Sustained Remission Without Corticosteroids Among Patients With Pemphigus Who Had Rituximab as First-Line Therapy: Follow-Up of the Ritux 3 Trial.

Importance: The Ritux 3 trial demonstrated the short-term efficacy and safety of first-line treatment with rituximab compared with a standard corticosteroid regimen in pemphigus. No data on the long-term follow-up of patients who received rituximab as first line are available. Objective: To assess the long-term efficacy and safety of the Ritux 3 treatment regimen. Design, Setting, and Participants: This 7-year follow-up study of the Ritux 3 trial included patients with pemphigus from 25 dermatology departments in France from January 1, 2010, to December 31, 2015. Exposure: Patients were initially randomized in the rituximab plus prednisone group or prednisone-alone group. Main outcomes and measures: The primary outcome was the 5- and 7-year disease-free survival (DFS) without corticosteroids, assessed by Kaplan-Meier curves. Secondary outcomes were occurrence of relapse, occurrence of severe adverse events (SAEs), and evolution of antidesmoglein (Dsg) antibody enzyme-linked immunosorbent assay values to predict long-term relapse. Results: Of the 90 patients in the Ritux 3 trial, 83 were evaluated at the end of follow-up study visit (44 in the rituximab plus prednisone group; 39 in the prednisone-alone group) with a median (IQR) follow-up of 87.3 (79.1-97.5) months. Forty-three patients (93%) from the rituximab plus prednisone and 17 patients (39%) from the prednisone-alone group had achieved complete remission without corticosteroids at any time during the follow-up. Patients from the rituximab group had much longer 5- and 7-year DFS without corticosteroids than patients from the prednisone-alone group (76.7% and 72.1% vs 35.3% and 35.3%, respectively; P < .001), and had about half the relapses (42.2% vs 83.7%; P < .001). Patients who received rituximab as second-line treatment had shorter DFS than patients treated as first line (P = .007). Fewer SAEs were reported in the rituximab plus prednisone group compared with the prednisone-alone group, 31 vs 58 respectively, corresponding to 0.67 and 1.32 SAEs per patient, respectively (P = .003). The combination of anti-Dsg1 values of 20 or more IU/mL and/or anti-Dsg3 values of 48 or more IU/mL yielded 0.83 positive predictive value and 0.94 negative predictive value to predict long-term relapse. Conclusions and Relevance: In this secondary analysis of the Ritux 3 trail, first-line treatment of patients with pemphigus with the Ritux 3 regimen was associated with long-term sustained complete remission without corticosteroid therapy without any additional maintenance infusion of rituximab.

The Role of T Follicular Helper Cells in Clinical Remission and Relapse in Patients with Pemphigus Treated with Rituximab.

BACKGROUND: Pemphigus is a rare chronic autoimmune disease. Recent studies have found that T follicular helper (Tfh) cells may play a role in autoimmune diseases. In this study, Tfh cells frequency, BCL6 gene expression, IL-21, and IL-6 cytokines levels were examined, with the aim of understanding the effect of RTX on these cells in the onset of clinical remission or relapse in patients with pemphigus. METHODS: 20 patients with pemphigus vulgaris and 20 healthy controls without any autoimmune diseases that were admitted to the Dermatology and Venereology Clinic of the Akdeniz University Hospital were included. Peripheral blood sample was taken from all individuals and studied to analyze Tfh cell distribution, IL-21 and IL-6 distribution in CD3+CD4+CXCR5+ lymphocytes with flow cytometry, plasma IL-21 levels with ELISA, and mRNA levels that refer to BCL6 expression with PCR. RESULTS: Circulating Tfh cell distribution and IL-21 and IL-6 distribution in CD3+CD4+CXCR5+ lymphocytes and mRNA levels that refer to BCL6 expression showed no difference between patient and control groups. However, in patients who had received rituximab treatment there was a significant reduction in Tfh cells compared with other groups. Plasma IL-21 levels were significantly higher in the patient group. CONCLUSIONS: We found that plasma concentrations of the cytokine IL-21 were greatly increased in the pemphigus compared with the control group. There were no significant differences in Tfh cell percentages between the patient and control groups. Tfh cells were decreased in patients who received rituximab treatment. Our findings show that the response to RTX in pemphigus causes a reduction in circulating T follicular helper cells, but not in the plasma IL-21 level. Further studies are required to clarify the role of Tfh cells in pemphigus vulgaris.

