Granulomatosis with Polyangiitis: A Rare but Clinically Important Disease for the Otolaryngologist.

INTRODUCTION: Granulomatosis with polyangiitis (GPA) is rare but debilitating autoimmune disease and commonly presents with sinonasal as well as other head and neck symptoms. AIMS: To summarize the ear, nose, and throat-specific symptomatology and management of GPA. METHODS AND RESULTS: We performed a literature review by using the PubMed search engine to provide a summary of recent and important literature that is pertinent to an otolaryngologist's clinical practice. We provide a guide on the pathophysiology, epidemiology, clinical features, investigation, and management (operative and nonoperative) of this important disease. CONCLUSIONS: This review illustrates the important role that an otolaryngologist can play in the work up and symptom management of patients with GPA. Knowledge of the common presenting symptoms as well as more rare presentations of GPA is extremely important for otolaryngologists as prompt diagnosis and management is extremely important to avoid significant morbidity and mortality.

Proteinase 3-specific antineutrophil cytoplasmic antibody-associated vasculitis.

Proteinase 3 (PR3)-specific antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is one of two major ANCA-associated vasculitis variants and is pathogenically linked to granulomatosis with polyangiitis (GPA). GPA is characterised by necrotising granulomatous inflammation that preferentially affects the respiratory tract. The small vessel vasculitis features of GPA are shared with microscopic polyangiitis. Necrotising granulomatous inflammation of GPA can lead to PR3-ANCA and small vessel vasculitis via activation of neutrophils and monocytes. B cells are central to the pathogenesis of PR3-ANCA-associated vasculitis. They are targeted successfully by remission induction and maintenance therapy with rituximab. Relapses of PR3-ANCA-associated vasculitis and toxicities associated with current standard therapy contribute substantially to remaining mortality and damage-associated morbidity. More effective and less toxic treatments are sought to address this unmet need. Advances with cellular and novel antigen-specific immunotherapies hold promise for application in autoimmune disease, including PR3-ANCA-associated vasculitis. This Series paper describes the inter-related histopathological and clinical features, pathophysiology, as well as current and future targeted treatments for PR3-ANCA-associated vasculitis.

The Joint Vasculitis Registry in German-speaking countries (GeVas): subgroup analysis of 266 AAV patients.

OBJECTIVES: Prospective long-term observational data on the disease course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were missing in Germany to date. Therefore, the Joint Vasculitis Registry in German-speaking countries (GeVas) has been established to follow the course of patients with AAV. The aim of this study is to present baseline data of patients with newly diagnosed and relapsing AAV enrolled in the GeVas registry. METHODS: GeVas is a prospective, web-based, multicentre, clinician-driven registry for the documentation of organ manifestations, damage, long-term outcomes, and therapy regimens in various types of vasculitis. Recruitment started in June 2019. RESULTS: Between June 2019 and October 2022, 266 patients with AAV were included in the GeVas registry: 173 (65%) with new-onset and 93 (35%) with relapsing AAV. One hundred and sixty-two (61%) patients were classified as granulomatosis with polyangiitis (GPA), 66 (25%) as microscopic polyangiitis (MPA), 36 (13%) as eosinophilic granulomatosis with polyangiitis (EGPA), and 2 (1%) as renal limited AAV. The median age was 59 years (51-70 years, IQR), 130 (51%) patients were female. Most patients were ANCA positive (177; 67%) and affected by general symptoms, pulmonary, ear nose throat (ENT), renal and neurological involvement. For induction of remission, the majority of patients received glucocorticoids (247, 93%) in combination with either rituximab (118, 45%) or cyclophosphamide (112, 42%). CONCLUSIONS: Demographic characteristics are comparable to those in other European countries. Differences were found regarding ANCA status, frequencies of organ manifestations, and therapeutic regimens. The GeVas registry will allow longitudinal observations and prospective outcome measures in AAV.

Epidemiology and treatment outcome of ANCA-associated vasculitis in South Korea: a nationwide, population-based cohort study.

