeared as painful erosion, ulcers, and desquamative gingivitis. Histopathology with the presence of acantholysis in the suprabasal area and direct immunofluorescence was the most definitive test for diagnosis. Systemic corticosteroids were the mainstay of treatment in conjunction with steroid sparing agents in some cases, with good results in difficult cases using rituximab. Overall, most patients achieved partial or complete clinical remission following appropriate treatment, although relapses were occasionally reported. Conclusions: Pemphigus in children and adolescents is rarely encountered; however, it should be included as a differential diagnosis of erosive/ulcerative lesions. Early identification, diagnosis, and treatment through a collaborative approach from dental practitioners are critical. Further research is required at multiple centers to gain a better understanding of the disease and to develop evidence-based guidelines for diagnosis and treatment of pediatric patients.