Pemphigus vulgaris versus Mucous Membrane Pemphigoid: Case Series

Pemphigus vulgaris (PV) and mucous membrane pemphigoid (MMP) are bullous autoimmune diseases that reach the oral mucosa and have common clinical features. The objective of the study was to present and compare the clinical manifestations of PV and MMP and the results of applied treatments. A case series of a stomatology service from 1985 to 2018. Data collection included epidemiological data, comorbidities, medications in use, duration of symptoms before the first visit, previous treatment, symptomatology, clinical description of lesions, presumptive diagnosis, histopathological description, extraoral manifestations, final diagnosis, treatment and follow-up. The medical records of 25 patients were analysed, 19 of whom were diagnosed with MMP and 6 with PV. The female gender was prevalent in MMP (84 %) and the male gender in PV (67 %). More than 60 % of patients complained of pain at their first visit. Patients with MMP took on average 6 months to seek professional help and patients with PV, about 2 months. Desquamative gingivitis was the most common lesion (63 %) in MMP and non-gingival ulcers (67 %) in PV. Minimal therapy was effective in all cases of MMP, and in PV one individual required minimal adjuvant therapy due to worsening of the case. Patients with PV have more intense signs and oral symptoms and may need more intensive treatment than patients with MMP. The use of topical and/or systemic corticosteroids was sufficient for most cases in both diseases.

Pénfigo vulgar (PV) y Penfigoide de la Membrana Mucosa (PMM) son enfermadades autoinmunes ampollosas que llegan a la mucosa oral y tienen características clínicas comunes. El objetivo de este estudio fue presentar y comparar las manifestaciones clínicas de PV y PMM y los resultados de los tratamientos aplicados. En el análisis se incluyó una serie de casos de un servicio de estomatología de 1985 a 2018. La recolección de información incluyó datos epidemiológicos, comorbilidades, medicamentos en uso, duración de los síntomas antes de la primera visita, tratamientos previos, sintomatología, descripción clínica de las lesiones, diagnóstico presuntivo, descripción histopatológica, manifestaciones extraorales, diagnóstico final, tratamiento y seguimiento. Se analizaron las historias clínicas de 25 pacientes, 19 de los cuales fueron diagnosticados de PMM y 6 de PV. El sexo feminino fue prevalente en PMM (84 %) y el sexo masculino en PV (67 %). Más del 60 % de los pacientes se quejaron de dolor durante la primera consulta. Los pacientes con PMM tardaron en promedio 6 meses en buscar ayuda profesional y los pacientes con PV, alrededor de 2 meses. La gingivitis descamativa fue la lesion más común (63 %) en PMM y las úlceras non gengivales (67 %) en PV. La terapia mínima fue efectiva en todos los casos de PMM, y en PV un individuo requirió terapia adyuvante mínima debido al empeoramiento del caso. Los pacientes con PV tienen signos y síntomas orales más intensos y pueden necesitar un tratamiento más intensivo que los pacientes con PMM. El uso de corticosteroides tópicos y/o sistémicos fue suficiente para la mayoría de los casos en ambas enfermedades.

Analysis of current status and risk factors of multidrug-resistant bacteria wound infections in patients with autoimmune bullous diseases / 中华皮肤科杂志

Objective:To investigate the current status of multidrug-resistant bacteria (MDRO) wound infections in patients with autoimmune bullous diseases (AIBDs), and to analyze their risk factors.Methods:A retrospective study was conducted, and inpatients with AIBDs accompanied by wound infections were collected from Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2020 to December 2022. A descriptive analysis was carried out to analyze the basic characteristics of these patients and pathogenic characteristics of MDRO. Univariate and binary logistic regression models were used to analyze independent risk factors for MDRO infections in patients with AIBDs. Differences between the MDRO infection group and common bacterial infection group were analyzed by using t test, Mann-Whitney U test and chi-square test. Results:Totally, 271 patients with AIBDs accompanied by wound infections were included, including 159 males (58.7%) and 112 females (41.3%), and 142 patients (52.4%) were aged over 60 years. Most patients with AIBDs were diagnosed with pemphigus vulgaris (131 cases, 48.3%), or bullous pemphigoid (99 cases, 36.5%). Bacterial culture was positive in all the patients, and 74 (27.3%) were infected with MDRO; a total of 108 strains of MDRO were detected, with relatively high detection rates of Staphylococcus (82 strains, 75.9%) and Enterobacter (15 strains, 13.9%). Significant differences were observed between the MDRO infection group and the common bacterial infection group in the duration of hospitalization, involved body surface area, proportions of patients self-modificating drug dosage, proportions of patients topically using antibiotic ointments, proportions of patients using immunosuppressants, duration of glucocorticoid use, maximum dose of glucocorticoids and the first albumin level at admission (all P < 0.05), while there were no significant differences in the gender, age, proportions of patients at first hospitalization, types of AIBDs, duration of education, body mass index, disease duration, proportions of smoking patients, proportions of drinking patients, proportions of patients with comorbid chronic diseases, surgical history, prevalence of hypoalbuminemia, prevalence of mucosal involvement, proportions of patients receiving topical glucocorticoids, proportions of patients using biological agents, duration of antibiotic use, and the first total protein level at admission between the two groups (all P > 0.05). Logistic regression analysis showed that the use of topical antibiotic ointments, use of immunosuppressants, maximum dose of glucocorticoids, and self-modification of drug dosage were independent risk factors for MDRO infections (all P < 0.05) . Conclusions:The patients with AIBDs were prone to develop MDRO infections in wounds, and Staphylococcus infections were the most common. The use of topical antibiotic ointments, use of immunosuppressants, high dose of glucocorticoids, and self-modification of drug dosage may increase the risk of infections in patients with AIBDs.

