Comparison between enzyme-linked immunosorbent assay and indirect immunofluorescence for detection of antineutrophil cytoplasmic antibodies / Comparação entre os métodos de ensaio imunoenzimático e imunoflurescência indireta para a pesquisa de anticorpos anticitoplasma de neutrófilos

ABSTRACT Objective To evaluate the performance of enzyme-linked immunosorbent assay and indirect immunofluorescence methods for the detection of antineutrophil cytoplasmic antibodies in a routine clinical laboratory setting. Methods A total of 227 samples were tested by indirect immunofluorescence and enzyme-linked immunosorbent assay with antigen specificity for antiproteinase 3 and antimyeloperoxidase. The proportions of positive samples were compared by McNemar hypotheses and agreement was described by Cohen's Kappa coefficient. Results The agreement of the tests was 96.5%, and the Kappa coefficient obtained was 0.70 (95%CI: 0.50-0.90; p<0.001). Considering indirect immunofluorescence as the gold standard, the sensitivity of the enzyme-linked immunosorbent assay was 0.62 and the specificity was 0.99, with diagnostic accuracy in 96% of cases. Some samples were negative in enzyme-linked immunosorbent assay and positive in indirect immunofluorescence. This situation occurred in all immunofluorescence patterns, but particularly in atypical patterns. Two samples with antiproteinase 3 positivity were considered negative in indirect immunofluorescence. Conclusion The enzyme-linked immunosorbent assay had high specificity but lower sensitivity. The performance of indirect immunofluorescence increases diagnostic sensitivity, while the search for antiproteinase 3 by enzyme-linked immunosorbent assay may also add diagnostic power.

RESUMO Objetivo Avaliar o desempenho das metodologias de ensaio imunoenzimático e imunofluorescência indireta para a detecção de anticorpos anticitoplasma de neutrófilos em um contexto de laboratório clínico de rotina. Métodos Foram testadas 227 amostras pelas metodologias de imunofluorescência indireta e ensaio imunoenzimático com especificidades para anticorpos antiproteinase-3 e antimieloperoxidase. As proporções de amostras positivas foram comparadas por hipóteses de McNemar, e a concordância foi descrita pelo coeficiente Kappa de Cohen. Resultados A concordância dos testes foi 96,5%, e o coeficiente Kappa obtido foi 0,70 (IC95%: 0,50-0,90; p<0,001). Utilizando a imunofluorescência indireta como padrão-ouro, a sensibilidade do ensaio imunoenzimático foi de 0,62 e a especificidade, 0,99, com acurácia diagnóstica em 96% dos casos. Algumas amostras apresentaram resultados negativos por ensaio imunoenzimático e positivos por imunofluorescência. Isso ocorreu em amostras com vários padrões de fluorescência, mas particularmente nos casos com padrões atípicos. Duas amostras com positividade antiproteinase 3 foram consideradas negativas por imunofluorescência. Conclusão Os métodos de ensaio imunoenzimático tiveram alta especificidade, mas sensibilidade inferior. A realização da imunofluorescência indireta aumenta a sensibilidade diagnóstica, ao mesmo tempo que a pesquisa de antiproteinase 3 por ensaio imunoenzimático também pode agregar poder diagnóstico.

Anca-associated crescentic glomerulonephritis in a child with isolated renal involvement / Glomerulonefrite rapidamente progressiva associada a ANCA em uma criança com acometimento renal isolado

ABSTRACT Pauci-immune glomerulonephritis (GN) is more common in elderly people compared to children and the etiology is not completely understood yet. Antineutrophil cytoplasmic antibody (ANCA) positivity occurs in 80% of the patients. We report a case of a 7-year-old girl who presented with malaise and mildly elevated creatinine diagnosed as ANCA-associated pauci-immune crescentic glomerulonephritis with crescents in 20 of 25 glomeruli (80%). Of these 20 crescents, 12 were cellular, 4 fibrocellular, and 4 globally sclerotic. She did not have purpura, arthritis, or systemic symptoms and she responded well to initial immunosuppressive treatment despite relatively severe histopathology. The patient was given three pulses of intravenous methylprednisolone (30 mg/kg on alternate days) initially and continued with cyclophosphamide (CYC; 2 mg/kg per day) orally for 3 months with prednisone (1 mg/kg per day). In one month, remission was achieved with normal serum creatinine and prednisone was gradually tapered. The case of this child with a relatively rare pediatric disease emphasizes the importance of early and aggressive immunosuppressive treatment in patients with renal-limited ANCA-associated pauci-immune crescentic GN even if with a mild clinical presentation. As in our patient, clinical and laboratory findings might not always exactly reflect the severity of renal histopathology and thus kidney biopsy is mandatory in such children to guide the clinical management and predict prognosis.

