Mucous Membrane Pemphigoid Patients Research Articles

Reactivity against the BP180 ectodomain in patients with bullous pemphigoid, mucous membrane pemphigoid, multiple sclerosis and Parkinson disease

AbstractThe 16th non‐collagenous domain (NC16A) of BP180 is the main antigenic target of autoantibodies in bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP). Commercially available assays detect serum autoantibodies against NC16A in the majority of BP (80%–90%) and in approximately 50% of MMP patients. However, a standardized test system for detecting antibodies against other regions of BP180 is still lacking. Moreover, anti‐BP180 autoantibodies have been found in neurological conditions such as multiple sclerosis and Parkinson disease. This study aimed at identifying primary epitopes recognized by BP autoantibodies on the BP180 ectodomain. Serum samples of 51 BP and 30 MMP patients both without anti‐NC16A reactivity were included along with 44 multiple sclerosis and 75 Parkinson disease sera. Four overlapping His‐tagged proteins covering the entire BP180 ectodomain (BP180(ec)1–4) were cloned, expressed, purified and tested for reactivity by immunoblot. IgG antibodies to BP180(ec)3 were detected in 98% of BP, 77% of MMP and 2% of normal human sera. Only weak reactivity was detected for neurological diseases against BP180(ec)1, BP180(ec)2 and BP180(ec)4, in 3%, 11% and 7% of tested multiple sclerosis sera, respectively. 8% of Parkinson disease sera reacted with BP180(ec)2 and 9% with BP180(ec)4. In conclusion, this study successfully identified epitopes recognized by BP autoantibodies outside the NC16A domain in pemphigoid diseases. These findings contribute to a better understanding of the immune response in BP and MMP with potential implications for a future diagnostic assay for NC16A‐negative pemphigoid patients.

Autoimmunity against laminin 332.

Laminin 332 is a heterotrimeric structural protein of the basal membrane zone (BMZ) of the skin and adjacent mucosal tissues. The importance of laminin 332 for the structural integrity of the BMZ is demonstrated by mutations in any of the three genes encoding for its three chains causing variants of junctional epidermolysis bullosa. Autoimmunity against laminin 332 is observed in mucous membrane pemphigoid (MMP) and in the rare patients with orf-induced pemphigoid. MMP is an autoimmune blistering disease with predominant mucosal manifestations and autoantibodies against the BMZ of the skin and orifice-close mucous membranes. The main autoantigens of MMP are type XVII collagen (BP180) and laminin 332 targeted in about 80% and 10-20% of patients, respectively. An increasing number of studies has highlighted the association of anti-laminin 332 MMP and malignancies that can be revealed in about a quarter of these patients. This data has led to the recommendation of current guidelines to assay for anti-laminin 332 reactivity in all MMP patients. The present review focuses on anti-laminin 332 MMP describing clinical features, its pathophysiology, and detection of serum anti-laminin 332 IgG. In addition, the available data about the occurrence of malignancies in anti-laminin 332 MMP, the underlying tumor entities, and its biology are detailed.

Immunopathogenesis of mucous membrane pemphigoid

Adetailed understanding of the immunopathogenesis of mucous membrane pemphigoid (MMP) is of particular importance in view of the mostly difficult diagnostics and treatment of this blistering autoimmune dermatosis. Astill unknown disturbance of the body's own immune tolerance leads to the formation of autoreactive cells. As the disease progresses these produce autoantibodies which are directed against structural proteins in the basement membrane zone(BMZ). After they bind to the target antigen, complement factors are deposited along the BMZ and inflammatory cells invade the underlying tissue and produce the characteristic subepithelial blistering. This inflammatory response is associated with fibrosis and scarring in many affected tissues. Most phases of MMP pathogenesis are poorly understood; however, the last few years have shed more light on this processes. These advances are mostly the result of animal and cell culture models. Typical clinical and immunopathological characteristics of MMP, such as oral, conjunctival and skin lesions, are reflected, for example, in an antibody transfer-induced mouse model for anti-laminin 332 MMP in adult mice. Dapsone, as first-line treatment for MMP patients, significantly reduced the severity of these symptoms, and fibrosis in the skin and mucous membranes was also found histologically, which makes the model well-suited for testing new therapeutic approaches for MMP patients and might be of help for further elucidation of the immunopathogenesis of MMP.

