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Razzaque A Ahmed - One of the best experts on this subject based on the ideXlab platform.
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Pemphigus vulgaris in pregnancy analysis of current data on the management and outcomes
Obstetrical & Gynecological Survey, 2009Co-Authors: Marisa Kardos, Danielle Levine, Hakan M Gurcan, Razzaque A AhmedAbstract:Objectives: The occurrence of Pemphigus vulgaris (PV) during pregnancy is rare. The purpose of this review was to describe management of PV in the mother, and report maternal and perinatal outcomes associated with the disease. Data Sources: A search of PubMed was conducted using the phrases “Pemphigus and pregnancy” and “neonatal Pemphigus.” The bibliographies of retrieved articles were also searched for relevant reports. Only articles in English and in which the diagnosis of Pemphigus had been made on the basis of histology or immunopathology were included. Tabulation, Integration, and Results: In 38 reports, pregnancies from 49 women with PV were described. Among the 40 patients in whom clinical profiles were provided, 33 had active disease and 7 were disease free. Prednisone was used in 37 of 49 (75%) patients with doses ranging from 5 to 300 mg/day (mean 152.5 mg). Concomitant therapies included plasmapheresis, plasma exchange, and dapsone in 1 patient each, and azathioprine in 5. Of the 44 live births, 20 (45%) neonates had PV lesions at birth and 24 (55%) were lesion-free. Five stillbirths were reported. In all neonates, PV lesions resolved within 1 to 4 weeks, either spontaneously or with mild topical corticosteroids treatment. Of the 5 intrauterine deaths, 1 was due to umbilical cord prolapse, 1 attributed to placental dysfunction, and 1 to cytomegalovirus pneumonitis. In the remaining 2, the cause was unknown. One neonate died 2 days after delivery due to meconium aspiration syndrome. Thus the aggregate perinatal mortality rate was 12% (6/49). Conclusions: The outcome of pregnancies complicated by Pemphigus is generally good, but achieving good outcomes likely depends on the collaborative efforts of the dermatologist and obstetrician. The available data suggest that the rate of perinatal mortality is increased, but these data may be subject to publication bias. Target Audience: bstetricians & Gynecologists, Family Physicians Learning Objectives: fter completion of this educational activity, the participant should be better able to describe appropriate medical therapies for Pemphigus vulgaris complicating pregnancy, and plan the management of pregnancies complicated by Pemphigus vulgaris.
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treatment of Pemphigus vulgaris with rituximab and intravenous immune globulin
The New England Journal of Medicine, 2006Co-Authors: Razzaque A Ahmed, Zachary Spigelman, Lisa A Cavacini, Marshall R PosnerAbstract:BACKGROUND Pemphigus vulgaris is a potentially fatal autoimmune mucocutaneous blistering disease. Conventional therapy consists of high-dose corticosteroids, immunosuppressive agents, and intravenous immune globulin. METHODS We studied patients with refractory Pemphigus vulgaris involving 30% or more of their body-surface area, three or more mucosal sites, or both who had inadequate responses to conventional therapy and intravenous immune globulin. We treated the patients with two cycles of rituximab (375 mg per square meter of body-surface area) once weekly for 3 weeks and intravenous immune globulin (2 g per kilogram of body weight) in the fourth week. This induction therapy was followed by a monthly infusion of rituximab and intravenous immune globulin for 4 consecutive months. Titers of serum antibodies against keratinocytes and numbers of peripheral-blood B cells were monitored. RESULTS Of 11 patients, 9 had rapid resolution of lesions and a clinical remission lasting 22 to 37 months (mean, 31.1). All immunosuppressive therapy, including prednisone, could be discontinued before ending rituximab treatment in all patients. Two patients were treated with rituximab only during recurrences and had sustained remissions. Titers of IgG4 antikeratinocyte antibodies correlated with disease activity. Peripheral-blood B cells became undetectable shortly after initiating rituximab therapy but subsequently returned to normal values. Side effects that have been associated with rituximab were not observed, nor were infections. CONCLUSIONS The combination of rituximab and intravenous immune globulin is effective in patients with refractory Pemphigus vulgaris.