RESUMO A glomerulonefrite (GN) pauci-imune é mais comum em idosos em comparação com crianças, e a etiologia ainda não é completamente compreendida. A positividade do anticorpo citoplasmático antineutrófilo (ANCA) ocorre em 80% dos pacientes. Relatamos o caso de uma menina de 7 anos de idade que apresentou mal-estar e creatinina discretamente elevada, diagnosticada como glomerulonefrite rapidamente progressiva pauci-imune associada a ANCA com crescentes em 20 dos 25 glomérulos (80%). Destes 20 crescentes, 12 eram celulares, 4 fibrocelulares e 4 globalmente escleróticos. Ela não apresentava púrpura, artrite ou sintomas sistêmicos e respondeu bem ao tratamento imunossupressor inicial, apesar da histopatologia relativamente grave. A paciente recebeu três pulsos de metilprednisolona intravenosa (30 mg/kg em dias alternados) inicialmente e continuou com ciclofosfamida (2 mg/kg por dia) por via oral durante 3 meses com prednisona (1 mg/kg por dia). Em um mês, a remissão foi alcançada com creatinina sérica normal e a prednisona foi gradualmente reduzida. O caso desta criança com uma doença pediátrica relativamente rara enfatiza a importância do tratamento imunossupressor precoce e agressivo em pacientes com GN rapidamente progressiva renal associada à ANCA, mesmo com uma apresentação clínica leve. Como em nossa paciente, os achados clínicos e laboratoriais podem nem sempre refletir exatamente a gravidade da histopatologia renal e, assim, a biópsia renal é obrigatória nessas crianças para orientar a conduta clínica e auxiliar no prognóstico.

ANCA associated vasculitis: experience of a tertiary care referral center / Vasculite associada a ANCA: experiência de um centro de referência de atendimento terciário

ABSTRACT Background and objectives: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a small vessel vasculitis with insufficient epidemiologic estimates in the United States. We aimed to determine demographic and clinical features of ANCA associated vasculitis patients presenting to a large tertiary care referral center in Upstate New York. Design, setting, participants, and measurements: A retrospective analysis of cases with pauci-immune GN on renal biopsy and clinical diagnosis of ANCA vasculitis presenting over 11 years was conducted. Outcomes of interest were: demographics, ANCA antibody positivity, patient and renal survival, and regional trends. Results: 986 biopsies were reviewed, 41 cases met the criteria for inclusion: 18 GPA, 19 MPA, and 4 double positive (anti-GBM disease plus ANCA vasculitis). Mean age at presentation was 52.4 years (SD 23.7), 23 (56%) were male and median creatinine was 2.6 mg/dL. The median patient follow up was 77 weeks (IQR 10 - 263 weeks), with a 3-month mortality rate of 5.7% and a 1-year estimated mortality rate of 12%. Thirteen patients required hemodialysis at the time of diagnosis; 7 patients came off dialysis, with median time to renal recovery of 4.86 weeks (IQR 1.57 - 23.85 weeks). C-ANCA positivity (p < 0.001) and C-ANCA plus PR3 antibody pairing (p = 0.005) was statistically significant in GPA versus MPA. P-ANCA positivity was observed in MPA versus GPA (p = 0.02) and double positive versus GPA (p = 0.002), with P-ANCA and MPO antibody pairing in MPA versus GPA (p = 0.044). Thirty-seven of the 41 cases were referred locally, 16 cases were from within a 15-mile radius of Albany, Schenectady, and Saratoga counties. Conclusions: ANCA vasculitis is associated with end stage renal disease and increased mortality. Our study suggests the possibility of higher regional incidence of pauci-immune GN in Upstate New York. Further studies should investigate the causes of clustering of cases to specific regions.

