Manifestaciones pulmonares al diagnóstico de 170 pacientes con vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos: cohorte retrospectiva de un centro universitario / Pulmonary manifestations at the diagnosis of 170 patients with vasculitis associated with anticytoplasmic neutrophil antibodies: retrospective cohort of a university center

INTRODUCCIÓN: Las Vasculitis Asociadas a Anticuerpos Anticitoplasma de Neutrófilos (VAA) son infrecuentes, pero de amplio espectro de presentación. Si bien el consenso de clasificación de Chapel Hill del año 2012, sigue vigente, la tendencia actual es clasificarlas de acuerdo al marcador inmunológico: anti-Proteinasa 3 (PR3) o anti-mieloperoxidasa (MPO). Las manifestaciones pulmonares clásicas son la hemorragia alveolar y los nódulos pulmonares. En los últimos 10 años se ha descrito la enfermedad pulmonar difusa (EPD). Los estudios epidemiológicos son escasos, y suelen representar en su mayoría poblaciones norteamericanas o europeas. El objetivo es describir las características del compromiso pulmonar al debut en VAA en un centro universitario. PACIENTES Y MÉTODO: De un total de 190 pacientes con diagnóstico de VAA se incluyeron 170 en seguimiento en nuestro centro. Se revisaron aspectos clínicos, demográficos, laboratorio e imagenológicos de los pacientes incluidos. RESULTADOS: De los 170 pacientes, 112 (65,88%) presentaron compromiso pulmonar. 106 (94,64%) de los pacientes fueron anticuerpos anti citoplasma de neutrófilos (ANCA) positivos; de estos, 56 (53,27%) MPO (+) y 39 (36,45%) PR-3 (+). Un tercio de los pacientes de ambos grupos presentó hemorragia alveolar. En los pacientes MPO (+) predomina la EPD (53,5%) y en PR-3 (+) los nódulos pulmonares (69,23%). Destaca la baja frecuencia de patología obstructiva asociada. CONCLUSIONES: El compromiso pulmonar en las VAA es prevalente y heterogéneo. En nuestra serie, destaca la frecuencia de EPD en VAA MPO (+), lo que releva la importancia del estudio con ANCA en paciente con diagnóstico y seguimiento por EPD.

INTRODUCTION: Antineutrophil Cytoplasmic Antibodies (ANCA) associated vasculitis (AAV) are uncommon, but of broad spectrum of presentation. Although the 2012 Chapel Hill classification consensus remains valid, the current trend is to classify them according to the immunological marker: anti-Proteinase 3 antibody (PR-3) or anti-Myeloperoxidase antibody (MPO). The classic pulmonary manifestations are alveolar hemorrhage and pulmonary nodules. Interstitial lung disease (ILD) has been described in the last 10 years. Epidemiological studies are scarce, and they usually represent mostly North American or European populations. The objective is to describe the characteristics of lung involvement upon debut in AAV in a university center. PATIENTS AND METHODS: Of a total of 190 patients diagnosed with AAV, 170 were included in follow-up at our center. Clinical, demographic, laboratory and imaging aspects of the included patients were reviewed. RESULTS: Of the 170 patients, 112 (65.88%) had lung involvement. 106 (94.64%) of the patients were ANCA (+); of these, 56 (53.27%) MPO (+) and 39 (36.45%) PR-3 (+). One third of the patients in both groups had alveolar hemorrhage. In MPO (+) patients, ILD predominates (53.5%) and in PR-3 (+) pulmonary nodules (69.23%). The low frequency of associated obstructive pathology stands out. CONCLUSIONS: Pulmonary manifestations in AAVs are frequent and heterogeneous. Locally, the association of ILD and AAV MPO (+) stands out, which highlights the importance of ANCA study in patients with diagnosis and follow-up by ILD.

