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Background: Pemphigus is a rare autoimmune disease characterized by the formation of blisters on the skin and mucous membranes, caused by autoantibodies against desmoglein, a key protein in cell adhesion. This study aims to compare demographic and clinical criteria between male and female patients with pemphigus referred to a referral hospital, utilizing data from the pemphigus diseases registry. Method: This retrospective cross‐sectional analysis focused on several key aspects age at disease onset, severity (measured by the Pemphigus Disease Area Index [PDAI]), types of pemphigus, duration of disease, and diagnostic criteria including the presence of antidesmoglein antibodies and findings from direct immunofluorescence (DIF). By examining these variables among a cohort selected based on their diagnosis of pemphigus, the study aimed to identify significant gender differences in disease manifestation, diagnosis, and progression. This approach is crucial for tailoring more effective gender‐specific management and treatment strategies for this rare autoimmune condition. Results: In a comprehensive analysis of 1218 pemphigus patients in the year 2021 from the hospital's registry, comprising 543 males (44.6%) and 675 females (55.4%), significant gender differences were identified in 9 out of 44 variables examined. The study revealed that males had a higher age at disease onset, more frequent clinical manifestations in the head, neck, and trunk areas, and greater severity of disease as measured by the PDAI score compared to females. Conversely, females exhibited higher instances of mucosal manifestations and a higher PDAI score for mucosal erosion blister of the lower gingiva. No significant gender differences were found in 21 variables, including the overall age of patients, specific clinical manifestations across various mucous membranes, types of pemphigus, and PDAI scores for mucosal erosions in particular locations, indicating a nuanced gender impact on the presentation and severity of pemphigus that necessitates tailored clinical approaches. Conclusion: The study highlights significant gender differences in the presentation and severity of pemphigus, underscoring the importance of gender‐specific approaches in the diagnosis and management of this condition. The findings contribute valuable insights into the complex nature of pemphigus and underline the necessity for further research to understand the underlying mechanisms driving these differences. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris (PV) is a chronic autoimmune mucocutaneous blistering disease. Autoantibodies are directed against desmogleins, leading to the formation of intraepithelial bullae. PV, as with other autoimmune mucocutaneous disorders of the oral cavity, presents diagnostic and therapeutic challenges. Approximately 50–70% of cases present first with oral lesions. The lesions commonly start as vesicles or bullae that rapidly rupture, leading to erosions and ulcerations. The palatal, gingival, buccal, and labial mucosa are the most commonly affected sites. Oral PV can mimic several other diseases that cause mucosal erosions and/or ulcerations, including erythema multiforme (EM). EM is an acute, immune-mediated, self-limited hypersensitivity condition primarily associated with herpes simplex infection. Oral lesions can be variable, but a very characteristic presentation with labial hemorrhagic erosions, ulcerations and crusting is commonly seen. In this case series, we present six cases of PV: one male patient and five female patients whose ages ranged from 34 to 65 years old. All patients presented with hemorrhage and crusting of the lips in addition to multiple intraoral erosions and ulcerations. Three patients presented with oral and skin lesions. All patients underwent biopsies, and a diagnosis of PV was confirmed. All patients were treated with steroids (topical and systemic) and variable steroid-sparing agents. This case series emphasizes that oral PV may be misdiagnosed as EM in a subgroup of patients who present with persistent lip hemorrhage and crusting. Therefore, a comprehensive history, clinical examination and incisional biopsies should be considered in such patients. [ABSTRACT FROM AUTHOR]

Introduction: Pemphigus vulgaris is a chronic autoimmune blistering disorder characterised by the production of autoantibodies against desmogleins, resulting in intraepithelial blister formation. Despite advancements in treatment options, some patients experience disease progression and an inadequate response to conventional therapies. Rituximab, a monoclonal chimeric antibody targeting CD20 on B-cells, has shown promise as an alternative therapeutic option. Case report: In this case report, we present the management of a 14-year-old child with pemphigus vulgaris who exhibited disease progression despite conventional treatment modalities. The patient was administered rituximab therapy, resulting in significant clinical improvement and disease control. Conclusions: The utilisation of rituximab as an adjunct or alternative therapy in refractory pemphigus cases offers a valuable treatment option. Further studies and long-term follow-up are necessary to determine the optimal dosing regimen and evaluate the safety and efficacy of rituximab in paediatric pemphigus patients. [ABSTRACT FROM AUTHOR]

This article explores the ways in which having a rare skin disease (pemphigus) can reveal and redefine individuals' interpersonal relationships and how they experience and use the support of loved ones. It examines two aspects of "care": emotional support and practical support (through the division of household labor). It takes a relational ontological approach that is especially attentive to the biographical repercussions of care, and its gendered dimensions in particular. Our analysis is mainly based on interviews with 25 individuals in France (13 women and 12 men) with pemphigus, a rare disease that affects the skin and mucus membranes that can be controlled through long-term medical treatment. Its burn-like lesions often take the form of blisters, making pemphigus a bullous disease. Use of the concepts of "caring for" and "caring about" prove heuristic in studying care relations, especially when taking a gendered perspective and probing underlying tensions. The distinction between caring "for" and "about" is also relevant to comprehending biographical disruption, which mainly results from a lack of emotional support when the negotiation of practical support has made it possible to normalize everyday life. [ABSTRACT FROM AUTHOR]

Introduction: Pemphigus vulgaris can show non-textbook clinical peculiarities, “pearls”. Case report: A middle-aged male presented with a single desquamating crust with impetiginisation in the parietal area of the scalp present for over 2 years. Clinicians initially suspected microbial causes of the disease, including folliculitis decalvans. The patient was prescribed oral itraconazole, and rifampicin with clindamycin without improvement. Since the H + E examination revealed unequivocal features of pemphigus vulgaris, the patient was referred for proper immunopathological diagnostics. Based on the clinical picture, H + E evaluation, direct immunofluorescence, which showed pemphigus IgG4 deposits, and multiparametric ELISA (increased level of anti-desmoglein 3 IgG antibodies), a cutaneous form of pemphigus vulgaris of the pemphigus chancre type was diagnosed. The patient received intralesional injections of betamethasone dipropionate/betamethasone phosphate and rituximab intravenously (total dose of 2 g) with significant improvement. Conclusions: This patient illustrates that appropriate treatment, in non-emergency cases, should be implemented only after diagnosing patients at the clinical-laboratory level. [ABSTRACT FROM AUTHOR]

Background: There have been several papers published about pemphigus. Bibliometric analysis is useful in determining the most significant research in a certain topic. By bibliometric research, we were able to determine the 100 most frequently reference articles in pemphigus. Aims and Objective: Using bibliometric tools to find and evaluate the top 100 most reference papers in pemphigus. Materials and Methods: On 19 February 2023, the Web of Science database was utilized to launch a title-specific search. Publications were listed in degrading order on the basis of their total citations. We examined the top 100 most reference pemphigus publications. Results: The years of publication varied from 1971 to 2020, with the 1990s being the most active. According to diverse study objectives, the 100 publications were separated into clinical aspects and diagnosis (20%), pathophysiology (52%), therapy (13%), epidemiology (8%), related disorders (1%) and others (6%). The 100 papers were published in 37 different publications. The top 100 reference articles included 54 first authors of 11 nations, most of whom came from North America and Europe. Stanley, J R, from Uniformed Services University of the Health Sciences, was the principal author. Conclusions: A thorough bibliometric research of the top 100 publications in pemphigus was provided by the research, which may be useful for future research. [ABSTRACT FROM AUTHOR]

