Caracterización de enfermedades glomerulares: análisis de 22 años de biopsias renales / Frequency of glomerular diseases in an analysis of 550 kidney biopsies

BACKGROUND: The frequency of glomerular diseases is dynamic and varies according to geographic area. AIM: To evaluate the frequency of primary and secondary glomerulopathies, their demographic profile and main clinical characteristics. MATERIAL AND METHODS: Renal biopsies from native kidneys performed between 1999 and 2020 were retrospectively reviewed. Demographic characteristics, clinical presentation, most relevant laboratory tests, frequency of primary and secondary glomerulopathies were analyzed. RESULTS: We analyzed 550 kidney biopsies from patients with a median age of 48 years (64% females). Nephrotic syndrome was the main indication for renal biopsy. Primary and secondary glomerulopathies occurred with similar frequency. Within the primary glomerulopathies, membranous nephropathy (34.1%) was the most common, followed by IgA nephropathy (31.1%) and focal segmental glomerulosclerosis (14.1%). Among the secondary glomerulopathies, lupus nephropathy was the most common (41.7%), followed by pauciimmune glomerulonephritis (27.1%) and diabetic nephropathy (6.4%). When comparing the results with other regions, significant differences were observed with reported frequencies in United States, Europe, Asia and the rest of Latin America. CONCLUSIONS: The most common primary glomerulopathies were membranous nephropathy and IgA nephropathy. Among the secondary glomerulopathies lupus nephropathy and pauci-immune glomerulonephritis were the most common. Compared to international registries, we observed a high proportion of membranous nephropathy and pauci-immune glomerulonephritis.

Bactericidal permeability increasing protein-anti-neutrophil cytoplasmic antibody- associated vasculitis complicated with bronchiectasis: a case report and literature review / 中华肾脏病杂志

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of systemic small vasculitis characterized by the detection of ANCA in serum. Bactericidal permeability enhancing protein (BPI) is one of the target antigens of ANCA. BPI-ANCA-associated vasculitis is not common clinically, and the combination of bronchiectasis is not accidental. The paper reported a case of BPI-ANCA-associated vasculitis with renal damage combined with bronchiectasis. We reviewed relevant literature to explore the characteristics of BPI-ANCA-associated vasculitis and the correlation between bronchiectasis and ANCA-associated vasculitis, so as to improve the clinician's understanding on this disease.

Anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis in human immunodeficiency virus infection: a case report and literature review / 中华肾脏病杂志

Anti neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a systemic disease characterized by small vessel wall inflammation and cellulose necrosis mediated by ANCA. Renal injury caused by AAV is called ANCA-associated glomerulonephritis (AAGN). The paper reported a case of AAV with renal damage combined with human immunodeficiency virus (HIV) infection. The patient was an elderly male with clinical manifestations of hematuria and uremia. Renal pathological examination showed AAV and renal injury. This case is the first report in China while reviewing the relevant literature, and it is still inconclusive whether this is an overlap of the two diseases or a specific pathological type of HIV-associated nephritis. We believe that AAV has the potential to occur in HIV-infected patients, so clinicians should not ignore the phenomenon of ANCA positivity in HIV-infected patients, and the follow-up of such patients needs to be enhanced. Clinical and renal pathological examinations are the main methods to diagnose HIV infection with AAV. At the same time, there are no clear guideline guidelines on how to administer immunosuppressive therapy for such patients who have immunodeficiency and are at higher risk of opportunistic infections, and in whom to make the best possible outcomes.

A case of anti-neutrophil cytoplasmic antibodies-associated vasculitis with ocular masses as the main manifestation / 中华肾脏病杂志

A case of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) with ocular masses as the main manifestation was reported. The patient was a middle-aged female, the initial symptom was eye swelling, pulmonary nodules were found before eye surgery, and further examination revealed proteinuria, hematuria and renal insufficiency. Renal pathology showed ANCA-associated glomerulonephritis. The final diagnosis was eye, kidney and lung lesions caused by AAV. Treatment with glucocorticoids and cyclophosphamide resulted in improvement in eye, kidney, and pulmonary lesions. Atypical clinical manifestations of AAV may lead to delayed diagnosis, and attention should be paid to the exclusion of AAV for ocular masses of unknown cause.

