Compromiso pulmonar en vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos / Pulmonary manifestations of anti-neutrophil cytoplasmic antibody associated vasculitis

This article reviews the pulmonary manifestations of anti-neutrophil cytoplasmic antibody associated vasculitis (AAV). Its frequency in the different phenotypes of the disease, clinical manifestations and updated therapeutic recommendations are reviewed, aiming to alert the medical community about the existence of these diseases. We pretend to stimulate a timely suspicion, diagnostic precision, and the implementation of effective therapies, to reduce the eventual sequelae derived from a diagnostic omission or an inappropriate treatment for the different clinical scenarios in which these diseases appear.

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.

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.

Severe Pulmonary Embolism, Thrombosis of Lower Extremity, Unexpected Mild Renal Disorder in MPO-ANCA Associated Vasculitis: A Case Report / 中国医学科学杂志(英文版)

Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis is an autoimmune disease usually with severe multiple dysfunction syndrome, especially prominent acute renal failure. A 65-year-old woman was admitted with progressive dyspnoea for six months and fever, sputum with blood, pain of the lower extremities and intermittent claudication for two days, indicating multiple organ involvement (respiratory system, blood vessels). The renal involvement was relatively mild, presenting with microscopic haematuria. The chest computed tomography demonstrated multiple pulmonary embolisms. Ultrasound and computed tomography angiography for the lower extremity vessels showed venous and arterial thrombosis. Exclusion of other diseases that can cause multiple organ damage and thrombosis, the positive perinuclear ANCA and MPO-ANCA strongly support the diagnosis of MPO-ANAC-associated vasculitis. The patient's physical condition has been greatly improved by treatment with corticosteroids and anticoagulation.

Antineutrophil cytoplasmic antibodies in patients treated with methimazole: a prospective Brazilian study / Anticorpos anticitoplasma de neutrófilos em pacientes tratados com metimazol: um estudo prospectivo brasileiro

Abstract Introduction: The side effects of antithyroid drugs are well known. Antineutrophil cytoplasmic antibody-associated vasculitis is a severe adverse reaction. Most studies evaluating antineutrophil cytoplasmic antibodies related to antithyroid drugs have been carried out with patients treated with propylthiouracil, but less information is available for methimazole. Furthermore, most studies that investigated antineutrophil cytoplasmic antibodies related to antithyroid drugs were conducted on Asian populations. Objective: To evaluate the frequency of antineutrophil cytoplasmic antibodies and antineutrophil cytoplasmic antibodies-positive vasculitis in an adult population of Brazilian patients treated with methimazole. Methods: This was a prospective study. We evaluated patients ≥18 years with Graves' disease who have been using methimazole for at least 6 months (Group A, n = 36); with Grave's disease who had been previously treated with methimazole but no longer used this medication for at least 6 months (Group B, n = 33), and with nodular disease who have been using methimazole for at least 6 months (Group C, n = 13). Results: ANCA were detected in 17 patients (20.7%). Four patients (4.9%) had a strong antineutrophil cytoplasmic antibodies-positive test. The frequency of antineutrophil cytoplasmic antibodies was similar in the groups. When Groups A and B were pooled and compared to Group C to evaluate the influence of Grave's disease, and when Groups A and C were pooled and compared to Group B to evaluate the influence of methimazole discontinuation, no difference was found in the frequency of antineutrophil cytoplasmic antibodies. No difference was observed in sex, age, etiology of hyperthyroidism, anti-TSH receptor antibodies, dose or time of methimazole use between patients with versus without antineutrophil cytoplasmic antibodies. The titers of these antibodies were not correlated with the dose or time of methimazole use. None of the antineutrophil cytoplasmic antibodies-positive patient had clinical event that could potentially result from vasculitis. Conclusion: This clinical study of a Brazilian population shows a considerable frequency of antineutrophil cytoplasmic antibodies in patients treated with methimazole but the clinical repercussion of these findings remains undefined.

