Actualización en el estudio de granulomatosis con poliangeitis (granulomatosis de Wegener) / Update in study of granulomatosis with polyangiitis (Wegener's granulomatosis)

Resumen:La granulomatosis con poliangeítis (GPA) es una vasculitis sistémica de pequeño vaso, que afecta más frecuentemente el tracto respiratorio y el riñón. Sus criterios diagnósticos se basan en la clínica, exámenes de laboratorio, imágenes e histología. El 90% son ANCA (anticuerpos anticitoplasma de neutrófilos) positivos. La histología muestra inflamación granulomatosa, necrosis y vasculitis. Los exámenes de imagen son de vital importancia en su estudio inicial y seguimiento, correspondiendo principalmente a técnicas tomográficas. La tomografía Computada (TC) es el método de elección para la evaluación de vía aérea superior y pulmón, con alta sensibilidad en afectación de cavidades nasal/paranasales, árbol bronquial y pulmón. La Resonancia Magnética está indicada en compromiso del sistema nervioso central y corazón. El PET/CT presenta alta sensibilidad en enfermedad tóraco-abdominal, es de utilidad en detectar lesiones no visibles con otras técnicas, y en control de tratamiento. El compromiso renal, de alta ocurrencia en GPA, presenta escasa traducción en las imágenes y es frecuentemente indetectable con imágenes, aunque el PET/CT puede ser positivo en casos de glomerulonefritis acentuada. La radiología simple no debe ser utilizada en el estudio de GPA dado su bajo rendimiento diagnóstico. El tratamiento se basa en terapia corticoidea e inmunosupresora. Las recaídas son frecuentes, por lo que estos pacientes requieren seguimiento a largo plazo.

Abstract:Granulomatosis with polyangiitis (GPA) is a systemic type of vasculitis that affects small vessels, most commonly involving the respiratory tract and kidneys. Diagnosis is based on clinical criteria, laboratory tests, imaging and histology. Ninety percent are ANCA (anti-neutrophilic cytoplasmic antibodies) positive. Histology demonstrates granulomatous inflammation, necrosis and vasculitis. Imaging studies are vital for the initial work-up and follow-up. Computed Tomography (CT) is the method of choice for evaluation of the upper airway and lungs, because of its high sensitivity detecting anomalies of paranasal sinuses, bronchial tree and lungs. Magnetic Resonance is indicated for evaluation of the central nervous system and heart. PET/CT has high sensitivity for thoracic and abdominal disease, is useful at detecting lesions not seen with other imaging techniques, and for follow-up. Renal involvement, very frequent on GPA, is usually undetectable at imaging, but may be seen at PET/CT in cases of marked glomerulonephritis. Plain X-rays should not be used for evaluation of GPA because of their low diagnostic performance. Treatment is based on corticosteroid and immunosuppressive therapy. Relapses are frequent, so these patients require long-term follow-up.

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.

Serum 25-hydroxyvitamin D levels in patients with Granulomatosis with Polyangiitis: association with respiratory infection

OBJECTIVES: To determine the possible association of serum 25-hydroxyvitamin D (25OHD) levels with disease activity and respiratory infection in granulomatosis with polyangiitis patients during two different periods: winter/spring and summer/autumn. METHODS: Thirty-two granulomatosis with polyangiitis patients were evaluated in the winter/spring, and the same patients (except 5) were evaluated in summer/autumn (n=27). The 25OHD levels were measured by radioimmunoassay. Disease activity was assessed by the Birmingham Vasculitis Activity Score Modified for Wegener's Granulomatosis (BVAS/WG) and antineutrophil cytoplasmic antibody (ANCA) positivity. Respiratory infection was defined according the Centers for Disease Control and Prevention criteria. RESULTS: 25OHD levels were lower among patients in winter/spring than in summer/autumn (32.31±13.10 vs. 38.98±10.97 ng/mL, p=0.04). Seven patients met the criteria for respiratory infection: 5 in winter/spring and 2 in summer/autumn. Patients with respiratory infection presented lower 25OHD levels than those without infection (25.15±11.70 vs. 36.73±12.08 ng/mL, p=0.02). A higher frequency of low vitamin D levels (25OHD<20 ng/mL) was observed in patients with respiratory infection (37.5% vs. 7.8, p=0.04). Serum 25OHD levels were comparable between patients with (BVAS/WG≥1 plus positive ANCA) and without disease activity (BVAS/WG=0 plus negative ANCA) (35.40±11.48 vs. 35.34±13.13 ng/mL, p=0.98). CONCLUSIONS: Lower 25OHD levels were associated with respiratory infection but not disease activity in granulomatosis with polyangiitis patients. Our data suggest that hypovitaminosis D could be an important risk factor for respiratory infection in granulomatosis with polyangiitis patients.