Pemphigus Vegetans of Hallopeau: A Case Report.

Dear Editor, Pemphigus vegetans (PV) of Hallopeau is a rare and indolent variant of pemphigus clinically characterized by vegetating lesions preceded by pustules mainly in flexural areas (1,2). This helps us to differentiate it from PV of Neumann, which is a more extensive and refractory disease, more alike to a pemphigus vulgaris outbreak with blisters which turn into vegetating plaques (3). We report the clinical presentation, course, and therapeutic response in a patient diagnosed with PV of Hallopeau from its early stage during a 3-year follow up. A 62-year-old man, non-smoker, presented at our clinic in July 2018 with hemorrhagic-serous crusts and fissures on the vermilion of the lower lip (Figure 1, a) and two merged circinate, sharply demarcated plaques on the right side of the groin (Figure 1, b). Plaque margins were elevated, with hypertrophic granulation tissue studded with pustules. Mucosal and cutaneous lesions persisted 6 and 4 weeks, respectively. The rest of the mucosa and skin were unaffected; the general state was good. The patient's family history for skin diseases was negative. The medical history included hypertension, atherosclerosis and hypercholesterolemia, hiatus hernia, and recent surgery (3 months prior) of an aortic abdominal aneurysm with reconstruction and synthetic graft placement. He was taking antihypertensives (fixed combination of 3 drugs, among them the ACE-inhibitor perindopril) with well-regulated blood pressure, statins, a pump-proton inhibitor, and acetylsalicylic acid. Differential blood count revealed eosinophilia. Histopathology finding showed acanthosis, suprabasal clefting with a suprabasilar bulla and acantholysis, prominent eosinophilic intraepidermal spongiosis, and heavy dermal infiltration of eosinophils and lymphocytes (Figure 2, a and b). The diagnosis of pemphigus was confirmed by direct immunofluorescence (DIF), which detected C3 deposits on the surface of keratinocytes throughout the epidermis of perilesional skin. Circulating pemphigus antibodies were detected by indirect IF. Only Dsg 3 antibodies were detected using an ELISA assay (233.23 RU/mL). After establishing the diagnosis of PV of Hallopeau, treatment with prednisolone 0.75 mg/kg/day orally in combination with adjuvant immunosuppression (azathioprine 100 mg daily) was started. Appropriate topical therapy with local steroids and antiseptic was applied. The steroid dose was titrated and gradually tapered down to the minimum required to control the disease - 10 mg. One-year remission was achieved. Azathioprine was withdrawn in October 2019 and since then the patient experienced a flare-up twice. The control of pemphigus flare-ups was achieved by a low dose of steroids (30 mg prednisolone orally). It remains debatable whether surgical trauma and radiology procedures such as angiographies (4) well as ACE-inhibitor drugs (5) triggered or aggravated the pemphigus. Early recognition and correct diagnosis of this rare type of pemphigus allows us to treat and control the disease successfully with lower doses of steroids, reducing complications to the minimum.

Pre-Infusion Checklist For Rituximab In Pemphigus Vulgaris Patients: Clinical Audit.

