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.

Progress on pathogenesis and treatment of ocular cicatricial pemphigoid / 国际眼科杂志(Guoji Yanke Zazhi)

@#Ocular cicatricial pemphigoid(OCP)is a special manifestation of mucosal pemphigoid(mucous membrane pemphigoid, MMP), and the pathogenesis is not clear at present. It can be caused by variety factors such as antigen-antibody reaction, inflammation cell infiltration, the action of various cytokines, elevated calcium ion levels and susceptibility genes. In the early period of diseases, conjunctival present chronic progressive fibrotic inflammation, later the corneal opacity and the neovascularization will eventually lose vision. Therefore, it is particularly important to carry out clinical standardized treatment for OCP patients in a timely manner. To use medicine to control the inflammation and delay the progression of the disease, for example, dapsone, intravenous immunoglobulin(IVIG), rituximab(RTX), tumor necrosis factor antagonists and adrenocorticoids. Surgical treatment can be considered appropriately when OCP patients are complicated by severe trichiasis, corneal disease and cataract.

Penfigoide de las mucosas a lo largo de los años en nuestro Servicio / Mucous membrane pemphigoid through the years in our Department

Introducción: el penfigoide de las mucosas (PM), antes llamado mucoso, cicatrizal o mucosinequiante, representa un grupo heterogéneo de enfermedades ampollares autoinmunes inflamatorias crónicas que comprometen las mucosas o la piel, con tendencia a dejar secuelas cicatrizales. Existen autoanticuerpos contra distintos componentes de la zona de la membrana basal (BPAG1, BPAG2, integrina α6ß4, laminina 332, colágeno VII, entre otros), por lo que la inmunofluorescencia directa (IFD) es de suma importancia, así como la clínica, para su diagnóstico.Objetivo: realizar una revisión de los casos de PM diagnosticados durante un período de 24 años (enero de 1997- marzo de 2021) en el Sector de Enfermedades Ampollares del Hospital Ramos Mejía para determinar la epidemiología, la clínica y la terapéutica de esta enfermedad.Diseño: estudio retrospectivo descriptivo y observacional, en el que se analizaron las características clínicas e inmunopatológicas de 34 pacientes con diagnóstico de PM atendidos en el Servicio de Dermatología del Hospital Ramos Mejía desde enero de 1997 hasta marzo de 2021. Materiales y métodos: mediante las historias clínicas y los regis-tros iconográficos, se evaluaron las siguientes variables: prevalencia del diagnóstico de PM en los pacientes atendidos en el Sector, sexo, edad, antecedentes personales, mucosas afectadas, tiempo de evolución hasta el diagnóstico, hallazgos en la IFD, seguimiento clínico y tratamientos instaurados. Resultados: se estudió la evolución clínica de 34 pacientes diagnosticados con PM (5,3% del total de pacientes evaluados en el Sector de Patologías Ampollares). El sexo más afectado fue el femenino y la edad promedio en el momento del diagnóstico fue de 64 años. El 70,6% de los pacientes presentaron comorbilidades asociadas como hipertensión e hipotiroidismo. La mayoría refirió algún evento emocional como factor desencadenante. El sitio más comprometido fue la mucosa ocular y la cavidad oral fue la segunda en frecuencia. El tiempo de evolución promedio hasta el momento del diagnóstico fue de 4 años y 11 meses. El hallazgo más frecuente en la IFD fue la IgG lineal. El 17,6% de los pacientes interrumpieron el seguimiento clínico. El tratamiento más utilizado fue el mofetil micofenolato, con el que se obtuvo buena respuesta terapéutica. Conclusiones: el PM es una enfermedad autoinmune infrecuente que compromete las mucosas y, ocasionalmente, la piel. En este estudio, se observó que la principal mucosa afectada fue la conjuntival, a diferencia de lo referido en la bibliografía internacional dermatológica. El diagnóstico interdisciplinario temprano es fundamental para evitar las secuelas irreversibles.

Introduction: mucous membrane pemphigoid (MMP), also known as benign mucous membrane pemphigoid, cicatricial or mucosynechial pemphigoid, belongs to an heterogeneous group of chronic inflammatory autoimmune blistering diseases, which involves the mucous membranes (oral, ocular, pharyngeal, nasal, esophageal, laryngeal and anogenital) and/ or skin with tendency to scar formation. There are autoantibodies against different components of the basement membrane zone (BPAG 1- BPAG2, Integrin α6ß4, Laminin 332, Col VII, among others). The direct immunofluorescence (DIF) will be of paramount importance, as well as the clinical diagnosis.Objective: review the cases diagnosed with mucous membrane pemphigoid for 24 years (January 1997- March 2021) in the Blistering Disease Clinic at the Dermatology Department at the Ramos Mejia Hospital to establish the epidemiologic, clinic presentation and available treatments in this pathology.Design: retrospective descriptive and observational study of the clinical and immunopathological characteristics of 34 patients with MMP that were treated at the Blistering Disease Clinic at the Dermatology Department at the Ramos Mejia Hospital between January 1997 and March 2021.Materials and methods: though the medical histories and the photographic registries, we evaluated the following variables: prevalence of MMP within the patients that came to consult at the Blistering Disease Clinic at the Dermatology Department, sex, age, personal history, the affected mucous, evolution time until the diagnosis, direct immunofluorescence findings, clinical follow-ups and treatments.Results: we studied the clinical evolution of 34 patients diagnosed with MMP at our institution (5.3% from the total of patients at the Blistering Disease Clinic).The most affected gender was female and the average age at diagnosis was 64 years. 70.6% presented comorbidities such as hypertension and hypothyroidism. Most of our patients referred an emotional triggering event. The most affected membrane mucous was the ocular one and the oral was the second one. The delay in diagnosis was 4 years and 11 months. Linear deposits of IgG was the most frequent result in the direct immunofluorescence. 17.6% did not continue clinical follow-up. Mycophenolate mofetil was the most used drug with a good therapeutic response. Conclusions: MMP is a rare autoimmune disease that affects mucous membrane and occasionally the skin. In this study, the ocular involvement was the most frequent one, differing with the international reports. The early interdisciplinary diagnosis is essential to avoid irreversible sequelae.