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.

Estenosis subglótica como manifestación inicial de granulomatosis de Wegener en una adolescente: Caso clínico / Subglottic stenosis as the initial manifestation of Wegener's granulomatosis in a teenager: Case report

La granulomatosis de Wegener es una vasculitis granulomatosa necrotizante de origen autoinmune que afecta, principalmente, a la vía aérea superior e inferior y los riñones. Es muy rara en los niños y adolescentes. Cuando se inicia a edad temprana, se asocia, con frecuencia, a estenosis subglótica. La estenosis subglótica es una manifestación potencialmente fatal de la granulomatosis de Wegener. Su diagnóstico requiere un alto grado de sospecha porque puede desarrollarse en ausencia de otros signos de actividad y, en ocasiones, es la manifestación inicial de la enfermedad. Se confirma mediante la visualización endoscópica de la lesión. El tratamiento es complejo; requiere, a menudo, de repetidas intervenciones, debido a reestenosis. Presentamos a una paciente de 13 años de edad con estenosis subglótica secundaria a granulomatosis de Wegener. Describimos las manifestaciones clínicas, el diagnóstico y el tratamiento de esta rara causa de dificultad respiratoria en la población pediátrica.

Wegener's granulomatosis is a necrotizing granulomatous vasculitis of autoimmune origin that primarily affects the upper and lower airways and kidneys. It is very rare in children and adolescents. When started at a young age it is often associated with subglottic stenosis. Subglottic stenosis is a potentially fatal manifestation of Wegener's granulomatosis. Its diagnosis requires a high index of suspicion since it might develop in the absence of other signs of activity. Occasionally, subglottic stenosis may present as the initial manifestation of the disease. Diagnosis is confirmed by endoscopic visualization of the lesion. The treatment is complex, and it often requires repeated interventions due to restenosis. We present a 13-year-old patient with subglottic stenosis secondary to Wegener's granulomatosis. We describe the clinical manifestations, diagnosis and treatment of this rare cause of respiratory distress in the pediatric population.

Bilateral acute angle-closure glaucoma as a first presentation of granulomatosis with polyangiitis (Wegener's) / Glaucoma de ângulo fechado bilateral agudo como uma primeira apresentação da granulomatose com poliangeíte (de Wegener)

ABSTRACT We report a case of bilateral acute angle-closure glaucoma in a patient with undiagnosed granulomatosis with polyangiitis (Wegener's). A 59-year-old man presented with a severe headache, ocular pain, blurred vision, shortness of breath, and mild fever. Clinical examination revealed conjunctival chemosis, corneal edema, and shallow anterior chambers. Closed angles were observed bilaterally on gonioscopy. The patient was treated with intravenous mannitol, oral acetazolamide, and anti-glaucomatous eye drops. Over the following two days, his vision improved and intraocular pressures decreased. Subsequently, laser iridotomies were performed bilaterally and the patient attended consultations with our departments of respiratory medicine, nephrology, and rheumatology and was subsequently diagnosed with granulomatosis with polyangiitis. Bilateral acute angle-closure glaucoma is a very rare ocular manifestation of granulomatosis with polyangiitis. The association of this clinical entity with Wegener's granulomatosis remains unknown.

RESUMO Relatamos um caso glaucoma bilateral agudo de ângulo fechado em um paciente sem diagnóstico prévio de granulomatose com poliangeíte (Wegener). Um homem de 59 anos apresentou-se com uma forte dor de cabeça, dor nos olhos, visão turva, dificuldade em respirar e febre baixa. Observamos quemose conjuntival, edema da córnea e câmara anterior rasa. A gonioscopia demonstrou ângulos fechados bilateralmente. Ele foi tratado com manitol intravenoso, acetazolamida oral, olho e colírios antiglaucomatosos. Durante os dois dias seguintes a sua visão melhorou e as pressões intra-oculares diminuíram. A seguir, foram realizadas iridotomias a laser bilateralmente e ele foi referido para os departamentos de doenças pulmonares, nefrologia e reumatologia. Ele foi diagnosticado com poliangeíte granulomatosa. Glaucoma bilateral agudo de ângulo fechado é uma entidade clínica muito rara e sua associação com a granulomatose de Wegener é desconhecida e deve acrescentar-se à lista de manifestações oculares de granulomatose com poliangeíte.

