Consensus on the treatment of autoimmune bullous dermatoses: bullous pemphigoid, mucous membrane pemphigoid and epidermolysis bullosa acquisita - Brazilian Society of Dermatology

Abstract: Bullous pemphigoid, mucous membrane pemphigoid and epidermolysis bullosa acquisita are subepidermal autoimmune blistering diseases whose antigenic target is located at the basement membrane zone. Mucous membrane pemphigoid and epidermolysis bullosa acquisita can evolve with cicatricial mucosal involvement, leading to respiratory, ocular and/or digestive sequelae with important morbidity. For each of these dermatoses, a literature review covering all therapeutic options was performed. A flowchart, based on the experience and joint discussion among the authors of this consensus, was constructed to provide treatment orientation for these diseases in Brazil. In summary, in the localized, low-risk or non-severe forms, drugs that have immunomodulatory action such as dapsone, doxycycline among others may be a therapeutic option. Topical treatment with corticosteroids or immunomodulators may also be used. Systemic corticosteroid therapy continues to be the treatment of choice for severe forms, especially those involving ocular, laryngeal-pharyngeal and/or esophageal mucosal involvement, as may occur in mucous membrane pemphigoid and epidermolysis bullosa acquisita. Several immunosuppressants are used as adjuvant alternatives. In severe and recalcitrant cases, intravenous immunoglobulin is an alternative that, while expensive, may be used. Immunobiological drugs such as rituximab are promising drugs in this area. Omalizumab has been used in bullous pemphigoid.

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.

Penfigoide de membranas mucosas com estenose esofágica grave / Mucous membrane pemphigoid with severe esophageal stricture

O penfigoide de membranas mucosas é entidade nosológica encarada como um fenótipo, que engloba várias dermatoses autoimunes com lesões bolhosas subepidérmicas, ocorrendo predominantemente nas membranas mucosas, com êxito cicatricial. O acometimento esofágico no penfigoide de membranas mucosas é raro e observado em pacientes com lesão disseminada. As alterações mais comuns são múltiplas membranas ou constrições esofagianas. No presente relato, os autores apresentam paciente com PMM sem lesões cutâneas e estenose esofágica grave, que entrou em remissão após uso de imunoglobulina venosa.

Mucous membrane pemphigoid (MMP) is a rare nosological entity. MMP consists of a clinical phenotype in which several autoimmune subepidermal bullous diseases are classified. It occurs predominantly in the mucous membranes and usually results in scarring. Esophageal involvement in MMP is rare and is generally seen in patients in whom lesions are widespread. The most common alterations are multiple esophageal membranes or strictures. In the present case, the authors report on a patient with MMP without any skin lesions and with severe esophageal strictures who went into remission following use of intravenous immunoglobulin.

Management of mucous membrane pemphigoid with dapsone plus weekly steroid injections in a young patient: a case report / Tratamento de penfigóide membranoso mucoso com dapsona e injeções semanais de esteróide em um paciente jovem: relato de caso

Purpose: Mucous Membrane Pemphigoid (MMP) is an autoimmune subepithelial blistering disorder usually affecting older individuals. This paper describes the pharmacological management of MMP in a young patient. Case description: A 23 year-old woman showed erythematous ulcerative gingiva in the maxillary palatal region and around the retromolar region. A perilesional excisional biopsy was done, and the histologic and immunohistochemical analysis confirmed the clinical diagnosis of MMP as the cause of desquamative gingivitis in this patient. The patient was treated with topical steroids plus daily Dapsone 100 mg and weekly steroid injections (40 mg). The lesions began to resolve after 12 weeks of therapy. Conclusion: This case of MMP in a young female patient was effectively managed with a combination therapy of topical steroids, Dapsone and steroid injections.

Objetivo: O penfigóide membranoso mucoso (PMM) é uma desordem autoimume subeptelial bolhosa que geralmente afeta indivíduos mais velhos. Este relato de caso descreve a abordagem farmacológica do PMM em uma paciente jovem. Descrição do caso: Uma paciente do sexo feminino, com 23 anos de idade, apresentava a gengiva eritematosa e ulcerada na região palatina e na região retromolar. A biópsia excisional total foi realizada e as análises histológica e de imuno-histoquímica confirmaram o diagnóstico clínico de PMM como causa da gengivite descamativa nesta paciente. A paciente foi tratada com esteróides tópicos, Dapsona 100 mg diariamente e injeções de esteróides mensais (40 mg). A resolução das lesões se iniciou após 12 semanas de terapia medicamentosa. Conclusão: Este caso de PMM em uma paciente jovem foi efetivamente tratado com uma terapia combinada de esteróides tópicos, Dapsona e injeções de esteróides.