Anca-positive vasculitis with full-house nephropathy, an unusual association: a case report and review of literature / Vasculite ANCA-positivo com nefropatia full-house, uma associação incomum: um relato de caso e revisão de literatura

Abstract Rapidly progressive glomerulonephritis is a medical emergency, with mortality around 20%. It is characterized by crescent glomerulonephritis and progressive loss of kidney function, hematuria, and proteinuria. Its classification is given by immunofluorescence detection of antibodies against glomerular basement membrane (Anti-MBG), immunocomplexes, or pauci-immune pattern. Its etiology should be based on clinical findings, immunological profile, age, sex, and histopathological characteristics. We present a case of a 27-year-old woman with symptoms consistent with rapidly progressive glomerulonephritis and biopsy findings of a full-house kidney nephropathy, with an early fatal outcome. An association of low incidence, as it is a case with a full-house pattern, and an autoimmune profile for negative systemic lupus erythematosus makes this a rare case. ANCA-associated vasculitis with full-house kidney disease was diagnosed, an unusual condition with up to 3% presentation and few reports in the literature, highlighting the importance of its reporting and contribution to the literature.

Resumo A glomerulonefrite rapidamente progressiva é uma emergência médica, com mortalidade em torno de 20%. É caracterizada por glomerulonefrite com crescentes e perda progressiva da função renal, hematúria e proteinúria. Sua classificação é dada pela detecção na imunofluorescência de anticorpos anti-membrana basal glomerular (Anti-MBG), imunocomplexos, ou padrão pauci-imune. Sua etiologia deve ser baseada em resultados clínicos, perfil imunológico, idade, sexo e características histopatológicas. Apresentamos o caso de uma mulher de 27 anos de idade com sintomas consistentes com uma glomerulonefrite rapidamente progressiva e achados de biópsia de uma nefropatia com padrão full-house que evoluiu com desfecho fatal precoce. A associação de um padrão full-house, que possui uma baixa incidência, com um perfil autoimune para lúpus eritematoso sistêmico negativo torna este um caso raro. Foi diagnosticado vasculite associada ao ANCA com doença renal com padrão full-house. Por se tratar de uma condição incomum com até 3% de apresentação e poucos registros na literatura, destacamos a importância de seu relato e sua contribuição para a literatura.

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.

Efficacy of rituximab in maintenance therapy for antineutrophil cytoplasmic antibody-associated vas-culitis / 中华风湿病学杂志

Objective:To evaluate the efficacy and safety of rituximab(RTX) as remission-mainten-ance therapy in antineutrophil cytoplasmic antibody(ANCA) associated vasculitis(AAV).Methods:Patients with AAV, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), treated with rituximab (RTX) in Peking Union Medical College Hospital during September 2005 to June 2021 were included into this study. Clinical data, relapse rate, time of first relapse and adverse events were collected and analyzed. The cumulative relapse rate was calculated by Kaplan-Meier, t test, and Man-Whithey U test and chi-square were used to compare differences between two groups. Results:① Thirty-nine AAV patients were enrolled, including 36 GPA and 3 MPA. During the 20(3, 104) months follow-up, 59.0%(23/39) patients had suffered relapses. The time for first relapse was 11(3, 42) months after remission. ② There were no difference in the relapse rate [60.0%(18/30) vs 55.6%(5/9), χ2=0.06, P=1.000), the time of first relapse [15(3, 42) vs 10(9, 30), Z=0.45, P=0.678], CD19 + B [23.5 (5, 148) cell/μl vs 3(2, 15) cell/μl, Z=0.57, P=0.605] and serum IgG [7.09(5.13, 13.90) g/L vs 9.72(5.32, 12.0) g/L, Z=0.36, P=0.770] between standard dose and low-dose groups. The rate of major relapse-free was significantly less in patients treated with standard dose than patients with reduced dose of RTX {87.1%[95% CI(73.4%, 100.8R%)] vs 64.3%[95% CI(23.1%, 105.4%)], χ2=7.59, P=0.006}. ③ There were no difference in relapse rate [50.0%(3/6) vs 60.6%(20/33), χ2=0.24, P=0.674], time of first relapse [23(6, 25) vs 11(3, 42), Z=0.05, P=0.982], CD19 + B[35(15, 50) cell/μl vs 10(0, 148) cell/μl, Z=0.95, P=0.382] and serum IgG[6.70(5.91, 7.49) g/L vs 7.69(3.78, 13.90) g/L, Z=0.48, P=0.700] between the fixed interval dosage and the on-demand dosage groups. There was no difference in the rate of major relapse-free between the two groups (100% vs 77.8%, χ2=1.79, P=0.181). ④ The incidence of infusion reaction was 5.1%(2/39) and infection was 20.5%(8/39). Serum IgG level was 4.37(3.78, 13.4) g/L at infection. There was no difference in safety between the standard and low-dose groups or between fixed interval and on-demand dosage groups ( P>0.05). Conclusion:There is no significant difference in relapse rate bet-ween the standard RTX dose and low-dose RTX induction therapy group, but the major relapse rate is sign-ificantly reduced in the standard dose RTX therapy. The relapse rate of fixed intervals dosage group is similar to that of on-demand dosage group. The safety profile of the standard dose and low-dose induction therapy groups or fixed intervals and on-demand dosage groups is similiar.