Estenosis subglótica en pacientes con granulomatosis con poliangeítis / Subglottic stenosis in patients with granulomatosis with polyangiitis

Introducción: La granulomatosis con poliangeítis (GPA) es una enfermedad autoinmune con múltiples manifestaciones otorrinolaringológicas. La estenosis subglótica (ESG) se reporta entre 8%-50% de los pacientes. Objetivo: Describir la presentación clínica y tratamiento de la ESG en pacientes con GPA. Material y método: Estudio descriptivo retrospectivo de los pacientes atendidos en el Departamento de Otorrinolaringología de la Pontificia Universidad Católica de Chile entre 2011 y 2015 con diagnóstico de GPA y ESG. Resultados: Diez pacientes (90% mujeres) con edad promedio al diagnóstico de 44,6 años. Los síntomas fueron: disnea (9/10), disfonía (6/10) y estridor (5/10). En el 80%, la ESG fue la presentación inicial de la GPA. El 90% presentó GPA localizada y 10% GPA sistémica. El 60% presentó anticuerpos anticitoplasma de neutrófilos (ANCA) negativo. Todos los pacientes recibieron glucocorticoides sistémicos, asociados a inmunosupresores y/o anticuerpos monoclonales. Una paciente requirió traqueostomía y dos pacientes han requerido dilatación endoscópica con balón asociado a inyección local de metilprednisolona. Conclusiones: La ESG puede ser la única manifestación de GPA. Los síntomas inespecíficos y la alta probabilidad de presentar ANCA negativo hacen difícil el diagnóstico. El manejo debe ser individualizado y multidisciplinario. La mayoría de nuestros pacientes pudieron ser manejados adecuadamente con tratamiento médico.

Introduction: Granulomatosis with polyangiitis (GPA) is an autoimmune disease that presents with multiple ENT manifestations. Subglottic stenosis (SGS) has been reported in 8-50% of the patients. Aim: To describe the clinical presentation and treatment of SGS in patients with GPA. Material and method: Retrospective review of clinical data from all patients consulting in the Otolaryngology department at Pontificia Universidad Católica de Chile from 2011 to 2015 with SGS and GPA diagnosis. Results: Ten patients (90% female) with average age at diagnosis of44.6 years. The symptoms were: dyspnea (9/10), dysphonia (6/10) and stridor (5/10). SGS was the initial presenting manifestation of GPA in 80% of patients. GPA was localized in 90% and systemic in 10% of patients, and anti-neutrophilic cytoplasmic antibodies (ANCA) were negative in 60% of patients. Systemic glucocorticoids were used in every patient, associated with immunosuppressants and/or monoclonal antibodies. One patient required tracheostomy and 2 patients were treated with endoscopic balloon dilation associated with local methylprednisolone injection. Conclusions: SGS can be GPA’s initial or unique manifestation. Diagnosis is hindered due to the unspecificity ofsymptoms and the high probability of presenting with negative ANCA. Individualized and multidisciplinary treatment is required. Most patients were treated pharmacologically with an adequate response in our series.

An update of neurological manifestations of vasculitides and connective tissue diseases: a literature review / Atualização das manifestações neurológicas das vasculitides e das doenças do tecido conjuntivo: revisão de literatura

Vasculitides comprise a heterogeneous group of autoimmune disorders, occurring as primary or secondary to a broad variety of systemic infectious, malignant or connective tissue diseases. The latter occur more often but their pathogenic mechanisms have not been fully established. Frequent and varied central and peripheral nervous system complications occur in vasculitides and connective tissue diseases. In many cases, the neurological disorders have an atypical clinical course or even an early onset, and the healthcare professionals should be aware of them. The purpose of this brief review was to give an update of the main neurological disorders of common vasculitis and connective tissue diseases, aiming at accurate diagnosis and management, with an emphasis on pathophysiologic mechanisms.

