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.

Henoch-Schönlein purpura with c-ANCA antibody in an adult

Abstract: The Henoch-Schönlein purpura is the vasculitis associated with deposits of immunoglobulin A in small vessels. Its association with cytoplasmic antineutrophil cytoplasmic antibodies is possible, but rare. This vasculitis is uncommon in adults and the main clinic manifestations are purpuric lesions in lower limbs with gastrointestinal symptoms and renal involvement. The present work describes a rare case of Henoch-Schönlein purpura in an adult with cytoplasmic antineutrophil cytoplasmic antibodies.

Púrpura de Schönlein-Henoch en adulto HIV positivo adicto a cocaína y ANCA-p positivo / Henoch-Schönlein purpura in a cocaine consumer man with HIV infection and ANCA-p positivity

La púrpura de Schönlein-Henoch (PSH) es una vasculitis de pequeños vasos con depósito de inmunocomplejos de IgA. La presentación en adultos es rara y grave. Los casos comunicados de PSH en pacientes infectados por HIV son escasos. Los anticuerpos anticitoplasma de neutrófilos (ANCA), detectados por inmunofluorescencia indirecta (IFI), se encuentran comúnmente en otras vasculitis sistémicas primarias pero rara vez en PSH y es aún más inusual el patrón perinuclear (ANCA-p). Por otra parte, la positividad de los ANCA puede ser detectada en una serie de condiciones patológicas distintas de las vasculitis de pequeños vasos en asociación a procesos infecciosos, incluyendo el HIV, o a consumo de cocaína, y en especial el patrón de ANCA-p vinculado a medicamentos o enfermedades autoinmunes e inflamatorias intestinales. Se presenta el caso de un varón de 35 años con hábitos tóxicos (cocaína, marihuana) que consultó por dolor abdominal, hematoquecia y lesiones purpúricas en extremidades inferiores, que agregó fiebre, artralgias y progresión de lesiones purpúricas asociadas a síndrome nefrítico y ANCA-p (+). Durante la internación se detectó infección por HIV. La biopsia renal evidenció una nefropatía a IgA que tuvo una respuesta favorable al tratamiento corticoideo y antiproteinúrico. La comunicación del caso obedece a la rareza de la presentación y a la complejidad para establecer el diagnóstico y la terapéutica. Aún resta dilucidar el rol de los ANCA en la etiopatogenia y el manejo de la PSH del adulto.

The Henoch-Schönlein purpura (HSP) is a small vessel vasculitis with IgA immune complex deposition. The presentation in adults is rare and severe. Reported cases of HSP in patients infected with HIV are scarce. Neutrophil cytoplasmic antibodies (ANCA) are commonly found in other systemic vasculitis, but rarely in HSP and even more unusual the perinuclear pattern. Beside small vessel vasculitis, positivity of ANCA can be detected in a number of different pathological conditions in association with infectious processes, including HIV, or cocaine use, and especially the pattern of ANCA-p, associated with drugs, inflammatory bowel or autoimmune diseases. We report the case of a 35 years old man with toxic habits (cocaine, marijuana) who consulted for abdominal pain, hematochezia and purpura on lower extremities, and later fever, joint pain and progression of purpura associated with nephritic syndrome and ANCA-p (+). During hospitalization HIV infection was detected. Renal biopsy showed IgA nephropathy with favorable response to corticosteroid and antiproteinuric treatment. The communication of the case is due to the rarity of the presentation and therapeutic diagnostic challenge. It remains to elucidate the role of ANCA in the pathogenesis and management of adult PSH.

Long-term Prognosis of Anti-Neutrophil Cytoplasmic Antibody-Negative Renal Vasculitis: Cohort Study in Korea

Few studies have reported on the long-term prognosis of anti-neutrophil cytoplasmic antibody (ANCA)-negative renal vasculitis. Between April 2003 and December 2013, 48 patients were diagnosed with renal vasculitis. Their ANCA status was tested using indirect immunofluorescence and enzyme-linked immunosorbent assays. During a median (interquartile range) follow-up duration of 933.5 (257.5-2,079.0) days, 41.7% of patients progressed to end stage renal disease (ESRD) and 43.8% died from any cause. Of 48 patients, 6 and 42 were ANCA-negative and positive, respectively. The rate of ESRD within 3 months was higher in ANCA-negative patients than in ANCA-positive patients (P = 0.038). In Kaplan-Meier survival analysis, ANCA-negative patients showed shorter renal survival than did ANCA-positive patients (log-rank P = 0.033). In univariate Cox-proportional hazard regression analysis, ANCA-negative patients showed increased risk of ESRD, with a hazard ratio 3.190 (95% confidence interval, 1.028-9.895, P = 0.045). However, the effect of ANCA status on renal survival was not statistically significant in multivariate analysis. Finally, ANCA status did not significantly affect patient survival. In conclusion, long-term patient and renal survival of ANCA-negative renal vasculitis patients did not differ from those of ANCA-positive renal vasculitis patients. Therefore, different treatment strategy depending on ANCA status might be unnecessary.