Renal Amyloidosis Secondary to ANCA-Associated Vasculitis: A Case Report / 中国医学科学杂志(英文版)

Renal amyloidosis secondary to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is extremely rare. Here, we reported a 77-year-old woman with ANCA-associated vasculitis. Renal biopsy with Masson trichrome staining showed pauci-immune crescentic glomerulonephritis, and electron microscopy showed amyloid deposition in the mesangial area. Immunofluorescence revealed kappa light chain and lambda light chain negative. Bone marrow biopsy revealed no clonal plasma cell. Finally, she was diagnosed as ANCA-associated vasculitis with secondary renal amyloid A amyloidosis.

Antithyroid drugs-induced antineutrophil cytoplasmic antibody-associated vasculitis in children: report of three cases and literature review / 中华肾脏病杂志

Objective:To explore clinicopathological features and prognosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in children induced by antithyroid drugs.Methods:The clinicopathological features, treatment and prognosis of 3 children with AAV induced by antithyroid drugs in the Department of Pediatric Nephrology and Rheumatology of the First Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively, and the literatures were reviewed.Results:(1) Among the 3 cases, there were 2 females and 1 male, whose ages were 12.6, 13.9 and 13.1 years old, respectively. All patients had medication history of propylthiouracil (PTU) and/or methimazole (MMI) before onset. Initial manifestation was pallor and renal involvements with nephrotic proteinuria, hematuria and renal function abnormality, while 2 of them had hypertension. Extrarenal manifestations were also presented: case 1 presented with rash, arthralgia and cardiac insufficiency; case 2 had brain involvement with repeated convulsions; case 3 presented with arthralgia and lung involvement. They were all tested positive for p-ANCA and MPO-ANCA. Initial renal histopathology of the 3 cases were consistent with ANCA-associated glomerulonephritis, which were classified into sclerosis, crescentic and mixed class respectively. After 8 months of treatments, repeated renal biopsy of case 3 had demonstrated progression to sclerosis class. Antithyroid drugs (PTU or MMI) were discontinued in 3 cases, and the children were all treated with corticosteroid combined with intravenous pulse cyclophosphamide therapy. Plasma exchange was performed in case 2 and case 3 due to rapidly progressive glomerulonephritis and disease recurrence (suspected pulmonary hemorrhage), respectively. Case 3 was treated with rituximab combined with mycophenolate mofetil after recurrence. The extrarenal symptoms relieved quickly after treatments in all cases. P-ANCA and MPO-ANCA became negative in case 1 and case 2 after 6 months of treatments but they were persistently positive in case 3. Three cases were followed up for 24 months, 10 months and 12 months, respectively: case 1 develop chronic kidney disease (CKD) stage 2 with normal urinalysis; case 2 develop CKD stage 5 and had sudden death at home at 10-month follow-up; case 3 develop CKD stage 4 with nephrotic proteinuria and microscopic hematuria. (2) There were totally 30 pediatric cases with AAV induced by PTU and MMI, including 27 reported cases in the literature and 3 cases in this study. Symptoms of AAV appeared in children after an average administration of (37.5±4.0) months of PTU (range from one month to 96 months and 8 months of MMI alone). Kidney (28 cases, 93.3%) and lung (12 cases, 40.0%) were commonly involved, while brain (2 cases, 6.7%) was rarely involved. The pathological changes of kidney were crescent nephritis (5/23) and necrotizing pauci-immune complex nephritis (11/23). The total remission rate was 93.3% (28/30) after antithyroid drugs withdrawal and treatment with corticosteroids and immunosuppressive therapy, however, there were still severe cases with progression to CKD stage 5, and death. (3) Thirty cases were divided into complete response group ( n=19) and incomplete response group ( n=11) according to the treatment response. Compared with complete response group, the proportions of massive proteinuria (8/11 vs 5/19), fibrinoid necrosis (7/9 vs 4/14), deposition of immune complex in renal tissues (6/9 vs 2/14) and administration of immunosuppressants (10/11 vs 5/19), and degree of tubular atrophy (0/1/2/3 grade, 2/4/2/1 vs 9/5/0/0) in incomplete response group were higher (all P<0.05). Conclusions:PTU and MMI can both induce AAV in children, and AAV may occur after short-term course of administration. Kidney and lung are commonly involved while brain involvement is rarely seen. Timely withdrawal of antithyroid drugs and proper treatments with corticosteroids and immunosuppressants can result in high remission rate, though there are still some severe cases. Nephrotic-range proteinuria, renal fibrinoid necrosis, immune-complex deposition and tubular atrophy may be the risk factors of AAV for poor prognosis.