As vasculites são um grupo heterogêneo de doenças autoimunes primárias ou secundárias a uma grande variedade de doenças infecciosas sistêmicas, malignas ou do tecido conjuntivo. Estas últimas são as que ocorrem com mais frequência, porém os mecanismos patogênicos ainda não foram plenamente determinados. Diversas e frequentes complicações do sistema nervoso central e periférico ocorrem nas vasculites e doenças do tecido conjuntivo. Em muitos casos, os distúrbios neurológicos têm evolução clínica atípica ou mesmo início precoce, ao que todos os profissionais de saúde devem estar cientes. O objetivo desta breve revisão foi atualizar os principais distúrbios neurológicos da vasculite comum e das doenças do tecido conjuntivo, visando ao diagnóstico e ao tratamento corretos, com ênfase nos mecanismos fisiopatológicos.

Infarto agudo do miocárdio como apresentação inicial de granulomatose eosinofílica com poliangiite (anteriormente, síndrome de Churg Strauss) / Acute myocardial infarction as Eosinophilic granulomatosis with polyangiitis (formerly Churg Strauss syndrome) initial presentation

A granulomatose eosinofílica com poliangiite é uma vasculite primária rara, caracterizada por hipereosinofilia, asma de surgimento tardio e granulomas eosinofílicos extravasculares. Relatamos um caso apresentado inicialmente com infarto do miocárdio e que, ulteriormente, teve prosseguimento apenas com asma, manifestações cutâneas e neuropatia periférica. Os parâmetros laboratoriais revelaram hipereosinofilia com um padrão perinuclear negativo de autoanticorpos citoplásmicos antineutrófilos (p-ANCA). A biópsia de pele demonstrou vasculite leucocitoclástica com infiltração eosinofílica, diante de uma angiografia coronária normal. Os sintomas do paciente melhoraram com metilprednisolona IV, pulsoterapia com ciclofosfamida e azatioprina.

Eosinophilic granulomatosis with polyangiitis is a rare primary vasculitic disease characterized by hypereosinophilia, late onset asthma and extravascular eosinophil granulomas. We report a case presented initially with acute myocardial infarction which later only proceed with asthma, skin manifestations and peripheral neuropathy. Laboratory parameters showed hypereosinohpilia with negative perinuclear pattern of antineutrophil cytoplasmic autoantibodies (p-ANCA). Skin biopsy showed leucocytoclastic vasculitis with eosinophilic infiltration while coronary angiography was normal. The patient's symptoms improved with IV methylprednisolone, pulse cyclophosphamide and azathioprine.

Estenosis subglótica y granulomatosis con poliangeítis (Wegener) en dos casos: Report of two cases / Subglottic tracheal stenosis in Wegener disease

Granulomatosis with polyangiitis (GPA) or Wegener's disease is characterized by a granulomatous vasculitis of the upper and lower airways and kidney. It involves the lower respiratory tract causing subglottic tracheal stenosis, which occurs in approximately 22% of patients. We report two females aged 40 and 52 years, admitted to the hospital with a subglottic tracheal stenosis. Their symptoms and management are reviewed. The frst patient responded to rituximab. The second patient required a tracheostomy.

Diagnóstico diferencial de nódulos pulmonares cavitados: a propósito de un caso clínico / Differential diagnosis of cavitary pulmonary nodules: a propos of a clinical case

El diagnóstico diferencial de nódulos pulmonares cavitados constituye un gran desafo en el cual, la clínica, la imagenología y los exámenes de laboratorio permiten una orientación etiológica en cutro grandes grupos: infecciosa, neoplásica, reumatológica y miscelánea. Presentamos el caso de una paciente gran fumadora y portadora de una diabetes mellitus descompensada, con nódulos pulmonares cavitados, en la cual el contexto clínico obligaba a plantear ciertas etiologías como las infecciosas y neoplásicas, pero cuya biopsia fue compatible con Granulomatosis con Poliangeítis (ex Granulomatosis de Wegener), sin una clínica ni exámenes de laboratorio concordantes con dicho hallazgo.

The differential diagnosis of cavitary pulmonary nodules is a great challenge, where the clinical context in addition to the image studies and laboratory tests are part of the key tools to guide the diagnostic process through 4 major etiological groups: infectious, neoplastic, rheumatologic and miscellaneous. We describe a case of a heavy smoker and complicated diabetic patient with cavitary pulmonary nodules, with a clinical context that induces certain etiologies such as infectious and neoplastic, but whose biopsy was compatible with Granulomatosis with polyangiitis (ex Wegener 's granulomatosis), without a clinical exam nor laboratory tests suggesting this finding.