Tratamiento sistémico del penfigoide cicatrizal ocular / Systemic treatment of ocular cicatricial pemphigoid

El penfigoide cicatrizal ocular (PCO) es una enfermedad ampollar autoinmune que produce daño conjuntival grave. Se conoce poco acerca de la respuesta del PCO al tratamiento inmunosupresor. Describimos un grupo de 76 pacientes con PCO, 62 mujeres y 14 hombres. La edad media al diagnóstico fue de 67 ± 14 años, con un retraso de 7.5 ± 10 años. Sesenta se siguieron en nuestro servicio por 19 ± 21 meses. De 51 en quienes se describe la gravedad de la enfermedad al inicio del tratamiento, fue leve en 19 pacientes, moderada en 19, grave en cinco y muy grave en ocho. Las drogas mayormente prescriptas fueron dapsona en 35 pacientes, de los que 23 la discontinuaron por efectos adversos, y metotrexate en 42, de los que nueve lo suspendieron. Otros recibieron azatioprina, ciclofosfamida y ciclosporina. A 17 se les indicaron corticoides orales, además del inmunosupresor. Cuatro combinaron dos drogas para controlar la enfermedad. Tres pacientes refractarios recibieron gammaglobulina EV con buena respuesta. De 48 evaluados, 39 mostraron mejoría, ocho no tuvieron cambios y uno progresó. En nuestra experiencia, metotrexate y azatioprina son efectivos, con baja toxicidad. Dapsona es útil en casos leves, con efectos adversos frecuentes. La gammaglobulina EV fue efectiva en casos refractarios.

Ocular cicatricial pemphigoid (OCP) is a blistering autoimmune disease that can produce severe conjunctival damage. Its response to immunosuppressive treatment is poorly known. We describe a group of 76 patients, 62 women and 14 men. Mean age at diagnosis was 67±14 years old, with a delay to diagnosis of 7.5±10 years. Sixty patients continued their follow up in our services for 19±21 months. Nineteen out of 51 had mild disease, 19 moderate, 5 severe and 8 very severe at onset of treatment. The more frequently prescribed drugs were dapsone, in 35 (23 discontinued it because of adverse effects), and methotrexate in 42 patients, nine of them stopped it. Other patients received azathioprine, cyclophosphamide and ciclosporine. Seventeen received oral steroids in addition to immunosuppresive drugs. Four patients combined two immunosupressive drugs to control their disease. In three refractory cases IV immunoglobulin (Ig) was administered with good response. From 48 evaluated patients, 39 improved with treatment, eight remained stable and one progressed. In our experience, methotrexate and azathioprine were effective drugs, with low toxicity. Dapsone was useful in mild cases, with frequent adverse effects. IVIg was effective for refractory cases.

A importância do diagnóstico precoce do penfigoide cicatricial: relato de caso / The importance of early diagnosis in cicatricial pemphigoid: case report

O penfigóide cicatricial é uma doença bolhosa inflamatória de caráter crônico e autoimune que afeta primariamente as superfícies mucosas. Auto anticorpos são produzidos contra o complexo de adesões dos hemidesmossomas da membrana basal da pele e mucosas. Afeta a cavidade bucal, laringe esôfago, membrana ocular e raramente a pele. A formação de cicatrizes é característica e pode resultar em cegueira, quando envolve a conjuntiva ocular. O envolvimento da mucosa bucal é observado na maioria dos pacientes e, quando acomete a gengiva, produz um quadro de gengivite descamativa. A etiologia é desconhecida, no entanto tem sido relatada a indução por drogas como possível desencadeador da doença. O diagnóstico é obtido com base na história clínica, biópsia e imunofluorescência direta. O tratamento é feito através de corticosteroide tópico ou sistêmico, na dependência da gravidade da doença. O presente trabalho tem por objetivo relatar um caso de penfigoide cicatricial onde a paciente apresentava apenas lesões bucais, tendo sido estabelecido o diagnóstico por meio da histopatologia através da microscopia óptica a qual apresentou aspecto bastante característico. O Tratamento intituído foi o uso de corticosteroide sistêmico. A paciente está em tratamento, com evolução satisfatória e compatível com o diagnóstico.