RESUMO Introdução e objetivos: A vasculite associada a anticorpos anticitoplasma de neutrófilo (ANCA) é uma vasculite de pequenos vasos com estimativas epidemiológicas insuficientes nos Estados Unidos. Nosso objetivo foi determinar características demográficas e clínicas de pacientes com vasculite associada à ANCA, apresentando-se a um grande centro de referência de atendimento terciário em Upstate New York. Formato, cenário, participantes e medidas: Foi realizada uma análise retrospectiva dos casos de GN pauci-imune em biópsias renais e diagnóstico clínico de vasculite ANCA por mais de 11 anos. Os resultados de interesse foram: dados demográficos, positividade de anticorpos ANCA, sobrevidas renal e de pacientes e tendências regionais. Resultados: 986 biópsias foram revisadas, 41 casos preencheram os critérios de inclusão: 18 GPA, 19 PAM, e 4 duplo-positivos (doença anti-MBG com vasculite ANCA). A média de idade na apresentação foi de 52,4 anos (DP 23,7), 23 (56%) eram do sexo masculino e mediana de creatinina de 2,6 mg/dL. O acompanhamento mediano dos pacientes foi de 77 semanas (IQR 10 - 263 semanas), com uma taxa de mortalidade de 3 meses de 5,7% e uma taxa de mortalidade estimada em 1 ano de 12%. Treze pacientes necessitaram de hemodiálise no momento do diagnóstico; 7 pacientes saíram da diálise, com tempo médio para recuperação renal de 4,86 semanas (IQR 1,57 - 23,85 semanas). A positividade para C-ANCA (p < 0,001) e o pareamento de anticorpos C-ANCA mais PR3 (p = 0,005) foram estatisticamente significantes em GPA versus PAM. A positividade de P-ANCA foi observada em PAM versus GPA (p = 0,02) e duplo positivo versus GPA (p = 0,002), com pareamento de anticorpos P-ANCA e MPO em PAM versus GPA (p = 0,044). Trinta e sete dos 41 casos foram encaminhados localmente, 16 casos foram de dentro de um raio de 15 milhas dos condados de Albany, Schenectady e Saratoga. Conclusões: A vasculite por ANCA está associada à doença renal terminal e aumento da mortalidade. Nosso estudo sugere a possibilidade de maior incidência regional de GN pauci-imune no norte do estado de Nova York. Novos estudos devem investigar as causas do acúmulo de casos em regiões específicas.

Antineutrophil cytoplasmic antibodies in Chinese patients with tuberculosis

Abstract INTRODUCTION: Based on reports, infection with Mycobacterium tuberculosis is believed to induce the development of antibodies that are considered to be biological indicators for the diagnosis of some other diseases. However, conflicting results have been published regarding the presence of antineutrophil cytoplasmic antibodies (ANCAs) in patients with tuberculosis. We aim to study the seroprevalence of ANCA in a population of Chinese patients with tuberculosis, which may lead to the misdiagnosis of vasculitic disorders. METHODS: The study was conducted from January 2016 to May 2017 to evaluate the presence of ANCA in 103 Chinese patients using indirect immunofluorescent assay. An enzyme-linked immunosorbent assay was performed for anti-myeloperoxidase (MPO) and anti-proteinase 3 (PR3) detection. RESULTS: Perinuclear ANCA (p-ANCA) was detected in 4.8% (5/103) of patients, whereas cytoplasmic ANCA (c-ANCA) was not detected; 1.9% (2/103) of patients with tuberculosis was positive for anti-MPO antibodies, and none had anti-PR3 antibodies. Both anti-MPO-positive patients were diagnosed with ANCA-associated vasculitides. CONCLUSIONS: ANCA positivity may be more related to vasculitis and immunological disorders than to a M. tuberculosis infection. Therefore, to improve diagnostic accuracy, patients with M. tuberculosis who are ANCA positive should be investigated for concurrent diseases, including the effects of drugs. Therefore, even in tuberculosis epidemic area, ANCA seropositivity, detected by ELISA, is still more suggestive of ANCA-associated vasculitides.

Compromiso renal en vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos. Recomendaciones de consenso de las Sociedades Chilenas de Nefrología y Reumatología / Renal involvement in antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides. Recommendations of the Chilean Societies of Nephrology and Rheumatology

Renal involvement is a frequent complication in antineutrophil cytoplasmic antibodies (ANCA)associated vasculitides, adding morbidity and mortality, such as chronic kidney disease and the need for renal replacement therapy. With the aim of reaching a consensus on relevant issues regarding the diagnosis, treatment and follow-up of patients with these diseases, the Chilean Societies of Nephrology and Rheumatology formed a working group that, based on a critical review of the available literature and their experience, raised and answered consensually a set of questions relevant to the subject. This document includes aspects related to the clinical diagnosis, the histological characteristics, the therapeutic alternatives to induce and maintain the remission of the disease, relapse surveillance strategies and complementary therapies.

ANCA-Positive pauci-immune crescentic glomerulonephritis in a patient with systemic lupus erythematosus / Glomerulonefrite rapidamente progressiva ANCA-Positiva pauci-imune em paciente com lúpus eritematoso sistêmico

Abstract The pauci-immune crescentic glomerulonephritis (PICGN) is generally associated with small-vessel vasculitis with a few reported cases associated with other autoimmune diseases such as Systemic Lupus Erythematosus (SLE). We present the case of a female 34-year-old patient with acute kidney injury symptoms with indication for renal replacement therapy in the context of clinical SLE diagnosis. A kidney biopsy was conducted and it was found that most glomeruli showed some segmental sclerosis with synechia to the Bowman's capsule. 67% of the glomeruli had fibroepithelial crescents. Moreover, the interstitial space had a moderate lymphomononuclear infiltration and mild fibrosis. In the arterioles, there were walls thickened by subintimal sclerosis. Direct immunofluorescence detected limited IgM and C3 deposits in capillary loops and negative mensangium for IgG, IgA and C1q. A therapy using corticosteroids and intravenous cyclophosphamide was initiated with stable evolution. PICGN associated with SLE is a rare pathology with clinical presentation, varied evolution and without a standard medical treatment.