Intercambio plasmático terapéutico por plasmafiltración: experiencia de 11 años de un centro / Therapeutic plasma exchange: experience in 102 patients

BACKGROUND: Therapeutic Plasma Exchange (TPE) is a procedure in which plasma and harmful macromolecules are separated from the rest of the blood components by centrifugation or filtration through membranes and are replaced with solutions with albumin and/or plasma. AIM: To communicate our experience using TPE by filtration. MATERIAL AND METHODS: Review of records of 655 TPE sessions performed in 102 patients aged 50 ± 18 years (64% women). The requirement of renal replacement therapy (RRT) and seven days and one year mortality were recorded. RESULTS: Forty five percent of patients had hypertension or diabetes. The main indications for TPE were pulmonary-renal syndrome (PRS) (62%) and antibody mediated graft rejection (29%), followed by neurological diseases (36%). Fifteen percent of patients required RRT for one year. Mortality at seven days and one year was 20 and 30%, respectively. Out of the total of deaths associated with kidney diseases, 88% corresponded to PRS and ANCA vasculitis. The main complications were thrombocytopenia in 41%, hypocalcemia in 18%, and hypotension in 16%. CONCLUSIONS: In our experience, TPE by filtration is a safe technique, with mild and preventable complications. Despite this, the reported mortality is high, which reflects the severity of the diseases that motivated the indication for TPE.

Prevalência de positividade do anticorpo ANCA em pacientes hemodialisados / Prevalence of Positive ANCA Antibody in Patients in Hemodialysis

Objetivo: Estimar a prevalência do anticorpo anticitoplasma de neutrófilos (ANCA) positivo em pacientes submetidos à hemodiálise, assim como também associar essa prevalência às características sociodemográficas e clínicas destes pacientes. Métodos: Estudo transversal realizado em 78 pacientes de uma Clínica de Hemodiálise no Sul de Santa Catarina nos meses de agosto a novembro de 2013. Foi realizada entrevista, coleta de dados em prontuário eletrônico e pesquisa do anticorpo anticitoplasma de neutrófilos por imunofluorescência indireta WAMA em plasma heparinizado. Resultados: A prevalência de anticorpo anticitoplasma de neutrófilos reagente em amostra titulada 1:10 foi de 24,4%, sendo que 10,3% apresentaram padrão c-ANCA e 14,1% apresentaram padrão p-ANCA, do total. Não foram observadas associações com características clínicas e sociodemográficas. Conclusão: Com base na alta prevalência de anticorpo anticitoplasma de neutrófilos positivo encontrada neste estudo, salienta-se a necessidade de mais estudos nesse grupo de pacientes para definição da contribuição deste exame no diagnóstico e prognóstico da doença renal e suas complicações

Objective: To estimate the Antibodies, Antineutrophil Cytoplasmic (ANCA) prevalence in patients submitted to hemodialysis, as well as associate this prevalence to sociodemographic and clinical characteristics of these patients. Methods: Cross-sectional study performed with 78 users from a Hemodialysis Clinic in Southern Santa Catarina on the period from August to November 2013. Interviews, data collection of electronic records and antibodies, antineutrophil cytoplasmic research by WAMA indirect immunofluorescence on heparinized plasma were performed. Results: The prevalence of ANCA reagent 1:10 titrated sample was 24.4%, and 10.3% had c-ANCA pattern and 14.1% had p-ANCA pattern, from total sample. No associations were observed with clinical and sociodemographic characteristics. Conclusions: Based on the high antibodies, antineutrophil cytoplasmic prevalence in this study, and no statistically significant association with clinical and sociodemographic characteristics, we emphasize the need for more studies on this group of patients to determine the contribution of this exam in the diagnosis and prognosis of kidney disease and its complications.

High levels of platelet-to-lymphocyte ratio may predict reduced risk of end stage of renal disease in Chinese patients with MPO-ANCA associated vasculitis / 中南大学学报(医学版)

OBJECTIVES@#Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality.@*METHODS@#The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality.@*RESULTS@#A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801).@*CONCLUSIONS@#PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.