Pulmonary renal syndrome in a case of wegener´s granulomatosis.

We report a case of a 42-year-old patient who presented with Wegener’s granulomatosis complicated by pulmonary renal syndrome, i.e., diffuse alveolar haemorrhage and rapidly progressive crescentic glomerulonephritis. The patient was treated with plasmapheresis and immunosuppressive drugs — intravenous cyclophosphamide and methyl prednisolone. The clinical, haematological and biochemical parameters improved substantially and remission is achieved.

Mastoidite e paralisia facial como manifestações iniciais de Granulomatose de Wegener / Mastoiditis and facial paralysis as initial manifestations of Wegener's Granulomatosis

A Granulomatose de Wegener (GW) é caracterizada por granulomas necrotizantes e vasculite. Sem tratamento a doença tem prognóstico pobre com índice de mortalidade de 90% em 2 anos. Diversos autores citam as manifestações otológicas no curso da GW, entretanto não é especificado em que momento da doença elas apareceram, isto é, se como manifestação inicial ou subsequente a outros achados. Objetivo: Descrever três casos confirmados de GW que apresentaram inicialmente mastoidite e evoluíram com paralisia facial periférica (PFP). Material e Método: Estudo de série de casos. Pacientes diagnosticados com GW que apresentaram inicialmente manifestações otológicas são descritos. Resultados: Os três casos descritos abriram o quadro com otalgia, otorreia e hipoacusia unilateral, associada a paralisia facial periférica ipsilateral. Tiveram resposta inadequada aos tratamentos instituídos o que motivou uma investigação de outras doenças associadas. Nessas circunstâncias, detectaram-se títulos positivos de ANCA-C em todos pacientes, confirmando-se o diagnóstico de GW, após período variável de investigação. Institui-se o tratamento para GW observando-se melhora do quadro clínico, regressão da PFP e melhora parcial dos limiares auditivos. Conclusão: Complicações de otites médias agudas (mastoidite e PFP) refratárias as terapêuticas habituais impõem a investigação de doenças associadas e a GW deverá ser pesquisada para que se possa fazer o diagnóstico o mais precocemente possível, alterando desta forma o prognóstico destes pacientes.

Wegener's Granulomatosis (WG) is characterized by necrotizing granulomas and vasculitis. If left untreated, the prognosis is poor - a 90% mortality rate within 2 years. Several authors have described the otologic manifestations of WG; these authors, however, have not mentioned the stage of the disease in which these findings present - whether as initial manifestations or subsequent to other findings. Aim: To describe three confirmed cases of WG with mastoiditis as the first manifestation, progressing to peripheral facial paralysis (PFP). Material and Method: A clinical series study. Patients diagnosed with WG that initially presented with otologic findings are described. Results: The three cases presented with unilateral otalgia, otorrhea, and hearing loss associated with ipsilateral PFP. None recovered in spite of the treatment; an investigation of associated diseases was therefore undertaken. Positive ANCA-C titers where detected in all patients, confirming the diagnosis of WG. Clinical improvement was seen after treatment of WG; the PFP regressed and hearing thresholds improved partially. Conclusion: Complications of otitis media (mastoiditis and PFP) that do not respond to the usual treatment require an investigation of associated diseases; WG should be included for an early diagnosis to change the prognosis in these patients.

Comprometimento da árvore respiratória na granulomatose de Wegener / Laryngeal and tracheobronchial involvement in Wegener's granulomatosis

INTRODUÇÃO: A granulomatose de Wegener (GW) é uma forma de vasculite sistêmica que envolve primariamente as vias aéreas superiores e inferiores e os rins. As manifestações mais frequentes nas vias aéreas são estenose subglótica e inflamações, estenoses da traqueia e dos brônquios. A visualização endoscópica das vias aéreas é a melhor ferramenta para avaliação, diagnóstico e manejo dessas alterações. OBJETIVOS: Descrever as alterações endoscópicas encontradas na mucosa das vias aéreas de um grupo de pacientes com GW submetido à broncoscopia no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) e relatar as intervenções terapêuticas broncoscópicas utilizadas em alguns casos. MÉTODOS: Foram estudados 15 pacientes com diagnóstico de GW provenientes do Ambulatório de Vasculites da Disciplina de Pneumologia do HC-FMUSP, encaminhados para a realização de broncoscopia no serviço de Endoscopia Respiratória do HC-FMUSP no período de 2003 a 2007. RESULTADOS: Dos 15 pacientes avaliados, 11 eram mulheres (73,33 por cento) com idade média de 34 ± 11,5 anos. Foram encontradas alterações das vias aéreas em 80 por cento dos pacientes, e o achado endoscópico mais frequente foi estenose subglótica (n = 6). Realizou-se broncoscopia terapêutica em três pacientes com estenose subglótica e em outros três com estenose brônquica, todos apresentando bons resultados. CONCLUSÃO: A broncoscopia permite diagnóstico, acompanhamento e tratamento das lesões de vias aéreas na GW, constituindo-se um recurso terapêutico pouco invasivo em casos selecionados.