Resumo A glomerulonefrite rapidamente progressiva pauci-imune apresenta-se geralmente associada a vasculite de pequenos vasos, com poucos casos associados a outras doenças imunes como o lúpus eritematoso sistêmico (LES). Apresentamos no presente artigo o caso de uma mulher de 34 anos de idade com sintomas de insuficiência renal aguda e indicação de terapia renal substitutiva, no contexto de diagnóstico clínico de LES. A biópsia renal realizada revelou que a maioria dos glomérulos apresentavam um certo grau de esclerose segmentar e sinéquias com a cápsula de Bowman. Sessenta e sete por cento dos glomérulos apresentava crescentes fibroepiteliais. Além disso, o espaço intersticial exibia infiltrado linfomononuclear moderado e fibrose discreta. Nas arteríolas, as paredes encontravam-se espessadas por esclerose subintimal. A imunofluorescência direta detectou depósitos limitados de IgM e C3 nas alças capilares e mesângio negativo para IgG, IgA e C1q. Tratamento com corticosteroides e ciclofosfamida endovenosa foi iniciado com evolução estável. A glomerulonefrite rapidamente progressiva pauci-imune associada a LES é uma patologia rara com manifestação clínica e evolução variada, sem tratamento clínico padronizado.

Anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus

Abstract: Background: The clinical significance of anti-neutrophil cytoplasmic antibodies in patients with new-onset systemic lupus erythematosus, especially in systemic disease accompanied by interstitial lung disease remains to be elucidated. Objectives: This study was designed to investigate the role of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients. Methods: A hundred and seven patients with new-onset SLE were enrolled. Presence of anti-neutrophil cytoplasmic antibodies in the sera was assessed by indirect immunofluorescence as well as enzyme linked immunosorbent assay against proteinase-3 and myeloperoxidase. Clinical features and laboratory parameters of patients were also recorded. All patients were subjected to chest X-ray, chest high-resolution computed tomography and pulmonary function test. Results: Forty-five systemic lupus erythematosus patients (45/107, 42%) were seropositive for anti-neutrophil cytoplasmic antibodies. Compared with anti-neutrophil cytoplasmic antibodies-negative patients, the anti-neutrophil cytoplasmic antibodies-positive patients had significantly higher incidence of renal involvement, anemia, and Raynaud's phenomenon as well as decreased serum level of complement 3/complement 4 and elevated erythrocyte sedimentation rate. In addition, there was a positive correlation between serum anti-neutrophil cytoplasmic antibodies level and disease activity of systemic lupus erythematosus. Furthermore, prevalence of interstitial lung disease in the anti-neutrophil cytoplasmic antibodies -positive patients (25/45, 55.6%) was obviously higher than that in the anti-neutrophil cytoplasmic antibodies-negative patients (15/62, 24.2%). Study limitations: The sample size was limited and the criteria for screening new-onset systemic lupus erythematosus patients might produce bias. Conclusions: The level of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients correlates positively with the disease activity and the prevalence of interstitial lung disease.

ANCA-positive vasculitis: Clinical implications of ANCA types and titers / Vasculite ANCA positiva: implicações clínicas dos tipos e dos títulos de ANCA

SUMMARY Introduction: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disease that can affect multiple organs, the kidney being one of the most affected. Apart from the diagnostics value of ANCA, they have also been advocated as biomarkers of the disease activity. Recently, the genetic changes found in polyangiitis associated with serine-protease proteinase 3 (PR3)-ANCA or myeloperoxidase (MPO)-ANCA raised the possibility of immune-pathogenic and therapeutic differences. Objective: To identify differences in the number of relapses, inflammatory markers, outcomes and renal histology related to the types of ANCA. To analyze the implications of ANCA titers in prognosis. Method: A retrospective observational study in a Portuguese tertiary hospital. Results: There were no differences in the progression of renal function, histological pattern and initial treatment with regard to ANCA subtypes. As for the evaluated parameters, there were no significant differences according to the types of ANCA, except for mean CRP values within the normal range, which was 6.3±1.3 mg/L for MPO-ANCA and 12.4±10.14 mg/L for PR3-ANCA (p=0.04). We found that 66.7% of the MPO-ANCA-positive showed no relapses versus 40% in the case of PR3-ANCA-positive. There was no correlation between the ANCA titers at presentation, during remission, and in the last evaluation, and the number of relapses. Conclusion: PR3-ANCA patients have a mean CRP value within the normal range significantly higher than that of MPO-ANCA patients (p=0.04), which seems to reveal greater inflammatory activity in the first.

