Introduction Pemphigus is an autoimmune bullous disease caused by autoantibodies against desmoglein (DSG) 1 and/or 3 and comprises two main subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). PV affects the skin and/or mucosa and includes two forms: mucocutaneous PV (mcPV; anti-DSG1 and anti-DSG3) and mucosal PV (mPV; anti-DSG3). PF, characterized by anti-DSG1 autoantibodies, is limited to the skin. Pemphigus is effectively treated with rituximab, a B cell-depleting therapy. However, about half of patients relapse, with a subset exhibiting a shift in clinical subtype following relapse, known as clinical phenotype transition. This study aims to investigate clinical phenotype transition in relapsed pemphigus patients following rituximab treatment. Methods A single centre, exploratory retrospective cohort study was conducted, reviewing the medical records of patients with pemphigus who received at least one treatment cycle of rituximab between December 2006 and December 2023. Clinical and immunological data were collected at several time points during the first cycle of rituximab treatment. Results 109 patients were included, of whom 44% (48/109) achieved sustained complete remission, while 56% (61/109) experienced relapse. Among the 61 patients who relapsed, 26% (16/61) experienced a clinical phenotype transition. All had an initial diagnosis of mcPV. Among these, 75% (12/16) transitioned from mcPV to mPV and 25% (4/16) from mcPV to PF. Clinical phenotype transitioned patients often remained seropositive for anti-DSG3 at clinical remission, a pattern not observed in patients who did not experience a clinical phenotype transition. Conclusions Clinical phenotype transition was observed exclusively in mcPV patients, suggesting that such changes do not represent a true alteration in disease subtype but rather reflect persistent activity of the same pathogenic autoantibody due to suboptimal B-cell depletion, suggesting undertreatment with rituximab. These findings support the need to refine rituximab treatment regimens to achieve complete B-cell depletion, reduce relapse rates, and optimize long-term disease control in pemphigus.

Comment on ‘Efficacy, safety, and B-cell depletion capacity of 3 rituximab dosing regimens in the treatment of moderate-to-severe pemphigus vulgaris and pemphigus foliaceus: A 52-week clinical trial’

The Multikinase Inhibitor Midostaurin Mitigates Loss of Intercellular Adhesion and Skin Blistering in Pemphigus Vulgaris.

Pemphigus is a group of rare autoimmune blistering disorders affecting the skin and mucosal surfaces, caused by pathogenic immunoglobulin G (IgG) autoantibodies targeting desmosomal cadherins, specifically desmoglein-1 and desmoglein-3, which are key components of desmosomes. There are two main forms of pemphigus: pemphigus vulgaris (PV) and pemphigus foliaceus (PF), with PV being the most common. Pemphigus can be life-threatening owing to the progressive loss of the epidermal and epithelial barrier function. However, the introduction of rituximab, an anti-CD20 monoclonal antibody, has significantly improved treatment outcomes in pemphigus. This review provides a comprehensive overview of the current treatment landscape for pemphigus, highlighting both established and emerging therapeutic approaches.

Bead aggregation assays with desmoglein and desmocollin for the evaluation of disease activity in pemphigus.