OBJECTIVES: To investigate the epidemiological features of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in South Korea. METHODS: We identified the index cases of GPA and MPA using the 2010-2018 Korean National Health Insurance Service database and the Rare Intractable Disease registry for the entire Korean population. Each disease's incidence and prevalence rates and trends over time were analysed. To assess the impact of disease on morbidity and mortality, a comparator group comprising the general population was established using nearest-neighbour matching by age, sex, income, and comorbidity index, at a 5:1 ratio. Morbidity outcomes included the initiation of renal replacement therapy and admission to the intensive care unit. RESULTS: We identified 546 and 795 patients with GPA and MPA, respectively. The incidence rates of both diseases increased with age, with peak incidence rates observed among patients aged ≥70 years. The incidence of MPA increased continuously over time, whereas that of GPA showed no significant changes. During the observation period, 132 (28.7%) and 277 (41.1%) patients in the GPA and MPA groups, respectively, died, which were significantly higher than that in the general population (standardised mortality ratio: 3.53 and 5.58, respectively) and comparator group (hazard ratio: 4.02 and 5.64, respectively). Higher mortality and morbidity rates were observed among patients with MPA than among those with GPA. CONCLUSIONS: In South Korea, the incidence of MPA has increased over time. Although both GPA and MPA had high rates of mortality and morbidity, MPA has a poorer prognosis than GPA.

Granulomatose com poliangiite: atualização do diagnóstico ao tratamento / Granulomatosis with polyangiitis: updates from diagnosis to treatment

Introdução: Granulomatose com poliangiite (GPA) é uma vasculite granulomatosa necrosante pauci-imune que afeta predominantemente pequenos vasos. É uma doença rara, de etiologia multifatorial, e constitui importante diagnóstico diferencial das síndromes pulmão-rim. Objetivo: atualizar os principais tópicos acerca da granulomatose com poliangiite, além de trazer perspectivas futuras e avanços no manejo clínico dessa vasculite. Metodologia: revisão de literatura realizada em 2018 a partir das publicações dos últimos 5 anos nas base de dados do PubMed Central® e da SciELO®. Resultados: 29 referências bibliográficas selecionadas, das quais: 16 revisões de leteratura; 2 revisões sistemáticas; 1 estudo transversal; 2 estudos caso-controle; 6 coortes; 2 consensos atualizados (1 brasileiro de 2017 e 1 internacional de 2017). Conclusão: a granulomatose com poliangiite é uma entidade de elevada morbimortalidade, e teve seu algoritmo de tratamento recentemente atualizado, conforme abordado nesta revisão. Novos estudos ainda em estão em andamento para avaliar a eficácia e segurança de novas abordagens terapêuticas.

Introduction: Granulomatosis with polyangiitis (GPA) is a pauci-immune necrotizing granulomatous vasculitis that affects predominantly small vessels. It is a rare disease with a multifactorial etiology and an important differential diagnosis of Pulmonary-renal syndromes. Objective: to update the main topics about granulomatosis with polyangiitis, in addition to bringing future perspectives and advances in the clinical management of this vasculitis. Methodology: literature review conducted in 2018 from the publications of the last 5 years in PubMed Central® and SciELO® databases. Results: 29 selected bibliographical references, of which: 16 literature reviews; 2 systematic reviews; 1 cross-sectional study; 2 case-control studies; 6 cohorts; 2 updated consensuses (1 Brazilian, 2017 and 1 international, 2017). Conclusion: granulomatosis with polyangiitis is an entity with high morbidity and mortality, and its treatment algorithm has recently been updated, as discussed in this review. Further studies are underway to evaluate the efficacy and safety of novel therapeutic approaches.