Uso excesivo de la prueba de ANCA / Overuse of the neutrophil cytoplasmic antibody test

La desproporcional y alta frecuencia de órdenes médicas de anticuerpos frente al citoplasma del neutrófilo (ANCA, por sus siglas en inglés) dirigidas a nuestros laboratorios clínicos evidencia el sobreuso de la prueba de ANCA. El uso indiscriminado de esta aumenta los gastos sin beneficio de salud. El laboratorio clínico es el eslabón de la cadena diagnóstica que más siente el uso excesivo de las solicitudes de ANCA, básicamente porque genera resultados falsos positivos que comprometen la utilidad clínica de la prueba, además de recargar innecesariamente el trabajo diario del laboratorio. La prueba de ANCA es una herramienta diagnóstica muy útil para las vasculitis sistémicas primarias, pero su valor en situaciones no vasculíticas así como en otras condiciones inflamatorias y en enfermedades infecciosas o tumorales, no ha sido demostrado.1,2 El descubrimiento de los ANCA cambió...(AU)

Clinical characteristics and prognostic factors in an argentinian cohort with ANCA-associated vasculitis / Características clínicas y factores pronósticos en una cohorte argentina de vasculitis asociada a ANCA

Abstract ANCA-associated vasculitis is a heterogeneous group of rare autoimmune conditions of unknown cause. Clinical characteristics and prognostic factors were analyzed in 47 patients: 20 (42.5%) with granulomatosis with polyangiitis, 17 (36.2%) with microscopic polyangiitis, 6 (12.8%) with renal-limited vasculitis, and 4 (8.5%) with eosinophilic granulomatosis with polyangiitis. Mean age at diagnosis was 53.5 ± 16.5 years and the median of BVAS (Birmingham Vasculitis Activity Score) was 14 (4-42). The most frequent clinical manifesta tions were: general in 44 (93.6%), renal in 30 (63.8%) and respiratory in 28 (59.6%). All received corticosteroids at the beginning of treatment. Intravenous cyclophosphamide was associated in 20 (42.5%) and oral route in 14 (29.8%); azathioprine in 3 (6.4%) and rituximab in 2 (4.2%). At a median follow-up of 35.5 months (range 0.14- 234), 21 relapses were recorded in 14 patients. Overall mortality was 3.5 deaths per 100 patient-year in the whole group. Those over 55 years old, the presence of alveolar hemorrhage, those with FFS (Five Factor Score) of 2, and patients with MPA had poor prognosis. Renal involvement, ANCA pattern and BVAS were not associated to a poorer prognosis.

Resumen Las vasculitis asociadas a ANCA son un grupo heterogéneo de entidades autoinmunes, poco frecuentes, de etiología desconocida. Analizamos las características clínicas y factores pronóstico en 47 pacientes: 20 (42.5%) granulomatosis con poliangeítis, 17 (36.2%) poliangeítis microscópica, 6 (12.8%) vasculitis limitada al riñón y 4 (8.5%) granulomatosis eosinofílica con poliangeítis. La edad promedio al diagnóstico fue 53.5 ± 16.5 años y la mediana de BVAS (Birmingham Vasculitis Activity Score) 14 (4-42). Las manifestaciones clínicas más frecuentes fueron: generales en 44 (93.6%), renales 30 (63.8%) y respiratorias en 28 (59.6%). Todos recibieron corticoides al inicio del tratamiento. Se asoció ciclofosfamida endovenosa en 20 (42.5%) y oral en 14 (29.8%); azatioprina en 3 (6.4%) y rituximab en 2 (4.2%). En una mediana de seguimiento de 35.5 meses (rango 0.14-234), se registraron 21 recaídas en 14 pacientes. La mortalidad fue 3.5 por cien pacientes-año en todo el grupo. Los mayores de 55 años, con presencia de hemorragia alveolar, FFS (Five Factor Score) de 2, y los casos con poliangeítis microscópica tuvieron peor pronóstico. El compromiso renal, el patrón de ANCA y el BVAS no se asociaron a peor pronóstico.