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treatment of Pemphigus vulgaris with rituximab and intravenous immune globulin
The New England Journal of Medicine, 2006Co-Authors: Razzaque A Ahmed, Zachary Spigelman, Lisa A Cavacini, Marshall R PosnerAbstract:Background Pemphigus vulgaris is a potentially fatal autoimmune mucocutaneous blistering disease. Conventional therapy consists of high-dose corticosteroids, immunosuppressive agents, and intravenous immune globulin. Methods We studied patients with refractory Pemphigus vulgaris involving 30% or more of their body-surface area, three or more mucosal sites, or both who had inadequate responses to conventional therapy and intravenous immune globulin. We treated the patients with two cycles of rituximab (375 mg per square meter of body-surface area) once weekly for 3 weeks and intravenous immune globulin (2 g per kilogram of body weight) in the fourth week. This induction therapy was followed by a monthly infusion of rituximab and intravenous immune globulin for 4 consecutive months. Titers of serum antibodies against keratinocytes and numbers of peripheral-blood B cells were monitored. Results Of 11 patients, 9 had rapid resolution of lesions and a clinical remission lasting 22 to 37 months (mean, 31.1). Al...
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rituximab a monoclonal antibody to cd20 used in the treatment of Pemphigus vulgaris
Journal of The American Academy of Dermatology, 2006Co-Authors: Abdul Kader El Tal, Razzaque A Ahmed, Zachary Spigelman, Marshall R PosnerAbstract:Background Rituximab is an anti-CD20 chimeric antibody that selectively targets B lymphocytes. Recently, it has been reported to be beneficial in treating Pemphigus vulgaris. Objective Our aim was to review the English-language literature on the treatment of Pemphigus vulgaris (PV) with rituximab and to determine its efficacy and influence on clinical outcome(s). Material and methods A retrospective review of the literature on the use of rituximab in the treatment of PV was conducted. Seventeen patients in 10 reports were described and their data were reviewed. Results The majority of patients received one course of rituximab along with conventional immunosuppressive therapy as concomitant therapy; 88% of the patients demonstrated improvement. More than half of the patients were followed up for more than 6 months after rituximab treatment; they appeared to be clinically disease free, but were still receiving conventional immunosuppressive therapy. Side effects in most patients were transient and infusion related. Serious infections occurred in 4 patients. One patient died. Limitations The sample size of this study is small; there is no uniformity of data collection or measurement of key and critical indices, and follow-up was limited. Conclusion Rituximab may be a promising agent in treatment of PV.
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treatment of Pemphigus vulgaris current and emerging options
American Journal of Clinical Dermatology, 2005Co-Authors: Shih Wei Yeh, Naveed Sami, Razzaque A AhmedAbstract:Background: Pemphigus vulgaris is a rare, chronic, autoimmune mucocutaneous blistering disease. The disease can progress to involve the skin and multiple mucosae. Pemphigus vulgaris can be associated with a high morbidity and significant mortality rate. Treatment of the condition can be challenging. Conventional therapy primarily consists of systemic corticosteroids and immunosuppressant agents. In some patients with Pemphigus vulgaris, these agents fail to provide an effective clinical response or have significant adverse effects. Methods: We evaluated data on 792 patients with Pemphigus vulgaris retrieved from PubMed, covering the period 1973–2004. Only patients reported in the English literature were included in this review. Recently, several new therapeutic agents and treatment modalities have been described for the treatment of patients with Pemphigus vulgaris. Some therapeutic agents that were used in the past and abandoned have recently regained favor. This review focuses on the therapeutic uses of dapsone, methotrexate, mycophenolate mofetil, chlorambucil, dexamethasone-cyclophosphamide pulse therapy, immunoablative therapy with cyclophosphamide, plasmapheresis, and extracorporeal photochemotherapy. Newer agents, such as intravenous immunoglobulin (IVIg) therapy and rituximab (an anti-CD20 chimeric monoclonal antibody), are also discussed. Results and conclusions: Among the oral agents, dapsone may be considered a first-line agent. This is primarily because the risk of potentially fatal adverse effects with this drug is lower than that associated with other available chemotherapeutic agents. In patients who are refractory to oral agents, alternative treatments have been used to prevent further disease progression. Recently, the use of IVIg therapy, with a defined protocol, has been reported to be beneficial. This therapy is promising since it may allow for discontinuation of all other therapies and is safe. The adverse effects from IVIg therapy are minimal. Furthermore, compared with other therapies, it provides a better quality of life.