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

Objective: 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).Conclusion: PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.

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.

Recommendations on the diagnosis and treatment of anti-neutrophil cytoplasmic antibody associated vasculitis in China / 中华内科杂志

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a group of systemic small vasculitis characterized by ANCA positive in serum. Three diseases are included in this group of diseases: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). In China, standardized diagnosis and treatment of AAV is still lacking. Based on the evidence and guidelines from China and abroad, the Chinese Rheumatology Association formulated the standardization of diagnosis and treatment of ANCA associated vasculitis. The purpose is to standardize the diagnosis of AAV and disease activity assessment, and recommend the treatment strategies.

Glomerulonefritis crescéntica secundaria a consumo de cocaína adulterada con levamisol. Reporte de un caso y revisión de la literatura / Crescentic glomerulonephritis associated with levamisole-adulterated cocaine. A case report and a review of the literature

Resumen Introducción: El levamisol es un fármaco antihelmíntico, también conocido por su uso como inmunomodulador el cual, como consecuencia de sus efectos tóxicos, fue retirado a finales del siglo XX. En el 2005, producto de un incremento en el diagnóstico de vasculitis pauci-inmune entre la población usuaria de sustancias psicoactivas, se documentó la adulteración con fines comerciales de la cocaína combinándola con levamisol, a partir de un aumento de manifestaciones reumáticas asociadas al consumo de dicha droga. Reporte de caso: Se presenta el caso de un adulto joven con antecedentes de síndrome de Alport y consumo reciente de sustancias psicoactivas. Se realiza biopsia renal demostrándose la presencia de glomerulonefritis crescéntica pauci-inmune. Por lo anterior, se relacionó este tipo de vasculitis de pequeño vaso con afectación renal y depósito de complejos inmunes al consumo de cocaína adulterada con levamisol. Discusión: El levamisol, medicamento aprobado por la FDA en 1991, actúa como inmunomodulador, antiparasitario y coadyuvante en quimioterapia. El levamisol produce un síndrome reumático caracterizado por la presencia de glomerulonefritis, hemorragia alveolar, púrpura retiforme, neutropenia y agranulocitosis en relación con la presencia de anticuerpos anticitoplasma de neutrófilo. Conclusión: El levamisol es conocido por sus propiedades antihelmínticas e inmunomoduladoras, adicionalmente puede producir efectos tóxicos ostensibles. Dado el alto consumo de cocaína entre la población indigente, la presencia de este adulterante constituye un problema de salud pública creciente.

Abstract Introduction: Levamisole is an anthelmintic drug, also known for its use as an immunomodulator which, because of its toxic effects, was withdrawn at the end of the 20th century. In 2005, because of an increase in the diagnosis of pauci-immune vasculitis among the population that uses psychoactive substances, the adulteration of cocaine for commercial purposes by combining it with levamisole was documented. Case Report: The case of a young adult with a history of Alport Syndrome and recent consumption of psychoactive substances is presented. A renal biopsy is performed, demonstrating the presence of pauci-immune crescentic glomerulonephritis. Therefore, this type of small vessel vasculitis with kidney involvement and immune complex deposition was associated with the use of cocaine adulterated with levamisole. Discussion: Levamisole, a drug approved by the FDA in 1991, acts as an immunomodulator, antiparasitic and adjuvant in chemotherapy. Levamisole produces a rheumatic syndrome characterized by the presence of glomerulonephritis, alveolar hemorrhage, retinal purpura, neutropenia, and agranulocytosis in association with the presence of anti-neutrophil cytoplasmic antibodies. Conclusion: levamisole is known for its anthelmintic and immunomodulatory properties, additionally it can produce ostensible toxic effects. Given the high consumption of cocaine among the indigent population, the presence of this adulterant constitutes a growing public health problem.