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The present study designed to evaluate the healing power of platelet‐rich fibrin (PRF) in terms of pain control and mucosal repair. A randomised, controlled, pilot clinical trial was conducted on 16 patients randomly distributed with 1:1 allocation ratio into two groups. The treatment group received PRF minced and mixed with orabase and the control group received clobetasol propionate 0.05% mixed with orabase. Pain reduction was evaluated as primary outcome along with mucositis healing as secondary outcome. A statistically significant difference in pain reduction was observed between the two groups (p ≤ 0.05). The clinical results at Day 7 has shown that PRF group had 100% pain reduction while, CP group had 32.5% reduction from base line. PRF offered superior clinical results providing rapid pain alleviation and accelerated ulcer healing compared to corticosteroids. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris (PV) is a rare autoimmune disorder characterized by blisters on the mucous membranes and skin. Autoimmunity is an important complication developing in predominantly antibody deficiencies, which is a subgroup of primary immunodeficiencies (PID). Herein, we present a patient with PV who had primary antibody deficiency and whose disease relapsed during the maintenance period of conventional immunosuppressive treatments but progressed to remission following high-dose intravenous immunoglobulin therapy. Thus, we aimed to create awareness for the study of primary immunodeficiencies in rare autoimmune bullous diseases. [ABSTRACT FROM AUTHOR]

Pemphigus represents a group of rare and severe autoimmune intra-epidermal blistering diseases affecting the skin and mucous membranes. These painful and debilitating diseases are driven by the production of autoantibodies that are mainly directed against the desmosomal adhesion proteins, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1). The search to define underlying triggers for anti-Dsg-antibody production has revealed genetic, environmental, and possible vaccine-driven factors, but our knowledge of the processes underlying disease initiation and pathology remains incomplete. Recent studies point to an important role of T cells in supporting auto-antibody production; yet the involvement of the myeloid compartment remains unexplored. Clinical management of pemphigus is beginning to move away from broad-spectrum immunosuppression and towards B-cell-targeted therapies, which reduce many patients’ symptoms but can have significant side effects. Here, we review the latest developments in our understanding of the predisposing factors/conditions of pemphigus, the underlying pathogenic mechanisms, and new and emerging therapies to treat these devastating diseases.

The clinical presentation of localized pemphigus foliaceus (PF) often involves photo exposed areas. We describe five cases of localized PF, two of which were rare locations for the disease in non-photo exposed areas, namely the genitalia and back. Patients were treated with topical corticosteroids and calcineurin inhibitors as well as systemic treatment with corticosteroids and dapsone. Each patient responded to treatment, with two achieving remission. No relapses occurred in any of these cases over a mean follow-up time of 3.7 years. A review of the English literature using MEDLINE® yielded 18 reported cases of localized PF. Most occurred in photo exposed areas such as the nose, cheeks, scalp, and other areas of the face. Two patients progressed to generalized involvement without treatment. Treatment regimens had much variation and included both topical and systemic agents. Localized PF is rare, and our findings suggest it may be controlled with topical therapy and systemic dapsone.

Background: Psoriasis and autoimmune bullous diseases (BD) are chronic, recurrent, immune-mediated pathologies, characterized by skin eruptions and associated symptoms: itching, pain, burning and stinging. Their influence on patients' quality of life (QoL) can be significant, affecting both physical and emotional well-being, and leaving an impact on daily activities and social relationships. Objective: This study aims to evaluate the QoL in individuals with psoriasis and BD (pemphigus, bullous pemphigoid and dermatitis herpetiformis). Material and methods: A cross-sectional, descriptive study was conducted on 50 patients admitted to the Dermatovenerology Clinic of the Mureş Clinical County Hospital, between July 2023 and February 2024, and diagnosed with psoriasis (34 patients) and BD (16 patients, with the predominance of pemphigus). Data were collected using two questionnaires: one included information about the patient, skin lesions, symptoms and treatment; the other was the Dermatology Life Quality Index (DLQI) questionnaire, where a higher score indicates a greater impact on the individual's QoL. The statistical analysis included Pearson and Spearman's correlation, t-tests and the Mann-Whitney test, with a significance level of p<0.05. Results : Psoriasis and BD had a moderate effect on patients' QoL, with an average DLQI value of 7.61 ± 6.04 for psoriasis and 8.81 ± 4.38 for BD. The most impacted aspects of QoL were clinical symptoms and feelings, while work and school were the least influenced. Statistically significant differences were observed in the DLQI values between patients receiving local and systemic treatment (3.9 ± 3.3 for psoriasis and 5.62 ± 1.92 for BD) and those without any treatment (8.91 ± 5.35, p=0.01 for psoriasis, 12.83 ± 3.43, p=0.0003 for BD). Regarding psoriasis, combined local and systemic treatment showed a lower DLQI value (3.9 ± 3.3) compared to local treatment alone (11.33 ± 7.39, p=0.01); in addition, a positive correlation was found between DLQI and disease extent (r=0.56, p=0.0005). No other significant correlations were identified for either psoriasis or BD. Conclusions: Psoriasis and BD moderately impair individuals' QoL. Patients receiving both local and systemic therapies experienced a better QoL compared to those without any treatment. Specifically, for psoriasis, combined local and systemic therapies demonstrated superiority in promoting a better QoL compared to local treatment alone. These findings emphasize the importance of therapeutic medical intervention for both conditions, together with adequate psychological and social support. [ABSTRACT FROM AUTHOR]

A case study details a rare presentation of pemphigus foliaceus, where a 65-year-old woman presented with annular erythematous lesions and peripheral pustules. Despite initial misdiagnosis, a combination of clinical, histopathological, and DIF findings confirmed the diagnosis, posing a diagnostic challenge due to its resemblance to other dermatological conditions like subcorneal pustular dermatoses, IgA pemphigus and pustular psoriasis.

Introduction: Patients qualified for the Polish government programme of treating severe pemphigus diseases with rituximab (RTX) available in 2018-2019 had to meet numerous criteria, including no active infectious disease. Aim: The clinical usefulness of tuberculosis screening with the QuantiFERON-TB Gold Plus (QFT-Plus) in native pemphigus patients selected for RTX treatment was statistically evaluated. Material and methods: Eighteen pemphigus patients were examined with QFT-Plus prior to the intended RTX therapy. Ninety hospital employees examined with QFT-Plus due to contact with a cleaning worker who was diagnosed with active pulmonary tuberculosis were the control group. Results: Six of 18 pemphigus patients had a positive QFT-Plus test result, one indefinite result and one initially indefinite and then negative. In the control group, 26 of 90 employees had a positive test result and none had an indefinite result. Statistical analysis by Fisher's exact test showed no statistically significant difference in QFT-Plus positive results between the groups (p = 0.5577). Only in 1 patient with recurrent mucocutaneous pemphigus vulgaris previously treated with traditional immunosuppression, lung changes were detected by computed tomography. No employee had any changes in the chest radiograph. Conclusions: Prior immunosuppression and autoimmunity might be the cause of indefinite test results, but they do not seem to increase positive results. In the native population, the QFT-Plus screening reveals a significant population exposure to M. tuberculosis infection independent of pemphigus autoimmunity, and such screening can be a starting point for identifying patients requiring anti-tuberculosis drug prophylaxis before combined RTX-glucocorticosteroid treatment. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 32-year-old man with pustules on the extremities of 1-month duration and recurrent oral erosions for 6 months. Topics include consulted dentists, ear-nose-throat specialists, and physicians for oral lesions; and examination showing a well-built lady with palatal erosions and targetoid lesions.