OBJECTIVE: To evaluate whether or not the pre-infusion checklist for rituximab was followed in patients of pemphigus vulgaris. Method: The audit, intervention and re-audit was conducted at the Dermatology Department, Medical Teaching Institution-Lady Reading Hospital, Peshawar, Pakistan, and comprised in-patients of pemphigus vulgaris, confirmed by skin biopsy and immunofluorescence, who received rituximab between January 1 to March 31, 2022. The randomly picked cases were reviewed to check if the standard guidelines for rituximab prior to infusion had been followed. After completion of the first audit cycle, the medical team was give awareness about the latest pre infusion rituximab guidelines, and they were also provided with a checklist and consent form to implement the change. Re-audit was performed from May to July, 2022, using the same method to see if improvements had been made. Data was analysed using SPSS 23. RESULTS: Of the 20 cases evaluated against 16 parameters, the first audit showed 7(43.5%) parameters to have been met across all cases. Re-audit comprised another set of 20 cases, and showed that 15(93.75%) parameters had been applied across the board Pneumococcal and influenza vaccine was the only element 1(6.25%) not touching universal application. CONCLUSIONS: Re-audit showed major improvement in compliance with the standard guidelines.

Pemphigus vulgaris as an immune-related adverse event in recurrent metastatic esophageal squamous cell carcinoma treated with ipilimumab plus nivolumab: a case report and literature review.

Ipilimumab plus nivolumab therapy is approved for patients with unresectable advanced esophageal squamous cell carcinoma (ESCC). Although a combination of immune checkpoint inhibitors (ICIs), compared to conventional chemotherapy, can improve overall survival in patients with advanced ESCC, this increases the incidence of immune-related adverse events (irAEs). Here, we describe an ESCC case that developed pemphigus vulgaris (PV), an extremely rare cutaneous irAE, during ipilimumab plus nivolumab treatment. The patient achieved a partial response to treatment. The PV was successfully managed after the cessation of ipilimumab and the use of a topical steroid. We should thus re-treat ESCC with nivolumab monotherapy. In the era of ICIs as standard cancer therapeutics, diagnostic criteria for blistering diseases need to be established to properly manage patients with cutaneous irAEs.

Ocular involvement in autoimmune bullous diseases.

Autoimmune bullous diseases represent a heterogenous group of disorders caused by autoantibodies against adhesion molecules; the location of the target protein determines the level of cleft formation. The spectrum of ocular lesions in autoimmune bullous diseases can range from mild symptoms to severe involvement with sight impairment and even, in some cases, blindness. In pemphigus vulgaris, the prevalence of ocular involvement has been reported to be between 7% and 26%. The most common clinical sign of ocular pemphigus vulgaris is bilateral conjunctivitis with hyperemia. Ocular involvement also occurs in 41% to 70% of patients with paraneoplastic pemphigus. The main ocular manifestations are bilateral cicatrizing conjunctivitis with symblepharon formation, and shortening of the fornices. In mucous membrane pemphigoid, ocular involvement is seen in 61% to 70% of patients; the most frequent ocular finding is cicatricial conjunctivitis. Patients with autoimmune bullous diseases having common ocular involvement should be assessed by an ophthalmologist to avoid serious complications. Diagnostic procedures and treatment require multidisciplinary care based on the close cooperation between dermatologists and ophthalmologists.

[Senear-Usher syndrome (seborrheic pemphigus): An exceptional case]. / Síndrome de Senear-Usher (pénfigo seborreico): un caso excepcional.

BACKGROUND: Among the autoimmune diseases causing erosive lesions and blisters on skin and mucous membranes is pemphigus. Within this is a rare subtype known as seborrheic pemphigus or Senear-usher syndrome which is characterized by broken blisters and crusts involving the seborrheic areas. CASE REPORT: A 40-year-old female patient, initially treated in a first level unit for a condition of 45 days of evolution, characterized by thick scabby lesions with an erythematous base, pruritic and painful, located in the center of the face, with posterior extension towards the abdomen, thorax, and extremities. Treatment consisted of prednisolone, with favorable evolution. The biopsy of the lesions with the diagnosis of seborrheic pemphigus. CONCLUSIONS: Senear-usher syndrome is a rare disease of multifactorial origin. Early diagnosis and adequate treatment are decisive factors to avoid the evolution and advanced forms of the disease.