Introduction Artificial intelligence and, in particular, machine learning (ML) methods have recently found broader applicability in many medical fields, including dermatology. They can be used to predict patient`s response to therapy, severity and activity of various diseases, including dermatologic conditions. ML particularly has been used for stratification of dermatoscopic features in dermatooncology (to classify malignant and benign skin neoplasms), as well as in patients with immune-related dermatoses (psoriasis, atopic dermatitis, acne, etc.). It is important to note that direct immunofluorescence reaction image analysis systems were most often used for patients with severe bullous dermatoses (BD) and showed high sensitivity in recognizing diagnostic data. However, it should be noted that simultaneous analysis of imaging, genetic, and immunologic data using ML techniques has not been performed. The goal of the study The study aimed to design a prognostic model to predict resistance to systemic glucocorticosteroids (CSs) in patients with BD, and to classify them into steroid-resistant and steroid-sensitive subgroups based on the obtained laboratory data on genomic (HLA-DRB1 and HLA-DQB1, A3669G polymorphism of the β-isoform of the glucocorticoid receptor (GR), expression of α- and β-isoforms of GR) and non-genomic (TNF- α, IL4, IL15, IL10, CXCL8, CLL11, granulysin) mechanisms, using ML methods to improve the accuracy of early diagnosis of these diseases and to ensure timely appointment of personalized therapy with immunosuppressive, cytostatic and biological drugs. Materials and Methods The study included 150 patients based on the evaluation of HLA-DRB1 and HLA-DQB1 alleles, A3669G polymorphism of the β-isoform of GR, and expression of α- and β-isoforms of GR by PCR. Of these, 107 patients were pemphigus (AP), 86 (57.3%) - pemphigus vulgaris (PV), 13 (8.67%) - pemphigus foliaceus (PF), 6 (4%) - paraneoplastic pemphigus (PNP), and 2 (1.4%) - pemphigus vegetans (Pveg); 29 (19.3%) with bullous pemphigoid (BP); 14 (9.33%) from the severe bullous allergic reaction group - Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN); and 92 healthy controls. 67 BD patients were included in the group in which cytokine, chemokine profiles, and granulysin levels in serum and blister fluid were detected and evaluated by ELISA. Of these, 43 patients with pemphigus, 11 - with BP, 13 - with SJS/TEN and 43 healthy controls. The following ML methods were used: logistic regression, support vector machine, “decision tree”, “random forest”, “gradient boosting”, operational analysis (AUC, ROC) and metrics “recall” and “precision”. Results The logistic regression method showed the highest metrics: “Recall” (1.000), “Precision” (0.938) and “ROC-AUC” (0.992), indicating that this model was quite accurate in distinguishing between classes and a very high probability of the algorithm correctly determining whether the person was patient with BD or healthy. We derived the formula P(Y=1)=1/(1+e^(-(-4.0479+0.1102∙Alfa) ) ), which indicates that when the expression value of α-isoform of GR exceeded 36.7 units, the probability of developing BD was more than 50% (95% CI: 1.084-1.150; significance: 1.116). The support vector machine highlighted the most significant features predictive for SR: DRB1 alleles in high resolution, such as DRB1*13:02; DQB1*05:02, DQB1*02:01, DQB1*05:01 and DQB1*03:01, and the presence of A3669G polymorphism of the β-isoform of GR. Conversely, alleles that increased the likelihood of lack of SR in BD patients included DQB1*06:02, DQB1*01:01, DQB*04:03, and DQB1*06:03. “CatBoost” and “random forest” methods most accurately predicted the likelihood of SR in BD patients when the following most significant features were present: high levels of IL15, IL4 and CXCL8 in blister fluid, high serum granulysin levels, diagnosis and severity of AP, administration of azathioprine (F1-metric: 0.538721, ROC AUC: 0.879167, Recall: 0.541667, Precision: 0.857143) and presence of type 2 diabetes mellitus. Conclusion The obtained formula enables determination tendency of the feature impact (high expression of α-isoform of GR) on the probability of BD using the odds ratio and to risk-stratify patients with a very high degree of accuracy. The random forest algorithm and the support vector machine enable us to classify BD patients into steroid-resistant and steroid-sensitive subgroups based on the level of HLA class II alleles and the presence of the A3669G polymorphism of the β-isoform of GR. Blister fluid can be used for diagnosis, differential diagnosis, prediction of the severity of BD, and evaluation of response to CSs therapy. In addition, blister fluid analysis will be able to predict patient`s response to conventional CSs therapy at early stages of the disease, allowing timely correction of treatment and thereby reducing the risk of potential complications and progression of BD.

Autoantibodies, in the blistering skin disease pemphigus primarily target desmosomal cadherins and cause loss of keratinocyte adhesion and epidermal blistering via signaling events. Pemphigus vulgaris is associated with autoantibodies (PV-IgG) against desmoglein (Dsg)1 and Dsg3 and pemphigus foliaceus (PF) with antibodies against Dsg1 only. In previous studies, protein kinase C (PKC) inhibition was protective in murine but not in human epidermis. Here, we investigated the roles of PKC subtypes for pemphigus pathogenesis. We applied the ex vivo human skin organ culture model, dispase-based dissociation assays, Western blot analysis, confocal and simulated emission depletion (STED) microscopy to study underlying mechanisms in vitro. First, we investigated the role of PKC subtypes for PV-IgG-induced epidermal blistering in human skin. Surprisingly, the inhibitor of atypical PKC isoforms (aPKC) CRT0066854 (CRT) completely abolished acantholysis whereas the conventional PKC (cPKC) inhibitor Gö6976 (Gö) did not. In cultured keratinocytes, both CRT and Gö were effective to inhibit loss of cell adhesion, keratin filament retraction and Dsg3 depletion in response to PV-IgG as well the pathogenic Dsg3-specific IgGs AK23 and 2G4. In contrast, reduced cell adhesion and keratin filament retraction in response to PKC activation by phorbol-12-myristate-13-acetate (PMA) and PF-IgG was blocked by inhibition of cPKC but not of aPKC. Mechanistically, both cPKC and aPKC were required for PV-IgG-induced translocation of PKC towards peripheral keratin filaments and conformational changes in Dp. These findings demonstrate that aPKC is critical for blistering in human epidermis in PV dependent on the autoantibody profile.