INTRODUCTION: Wegener's granulomatosis (WG) is a form of systemic vasculitis that involves primarily the upper and lower airways and the kidneys. The most frequent airway manifestations include subglottic stenosis and inflammation, and tracheal and bronchial stenoses. The endoscopic visualization of the airways is the best tool for assessing, diagnosing and managing those changes. OBJECTIVES: To describe the endoscopic abnormalities found in the airway mucosa of a group of patients with WG undergoing bronchoscopy at Hospital das Clínicas of the Faculdade de Medicina, Universidade de São Paulo (HC-FMUSP), and to report the therapeutic bronchoscopic interventions used in some cases. METHODS: The study assessed 15 patients diagnosed with GW from the Vasculitis Outpatient Clinic of the Department of Pulmonology, HC-FMUSP, referred for bronchoscopy at the Service of Respiratory Endoscopy, HC-FMUSP, from 2003 to 2007. RESULTS: Fifteen patients were studied [11 females (73.33 percent)]; mean age, 34 ± 11.5 years. Airway changes were found in 80 percent of the patients, and the most frequent endoscopic finding was subglottic stenosis (n = 6). Therapeutic bronchoscopy was performed in three patients with subglottic stenosis and in other three patients with bronchial stenosis, all showing good results. CONCLUSION: Bronchoscopy allows for diagnosing, monitoring, and treating the airway lesions in WG, being a minimally invasive therapeutic option in selected cases.

Panhypopituitarism due to Wegener's granulomatosis / Pan-hipopituitarismo causado pela granulomatose de Wegener

Wegener's granulomatosis (WG) is a multi-system necrotizing granulomatous vasculitis which classically affects the upper respiratory tract, lungs and kidneys. Pituitary participation has been described in 24 patients in the literature to date. The aim of this article is to report a case of pituitary involvement in WG, and to present a literature review on this association. We present a female patient with WG who evolved with central diabetes insipidus (CDI), panhypopituitarism, and mild hyperprolactinemia. MRI showed an infiltrative pattern. Pituitary involvement has been reported in around 1 percent of patients with WG, mostly in women. It is represented by CDI and hypopituitarism. MRI generally shows pituitary enlargement, stalk thickening and loss of hyperintensity of the neurohypophysis. Permanent endocrine therapy is generally needed. WG should be considered in cases of CDI and hypopituitarism, essentially if a vasculitis is suspected and more common sellar disorders have been ruled out.

A granulomatose de Wegener (GW) é uma vasculite necrotizante multissistêmica que afeta classicamente o trato respiratório superior, pulmões e rins. O envolvimento da hipófise foi descrita em 24 pacientes na literatura, até hoje. O objetivo deste artigo é relatar um caso de GW com envolvimento pituitário, e apresentar uma revisão da literatura sobre esta associação. Apresentamos uma paciente com GW que evoluiu para diabetes insipidus central (DIC), panhipopituitarismo e leve hiperprolactinemia. A RM mostrou um padrão infiltrativo. O envolvimento da hipófise foi relatado em cerca de 1 por cento dos pacientes cm GW, na sua maioria mulheres. A desordem é representada por DIC e hipopituitarismo. A RM geralmente mostra o aumento da hipófise, aumento da espessura da haste, e perda da hiperintensidade da neurohipofise. Normalmente, é necessária terapia endócrina permanente. A GW é geralmente considerada nos casos de DIC e hipopituitarismo, essencialmente se há suspeita de vasculite e quando desordens selares mais comuns foram descartadas.