A case study is presented of a 35-year-old woman with a 7-year of history of Hailey-Hailey disease(HHD) presented with severe recalcitrant disease including extensive erosive patches and plaques in the intertriginous areas of the bilateral axillae, groin, and inframammary folds. It discusses that HHD is a rare blistering dermatosis characterized by recurrent erythematous plaques; and concludes Electron beam radiotherapy is a potential treatment option for local control in patients.

OBJECTIVE: Pemphigus vulgaris is an autoimmune blistering disease affecting the mucosal surfaces as well as the skin. Twenty-eight retrospective studies about the epidemiologic data of pemphigus vulgaris patients have been performed previously in the literature. METHODS: In this retrospective study, we evaluated 320 pemphigus vulgaris patients who applied to the bullous diseases clinic of Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Department of Dermatology, between the years 1999–2019. Epidemiologic data, diagnostic modalities, comorbidities and treatment modalities were noted. RESULTS: The female to male ratio was 1.39. The mean age of diagnosis was 50.4±13.7 years, 50.8±12.5 years for males and 50.0±14.5 years for females. The average disease duration was 99.0±74.4 months; it was 91.6±67.2 months for males and 104.5±79.0 months for females. At the time of diagnosis, 88.7% of our patients had mucosal lesions and 68.4% of our patients had cutaneous lesions. The most common side effects were hypertension, diabetes mellitus, osteoporosis and hyperlipidemia. Adjuvant therapy was initiated 332 times. Azathioprine was used in 260 patients,Mycophenolate sodium was used in 30 patients, Mycophenolate mofetil was used in 42 patients, IVIG was used in 52 patients, Rituximab was used in 51 patients. CONCLUSION: Pemphigus vulgaris is a disease that is more commonly seen in female patients. It has a peak incidence in the fifth decade and there is not a statistically significant difference between the age of diagnosis between the genders. It is a chronic disease with a long follow-up period; again, there no statistically significant difference between the two genders. The most commonly encountered comorbidities are hypertension, hyperlipidemia, diabetes mellitus and osteoporosis, which are due to the use of corticosteroids. [ABSTRACT FROM AUTHOR]

Desmoglein 3 chimeric autoantibody receptor T cells (DSG3-CAART) expressing the pemphigus vulgaris (PV) autoantigen DSG3 fused to CD137-CD3ζ signaling domains, represent a precision cellular immunotherapy approach for antigen-specific B cell depletion. Here, we present definitive preclinical studies enabling a first-in-human trial of DSG3-CAART for mucosal PV. DSG3-CAART specifically lysed human anti-DSG3 B cells from PV patients and demonstrated activity consistent with a threshold dose in vivo, resulting in decreased target cell burden, decreased serum and tissue-bound autoantibodies, and increased DSG3-CAART engraftment. In a PV active immune model with physiologic anti-DSG3 IgG levels, DSG3-CAART inhibited antibody responses against pathogenic DSG3 epitopes and autoantibody binding to epithelial tissues, leading to clinical and histologic resolution of blisters. DSG3 autoantibodies stimulated DSG3-CAART IFN-γ secretion and homotypic clustering, consistent with an activated phenotype. Toxicology screens using primary human cells and high-throughput membrane proteome arrays did not identify off-target cytotoxic interactions. These preclinical data guided the trial design for DSG3-CAART and may help inform CAART preclinical development for other antibody-mediated diseases. [ABSTRACT FROM AUTHOR]

Background: Pemphigus vulgaris is an autoimmune disorder that involves intraepithelial blistering and sores of the skin and mucous membranes. The average age of onset is between 50 and 70 years. Pemphigus rarely occurs in children. It correlates with the level of circulating autoantibodies; therapeutic plasma exchange is hypothesized to remove pathogenic autoantibodies, and this is necessary in refractory severe cases.Case Presentation: A 14-year-old Asian girl came to our hospital with blisters and erosions all over her body and in the oral mucosa. She was diagnosed with pemphigus vulgaris by skin biopsy about 3 months before hospitalization. She was admitted to the intensive care unit due to aggressively worsening symptoms, extensive lesions, dehydration, and electrolyte imbalance secondary to excess fluid loss from the skin wounds and sepsis secondary to infection of the exposed wounds. She did not respond to prednisone and azathioprine therapy but was successfully treated with plasmapheresis.Conclusion: The purpose of this case report is to describe an aggressive presentation of pemphigus vulgaris, especially because the onset of the disease in our patient was at an early age. The disease rarely begins in childhood, and this case report highlights the importance of plasmapheresis as a useful intervention in patients with pemphigus vulgaris who are not responding to conventional therapy, taking into account that there is a paucity of studies showing the effectiveness of plasmapheresis in inducing partial or complete remission in young patients. [ABSTRACT FROM AUTHOR]

Introduction: Pemphigus is an autoimmune intra-epidermal bullous disease of the skin and mucosae. Aim: To retrospectively evaluate the course, prognosis and clinical features of pemphigus. Material and methods: The files of 196 pemphigus patients admitted to our clinic between December 1995 and December 2014 were collected and analysed. Results: The male to female ratio among patients was 1 : 1.88. Pemphigus vulgaris (PV) was the most common clinical variant observed in 175 (89.3%) of the patients, followed by pemphigus foliaceus (PF) in 14 (7.1%) of the patients. The mean patient age at disease onset was 50 years. PV presented itself as skin lesions in 55 (31.4%) of the patients and as oral mucosa lesions in 120 (68.6%) of the patients. Complete remission and treatment withdrawal were obtained in 112 (57.1%) of the patients, for a mean period of 2.91 ±2.66 years (range: 4 months to 13 years). The mortality rate was 6%, and relapse occurred in 16 (14.3%) of the patients for a mean relapse period of 2.15 ±1.88 years (range: 6 months to 7 years). Mucocutaneous pemphigus (MCP) was the major clinical pattern observed in 96 (49%) of the patients. Conclusions: Within our study population, pemphigus predominately affected females, and the most common clinical variant was PV, a subtype that frequently occurs in middle-aged individuals. MCP was the most common clinical pattern. Although MCP and higher doses of corticosteroids were needed to control pemphigus, they did not seem to influence the prognosis. [ABSTRACT FROM AUTHOR]

Background: Pemphigus vulgaris patients with exclusive oral involvement (OPV) treated with conventional immunosuppressive therapy may be non-responders or experience severe side effects and/or relapses. In such cases, rituximab could be used as an adjuvant in recalcitrant OPV patients.Methods: A retrospective single-center study on patients with oral pemphigus vulgaris treated with RTX at a dose of 375 mg/m2 was performed, evaluating the complete clinical and immunological remission, side effects of RTX, and possible correlation between anti-desmoglein (Dsg) 3 antibodies and clinical remission.Results: We treated 10 OPV patients, of which 60% had a moderate and 40% mild disease severity before therapy with RTX. Complete clinical remission (CCR) was achieved in 100% of OPV patients, of which 20% developed side effects and 20% experienced a relapse in a mean time of 15.2 ± 10.2 weeks. The mean time for CCR was achieved in 19.8 ± 10.3 weeks, whereas the duration of the CCR consisted in 37.4 ± 33.5 weeks. OPV patients underwent a mean follow-up of 57.2 ± 37.7 weeks. In all patients, the mean of pemphigus disease area index (PDAI) decreased from 20.3 ± 14.1 to 0.4 ± 0.0, whereas the mean Dsg3 value dropped from 157.1 ± 40.6 to 67.0 ± 26.6 after therapy with RTX. However, no correlation was found between PDAI and anti-Dsg3 antibodies before and after therapy with RTX (P > .05).Conclusions: RTX represents a valid and safe alternative as an adjuvant in OPV patients with low rate of relapses and side effects. [ABSTRACT FROM AUTHOR]