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.

Long-term outcomes of fornix reconstruction and cicatricial entropion repair in ocular mucous membrane pemphigoid and drug-related secondary pemphigoid

ObjectifExaminer les résultats à long terme de la reconstruction du fornix oculaire et de la réparation de l'entropion cicatriciel en présence d'une pemphigoïde de la muqueuse oculaire (MMP, pour mucous membrane pemphigoid) et d'une MMP secondaire. MéthodesOn a procédé à un examen rétrospectif des dossiers médicaux de patients qui présentaient une MMP et qui devaient subir une reconstruction du fornix oculaire (greffe de membrane amniotique ou greffe de muqueuse buccale) ou une réparation de l'entropion cicatriciel (intervention de Wies) entre le 1er janvier 2000 et le 1er septembre 2020. La biopsie de la muqueuse des patients était positive et/ou ces derniers présentaient des caractéristiques cliniques typiques d'une MMP ou d'une MMP secondaire. Le paramètre primaire consistait en une réussite globale de la reconstruction du fornix oculaire mesurée par le maintien de sa profondeur lors de la dernière visite de suivi. La disparition du trichiasis, l'acuité visuelle et le soulagement des symptômes subjectifs comptaient au nombre des paramètres secondaires. RésultatsAinsi, 8 patients (10 yeux) présentant un diagnostic de MMP (3 hommes et 5 femmes; âge médian : 71 ans) et 4 patients (4 yeux) présentant un diagnostic de MMP secondaire (2 femmes et 2 hommes; âge médian : 87 ans) ont été admis à l’étude. La durée moyenne du suivi était de 22,7 mois (fourchette : 0,3–87,5 mois) dans le cas des patients présentant une MMP et de 15,4 mois (fourchette : 3,0–43,9 mois) dans celui des patients présentant une MMP secondaire. Dans le groupe MMP, 30,0 % des yeux ont fait l'objet d'une reconstruction du fornix oculaire, 60,0 % des yeux ont fait l'objet d'une réparation de l'entropion et 10,0 % des yeux ont subi les 2 formes d'intervention. La récurrence d'un symblépharon et la perte de la profondeur du fornix oculaire sont apparues dans tous les yeux qui présentaient une MMP en moyenne 6,4 ± 7,0 mois après l'intervention; le trichiasis avait réapparu chez tous les patients lors de la dernière visite de suivi. Chez les patients qui présentaient une MMP secondaire, 75,0 % des yeux ont présenté une récurrence du symblépharon, et 66,7 %, une récurrence du trichiasis. On a noté un soulagement à court terme des symptômes tant dans la MMP que dans la MMP secondaire. ConclusionsLa reconstruction du fornix oculaire et la réparation de l'entropion cicatriciel au sein de notre cohorte de patients présentant une MMP ou une MMP secondaire ont donné lieu à un soulagement à court terme des symptômes, mais une récurrence s'est produite en moyenne 6 mois après l'intervention.

Anti-laminin 332 antibody detection using biochip immunofluorescence microscopy in a real-life cohort of Italian patients with mucous membrane pemphigoid.