Meningitis granulomatosa, glomerulonefritis rápidamente progresiva y vasculitis / Granulomatous meningitis, crescentic glomerulonephritis and vasculitis

El compromiso meníngeo es una manifestación infrecuente de la granulomatosis de Wegener. Puede manifestarse como cefalea con hiperproteinorraquia y engrosamiento de la duramadre con aspecto granulomatoso, que se observa en la resonancia magnética. Presentamos un varón de 57 años con granulomatosis de Wegener que debutó con compromiso de vías aéreas superiores, oídos, órbitas y meningitis granulomatosa asintomática y que posteriormente evolucionó con mononeuritis múltiple y glomerulonefritis crescéntica ANCA positiva. La presencia de ANCA y el compromiso sistémico (vías aéreas superiores, oído, órbitas, nervios periféricos, duramadre y glomerulonefritis rápidamente progresiva) permitieron en este caso llegar a un diagnóstico de certeza e iniciar el tratamiento inmunosupresor combinado (corticoides y ciclofosfamida). Evolucionó con remisión clínica y serológica (negativización de ANCA), pero persistiendo leve deterioro secuelar auditivo y de la función renal, sin recidiva de la enfermedad de base.

Meningeal involvement is an infrequent manifestation of Wegener's granulomatosis. Clinical manifestations can be headache with high protein level in the cerebrospinal fluid and an enhanced MRI signal of granulomatous thickening of the duramater in the brain. We report a 57 year-old male with Wegener granulomatosis with onset manifestations of asymptomatic granulomatous meningitis, upper respiratory tract, ears and orbits involvement. He progressively developed ANCA positive multiple mononeuritis and crescentic glomerulonephritis. The diagnostic confirmation of Wegener's granulomatosis based on a positive ANCA test and on the evidence of systemic disease (crescentic glomerulonephritis and involvement of the upper respiratory tract, ears, orbits, peripheral nerves and duramater) allowed a prompt initiation of aggressive immunosuppressive treatment with systemic cyclophosphamide and high - dosis corticosteroids. The patient entered into a sustained clinical remission with mild residual neurosensorial hearing loss and renal failure.

Suppurative dacroadenitis causing ocular sicca syndrome in classic Wegener’s granulomatosis.

Wegener’s granulomatosis (WG) is a multisystem vasculitic disorder which can commonly afflict various components of the eye. Here we describe some unusual ocular manifestations of the disease in one patient. A young male with history of upper respiratory tract symptoms including epistaxis, nasal stuffiness and maxillary sinus pain presented with bilateral lacrimal gland abscess and ptosis. Lacrimal gland biopsy revealed granulomatous vasculitis. Lung cavities, positive cytoplasmic-antineutrophil cytoplasmic antibodies and high titers of serine proteinase-3 antibodies confirmed the diagnosis of WG. The patient developed dry eyes after a month of first presentation. There was no dryness of mouth, suggesting the absence of salivary gland involvement, and antinuclear antibodies as well as antibodies against Ro and La antigens classical of primary Sjogren’s syndrome were absent. Granulomatous vasculitis of lacrimal gland leading to abscess formation and dryness of eyes has not been described in WG and reflects the aggressive nature of inflammatory process in this disease.

Otomastoiditis como manifestación clínica inicial de granulomatosis de Wegener / Otomastoiditis as an initial clinical manifestation of Wegener's granulomatosis

La granulomatosis de Wegener (GW) forma parte del grupo de vasculitis primarias, de vasos pequeños y medianos, asociadas a anticuerpos anticitoplasma de neutrófilos (ANCA). Esta enfermedad puede afectar cualquier órgano, especialmente vías aéreas superiores, inferiores y el riñón. Muy raramente la primera y única manifestación clínica de GW generalizada es la otomastoiditis. Presentamos el caso de un paciente que inició su enfermedad con una inflamación del oído medio, sin respuesta al tratamiento habitual. Posteriormente agregó compromiso nasal, pulmonar y renal. La determinación de anticuerpos anticitoplasma de neutrófilos y la biopsia transbronquial confirmaron el diagnóstico de GW. Comunicamos este caso para referir que la otomastoiditis del adulto, refractaria al tratamiento habitual, puede raramente ser la primera y única manifestación clínica de la GW.