Acometimento de nervos cranianos na granulomatose com poliangeíte (GPA) C-ANCA negativo / Cranial nerve impairment in granulomatosis with polyangeitis (GPA) C-ANCA negative

RESUMO O presente relato tem o objetivo de mostrar um caso incomum de Granulomatose com Poliangeíte (GPA), que previamente era denominada Granulomatose de Wegener. Trata-se de é uma doença multissistêmica, caracterizada por inflamação granulomatosa necrotizante e vasculite que envolve principalmente o trato respiratório superior e inferior, embora não raramente, exista comprometimento neurológico.

ABSTRACT This report aims to show an unusual case of granulomatosis with polyangeitis (GPA), previously known as Wegener's granulomatosis. It is a multisystemic disease characterized by necrotizing granulomatous inflammation and vasculitis involving mainly the upper and lower respiratory tract, although not infrequently, there is neurological impairment.

Enfermedad de Wegener o granulomatosis con poliangeítis. Presentación de un caso / Wegener´s disease or granulomatosis with polyangiitis. Case presentation

RESUMEN La enfermedad de Wegener o granulomatosis con poliangeítis, es una enfermedad rara, que se caracteriza por presentar una vasculitis sistémica primaria granulomatosa, con afectación de las vías aéreas superiores, inferiores y el riñón. Se exponen las características clínicas y resultados de los exámenes complementarios realizados a un paciente del sexo masculino, de 24 años de edad, con rinitis, hemorragia pulmonar, insuficiencia renal aguda y anticuerpos anticitoplasmas de neutrófilos positivos (AU).

ABSTRACT Wegener´s disease or granulomatosis with polyangiitis is a rare disease, characterized for presenting a primary granulomatous systemic vasculitis, with affectation of the upper and lower airways and the kidneys. The authors expose clinical characteristics and the results of the complementary exams performed to a male patient, aged 24 years, with rhinitis, pulmonary hemorrhage, acute renal insufficiency, and anti-cytoplasmic antibodies of positive neutrophils (AU).

Enfermedad de Wegener o granulomatosis con poliangeítis. Presentación de un caso / Wegener´s disease or granulomatosis with polyangiitis. Case presentation

RESUMEN La enfermedad de Wegener o granulomatosis con poliangeítis, es una enfermedad rara, que se caracteriza por presentar una vasculitis sistémica primaria granulomatosa, con afectación de las vías aéreas superiores, inferiores y el riñón. Se exponen las características clínicas y resultados de los exámenes complementarios realizados a un paciente del sexo masculino, de 24 años de edad, con rinitis, hemorragia pulmonar, insuficiencia renal aguda y anticuerpos anticitoplasmas de neutrófilos positivos (AU).

ABSTRACT Wegener´s disease or granulomatosis with polyangiitis is a rare disease, characterized for presenting a primary granulomatous systemic vasculitis, with affectation of the upper and lower airways and the kidneys. The authors expose clinical characteristics and the results of the complementary exams performed to a male patient, aged 24 years, with rhinitis, pulmonary hemorrhage, acute renal insufficiency, and anti-cytoplasmic antibodies of positive neutrophils (AU).

Rinosinusitis recalcitrante por granulomatosis eosinofílica con poliangeítis: reporte de un caso clínico y revisión de la literatura / Chronic recalcitrant rhinosinusitis secondary to eosinophilic granulomatosis with polyangiitis: report of a case and literature review

RESUMEN Se expone el caso de un paciente de 40 años con diagnóstico de granulomatosis eosinofílica con poliangeítis subyacente a una rinosinusitis crónica recalcitrante. Se describe el caso y se discuten aspectos relevantes de la literatura al respecto.

ABSTRACT We report the case of a 40-year-old man with diagnosis of chronic recalcitrant rhino-sinusitis secondary to eosinophilic granulomatosis with polyangiitis. We described the case and discuss relevant aspects of the literature about it.