Mucous membrane pemphigoid (MMP) with anti-laminin 332 autoantibodies may be associated with malignancies, however, current serological assays have considerable limitations. At present, no commercial test for anti-laminin 332 antibodies is available, restricting the diagnosis to specialized laboratories worldwide. Biochip immunofluorescence microscopy has shown promising results in selected cohorts of laminin 332-MMP patients. Objectives: To detect anti-laminin 332 antibodies by biochip immunofluorescence microscopy in a real-life cohort of MMP patients and compare the results with those from traditional immunoblotting. Sera were obtained from 31 patients with MMP, 28 with bullous pemphigoid, five with pemphigus vulgaris, five with paraneoplastic pemphigus, five with linear IgA bullous dermatosis, and 10 controls, and analysed by biochip immunofluorescence using human cells expressing laminin 332. Immunoblotting was performed using purified laminin 332. MMP involved the oral mucosa in 65%, ocular mucosa in 9%, oral and ocular mucosae extensively in 13% as well as other mucosae in 13% of patients. Concomitant cutaneous involvement was reported in 35% of patients. Three MMP patients had an underlying malignancy. Anti-laminin 332 antibodies were detected in 2/31 (6%) cases by both methods. Based on immunoblotting, both laminin 332-positive sera reacted with α3 chain (in one case also with β3 chain). Both patients with anti-laminin 332 antibodies had extensive mucosal involvement and only one had cancer. Anti-laminin 332 antibodies were not detected in control groups. Biochip immunofluorescence is an appropriate technique to detect anti-laminin 332 antibodies which should be tested in patients with MMP.

S2k Guideline for the diagnosis and treatment of mucous membrane pemphigoid.

Mucous membrane pemphigoid (MMP) is a pemphigoid disease with predominant mucous membrane involvement. It mainly affects the mucous membranes of the mouth, eyes, nose and pharynx, but also the larynx, trachea, esophagus, genital and perianal regions. The manifestation of the disease covers a wide spectrum from gingival erythema and single oral lesions to severe tracheal strictures that obstruct breathing and conjunctival scarring with marked visual impairment and, not infrequently, blindness. In addition to a clinical picture of predominant mucosal involvement, diagnosis is based on direct immunofluorescence of a peri-lesional biopsy and serology. The main target antigen is BP180 (collagen XVII), and reactivity with laminin 332 is associated with malignancy in approximately 25% of MMP patients. The treatment of MMP is challenging. On the one hand, due to the involvement of different mucous membranes, good interdisciplinary cooperation is required; on the other hand, due to the rarity of the disease, no randomized controlled clinical trials are available. The aim of this guideline is to present the clinical picture, including severity and scoring systems, and to give guidance for diagnosing and treating this complex disease. In MMP, interdisciplinary cooperation plays an essential role as well as the prompt diagnosis and initiation of adequate therapy in order to avoid irreversible damage to the mucous membranes with serious complications.

Rituximab in Mucous Membrane Pemphigoid: A Monocentric Retrospective Study in 10 Patients with Severe/Refractory Disease.

Rituximab (RTX) is a monoclonal antibody directed against CD20 antigen indicated in an increasing number of immune-mediated diseases. While its efficacy in pemphigus vulgaris has been widely investigated, only a few data about its possible role in pemphigoid diseases have been reported in the literature. Accordingly, herein we evaluated a case series of patients with mucous membrane pemphigoid (MMP) treated with RTX. We included patients with a history of severe/refractory MMP who received at least one cycle of intravenous RTX between May 2018 and December 2021 and had 6 months of follow-up time. Disease control (DC) was our early endpoint, while complete remission (CR) and partial remission (PR) were late endpoints. CR off-therapy, relapses, and adverse events were evaluated as well. Our population included 10 MMP patients. Eight out of ten patients (80%) achieved DC in a mean of 8 weeks, while two patients with ocular MMP were non-responders. Among the eight patients who achieved DC, two reached CR off therapy, two CR on minimal therapy, and two achieved PR on minimal therapy. In our case series, the addition of RTX to conventional therapies was demonstrated to be safe and effective in reaching rapid disease control in the majority of refractory MMP patients.

On the Current Care Situation and Treatment of Ocular Mucous Membrane Pemphigoid in Germany.