ANTECEDENTES: Dentro de las enfermedades autoinmunes que provocan lesiones erosivas y ampollas en la piel y las mucosas se encuentra el pénfigo. Un subtipo raro de esta enfermedad es el pénfigo seborreico, o síndrome de Senar-Usher, caracterizado por ampollas rotas y costras que afectan las áreas corporales que secretan grasa. REPORTE DE CASO: Paciente femenina de 40 años, atendida inicialmente en una unidad de primer nivel por un cuadro de 45 días de evolución, caracterizado por lesiones costrosas gruesas de base eritematosa, pruriginosas y dolorosas, de localización centro-facial, con posterior extensión hacia el abdomen, tórax y extremidades. El tratamiento consistió en prednisolona, con evolución favorable. La biopsia de las lesiones confirmó el diagnóstico de pénfigo seborreico. CONCLUSIONES: El síndrome de Senear-Usher, o pénfigo seborreico, es una enfermedad excepcional, de origen multifactorial. El diagnóstico oportuno y tratamiento adecuado son factores decisivos para evitar la evolución de la enfermedad a formas avanzadas.

Pemphigus Vulgaris: More Than Just a Skin Disease.

INTRODUCTION: Pemphigus is a group of autoimmune diseases of the skin and mucous membranes that is characterized by multiple bullae formation. It is caused by autoantibodies directed against the cell surface of keratinocytes, resulting in the loss of cell-cell adhesion of keratinocytes. This disease can be very debilitating and difficult to treat if large surface areas are involved. METHODS: We performed a retrospective review of a complex case of pemphigus vulgaris in a 24-year-old man who develop partial-thickness skin lesions distributed throughout the entire body with a total body surface of 80% short after an episode of strep throat treated with amoxicillin. RESULTS: The patient had a complicated hospital course in which the standard treatment of the disease led to adverse effects that were successfully managed at our busy burn center. CONCLUSIONS: Pemphigus vulgaris is a complex skin disease in which treatment techniques carry their risk and must be tailored to the patient's specific needs. Treatment of this conditions at a burn center would be beneficial as demonstrated with conditions like Stevens-Johnson syndrome and toxic epidermal necrolysis.

Blocking soluble Fas Ligand ameliorates pemphigus: PC111 efficacy in ex-vivo human pemphigus models.

Pemphigus is a life-threatening, chronic, autoimmune bullous disease affecting both the skin and the mucous membranes. Based on the mainstream concept that blister formation occurs upon binding of autoantibodies to their antigen proteins (desmoglein1, DSG1 and desmoglein3, DSG3), current therapies mostly aim to suppress the immune system. To avoid the severe side effects associated with the chronic use of immunosuppressive treatments, we have developed PC111, a fully human monoclonal antibody targeting human Fas ligand (FasL). We have provided a number of in vitro and in vivo evidences showing that soluble FasL induces keratinocyte apoptosis followed by acantholysis. An anti-murine FasL prevents blister formation in the pemphigus neonatal mouse model. To confirm the mechanism of action (MoA) and the efficacy of PC111 in a human pemphigus context, we used the keratinocyte dissociation assay and two independent Human Skin Organ Cultures (HSOC) pemphigus models. PC111 reduced acantholysis in vitro, as shown by the dose-dependent reduction of fragments in the monolayer cultures. In the first HSOC model, normal human skin was subcutaneously injected with a scFv antibody fragment directed against DSG1 and DSG3, resulting in a severe acantholysis (70-100%) after 24 hours. PC111 inhibited blister formation to around 50% of control. In the second model, normal human skin was injected with a mixture of pemphigus patients' autoantibodies resulting in a less severe acantholysis (20-30%). PC111 significantly suppressed blister formation to more than 75% up to 72 hours. These results confirm PC111 MoA and demonstrates the efficacy of the anti-FasL antibody also in a pemphigus setting.

