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.

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.

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.

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.

The expression and clinical significance of neutrophil myeloperoxidase in patients with myeloperoxidase-antineutrophil cytoplasmic antibody associated vasculitis / 中华内科杂志

Objective:To investigate the expression and clinical significance of neutrophil myeloperoxidase (MPO) in patients with MPO-antibody associated vasculitis (AAV).Methods:Thirty-six newly diagnosed MPO-AAV patients who were hospitalized in the First Affiliated Hospital, Anhui Medical University from July 2018 to June 2021 were enrolled,and 36 age and sex matched healthy subjects were selected as controls. Neutrophil MPO level was detected by flow cytometry (FCM) and MPO mRNA was tested by real time quantitative polymerase chain reaction (RT-qPCR) in all subjects. Serum complement fragment C5 (C5a) and MPO in both groups and serum MPO-anti-antineutrophilic cytoplasmic antibody(ANCA) in MPO-AAV group were measured by enzyme linked immunosorbent assay (ELISA), while the disease activity was evaluated by Birmingham vasculitis activity score-V3 (BVAS-V3).Results:Compared with the heathy control group, the expression of MPO mRNA in neutrophils, serum MPO and complement C5a in MPO-AAV group were significantly higher[MPO mRNA:30.2±11.5 vs. 1.9±0.6, P<0.001;MPO:(112.0±68.7) IU/L vs. (87.4±22.9) IU/L, P=0.01; C5a:(187.3±90.3) ng/ml vs. (107.3±31.1) ng/ml, P<0.001; respectively], while the mean fluorescence intensity (MFI) of MPO in neutrophils were significantly lower [ 1 343.3±723.4 vs. 2 868.0±1 136.5, P<0.001]. In MPO-AAV group, the expression of neutrophil MPO mRNA was positively correlated with serum MPO-ANCA and MPO levels ( r=0.537, P=0.001 and r=0.358, P=0.032; respectively). Multiple regression analysis suggested that neutrophil MPO mRNA expression was positively correlated with serum MPO-ANCA level ( β=0.695, P=0.006); neutrophil MPO level was negatively correlated with serum MPO-ANCA, MPO and complement C5a levels ( r=-0.335, P=0.046; r=-0.372, P=0.026; r=-0.577, P<0.001; respectively). Further, neutrophil MPO level was negatively correlated with serum complement C5a level ( β=-0.374, P=0.043). BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils, serum MPO-ANCA, MPO and complement C5a ( r=0.598, P<0.001; r=0.599, P<0.001; r=0.537, P=0.001; r=0.415, P=0.012; respectively) and negatively correlated with MPO level in neutrophils ( r=-0.342, P=0.041). In multiple regression analysis it suggested that BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils ( β=0.511, P=0.002). Conclusion:In MPO-AAV patients, MPO synthesis and release in neutrophils are both significantly increased, which might be influenced by serum MPO-ANCA and C5a, respectively. Furthermore, MPO synthesis activity in neutrophils is an independent factor related to disease activity.

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.

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.

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.

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.

Síndrome pulmón-riñón en pacientes con hallazgos incidentales de agentes infecciosos / Pulmonary-renal syndrome in patients with incidental findings of infectious agents

El síndrome pulmón-riñón (SPR) o síndrome reno-pulmonar es la combinación de glomerulonefritis aguda rápidamente progresiva (GNARP) y hemorragia alveolar difusa (HAD) de causa autoinmune. El SPR fue inicialmente descrito por Goodpasture en el contexto del síndrome anti-membrana basal glomerular (MBG). Actualmente, las vasculitis asociadas a ANCA (VAA) explican el 60% (rango 56­77.5%) de casos, el síndrome de Goodpasture el 15% (12.5­17.5%), y un 10% de casos se deben a otras causas. El SPR presenta un gran espectro clínico, desde la capilaritis pulmonar fulminante con HAD y falla respiratoria aguda, hasta formas más sutiles de enfermedad sólo detectables mediante lavado bronquio-alveolar (LBA). El objetivo de este estudio es presentar la primera serie peruana de SPR asociada a agentes infecciosos. Reportamos 3 casos, dos correspondieron a lupus eritematoso sistémico y uno a vasculitis asociada a poliangeítis microscópica. El primer caso se asoció a sobreinfección por C. tropicalis; el segundo caso a A. fumigatus y C. albicans; y el tercero a infestación por A. lumbricoides. Todos los casos se presentaron en mujeres, requirieron soporte ventilatorio invasivo y hemodiálisis, y dos resultaron letales. Concluimos que, el SPR es una condición clínica grave comúnmente asociada a sobreinfecciones o infestaciones, y que conlleva una elevada morbilidad y mortalidad. Puesto que no existen características clínicas específicas, resulta crucial tener un alto índice de sospecha. Las investigaciones pertinentes­pruebas inmunológicas, imagenológicas, y biopsia cutánea, renal y/o pulmonar­para precisar la etiología deben realizarse sin demora ya que el tratamiento precoz puede cambiar el pronóstico de estos pacientes(AU)

Pulmonary-renal syndrome (PRS) or reno-pulmonary syndrome is the combination of acute rapidly progressive glomerulonephritis (RPGNARP) and autoimmune diffuse alveolar hemorrhage (DAH). RPS was initially described by Goodpasture in the context of anti-glomerular basement membrane (GBM) syndrome. Currently, ANCA-associated vasculitides (AAV) explain 60% (range 56­77.5%) of cases, Goodpasture syndrome 15% (12.5­17.5%), and 10% of cases are due to other causes. PRS presents a wide clinical spectrum, from fulminant pulmonary capillaritis with ADH and acute respiratory failure, to subtler forms of disease that can only be detected by bronchoalveolar lavage (BAL). The objective of this study is to present the first Peruvian series of SPR associated with infectious agents. We report 3 cases, two corresponded to systemic lupus erythematosus and one to vasculitis associated with microscopic polyangiitis. The first case was associated with superinfection by C. tropicalis; the second case to A. fumigatus and C. albicans; and the third to infestation by A. lumbricoides. All cases occurred in women, required invasive ventilatory support and haemodialysis, and two were fatal. We conclude that SPR is a serious clinical condition commonly associated with superinfections or infestations, and that it carries high morbidity and mortality. Since there are no specific clinical features, a high index of suspicion is crucial. Relevant investigations­immunological tests, imaging tests, and skin, kidney, and/or lung biopsies­to specify the etiology should be carried out without delay, since early treatment can change the prognosis of these patients(AU)

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.

