Cicatricial Pemphigoid Research Articles

Autoimmune bullous dermatoses in cancer patients treated by immunotherapy: a literature review and Italian multicentric experience.

Cutaneous immune-related adverse events are frequently associated with immune checkpoint inhibitors (ICIs) administration in cancer patients. In fact, these monoclonal antibodies bind the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1/ligand 1 leading to a non-specific activation of the immune system against both tumoral cells and self-antigens. The skin is the most frequently affected organ system appearing involved especially by inflammatory manifestations such as maculopapular, lichenoid, psoriatic, and eczematous eruptions. Although less common, ICI-induced autoimmune blistering diseases have also been reported, with an estimated overall incidence of less than 5%. Bullous pemphigoid-like eruption is the predominant phenotype, while lichen planus pemphigoides, pemphigus vulgaris, and mucous membrane pemphigoid have been described anecdotally. Overall, they have a wide range of clinical presentations and often overlap with each other leading to a delayed diagnosis. Achieving adequate control of skin toxicity in these cases often requires immunosuppressive systemic therapies and/or interruption of ICI treatment, presenting a therapeutic challenge in the context of cancer management. In this study, we present a case series from Italy based on a multicenter, retrospective, observational study, which included 45 patients treated with ICIs who developed ICI-induced bullous pemphigoid. In addition, we performed a comprehensive review to identify the cases reported in the literature on ICI-induced autoimmune bullous diseases. Several theories seeking their underlying pathogenesis have been reported and this work aims to better understand what is known so far on this issue.

Utility of C3d and C4d immunohistochemical staining in formalin-fixed skin or mucosal biopsy specimens in diagnosis of bullous pemphigoid and mucous membrane pemphigoid

Bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP) sometimes have overlapping clinical, histopathological, and direct immunofluorescence (DIF) features in the early stages. Complement deposition is an intrinsic component of the patho-mechanism of BP in contrast to MMP. Hence immunohistochemistry (IHC) for C3d and C4d may be helpful in differentiating the two disorders. Seventy-four patients of BP and 18 patients of MMP along with 10 negative controls were enrolled in this study. C3d and C4d IHC was performed in formalin-fixed skin biopsy specimens. C3d IHC staining in BP/MMP had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 59.2%/41.2%, 100%/100%, 100%/100%, 25.6%/50.0%, respectively. C4d IHC staining in BP/MMP had a sensitivity, specificity, PPV and NPV of 26.8%/17.6%, 100%/100%, 100%/100% and 16.1%/41.7%, respectively. Receiver operator analysis showed utility of C3d in diagnosing both BP [Area under curve (AUC) = 0.8, p = 0.0001] and MMP (AUC = 0.71; p = 0.001). C4d was useful in diagnosis of BP (AUC = 0.5; p = 0.0001), but not MMP (AUC = 0.6; p = 0.064). Hence, C3d is a better diagnostic modality for BP as compared to C4d, whereas C3d and C4d have lower diagnostic importance in MMP. C3d IHC can be employed in diagnosing BP when a second biopsy for direct immunofluorescence (DIF) is not possible or where a facility for IF microscopy does not exist.

A rare case report of bullous pemphigoid and ocular cicatricial pemphigoid

This report presents a rare case of a 47-year-old male patient with ocular cicatricial pemphigoid and bullous pemphigoid, five months after receiving the first dose of COVID-19 vaccine. The patient presented with redness, burning sensation, and photophobia in the scalp and oral cavity.

Ocular involvement in autoimmune bullous diseases

Autoimmune bullous diseases represent a heterogenous group of disorders caused by autoantibodies against adhesion molecules; the location of the target protein determines the level of cleft formation. The spectrum of ocular lesions in autoimmune bullous diseases can range from mild symptoms to severe involvement with sight impairment and even, in some cases, blindness. In pemphigus vulgaris, the prevalence of ocular involvement has been reported to be between 7% and 26%. The most common clinical sign of ocular pemphigus vulgaris is bilateral conjunctivitis with hyperemia. Ocular involvement also occurs in 41% to 70% of patients with paraneoplastic pemphigus. The main ocular manifestations are bilateral cicatrizing conjunctivitis with symblepharon formation, and shortening of the fornices. In mucous membrane pemphigoid, ocular involvement is seen in 61% to 70% of patients; the most frequent ocular finding is cicatricial conjunctivitis. Patients with autoimmune bullous diseases having common ocular involvement should be assessed by an ophthalmologist to avoid serious complications. Diagnostic procedures and treatment require multidisciplinary care based on the close cooperation between dermatologists and ophthalmologists.

A case of mucous membrane pemphigoid masquerading as an adverse food reaction in the allergy clinic

Adverse food reactions are a common reason for allergist consultation. Many patients assume their symptoms to be allergic in nature, but severe conditions like mucous membrane pemphigoid (MMP) can be missed if not considered. We report the case of a patient presenting with concern for food allergy found to have MMP.