Daniel N. Sauder - One of the best experts on this subject based on the ideXlab platform.
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In Vitro and In Vivo Expression of Interleukin-1α and Tumor Necrosis Factor-α mRNA in Pemphigus vulgaris: Interleukin-1α and Tumor Necrosis Factor-α are Involved in Acantholysis
The Journal of investigative dermatology, 2000Co-Authors: Claudio Feliciani, Paola Toto, Saman Mohammad Pour, G. Coscione, Paolo Amerio, Gulnar Shivji, Binghe Wang, Daniel N. SauderAbstract:Keratinocyte-derived cytokines have been implicated in the pathogenesis of a number of skin diseases. In this study we examined the possible role of keratinocyte-derived cytokines in the development of acantholysis in Pemphigus vulgaris. Nineteen patients with Pemphigus vulgaris, demonstrating the characteristic clinical, pathologic, and immunopathologic findings were studied. In situ immunolabeling demonstrated the presence of two cytokines interleukin-1α and tumor necrosis factor-α, in lesional and perilesional areas. Results were confirmed by reverse transcriptase–polymerase chain reaction, demonstrating overexpression of both cytokines in vivo . To study the role of these cytokines in the pathogenesis of Pemphigus vulgaris both in vitro and in vivo studies were performed. The results of the in vitro study demonstrated that Pemphigus vulgaris IgG induced interleukin-1α and tumor necrosis factor-α mRNA in the skin. The potential pathogenic role of these mediators was demonstrated by a blocking study using antibodies against human interleukin-1α and tumor necrosis factor-α in keratinocytes cultures. A combination of anti-interleukin-1α and anti-tumor necrosis factor-α antibodies inhibited in vitro Pemphigus vulgaris IgG induced acantholysis. To confirm the role of interleukin-1 and tumor necrosis factor-α in Pemphigus, we utilized passive transfer studies using interleukin-1 deficient mice (ICE–/–, interleukin-1β–/–) and tumor necrosis factor-α receptor deficient mice (TNFR1R2–/–). Both groups demonstrated a decreased susceptibility to the passive transfer of Pemphigus. Our data support the role of cytokines interleukin-1 and tumor necrosis factor-α in the pathogenesis of Pemphigus vulgaris.
Paolo Amerio - One of the best experts on this subject based on the ideXlab platform.
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In Vitro and In Vivo Expression of Interleukin-1α and Tumor Necrosis Factor-α mRNA in Pemphigus vulgaris: Interleukin-1α and Tumor Necrosis Factor-α are Involved in Acantholysis
The Journal of investigative dermatology, 2000Co-Authors: Claudio Feliciani, Paola Toto, Saman Mohammad Pour, G. Coscione, Paolo Amerio, Gulnar Shivji, Binghe Wang, Daniel N. SauderAbstract:Keratinocyte-derived cytokines have been implicated in the pathogenesis of a number of skin diseases. In this study we examined the possible role of keratinocyte-derived cytokines in the development of acantholysis in Pemphigus vulgaris. Nineteen patients with Pemphigus vulgaris, demonstrating the characteristic clinical, pathologic, and immunopathologic findings were studied. In situ immunolabeling demonstrated the presence of two cytokines interleukin-1α and tumor necrosis factor-α, in lesional and perilesional areas. Results were confirmed by reverse transcriptase–polymerase chain reaction, demonstrating overexpression of both cytokines in vivo . To study the role of these cytokines in the pathogenesis of Pemphigus vulgaris both in vitro and in vivo studies were performed. The results of the in vitro study demonstrated that Pemphigus vulgaris IgG induced interleukin-1α and tumor necrosis factor-α mRNA in the skin. The potential pathogenic role of these mediators was demonstrated by a blocking study using antibodies against human interleukin-1α and tumor necrosis factor-α in keratinocytes cultures. A combination of anti-interleukin-1α and anti-tumor necrosis factor-α antibodies inhibited in vitro Pemphigus vulgaris IgG induced acantholysis. To confirm the role of interleukin-1 and tumor necrosis factor-α in Pemphigus, we utilized passive transfer studies using interleukin-1 deficient mice (ICE–/–, interleukin-1β–/–) and tumor necrosis factor-α receptor deficient mice (TNFR1R2–/–). Both groups demonstrated a decreased susceptibility to the passive transfer of Pemphigus. Our data support the role of cytokines interleukin-1 and tumor necrosis factor-α in the pathogenesis of Pemphigus vulgaris.