Paraneoplastic pemphigus misdiagnosed as juvenile dermatomyositis: A case report.

Paraneoplastic pemphigus (PNP) is a rare autoimmune skin disease closely related to tumors, characterized by a maculopapular rash with mucosal pain, bronchiole occlusion, and respiratory failure may occur over time, even resulting in death. We report a rare case of a child with autoimmune PNP misdiagnosed as juvenile dermatomyositis (JDM), and summarize the key points of differentiation of clinical manifestations and auxiliary examinations of PNP and JDM. When the diagnosis is not clear because the patient has features not typical of JDM, then skin biopsy and other diagnostic studies should be considered prior to any immunosuppressive therapy, as this could potentially obscure and delay the diagnosis of malignancy.

Paraneoplastic pemphigus and Castleman's disease: a case report and a revision of the literature.

BACKGROUND: In literature, a few reports described an association between paraneoplastic pemphigus (PNP) and Castelman's disease (CD), but no consensus have been proposed for the diagnostic-therapeutical approach. Aim of this study is to present a case report and explore the relationship between PNP and CD in pediatric patients, focusing on clinical manifestations, histopathological findings, treatment and outcome to find elements for an early diagnosis. CASE PRESENTATION: We present the clinical case of a 13 years old girl with a challenging diagnosis of PNP and CD who underwent therapy at first with Rituximab and then with Siltuximab, for the control of symptoms. CONCLUSIONS: Reviewing literature, 20 clinical cases have been described in the pediatric age. Diagnosis may be challenging, requiring an average of 3 months (range from 3 weeks to 2 years). In all cases, the initial manifestations were mucocutaneous lesions, especially oral lesions with poor response to conventional treatment. Systemic symptoms may be present as well. Therapeutical approach is still discussed with no consensus. Almost all patients received corticosteroids with poor response. Other drugs including azathioprine, methotrexate, cyclosporine and monoclonal antibodies have been evaluated for the control of the disease. Further studies and experimental trials urge to define the diagnostic criteria and therapy protocol.

A clinic-epidemiological study of 148 patients of pemphigus at Lady Reading Hospital, Peshawar: a case series.

A seven-year retrospective study was held at the Department of Dermatology, Lady Reading Hospital, Peshawar, between 2013 to 2020 to determine the demography and clinical features of pemphigus. Among 148 patients included in this study 88 (58%) were females and 60 (40%) were males with a female to male ratio of 1.46:1. Average age at onset of the disease was 38±12 years (range 14-75 years). On the basis of Autoimmune Bullous Skin Disorder Score (ABSIS), 14 (9.3%) patients had mild disease, 58 (38.7%) had moderate disease, and 76 (50.7%) patients had severe disease. In total, 144 (96%) patients had pemphigus vulgaris, 3 (2%) patients had pemphigus foliaceous and 1 (0.7%) patient had paraneoplastic pemphigus. Severe pemphigus was more frequently associated with multiple relapses (p=0.00). This study shows poor prognostic factors like severe pemphigus vulgaris associated with multiple relapses. Five years of follow-up shows that complete remission on minimal therapy was achieved more in patients who received Rituximab.

Autoimmune Skin Conditions: Autoimmune Blistering Disease.

There are many types of autoimmune blistering skin disease. Two of the most common are bullous pemphigoid and pemphigus vulgaris. Bullous pemphigoid is characterized by tense bullae created by a subepidermal split resulting from autoantibodies targeted at the hemidesmosomes at the dermal-epidermal junction. Bullous pemphigoid typically occurs in elderly people and often can be drug-induced. Pemphigus vulgaris is characterized by flaccid bullae because of an intraepithelial split triggered by autoantibodies targeting desmosomes. Diagnosis can be made for both conditions by physical examination, biopsy for routine histology, biopsy for direct immunofluorescence, and serologic studies. Both bullous pemphigoid and pemphigus vulgaris are associated with significant morbidity and mortality and diminished quality of life, making early recognition and diagnosis paramount. Management proceeds in a stepwise approach using potent topical corticosteroids along with immunosuppressant drugs. Rituximab recently has been shown to be the drug of choice for most people with pemphigus vulgaris.