Ocular mucous membrane pemphigoid

Mucous membrane pemphigoid refers to aheterogeneous group of autoimmune diseases with subepidermal blister formation that can affect all mucous membranes with varying frequencies. This is a rare disease without any geographic or sexual predisposition that is characterized by recurrent inflammation and progressive scarring. The specific diagnostics can be negative in up to 50% of cases. The diagnosis is predominantly made in patients aged 60-80years. Ophthalmologists play an important role in the care of affected individuals as the conjunctiva is the second most frequent site of involvement. The treatment is often tedious and primarily consists of long-term systemic immunosuppression.

Current dermatology guidelines in Germany-selected recommendations from 2021 and 2022

Guidelines are systematically developed decision-making aids to ensure appropriate clinical care for specific medical conditions. In Germany, dermatological guidelines are developed under the aegis of the German Dermatological Society (DDG) and the Professional Association of German Dermatologists (BVDD), while European and international guidelines are published by organisations such as the European Centre for Guidelines Development (EuroGuiDerm), founded by the European Dermatology Forum (EDF) in cooperation with the Division of Evidence-Based Medicine at Charité-Universitätsmedizin Berlin. In 2021 and 2022, the German guidelines were revised or developed on topics such as the management of anticoagulation during dermatological procedures, chronic pruritus, contact dermatitis, laser therapy of the skin, psoriasis vulgaris, rosacea, extracorporeal photopheresis, onychomycosis, mucous membrane pemphigoid and prevention of skin cancer. Aselection of the most important recommendations and innovations in the guidelines is summarized here.

Efficacy of anti-desmoglein 1 and anti-desmoglein 3 levels by enzyme-linked immunosorbent assay compared to biopsy of chronic oral ulcerative diseases with positive Nikolsky's sign to diagnose oral pemphigus vulgaris with or without skin involvement: a retrospective institutional observational pilot study

We assessed the efficacy of anti-desmoglein 1 (anti-DSG1) and anti-DSG3 levels by enzyme-linked immunosorbent assay (ELISA) as a preliminary diagnostic test in the diagnosis of oral pemphigus vulgaris (OPV) with or without skin involvement compared to biopsy. We retrospectively analyzed data collected from 23 patients (mean age 45.13 years) who had presented with chronic oral ulcerations, desquamative gingivitis, and a positive Nikolsky's sign. We performed ELISA, histopathologic examination, and direct immunofluorescence (DIF) and then calculated the sensitivity and specificity of the results of ELISA, histopathology, DIF, and the presence of a positive Nikolsky's sign in diagnosis. The ELISA results showed that 18 patients had elevated anti-DSG3 levels, of whom 8 also had elevated anti-DSG1 levels. The histopathology results indicated that 18 patients had OPV, of whom 4 had oral lichen planus, and 1 had sub-epithelial blistering disease confirmed to be mucous membrane pemphigoid MMP by DIF. ELISA, histopathology, and DIF had a 100% sensitivity and specificity, and the presence of a positive Nikolsky's sign had a sensitivity and specificity of 100% and 78.26%, respectively. Measurement of anti-DSG1 and anti-DSG3 levels by ELISA warrants consideration as a first-line diagnostic test for early detection of OPV with or without skin involvement over biopsy.

The top 10 research priorities for the treatment of bullous pemphigoid, mucous membrane pemphigoid and pemphigus vulgaris in the UK: results of a James Lind Alliance Priority Setting Partnership.

To identify priorities for future research into the treatment of bullous pemphigoid, mucous membrane pemphigoid and pemphigus vulgaris, we conducted a Priority Setting Partnership (PSP) using James Lind Alliance methodology. The top 10 priorities identified in this PSP represent the key questions that patients, carers and healthcare professionals have about the treatment of these diseases and which future research will hopefully address.

Mucosal anomalies in autoimmune bullous diseases

Mucosal anomalies are frequently seen in autoimmune bullous diseases, particularly in pemphigus vulgaris and mucous membrane pemphigoid. The blistering, erosions, ulceration or erythema may present anywhere on the oral mucosa, but also on other mucosal sites. A differential diagnosis is needed of (erosive) oral lichen planus, systemic autoimmune disease, inflammatory bowel diseases, chronic graft-versus-host disease, infectious causes, Behçet's syndrome and recurrent aphthous stomatitis. A quick diagnosis and initiation of adequate treatment are important because of the potential severity of the disease and to prevent complications due to cicatrization. Besides a biopsy for histopathological analysis, a perilesional biopsy for direct immunofluorescence microscopy and immunoserological tests are needed for diagnosis of pemphigus or pemphigoid. In addition to a mucosal biopsy, a biopsy for direct immunofluorescence of the skin can contribute to a diagnosis of a bullous disease. Besides topical corticosteroids, immunosuppressive treatment is often required for treating autoimmune bullous diseases, such as treatment with rituximab in patients with pemphigus.

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.