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.

Update on vasculitis: an overview and dermatological clues for clinical and histopathological diagnosis - part I

Abstract The term vasculitis refers to the inflammation of vessel walls. It may range in severity from a self-limited disorder in one single organ to a life-threatening disease due to multiple organ failure. It has many causes, although they result in only a few histological patterns of vascular inflammation. Vessels of any type and in any organ can be affected, a fact that results in a broad variety of signs and symptoms. Different vasculitides with indistinguishable clinical presentations have quite different prognosis and treatments. This condition presents many challenges to physicians in terms of classification, diagnosis, appropriate laboratory workup, and treatment. Moreover, it compels a careful follow-up. This article reviews the Chapel-Hill 2012 classification, etiology, recent insights in pathophysiology, some important dermatological clues for the diagnosis and summarizes treatment of some of these complex vasculitis syndromes.

Psicosis y alteraciones en la sensopercepción como manifestaciones atípicas de la poliangitis microscópica / Psychosis and alterations in sensory perception as atypical manifestations of microscopic polyangiitis

RESUMEN La poliangitis microscópica es una vasculitis sistémica, asociada a la positividad de anticuerpos anticitoplasma de neutrófilos, caracterizada por el compromiso necrosante de los vasos de pequeño calibre. Las manifestaciones clínicas de la poliangitis microscópica son variadas y las formas más severas se manifiestan con glomerulonefritis rápidamente progresiva y capilaritis pulmonar. El compromiso nervioso afecta principalmente el sistema periférico. La afectación a nivel central no es común, y hallazgos clínicos de psicosis y alteración del comportamiento son bastante infrecuentes en el contexto de estas enfermedades autoinmunes.

A B S T R A C T Microscopic polyangiitis is a systemic anti-neutrophil cytoplasmic antibody-associated vasculitis, and is associated with the necrotising small calibre vessels. Its clinical manifestations are varied, and the most severe forms manifest with rapidly progressive glomerulonephritis and pulmonary capillaritis. In the nervous system, it mainly involves the peripheral system. Involvement of the central nervous system is not common, and clinical findings of psychosis and behaviour alterations are infrequent.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

SUMMARY Churg-Strauss syndrome, Eosinophilic granulomatosis with polyangiitis (EGPA), is a systemic vasculitis that affects small- to medium-sized vessels. It is rare and part of the Anti-neutrophil cytoplasm antibody-associated vasculitis (ANCA) group. We present a 37-year-old man, with a previous history of asthma, that was sent to the ED due to 2 weeks of productive cough, occasional dyspnea on exertion, fever (one week), asthenia, and anorexia. Upon physical examination, he was subfebrile and tachycardic. He had leukocytosis (17.00 x10^9/L) and eosinophilia of 20.0 % (3.4 X10^9/L), creatinine level of 1.5 mg/dL, subtle elevation on liver function tests and CRP of 10.82mg/dL. On Chest X-Ray, there was infiltrate on the right pulmonary base. Due to a strong suspicion of EGPA, he was started on 80mg of prednisolone from admission. ANCA MPO was positive, with the remaining auto-immune study negative. He underwent Thorax CT (under corticotherapy) without relevant changes, as well as bronchoalveolar lavage, without macroscopic signs of alveolar hemorrhage. Because of active urinary sediment, nephrotic proteinuria (6.5g/24h), and acute renal failure he underwent a renal biopsy, which revealed pauci-immune crescentic glomerulonephritis, with predominantly acute findings (in the context of ANCA-MPO Vasculitis - EGPA). After the biopsy, he received three 1g methylprednisolone pulses and was started on Cyclophosphamide. He remained asymptomatic and renal function was restored. This case highlights the importance of integrating all findings in one clinical scenario to prevent a more complex disease diagnosis, with a specific treatment, from being missed.