Resumo Introdução: Os efeitos adversos de drogas antitireoidianas são conhecidos. Vasculite associada a anticorpos anticitoplasma de neutrófilos é uma reação adversa grave. A maioria dos estudos que avaliam anticorpos anticitoplasma de neutrófilos relacionado a drogas antitireoidianas envolveu pacientes tratados com propiltiouracil, entretanto menos informação se encontra disponível para o metimazol. Além disso, a maioria dos estudos que investigaram anticorpos anticitoplasma de neutrófilos relacionado a drogas antitireoidianas foi conduzida em populações asiáticas. Objetivo: Avaliar a frequência de anticorpos anticitoplasma de neutrófilos e vasculite anticorpos anticitoplasma de neutrófilos-positivo em uma população adulta de pacientes brasileiros tratados com metimazol. Método: Este foi um estudo prospectivo. Avaliamos pacientes ≥ 18 anos com doença de Graves com o uso de metimazol há pelo menos seis meses (Grupo A, n = 36); com doença de Graves previamente tratados com metimazol, mas que não usaram esse medicamento por pelo menos seis meses (Grupo B, n = 33) e com doença nodular em uso de metimazol há pelo menos seis meses (Grupo C, n = 13). Resultado: Anticorpos anticitoplasma de neutrófilos foram detectados em 17 pacientes (20,7%). Quatro pacientes (4,9%) tinham anticorpos anticitoplasma de neutrófilos fortemente positivos. A frequência de anticorpos anticitoplasma de neutrófilos foi semelhante nos grupos. Quando os Grupos A e B foram somados e comparados ao Grupo C para avaliar a influência da doença de Graves, e quando os Grupos A e C foram somados e comparados ao Grupo B para avaliar a influência da interrupção do metimazol, não foi encontrada diferença na frequência de anticorpos anticitoplasma de neutrófilos. Não houve diferença em relação a sexo, idade, etiologia do hipertireoidismo, anticorpos antirreceptor de TSH, dose ou tempo de uso de metimazol entre pacientes com e sem anticorpos anticitoplasma de neutrófilos. Os títulos desses anticorpos não se correlacionaram com dose ou tempo de uso de metimazol. Nenhum paciente anticorpos anticitoplasma de neutrófilos-positivo apresentou evento clínico resultante de vasculite. Conclusão: Este estudo clínico de uma população brasileira apresenta frequência considerável de anticorpos anticitoplasma de neutrófilos em pacientes tratados com metimazol, mas a repercussão clínica desse achado permanece indefinida.

Síndrome pulmón-riñón: serie de 12 casos / Pulmonary renal syndrome: series of 12 cases

El síndrome pulmón-riñón es una entidad infrecuente, que comprende un gran espectro de patologías, como las vasculitis asociadas a ANCA y la enfermedad por anticuerpos antimembrana basal glomerular entre otras. Se describen en esta serie 12 casos donde las entidades más prevalentes fueron las antes mencionadas, observándose además un caso de lupus y uno de granulomatosis con poliangeítis, que se encuentran dentro de las causas menos frecuentes. La forma de presentación clínica inicial fue simultánea renal y pulmonar en 5/12 pacientes y renal en 7/12 de los mismos. El diagnóstico temprano de dichas patologías basándose en criterios clínicos, radiológicos, de laboratorio e histológicos, permite instaurar terapéuticas tempranas como la inmunosupresión y plasmaféresis, pudiendo prevenir complicaciones tales como las infecciones y la insuficiencia renal crónica terminal, siendo las primeras la principal causa de muerte (AU)

Pulmonary-renal syndrome is an infrequent condition. It includes a wide variety of conditions such as ANCA (antineutro-phil cytoplasmic autoantibody) associated with systemic vasculitis and anti-GBM (anti-glomerular basement membrane) disease among others. In this series we describe twelve cases, in which the most prevalent diseases were the above mentioned as well as one case of lupus and one of granulomatosis with polyangiitis (these being less frequent causes). The clinical presentation was both renal and pulmonary simultaneously in five of twelve patients and renal in seven of twelve patients. Early diagnosis of this condition on the basis of clinical, radiological, histological and analytic criteria allows early treatments such as immunosuppression and plasma exchange, thus avoiding complications such as infections (the main cause of death) and terminal chronic renal failure (AU)

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.

Comparison of disease activities and extent measurements for anti-neutrophil cytoplasmic autoantibody-associated vasculitis / 北京大学学报(医学版)

OBJECTIVE@#To investigate the significance of a set of seven disease activities and extension measurements and their correlations between one and another for anti-neutrophil cytoplasmic autoantibody associated vasculitis (AAV).@*METHODS@#A total of 121 patients from Peking University International Hospital and Fouth Medical Center of PLA General Hospital with confirmed diagnoses of AAV clinically were enrolled in the study, including 15 cases of eosinophilic granulomatous with polyangiitis (EGPA), 59 cases of granulomatous with polyangiitis (GPA) and 47 cases of microscopic polyangiitis (MPA). A hundred and twenty-one AAV patients were divided into death group and survival group according to their survival conditions. A set of seven disease assessment scales including Birmingham vasculitis activity score (BVAS)-1994, BVAS-2003, as well as BVAS/GPA, vasculitis damage index (VDI), disease extent index (DEI), five factor score (FFS)-1996, and FFS-2009 were measured and scored one by one, and their relationships which were represented by Spearman correlation coefficient were compared between one and another.@*RESULTS@#BVAS-1994, BVAS-2003, as well as BVAS/GPA, VDI, DEI, and FFS, all of those seven evaluation indexes of the AAV patients in the death group were significantly higher than those in the survival group (P<0.05). Except for BVAS/GPA, all those above indicators in the patients with EGPA were lower than those in the patients with GPA and those in the patients with MPA, and those in all of the AAV patients as a whole group. There were high correlations among BVAS-2003, BVAS-1994 and BVAS/GPA (r values were 0.9 and 0.7, respectively); BVAS-1994 was fairly correlated with BVAS/GPA (r=0.69); FFS-1996 and FFS-2009 were highly correlated (r=0.73) with each other; BVAS-1994, BVAS-2003 and BVAS/GPA were fairly correlated with DEI (with r values of 0.62, 0.65, and 0.62, respectively); VDI was also fairly correlated with BVAS-1994 and with BVAS-2003 (r values were 0.49 and 0.52, respectively).@*CONCLUSION@#All of those seven AAV assessment indicators above can be used as indicators of disease activity and prognosis in AAV patients, most of which were relevant within one and another. There were high correlations among BVAS-2003, BVAS-1994 and BVAS/GPA, and besides, there were also high correlations between FFS-1996 and FFS-2009.