Ocular involvement in mucous membrane pemphigoid (MMP) is relatively rare, with a prevalence of 25 cases per million population, equating to approx. 2,100 patients throughout Germany. Diagnosis can be difficult - especially in cases of isolated ocular involvement - and treatment can be complex and lengthy. Immunosuppressants or immunomodulatory drugs are often used. Due to the complexity of diagnosis and treatment, MMP patients are usually referred to specialized centers. The aim of this project was to evaluate the current care situation of patients with ocular MMP in Germany. A paper-based survey was designed and sent to all university eye clinics and other specialized centers in Germany in April 2020. The survey asked about the existence of a specialized outpatient service, the total annual number of patients with MMP, the annual number of newly diagnosed patients, any interdisciplinary collaboration for diagnostic or therapeutic purposes, as well as the local and systemic therapy used. Of a total of 44 clinics, 28 (64%) responded, reporting a total average of 27 ± 42 (0 - 200) patients and 3.6 ± 2.2 (0 - 10) new cases per year. This corresponds to a total of 741patients. Only nine (32%) of the responding clinics offer specialized MMP clinics. 93% of the centers collaborate with the local dermatology department. 79% perform serological and histological diagnostics in-house. About half of the centers (n = 16) apply a standardized treatment regime. Systemic glucocorticoids (66.7%) are most commonly used, followed by mycophenolate mofetil and dapsone (57.1%), rituximab (33.3%), azathioprine and cyclophosphamide (28.6%), as well as methotrexate (19.0%). The least frequently used treatment is intravenous immunoglobulin (14.3%). This survey of German ophthalmology departments obtained data from about one third of the estimated total cohort of all patients with MMP in Germany. These are presumed to be exclusively patients with at least one ocular involvement. The complex care of these patients is usually provided in collaboration with a dermatologist and with the use of systemic anti-inflammatory medication. Currently, an ophthalmological MMP register is being established to better record the epidemiology and care situation of this rare disease in Germany and to improve it in the long term.

Human Oral Mucosal Fibroblasts from Limbal Stem Cell Deficient Patients as an Autologous Feeder Layer for Epithelial Cell Culture

Purpose To investigate if human oral mucosal fibroblasts (HOMF) from patients with limbal stem cell deficiency (LSCD) can be used as an autologous feeder layer to support the culture of epithelial cells for potential clinical use. Methods HOMF were isolated from oral mucosal biopsies obtained from the following groups of patients with LSCD: aniridia, mucous membrane pemphigoid (MMP), Stevens–Johnson syndrome (SJS), and ectodermal dysplasia (ED). The ability of these cells to support the culture of human limbal epithelial cells (HLE) was compared to that of HOMF from non-LSCD donors and 3T3s commonly used to culture epithelial cells for use in the clinic to treat LSCD. Results HOMF were successfully obtained by explant culture for 3/3 aniridia patients, 3/3 MMP patients, 1/3 SJS patients, and 1/1 ED patients. All HOMF cultured from these LSCD groups supported the expansion of HLE with epithelial culture times and total colony forming efficiency (CFE) comparable to those achieved on HOMF isolated from donors without LSCD. PCR showed that all HLE cultured on LSCD donor HOMF expressed p63α, CK15, PAX6, CK12, and MUC16 as did HLE cultured on the control non-LSCD donor HOMF and 3T3s. Western blotting detected CK15 and MUC16 protein expression in all groups. Conclusions HOMF from patients with LSCD can be successfully used to support the expansion of epithelial cells. These cells may therefore be useful as autologous feeder fibroblasts for the expansion of epithelial cells for use in the clinic to treat LSCD.

A Probing of the Issue of Detecting IgG, IgG4 and IgA Antibodies to Laminin 332 Epitopes in Mucous Membrane Pemphigoid: A Clinical-Laboratory Experience of a Single Central European University Dermatology Department.