ABSTRACT Pemphigus vulgaris (PV) and foliaceus (PF) are rare autoimmune blistering diseases traditionally treated with systemic corticosteroids, immunosuppressants, intravenous immunoglobulins, and rituximab. Nonetheless, a subset of patients remains refractory or has contraindications to these conventional therapies. We present three cases of PV and PF treated with dupilumab. Two patients exhibited rapid clinical improvement. However, one patient with pemphigus foliaceus showed no response to dupilumab treatment, leading to its discontinuation. Recent reports have documented nine cases of pemphigus treated with dupilumab (six PV and three PF). The cases showed a rapid clinical improvement, although dosing regimens varied. One patient discontinued treatment due to lack of efficacy after 4 weeks of follow‐up. Dupilumab appears to be a promising therapeutic alternative for patients with PV and PF. Further studies are needed to evaluate its efficacy.

Background/Objectives: Pemphigus vulgaris (PV) and foliaceus (PF) are autoimmune blistering diseases mediated by IgG antibodies directed against desmogleins 1 and 3 and are still considered life-threatening disorders. In recent years, rituximab has been shown to be very effective, especially in PV and mainly in short follow-ups. The role of rituximab in achieving long-lasting complete clinical remission (cCR) in pemphigus still needs to be determined. Therefore, the aim of our study was to assess the efficacy, measured by achieving long-lasting cCR, and safety of rituximab in both PV and PF over an 8-year follow-up in light of several factors (body mass index—BMI, severity of disease—PDAI, age, gender, disease duration, COVID-19 period). Methods: In total, 28 patients with pemphigus were treated with rituximab and followed-up at one center. The entire analysis was performed using statistical methods. Results: Long-lasting cCR was achieved in 5 out of 6 patients (83%) with PF and 10 of 22 (45.5%) patients with PV. Univariate and multivariate analysis disclosed that studied factors did not statistically correlated with achieving long-lasting cCR. Among studied patients, few developed side effects, mainly urinary tract infection; one patient had sepsis, and one patient died. Conclusions: This study has demonstrated that rituximab is highly effective in PF and quite effective in PV over an 8-year follow-up in relation to independently studied factors. Moreover, the COVID-19 pandemic was not a negative factor influencing cCR achievement since 82% of patients treated with rituximab during that time still achieved cCR.

ABSTRACT Objectives: Rituximab induces a rapid remission in most patients with pemphigus. To evaluate the efficacy and adverse effects of rituximab in the treatment of pemphigus at the Vietnam National Hospital of Dermatology and Venereology. Methods: A retrospective study was conducted on 41 patients with pemphigus who attended our hospital between 2019 and 2024. Each enrolled patient received two doses of rituximab (1000mg per dose) administered as intravenous infusions two weeks apart. Subsequently, a maintenance dose of 1000mg was administered intravenously at month 6 or 12, followed by every 6 months based on clinical evaluation. The efficacy and safety of the treatment were assessed through pemphigus disease area index (PDAI) evaluations conducted before and after therapy, monitoring clinical responses, and recording any adverse events during follow-up. Results: 41 patients with pemphigus (pemphigus vulgaris: 39 patients, pemphigus foliaceus: 2 patients) who were treated with rituximab and followed for a median period of 20.5 months. The average patient age was 49.2 years, with males representing 31.7% of the cohort. The mean number of infusions administered per patient was 3.02. Complete remission was achieved in 32 (78%) patients, and all patients responded to treatment. The mean time to achieve disease control and complete remission was 4.8 ± 1.1 weeks and 8.2 ± 3.8 months, respectively. Relapse occurred in six (14.6%) patients after an average duration of 17.0 ± 2.5 months. One patient developed pneumonia as an infectious complication and subsequently died. Conclusions: Rituximab is a highly effective therapeutic agent for the management of pemphigus. It enables rapid disease control and achieves high rates of complete remission.