Wegener's granulomatosis (WG) forms part of a group of primary vasculitis of the small and medium-sized blood vessels, associated with antineutrophil cytoplasmic antibodies (ANCA). This disease may affect any body organ, especially the upper and lower airways and the kidneys. Hardly ever is otomastoiditis the first and only clinical manifestation of generalized Wegener's granulomatosis. We present the case of a patient whose disease started with the inflammation of the middle ear, which was unresponsive to the usual treatment. Later he developed nasal, pulmonary and renal compromise. The determination of ANCA and a transbronchial biopsy confirmed the diagnosis of WG. We report this case to express the view that otomastoiditis in adults, which is refractory to the usual treatment, may seldom be the first and only clinical manifestation of WG.

Trombose em artérias pulmonares pequenas e médias em granulomatose de Wegener: um estudo com microscopia confocal por varredura a laser / Thrombosis in small and medium-sized pulmonary arteries in Wegener's granulomatosis: a confocal laser scanning microscopy study

OBJETIVO: A granulomatose de Wegener (GW) pode causar dano nas células endoteliais e fenômenos tromboembólicos. Entretanto, poucos estudos analisaram a microcirculação pulmonar - artérias pulmonares de pequeno/médio calibre (APPMC) - em pacientes com GW. O objetivo deste estudo foi quantificar trombos de fibrina em amostras de APPMC de pacientes com GW. MÉTODOS: Analisamos 24 APPMC de seis pacientes com GW e 16 APPMC de quatro pacientes controles sem WG. Utilizamos CD34 para a marcação do endotélio em todas as amostras e microscopia confocal a laser para detectar trombos de fibrina intravasculares. Calculamos a área total do vaso, a área livre do lúmen e a área trombótica. RESULTADOS: A média da área total do vaso foi similar no grupo GW e no grupo controle (32.604 µm² vs. 32.970 µm², p = 0,8793). Trombos foram identificados em 22 das 24 APPMC (91,67 por cento) no grupo GW, e em nenhuma do grupo controle (p < 0,0001; OR = 297 (IC95 por cento: 13,34-6.612). A média da área trombótica foi maior no grupo GW do que no grupo controle (10.068 µm² vs. 0.000 µm², p < 0,0001). Em contraste, a média da área livre do lúmen foi menor no grupo GW que no grupo controle (6.116 µm² vs. 24.707 µm², p < 0,0001). CONCLUSÕES: A microscopia confocal a laser mostrou uma associação significante entre trombose microvascular pulmonar e GW. Isso sugere um possível papel da trombose microvascular na fisiopatologia da GW pulmonar, evocando o potencial benefício da anticoagulação na GW pulmonar. Entretanto, novos estudos são necessários para confirmar nossos achados, assim como um ensaio clínico randomizado a fim de testar o papel da anticoagulação no tratamento de pacientes com GW pulmonar.

OBJECTIVE: Wegener's granulomatosis (WG) can cause endothelial cell damage and thromboembolic events. Nevertheless, there have been few studies on the pulmonary microcirculation-small and medium-sized pulmonary arteries (SMSPA)-in patients with WG. The objective of this study was to quantify fibrin thrombi in the SMSPA of patients with WG. METHODS: We analyzed 24 SMSPA samples collected from six patients with WG and 16 SMSPA samples collected from four patients without WG. In all samples, we used the endothelial cell marker CD34 and confocal laser scanning microscopy in order to detect intravascular fibrin thrombi. We calculated the total vessel area, the free lumen area, and the thrombotic area. RESULTS: The mean total vessel area was similar in the WG and control groups (32,604 µm² vs. 32,970 µm², p = 0.8793). Thrombi were present in 22 (91.67 percent) of the 24 WG group samples and in none of the control group samples (p < 0.0001; OR = 297; 95 percent CI: 13.34-6,612). The mean thrombotic area was greater in the WG group samples than in the control group samples (10,068 µm² vs. 0.000 µm²; p < 0.0001). In contrast, the mean free lumen area was smaller in the WG group samples than in the control group samples (6,116 µm² vs. 24,707 µm²; p < 0.0001). CONCLUSIONS: Confocal laser scanning microscopy revealed a significant association between pulmonary microvascular thrombosis and WG. This suggests a possible role of microvascular thrombosis in the pathophysiology of pulmonary WG, evoking the potential benefits of anticoagulation therapy in pulmonary WG. However, further studies are needed in order to confirm our findings, and randomized clinical trials should be conducted in order to test the role of anticoagulation therapy in the treatment of patients with pulmonary WG.