PurposeMucous membrane pemphigoid (MMP) is a very rare autoimmune bullous disease, affecting predominantly the mucosae and characterized by autoantibodies to the epithelial basement membrane components. Laminin 332 (Ln-332) is one of the most probable antigens with association with malignancy. The laboratory diagnosis of Ln-332-mediated autoimmunity is troublesome. The aim here was to comparatively examine IgG, IgG4, and IgA autoantibodies specific to α3, β3 or γ2 subunits of Ln-322 in MMP patients using the BIOCHIP mosaic-based indirect immunofluorescence technique (IIF).Patients and MethodsSera from 15 MMP patients were studied. BIOCHIP mosaic-based Ln-332 IIF, direct immunofluorescence, ELISA tests for anti-BP180/BP20 IgG antibodies and statistical analyses were performed.ResultsOf all the 15 sera examined for IgG4 antibodies, only 1 (6.67%) reacted with the α3 chain, 0 with the β3 chain, and 0 with the γ2 chain. No positive reactivity was seen with the IgG and IgA antibodies. BIOCHIP mosaic-based IIF with Ln-332 showed 100% sensitivity, 8% specificity, 21% positive predictive value, and 100% negative predictive value in relation to the diagnostic gold standard of DIF. The concomitant malignancies were revealed in three cases.ConclusionThe detection of antibodies to Ln-332 chains is occasional in Polish MMP sufferers. Still, the evaluation of IgG4 antibodies in MMP can reduce the false-negative results.

European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part II.

This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus‐based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue‐bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10–25% of patients laminin 332 is recognized. In 25–30% of MMP patients with anti‐laminin 332 reactivity, malignancies have been associated. As first‐line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first‐line regimens. Additional recommendations are given, tailored to treatment of single‐site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high‐quality randomized controlled trials.

European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part I.

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus‐based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono‐ or multisite involvement. Patients’ autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the ‘Cicatrising Conjunctivitis Assessment Tool’ and the Oral Disease Severity Score (ODSS). Patient‐reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course.

Towards therapeutic drug monitoring of mycophenolic acid in mucous membrane pemphigoid: A retrospective single-centre study.

Mycophenolate mofetil (MMF) is theoretically a treatment of choice for mucous membrane pemphigoid (MMP), due to its good long-term tolerance and efficacy especially in elderly patients. However, no therapeutic monitoring is currently performed despite its large inter-individual variability. The aim of this study was to investigate the exposure/effect relationship based on the area under the curve (AUC) or trough level of mycophenolic acid in MMP patients. Thirteen patients (n=29 AUC measurements performed between February 2013 and November 2016) treated for MMP at Limoges University Hospital were evaluated using the Mucous Membrane Pemphigoid Disease Area Index score, and patients were classified as improvement (>50% decrease vs. baseline) vs. stabilisation (<50%) or non-response (no improvement). AUC was estimated using a population pharmacokinetic model and Bayesian estimation. The association between exposure parameters, demographic variables and response group was investigated using time-dependent Cox models, and an AUC threshold for 'improvement' was also investigated. An improvement was observed in approximately 70% of the patients. Only the MPA AUC0-24h was retained in the multivariate analysis with a decreased risk of stabilisation/non-response per 10mg*h/L increase, (HR=0.64, 95% CI=[0.43-0.94], P=0.0038). That led to an AUC0-24h threshold of 89mg*h/L associated with excellent performances (AUC ROC=0.828, Sen=75%, Spe=100%, P=0.0001). An association between MPA exposure and disease was observed. Therapeutic drug monitoring can be proposed with an AUC0-24h threshold of 89mg*h/L. It might improve the long-term response of patients to this drug with better tolerance than rituximab or cyclophosphamide.