Distúrbios de condução cardíaca e taquicardia ventricular como complicação da granulomatose com poliangiíte em uma paciente. Relato de caso e revisão da literatura / Heart conduction system defects and sustained ventricular tachycardia complications in a patient with granulomatosis with polyangiitis. A case report and literature review

RESUMO A granulomatose com poliangiíte é um raro distúrbio inflamatório sistêmico que se caracteriza por vasculite de pequenas artérias, arteríolas e capilares, associada a lesões granulomatosas necrotizantes. Este artigo relata o caso de uma paciente com diagnóstico prévio de granulomatose com poliangiíte, admitida à unidade de terapia intensiva com quadro de crises convulsivas e instabilidade hemodinâmica em razão de bloqueio atrioventricular completo. Estas manifestações se associaram a múltiplos episódios de taquicardia ventricular sustentada; não havia alterações estruturais cardíacas, nem se detectaram distúrbios hidroeletrolíticos. Na unidade de terapia intensiva, a paciente foi submetida à implantação de marca-passo provisório, imunossupressão com uso de corticosteroides e terapia imunobiológica, resultando em melhora hemodinâmica completa. Distúrbios graves da condução cardíaca em pacientes com granulomatose com poliangiíte são raros, mas associam-se à grande morbidade. O reconhecimento precoce e o uso de intervenções específicas são capazes de prevenir a ocorrência de desfechos desfavoráveis, especialmente na unidade de terapia intensiva.

ABSTRACT Granulomatosis with polyangiitis is a rare systemic inflammatory disorder characterized by vasculitis of the small arteries, the arterioles and the capillaries together with necrotizing granulomatous lesions. This case reports on a young female patient, previously diagnosed with granulomatosis with polyangiitis, who was admitted to the intensive care unit with seizures and hemodynamic instability due to a complete atrioventricular heart block. The event was associated with multiple episodes of sustained ventricular tachycardia without any structural heart changes or electrolyte disturbances. In the intensive care unit, the patient was fitted with a provisory pacemaker, followed by immunosuppression with corticosteroids and immunobiological therapy, resulting in a total hemodynamic improvement. Severe conduction disorders in patients presenting granulomatosis with polyangiitis are rare but can contribute to increased morbidity. Early detection and specific intervention can prevent unfavorable outcomes, specifically in the intensive care unit.

Granulomatosis de Wegener con afectación supraglótica / Wegener granulomatosis with supraglottic involvement

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XXIX Reunión da Sociedade Galega de Neuroloxía. Comunicaciones: Vigo, Pontevedra, 8-9 de mayo de 2015 / XXIX Reunión da Sociedade Galega de Neuroloxía. Communications

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Lesión destructiva de la línea media, a propósito de un caso / Midline destructive lesion. Case report

Introducción: El síndrome destructivo de la línea media es una entidad caracterizada por un conjunto de signos y síntomas secundarios a la afección, generalmente destructiva, de localización medio facial. Objetivos: Presentación de caso clínico y revisión bibliográfica. Reporte de caso: Varón de 38 años procedente de Chaco con diagnóstico de Leishmaniasis mucocutánea que cursó internación por una lesión destructiva de la línea media que luego de múltiples planteos diagnósticos y estudios complementarios se llega al diagnóstico final de vasculitis granulomatosa con poliangeitis (granulomatosis de Wegener).Discusión Estos pacientes representan un desafío diagnóstico en medicina interna, debido a las múltiples etiologías capaces de desarrollarlo, con manifestaciones clínicas similares pero con pronóstico y tratamiento diferente.

Introduction:Midline destructive syndrome is an entity characterized by a group of signs and symptoms, secondary to the condition, usually destructive and located in the middle of the face.Objectives: Clinical case report and literature review.Case Report: 38 year old male patient, from Chaco, with mucocutaneous Leishmaniasis diagnosis, who was hospitalized due to a midline destructive lesion. After multiple diagnostic options and complementary studies, the final diagnosis ofgranulomatosis with polyangiitis vasculitis (Wegener's granulomatosis) is reached. Discussion: These patients pose a diagnostic challenge in internal medicine, due to the multiple etiology factors that can be responsible of its development, with similar clinical symptoms but with a different treatment and prognosis.