RESUMO Introdução: a vasculite associada aos anticorpos anticitoplasma de neutrófilos (ANCA) é uma doença autoimune que pode acometer vários órgãos, sendo o rim um dos mais afetados. Além dos ANCA serem marcadores de diagnóstico, foram também defendidos como marcadores de atividade. Recentemente as alterações genéticas encontradas entre as poliangeítes serina-protease 3 da proteinase (PR3)-ANCA ou mieloperoxidase (MPO)-ANCA levantam a possibilidade de diferenças imunopatogênicas e terapêuticas. Objetivos: identificar diferenças quanto a número de recidivas, marcadores inflamatórios, desfechos e histologia renal relativamente aos tipos de ANCA. Analisar implicações dos títulos de ANCA no prognóstico. Método: estudo retrospectivo observacional em hospital terciário português. Resultados: não se verificaram diferenças quanto à evolução da função renal, ao padrão histológico e ao tratamento inicial relativamente aos subtipos de ANCA. Nos parâmetros analíticos avaliados, não se verificaram diferenças significativas relativas aos tipos de ANCA, à exceção do valor médio de PCR no intervalo que foi de 6,3±1,3 mg/L nos MPO-ANCA e 12,4±10,14 mg/L nos PR3-ANCA (p=0,04). Verificamos que 66,7% dos MPO-ANCA positivos não apresentaram recidivas versus 40% dos PR3-ANCA positivos. Não se verificou nenhuma correlação entre os títulos de ANCA à apresentação, durante a remissão e na última avaliação com o número de recidivas. Conclusão: os indivíduos PR3-ANCA apresentaram um valor médio de PCR nos intervalos superior aos indivíduos MPO-ANCA (p=0,04), o que parece evidenciar uma maior atividade inflamatória nos primeiros.

Co-existing proteinase 3-antineutrophil cytoplasmic antibody-associated vasculitis with immunoglobulin A nephropathy

No abstract available.

Vasculite sistêmica da síndrome de Cogan associada ao PR3-ANCA. Relato de caso / Systemic vasculitis of Cogan's syndrome associated with PR3-ANCA. Case report

JUSTIFICATIVA E OBJETIVOS: A síndrome de Cogan (SC)caracteriza-se pela presença de ceratite intersticial não luética associada a manifestações de disfunção vestibulococlear. Este artigo tem como finalidade dar continuidade ao relato de caso da SC publicado nesse periódico em 2009, que mostra, agora em 2014, o acompanhamento ambulatorial durante 60 meses, os resultados laboratoriais, o tratamento realizado e faz uma breve revisão bibliográfica dos marcadores imunológicos. Também, como objetivo principal, apresentar essa rara entidade nosológica que, quando não tratada no início dos sintomas com imunossupressores, pode causar anacusia em 50% e amaurose em 10% dos pacientes e, em sua forma atípica, cursar com vasculite sistêmica. Como não encontramos citações na literatura mundial dessa associação - vasculite da SC com positividade de anticorpos dirigidos contra citoplasma de neutrófilos (c-ANCA) direcionados especificamente contra o antígeno serinaproteinase 3(PR3) - consideramos prudente novos artigos serem publicados no sentido de confirmar ou não esses achados clínico-laboratoriais. Ressaltamos que o paciente evoluiu satisfatoriamente para a cura, visto que permanece assintomático e com os exames de atividade inflamatória normais. RELATO DO CASO: Paciente do sexo masculino, 43 anos, branco, casado, comerciário,foi internado por 15 dias por apresentar hiperemia conjuntival, mialgias e febre com 30 dias de evolução. O diagnóstico foi realizado a partir do 11° dia, quando surgiram as seguintes manifestações: nistagmo, ataxia de marcha, tontura, náuseas e vômitos aos movimentos, dores articulares no punho, joelho e tornozelo esquerdos, acompanhadas de rubor e calor, acrescidas de sufusões hemorrágicas subungueais dolorosas em três dedos da mão esquerda, sugestivas de vasculite sistêmica. CONCLUSÃO: Este relato de caso apresenta aos profissionais médicos essa entidade rara, de difícil diagnóstico e de repercussões graves quando não bem tratada. Além disso,...