The efficacy of rituximab in patients with mucous membrane pemphigoid

Objective Mucous membrane pemphigoid (MMP) is an autoimmune blistering disorder with tendency to scarring. Long term immunosuppressive treatment may be required to minimize the consequences of the disease. Methods In this retrospective study, we investigated the efficacy of rituximab (RTX) in MMP patients and compare the beneficial effects of early versus late administration of RTX. Medical records of 24 MMP patients who were treated with 500 mg RTX on day 1, then weekly for 4 consecutive weeks were reviewed. Results Twenty-one patients (87.5%) reached disease control (DC) at the mean interval of 4.95 months (SD: 5.15; range: 1–24) after RTX. Complete remission (CR) with scarring was achieved in 45.8% (n = 11) and 33.3% (n = 8) attained CR without any residual scar (total CR with or without scar 79.1%). Two patients (8.3%) reached partial remission including persistent gingivitis. Only one patient progressed from non-cicatricial to cicatricial MMP despite receiving RTX. 47.6% (n = 10) of patients experienced relapse after achieving DC at a mean interval of 15.2 months (range: 6–30, SD: 7.0). Considerably, earlier the RTX was administered, sooner the DC was obtained (Pearson r = 0.742, p-value < .001). Conclusions These results suggest that RTX may prevent further scarring and progression in MMP patients especially if administered early.

Autoantibody Detection for Diagnosis in Direct Immunofluorescence-Negative Mucous Membrane Pemphigoid: Ocular and Other Sites Compared

To assess whether a panel of serum pemphigoid autoantibody tests could be used to confirm an immunopathologic diagnosis of mucous membrane pemphigoid (MMP) in direct immunofluorescent negative (DIF-) MMP patients. Prospective cross-sectional study. Seventy-six patients with multisite MMP with 45 matched control participants. Enzyme-linked immunosorbent assays (ELISAs) for BP180 and BP230 (MBL International), immunoglobulin A (IgA) A and immunoglobulin G indirect immunofluorescence (IIF) on human salt-split skin and the keratinocyte footprint assay for anti-laminin 332 antibodies. Sensitivity and specificity of autoantibody detection and significant differences for individual tests and test combinations for MMP involving different sites. All DIF- patients (24/73 [31.8%]) had either ocular-only disease or ocular involvement in multisite disease. Serum pemphigoid autoantibodies were detected in 29 of 76 MMP patients (38.2%) compared with 3 of 45 control participants (6.7%). Autoantibody reactivity detected by any 1 or more of the tests was present in 6 of 24 DIF- patients (25%) compared with 22 of 49 DIF positive (DIF+) patients (44.9%). Ocular-only MMP serum reactivity was not significantly different for any test or test combination compared with control participants, whereas DIF- multisite ocular MMP differed for 1 ELISA and 3 of 7 test combinations. By contrast, for DIF+ nonocular MMP patients, all the individual tests, apart from IgA IIF, and all test combinations were significantly different compared with those for control participants. For the entire MMP cohort, the sensitivity of all individual tests was low, having a maximum of 21.05% for BP180 reactivity but increasing to 38.16% for an optimal test combination. Disease activity was associated strongly with positive serologic findings. Pemphigoid serum autoantibody tests did not provide immunopathologic evidence of MMP in ocular-only MMP patients but showed limited value in DIF- multisite ocular MMP patients. The requirement for immunopathologic confirmation of MMP by autoantibody detection is inappropriate for DIF- ocular-only MMP patients, resulting in missed diagnoses, delayed therapy, and poor outcomes. Alternative diagnostic criteria for ocular-only MMP are required to exclude the other causes of scarring conjunctivitis until more sensitive and specific immunopathologic tests become available.

A study into the best sites to biopsy for a diagnosis of pemphigus vulgaris or mucous membrane pemphigoid