Surgical management of gingival recessions in patients with refractory gingival pemphigus vulgaris: A multidisciplinary challenge.

BACKGROUND: Mucogingival surgery for root coverage of gingival recessions (GRs) is usually performed in patients with unremarkable periodontal and systemic health. However, the predictable results of surgical procedures and increasingly high aesthetic expectations of patients necessitate optimal management of GR also in patients with systemic conditions that affect the oral cavity. In patients with pemphigus vulgaris (PV), mucosal fragility and complicated surgical management of inflamed soft tissues are major challenges. METHODS AND RESULTS: A 36-year-old female patient with PV and deep GR on the mandibular incisors is presented. After initial unresponsiveness to steroids and immunosuppressants, complete clinical remission was achieved through repeated rituximab infusions and topical platelet-rich plasma. After > 1 year of stable clinical remission off therapy the patient successfully underwent surgical procedures for vertically coronally advanced flap with connective tissue graft. CONCLUSIONS: To the best of our knowledge, no studies have described the surgical management of GR in PV patients. Although controlled studies are required to confirm present results, complete and stable clinical remission is necessary to avoid complications. Collaboration among dermatologists, oral medicine specialists, and periodontologists is essential to determine whether mucogingival surgery for root surface exposure is indicated for PV patients. KEY POINTS: Why are these cases new information? This is the first report of root coverage in a patient with oral PV What are the keys to the successful management of these cases? The achievement of complete and stable clinical remission from oral PV Multidisciplinary collaboration among dermatologists, oral medicine specialists, and periodontologists What are the primary limitations to success in these cases? The refractoriness of gingival lesions induced by PV Poor mucogingival conditions of inflamed gingival tissues exacerbated by PV.

Localized CO2 laser treatment of a recalcitrant oral ulceration in pemphigus vulgaris.

INTRODUCTION: Recalcitrant oral lesions of pemphigus vulgaris (PV), an autoimmune blistering disease, can result in significant discomfort, difficulty in eating, and maintaining oral hygiene. Increasing the dosage of systemic medications to control such localized lesions results in an increased risk of adverse effects. CASE PRESENTATION: We describe a male patient diagnosed at age 51 with PV by oral biopsy that included a direct immunofluorescence examination. After further baseline laboratory testing, he was started on prednisone and mycophenolate. These medications were slowly tapered with adjustments guided by clinical signs. Mycophenolate was replaced with intravenous immunoglobulin monthly infusions due to adverse effects about 2 years after initiation. During the 4.5-year follow-up period after diagnosis, his oral and skin lesions were well-controlled apart from minor transient flares. However, a painful ulcerated lesion on the facial gingiva between #11 and 12 was nonresponsive, even with the use of topical clobetasol in trays. A carbon dioxide (CO2 ) laser was used to vaporize the recalcitrant lesion under local anesthesia. The procedure resulted in complete healing of ulceration with no recurrence until the most recent examination, 2 years postlaser surgery. CONCLUSION: Adjunctive procedures that can facilitate a decrease in the cumulative dosage of corticosteroids and immunosuppressants have great value in the management of PV. CO2 laser vaporization is safe, with minimal morbidity and no long-term side effects. It should be considered an adjunctive treatment option for the management of recalcitrant lesions in patients with oral PV. KEY POINTS: Why is this case new information? To our knowledge, this is the second report on the use of a CO2 laser in the treatment of recalcitrant oral lesions of PV and the first report with a documented long-term resolution of the treated lesions. What are the keys to the successful management of this case? A localized recalcitrant lesion was treated with this approach. All other mucosal and cutaneous sites were well controlled on the patient's systemic medication regimen. What are the primary limitations to success in this case? This approach is only relevant for the management of recalcitrant lesions in patients whose disease activity is otherwise well controlled. The availability of specialized equipment and trained clinicians is necessary.