Dedee F. Murrell - One of the best experts on this subject based on the ideXlab platform.
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Pemphigus vulgaris an evidence based treatment update
Drugs, 2015Co-Authors: Dedee F. Murrell, Cathy Y ZhaoAbstract:While a variety of intervention options have been described for Pemphigus vulgaris, the optimal treatment strategy has not been established. The objective of this systematic review is to assess the literature on the efficacy and safety of interventions for the treatment of Pemphigus vulgaris. Five electronic databases were searched, including The Cochrane Skin Group’s Specialized Register, The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE and Latin American and Caribbean Health science Information database (LILACS). Five trial registers as well as reference lists of included RCTs were also searched. Any published randomised controlled trial (RCT) on intervention for Pemphigus vulgaris was included, provided the diagnosis of Pemphigus vulgaris was confirmed with appropriate clinical features, histopathology and immunofluorescence studies. Studies which included forms of Pemphigus other than Pemphigus vulgaris were excluded. Altogether 18 RCTs were identified including 16 distinct interventions. Included studies were assessed for patient selection, methods of randomisation, blinding, follow-up and selective reporting. Current evidence is incomplete and inconclusive. The interventions which appear promising, but will require further evaluation include adjuvant mycophenolate mofetil (MMF), azathioprine, intravenous immunoglobulins (IVIG), sulfasalazine and pentoxifylline, infliximab, epidermal growth factor and pimecrolimus. Interventions with inconclusive evidence include high (120–180 mg) versus low (45–60 mg) prednisone dosage, pulsed dexamethasone, cyclophosphamide, dexamethasone–cyclophosphamide pulse therapy (DCP), cyclosporine, dapsone, etanercept, acyclovir and tacrolimus. Our review is limited by the small number of high-quality RCTs and variety of outcome measures, precluding the performing of a meta-analysis. The optimal treatment strategy for Pemphigus vulgaris remains unclear. Higher quality RCTs are required in the future to re-evaluate many interventions and to explore other unstudied interventions.
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A systematic review of randomized controlled trials for Pemphigus vulgaris and Pemphigus foliaceus.
Journal of the American Academy of Dermatology, 2011Co-Authors: Linda K Martin, Victoria P Werth, Elmer V. Villaneuva, Dedee F. MurrellAbstract:Background A range of interventions has been described for the treatment of Pemphigus; however, the optimal therapeutic strategy has not been established. Objective We sought to evaluate the safety and efficacy of interventions for Pemphigus vulgaris and Pemphigus foliaceus. Methods We undertook a systematic review and meta-analysis according to the methodology of the Cochrane Collaboration. We selected randomized controlled trials including participants with the diagnosis of Pemphigus vulgaris or Pemphigus foliaceus confirmed with clinical, histopathological, and immunofluorescence criteria. All interventions were considered. Primary outcomes studied were remission and mortality. Secondary outcomes included disease control, relapse, Pemphigus severity score, time to disease control, cumulative glucocorticoid dose, serum antibody titers, adverse events, and quality of life. Results Eleven studies with a total of 404 participants were identified. Interventions assessed included prednisolone dose regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor, and traditional Chinese medicine. We found some interventions to be superior for certain outcomes, although we were unable to conclude which treatments are superior overall. Limitations Many interventions for Pemphigus have not been evaluated in controlled trials. All studies were insufficiently powered to establish definitive results. Conclusions There is inadequate evidence available at present to ascertain the optimal therapy for Pemphigus vulgaris and Pemphigus foliaceus. Further randomized controlled trials are required.