Background: The immune bullous disorders are characterized by a pathogenic immune response against the structural proteins of keratinocytes or dermoepidermal basement membrane zone. Septicemia and bacterial skin infections are the main causes of mortality and morbidity in immunobullous disorders. Aim: To study the bacteriological profile of active cutaneous lesions present in autoimmunobullous disorders and their antibiotic sensitivity patterns. Materials and Methods: A cross-sectional study conducted from September 2022 to June 2024. Cases confirmed by biopsy and/or immunofluorescence with clinically active cutaneous lesions were included for culture and sensitivity. Results: Out of the 85 patients diagnosed with autoimmunobullous disorders, 48 (56.5%), 18 (21.2%), and 15 (17.6%) had pemphigus vulgaris (PV), pemphigus foliaceus, and bullous pemphigoid (BP), respectively. The study included patients ranging in age from 0 to 85 years old. The most commonly affected groups were young adults in the 20–29 years’ age range and older patients in the 60–69 age range, with a bimodal distribution. Females outnumbered males. The percentage of nonsterile swabs on pus culture and sensitivity was 47.1%, which was lower than the percentage on sterile swabs (54.5%). The most common organism isolated was Staphylococcus aureus (SA) (92.25%) in which 37.5% was resistant to methicillin, followed by Pseudomonas aeruginosa (5%) and Klebsiella pneumoniae (2.5%). Pemphigus foliaceus patients (55%) had the highest rate of bacterial growth, followed by PV (39.86%) and BP patients (33.33%). The majority of BP cases (66.67%) had sterile pus cultures, which were subsequently followed by pemphigus foliaceus (45%) and PV (63.14%). SA was 100% sensitive to antibiotics teicoplanin, linezolid, nitrofurantoin, vancomycin, tigecycline, followed by trimethoprim/sulfamethoxazole (94.44%), rifampicin (88.89%), oxacillin (88.89%), daptomycin (88.89%), and azithromycin (77.27%). The most resistant antibiotic to SA was benzyl penicillin (83.33%), which was followed by erythromycin (38.88%), ciprofloxacin (77.77%), and levofloxacin (61.11%). The sensitivity pattern for methicillin-resitant SA (MRSA) to vancomycin was 100% followed by tetracycline (93.33%), tigecycline (93.33%), trimethoprim/sulfamethoxazole (93.33%), and nitrofurantoin (86.67%). The antibiotics with the highest MRSA resistance were erythromycin (73.88%), ciprofloxacin (86.777%), levofloxacin (86.67%), and benzyl penicillin (100%). Conclusion: In 45% of the cases, bacterial growth was seen, and SA was the most commonly isolated organism. Secondary cutaneous bacterial infection was more common in pemphigus foliaceus. The most resistant antibiotic was benzyl penicillin, while vancomycin was 100% sensitive to MRSA.

BackgroundPatients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia have autoantibodies directed against different proteins in the skin and internal organs. In this study we investigated autoantibodies in the intervertebral disk (IVD) and surrounding spinal structures since most patients suffer from back pain.MethodsWe tested autoreactivity using indirect immunofluorescence, reflectance, and confocal microscopy using patient autoantibodies, with both human and bovine tissue as antigen sources. We tested 45 sera from patients and 45 control sera from the endemic area matched by age, sex, demographics, and work activity. Additional mass bone density and trabecular bone score (TBS) were determined in selected cases.ResultsMost of the patient sera revealed polyclonal autoreactivity against previously known and new neural receptors present in the IVD (translamellar cross-bridges of the annulus fibrosus and the nucleus pulposus), neurovascular bundles, and paraspinal neurovascular packages as well as in the anterior and posterior longitudinal ligaments (P<0.001). Patient autoantibodies co-localized with commercial antibodies to MYZAP, desmoplakins I–II, plakophilin-4, and ARVCF (P<0.001). Controls were negative. Triton X-100 and paraformaldehyde allowed us to see the complex morphological 3-dimensional shape of the nerves and receptors. We also found that the patients showed altered microarchitecture of the lumbar spine and low trabecular density, thus suggesting osteoporosis and/ or osteopenia.ConclusionsThe autoantibodies to neural receptors in the IVD and surrounding structures and the osteopenia may contribute to patient back pain. Also, El Bagre-EPF autoantibodies provide a new tool to study the complexity of these neural receptors.