Rapidly progressive glomerulonephritis and acute kidney injury associated with cocaine use - Case report / Glomerulonefrite rapidamente progressiva e lesão renal aguda associada ao uso de cocaína - Relato de caso

ABSTRACT A wide spectrum of renal complications can occur with acute and chronic use of cocaine. Most cases are related to rhabdomyolysis, but other mechanisms are malignant hypertension, renal ischemia, and rapidly progressive glomerulonephritis (RPGN) associated-ANCA vasculitis. In recent years, the use of cocaine adulterated with levamisole has been associated with ANCA vasculitis and pauci-immune RPGN. RPGN is clinically manifested as a nephritic syndrome with a rapid and progressive decline in renal function, and its histopathological finding is the presence of crescents in more than 50% of the glomeruli. We report a case of a 38-year-old man chronic user of cocaine, alcohol, and cigarettes who had red urine, oliguria, swollen legs and eyelids, as well as the uremic symptoms anorexia, emesis, and mental confusion. He was admitted with acute kidney injury and performed six hemodialysis sessions during the first 16 days of hospitalization and then was transferred to a tertiary hospital for diagnostic investigation. Tests of ANF (antinuclear factor), ANCA, anti-DNA, serology for hepatitis B, C, and HIV virus were negative. A renal percutaneous biopsy revealed crescentic glomerulonephritis with mild tubular atrophy. The patient underwent pulse therapy with methylprednisolone (for 3 days) and cyclophosphamide. Then he maintained daily prednisone and monthly intravenous cyclophosphamide and evolved with progressive improvement of renal function.

RESUMO Um amplo espectro de complicações renais pode ocorrer com o uso agudo e crônico de cocaína. A maioria dos casos está relacionada à rabdomiólise, mas outros mecanismos são hipertensão maligna, isquemia renal e glomerulonefrite rapidamente progressiva (GNRP) associada à vasculite por ANCA. Nos últimos anos, o uso de cocaína adulterada com levamisol tem sido associado à vasculite por ANCA e GNRP pauci-imune. A GNRP se manifesta clinicamente como uma síndrome nefrítica, com um declínio rápido e progressivo da função renal, e seu achado histopatológico é a presença de crescentes em mais de 50% dos glomérulos. Relatamos um caso de um homem de 38 anos, usuário crônico de cocaína, álcool e cigarros que apresentava urina vermelha, oligúria, pernas e pálpebras inchadas, além dos sintomas urêmicos, anorexia, êmese e confusão mental. Foi internado com lesão renal aguda e realizou seis sessões de hemodiálise durante os primeiros 16 dias de internação, e depois foi transferido para um hospital terciário para investigação diagnóstica. Os testes de ANF (fator antinuclear), ANCA, anti-DNA, sorologia para vírus da hepatite B, C e HIV foram negativos. Uma biópsia percutânea renal revelou glomerulonefrite crescente, com leve atrofia tubular. O paciente foi submetido à pulsoterapia com metilprednisolona (por 3 dias) e ciclofosfamida. Em seguida, ele manteve a prednisona diária e a ciclofosfamida intravenosa mensal e evoluiu com melhora progressiva da função renal.

Case for diagnosis. Cutaneous small vessel vasculitis (anti-proteinase 3 positive), fever, hemoptysis, and lung cavitation in an adult

Abstract Small vessel vasculitis with anti-proteinase antibodies 3 is an atypical clinical presentation of tuberculosis. The authors present the case of a 47-year-old male patient, with palpable purpura and palmoplantar hemorrhagic blisters, with subsequent dissemination. He presented severe pulmonary symptoms with cavitation, fever, hemoptysis, and high levels of anti-proteinase 3. Histopathological assessment of the skin revealed small vessel vasculitis; pulmonary histopathology showed granulomas with caseation. Bronchoalveolar lavage was positive for alcohol-acid-fast bacilli. In countries with a high prevalence of tuberculosis, the presence of autoantibodies in a patient with vasculitis, fever, and pulmonary cavitation requires investigation of infectious causes.