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Diagnosis and Clinical Features of Pemphigus vulgaris
Dermatologic clinics, 2011Co-Authors: Supriya S. Venugopal, Dedee F. MurrellAbstract:Autoimmune bullous diseases are associated with autoimmunity against structural components that maintain cell-cell and cell-matrix adhesion in the skin and mucous membranes. They include those where the skin blisters at the basement membrane zone and those where the skin blisters within the epidermis (Pemphigus vulgaris, Pemphigus foliaceus, and other subtypes of Pemphigus). The variants of Pemphigus are determined according to the level of intraepidermal split formation. There are 5 main variants of Pemphigus: Pemphigus vulgaris, Pemphigus foliaceus, Pemphigus erythematosus, drug-induced Pemphigus, and paraneoplastic Pemphigus. This review focuses only on Pemphigus vulgaris.
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interventions for Pemphigus vulgaris and Pemphigus foliaceus
Cochrane Database of Systematic Reviews, 2009Co-Authors: Linda K Martin, Ana Liza Agero, Victoria P Werth, Elmer Virgil Villanueva, Janet Segall, Dedee F. MurrellAbstract:Background A range of interventions have been described for treatment of Pemphigus, however the optimal therapeutic strategy has not been established. Objectives To assess the efficacy and safety of all interventions used in the management of Pemphigus vulgaris and Pemphigus foliaceus. Search methods We searched the Cochrane Skin Group Specialised Register (October 2008), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2008), MEDLINE (2003 to October 2008), EMBASE (2005 to October 2008), LILACS (1981 to October 2008), Ongoing Trials Registers, reference lists of articles, conference proceedings from international Pemphigus meetings and contacted experts in the field. Selection criteria Randomised controlled trials of any intervention in Pemphigus vulgaris or Pemphigus foliaceus. Data collection and analysis Two authors independently assessed quality and extracted data from studies. All investigators were contacted for further information. Adverse events were identified from included studies. Main results Eleven studies with a total of 404 participants (337 Pemphigus vulgaris, 27 Pemphigus foliaceus and 40 not specified ) were identified. The quality of included studies was not high, the majority of studies did not report allocation concealment, and power was limited by very small sample sizes. Interventions assessed included prednisolone dose regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor and traditional Chinese medicine. Ten studies included participants with newly diagnosed or newly active recurrent disease, and one trial included participants in maintenance phase. There was sufficient data for 4 meta-analyses, each pooling results of two studies only. For the majority of interventions, results were inconclusive. We found some interventions to be superior for certain outcomes, although we were unable to conclude which treatments are superior overall. Mycophenolate was more effective in achieving disease control than azathioprine (1 study; n=40; RR 0.72; 95% CI 0.52 to 0.99, NNT 3.7). There was evidence of a steroid-sparing benefit of azathioprine (1 study; n=57; MWD -3919 mg prednisolone; 95% CI -6712 to -1126) and cyclophosphamide (1 study; n=54; MWD -3355 mg prednisolone; 95% CI -6144 to -566) compared to glucocorticoids alone. Topical epidermal growth factor decreased time to control (1 study; n=20; HR 2.35; 95% CI 1.62 to 3.41). Authors' conclusions There is inadequate information available at present to ascertain the optimal therapy for Pemphigus vulgaris or Pemphigus foliaceus. Further research is required, especially to assess the optimal glucocorticoid dose, the role of adjuvant immunosuppressive medications, and long-term adverse events to improve harm:benefit analyses.
Adela R Cardones - One of the best experts on this subject based on the ideXlab platform.
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comparison of rituximab and conventional adjuvant therapy for Pemphigus vulgaris a retrospective analysis
PLOS ONE, 2018Co-Authors: Ashwin Agarwal, Russell P Hall, Lionel L Banez, Adela R CardonesAbstract: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-a-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.