Childhood Bullous Pemphigoid with atypical immunopathology: A case series

@#Bullous pemphigoid (BP) is a rare autoimmune blistering disorder primarily affecting older adults, with limited occurrences in children. BP in children typically manifests as large, tense blisters on the skin, often on flexural areas. It also more often affects the oromucosal areas and the face in children than in adults. Diagnosis involves histopathological examination revealing eosinophilic spongiosis or subepidermal split, immunofluorescence tests highlighting immunoglobulin G (IgG) and C3 depositions, and immunological assays detecting BP180 and BP230 IgG autoantibodies. This report presents two cases of childhood BP (CBP) with atypical immunopathological findings. Clinically, the two cases had generalized plaques and bullae, including the face. The first case exhibited the characteristic linear deposits of IgG and C3 on the basement membrane through direct immunofluorescence (DIF) and revealed negative anti‑BP180 antibodies on enzyme‑linked immunosorbent assay (ELISA). In contrast, the second case showed negative DIF results, despite clinical suspicion, but had positive anti‑BP180 IgG antibodies on ELISA. It is, therefore, crucial to consider the complete clinical presentation of the patient, in conjunction with the histological findings and immunopathologic assessments to diagnose CBP.

Methylprednisolone combined with mycophenolate mofetil for the treatment of oral mucosal pemphigoid: a case report and literature review / 口腔疾病防治

Objective@#To investigate the application of mycophenolate mofetil (MMF) in oral mucosal pemphigoid and provide a clinical reference.@*Methods@#One case of glucocorticoids combined with MMF in the treatment of oral mucosal pemphigoid was reported, and the clinical application of MMF in oral mucosa-related bullous diseases was discussed.@*Results@#One patient with a clinical diagnosis of “oral mucosal pemphigoid” was treated with methylprednisolone (36 mg, qd, morning dose) or combined hydroxychloroquine sulfate (0.1 g/time, bid) and thalidomide capsules (50 mg, qd, bedtime) and other drugs. The patient’s disease was slowly controlled but prone to recurrence. The treatment regimen was immediately adjusted, i.e., methylprednisolone (36 mg, qd, morning dose) was combined with MMF (0.5 g/time, bid) for 2 weeks, which resulted in ideal lesion healing control. After 8 weeks of methylprednisolone combined with MMF, the dose of methylprednisolone was gradually reduced to 12 mg, qd, and MMF was reduced to 0.5 g, qd, the patient’s symptoms improved significantly, and no obvious lesions were found in the mouth. The dose was then reduced and maintained according to the principle of pemphigoid treatment. Methylprednisolone (8 mg, qd, morning dose) and MMF (0.5 g, qd) have been used for 6 months of maintenance treatment, and they are still being followed up. As yet, the patient’s condition is stable without obvious lesions and new blisters, and no obvious side effects have been observed. A review of the literature shows that MMF is widely used in the field of dermatology to treat a variety of immune diseases, such as connective tissue diseases and autoimmune blistering diseases. According to the reports of adverse reactions to MMF, digestive system reactions are the most common adverse reactions; therefore, patients with active gastrointestinal diseases should be treated with caution, followed by bone marrow suppression, and it is recommended to monitor liver function and blood routine in patients using MMF. The safety and efficacy of MMF for treating pemphigoid involving the skin have been reported in the literature, but oral mucosal doctors still lack experience for treating mucous membrane pemphigoid.@*Conclusions@#As a new immunosuppressant, MMF has high safety and no obvious side effects and can be considered as a combination adjuvant drug for patients with severe clinical disease and refractory oral mucosal pemphigoid.