Granulomatosis with polyangiitis with nasal symptoms as the first clinical manifestation: clinical analysis of 18 cases / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze and summarize the diagnosis, treatment and prognosis of granulomatosis with polyangiitis (GPA) with nasal symptoms as the first clinical manifestation. Methods: The data of 18 patients of GPA with nasal mucosal symptoms as the first clinical manifestation from the Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University between 2005 and 2019 was collected, including 8 males and 10 females, aged from 5 to 68 years. Nasal endoscopy, imaging examination, laboratory examination, immunological and histopathological examination of nasal mucosa were completed. All patients were treated with glucocorticoid combined with cyclophosphamide and were followed up for 2 to 15 years. Descriptive statistical method was used for analysis. Results: All the 18 patients had the nasal mucosal symptoms as the first clinical manifestation, including nasal obstruction, running nose and epistaxis. Nasal endoscopy showed swelling, erosion, scab and bleeding of nasal mucosa, and 6 cases had nasal septal perforation. Nasal sinus CT scan showed high density shadow of sinus, as well as hyperostosis and osteosclerosis. CT imaging features of pulmonary showed nodular lesion or patchy infiltration in 12 patients and cavitation was found in 6 cases. Laboratory results showed that 13 cases were positive for anti-neutrophil cytoplasmic antibodies (ANCA), and 5 cases were negative. During follow-up period, thirteen patients were symptomatic controlled and survived; two patients died of disease progression; one patient gave up treatment and died; two patients were lost to follow-up. Conclusions: Nasal symptoms are the first clinical manifestation of GPA. Early diagnosis and early treatment with glucocorticoid combined with cyclophosphamide can effectively improve the survival rate.

Antineutrophil cytoplasmic antibody profiles differ according to type of primary sclerosing cholangitis and autoimmune hepatitis

OBJECTIVES: To determine the frequency of the antineutrophil cytoplasmic antibodies (ANCA), antiproteinase-3 and antimyeloperoxidase, in primary sclerosing cholangitis (PSC) with or without inflammatory bowel disease (IBD+ or IBD-) and in different types of autoimmune hepatitis (AIH). Additionally, to verify the agreement between ANCA patterns by indirect immunofluorescence and their antigenic specificities by ELISA. METHODS: For this study, 249 patients were enrolled (42 PSC/IBD+; 33 PSC/IBD-; 31 AIH type-1; 30 AIH type-2; 31 AIH type-3; 52 primary biliary cirrhosis; 30 healthy controls) whose serum samples were tested for ANCA autoantibodies. RESULTS: There were fewer female subjects in the PSC/IBD- group (p=0.034). Atypical perinuclear-ANCA was detected more frequently in PSC/IBD+ patients than in PSC/IBD- patients (p=0.005), and was significantly more frequent in type-1 (p<0.001) and type-3 AIH (p=0.012) than in type-2 AIH. Proteinase-3-ANCA was detected in 25 samples (only one with cytoplasmic-ANCA pattern), and more frequently in PSC/IBD+ than in PSC/IBD- patients (p=0.025). Myeloperoxidase-ANCA was identified in eight samples (none with the perinuclear-ANCA pattern). Among the 62 reactive samples for atypical perinuclear-ANCA, 13 had antigenic specific reactions for proteinase-3 and myeloperoxidase. CONCLUSIONS: PSC/IBD+ differed from PSC/IBD- in terms of sex and proteinase 3-ANCA and atypical perinuclear-ANCA reactivity, the latter of which was more frequently detected in type-1 and type-3 AIH than in type-2 AIH. There was no agreement between ANCA patterns and antigenic specificities in IBD and autoimmune liver diseases, which reinforces the need for proteinase-3 and myeloperoxidase antibody testing.