Over 20% of patients with chronic wounds have an autoimmune disease. Bullous autoimmune dermatoses hold a special place among the dermatological pathologies associated with chronic ulcers, Wound surfaces in this group of patients quickly become infected without prudent care. Besides, the treatment of ulcers in patients with bullous dermatoses is quite a challenging task, as even minimal skin injury during dressing changes can lead to the development of an ulcer defect. In this regard, a clinical case report of a female patient diagnosed with “pemphigus foliaceus with concomitant rapidly progressive multiple sclerosis” receiving biological therapy appears to have interesting features. The main complaint included chronic ulcerous defects in the intergluteal fold area, which persisted for a long period. In addition to standard therapy for pemphigus foliaceus, the female patient’s wound was treated with LUOFUCON extra silver alginate dressing for 3 weeks, which was changed every 7 days. During the therapy, almost complete epithelialization of the wound surface was achieved by day 12. This case demonstrates the need to pay careful attention to wound hygiene, especially in cases of hard-to-heal ulcers. The antimicrobial dressings, along with the sanitation of the wound surface, can effectively combat infection. Alginate dressings absorb wound fluid and maintain a moist environment, which, together with a powerful antibacterial effect, improves the wound microenvironment and promotes faster epithelialization. At the same time, the dressings neither stick to the wound bed, nor injure it during dressing changes, which is especially important in patients with bullous dermatoses.

Efficacy, safety, and B-cell depletion capacity of 3 rituximab dosing regimens in the treatment of moderate-to-severe pemphigus vulgaris and pemphigus foliaceus: A 52-week clinical trial.

Prurigo nodularis imitators unmasked.

Background Pemphigus relapse after rituximab treatment remains a challenge. Aim To correlate the change trends of immunological biomarkers with timing of pemphigus relapse, and identify its predictors following rituximab treatment Methods This prospective cohort study included 44 patients with pemphigus treated with a rituximab biosimilar (Rheumatoid arthritis protocol). Clinical data were recorded at baseline, and immunological biomarkers (anti-DSG1, anti-DSG3, anti-AChRM3, CD19+ B-cells, CD19+27+ memory B-cells) were estimated at baseline and every three months till 12 months. Patients were clinically followed-up for 2 years or until relapse and grouped as early (<12 months) relapse, relapsing between 12-24 months, and no relapse till 24 months. Results Twenty-four (54.5%) patients relapsed by 2 years, with 18 (75%) relapsing within the first year. Early (3-6 months) rise in CD19+ B-cells, anti-DSG3 and anti-DSG1 levels, and delayed (9-12 months) anti-DSG3 rise distinguished early from late relapse, while patients remaining relapse-free exhibited no significant immunological changes. At month 6, 73.3% of early relapsing patients had anti-DSG3 >120 RU/mL, as compared to 27.3% of patients without early relapse (p=0.008). Early relapse rates were significantly higher in patients with incomplete B-cell depletion at 3 months (100% vs 35%; p=0.02). There was no significant difference in the relapse rates based on B-cell repopulation (p=0.20). Incomplete B-cell depletion at 3 months and/or anti-DSG3 >120 RU/mL at 6 months had a positive and negative predictive value of 64.7% and 87.5% respectively, for early relapse. Limitations Relatively small and heterogeneous sample, including both pemphigus vulgaris and foliaceus, as well as treatment-naïve and relapsed patients Conclusion Patients with incomplete B-cell depletion and/or rising anti-DSG3 are at risk for early relapse and may benefit from closer monitoring or a maintenance rituximab infusion at 6 months.

A new variant of endemic pemphigus foliaceus, El Bagre-EPF, is an orphan autoimmune disease occurring in El Bagre and neighboring municipalities in Colombia, South America. We aimed to evaluate current state-of-the-art databases and protein-protein interactomes, focusing on post-translational modifications as potential tools to study interactions among El Bagre-EPF antigen proteins. We consulted multiple databases for the known target antigens and their protein-protein interactions. We searched for their network nodes (they represent proteins; each node corresponded to all the proteins produced by a single, protein-coding gene locus). We also searched for any post-translational modifications. We identified similarities in proteins bound by several autoantigens but also found differences in protein linkages. We found that desmoglein, periplakin, desmoplakins, and proteins from subfamilies of the Armadillo repeat proteins and some spectrin domains linked to other cell junctions; these played important roles in membrane-plaque and intermediate filament junctions. A typical drawback in current databases is the lack of information on lipid-protein interactions. Our results show that state-of-the-art protein databases as tools for studies of interactomes fall short in areas including tertiary and quaternary protein interactions and in vivo protein functioning. Enhanced three-dimensional or multi-dimensional functions are required for more accurate interactome analyses.