Penfigóide cicatricial no trato aerodigestivo superior: relato de dois casos / Cicatricial pemphygoid in the upper aerodigestive tract: report of two cases

Penfigóide Cicatricial (Penfigóide Cicatricial de Membrana Mucosa) é uma doença auto-imune inflamatória crônica caracterizada pela presença de bolhas subepiteliais em membranas mucosas e, ocasionalmente na pele. Pode haver acometimento oral, nasal, faríngeo, laríngeo, ocular, esofágico, anogenital e de pele, predominantemente em pacientes na quinta e sexta décadas de vida. O tratamento preconizado inclui corticóides sistêmicos e agentes imunossupressores. Descrevemos neste trabalho dois casos com a doença em atividade, sendo que um evoluiu com complicação séptica pelo uso de imunossupressor e outro que apresentou estenose supraglótica exigindo traqueotomia.

Cicatricial pemphygoid (mucous membrane cicatricial pemphygoid) is a chronic autoimmune inflammatory disease characterized by subepithelial bubbles in mucous membranes and, occasionally on the skin. It may affect the mouth, the nose, pharynx, larynx, the eyes, esophagus, anus, genitals and skin; especially affecting patients between fifty and sixty years of life. Treatment includes systemic steroids and immunosuppressive agents. In the present paper we describe two cases with the active disease, and one of them had sepsis because of using immunosuppressive agents and another that presented supraglottic stenosis requiring tracheostomy.

Penfigoide benigno de las mucosas: reporte de caso clínico / Benign pemphigoid of the oral mucosa: report of a clinical case

El penfigoide benigno de las mucosas es una enfermedad autoinmune ampollar. En un 80 por ciento de los casos está afectada la mucosa oral, de ahí la importancia que dicha enfermedad la conozca el odontólogo general y el especialista. El siguiente caso muestra el compromiso de la mucosa gingival en una paciente de 12 años de edad.

Cicatricial pemphigoid: a case report

Cicatricial pemphigoid is a rare idiopathic chronic and progressive autoimmune blistering disorder of late middle age, and more common in women. We report a case of 44-year-old female patient who had been diagnosed and treated as a case of Behcet's disease for three years. In June 2002, the patient was admitted to the Rheumatology Department-Royal Rehabilitation Center with severe painful mouth ulcerations, redness of eyes with excessive sticky discharge and dysphagia. Clinical findings and laboratory tests including immunofluorescent study were diagnostic of Cicatricial pemphigoid. The patient was treated with oral methotrexate, prednisolone and artificial teardrops followed by surgical release of conjunctival scarring

Terapia imunossupressora em penfigóide ocular cicatricial / Immunossupressive therapy in ocular ciciatricial pemphygoid

Penfigóide Ocular Cicatricial é uma doença crônica, progressiva e auto-imune das membranas mucosas. Neste estudo acompanhou-se 15 pacientes submetidos à terapia imunossupressora por um período médio de 13 meses. A resposta ao tratamento foi avaliada em relaçäo à diminuiçäo da atividade inflamatória e parada da progressäo da doença. O diagnóstico foi tardio: 69 por cento dos pacientes apresentaram visäo pior que 20/200 e 86 por cento estavam em estágios avançados da doença no exame inicial. Resposta clínica ao tratamento inicial com Dapsone foi observada na maioria dos pacientes. Em 3 casos foi necessária a substituiçäo por methotrexate. Em um paciente iniciou-se o tratamento com ciclofosfamida devido à intensidade inflamatória do quadro ocular. A imunodepressäo sistêmica é o tratamento de escolha para penfigóide, porém deve ser feita por médicos treinados, já que säo drogas potencialmente letais

Penfigoide benigno de las mucosas: reporte de caso con lesiones gingivales y expresión palmar / Benign mucous membrane pemphigoid: report of a case with gingival and palmar expressions

El penfigoide benigno de las mucosas es una enfermedad que tradicionalmente se presenta en boca. Su diagóstico y tratamiento debe ser realizado por un grupo multidisciplinario de profesionales donde intervienen periodoncistas, patólogos clínicos e histopatólogos bucales. El siguiente caso muestra un abordaje integrado de especialistas, lo que se tradujo en la resolución total de la entidad en el paciente. Se realiza revisión bibliográfica y propuesta de tratamiento