RESUMO A vasculite de Churg-Strauss, granulomatose eosinofílica com poliangeíte (EGPA), é uma vasculite sistêmica que afeta vasos de pequeno e médio calibre. É rara e pertence ao grupo de vasculites associadas a anticorpos anticitoplasma de neutrófilos (Anca). Apresenta-se um homem de 37 anos, com antecedentes de asma, que recorre ao SU por tosse produtiva com dois meses de evolução, dispneia ocasional em esforço, febre (uma semana de evolução), astenia e anorexia. Ao exame objetivo apresentava-se subfebril e taquicárdico. Analiticamente com leucocitose (17,00 x10^9/L) e eosinofilia de 20,0% (3,4 X10^9/L), creatinina de 1,5 mg/dL, discreta alteração das provas de função hepática e PCR de 10,82 mg/dL. Na radiografia de tórax objetivava-se infiltrado na base pulmonar direita. Por elevada suspeita de EGPA, iniciou prednisolona 80 mg desde a admissão. Anca MPO+, com restante estudo de autoimunidade negativo. Realizou TC tórax (sob corticoterapia) sem alterações de relevo, bem como lavado bronco-alveolar, sem sinais macroscópicos de hemorragia alveolar. Por sedimento urinário ativo, proteinúria na faixa nefrótica (6,56 g/24h) e lesão renal aguda, realizou biópsia renal que revelou glomerulonefrite crescêntica pauci-imune, com achados predominantemente agudos (no contexto de Vasculite Anca-MPO - EGPA). Após biópsia, realizou três pulsos de 1 g de metilprednisolona e iniciou ainda ciclofosfamida. Ficou assintomático e com recuperação da função renal. Este caso realça a importância de integração de todos os achados num só cenário a fim de evitar que escape o diagnóstico de uma doença mais complexa e com um tratamento específico.

Clinical characteristics and prognosis of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis / 第二军医大学学报

Objective: To analyze the clinical characteristics and prognosis of patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV). Methods: Clinical data (general information, clinical manifestation, and laboratory indexes) of 168 patients newly diagnosed as AAV between Jul. 2008 and Dec. 2016 were retrospectively analyzed. Patients were followed up for a median period of 12 months (range, 1-96 months). End-point event was death. Results: There were 152 cases of microscopic polyangiitis (MPA), 14 cases of granulomatous polyangiitis (GPA) and 2 cases of eosinophilic granulomatosis with polyangiitis (EGPA). MPO-ANCA was positive in 145 (86.3%) patients and PR3-ANCA was positive in 20 (11.9%) patients. Forty-nine patients died, 91 patients survived, and 28 patients lost their visits. Interstitial lung disease and renal involvement were more common in MPA patients as compared with GPA patients (50.7% [77/152] vs 14.3% [2/14], 78.9% [120/152] vs 50.0% [7/14], all P<0.05). Estimated glomerular filtration rate (eGFR) in MPA patients was significantly lower than that in GPA patients (14.23 [7.27, 71.49] mL/[min · 1.73 m2] vs 104.08 [16.61, 135.72] mL/[min · 1.73 m2], P<0.05). Compared with PR3-ANCA positive patients, MPO-ANCA positive patients was more elder ([64.01 ± 10.62] years vs [50.50±16.88] years), had more renal involvement (77.9% [113/145] vs 50.0% [10/20]) and lower eGFR (19.00 [9.40, 42.85] mL/[min · 1.73 m2] vs 149.40 [86.75, 249.45] mL/[min · 1.73 m2], all P<0.05). Compared with the survivals, the dead patients were older ([67.45±10.61] years vs [61.98 ± 12.52] years), had higher incidence of interstitial lung disease (59.2% [29/49] vs 41.8% [38/91]), higher Birmingham vasculitis activity score (BVAS) (18.53 ± 8.02 vs 13.68 ± 5.98), lower eGFR (8.58 [5.73, 22.07] mL/[min · 1.73 m2] vs 45.15 [11.54, 120.79] mL/[min · 1.73 m2], lower blood sodium concentration (137.00 [134.00, 140.00] mmol/L vs 139.00 [136.00, 141.00] mmol/L), lower albumin level ([28.41 ± 5.24] g/L vs [31.92 ± 5.91] g/L), and higher serum D-dimer level (2.84 [1.20, 6.28] mg/L vs 2.24 [0.80, 3.69] mg/L) (all P<0.05). Multivariate Cox proportional regression analysis showed that age, eGFR, serum albumin level and BVAS were independent influence factors of death (hazard ratio =1.058, 0.987, 0.932, and 1.086, all P<0.05). Conclusion: The clinical manifestations of AAV are mostly pulmonary and renal involvement. Age, eGFR, serum albumin level and BVAS are independent risk factors of death in AAV patients. Interstitial lung disease, high level of D-dimer and hyponatremia may be associated with prognosis of AAV.

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.