Pemphigus vulgaris (PV) and mucous membrane pemphigoid (MMP) are rare and potentially serious conditions that cause painful blisters or erosions to develop in the mouth, nose, throat, oesophagus, genitalia and skin. One of the main complications unique to MMP is that it may scar affected sites, particularly the eyes. Both diseases generally occur in older adults. To confirm the diagnosis of PV and MMP, a biopsy has traditionally been taken from near the affected area (perilesional). Where only mucosal surfaces are involved, the mouth is the most accessible site, however this can be difficult because the lining of the mouth is fragile. The aim of this study was to compare outcomes of a biopsy of normal healthy-looking tissue lining the inner cheek (buccal mucosa) with a perilesional biopsy. The authors, based in the U.K., analysed the biopsy location and results of 251 MMP and 77 PV patients. They have shown that a biopsy of normal buccal mucosa tissue is as good as a perilesional biopsy for diagnosis of oral PV. For MMP patients with multiple oral surfaces affected, biopsy of normal buccal mucosa was almost equal to taking a perilesional sample for diagnosis. For MMP patients with only the gums affected, neither a perilesional biopsy from the gum nor a normal buccal mucosal biopsy were reliable enough to always confirm the diagnosis. Importantly for this group of patients, the authors have shown that a biopsy from the junction between the lining of the cheek and gum gave a positive result in all cases. A punch biopsy taken from normal buccal mucosa tissue is a simple and safe practical method for diagnosing all patients with oral PV and all MMP patients, with the exception of those with gum only lesions. This is a summary of the study: The optimal oral biopsy site for diagnosis of mucous membrane pemphigoid and pemphigus vulgaris

A Retrospective Study of Patient-Reported Data of Bullous Pemphigoid and Mucous Membrane Pemphigoid From a US-Based Registry.

Bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP) are rare chronic autoimmune disorders characterized by subepidermal blistering. For the United States, there is a limited amount of studies in BP and MMP that address disease demographics and clinical data. In order to more comprehensively examine disease demographics and clinical factors, we performed a retrospective analysis of patient-reported data of 138 BP and 165 MMP patients enrolled in the International Pemphigus & Pemphigoid Foundation (IPPF) disease registry from 2010–2016. Patient-reported data was compared to Physician/Investigator reported data generated in our own local patient population (Western New York; 19 BP and 43 MMP patients). We confirm a female predominance in BP (M:F ratio 1:2.1) and MMP (M:F ratio 1:4.3), and a late onset within the 6th decade of life (average age at diagnosis, 59.1 ± 17.5 years for BP and 54.8 ± 11.2 years for MMP). MMP patients were significantly more likely to have a delay in diagnosis >12 months than BP patients (38 vs. 21%, respectively). Similar to other autoimmune conditions, a large number of BP (34%) and MMP (35%) patients present with other co-existing autoimmune disorders, with the most common being thyroid disease for both groups. Increased illness activity was paralleled by an increase in severe limitations of daily activities. The vast majority of of both BP and MMP patients received high intensity immunosuppression (49%). However, the majority of BP patients reported therapy with prednisone combined with other immunosuppressants (40%), while the majority of MMP patients received immunosuppressants other than prednisone (55%). With the exception of age at diagnosis, the clinical and demographic findings from both the national and local datasets were largely consistent with each other, and support those reported in other countries.

Detachment of keratinocytes at the basement membrane zone caused by inhibitory effect of the antibodies from sera of mucous membrane pemphigoid patients.

Detachment of keratinocytes at the basement membrane zone caused by inhibitory effect of the antibodies from sera of mucous membrane pemphigoid patients.

Mucous Membrane Pemphigoid-Associated Malignancies: Case Series and a Brief Overview of the Literature.

Mucous membrane pemphigoid (MMP) is a heterogeneous group of blistering disorders affecting the mucosae with or without skin involvement, characterized by the presence of autoantibodies to components of the basement membrane zone, including the bullous pemphigoid antigen BP180 and β4 integrin. Current literature has shown that a minority of patients present circulating antibodies to laminin-332 and this population seems to be associated with a relatively high risk of malignancy. To present our personal case series of patients with MMP-associated malignancy from a dermatology university hospital. Twenty-two patients affected by MMP were seen in the period between 2001 and 2016; in 4 patients (18%) an associated cancer was detected. These patients were 2 men and 2 women, with a mean age of 69.7 years (range, 48-83). The associated malignancies included a breast cancer, a pancreatic adenocarcinoma, a metastatic laryngeal carcinoma, and a hepatic carcinoma. All patients had negative results for both BP180 and laminin-332 autoantibodies. We confirm that MMP patients have a relatively high possibility of developing a solid cancer, but the autoantibody detection is not mandatory and is probably correlated with the severity of the disease.