Treatment Of Mucous Membrane Pemphigoid Research Articles

Intravenous Ig Ameliorates Disease in a Murine Model of Anti–Laminin 332 Mucous Membrane Pemphigoid

Intravenous Ig (IVIg) is used to treat mucous membrane pemphigoid, although its therapeutic effectivity is not sufficiently supported by randomized controlled clinical trials, and its mode of action is only insufficiently understood. We have examined the effect of IVIg in a mouse model of anti-laminin 332 mucous membrane pemphigoid and found that IVIg ameliorates both cutaneous and mucosal inflammatory lesions. Our investigation into the modes of action of IVIg in mucous membrane pemphigoid indicated effective anti-inflammatory mechanisms beyond the enhanced degradation of IgG mediated through inhibition of the FcRn. Our results suggest that IVIg curbs the activation of neutrophils at several levels. This includes a direct, immediate inhibitory effect on neutrophil activation by immune complexes but not C5a, which blunts the release of ROS and leukotriene B4 from neutrophils. IVIg also suppresses the formation of neutrophil extracellular traps in response to calcium ion ionophore. Invivo treatment with IVIg altered the transcriptome of blood leukocytes and bone marrow neutrophils toward less proinflammatory phenotypes. Collectively, our results support the effectivity of IVIg in the treatment of mucous membrane pemphigoid and indicate that effects on neutrophils at multiple levels may significantly contribute to its therapeutic effects.

Retrospective analysis of the long-term therapeutic effectiveness and safety profile of rituximab in the treatment of mucous membrane pemphigoid in a German university center between 2008 and 2019.

The B-cell-depleting anti-CD20 antibody rituximab (RTX) is often used as an adjuvant drug for the treatment of refractory cases of mucous membrane pemphigoid (MMP). This study aims to determine the therapeutic effectiveness and the safety profile of RTX in MMP. The medical records of all cases of MMP treated with RTX between 2008 and 2019 in our university medical center located in northern Germany, which specialized in autoimmune blistering skin diseases, were retrieved and systemically analyzed for treatment responses and potential adverse events over a median period of 27 months. We identified 18 MMP patients who received at least one cycle of RTX to treat MMP. RTX was always used as an adjuvant treatment, and its application did not change concomitant treatments. Under treatment with RTX, 67% of the patients achieved an improvement in their disease activity within 6 months. This was also reflected in a statistically significant reduction in the Mucous Membrane Pemphigoid Disease Index (MMPDAI) activity score. The frequency of infections under RTX treatment increased only slightly. The use of RTX is associated with an attenuation of MMP in a large proportion of MMP patients in our study. At the same time, its application was not found to further increase the susceptibility of the most strongly immunocompromised population of MMP patients to opportunistic infections. Collectively, our results suggest that the potential benefits of RTX outweigh its risks in patients with refractory MMP.

Rituximab combined with conventional therapy vs conventional therapy alone for the treatment of mucous membrane pemphigoid: A retrospective review

Rituximab combined with conventional therapy vs conventional therapy alone for the treatment of mucous membrane pemphigoid: A retrospective review

Rituximab combined with conventional therapy versus conventional therapy alone for the treatment of mucous membrane pemphigoid (MMP)

The use of rituximab for refractory autoimmune blistering diseases is increasing. Data related to rituximab for the treatment of mucous membrane pemphigoid (MMP) are limited. We sought to compare the efficacy of adding rituximab with traditional immunosuppressive therapies in the treatment of MMP. The primary outcome was achievement and time to disease control. Patients with a diagnosis of MMP from August 2001 to June 2015 who had greater than 6 months of follow-up after the initiation of therapy were reviewed. In all, 24 patients were treated with rituximab and 25 were treated with conventional immunosuppression. Of patients, 100% in the rituximab group achieved disease control compared with 40% in the conventional group (P < .01), with a mean time to disease control of 10.17 months and 37.7 months (P = .02). Adverse events were seen in 33% of patients after rituximab, compared with 48% of patients in the conventional group (P = .2). Rituximab dosing was not uniform and the 2 groups were not matched in terms of disease severity, nor were they randomized. Our study indicates that the addition of rituximab to conventional therapy in patients with MMP results in more rapid and sustained disease control with potentially fewer adverse events.

Heat shock protein 90 inhibition: A potential double- or triple-edged sword in the treatment of mucous membrane pemphigoid

Mucous membrane pemphigoid (MMP) is a subtype of autoimmune subepidermal blistering diseases characterized by autoantibodies to structural components of the hemidesmosome primarily affecting mucous membranes. Inflammation-related progressive scarring can lead to serious complications, including blindness, and the disease may be associated with malignancy. Conventional immunosuppressive treatment is often insufficiently effective and limited due to side effects, warranting new therapeutic options ideally targeting both inflammation and extensively recalcitrant cicatrization. Heat shock protein 90 (Hsp90) is a cell stress-inducible chaperone required for the function of a large number of client proteins, and its pharmacological inhibition has proven to be effective and relatively safe in patients with cancer. Recent observations also suggest a promising role of Hsp90 as drug target in preclinical in vivo murine models of autoimmune diseases such as subepidermal bullous and fibrotic autoimmune disorders comprising epidermolysis bullosa acquisita and systemic sclerosis, respectively, which exhibit some pathophysiological features reminiscent of MMP. This article thus hypothesizes that Hsp90 blockade could represent a double-edged sword in MMP treatment by targeting pathogenic factors of inflammatory blister and fibrosis formation. Moreover, Hsp90 inhibitors could even be proclaimed as a triple-edged sword in case of an underlying malignancy. Future studies investigating the role of Hsp90 in MMP are needed to clarify whether Hsp90 inhibition could become a novel treatment approach for patients with this potentially devastating disease.