Bullous pemphigoid in India: Review of cases registered in an autoimmune bullous disease clinic

Background: Information on bullous pemphigoid in an Indian context is scarce. Aim: To report clinico-demographic profile, associated comorbidities and prescription pattern of bullous pemphigoid patients in India. Methods: This was a retrospective study, where past records of all bullous pemphigoid patients diagnosed and treated between November 2013 and October 2019 were accessed and analysed. Patients having a compatible clinical presentation with either histopathological and/or direct immunofluorescence evidence of bullous pemphigoid were included. Results: There were 96 bullous pemphigoid patients, with a male: female ratio of 1.6:1. The mean age at diagnosis was 62.5 ± 2.2 years, with mean duration of illness 27.5 ± 4.5 months before presentation. Comorbidities were present in 80 (83%) patients, with type 2 diabetes mellitus (38.5%), hypertension (36.4%) and neurological illness (16.7%) being the commonest ones. Clinically, blisters were the predominant presentation in 81 (84.4%) patients. The majority (87.5%) of patients showed a predominant eosinophilic infiltrate on histopathology. Direct immunofluorescence revealed immunoglobulin G deposits with complement C3 in 77 (80.2%) cases. The majority of patients (77.1%) were treated with oral prednisolone, either alone (11.5%) or in combination (65.6%) with other topical and systemic agents. Topical steroids were used in 29.1%, azathioprine in 28%, dapsone in 16.7% and omalizumab in 6.2% of patients. Limitations: The study is retrospective. Immunofluorescence on salt split skin, direct immunofluorescence serration pattern analysis, and immunoblotting were not performed. Hence, there is a possibility that a few included cases were suffering from other subepidermal autoimmune bullous diseases like epidermolysis bullosa acquisita or anti-p200 pemphigoid. Conclusion: Bullous pemphigoid patients in this study had a younger age of onset and showed male preponderance. Comorbidities like type 2 diabetes, hypertension and neurological disorders were freq

Survival and prognostic factors in bullous pemphigoid: A retrospective cohort study

Background: Bullous pemphigoid is the most common subepidermal autoimmune blistering disease. Till now, the reported prognostic factors in bullous pemphigoid vary considerably. Aims: The purpose of this study was to determine the overall survival rate and prognostic factors in bullous pemphigoid. Methods: We conducted a retrospective cohort study on newly diagnosed bullous pemphigoid patients between July 2001 and November 2019 in a referral unit for autoimmune blistering skin diseases in Romania. Results: One hundred forty-eight patients were included in the study. The Kaplan–Meier overall survival rates at 1, 3, 5 and 10 years were respectively 74.2% (95% confidence interval, 67.5–81.6%), 53.4% (45.7–62.2%), 43.6% (35.9–53%) and 31.3% (23.5–41.7%). The median follow-up among survivors was 48 months (interquartile range: 11–150). Ninety (60.8%) patients died during the follow-up period; of them, 38 (42.2%) had active disease at the time of death. Advanced age, neurological diseases, valvular heart disease, malignancies, use of statins, skin infections and extensive cutaneous involvement were linked to poorer outcomes, while the use of topical corticosteroids was associated with increased overall survival. Limitations: This study lacks a control cohort to validate the obtained results. It was conducted in a retrospective manner in a single centre. In addition, indirect immunofluorescence microscopy was not performed in all patients. Conclusion: Beyond ageing and neurological comorbidities, the prognosis of bullous pemphigoid patients was significantly influenced by the presence of skin infections, valvular heart disease, use of statins and extensive cutaneous involvement. Topical corticosteroid treatment was associated with increased survival in these patients

Role of neutrophil-to-lymphocyte, neutrophil-to-eosinophil and platelet-to-lymphocyte ratios in the diagnosis of bullous pemphigoid and Pemphigus disease

Context: Bullous pemphigoid (BP) and “Pemphigus diseases” (PD) can have overlapping clinical manifestations and accurate distinction is crucial for appropriate management. Aims: The study aimed at analyzing the utility of simple hematological markers of systemic inflammation like neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-eosinophil ratio (NER), and platelet-to-lymphocyte ratio (PLR) in clinical decision making in the setting of clinical differentials of BP and PD in a particular case. Methods: This single-centre based retrospective observational analytical study included adult subjects newly diagnosed to have BP (n=66) or PD (n=53), confirmed with direct immune-fluorescence testing, over a period of six years. Blood counts performed using Coulter™ hematology analyser, at the time of their initial presentation, were retrieved from the hospital medical records, and the leucocyte ratios were calculated.Statistical Analysis: The data were compared between the two groups, using Mann–Whitney U test and chi-square test /Fisher's exact test. ROC curve analysis was performed to estimate cut-off values. Results: The BP group had a significantly higher NLR, total leukocyte counts (TLC), absolute eosinophil counts (AEC), and absolute lymphocyte counts (ALC), and lower NER values compared to the PD group (P < 0.05). Areas under ROC for NLR, NER, TLC, AEC, and ALC were between 0.5 and 0.7. NLR ? 7, AEC ? 2055/cumm, and TLC ? 15,000/cumm had a specificity of 90.6, 100, and 100% respectively for identifying BP patients out of the two groups, but with a low sensitivity of 22.7, 21, and 22.7%, respectively. Conclusions: NLR can be a valuable diagnostic adjunct in subtyping autoimmune bullous disorders, albeit in a small proportion of cases.