Armonización de la determinación de ANCA por inmunofluorescencia indirecta: primera reunión argentina / Harmonization of the determination of ANCA by indirect immunofluorescence: first argentine meeting / Harmonização da determinação de ANCA por imunofluorescência indireta: primeira reunião argentina

Resumen La determinación de anticuerpos anti-citoplasma de neutrófilos (ANCA) es utilizada en la clínica diaria como una herramienta diagnóstica en distintas formas de vasculitis de pequeños vasos (vasculitis asociadas a ANCA), incluyendo la granulomatosis con poliangeítis (antes: granulomatosis de Wegener), poliangeítis microscópica y granulomatosis eosinofílica con poliangeítis (antes: síndrome de Churg-Strauss), y como apoyo diagnóstico de colitis ulcerosa, colangitis esclerosante primaria y enfermedad de Crohn. Estos anticuerpos están dirigidos contra distintos epítopos antigénicos de diferentes proteínas presentes en el citoplasma del neutrófilo. La determinación de ANCA, habitualmente realizada por la técnica de inmunofluorescencia indirecta (IFI), presenta cierto grado de complejidad en la definición de las imágenes de los diferentes patrones, variabilidad en la forma de trabajo y expresión de resultados. El 24 de octubre de 2018 en el marco del X Congreso Argentino de la Calidad en el Laboratorio Clínico y VIII Jornadas Latinoamericanas de la Calidad en el Laboratorio Clínico, en la Ciudad de Buenos Aires, se realizó una reunión de Armonización de la Determinación de ANCA por IFI con el objeto de presentar, discutir y consensuar los distintos aspectos que se presentan en esta técnica. Las propuestas iniciales fueron discutidas arribándose a recomendaciones generales para proporcionar estándares de trabajo e interpretación de imágenes con el objeto de disminuir la variabilidad de resultados entre los laboratorios clínico-inmunológicos.

Abstract Anti-neutrophil cytoplasmic antibodies (ANCA) tests are widely used in daily clinical practice as a useful tool for the diagnosis of pathologies such as granulomatosis with polyangiitis, microscopic polyangiitis, pauci-immune necrotizing segmental glomerulonephritis and eosinophilic granulomatosis with polyangiitis, ulcerative colitis, primary sclerosing cholangitis, Crohn's disease, etc. These antibodies are directed against different antigenic epitopes of various proteins which are present in the neutrophil cytoplasm. ANCA testing is usually carried out by using indirect immunofluorescence (IIF) method. The determination of ANCA presents some difficulties in the definition of the images of the different patterns, work protocols and result reports uniformity. The "Harmonization Conference on the Determination of ANCA by IIF" was held within the framework of the X Argentine Congress on Quality in the Clinical Laboratory and VIII Latin American Conference on Quality in the Clinical Laboratory, in Buenos Aires, Argentina, on October 24, 2018, in order to present, discuss and agree on different aspects of this method. Some initial proposals were discussed, arriving at general recommendations to provide standards of work and an image interpretation, with the aim of reducing the variability of results among the clinical-immunological laboratories.

Resumo A determinação de anticorpos anti-citoplasma de neutrófilos (ANCA) é utilizada na prática clínica diária como um suporte diagnóstico para várias patologias, como granulomatose com poliangiite, poliangiite microscópica, glomerulonefrite segmentar necrotizante pauci-imune e granulomatose eosinofílica com poliangiite, poliarterite nodosa, colite ulcerosa, colangite esclerosante primária, doença de Crohn. Esses anticorpos são dirigidos contra diferentes epítopos antigênicos de diferentes proteínas presentes no citoplasma do neutrófilo. A determinação de ANCA, normalmente realizada pela técnica de imunofluorescência indireta IFI, apresenta certo grau de complexidade na definição das imagens dos diferentes padrões, variabilidade na forma de trabalho e expressão de resultados. Em 24 de outubro de 2018, no âmbito do X Congreso Argentino de la Calidad en el Laboratorio Clínico (X Congresso Argentino da Qualidade no Laboratório Clínico) e VIII Jornadas Latinoamericanas de la Calidad en el Laboratorio Clínico (VIII Jornadas Latino-americanas da Qualidade no Laboratório), na cidade de Buenos Aires, foi realizada uma Jornada de Harmonização da Determinação de ANCA pelo IFI a fim de apresentar, discutir e concordar sobre os diferentes aspectos que são apresentados nesta técnica. As propostas iniciais foram discutidas, chegando a recomendações gerais para fornecer padrões de trabalho e interpretação de imagens visando reduzir a variabilidade de resultados entre os laboratórios clínico-imunológicos.

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: overview and relevant dermatological aspects for the clinical and histopathological diagnosis - Part II

Abstract Vasculitis is a group of several clinical conditions in which the main histopathological finding is fibrinoid necrosis in the walls of blood vessels. This article assesses the main dermatological aspects relevant to the clinical and laboratory diagnosis of small- and medium-vessel cutaneous and systemic vasculitis syndromes. The most important aspects of treatment are also discussed.

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.