The novel fibrosis index at diagnosis may predict all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis without substantial liver diseases

OBJECTIVES: Antineutrophil cyto plasmic antibody-associated vasculitis (AAV) is a fatal disease. Currently, predictors of mortality due to AAV are based on the distribution of organ involvement. The novel fibrosis index (NFI) is an index composed of laboratory results that reflect the degree of liver fibrosis. This study aimed to evaluate whether NFI can predict poor outcomes in patients with AAV without substantial liver disease. METHODS: A total of 210 patients with immunosuppressive drug-naïve AAV were retrospectively reviewed. NFI was calculated as follows: NFI=(serum bilirubin × (alkaline phosphatase)2)/(platelet count×(serum albumin)2). NFI cut-off was set at 1.24 (the highest quartile). Poor outcomes were defined as all-cause mortality, relapse, and end-stage renal disease (ESRD). RESULTS: During the median 34.5 months of follow-up, 21 patients (10%) died, 72 patients (34.3%) relapsed, and 38 patients (18.1%) had ESRD due to AAV progression. The median calculated NFI was 0.61, and it was higher in AAV patients with all-cause mortality than in those without mortality, but the difference was not statistically significant (1.26 vs. 0.59). AAV patients with NFI at diagnosis ≥1.24 exhibited a significantly lower cumulative patient survival rate than those with NFI at diagnosis <1.24 (p=0.002). Multivariate Cox hazard model analysis showed that NFI at diagnosis ≥1.24 was an independent predictor of all-cause mortality in AAV (hazard ratios [HR] 2.850, 95% confidence interval [CI] 1.026, 7.910). CONCLUSIONS: NFI ≥1.24, which may be an independent predictive marker for all-cause mortality in AAV patients without substantial liver disease.

Clinicopathological features of children with lupus nephritis with positive antineutrophil cytoplasmic antibody / 中国当代儿科杂志

OBJECTIVE@#To study the clinicopathological features of children with lupus nephritis (LN) with positive anti-neutrophil cytoplasmic antibody (ANCA).@*METHODS@#A retrospective analysis was performed for the children who were diagnosed with LN in the First Affiliated Hospital of Sun Yat-sen University from January 2003 to December 2019. According to the results of serum ANCA, they were divided into two groups: ANCA-positive group (@*RESULTS@#Compared with the ANCA-negative group, the ANCA-positive group had a significant reduction in leukocytes and a significant increase in erythrocyte sedimentation rate (@*CONCLUSIONS@#Children with ANCA-positive LN tend to have more severe renal pathological injury, which is not exactly parallel with clinical manifestations, suggesting that timely renal biopsy is of great importance.

Anca negative pauci-immune crescentic glomerulonephritis and mixed connective tissue disease: a case study / Glomerulonefrite crescêntica pauci-imune ANCA-negativa e doença mista do tecido conjuntivo: relato de um caso

Abstract One of the most common causes of rapidly progressive glomerulonephritis (RPGN) is pauci-immune crescentic glomerulonephritis (CrGN). In the majority of cases, this condition has a positive serologic marker, the anti-neutrophil cytoplasmic antibodies (ANCAs), but in approximately 10% there are no circulating ANCAs, and this subgroup has been known as the ANCA-negative pauci-immune CrGN. RPGN can be associated with systemic diseases, but there are only few case reports describing the association with mixed connective tissue disease (MCTD). The authors report a case of ANCA-negative CrGN associated with a MCTD.

Resumo Uma das causas mais comuns da glomerulonefrite rapidamente progressiva (GNRP) é a glomerulonefrite crescêntica (GNC) pauci-imune. Na maioria dos casos, a patologia apresenta um marcador sorológico positivo, o anticorpo anticitoplasma de neutrófilos (ANCA), mas em cerca de 10% dos pacientes não há ANCAs circulantes, perfazendo um subgrupo da patologia conhecido como GNC pauci-imune ANCA-negativa. A GNRP pode estar associada a doenças sistêmicas, mas são poucos os relatos de caso que descrevem sua associação com doença mista do tecido conjuntivo (DMTC). O presente artigo relata um caso de GNC ANCA-negativa associada a DMTC.