Penfigoide ampolloso de origen idiopático

Introducción: El penfigoide ampolloso es una dermatosis vesicular ampollosa autoinmunitaria subepidérmica, asociada a la formación de autoanticuerpos que reconocen autoantígenos en la zona de la membrana basal. El tratamiento inmunomodulador con corticoides es la primera línea en el control de la enfermedad. Objetivo: Presentar el caso clínico de un paciente con diagnóstico de penfigoide ampolloso de origen idiopático. Caso clínico: Paciente masculino de 81 años con lesiones ampollosas dolorosas a la palpación de contenido serohemático, tamaño variado, bordes regulares y base eritematosa a nivel generalizado. La evaluación inicial sugiere diagnóstico de penfigoide ampolloso e infección bacteriana activa de las lesiones en la piel. Se solicitan exámenes de laboratorio e imágenes diagnósticas, se descartan etiologías infecciosas, autoinmunes o neoplásicas asociadas, se inicia tratamiento con corticosteroides intravenosos con adecuada evolución clínica. Finalmente, no se identifican enfermedades asociadas a las lesiones ampollosas del paciente. Conclusión: El penfigoide ampolloso es una entidad poco frecuente, con una elevada tasa de mortalidad si se realiza un diagnóstico y tratamiento tardío. Reconocer las principales manifestaciones y variantes clínicas de esta enfermedad permite un oportuno enfoque diagnóstico y terapéutico, este último basado en el control de la respuesta inflamatoria contra la piel y otros órganos.

Introduction: Bullous pemphigoid is a subepidermal autoimmune bullous vesicular dermatosis associated with the formation of autoantibodies that confirm autoantigens in the basement membrane area. Immunomodulatory treatment with corticosteroids is the first line in the control of the disease. Objective: To present the clinical case of a patient diagnosed with a bullous pemphigoid of idiopathic origin. Clinical case: 81-year-old male patient with blistering lesions that are painful on palpation with serohematic content, varied in size, regular borders and a generalized erythematous base; that the initial evaluation suggests a diagnosis of bullous pemphigoid and active bacterial infection of the skin. Laboratory tests and diagnostic images are requested, infectious, autoimmune or associated neoplastic etiologies are ruled out, treatment with intravenous corticosteroids is started with adequate clinical evolution. Finally, no diseases associated with the patient's blistering lesions were identified. Conclusion: Bullous pemphigoid is a rare entity, with a high mortality rate if a late diagnosis and treatment is performed. Recognizing the main manifestations and clinical variants of this disease allows for a timely diagnostic and therapeutic approach, the latter based on the control of the inflammatory response against the skin and other organs.

Analysis of the autoimmune response to BP180 in Chinese stroke patients

Abstract Background Significant association between bullous pemphigoid (BP) and stroke has been reported. This study aimed to evaluate the level of anti-BP180 antibody in stroke patients to explore the relationship between BP and stroke in their pathogenesis. Methods We collected serum samples from stroke patients and matched controls between February 2019 and June 2020. The anti-BP180 antibody levels were measured by enzyme-linked immunosorbent assay (ELISA). Results A total of 1183 stroke patients including 970 with cerebral infarction (CI), 192 with intracerebral hemorrhage (ICH), 21 with CI and ICH, and 855 controls were enrolled in this study. Anti-BP180 autoantibody values were significantly higher in stroke patients than in controls (p < 0.001). Anti-BP180 autoantibody-positive rates were 12.51% (148) in stroke patients and 4.68% (40) in controls (p < 0.001, OR = 2.65). In anti-BP180 autoantibody-positive subjects, the values were significantly higher in stroke patients than in controls (p < 0.001). However, only 10 (6.76%) stroke patients and 3 (7.5%) controls had high values (> 100 RU/mL) (p = 0.87). Stratified analysis showed that anti-BP180 antibody positive rates were independent of age, sex, and stroke subtypes in the stroke group. Positive rates in patients with both CI and ICH were nearly two times higher than those in patients with either CI or ICH alone (p = 0.11, OR = 1.94). Study limitations This study had a limited sample size and lacked quantitative criteria for stroke severity. Conclusions Anti-BP180 antibody values and positive rates were higher in stroke patients than in controls, suggesting that stroke patients may have higher of developing BP.

Penfigoide gestacional. Reporte de caso

El penfigoide gestacional, antes conocido como herpes gestacional, es una dermatosis rara, ampollosa, autoinmune y específica del embarazo. Aunque la etiología no se conoce del todo, la mayoría de los pacientes desarrollan anticuerpos contra una proteína hemidesmosomal transmembrana de 180 kDa. Los síntomas que definen la enfermedad son el picor intenso y las lesiones urticariales que evolucionan hacia ampollas dolorosas. Las lesiones comienzan en la región periumbilical en el 90% de los casos y se extienden rápidamente a otras zonas del cuerpo, a excepción de la cabeza y las mucosas. Es más frecuente en el segundo o tercer trimestre. En las muestras de biopsia de piel, la tinción de inmunofluorescencia directa valida el diagnóstico. Los corticoides tópicos pueden ser utilizados para tratar los síntomas leves, mientras que los corticoides orales y los antihistamínicos deben usarse para tratar los casos graves. Se presenta un caso de penfigoide gestacional.