Background: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune blistering disorders characterized by pathogenic autoantibodies against desmosomal adhesion proteins, leading to cutaneous and mucosal erosions. The extensive skin barrier disruption, combined with immunosuppressive therapies, predisposes patients to severe and recurrent infections, significantly impacting morbidity and mortality. Objective: This review examines the epidemiology, microbiological profiles, risk factors, and clinical management of infections in pemphigus patients, with a focus on bacterial, viral, fungal, and opportunistic pathogens. Methods: A comprehensive literature review was conducted using PubMed, Scopus, and Web of Science, analyzing studies on infectious complications in pemphigus from 1990 to 2024. Results: The most prevalent infections include Staphylococcus aureus and Streptococcus pyogenesbacteremia, herpes simplex virus (HSV) reactivation, disseminated candidiasis, and opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP) in heavily immunosuppressed individuals. Corticosteroids and rituximab further exacerbate infection risks by inducing lymphopenia and hypogammaglobulinemia. Conclusion: Prophylactic antimicrobial strategies, early diagnosis, and judicious immunosuppression titration are critical in reducing infection-related complications in pemphigus. Multidisciplinary approaches involving dermatologists, infectious disease specialists, and microbiologists are essential for optimizing outcomes.

A case of pemphigus foliaceus identified after deucravacitinib treatment in a patient mistaken for psoriasis

Abstract Pemphigus encompasses a rare group of autoimmune bullous diseases characterized by blisters and erosions of the skin and mucosal membranes. Rituximab, an anti-CD20 chimeric monoclonal antibody that reduces circulating B cells, is an effective treatment for pemphigus. Its use as a first-line agent is now part of both the European Union and US guidelines, but commissioning criteria set out by National Health Service England consider rituximab as a third-line treatment for this condition. There is growing evidence that delayed prescription of rituximab can prolong time to disease remission and worsen disease-associated morbidity. We report a retrospect analysis of 38 patients with pemphigus vulgaris (PV) and pemphigus foliaceus (PF) prescribed rituximab from 2014 to 2024 in a single tertiary centre. Overall, 86% (n = 33) had PV and 14% (n = 5) had PF. Our cohort included 20 male and 18 female patients, and the age at diagnosis ranged from 23 to 84 years. Diagnosis was with histopathology, direct immunofluorescence and serology, including indirect immunofluorescence and/or enzyme-linked immunosorbent assay (desmogleins 1 and 3). All patients received prednisolone, ranging from 0.5 mg kg−1 to 1 mg kg−1. Second-line treatment was with mycophenolate mofetil in 76% (n = 29), azathioprine in 7% (n = 3) and dapsone in 5% (n = 2). Third-line treatments included azathioprine, dapsone and methotrexate. Patients received an average of 2.3 treatment modalities before rituximab. The interval between diagnosis and commencing rituximab varied between 1 month and 6 years, with patients diagnosed more recently tending to start rituximab sooner. Rituximab was administered as two doses of 1 g spaced 14 days apart. Complete remission was achieved by 52% (n = 20) of patients 6 months after starting rituximab. Of these, 85% were still taking prednisone and/or mycophenolate mofetil at 6 months, with further reduction and cessation of these medications documented over a longer timeframe. Partial remission was achieved by 42% (n = 16) 6 months after rituximab. Ten patients relapsed and required a second treatment with rituximab. The interval between the initial rituximab and disease relapse in these patients was 1–5 years. Three patients were treated with a third course of rituximab and one patient required a fourth course. Patients given rituximab at a later stage in their disease had a higher cumulative dose of prednisolone. The patients requiring multiple courses of rituximab or taking longer to achieve complete remission had a longer duration between diagnosis and initial rituximab treatment. Our real clinic findings highlight the management of patients with severe or recalcitrant pemphigus. The results are corroborated by the increasing body of convincing medical evidence suggesting that earlier administration of rituximab for pemphigus is both safer and more efficacious than standard therapy and make a case for earlier use of rituximab in this challenging cohort.