Lesión destructiva de la línea media, a propósito de un caso / Midline destructive lesion. Case report

Introducción: El síndrome destructivo de la línea media es una entidad caracterizada por un conjunto de signos y síntomas secundarios a la afección, generalmente destructiva, de localización medio facial. Objetivos: Presentación de caso clínico y revisión bibliográfica. Reporte de caso: Varón de 38 años procedente de Chaco con diagnóstico de Leishmaniasis mucocutánea que cursó internación por una lesión destructiva de la línea media que luego de múltiples planteos diagnósticos y estudios complementarios se llega al diagnóstico final de vasculitis granulomatosa con poliangeitis (granulomatosis de Wegener).Discusión Estos pacientes representan un desafío diagnóstico en medicina interna, debido a las múltiples etiologías capaces de desarrollarlo, con manifestaciones clínicas similares pero con pronóstico y tratamiento diferente. (AU)

Introduction:Midline destructive syndrome is an entity characterized by a group of signs and symptoms, secondary to the condition, usually destructive and located in the middle of the face.Objectives: Clinical case report and literature review.Case Report: 38 year old male patient, from Chaco, with mucocutaneous Leishmaniasis diagnosis, who was hospitalized due to a midline destructive lesion. After multiple diagnostic options and complementary studies, the final diagnosis ofgranulomatosis with polyangiitis vasculitis (Wegeners granulomatosis) is reached. Discussion: These patients pose a diagnostic challenge in internal medicine, due to the multiple etiology factors that can be responsible of its development, with similar clinical symptoms but with a different treatment and prognosis. (AU)

Granulomatosis con poliangeítis (Wegener). Descripción de 15 casos / Granulomatosis with polyangiitis (Wegener). Description of 15 cases

Introducción. La granulomatosis con poliangeítis (GP) es una vasculitis necrosante de causa desconocida, que afecta a vasos de mediano y pequeño calibre. Se asocia a anticuerpos anticitoplasma de neutrófilo (ANCA). Afecta con más frecuencia a los aparatos respiratorio y renal, y la característica anatomopatológica más relevante es la presencia de granulomas necrosantes. Objetivos. Detallar las características de una serie de 15 pacientes con GP diagnosticados en un centro universitario de referencia. Pacientes y métodos. Diseño retrospectivo: entre 1984 y 2009 se diagnosticaron 15 pacientes con GP en nuestro centro. De todos ellos se obtuvieron de forma retrospectiva datos epidemiológicos, clínicos, analíticos, estudios anatomopatológicos y tratamiento recibido. Se consideró criterio de inclusión la biopsia diagnóstica de GP. Resultados. Se diagnosticaron de GP 15 pacientes: 12 varones y 3 mujeres. Edad media en el momento del diagnóstico: 52,2 años (14-78). Antecedente de tabaquismo: 12 pacientes. Se practicó una biopsia que fue diagnóstica en todos los pacientes. Los ANCA resultaron positivos en 11 casos, y de éstos 6 correspondían a un patrón citoplasmático c-ANCA. Todos los pacientes tuvieron afectación pulmonar y siete (46%) tuvieron afectación renal. Todos los pacientes recibieron como tratamiento de inducción glucocorticoides endovenosos y ciclofosfamida. Cinco han fallecido. Conclusiones. Las características clínicas de la presente serie no difieren de las descritas por otros autores. El antecedente de tabaquismo fue más frecuente de lo esperado. Los fármacos más utilizados fueron los glucocorticoides y la ciclofosfamida (oral y en emboladas). La evolución generalmente fue desfavorable, con brotes o complicaciones debidas al estado de inmunosupresión, con excepción de las formas localizadas. Es preciso mantener el tratamiento inmunosupresor de forma indefinida en la mayoría de los casos (AU)