BACKGROUND AND OBJECTIVES: Cogan's syndrome (CS) is characterized by the occurrence of non-luetic intersticial keratitis associated with vestibulocochlear dysfunction signs. This article aims to give continuity to a report on the CS published in this journal in 2009, and proposes to show a 60-month outpatient follow-up, laboratory results and treatment prescribed, as well as to give a brief literature review on immunological markers, as far as 2014. It also has the primary aim of presenting this rare nosological entity which, if not treated with immunosuppressive drugs at the onset of symptoms, can lead to deafness in 50% of the patients and amaurosis in 10% of them, and occur concomitantly with systemic vasculitis in its atypical form. As international literature citations on the CS vasculitis association with positivity of antibodies against neutrophil cytoplasm (c-ANCA) specifically directed against cytoplasmic antigen serine proteinase 3 (PR3) have not been found, it is suggested that new articles should be published in order to either confirm or deny these clinical and laboratory findings. It is noteworthy that the patient progressed satisfactorily towards healing, and remains asymptomatic with negative inflammatory activity exam results. CASE REPORT: a 43 year-old married male Caucasian salesclerk from Piratini (RS) was hospitalized for a 15-day period showing conjunctival hyperemia, myalgia and fever following a thirty-day evolution period. Diagnosis was only reached on the 11th day when the following signs appeared: nystagmus, motor ataxia, dizziness, nausea and vomiting upon moving, joint pain in the left wrist, knee and ankle, accompanied by redness and heat, in addition to painful subungual hemorrhagic suffusions in three left-hand fingers compatible with systemic vasculitis. CONCLUSION: This case describes a rare syndrome of difficult diagnosis and serious implications when not properly treated...

Clinical features and prognostic factors of Churg-Strauss syndrome

BACKGROUND/AIMS: Churg-Strauss syndrome (CSS) is a rare systemic necrotizing small-vessel vasculitis, with accompanying bronchial asthma, eosinophilia, and eosinophilic infiltration of various tissues. The purposes of our study were to characterize the clinical features of CSS and to identify factors associated with CSS prognosis in Koreans. METHODS: Medical records were reviewed retrospectively for all physician-diagnosed CSS patients in the Seoul National University Hospital between January 1990 and March 2011. RESULTS: Data from 52 CSS patients were analyzed. The respiratory tract was the most commonly involved organ (90.4%). Renal involvement was less frequent in antineutrophilic cytoplasmic antibody (ANCA)(-) patients than in ANCA(+) patients (p = 0.048). Clinical remission occurred in 95.3% of patients, but 16.3% of them relapsed. Patients who maintained remission for more than 6 months were relatively older (median, 51 years) at diagnosis (p = 0.004), had been diagnosed in earlier stages (p = 0.027), showed more frequent respiratory involvement (p = 0.024) and generalized symptoms (p = 0.039), and showed less frequent cutaneous involvement (p = 0.030) than those who did not achieve persistent (> 6 months) remission. Patients who achieved persistent remission also showed higher C-reactive protein (CRP) levels (p = 0.031) than those who did not. CONCLUSIONS: ANCA(-) CSS patients showed less frequent renal involvement. Characteristics of good responders were older age, diagnosis at earlier stages, less cutaneous involvement, more respiratory involvement, high CRP values, and more generalized symptoms.

Fibrosis pulmonar asociada a vasculitis con anticuerpos anticitoplasmáticos positivos / Pulmonary fibrosis associated with anti-neutrophil cytoplasmic antibody-positive vasculitis

Las complicaciones pulmonares más conocidas de las vasculitis con anticuerpos anticitoplasmáticos de los neutrófilos (ANCA) positivos (VAA), son la hemorragia alveolar, los granulomas y la estenosis de la vía aérea. En los últimos años han aparecido algunos informes aislados que muestran la asociación con fibrosis pulmonar (FP), sugiriendo que ésta sería otra complicación de las VAA. En este trabajo informamos dos casos con dicha asociación describiendo sus características clínicas, tomográficas e inmunológicas. Dado que en la asociación de FP y VAA notificada en los últimos años, la FP puede ser su primera manifestación, podría ser necesaria la búsqueda de ANCA en pacientes con FP, como causa de la misma y por el posible desarrollo posterior de vasculitis.

The most frequently observed pulmonary complications of vasculitis (AAV) with anti-neutrophil cytoplasmic positive antibodies (ANCA) are alveolar hemorrhage, granulomas and airway stenosis. In recent years, some reports have been published that show the association of vasculitis with pulmonary fibrosis (PF), suggesting that it may be another complication of AAV. We report and describe here two cases with such association, and their clinical, tomographic and immunological characteristics. Given that in the association between PF and AAV, as reported in the last years, PF could be the first manifestation of AAV, the search for ANCA in patients with PF may be necessary, as a cause of it and for the possible subsequent development of vasculitis.