Comportamiento clínico y factores asociados a mortalidad temprana en una cohorte de pacientes chilenos con vasculitis asociadas a anticuerpos anti citoplasma de neutrófilos (VAA) / Variables associated with mortality in 103 patients with anti-neutrophil cytoplasmic antibodies associated vasculitis

Background: Cumulative survival in patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (VAA) is 88 and 78% at 1 and 5 years, respectively. Despite this, mortality continues to be 2.7 times higher than the general population. Differences in the clinical profile of VAA in different ethnicities have been observed. Aim: To identify factors at the time of diagnosis, associated with mortality at one year of follow-up and to describe the clinical characteristics of these patients. Material and Methods: We identified in local databases and reviewed clinical records of patients with VAA with at least one year of follow up in a clinical hospital. Demographic and laboratory parameters and clinical activity scores were analyzed. Results: Of 103 patients with VAA identified, 65 met the inclusion criteria and were analyzed. Their age ranged from 45 to 63 years and 56% were women. Thirty-five patients (54%) were diagnosed as granulomatosis with Polyangiitis (GPA) and 30 patients (46%) with Microscopic Polyangiitis (MPA). The frequency of renal disease was 53% and pulmonary involvement occurred in 72%. At one year of follow-up 11 patients died resulting in a mortality of 17%. Seven patients died within three months after diagnosis. MPO ANCA were more common than PR3 ANCA. In the multivariate analysis, the presence of ophthalmological involvement, lung kidney syndrome and a Five Factor Score (FFS) of 1 or more were independent factors associated with mortality at one year. Conclusions: In these patients, pulmonary manifestations predominate. Lung kidney syndrome, ophthalmological involvement and a FFS score ≥ 1 were associated with mortality.

Value of anti-neutrophil cytoplasmic antibody in assessing the severity of bronchiolitis obliterans in children / 中国当代儿科杂志

OBJECTIVE@#To study the value of anti-neutrophil cytoplasmic antibody (ANCA) in assessing the severity of bronchiolitis obliterans (BO) in children.@*METHODS@#A prospective analysis was performed on 59 children who were diagnosed with BO from June 2009 to October 2014. ELISA was used to measure the concentrations of myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA in serum. According to the results of ELISA, the children were divided into three groups: double-negative ANCA (n=22), single-positive ANCA (n=17), and double-positive ANCA (n=20). The three groups were compared in terms of the scores of BO risk factors, clinical symptoms, chest high-resolution computed tomography (HRCT), and lung pathology on admission, as well as the changes in the expression level of ANCA and the scores of clinical symptoms and chest HRCT over time.@*RESULTS@#Compared with the double-negative ANCA group, the double-positive ANCA group had a significantly higher score of BO risk factors (P0.05). The single-positive ANCA and double-positive ANCA groups still had a significantly higher score of clinical symptoms than the double-negative ANCA group (P<0.05).@*CONCLUSIONS@#The expression level of ANCA is correlated with the severity of BO in children and thus has certain clinical significance in disease evaluation.

Diffuse Systemic Sclerosis in a Patient with Primary Biliary Cirrhosis and Autoimmune Hepatitis Overlap Syndrome: A Case Report

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.

Vasculitis asociada a anticuerpos anticitoplasma de neutrófilos: poliangeítis microscópica / Antineutrophil Cytoplasmic Antibody Associated Vasculitis: Microscopic Polyangiitis

La poliangeítis microscópica se define como una enfermedad autoinmune, multisistémica, de rara incidencia, asociada a anticuerpos anticitoplasma de neutrófilos. Se caracteriza por presentar vasculitis necrotizante de pequeños vasos, no granulomatosa y ausencia de depósito de inmunocomplejos, que afecta predominantemente el tejido renal, pulmonar y cutáneo. Se presenta un paciente masculino, 49 años, sin antecedentes patológicos. Presenta cuadro clínico de 30 días de evolución con tos seca de tipo irritativa, que evoluciona a tos productiva, hemoptisis, disnea de moderado esfuerzo, astenia y edema con fóvea en zonas en declive. Tenía anemia grave y los estudios imagenológicos de tórax evidenciaron infiltrados difusos con aspecto de vidrio deslustrado. Se inició terapia inmunosupresora con metilprednisolona y ciclofosfamida y profilaxis antibiótica. Se obtuvo una disminución en el puntaje de la escala de actividad vasculítica y la posterior remisión; sin embargo, debido al daño tisular renal, no hubo mejoría en la tasa de filtrado glomerular, por lo que el paciente se mantiene en terapia de sustitución renal permanente. Es trascendental el conocimiento de las manifestaciones clínicas, procedimiento diagnóstico y tratamiento de esta enfermedad, ya que, a pesar de su rara incidencia, posee una llamativa morbimortalidad que puede modificarse significativamente con un diagnóstico y tratamiento oportunos(AU)