Introduction. Pemphigus vegetans is the least common form of pemphigus. Typical clinical presentation of the condition involves blisters transforming into papillous or pustular eruptions. Treatment consists of administration of systemic glucocorticosteroids as a monotherapy, or combined with immunosuppressants. Objective. Presentation of a case of pemphigus vegetans of possible drug-induced aetiology and severe course. Case report. A 58-year old man was admitted with papillous lesions persisting for few weeks in the anogenital area, axillae and ear lobes. For several months the man has been using the hypotensive medication - enalapril. Pemphigus vegetans was diagnosed based on the clinical presentation and the immunopathological examination. Enalapril was discontinued and prednisone was introduced at the maximum dose of 2 mg/kg/day, with subsequent improvement of the condition. Considering adverse effects of chronic glucocorticosteroid therapy, azathioprin was also introduced at the dose of 50 mg/day, with gradual reduction of the prednisone dose over time. The patient in good general and local condition remains under supervision of a dermatologist. Conclusions. A case of a patient is presented with lesions initially suggesting papillary pyroderma. As a result of rapid progression the disease significantly hindered the patient's everyday functioning. Pemphigus vegetans in this patient may have been induced by enalapril. [ABSTRACT FROM AUTHOR]

This qualitative study conducted in France of "individuals living with a pemphigus" (ILPs; N = 54) highlights the taxing diagnostic trajectory of those suffering from these rare autoimmune diseases. Beyond enduring a diagnostic period that may prove long, during their numerous medical appointments, these individuals internalize the expectations of the medical professionals who are treating them. In some cases, numerous inconclusive medical tests and, at times, a doctor's condescension may push the patient toward a process of renunciation. This article relates the ILPs' critiques of the medical work conducted during the trying diagnostic period. [ABSTRACT FROM AUTHOR]

Background: Pemphigus is a chronic potentially life-threatening autoimmune blistering disease affecting the skin and/or mucous membranes. Rituximab is being increasingly used and found efficacious in the treatment of pemphigus. Objective: To present the Middle-Eastern experience with the use of rituximab in pemphigus. Methods: A retrospective analysis of patient files was conducted which revealed 23 patients of pemphigus who were treated with rituximab (either alone or with IVIG) in the dermatology department of a tertiary care hospital from July 2004 to December 2014. Results: The mean time to disease control was 8 weeks (median 5 weeks and range 2-30 weeks). 90.9% attained early study end point with the first cycle of rituximab. The remaining 9.1% needed an additional course of rituximab + IVIG to attain disease control. 90.5% of our patients attained complete remission during the study period. The average time to attain complete remission on minimal treatment was 25.4 weeks and partial remission on minimal treatment was attained after a mean period of 18.3 weeks. Rituximab was well tolerated by our patients and the rate of adverse-effects in our cohort was comparable to the previous reports. Conclusions: Rituximab is an effective and safe treatment for pemphigus and should be considered earlier in the algorithm of pemphigus treatment. [ABSTRACT FROM AUTHOR]

Background: Since the first description of feline pemphigus foliaceus (PF) more than 30 years ago, numerous case reports have been published, while larger case series have remained rare. This large body of information, if extrapolated, could address clinical discrepancies and expand our knowledge about the treatment of feline PF. This manuscript reviews cases of feline PF published between 1950 and 2016 and adds additional 35 original cases to provide further insight into the clinical aspect and treatment outcome of this disease. Results: Feline PF, while being a primary acantholytic pustular dermatosis, presents most often with crusts and erosions that predominantly affect the face and feet. More than half of cats with active disease exhibits non-dermatological signs such as lethargy, fever and/or anorexia. The prognosis of feline PF is good as the majority of cats rapidly achieve disease control even with the most basic treatment such as glucocorticoid monotherapy. Most PF-affected cats, however, require long-term treatment and, like other autoimmune diseases, feline PF has a tendency to relapse spontaneously or with treatment changes. Conclusions: Therefore, despite the overall good prognosis cats with PF can be given, owners should be informed and prepared for these circumstances, which may reduce the risk of euthanasia in the case of disease relapse, and improve treatment compliance. [ABSTRACT FROM AUTHOR]

Purpose: The objective of the current study was to evaluate the effect of intravenous methylprednisolone pulse therapy on myocardial repolarization alterations, especially QT dispersion in anticipation of cardiovascular risks in patients with pemphigus vulgaris. Methods: The current study is a prospective-controlled study on the electrocardiographic changes after methylprednisolone pulse therapy in 50 patients with pemphigus vulgaris. Results: A total of 50 patients (28 female and 22 male) were included in our study. The mean heart rate was significantly higher in male patients both before (92 ± 10.80 versus 82.75 ± 12.01 ms) and after pulse therapy (102.73 ± 14.26 versus 91.07 ± 15.02 ms) (p value < .01). The value of heart rate was significantly greater after receiving steroid pulse therapy. Corrected QT dispersion before pulse therapy was 19.92 ± 8.2 ms that increased to 40.68 ± 18.12 ms after treatment (p value < .001). Conclusion: Our study shows that there is a relationship between pulse steroid infusion and increased predisposition to the occurrence of cardiac arrhythmias. QT dispersion could be a good marker to assess this risk in these patients. [ABSTRACT FROM AUTHOR]

Introduction: Many mucocutaneous conditions affect the skin and oral cavity. Common conditions include lichen planus, pemphigus, and pemphigoid. This case report shows an atypical presentation of a mucocutaneous condition wherein histopathology was required for definitive diagnosis and treatment. Case Presentation: A 51‐year‐old African American male self‐reported to a private periodontal practice with a chief complaint of sporadic painful oral lesions of about 2 months duration. The patient also reported painful throat lesions. He had been previously treated for a sore throat followed by unspecified inflammation of the epiglottis. Clinical examination revealed diffuse bilateral eye redness, numerous intraoral ulcerations on soft and hard palate and floor of the mouth with trouble swallowing. Oral and ocular presentation suggested a differential diagnosis of cicatricial pemphigoid. Pemphigoid and lichen planus were also considered. Ophthalmologic exam revealed only allergies and no other abnormality. Soft tissue biopsies showed intraepithelial separation between the spinous layer and basement membrane. Direct and indirect immunofluorescence showed strong immunoglobulin G and moderate C3 reactivity confirming a diagnosis of pemphigus vulgaris (PV). A rheumatologist initially treated the patient with a daily combination regimen of methylprednisolone and mycophenolate mofetil. Lesions improved after a few weeks on the regimen. Reduction of medications resulted in return of oral and throat lesions. Resumption of the regimen resulted in lesion remission. Azathioprine replaced the mycophenolate mofetil, and then was gradually stopped after methylprednisolone cessation. Lesions have not reappeared for 1 year. Conclusion: This case illustrates that early diagnosis of mucocutaneous lesions leads to proper treatment and possible remission. [ABSTRACT FROM AUTHOR]