Lesões destrutivas da linha média induzidas por cocaína com ANCA positivo mimetizando a granulomatose de Wegener / Cocaine-induced midline destruction lesions with positive ANCA test mimicking Wegener's granulomatosis

O uso crônico de cocaína por inalação pode causar lesões destrutivas de linha média (LDLMIC), que podem ser difíceis de distinguir das lesões da granulomatose de Wegener (GW) nos ouvidos, nariz e garganta. Descrevemos o caso de uma paciente de 43 anos admitida com história de dois anos de obstrução nasal e rinorreia. Ela havia recebido o diagnóstico de GW há cinco meses e estava em tratamento com prednisona e ciclofosfamida. Ao exame físico apresentava perfuração de septo nasal e palato. Exames de laboratório mostraram elevação das proteínas de fase aguda e teste p-ANCA positivo. Ensaios ELISA antiproteinase 3 e mieloperoxidase foram negativos. Tomografia computadorizada (TC) dos seios paranasais mostrou destruição de septo nasal e palato, bem como sinusite maxilar bilateral. TC de tórax resultou normal. Biópsia da mucosa nasal revelou infiltrado inflamatório sem granuloma ou vasculite. Quando questionada, admitiu ser usuária de cocaína há cinco anos. Os imunossupressores foram suspensos e a paciente não mais fez uso da droga. Ela está sendo monitorada há seis meses e não desenvolveu novas lesões ou sintomas de outros órgãos. O diagnóstico diferencial em pacientes com LDLMIC pode ser desafiador. A avaliação deve incluir pesquisa de uso intranasal de cocaína. Embora o teste de ANCA não diferencie claramente o ANCA encontrado em alguns pacientes com LDLMIC daqueles em pacientes com GW, o envolvimento localizado e os achados de biópsia não típicos de vasculite granulomatosa de pequenos vasos devem ser reconhecidos como características das lesões induzidas por cocaína.

Chronic use of cocaine by inhalation may induce midline destructive lesions (CIMDL), which can sometimes be difficult to distinguish from the ear, nose and throat lesions of Wegener's Granulomatosis (WG). We describe the case of a 43-year-old female patient admitted with a two-year history of nasal obstruction and rhinorrhea. She had been diagnosed with WG for five months, being on prednisone and cyclophosphamide. On her physical examination, perforation of her nasal septum and palate was observed. Laboratory tests showed elevated acute phase proteins and a positive p-ANCA test. ELISA assays anti-proteinase 3 and myeloperoxidase were negative. The paranasal sinus computed tomography (CT) showed destruction of the nasal septum and palate, in addition to bilateral maxillary sinusitis. Chest CT was normal. Nasal mucosal biopsy revealed an inflammatory infiltrate, with neither granuloma nor vasculitis. When questioned, she admitted being a cocaine user for five years. Medical therapy and cocaine use were withdrawn. She has been followed up for six months and no other lesion or other organ symptoms occurred. Differential diagnosis in patients with midline destructive lesions can be very challenging. Evaluation should include enquiry about intranasal use of cocaine. Although ANCA testing does not clearly differentiate the ANCA found in some patients with CIMDL from those found in WG patients, the localized involvement and the biopsy findings non-characteristic of small vessel granulomatous vasculitis should be recognized as features for cocaine-induced lesions.

Renal histology in pauci-immune rapidly progressive glomerulonephritis: 8-year retrospective study.

Context: The need to perform reporting of renal biopsies of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides in a more uniform manner required relook at our eight-year data. Aims: To document detailed renal histopathology of pauci-immune rapidly progressive glomerulonephritis (RPGN) and also to seek any significant differences in renal histology of C-ANCA-positive, P-ANCA-positive, and ANCA-negative patients. Materials and Methods: A detailed analysis of the histopathologic features of renal biopsies of 48 patients in whom a diagnosis of pauci-immune glomerulonephritis was concluded on renal biopsy and who presented clinically as rapidly progressive renal failure was done. Statistical Analysis Used: One-way ANOVA and Pearson Chi square tests. Results: Compared with ANCA +ve patients, the ANCA -ve patients were much younger (46.85 ± 16.12 years vs 34.28±15.94 years). No significant differences were found between renal lesions of C-ANCA, P-ANCA, and ANCA-negative patients, except for diffuse tubular atrophy which was more severe and more frequently present with P-ANCA positivity (P value=0.013). Conclusions: Pauci-immune RPGN (irrespective of ANCA status) is a relatively rare disorder in patients who are undergoing the renal biopsy at our institute, constituting 2% of all renal biopsies submitted. It is mandatory to have ANCA serology status during reporting of a kidney biopsy showing pauci-immune crescentic or necrotizing glomerulonephritis. Also, if a uniform reporting strategy is followed throughout the country, the studies from this vast country will be comparable.

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.

A decade long experience of anti-neutrophil cytoplasmic antibody testing in a tertiary care referral center in North India: Perspective from a developing country.