Pemphigoid gestationis, formerly known as herpes gestationis, is a rare, blistering, autoimmune, pregnancy-specific dermatosis. Although the etiology is not fully understood, most patients develop antibodies against 180 kDa transmembrane hemidesmosomal protein. The defining symptoms of the disease are intense itching and urticarial lesions that evolve into painful blisters. Lesions begin in the periumbilical region in 90% of cases and spread rapidly to other areas of the body, except for the head and mucous membranes. It is most frequent in the second or third trimester. In skin biopsy specimens, direct immunofluorescence staining validates the diagnosis. Topical corticosteroids can be used to treat mild symptoms, while oral corticosteroids and antihistamines should be used to treat severe cases. A case of pemphigoid gestationis is presented.

Clinical characteristics and treatment of eight cases of pemphigus/bullous pemphigoid complicated by herpes simplex virus infection / 中华皮肤科杂志

Objective:To retrospectively analyze clinical characteristics and treatment of pemphigus/bullous pemphigoid (BP) complicated by herpes simplex virus (HSV) infection.Methods:Inpatients with pemphigus/BP complicated by HSV infection were collected from Wuhan No.1 Hospital from 2016 to 2021, and their clinical characteristics, treatment and follow-up results were retrospectively analyzed.Results:Among the 8 patients with pemphigus/BP complicated by HSV infection, there were 2 males and 6 females, and their age was 50.6 ± 8.3 years. Five of them were diagnosed with pemphigus vulgaris (PV), 1 with pemphigus foliaceus (PF), and 2 with BP. Seven were infected with HSV-1, and 1 with HSV-2. All the 8 patients were given systemic glucocorticoids and immunosuppressive agents for the treatment of pemphigus or BP, and were admitted to the hospital due to resistance to the treatment. Seven patients presented with exacerbation or recurrence of primary lesions, and 1 presented with enlarged lesions all over the body. HSV infection-induced lesions were located on the trunk in 4 cases, on the oral mucosa in 4, on the scalp in 3, and on the face in 2; lesions mainly manifested as irregular erosions with blood crusts, and some centrally umbilicated pustules; 7 patients had obvious pain at the lesional sites. During HSV infection, anti-desmoglein 1 antibody levels decreased in all the 6 patients with pemphigus, and anti-desmoglein 3 antibody levels decreased in 4 of the 5 patients with pemphigus vulgaris; anti-BP180 antibody levels decreased in 1 patient with BP, but increased in the other one with BP. After antiviral therapy at adequate doses for adequate durations (7- to 14-day treatment with valacyclovir alone or in combination with ganciclovir), HSV infection was controlled, the autoimmune bullous skin disorder intensity scores decreased compared with those before the antiviral therapy, and pain was significantly relieved in all the patients. No dose adjustment of glucocorticoids or other immunosuppressive agents was made during antiviral therapy in all patients.Conclusion:HSV infection should be considered when patients with pemphigus/BP suffer from recurrence or exacerbation and poorly respond to conventional treatment; for patients with pemphigus/BP complicated by HSV infection, systemic antiviral therapy at adequate doses can be used to control the disease condition without modifying the conventional immunosuppressive regimen.