Pemphigus is a bullous autoimmune disease that affects the skin and mucous membranes. It is very difficult to establish the etiology and the triggering factors that influence reactivations in pemphigus vulgaris (PV). The case of a 33-year-old male with chronic history of intranasal cocaine consumption is presented in this report. We present the clinical case of the patient, followed for a total of 86 weeks, with ten relapses secondary to probable cocaine use. The patient was admitted to the emergency department after presenting polymorphic dermatosis characterized by blisters, vesicles, and excoriations extending from the oral cavity to the thorax, and to the inguinal and genital regions, affecting approximately 35 % of the body surface area with a score of 56 on the Pemphigus Skin Disorder Index. Skin biopsies were compatible with PV diagnosis. The patient had clinical improvement with a combination of methylprednisolone 500 mg intravenously (IV) and cyclophosphamide 500 mg IV every 15 days, along with prednisone 50 mg orally (PO) q24 h and mycophenolic acid 500 mg PO q6 h. Persistent cocaine use is highly likely to be the factor triggering lesion reactivation and responsible for the torpid evolution. We cannot definitively conclude whether the change from azathioprine to mycophenolic acid after the tenth relapse was the adjuvant medication responsible for the end of the consolidation phase and complete remission on therapy. This case study could potentially serve as a guide for management of patients who continuously persist with cocaine use, leading to a clinical picture refractory to multiple therapeutic schemes. [ABSTRACT FROM AUTHOR]

Background: The anti-CD20 monoclonal antibody rituximab has immune-modulatory effects similar to intravenous immunoglobulin (IVIG). We performed a systematic review and meta-analysis to determine the efficacy and safety of rituximab in autoimmune diseases that are also treated with IVIG.Study Design and Methods: The most common indications for immune modulation with IVIG, as identified from a 2012 regional audit in Canada, were chronic inflammatory demyelinating polyneuropathy (CIDP), immune thrombocytopenia (ITP), myasthenia gravis, multifocal motor neuropathy, Guillain-Barré syndrome, systemic lupus erythematosus (SLE), Sjogren's syndrome, and pemphigus vulgaris. We searched MEDLINE, EMBASE, and the Cochrane Library until July 2016 for studies evaluating rituximab in each of these conditions. The primary outcome in our meta-analysis was clinical response at 6 months as defined by disease-specific criteria in randomized trials. We also calculated pooled proportions of responders within disease types from observational studies.Results: Ninety-five rituximab studies were identified: 86 were observational studies in patients with ITP (n = 1746), SLE (n = 1047), pemphigus vulgaris (n = 564), Sjogren's syndrome (n = 138), myasthenia gravis (n = 66), and CIDP (n = 31) and nine were randomized controlled trials (n = 992) in patients with ITP, SLE, and Sjogren's syndrome that compared rituximab with placebo plus standard of care. Among randomized trials, response rates were higher with rituximab (relative risk, 1.38; 95% confidence interval [CI], 1.05-1.83). The pooled proportion of rituximab responses ranged from 94% (95% CI, 88%-98%) for pemphigus vulgaris to 48% (95% CI, 30%-66%) for CIDP. Rituximab was generally well tolerated in observational studies although in the randomized trials, adverse events were more common in the rituximab group.Conclusion: Rituximab is an immune-modulating agent with biologic activity across many autoimmune conditions. Our data support the use of comparative trials with broad eligibility criteria to evaluate rituximab as an alternative to IVIG in autoimmune diseases. [ABSTRACT FROM AUTHOR]

Objective: Cassia fistula L. fruit extract has been traditionally used in the treatment of pemphigus vulgaris (PV) lesions in Iran. The aim of this study was to determine the efficacy of C. fistula fruit gel on healing time of PV lesions in a clinical setting. Materials and Methods: This was a randomized, double-blind placebo-controlled clinical trial that was performed in dermatology ward at Saadi hospital, affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. Right- or left- sided lesions of PV patients on standard systemic treatment were randomized for treatment with either C. fistula fruit gel or placebo prescribed twice daily. The largest diameter of each lesion was measured at the baseline (day 0) and on days 10 and 20. Epithelialization Index (EI), as outcome measure was calculated and compared between the two groups. Results: The present study comprised 20 patients, with overall 82 cutaneous lesions including 41 lesions in the C. fistula fruit gel group and 41 lesions in the placebo group. The EI in the C. fistula fruit gel group was significantly higher than that of the placebo group both on day 10 (65±28vs 30±34; p=0.001) and at the end of the study (91±22 vs 69±49; p=0.003). Conclusion: Topical application of C. fistula fruit gel can be considered as an effective adjuvant therapy in treatment of PV. [ABSTRACT FROM AUTHOR]

Background: Rituximab is a promising steroid sparing agent used in the treatment of moderate to severe pemphigus vulgaris. Its exact place in the algorithm of pemphigus treatment, vis-à-vis other, conventional adjuvant therapy (CAT) is not known. Objective: To describe and compare disease course outcomes and morbidity among patients with moderate to severe pemphigus who received rituximab therapy (RT) in addition to prednisone and CAT, versus those who were treated with prednisone and CAT alone. Methods: A 16-year retrospective case control study was designed with adult patients who were seen at the Duke University Dermatology Immunodermatology clinic from 1999–2015, who had a diagnosis of pemphigus vulgaris, and required prednisone and at least 1 systemic CAT. All patients had at least 6 months follow up from the initial visit. Interventions included RT, systemic CAT, and prednisone. The main outcome measured was prednisone intake. Secondary outcomes were complete remission (CR) and partial remission (PR). Results: 40 patients were included in the study. All initially received prednisone and at least 1 systemic CAT. 13/40 eventually went on to receive RT, while 27/40 remained on CAT (CAT-only). Patients in the RT group, pre-RT, had a median prednisone intake of 658.57 mg/month. Rituximab treatment significantly reduced this to 177.22 mg/month (p = 0.002). Median prednisone intake of the CAT-only group was 141.33 mg/month. This was significantly less than Pre-RT (p = 0.01) and on par with Post-RT intake (p = 0.58). 54% of patients in the RT group and 64% of those in the CAT-only group achieved CR. All patients in the RT group and 96% of those in the CAT-only group achieved at least PR. Conclusions: 32.5% of our patients with moderate to severe pemphigus vulgaris failed prednisone and traditional CAT treatment and required rituximab therapy. Rituximab reduced the monthly prednisone intake in these patients by 73%. This suggests that a subset of patients with moderate to severe pemphigus may benefit from early institution of rituximab therapy. Rituximab significantly reduces the monthly prednisone requirement among CAT-resistant pemphigus vulgaris patients to levels on par with CAT-responsive patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: The average incidence of pemphigus reported from European countries ranged between 0.5 and eight cases per one million inhabitants. Studies on epidemiology of pemphigus group in entire Province of Poland over a period of more than a decade are lacking. Aim: To analyze the incidence of pemphigus vulgaris (PV) and pemphigus foliaceus (PF) in Podlaskie Province (North‐East Poland) in years 2001–2015 with regard to patients’ age, gender, and residency. Results: Sixty‐six cases of pemphigus were diagnosed in the period analyzed: 44 cases of PV (66.67%) and 22 of PF (33.33%). Female to male ratio was 2.88. The average incidence of PV and PF together was 3.67 ± 2.19 per one million inhabitants. In females the incidence was 5.34 ± 3.20 and in males, 1.90 ± 1.91 (P < 0.05). The incidence in inhabitants of rural areas was 4.96 ± 4.07 and those of urban areas, 2.70 ± 2.01 (P < 0.05). The age of the pemphigus onset was 54.69 ± 12.58 for PV and 64.24 ± 13.33 for PF (P < 0.05). The majority of PV and PF patients were residents of urban areas and rural areas, respectively. Conclusions: The incidence of pemphigus group in Podlaskie Province was within the range of the average incidence rates reported from other European countries. Surprisingly, the female to male ratio was the highest in Europe. Moreover, for the first time we have demonstrated that the incidence was higher in the population living in rural than in urban areas. Similar studies in other regions of Poland are needed. [ABSTRACT FROM AUTHOR]