Background: In a developing, tropical country like India, discontinuous power supply, high temperatures during summer, and lack of consistent cold chain and funds provide a challenging atmosphere for anti-neutrophil cytoplasmic antibody (ANCA) testing and reporting. However, a simple in-house test and testing algorithm are described here, which have been developed and tested over time. Materials and Methods: An analysis of a decade of testing and reporting of ANCA in the Department of Immunopathology in a tertiary referral health care center was performed to highlight the importance of testing for ANCA in proposed 1999 guideline recommended indications. Results: A total of 4195 ANCA tests were conducted from 2000 to 2009. Overall, 2060 (49%) requests had indications which met the 1999 guidelines, while the remaining 2135 (51%) fell outside the guidelines. A total of 350 samples (8.3%) were positive for ANCA on indirect immunofluorescence (IIF), out of which 212 were guideline recommended and 138 (3.2%) were non-guideline recommended ANCA requests; thus, 3.2% of non-small vessel ANCA associated vasculitis (non-SVAAV) conditions showed false positive results when the population was otherwise unselected. Maximum requests (1432) were for rapidly progressive renal failure/acute renal failure. Conclusions: The audit shows that compliance with guidelines for ANCA testing would decrease the number of false positive results. In-house screening for ANCA by IIF is cost-effective and must be performed at least twice on two different samples from the same patient or on two different sets of ANCA preparations in all the cases who requested ANCA testing with a proposed 1999 guideline recommended indication.

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.

Diagnostic dilemma of antineutrophil cytoplasmic antibody seropositivity in human immunodeficiency virus infection.

We present a case of a 48-year-old male who was diagnosed and treated for Wegener’s granulomatosis on the basis of history, clinical features, computed tomography (CT) and antineutrophil cytoplasmic antibodies (ANCA) positivity. The patient initially improved and later on during course of the disease he was found to be human immunodeficiency virus (HIV) seropositive. The potential pitfalls of cANCA in a HIV-infected patient are discussed.

Características generales de 29 pacientes con vasculitis de pequeños vasos / General characteristics of 29 patients with small vessel vasculitis

El objetivo de esta serie fue describir las características generales y manifestaciones clínicas de pacientes con vasculitis de pequeños vasos que concurrieron al servicio de autoinmunidad de un hospital de la comunidad y compararlas con la literatura. Se revisaron de manera retrospectiva las historias clínicas archivadas bajo el rótulo de vasculitis en un período de 16 años. Se seleccionaron aquellos pacientes que cumplieran criterios diagnósticos de vasculitis de pequeños vasos. Se extrajeron los datos de interés y se constató la supervivencia mediante contacto telefónico. Posteriormente se realizó una búsqueda bibliográfica y se compararon los resultados. Se incluyeron 13 pacientes con granulomatosis de Wegener, 6 con síndrome de Churg Strauss y 10 con poliangeítis microscópica. El 55% (16) fueron menores de 55 años al diagnóstico y hubo predominio del sexo femenino (2.6:1). La demora diagnóstica fue mayor a un año en el 46% de los casos. Los sistemas más frecuentemente afectados fueron respiratorio y otorrinolaringológico. El 79% presentó anticuerpos anti-citoplasma de neutrófilos (ANCA) positivos. La mortalidad fue del 24% (7/29). Al comparar las características de los pacientes incluidos en esta serie con lo descripto en la literatura, se hallaron diferencias en cuanto a la forma de presentación, sistemas comprometidos y porcentaje de pacientes ANCA positivos; además se observó que el resultado negativo de este marcador parece asociarse con mayor demora diagnóstica y en consecuencia peor pronóstico, lo que remarca su importancia como herramienta adicional no invasiva al momento del diagnóstico.

The objective of this series was to describe the general characteristics and clinical manifestations of patients with small vessel vasculitis who were assisted in the autoimmunity department of a community public hospital and to compare the results with the literature. Clinical records under the label of vasculitis in a period of 16 years were reviewed in a retrospective way. All patients selected fulfilled diagnostic criteria of small vessel vasculitis. The data were extracted and the analysis of survival was completed by phone. Later a bibliographical search was carried out and the results were compared. Thirteen patients with Wegener's granulomatosis, 6 with Churg-Strauss syndrome and 10 with microscopic polyangiitis were included. Fifty five percent (16) were under 55 years old when diagnosis was made and male/female ratio was 2.6 to 1. The diagnostic delay was over a year in 46% of the cases. Respiratory and ear-nose-throat were the most frequently affected systems. Anti-neutrophil cytoplasmic antibodies were present in 79% of patients. Overall mortality was 24% (7/29). There were several differences between the results of our series and the literature: the presentation form, affected systems and percentage of patients with anti-neutrophil cytoplasmic antibodies. Greater diagnostic delay and worse prognosis were observed in anti-neutrophil cytoplasmic antibody negative patients. Special attention should be given to these antibodies since they constitute a significant tool at the time of diagnosis.