A clinical analysis of 74 cases of bullous pemphigoid with stroke / 中华皮肤科杂志

Objective:To investigate differences in clinical characteristics between bullous pemphigoid (BP) patients with stroke and those without, and their relationship with the prognosis of stroke.Methods:A retrospective analysis was performed on medical records of 330 BP inpatients in the First Affiliated Hospital of Zhengzhou University from September 2012 to April 2020. These patients were divided into BP + stroke (ST) group and BP - ST group according to whether they were accompanied by stroke, and clinical manifestations and relevant laboratory examination results were compared between the two groups. According to the stroke outcome score assessed by modified Rankin Scale (mRS), patients in the BP + ST group were further divided into good-prognosis ST group (mRS ≤ 2 points) and poor-prognosis ST group (mRS > 2 points), and subgroup analysis was conducted. Correlations between measurement data (such as age, disease course and laboratory examination results) and mRS scores were analyzed.Results:In the BP - ST group (256 cases), 151 were males and 105 were females, and their age ranged from 19 to 92 (66.8 ± 13.6) years; in the BP + ST group (74 cases), 45 were males and 29 were females, and their age ranged from 48 to 92 (74.6 ± 9.6) years; Compared with the BP - ST group, the BP + ST group showed older age ( t = -5.57, P < 0.001), shorter disease course of BP ( Z = -3.07, P = 0.002), and higher anti-BP180 IgG antibody levels (215.0 [157.2, 283.1] U/ml vs. 155.0 [63.9, 279.8] U/ml; Z = -2.12, P = 0.034). The distribution of skin lesions significantly differed between the two groups ( χ2 = 10.51, P = 0.015), and the BP + ST group showed a significantly lower proportion of patients with generalized lesions ( P<0.05), but a higher proportion of patients with lesions on the limbs ( P<0.05). Subgroup analysis showed significant differences in the patients′ age, BP course, lesion distribution and anti-BP180 IgG antibody levels among the good-prognosis ST group, poor-prognosis ST group and BP - ST group ( F = 10.83, P<0.001; Z = 17.24, P<0.001; χ2 = 15.57, P = 0.026; Z = 6.29, P = 0.043, respectively). There was no significant difference in the age between the good-prognosis ST group and poor-prognosis ST group (adjusted P = 1.000), but the patients were significantly older in the two above groups than in the BP - ST group (adjusted P = 0.001, 0.007, respectively) ; the poor-prognosis ST group showed significantly shorter BP courses (adjusted P = 0.016, < 0.001, respectively) and a higher proportion of patients with lesions on the limbs (both P < 0.05) compared with the good-prognosis ST group and BP - ST group, and significantly higher serum anti-BP180 IgG antibody levels compared with the BP - ST group (226.2 [163.6, 285.8] U/ml vs. 155.0 [63.9, 279.8] U/ml; adjusted P = 0.037). There were no significant differences in the gender distribution, lesional morphology, percentages and counts of peripheral blood eosinophils, serum total IgE levels, and anti-BP230 IgG antibody levels between the BP + ST group and BP - ST group (all P > 0.05), or among the good-prognosis ST group, poor-prognosis ST group and BP - ST group (all P > 0.05). Correlation analysis in the BP + ST group showed a significantly negative correlation between the BP course and mRS scores ( r = -0.33, P = 0.004), and a significantly positive correlation between the anti-BP180 IgG antibody levels and mRS scores ( r = 0.34, P = 0.032) . Conclusion:There were differences in the patients′ age, BP course, lesion distribution, and anti-BP180 IgG antibody levels between the BP patients with stroke and those without, and the differences were more obvious between the poor-prognosis ST group and BP - ST group.

Epitope spreading in autoimmune bullous diseases / 中华皮肤科杂志

Epitope spreading often occurs in patients with autoimmune bullous diseases (ABDs), resulting in exposure of more antigenic epitopes, aggravation or transformation of pre-existing diseases, or concurrence of other diseases. With the increase in the immunological evidence for epitope spreading, more and more scholars have realized that epitope spreading plays an important role in the development of ABDs. This review introduces the phenomenon of epitope spreading in ABDs from 4 aspects, including the concurrence of or transformation between different types of pemphigoid, different types of pemphigus, pemphigus and pemphigoid, as well as between ABDs and other skin diseases.

Application of biologic agents in the treatment of bullous pemphigoid / 中华皮肤科杂志

In recent years, new therapeutic targets for bullous pemphigoid (BP) have continued to emerge, and new biologic agents targeting pathogenic antibodies, complements, T helper type 2 (Th2) and Th17 cytokines in BP have also successively entered clinical trials, e.g., the CD20-targeting antibody rituximab and the IgE-targeting antibody omalizumab have been applied in clinical practice and have benefited some patients with refractory BP. This review summarizes the literature and clinical trials related to biologic agents as the treatment strategy for BP, analyzes and discusses clinical application of new biological agents in BP, in order to provide new ideas for the treatment of refractory BP.

Tratamiento del penfigoide de membranas mucosas con ácido hialurónico en gel al 0,2%. Reporte de caso / Treatment of mucous membrane pemphigoid with 0.2% hyaluronic acid gel. Case Report

RESUMEN El Penfigoide de membranas mucosas es un trastorno ampollar subepitelial, inflamatorio, autoinmune que afecta las mucosas del cuerpo. El 80% de los casos se presentan en la mucosa bucal. El tratamiento consiste en la administración de corticoesteroides y antimicrobianos. El objetivo de este articulo es describir la eficacia del ácido hialurónico en gel al 0,2% en el tratamiento del penfigoide de membranas mucosas. Se reporta el caso de una mujer de 57 años de edad con artritis reumatoide y penfigoide de membranas mucosas en el labio superior e inferior con tres meses de evolución. Las lesiones son tratadas con ácido hialurónico en gel al 0,2% obteniendo excelentes resultados. El tratamiento con ácido hialurónico demostró efectividad en la reducción del dolor y inflamación, sanando las lesiones sin necesidad de suspender o ajustar la dosis de los fármacos.