Hailey--Hailey disease also known as Familial benign chronic pemphigus is a relatively uncommon disease characterized by painful erosions, vesicles, pustules and scaly erythematous plaques on the neck, axillae, groins and perineum. A case of 27 years old male with history of recurrent, itchy, erythematous, papules and vesicles over the groins presented to the dermatology OPD. A clinical diagnosis of Hailey -- Hailey disease was made which was confirmed later by histopathological examination. He was treated with tacrolimus ointment and showed a remarkable improvement. [ABSTRACT FROM AUTHOR]

Superficial pemphigus in dogs is an autoimmune skin disorder. The disease is characterised by the binding of auto-antibodies to desmosomal molecules including desmocollin-1, a major auto-antigen in dogs. However, data on the expression of epidermal proteins in dogs are still limited. Therefore, the aim of this study was to investigate the keratins and epidermal proteins in dogs with superficial pemphigus using immunohistochemistry. Skin biopsies were performed on dogs with pemphigus foliaceus (n=10), pan-epidermal pustular pemphigus (n=4) and pemphigus erythematosus (n=1). Immunostaining for keratin 5 and keratin 10 showed a premature and discontinuous pattern in the suprabasal layers of all pemphigus skin samples compared to the control group (P<0.05). Filaggrin, desmocollin-1 and claudin-1, but not involucrin, were significantly reduced (P<0.05). Inflammatory cells markedly infiltrated in the dermis and the lower epidermis of all pemphigus skins. This is the first report that associates changes in the expression of keratin 5, keratin 10, filaggrin and claudin-1 with reduced desmocollin-1 expression and subsequent loss of the epidermal barrier in superficial pemphigus. [ABSTRACT FROM AUTHOR]

Oral erosions of pemphigus vulgaris (PV) represent a therapeutic challenge. In this work we compared intralesional injection of steroids (ILS) and autologous platelet-rich plasma (PRP) treatment of oral erosions of PV. In this split-mouth randomized double blind study, one side of the buccal mucosa of 11 PV patients was injected with 10 mg/ml triamcinolone and the opposite side was injected with 1 millilitre of autologous PRP every 14 days for 3 months. The percentage of clinical improvement, pemphigus disease area index and pain score were recorded before and after therapy. Out of 11 recruited patients, only 9 completed the study. Seven out of the nine patients (78%) showed improvement in PDAI and/or pain score. The mean oral PDAI of the steroid injected sides decreased from 2.3 to 0.9. The mean oral PDAI of the PRP injected sides decreased from 2.6 to 1.0. No significant difference was detected in clinical improvement, PDAI and pain score between autologous PRP and ILS in the treatment of oral erosions of PV. Autologous PRP can be used for the treatment of resistant oral erosions of PV when ILS is contraindicated. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris (PV) is a life-threatening disease belonging to the pemphigus group of autoimmune intra-epidermal bullous diseases of the skin and mucosae. The therapeutic management of PV remains challenging and, in some cases, conventional therapy is not adequate to induce clinical remission. The cornerstone of PV treatment remains systemic corticosteroids. Although very effective, long-term corticosteroid administration is characterized by substantial adverse effects. Corticosteroid-sparing adjuvant therapies have been employed in the treatment of PV, aiming to reduce the necessary cumulative dose of corticosteroids. Specifically, immunosuppressive agents such as azathioprine and mycophenolate mofetil are widely used in PV. More recently, high-dose intravenous immunoglobulins, immunoadsorption, and rituximab have been established as additional successful therapeutic options. This review covers both conventional and emerging therapies in PV. In addition, it sheds light on potential future treatment strategies for this disease. [ABSTRACT FROM AUTHOR]

Autoantibodies binding to the extracellular domains of desmoglein (Dsg) 3 and 1 are critical in the pathogenesis of pemphigus by mechanisms leading to impaired function of desmosomes and blister formation in the epidermis and mucous membranes. Desmosomes are highly organized protein complexes which provide strong intercellular adhesion. Desmosomal cadherins such as Dsgs, proteins of the cadherin superfamily which interact via their extracellular domains in Ca2+-dependent manner, are the transmembrane adhesion molecules clustered within desmosomes. Investigations on pemphigus cover a wide range of experimental approaches including biophysical methods. Especially atomic force microscopy (AFM) has recently been applied increasingly because it allows the analysis of native materials such as cultured cells and tissues under near-physiological conditions. AFM provides information about the mechanical properties of the sample together with detailed interaction analyses of adhesion molecules. With AFM, it was recently demonstrated that autoantibodies directly inhibit Dsg interactions on the surface of living keratinocytes, a phenomenon which has long been considered the main mechanism causing loss of cell cohesion in pemphigus. In addition, AFM allows to study how signaling pathways altered in pemphigus control binding properties of Dsgs. More general, AFM and other biophysical studies recently revealed the importance of keratin filaments for regulation of Dsg binding and keratinocyte mechanical properties. In this mini-review, we reevaluate AFM studies in pemphigus and keratinocyte research, recapitulate what is known about the interaction mechanisms of desmosomal cadherins and discuss the advantages and limitations of AFM in these regards. [ABSTRACT FROM AUTHOR]

Summary: Background: Oxidative stress and low antioxidant status are implicated in the pathogenesis of inflammatory and autoimmune diseases. Pemphigus vulgaris (PV) is an extremely severe autoimmune bullous dermatosis characterized by intraepithelial bullae on the skin and mucosa, and its antioxidant status is not fully understood. Aim: To assess correlations between PV and serum antioxidant levels of bilirubin, uric acid (UA) and albumin. Methods: We enrolled 116 patients newly diagnosed with PV who were admitted to the First Affiliated Hospital of Guangxi Medical University (Guangxi, China), and 108 healthy controls (HCs). Clinical characteristics and laboratory parameters of patients were retrospectively analysed. Results: Our survey shows that compared with the HC groups, serum levels of bilirubin [total bilirubin (Tbil), direct bilirubin (Dbil) and indirect bilirubin (Ibil)], UA and albumin were significantly lower in patients with PV, regardless of sex. In all groups, serum Tbil, Dbil, Ibil, UA and albumin levels were lower for women than for men. Severity of pemphigus was slightly negatively associated with Tbil, Dbil and Ibil, but was not associated with UA or albumin. Moreover, when the data were adjusted for the covariances of age and sex separately, Tbil, Dbil, Ibil, UA and albumin were all relevant to PV. Conclusions: Our findings demonstrate that serum levels of bilirubin (Tbil, Dbil and Ibil), UA and albumin are reduced in patients with PV supporting the hypothesis that oxidative stress and antioxidant status are important in the pathogenic mechanism of PV. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris (PV) is a rare autoimmune disease due to the production of pathogenic autoantibodies directed against desmoglein 1 and 3, usually affecting both skin and mucous membranes. Recently, rituximab, a chimeric IgG1 monoclonal antibody which targets the CD20 molecules have been regarded as a promising treatment for PV. In this study, a systematic review was conducted to conclude on how and which PV patients could benefit from rituximab infusion. Search in PubMed results in 114 relevant studies, which met the criteria. Total of 1085 PV patients with different conditions, including unresponsive childhood/juvenile or adult PV patients, women of childbearing age, those with chronic infections with the risk of reactivation have been evaluated. Although the majority of these patients well responded to rituximab, some of them did not respond, and the paucity of patients experienced exacerbation of disease. In addition to the rituximab monotherapy or its combination with conventional therapies, different novel combination therapies of rituximab with immunoadsorption and/or IVIg have shown promising results. Moreover, using rituximab as the first-line treatment has emerged recently. Pneumocystis carinii pneumonia and septicemia were found as the two fatal and serious adverse events associated with rituximab. Moreover, development or reactivation of herpes simplex and herpes zoster and cytomegalovirus should be warned. Similar to the adults, those with childhood and juvenile PV could be successfully treated with rituximab. Although rituximab seems to trigger reactivation of chronic infections, such as viral hepatitis and HIV infection, no related report was found. Administration of rituximab in approximately ten months before conception also was found safe and effective for a successful pregnancy. In conclusion, rituximab is very effective in adult and childhood/juvenile PV. However, there is a risk of not responding, exacerbation of disease and development of fatal infections. Moreover, it seems to be a promising first-line treatment for refractory PV. [ABSTRACT FROM AUTHOR]