Diagnostics of ocular mucous membrane pemphigoid

The diagnosis of ocular mucous membrane pemphigoid (MMP) remains achallenge as the timing and choice of diagnostic methods have adecisive influence on its quality. Asystematic approach is required that includes acomprehensive medical history, critical evaluation of the clinical findings and targeted laboratory testing. The diagnosis is complicated by the fact that some patients present purely clinically the symptoms of MMP without fulfilling the required immunohistochemical and laboratory criteria. Basically, the diagnosis of ocular MMP is based on three pillars: 1) medical history and clinical findings, 2) positive immunohistological (direct immunofluorescence) tissue sample and 3) specific serological autoantibodies. As the diagnosis of ocular MMP often implies prolonged systemic immunomodulatory treatment in predominantly older patients, the accurate diagnosis and approach are of critical relevance. The aim of this article is to present the recently updated diagnostic procedure.

Vesiculobullous Lesions of the Oral Cavity.

Several dermatological conditions may manifest in the oral cavity, particularly those that are immune-mediated, and they must be distinguished from the various other types of oral ulcerations. This chapter discusses the clinical features, pathogenesis, differential diagnosis, and diagnostic features, including histology and immunofluorescence findings, as well as management of vesiculobullous diseases. These diseases include pemphigus Vulgaris, benign mucous membrane pemphigoid, bullous pemphigoid, and epidermolysis bullosa acquisita. These diseases have a significant impact on the quality of life, as they can lead to serious complications, depending on the extent of the disease. Therefore, early recognition is crucial, helping to reduce disease-related morbidity, mortality and prevent life-threatening complications.

Initial results of the German ocular pemphigoid register

Mucous membrane pemphigoid (MMP) is arare disease that presents clinicians with adiagnostic and therapeutic challenge. The aim of this article is to present the German ocular pemphigoid register, which is aretrospective data collection and acollaborative network to improve the care of these patients. It was founded in 2020 and currently comprises 17eye clinics/cooperation partners. An initial evaluation of the results shows aknown epidemiological profile and an expected high proportion of patients with negative diagnostics (48.6%) despite aclinically suspected diagnosis. In this register study predominantly recruiting from eye clinics, the proportion of patients with a strictly ocular involvement was 65.4%. Also of interest was the high number of patients with glaucoma (22.3%) as the most frequent comorbidity. Based on the working group formed, aprospective survey will be conducted in the future, which enables afollow-up.

Differential diagnoses of ocular mucous membrane pemphigoid

Overall, conjunctival scarring is rare and often overlooked during routine examination. However, the differential diagnostic distinction of cicatricial mucous membrane pemphigoid from other causes is crucial for further treatment planning. Other entities that lead to conjunctival scarring, are ocular rosacea, ocular graft-versus-host disease, atopic keratoconjunctivitis, infections, trauma and further sometimes very rare diseases. Most of these differential diagnoses have in common that conjunctival scarring does not progress indefinitely if untreated, in contrast to mucous membrane pemphigoid.

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.

077 Cicatricial bullous pemphigoid and sjogren's syndrome: Case report in an elderly female

077 Cicatricial bullous pemphigoid and sjogren's syndrome: Case report in an elderly female

543 Mucous membrane pemphigoid is associated with multiple somatic and psychiatric comorbidities

543 Mucous membrane pemphigoid is associated with multiple somatic and psychiatric comorbidities

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.

Clinical Approach to Ocular Cicatricial Pemphigoid.

To evaluate the demographic data, ocular and systemic findings, clinical management, and outcomes of patients with ocular cicatricial pemphigoid (OCP). The medical records of 11 patients diagnosed as having OCP in the ophthalmology department of Ege University between 2008 and 2021 were evaluated retrospectively. The patients' mean follow-up time was 14±5.76 months. All eyes (100%) had conjunctival involvement and 18 (81.81%) had corneal involvement. According to the Tauber staging system, 7 (31.81%), 8 (36.36%), and 7 (31.81%) of the eyes were stage 2, 3, and 4, respectively. The diagnosis was confirmed in 6 (66.66%) of 9 patients who underwent biopsy. Amniotic membrane transplantation was performed in 7 eyes, entropion surgery in 2 eyes, and electrocauterization for trichiasis in 5 eyes. Systemic involvement was observed in 45.45% (5/11) of patients, most commonly oral mucosal involvement (18.18%). Review of medical records showed that alkylating agents, steroids, and dapsone were used in patients treated before 2020. Mycophenolate mofetil was preferred to be used in combination with corticosteroids. Although treatment responses before mycophenolate mofetil usage could not be evaluated well because of loss to follow-up, 4 (66.66%) of 6 patients who received steroid treatment combined with mycophenolate mofetil showed partial or complete clinical remission. No serious side effects and drug withdrawal were observed. OCP is a sight-threatening autoimmune disease that affects older adults. Although positive biopsy results are valuable for diagnosis, negative results do not exclude the diagnosis. The main treatment is systemic immunosuppressives. Disease activity can be suppressed, especially with early initiation of drug therapy. These patients require a multidisciplinary approach. Especially in the presence of isolated ocular findings, ophthalmologists should be able to make the decision to start immunosuppressive treatment, and systemic treatment should not be delayed.