ABSTRACT Mucous membrane pemphigoid is a subepithelial, inflammatory, autoimmune blistering disorder that affects the body's mucous membranes. Most of the cases appear in the oral mucosa. Corticosteroids and antimicrobials are the election treatment. This article describes the efficacy of 0.2% hyaluronic acid gel in mucous membrane pemphigoid. We report a case of a 57-year-old female patient with rheumatoid arthritis and mucous membrane pemphigoid in the upper and lower lips with three months of evolution. Lesions were treated with 0.2% hyaluronic acid gel, obtaining excellent results. The treatment of hyaluronic acid to mucous membrane pemphigoid demonstrated effectiveness in reducing inflammation, pain, and healing of the mucosa, without the need to suspend or adjust the dose of the drugs.

Bullous pemphigoid and milia: prevalence and clinical laboratory findings in a Brazilian sample

Abstract Background: Bullous pemphigoid (BP) associated with milia lesions has been increasingly reported, but its prevalence has not been reported in a Brazilian BP population yet. Objectives: To describe the occurrence and clinical-laboratorial findings of BP-milia association in a southeastern Brazilian sample. Methods: A descriptive study based on the medical charts of 102 BP patients was accomplished. Clinical and laboratory data of BP-milia patients were compiled. Total serum IgE measurements, immunoblot assays based on basement membrane zone antigens, and HLA-DQ alleles typing were performed. Results: Milia was evident in 8 (7.8%) BP patients, five males, aged between 46 and 88 years. Increased total IgE levels were determined in 7 (87.5%) of the eight patients. In five of eight patients, immunoblotting showed IgG reactivity against the BP180-NC16a domain but not against collagen VII or laminin-332; it also revealed reactivity against the BP180 C-terminal domain or LAD-1, or both in four of them. The HLA-DQB1*03:01 and HLA-DQA1*05:05 alleles were identified in three of five BP-milia patients. Moreover, three of five cases presented the HLA-DQB1*06 allelic group. Study limitations: HLA determination was performed in five patients. Conclusions: Milia formation in BP patients seems to be less uncommon than previously admitted. Laboratory data revealed increased IgE; autoantibodies against the BP180 C-terminal domain or LAD-1, or both; and the HLA-DQB1*06 allelic group, described for the BP-milia association. Careful determination of antibodies against basement membrane zone molecules and HLA characterization in different populations may provide further insights into this association. © 2022 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

A case series on bullous pemphigoid like scabies: A diagnostic challenge

Scabies is an ectoparasitic infection caused by Sarcoptes scabiei var. hominis in humans. Accurate figures of the prevalence of scabies are difficult to obtain, it seems to affect around 100�0 million people worldwide. Scabies is usually transmitted by close intimate physical contacts, such as the sharing of a bed or prolonged hand-holding. Scabies mites survive for 24� h outside of human bodies. Itching is the most obvious manifestation of scabies, which is usually sparing the face in adult classic scabies. The onset occurs 3�weeks after acquiring the infection. Bullous pemphigoid-like scabies is one of the atypical and rare forms of scabies that may be overlooked and mismanaged, where only 44 cases worldwide with this mode of presentation were reported. Here, we reported a series of three cases of bullous pemphigoid-like scabies, which presented with nocturnal itching and vesiculobullous lesions that are to the best of our knowledge the first cases reported in our country.

Ocular cicatricial pemphigoid. From a rheumatology and ophthalmology point of view / Penfigoide ocular cicatrizal, enfoque diagnóstico y terapéutico integral entre el oftalmólogo y el reumatólogo

ABSTRACT Ocular cicatricial pemphigoid (OCP) is a chronic, immune-mediated, bullous, cicatricial disease within the spectrum of mucocutaneous membranous pemphigoids (MMP). Although the diagnosis is often ophthalmological, due to the autoimmune nature of the pathology, it requires a joint approach with rheumatologists and immunologists. The objective of this narrative review was to explore the evidence available in the literature from 2000 to 2020 with respect to clinical manifestations, diagnosis, and treatment. The clinical presentation varies widely, from mild cases with slow progression of years of progression, to severe cases with a torpid and rapidly progressive evolution to fibrosis, refractory to multiple treatments. A com plete evaluation of the patient will help guide the diagnosis. The gold standard for diagnosis is conjunctival biopsy with direct immunofluorescence, although on occasions it can be reached if the symptoms are characteristic. Treatment is local and systemic according to its severity and evolution. The evidence on topical and systemic therapeutics is obtained mainly from uncontrolled observational and experimental studies. Immunomodulatory therapy has made it possible to preserve vision and, in many cases, prevent sequelae. The evolu tion is linked to the early diagnosis and immunosuppressive treatment, so it is essential to be aware of this disease, the diagnostic methods, as well as the immunomodulating and immunosuppressive therapies available.