Objective The present work was conducted to assess the outcome of dexamethasonecyclophosphamide pulse (DCP) therapy in pemphigus. Methods The present work was designed as a retrospective tertiary urban hospital based, observational study during the period from Jan 2012 to Dec 2016. Data regarding clinical details about the disease, previous treatments, phases of therapy, remission, relapse, cure, default and reasons for default, death and causes of death and adverse effects of therapy were evaluated. Results Out of 102 patients of pemphigus on DCP therapy, majority (n=42) of them belonged to age group of 40 to 49years. Mean age of patients was 42.08 years with a range of 24 to 65 years. Male to female ratio was 1:1.48. Of the 102 patients, 30 patients were in phase I, 23 were in phase II, 12 were in phase III and 37 were in phase IV. Mean number of pulses required for remission, that is, for completion of phase I were 5.2 months (range, 2-15 months). Majority (n=47, 65.3%) of them needed 4-7 pulses to achieve remission. Among 72 patients who achieved remission, a total 15 patient relapsed. Infusion-related reactions were the most common immediate adverse effect and generalized weakness/malaise were the most common delayed adverse effect recorded. Nine (7.7%) patients died while on DCP therapy and the most common (n=5) cause of death was septicaemia. Conclusion The DCP therapy was found to be effective in inducing and maintaining remission in pemphigus, provided the patients receive regular and complete treatment. The costeffectiveness is definitely superior to other treatment modalities (biologics), which is of utmost importance in our setup as majority of patients belonged to poor socioeconomic strata, although the relapse rate and mortality rate were higher compared to other studies. [ABSTRACT FROM AUTHOR]

Background: Pemphigus is a group of autoimmune blistering diseases characterized by loss of keratinocyte cell adhesion that leads to blister formation clinically. Induction of apoptosis or of proapoptotic proteins by pemphigus immunoglobulin G (IgG) may be part of the mechanism by which IgG induces acantholysis. Some of the current data suggest that activation of proapoptotic proteins such as bax and caspase cysteine proteinases may sensitize cells to the acantholytic effects of pemphigus IgG. Thus, a central role of apoptosis in the mechanisms of blister induction is well recognized. Aims: This study aims (a) To find which pathway of apoptosis is involved in the pathogenesis of pemphigus and (b) to evaluate the expression of bax and caspase-8 and its key role in pemphigus. Materials and Methods: The study was conducted on 21 samples of oral pemphigus. The presence of apoptosis was evaluated in the sections taken from histopathologically diagnosed oral pemphigus archival blocks using peroxidase-antiperoxidase immunohistochemical method. Results: The expression and staining intensity of pro-apoptotic marker bax and apoptotic marker caspase-8 were observed in the various areas with varying intensity in different samples. The result was subjected to statistical analysis. Conclusion: The results obtained in the present study suggest that the process of apoptosis occurs in PV. Hence, inhibition of apoptosis in the patients could reduce the severity of the lesions, and they could also represent new specific targets for pemphigus treatment. [ABSTRACT FROM AUTHOR]

Systemic administration of corticosteroid (CS) remains the standard gold treatment for pemphigus. However, because of several long-term adverse effects, steroid-sparing agents are usually prescribed in combination with CSs. Despite the high number of available studies, the choice of best drugs to treat pemphigus remains controversial. Therapeutic approaches for pemphigus can be divided into traditional treatment and emerging ones. Personalized medicine, which aims to increase the efficacy as well as reduce adverse effects of treatments, could be considered as the future option. Here, the most common agents, including azathioprine (AZA), mycophenolate mofetil (MMF), methotrexate (MTX), cyclophosphamide (CP), rituximab (RTX) and intravenous immunoglobulin (IVIg) have been discussed in detail and compared. Besides, the efficacy and safety profiles of the less frequently used agents such as cyclosporine, dapsone, mizoribine, chlorambucil, plasmapheresis, immunoadsorption and hematopoietic stem cell transplantation have been evaluated. Moreover, some emerging therapeutic options for pemphigus patients, such as B cell activating factor (BAFF), proliferation-inducing ligand (APRIL) inhibitors, anti-cytokine therapy, co-stimulatory and co-inhibitors manipulators and inhibitors of pathogenic signaling pathways (e.g., p38MAPK, c-Myc and EGFR) have been described. In addition to the conventional approaches, some clues to moving towards personalized medicine for the treatment of pemphigus have been proposed. According to the last evidence, seven available first-line combination therapies, including RTX + IVIg, CS + RTX, CS + MMF, CS + AZA, CS + MTX, CS + CP and CS + IVIg were suggested and compared. Subsequently, the most optimum drugs for three different conditions, including patients with no pregnancy or infection, those at high risk of development/reactivation of infection or pregnant women were suggested. [ABSTRACT FROM AUTHOR]

The dermal-epidermal junction consists of a network of several interacting structural proteins that strengthen adhesion and mediate signalling events. This structural network consists of hemidesmosomal-anchoring filament complexes connecting the basal keratinocytes to the basement membrane. The anchoring filaments in turn interact with the anchoring fibrils to attach the basement membrane to the underlying dermis. Several of these structural proteins are recognized by autoantibodies in pemphigoid diseases, a heterogeneous group of clinically and immunopathologically diverse entities. Targeted proteins include the two intracellular plakins, plectin isoform 1a and BP230 (also called bullous pemphigoid antigen ( BPAG) 1 isoform e ( BPAG1e)). Plectin 1a and BP230 are connected to the intermediate filaments and to the cell surface receptor α6β4 integrin, which in turn is connected to laminin 332, a component of the anchoring filaments. Further essential adhesion proteins are BP180, a transmembrane protein, laminin γ1 and type VII collagen. Latter protein is the major constituent of the anchoring fibrils. Mutations in the corresponding genes of these adhesion molecules lead to inherited epidermolysis bullosa emphasizing the importance of these proteins for the integrity of the dermal-epidermal junction. This review will provide an overview on the structure and function of the proteins situated in the dermal-epidermal junction targeted by autoantibodies. [ABSTRACT FROM AUTHOR]