The cicatricial pemphigoid is a bullous disease of character chronic inflammatory and autoimmune diseases primarily affecting the mucosal surfaces. Auto-antibodies are produced against the hemidesmosomal complex of members of the basal membrane of the skin and mucous membranes. Affects the oral cavity, larynx, esophagus, eye membrane and rarely the skin. The formation of scar tissue is characteristic and can result in blindness if it involves the ocular conjunctiva. The involvement of the oral mucosa is observed in most patients and when affects the gingiva produces a table of gingivitis peel. The etiology is unknown, however, has been reported to be induced by drugs as a possible trigger of the disease. The diagnosis is made based on clinical history, biopsy and direct immunofluorescence. Treatment is realized by topical or systemic corticosteroids, depending on the severity of the disease, This study aims to report a case of cicatricial pemphigoid in which the patient had oral lesions only was the diagnosis established by histopathology by light microscopy which showed very characteristic appearance. The treatment was the use of systemic corticosteroids. The patient is in treatment, with satisfactory evolution and is compatible with the disgnosis.

Surgical treatment of corneal complications in patients with ocular cicatriciai pemphigoid / 眼科

Objective To observe the outcome of patients with ocular cicatricial pemphigoid (OCP) after amniotic membrane grafting or penetrating keratoplasty.Design Retrospective,noncomparative case series.Participants 3 consecutive OCP patients (4 eyes),were included.Methods For 3 patients (4 eyes) in this study,preoperative visual acuity was from HM/5 cm to HM/10 cm.The symblepharon (gradeⅢ) of 2 patients (3 eyes) were detached and amniotic membrane was transplanted,and bandage contact lens were used till 2 months after operations.The other patient (1 eye) was undergone penetrating keratoplasty with glycerol-cryopreserved cornea because of corneal ulcer and perforation.Main Outcome Measures Visual acuity,recovering of conjunctiva and cornea.Results Am- niotic membrane dissolved about 1 month after operation in 2 patients (3 eyes).Symblepharon changed from gradeⅢto gradeⅡ,visual acuity increased to 0.04-0.05,central corneal epithelium was regenerated significantly,and a little new vessel appeared at corneal lim- bus in 2 patients (2 eyes).The graft deliquesced in the patient with penetrating keratoplasty at 20 days after operation and undergone penetrating keratoplasty again after 1 month.In this patient,the graft molten induced the ocular contents run-off and became eyeball at- rophy eventually.Conclusion Our small sample study shows that the symblepharon detachment and amniotic membrane transplantation is effective for improving visual acuity in OCP with ocular surface dysfunction.However,because of various factors,penetrating kerato- plasty is ineffective for OCP with perforating corneal ulcer.

A Case of Epidermolysis Bullosa Acquisita (Cicatricial pemphigoid-like type) / 대한피부과학회지

Epidermolysis bullosa acquisita (EBA) is an uncommon autoimmune subepidermal blistering disorder and has four clinical subtypes. Among the four types of EBA, the cicatricial pemphigoid-like type is rarer than the other types and clinically the worst one. We experienced a case of cicatricial pemphigoid-like type of EBA in a 69-year-old woman, whose initial symptom was painful erosive lesions of oral mucous membrane before development of ocular and bullous cutaneous lesions. The clinical, histopathological findings and immunoblot assay were all typical of the disease. The course of her disease showed remissions by treatments including corticosteroid and intravenous immunoglobulin, but each time with exacerbations.

Subepidermal Blistering Diseases with Coexistent IgG and IgA Anti-BMZ Antibodies: Epidermolysis and Cicatricial Pemphigoid / 대한피부과학회지

A 21 year-old lady had erythemas and bullae on the trunk for 20 days. Biopsy specimens showed subepidermal blister and deposits of IgG and IgA along the basement membrane zone (BMZ). Her serum antibodies of IgG and IgA were observed to recognize 290/145 kD antigens derived from A431-cell line. The other patient of 62 year-old woman had recurrent oral erosions and erosio-ulcerative plaques on her anterior chest for the past 2 years. Tissue specimens showed subepidermal blister and deposits of IgG and IgA at the BMZ. The patients serum had IgG and IgA antibodies which had binding specificities to the 230 kD pemphigoid antigen. The above two cases of epidermolysis billosa acquisita and cicatricial pemphigoid with IgG and IgA antibodies of comparable titers in each may be rarely encountered ones.

Ocular Cicatricial Pemphigoid

Ocular cicatricial pemphigoid isa chronic, progressive disease characterized by cicatricial shrinkage of the conjunctiva, entropion, trichiasis, xerosis, and finally reduced vision from corneal opacification. It is a relatively rare, autoimmune disease. In the early stages, it can be easily overlooked as simple chronic conjunctivitis, so it can be untreated. We report a case of ocular cicatricial pemphigoid that resulted in significant morbidity. We were able to control the progression of cicatrization with aggressive immunosuppressive therapy.