RESUMEN El penfigoide ocular cicatrizal (POC) es una enfermedad crónica, inmunomediada ampollar, mucosinequiante, comprendida dentro del espectro de penfigoides membranosos mucocutáneos (PMM). El diagnóstico es, con frecuencia, oftalmológico, pero debido al carácter autoinmune de la patología, requiere el abordaje en conjunto con reumatólogos e inmunólogos. El objetivo de esta revisión narrativa fue explorar la evidencia disponible en la literatura, desde el año 2000 hasta el 2020, en lo que respecta a sus manifestaciones clínicas, diagnóstico y tratamiento. La presentación clínica varía ampliamente, desde casos leves con progresión lenta de años de evolución hasta casos severos con evolución tórpida y rápidamente progresiva a la fibrosis, refractarios a múltiples tratamientos. Una evaluación completa del paciente ayudará a guiar el diagnóstico. El estándar de oro diagnóstico es la biopsia conjuntival con inmunofluorescencia directa, si bien en ocasiones puede diagnosticarse por la clínica característica. El tratamiento es local y sistêmico de acuerdo con su severidad y evolución. En los últimos 20 anos, la evidencia sobre los tratamientos tópicos y sistêmicos corresponde en su mayoría a estudios observacionales y experimentales no controlados. Los métodos de tratamiento inmunomoduladores han permitido preservar la visión y, en muchos casos, prevenir secuelas. La evolución está ligada al diagnóstico temprano y a los tratamientos disponibles, por lo que es fundamental el conocimiento de esta patología, los métodos diagnósticos y los tratamientos inmunomoduladores e inmunosupresores.

Optimization of indirect immunofluorescence on salt-split skin and its application in detection of bullous pemphigoid antibodies / 中华皮肤科杂志

Objective:To optimize indirect immunofluorescence on salt-split skin (IIF-SSS), and to evaluate its performance in detection of bullous pemphigoid (BP) antibodies.Methods:Normal human foreskin and non-foreskin skin tissues were used to prepare salt-split substrates under 3 different experimental conditions: traditional group rotated at 4 ℃ for 48 - 72 hours, low-temperature immersion group soaked at 4 ℃ for 48 - 72 hours, room-temperature immersion group soaked at 25 ℃ (range: 23 - 27 ℃) for 24 hours. Serum samples were obtained from 20 patients with bullous pemphigoid (BP) in Hospital of Dermatology, Chinese Academy of Medical Sciences between August 2019 and August 2020, and subjected to IIF on the intact skin or salt-split substrates by using a multiple dilution method. Paired-sample t test was used for comparisons of means between two paired samples. Results:No dermal-epidermal separation was observed in the substrates prepared in the low-temperature immersion group at 48 - 72 hours, while dermal-epidermal separation occurred in the lower lamina lucida of the foreskin and non-foreskin substrates in the room-temperature immersion group and the traditional group. For the 20 patients with BP, the reciprocal end-point titers ( M[ Q1, Q3]) detected with the salt-split non-foreskin skin and salt-split foreskin in the room-temperature immersion group, and with the salt-split non-foreskin skin in the traditional group were 5 120 (2 560, 17 920), 1 280 (640, 2 560), 1 280 (640, 2 560), respectively. Moreover, 19 (95%) patients with BP showed that the reciprocal end-point titers detected with the substrates in the room-temperature immersion group were 1 - 5 times those in the traditional group ( t = 8.04, P<0.001), suggesting that the performance of salt-split skin in the room-temperature immersion group was superior to that in the traditional group in the detection of BP antibodies; however, there was no significant difference in the reciprocal end-point titers of BP antibodies between the salt-split foreskin in the room-temperature immersion group and salt-split non-foreskin skin in the traditional group ( t<0.001, P>0.05). The reciprocal end-point titers in 20 BP sera detected by conventional IIF on the intact non-foreskin skin and foreskin were 320 (160, 640) and 480 (160, 1 120), respectively; the reciprocal end-point titers detected by IIF on the salt-split foreskin and non-foreskin skin in the room-temperature immersion group, as well as on the salt-split non-foreskin skin in the traditional group, were all consistent with or 1 - 7 times higher than those detected by conventional IIF ( t = 6.47, 14.83, 5.26, respectively, all P<0.001) . Conclusion:The soaking method at room temperature 25 ℃ (23 - 27 ℃) for preparing salt-split substrates has advantages of short duration and simple procedure, and the sensitivity of IIF-SSS using the substrates prepared by this method is equal or superior to the traditional salt-split method for detecting BP antibodies.

Bullous pemphigoid and its immune-mediated comorbidities / 中华皮肤科杂志

Bullous pemphigoid (BP) can be comorbid with a variety of immune diseases, such as immune skin diseases (psoriasis, vitiligo, alopecia areata and various other immune bullous diseases) , immune digestive diseases (inflammatory bowel disease, primary biliary cirrhosis) , autoimmune thyroid diseases, autoimmune rheumatic diseases (rheumatoid arthritis, dermatomyositis, scleroderma and systemic lupus erythematosus) , immune renal diseases (immune nephropathy, renal allograft rejection) and acquired hemophilia A. The above comorbidities markedly affect the quality of life of and treatment options for patients. This review elaborates on currently reported immune diseases associated with BP and their concomitant mechanisms.