Treatment of Mucous Membrane Pemphigoid With Mycophenolate Mofetil

To evaluate the clinical outcomes of mycophenolate mofetil (MMF) treatment of mucous membrane pemphigoid (MMP). This is a retrospective analysis of consecutive patients with clinical MMP seen in the Ocular Surface Disease Clinic at the Wills Eye Institute, between January 1, 2004, and December 31, 2010, treated with MMF. The main outcomes measured were control of inflammation and discontinuation of MMF. A total of 23 MMP patients taking MMF were identified. The median age of the MMF-treated patients was 77.0 years. Eleven of the 23 patients (47.8%) had biopsy-proven MMP. All patients were at least Foster grading system stage 2, with most stage 3 or 4. Eight patients (34.8%) failed previous treatments with dapsone, methotrexate, prednisone, azathioprine, cyclophosphamide, or 6-mercaptopurine. The average duration of MMF treatment was 23.32 ± 33.17 months (range 1-124.83 months, median 7.4 months). Of the 23 patients with MMP, control of inflammation was achieved with MMF within 3 months for 56.5% [95% confidence interval (CI) 54.5-59.6], within 6 months for 69.6% (95% CI 65.2-76.6), and within 12 months for 82.6% (95% CI 75.3-92.4) of the patients. Nineteen patients (82.4%) achieved control of inflammation, with 16 of the 19 (84.2%) achieving control of inflammation with MMF as monotherapy. Fifteen patients were treated with MMF as initial therapy. Twenty-one percent of patients (5 of 23) were taken off MMF for failure of inflammatory control (4) or an allergic reaction (1). Treatment of MMP with MMF in this uncontrolled case series resulted in control of inflammation in the majority of patients with minimal side effects. Our data support consideration of MMF as an initial treatment option for active ocular MMP.

Treatment of mucous membrane pemphigoid with the combination of mycophenolate mofetil, dapsone, and prednisolone: a case series

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disorder characterized by inflammation, blistering, and scarring and predominantly occurring at mucous membranes. Successful treatment can be challenging, and uncontrolled disease may result in significant morbidity with scarring of the conjunctiva and oropharynx leading to blindness and dysphagia, respectively. We report safe successful treatment of 6 patients with significant MMP-related oral inflammation with the use of a previously unreported combination of mycophenolate mofetil, dapsone, and prednisolone given at relatively low doses. We propose that this combination of treatments should be investigated further.

Successful Treatment of Mucous Membrane Pemphigoid with the Anti-CD-20 Antibody Rituximab

Mucous membrane pemphigoid (MMP) is an often diffi-cult-to-treat autoimmune bullous disease characterized by circulating auto-antibodies targeting the dermo-epidermal junctional zone (1–3). Due to limited disease control and/or severe adverse reactions to glucocorticoids and conventional immunosuppressants, alternative treatment options are frequently needed. We describe here the first successful therapy of refractory MMP with rituximab, a humanized anti-CD20 monoclonal antibody depleting B-lymphocytes (4, 5), that resulted in a complete and persisting remission.CASE REPORT

Successful Treatment of Mucous Membrane Pemphigoid With Etanercept in 3 Patients

Mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid, is a serious, autoimmune, blistering disorder that can result in blindness and other complications as a result of scarring of the mucous membranes. Effective treatment modalities are often toxic. Herein, we describe a novel therapeutic approach that is based on 2 reports in the literature of the successful use of etanercept to treat MMP. Three patients with MMP were treated with subcutaneous injections of 25 mg of etanercept twice weekly. All 3 patients had oral mucosal involvement, and 1 had severe, recalcitrant, ocular disease. Oral mucosal disease improved in all 3 patients. The patient with ocular involvement experienced stabilization of progression. Effective treatment modalities for MMP are often toxic. Etanercept may be an effective treatment option for MMP of the oral and ocular mucous membranes. This therapy should be considered as an alternative treatment option for patients who would require other aggressive systemic treatments, such as cyclophosphamide, corticosteroids, azathioprine sodium, and intravenous immunoglobulin.

Successful treatment of mucous membrane pemphigoid with tacrolimus

Mucous membrane pemphigoid (MMP) is a heterogeneous group of autoimmune, chronic inflammatory ubepithelial vesiculobullous disorders, predominantly affects the mucous membranes of the oral cavity and eyes of the elderly population. Oral manifestations of pemphigoid include desquamative gingivitis, ulcers, erythematous patches, erosions, vesicles and bullae located on the attached gingiva, palate, buccal mucosa, labial mucosa, and tongue. Diagnosis is based on history, clinical features and a biopsy stained with hematoxylin and eosin (H&E), and also direct and indirect immunofluorescence. Topical and systemic corticosteroids are the most commonly used medications for managing pemphigoid. Recently, topical tacrolimus has been successfully used in the treatment of ocular and skin pemphigoid. In this report we present a patient with longterm recalcitrant MMP that did not respond to conventional treatment but as treated successfully with tacrolimus ointment.

Steroid-induced myopathy and diabetes: Report of a case

Corticosteroid therapy may give rise to a large number of side effects of varying degrees of severity. A case is presented in which systemic steroids used in the treatment of mucous membrane pemphigoid resulted in the development of diabetes mellitus and muscle wasting.