Dupilumab as a novel therapy for bullous pemphigoid: A multicenter case series.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disorder occurring mostly in the elderly that lacks adequate treatments. OBJECTIVE: To describe our experience using dupilumab in a series of patients with BP. METHODS: This is a case series of patients from 5 academic centers receiving dupilumab for BP. Patients were eligible if they had a clinical diagnosis of BP confirmed by lesional skin biopsy evaluated by one of more of the following: hematoxylin and eosin staining, direct immunofluorescence, or enzyme-linked immunosorbent assay for BP180 or BP230, or both. RESULTS: We identified 13 patients. Patients were an average age of 76.8 years, and the average duration of BP before dupilumab initiation was 28.8 months (range, 1-60 months). Disease clearance or satisfactory response was achieved in 92.3% (12 of 13) of the patients. Satisfactory response was defined as clinician documentation of disease improvement and patient desire to stay on the medication without documentation of disease clearance. Total clearance of the BP was achieved in 53.8% (7of 13) of patients No adverse events were reported. LIMITATIONS: Include small sample size, lack of a control group, lack of a standardized assessment tool, and lack of standardized safety monitoring. CONCLUSION: Dupilumab may be an additional treatment for BP, leading to disease clearance or satisfactory response in 92.3% of patients, including in those in whom previous conventional therapy had failed.

Definitions and outcome measures for mucous membrane pemphigoid: recommendations of an international panel of experts.

Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index.

Treatment of pemphigus vulgaris: current and emerging options.

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.

Eyelid skin involvement in pemphigus foliaceus.

PURPOSE: To report the involvement of eyelid skin in a patient with pemphigus foliaceus. METHODS: Retrospective, interventional case report of a patient with pemphigus foliaceus involving both eyelids. The diagnosis of pemphigus foliaceus was based on histopathology and confirmed by direct immunofluorescence and immunoblot. Failure to respond to conventional immunosuppressive therapy, including high-dose corticosteroids, methotrexate, azathioprine, dapsone, and mycophenolate mofetil, necessitated the use of intravenous immunoglobulin (IVIg) therapy. RESULTS: After successful treatment with IVIg, no change in visual acuity or other sequelae secondary to ocular pemphigus foliaceus were observed. Normal ocular architecture was maintained. Clinical remission was observed after successful therapy. CONCLUSIONS: Pemphigus foliaceus involves the skin of the eyelid and does not involve the conjunctiva. The patient did not respond to conventional immunosuppressive therapy. The use of IVIg as mono-therapy resulted in long-term clinical remission.

Influence of intravenous immunoglobulin therapy on autoantibody titers to desmoglein 3 and desmoglein 1 in pemphigus vulgaris.

Pemphigus vulgaris (PV) is an autoimmune mucocutaneous blistering disease. Recently, patients with mucosal involvement have been described to have autoantibodies to desmoglein 3 (dsg), while patients with mucocutaneous disease have autoantibodies to dsg 1 and dsg 3. The objective of this study was to prospectively analyze, over a 24-month period, the influence of intravenous immunoglobulin (i.v.Ig) therapy on autoantibody titers to dsg 3 and dsg 1, in two groups of patients with severe PV. Group A consisted of 11 patients with mucocutaneous involvement and group B consisted of 10 patients with only mucosal involvement. Levels of autoantibodies to dsg 3 and 1 were measured by ELISA, at monthly intervals. Prior to therapy initiation, group A patients' sera showed a high ELISA index value of both dsg 3 and 1 antibodies, while group B patients had a high index value to only dsg 3. During i.v.Ig therapy, a progressive decline in the ELISA index values was observed in all patients. After the initiation of i.v.Ig therapy, in group A, a statistically significant reduction (p < 0.05) in ELISA index value to dsg 3 and 1 was detected after four and five months, respectively. In Group B, a significant decline in the mean autoantibody titer values to dsg 3 (p < 0.05) was observed after six months of i.v.Ig therapy. Group A patients had a negative ELISA index value to dsg 3 and 1 after a mean period of 21 and 20 months, respectively. Group B patients had a negative dsg 3 score after a mean period of 22 months. These results indicate that autoantibody titers to dsg 3 and 1, as measured by ELISA, can be used to monitor the serological response to treatment in PV patients. A sustained serological remission is observed in patients treated with i.v.Ig therapy. .

Pemphigus vulgaris in pregnancy: analysis of current data on the management and outcomes.

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: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After 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.