Mucous membrane pemphigoid (MMP) is a rare, chronic and often aggressive subepidermal autoimmune blistering disease potentially affecting several mucous membranes with blisters and secondary erosions and scars. The pathogenesis of MMP is poorly understood, and the contribution of genetic predispositions, other than HLA class II allele variants to MMP, is unknown. The objective of this study is to identify susceptibility genes for MMP in a British cohort of MMP patients. A GWAS was conducted in a British cohort of 106 MMP patients. Publicly available genotypes of 2900 blood donors of the UK Blood Service and of 6740 individuals of the 1958 British Birth Cohort served as control. Subsequently, putative susceptibility genes were independently replicated in a German cohort of 42 MMP patients. The GWAS found 38 SNPs in 28 haploblocks with an odds ratio >2 reaching genomewide significance ( P < 5.7 × 10−7). Replication confirmed an association of MMP with SNPs in rs17203398 (OR: 3.9), located intronically in the β-galactocerebrosidase gene ( GALC) on chromosome 14 and with recessive polymorphisms in rs9936045 (OR: 3.1) in the intergenic region between CASC16 and CHD9 on chromosome 16. The risk of developing MMP is partially genetically determined. SNPs in GALC enhance the risk for MMP, indicating that β-galactocerebrosidase may be involved in the pathogenesis of MMP. Likewise, impacts of polymorphisms in the intergenic region between CASC16 and CHD9 on the activity of neighbouring genes may facilitate the emergence of MMP. The putative role of both polymorphisms requires functional studies in the future. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris ( PV) and bullous pemphigoid ( BP) are autoimmune blistering diseases, and substantial numbers of CD163+ tissue-associated macrophages ( TAMs) are detected in both diseases. PV and BP possess different subsets of helper T cells, suggesting that the cytokine profiles of PV and BP might be different. The purpose of this study was to investigate the microenvironment of lesional skin and serum of PV and BP patients, focusing on the immunomodulatory factors related to TAMs, such as periostin ( POSTN), chemokines, cytokines and matrix metalloproteinases (MMPs). We first performed immunohistological staining of POSTN in PV and BP lesions. POSTN was prominent in the superficial dermis in both PV and BP lesions. Next, to validate the activation of CD163+ TAMs in PV and BP patients, we examined the serum levels of soluble (s) CD163. The serum sCD163 levels in PV and BP patients are significantly higher than in healthy controls. To further elucidate the molecular mechanisms of the effects of POSTN on CD163+ TAMs in PV and BP, we examined chemokines, MMPs and cytokines selected by DNA microarray database. The serum CXCL5 levels from PV patients are significantly higher than those in BP patients and healthy controls. The IL-36γ expression on infiltrating macrophages was prominent only in the lesional skin of PV, while the MMP12 deposition was detected in both PV and BP lesions. Our results shed light on the novel pathogenesis of PV through CD163+ TAMs. [ABSTRACT FROM AUTHOR]

We describe our experience with a 44-year-old man who presented with hematemesis and sudden-onset chest pain. His past medical history was of pemphigus vulgaris of 3 years' duration. Large white membranes were pulled out perorally forming approximate 8-cm-long tubes, which were highly suspicious of shredded whitish membranes detaching from the underlying intact mucosa of esophagus. Emergency endoscopic findings confirmed the presence of severe erosions and bleeding in the lower tubular esophagus according with the exfoliative membranes. The patient received a diagnosis of exfoliative esophagitis with pemphigus vulgaris. Exfoliative esophagitis with pemphigus vulgaris is a rare disease with low prevalence. Surgical resection of the esophagus should be considered once upper gastrointestinal bleeding is not well-controlled. Our understanding of exfoliative esophagitis with pemphigus vulgaris remains largely limited, and further studies should be needed to explore the exact molecular mechanisms. [ABSTRACT FROM AUTHOR]

Inflammatory myofibroblastic tumor (IMT) is a peculiar low-grade neoplasm of spindle cell fibroblasts and myofibroblasts in an inflammatory background. The lung is the most common site of involvement. Here, we report a case of paraneoplastic pemphigus (PNP)-associated with an extensive retroperitoneal IMT. The patient had a favourable response following treatment with a low dose of systemic steroid, mycophenolate mofetil, and intravenous immunoglobulin (IVIG). He subsequently underwent surgery for resection of the tumor with nephrectomy and five courses of IVIG were administered after surgery due to a minor relapse. He was in remission in her last follow-up visit 16 months after surgery. The occurrence of PNP with IMT is notable; early detection and treatment are crucial for this tumor-associated autoimmune disease. [ABSTRACT FROM AUTHOR]

Introduction/background:Treatment of benign familial pemphigus or Hailey–Hailey disease (HHD), a rare inherited condition associated with a significant impairment of quality of life, is often challenging and disappointing with frequent relapses and infectious complications. Topical photodynamic therapy (PDT) may offer new perspectives in this difficult setting. Material and methods:Eight patients with long-lasting HHD lesions refractory to multiple treatments were treated on at least one involved site with PDT using methyl-amino levulinate with a standardized protocol of three sessions of irradiation separated by 3-week intervals. Results:A complete or partial clearing was achieved in all treated areas, and the result was satisfactorily maintained in all cases after a follow-up period ranging from 3 to 36 months. Results were of higher quality in non-inguinal areas. Tolerance was overall acceptable with local pain during and shortly after irradiation being the main limiting factor. Discussion/conclusion:Our series, although limited in size, emphasizes the interest of PDT in this difficult condition even though results may be incomplete. Treatment-related pain can be adequately managed by prior analgesics, cooling with sprayed water and local tumescent anesthesia. Overall, PDT appears as a relevant option in refractory HHD management with a favorable benefit/risk ratio. [ABSTRACT FROM AUTHOR]

The article offers information on the guidelines provided by the British Association of Dermatologists in the year 2017 for managing the pemphigus vulgaris disorder. Topics discussed include the objectives and limitations of the guidelines, involvement of stakeholders and the developmental methodology for the guidelines. Details regarding laboratory diagnosis, monitoring and therapeutic evaluation of the disease are presented.

Objective To study the various clinical presentations - age of onset, sex preponderance, course of disease and histopathological patterns of autoimmune vesiculobullous disorders and correlate clinical and histopathological findings and immunofluorescence with clinical and histopathological findings in few affordable cases. Methods The present descriptive study was undertaken in a tertiary care hospital over a period of 2 years. It included 50 patients of autoimmune vesicobullous diseases fulfilling inclusion criteria. Diagnosis was established by clinical and histopathological findings. Direct immunofluorescence (DIF) testing was done in few affordable patients. Results Autoimmune vesiculobullous disorders constituted 0.128% of skin disease. Pemphigus vulgaris (62%) constituted the most common vesiculobullous disorder. Females (58%) outnumbered males (42%). The age group ranged from 11 years to 85 years and the mean age was 46.2 (15.6) years. The duration of the diseases ranged from less than a week to more than a year. Tzanck smear findings revealed acantholytic cells in 90.3% cases of pemphigus vulgaris and all cases of pemphigus foliaceus and pemphigus erythematosus. Correlation between clinical and histopathological findings was seen in 96% of cases and that between histopathological and DIF findings in 89% of cases. Conclusion After the preliminary clinical and cytological diagnosis, histopathology and DIF are required to confirm the diagnosis. Considering the socioeconomic situations of the patients and unavailability of immunofluorescence technique widely, the study showed that clinical features and histopathology are fairly specific and cost-effective in arriving at the diagnosis. [ABSTRACT FROM AUTHOR]