ANCA associated vasculitis in patients from Saudi Arabia

Objective: To explore clinical and laboratory features, therapy and outcome of antineutrophil cytoplasmic antibodies [ANCA] associated vasculitis [AAV] patients from our tertiary care center

Methods: This study of AAV patients seen in Rheumatology clinics at King Khalid University hospital [KKUH], King Saud University, Riyadh during the period 1990-2014 was carried out retrospectively. Demographic, clinical, haematological and immunological parameters along with therapy, complications and outcome were retrieved from patients' medical charts. Different characteristics were compared between the three groups of AAV; GPA [Granulomatosis with polyangiitis], MPA [Microscopic polyangiitis] and EGPA [Eosinophilic granulomatosis with polyangiitis]

Results: We identified 34 AAV patients [21 males: 13 females; 31 Saudis: 3 non-Saudis] comprising of 23 GPA, 2 MPA and 9 EGPA cases. The mean age of onset was 42.1 +/- 17.6 years [range 11-75] and mean duration of disease was 8.7 +/- 5.1 years [range 1-20]. The most frequently affected system was pulmonary in all AAV [73.5%], GPA [65.2%] and EGPA [100%] while it was renal in MPA [100%] patients. Ophthalmological and upper airways involvement was higher in GPA. Neurological involvement was higher in EGPA [p<0.05]. ANCA were detected in 79.4% of AAV patients, of them c-ANCA were 77.8% and p-ANCA 22.2%. ANCA was positive in 91.3% GPA, 100% MPA and 44.4% EGPA patients. In GPA c-ANCA were detected in 80.9% and p-ANCA in 17.4%, in MPA, c-ANCA were detected in 50% and p-ANCA in 50%, in EGPA, c-ANCA were observed in 75% and p-ANCA in 25%. GPA patients had PR3 specificity in 93.3%, and MPO in 6.7%, PR3 was present in all MPA patients [100%], while EGPA patients had MPO [100%]. Therapy administered were corticosteroids [100%], intravenous cyclophosphamide [58.8%], azathioprine [50%] and rituximab [11.8%]. Infections were noted in 29.4%

Conclusions: The 10-year survival in our AAV patients was 95%. ANCA pattern was similar to Caucasian AAV patients and different from Japanese and Chinese AAV patients

[Antithyroid drugs induced vasculitis]

The aim of this article is to review current information documented on antithyroid drug induced vasculitis. MEDLINE was searched for studies between 1960 and 2009 with the key words [antithyroid drugs and vasculitis], [antithyroid drugs and diffuse alveolar hemorrhage], and [antithyroid drugs and glomerolonephritis]. Ninety-two articles met the selection criteria. The data obtained showed that 15 to 46% of patients treated with propylthiouracil [PTU] developed anti-neutrophil cytoplasmic antibody [ANCA], in contrast to 0 to 3% of the patients treated with methimazole [MMI], the former being the most often reported for causing vasculitis, a disease seen most commonly in association with Graves' disease. Signs of PTU-induced vasculitis include fever, malaise, anemia, lymphadenopathy, skin lesions, arthralgia, hematuria/proteinuria, diffuse alveolar hemorrhage [DAH], pleural effusion, and crescentic glomerulonephritis. Once PTU-induced vasculitis is determined, the simple withdrawal of PTU usually causes resolution of the symptoms within 1-4 weeks. Overall prognosis of antithyroid drug-induced vasculitis is much better than that of primary vasculitis. Antithyroid medications such as PTU can induce [ANCA]-associated vasculitis. Its pathogenesis might be multifactorial. Diagnosis is based on the relationship between clinical vasculitis, and the antithyroid drugs prescribed, and the excluding of any other medical states that mimic vasculitis. After the diagnosis, antithyroid drugs should be discontinued immediately, and the prognosis is usually good