Background. Granulomatosis with polyangiitis (GP) is a necrotizing vasculitis of unknown etiology that involves small and medium caliber vessels. It is associated with anti neutrophil cytoplasm antibodies (ANCA). It most often affects the respiratory tract and the kidneys and its most important pathologic feature is the presence of necrotizing granulomas. Objectives. To detail the features of 15 patients with GP diagnosed in a university referral center. Patients and methods. Retrospective study: between 1984 and 2009, 15 patients with GP were diagnosed in our center. Epidemiological, clinical, laboratory test as well as pathologic studies and treatment were retrospectively analyzed. Biopsy diagnosis of GP was considered as an inclusion criterion. Results. Fifteen patients were diagnosed: 12 men and 3 women. Mean age at diagnosis: 52.2 years (14-78). 12 patients had a history of smoking. A biopsy was diagnostic in all patients. ANCA were positive in 11 cases, 6 had a cytoplasmic c-ANCA pattern. All patients had pulmonary involvement and seven (40%) had renal involvement. All patients received intravenous glucocorticoids and cyclophosphamide as induction therapy. During the disease progression 5 patients died. Conclusions. The clinical features of this series do not differ from those described by other authors. However, a history of smoking is more common than expected. Frequently used drugs were glucocorticoids and cyclophosphamide (oral and pulse therapy). The course was usually unfavorable, with outbreaks or complications due to immunosuppression, except for those with limited forms. Immunosuppressive therapy should be maintained indefinitely in most cases (AU)

Papel del otorrinolaringólogo en el diagnóstico y seguimiento de pacientes con vasculitis primarias / Role of the ears, nose and throat specialist in the diagnosis and follow up of patients with primary vasculitidies

Las primeras manifestaciones de algunas vasculitis ocurren en órganos de la cabeza y el cuello; sin embargo, pocos especialistas las diagnostican en forma temprana ya que las infecciones y la alergia son más comunes. Entre ellas, signos y síntomas como epistaxis, obstrucción nasal, rinorrea serosanguinolenta, dolor ardoroso en región nasosinusal, cefalea, pólipos e incluso costras nasales, pueden encontrarse en personas que viven en ciudades con altos índices de contaminación y baja humedad, en pacientes con infecciones como el escleroma respiratorio, en aquellos sometidos a radioterapia y como consecuencia de otras condiciones; sin embargo, bajo las costras pueden crecer microorganismos como Staphylococcus aureus y también pueden hallarse señales que se pueden relacionar con vasculitis activa. El otorrinolaringólogo es uno de los primeros médicos a los que acuden pacientes con estos signos y síntomas, por lo que reconocer estas manifestaciones e integrar diagnósticos más oportunos en colaboración con otros especialistas es importante. Debido a la frecuencia con la que presentan como primeros signos y síntomas los otorrinolaringológicos, seleccionamos tres enfermedades vasculíticas para este artículo: granulomatosis con poliangitis (Wegener), el síndrome de Churg Strauss y la policondritis recurrente (AU)

First manifestations of vasculitis can appear on the head and neck, still few physicians are aware of these diseases, as they are unspecific and because other conditions like infections and allergies are more frequent. Among them, signs and symptoms like epistaxis, nasal obstruction, discharge, burning pain of sinonasal region, headache, sinus polyps and crusts, the latter found in people who live in highly polluted cities with low humidity, in patients with respiratory scleroma, atrophy, those receiving local radiotherapy, and due to other conditions. Under the crusts, many infectious agents, like Staphylococcus aureus may grow and, in addition, other signs related to active vasculitis may be found. The ENT specialist is one of the first physicians visited by patients with these signs and symptoms. Their recognition is important to readily diagnose these diseases. We have selected three vasculitidies for discussion in this paper: granulomatosis with polyangiitis (Wegener), Chrug-Strauss syndrome and relapsing polychondritis, since these three diseases present initial ENT problems with high frequency (AU)

Presentación de un caso de vasculitis de Wegener / Presentation of a case of Wegener’s vasculitis

Se presenta una paciente con granulomatosis de Wegener en su forma localizada y se efectúa una actualización de las manifestaciones clínicas, el diagnóstico y el tratamiento.