Subcorneal pustular dermatosis-type IgA pemphigus associated with multiple myeloma: A case report and literature review.

Immunoglobulin A (IgA) pemphigus, also known as intercellular IgA dermatosis, is a rare autoimmune bullous disease presenting with IgA anti-keratinocyte cell surface autoantibodies. Concomitant lymphoproliferative disorders have been reported in IgA pemphigus, including IgA monoclonal gammopathy of undetermined significance and IgA type multiple myeloma (MM). A 35-year-old Japanese woman with a 3-year history of pruritic papulovesicles on her lower legs and trunk was referred to our department. Histopathological examination revealed acantholytic blisters, and results of both direct and indirect immunofluorescence were negative. Direct and indirect immunofluorescence were still negative 3 years and 7 months later. Approximately 7 years after her first visit, the patient was re-referred to us because of disease exacerbation. Histopathological findings revealed subcorneal blistering with acantholysis, in which neutrophil-dominant inflammatory cells were present. Indirect immunofluorescence was positive for IgA on the epidermal cell surface and both desmoglein (Dsg) 1/3 and (Dsc) desmocollin 1-3 enzyme-linked immunosorbent assays (ELISAs) for IgA were positive. The histological findings and positive Dsc1 IgA ELISA led to the diagnosis of subcorneal pustular dermatosis (SPD)-type IgA pemphigus. Further examination revealed hyper-IgA globulinemia, increased serum IgA-κ protein, and increased plasma cells in the bone marrow, enabling the diagnosis of IgA type MM. Daratumumab, lenalidomide, and dexamethasone (DLd) therapy was effective for both the MM and the skin lesions, resulting in negative results on Dsg1/3 and Dsc1-3 IgA ELISAs. The association between IgA pemphigus and IgA type multiple myeloma remains unclear, and only seven cases including the present case have been reported. Literature review revealed associations between SPD-type and IgA κ chain in IgA pemphigus and MM, and that in most cases the onset or diagnosis of MM was simultaneous or occurred after the diagnosis of IgA pemphigus. Therefore, clinicians should be aware of the development of multiple myeloma during the clinical course of patients with SPD-type IgA pemphigus.

Elevated serum level of B-cell activating factor (BAFF) after rituximab therapy in pemphigus vulgaris patients suggests a possible therapeutic efficacy of B-cell depletion therapies combined with anti-BAFF agents.

BACKGROUND: Rituximab is widely used for treatment of pemphigus patients. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) play key roles in B cell survival, maturation, and differentiation. Here, the effect of rituximab on BAFF and APRIL in patients with pemphigus vulgaris (PV) was studied. METHODS: Fifty PV cases and 56 healthy individuals were recruited. Patients received rituximab for a period of 6 months. The levels of BAFF and APRIL were measured in the serum samples. The frequency of CD19+ B cells was measured by flow cytometry. RESULTS: The level of BAFF was significantly higher in the patients at the baseline level than controls (P = 0.0005). The level of BAFF was significantly higher at the 3rd month follow-up compared to the baseline (P = 0.033). There was a significant increase in the BAFF level at the 6th month follow-up compared to baseline (P = 0.0134). There was no significant difference in the CD19+ B cells/total lymphocytes ratio in the PV patients between the 3rd and 6th month follow-ups. CONCLUSIONS: Elevated BAFF in the sera could be associated with PV immunopathogenesis. Inhibition of BAFF after rituximab therapy might interfere with repopulation of B cells and confer a therapeutic approach in PV.