Microscopic Polyangiitis is defined as an autoimmune, multisystemic, low prevalence disease, associated to antineutrophil cytoplasmic antibody. Characterized by necrotizing vasculitis of small vessels, with no granulomatous inflammation and absence of immune complex deposits, predominantly affecting renal, pulmonary and cutaneous tissue. 49-year old male patient with no past medical history. Refers symptomatology that started thirty days ago, characterized by dry cough, that evolves to productive cough, hemoptysis, exertional dyspnea, asthenia and pitting edema. Laboratory tests show severe anemia, glomerular filtration rate of 6.9 ml/min/1.73m2, hematuria, proteinuria, positive presence of antineutrophil cytoplasmic antibodies and anti-myeloperoxidase antibodies, additional thoracic imaging shows ground glass opacities consolidations. Immunosuppressive therapy is started with Methylprednisolone and Cyclophosphamide along with antibiotic prophylaxis, resulting in a decrease in the vasculitis activity score with subsequent remission; however due to renal tissue damage, there is no improvement in the glomerular filtration rate and the patient continues receiving renal replacement therapy. Due to its striking morbidity and mortality, we consider of great importance the knowledge of its clinical presentation, diagnostic procedures and treatment, in order to obtain a positive impact on the patient's quality of life and survival rate(AU)

Paquimeningitis hipertrófica en vasculitis anca positivo: reporte de caso y revisión de la literatura / Hypertrophic pachymeningitis in positive ANCA vasculitis: case report and literature review

La paquimeningitis hipertrófica (PH), es una manifestación poco frecuente de la vasculitis asociada a anticuerpos anti-citoplasma de neutrófilo (ANCA). La literatura describe compromiso de sistema nervioso central (SNC) en 2-8% de los casos en pacientes con vasculitis pauciinmune. Se presenta el caso de un paciente con antecedente de vasculitis anti-mieloperoxidasa (MPO) con un mes de evolución de cefalea hemicraneana izquierda. La resonancia magnética cerebral contrastada evidencia marcado engrosamiento y realce meníngeo dural en el hemicráneo izquierdo, predominante en el tentorio y la fosa posterior. Se descartaron causas infecciosas por lo que se llegó a la conclusión de compromiso meníngeo asociado a vasculitis. Se inició manejo inmunosupresor con mejoría del cuadro clínico. La rápida identificación y manejo de esta entidad puede cambiar su pronóstico sombrío. Se realizó una revisión de la literatura para brindar una herramienta para la toma de decisiones para los médicos que se enfrentan a esta entidad.

Hypertrophic pachymeningitis (PH) is a rare manifestation of vasculitis associated with anti-neutrophil cytoplasm antibodies (ANCA). The literature describes central nervous system (CNS) involvement in 2-8% of cases in patients with pauciimmune vasculitis. We present the case of a patient with a history of anti-Myeloperoxidase (MPO) vasculitis with a 1-month history of left-sided headache. Contrast brain magnetic resonance was performed with evidence of marked thickening and dural meningeal enhancement in the left hemicranium, predominantly in the region of the tentorium and posterior fossa. Infectious causes were ruled out and the meningeal compromise associated with vasculitis was concluded. Immunosuppressive management was started with improvement of the clinical picture. Rapid identification and management of this entity can change its bleak outlook. A systematic review of the literature was carried out in order to provide a decision-making tool for physicians facing this entity.