Vasculitis asociadas a anticuerpos anti-citoplasma de neutrófilos: Clínica y tratamiento / Anti-neutrophil cytoplasmic antibody-associated vasculitis: Clinical aspects and treatment

Las vasculitis asociadas a anticuerpos anti-citoplasma de neutrófilos (ANCA) comprenden a un grupo de enfermedades caracterizadas por la inflamación de la pared de pequeños vasos. Analizamos las características epidemiológicas y clínicas en una serie de 47 pacientes: 23 (49%) granulomatosis de Wegener (GW), 15 (32%) poliangeítis microscópica (PAM) y nueve (19%) vasculitis limitada al riñón (VLR). La edad media al inicio de los síntomas fue de 50.7 ± 14.9 años. La manifestación clínica más frecuente fue el compromiso renal en 41 (87%) pacientes, seguido por el pulmonar en 26 (55%) y el otorrinolaringológico en 17 (36%). En 26 (55%) se asoció compromiso renal y pulmonar. La forma clínica más frecuente fue la generalizada en 23 (49%), seguida por la grave en 18 (38%). El 89% presentaron determinaciones de ANCA positivas. Cuatro (8%) no recibieron tratamiento inmunosupresor de inicio. De los 43 que recibieron tratamiento de inicio, 29 (67%) tuvieron remisión completa, con un tiempo de remisión promedio de 35.3 meses. Once (26%) presentaron recaídas, diez (91%) recaídas mayores y uno (9%) menor. Doce (28%) fallecieron, siete en forma temprana y cinco durante la evolución de la enfermedad. Quince (31%) evolucionaron a insuficiencia renal crónica. Los 26 pacientes en seguimiento tuvieron respuesta al tratamiento y 20 (77%) de ellos estaban en remisión al finalizar el estudio. Las vasculitis asociadas a ANCA continúan siendo enfermedades de alta morbilidad y mortalidad, a pesar de las mejorías logradas con los tratamientos inmunosupresores.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, comprise a group of diseases characterized by inflammation of the wall of small vessels. We analyzed epidemiological and clinical characteristics in a series of 47 patients, 23 (49%) with Wegener granulomatosis (WG), 15 (32%) with microscopic polyangiitis (MPA) and nine (19%) with renal limited vasculitis (RLV). The mean age at onset of symptoms was 50.7 ± 14.9 years. The most frequent clinical manifestation was renal involvement in 41 (87%), followed by pulmonary manifestations in 26 (55%) and ENT involvement in 17 (36%). In 26 (55%) it presented with simultaneous pulmonary and renal involvement. The most frequent clinical category was the generalized form in 23 (49%), followed by the severe form in 18 (38%). Eighty nine percent of patients had positive ANCA test. Four (8%) received no immunosuppressive treatment. Of the 43 patients who were treated, 29 (67%) achieved complete remission with an average length of remission of 35.3 months. Eleven (26%) had a relapse, ten (91%) had a major relapse and one had a minor relapse. Twelve (28%) patients died, seven died early and five late during the course of the disease. Fifteen (31%) progressed to chronic renal failure. All 26 patients in follow-up had response to treatment and 20 (77%) were in remission at the end of the study. Despite the improvements achieved with immunosuppressive treatments, morbidity and mortality rates in ANCA-associated vasculitis remain high.

A Case of Elderly-Onset Crescentic Henoch-Schonlein Purpura Nephritis with Hypocomplementemia and Positive MPO-ANCA

Henoch-Schonlein purpura (HSP) is common in childhood and often self-limiting. There have been limited studies on elderly-onset HSP nephritis (HSPN). A 76-yr-old man was transferred to our hospital with a 1-month history of oliguria, abdominal pain, edema and palpable purpura in the legs. Three months ago, he was admitted to another hospital with jaundice, and consequently diagnosed with early common bile duct cancer. The patient underwent a Whipple's operation. Antibiotics were administrated because of leakage in the suture from the surgery. However, he showed progressive renal failure with edema and purpura in the legs. Laboratory investigations showed serum creatinine 6.4 mg/dL, 24-hr urine protein 8,141 mg/day, myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) 1:40 and C3 below 64.89 mg/dL. Renal biopsy showed crescentic glomerulonephritis, as well as mesangial and extracapillary Ig A deposition. We started steroid therapy and hemodialysis, but he progressed to end-stage renal failure and he has been under maintenance hemodialysis. We describe elderly onset HSPN with MPO-ANCA can be crescentic glomerulonephritis rapidly progressed to end stage renal failure.

Granulomatosis de Wegener y tuberculosis: Una mala combinación / Wegener's granulomatosis and tuberculosis: A bad combination

La enfermedad de Wegener es una vasculitis de pequeños y medianos vasos asociada a anticuerpos anticitoplasma del neutrófilo (ANCA). Dentro de los órganos blancos, el pulmón se encuentra comprometido en el 85% de los casos. Numerosas entidades deben ser consideradas en el diagnóstico diferencial, entre ellas, la tuberculosis pulmonar. Presentamos el caso de un hombre de 54 años de edad, con diagnóstico en el año 1996 de enfermedad de Wegener, que comienza en agosto de 2007 con expectoración hemoptoica, disnea de esfuerzo progresiva y esputo con baciloscopia BAAR (+), por lo que inicia tratamiento antituberculoso. La baciloscopia no se constata en dos lavados broncoalveolares contemporáneos. Evoluciona con deterioro de la función renal, púrpura palpable y anticuerpos anticitoplasma del neutrófilo patrón citoplasmático (ANCA-c) positivo. Se interpreta reactivación de su enfermedad de base. Inicia tratamiento inmunosupresor y hemodiálisis y suspende tratamiento antituberculoso. Un mes después del alta se reinterna con cuadro similar al previo, con esputo seriado positivo para BAAR.

Wegener's disease is a vasculitis of small and medium-sized vessels associated with anti-neutrophil cytoplasm antibodies (ANCA). Within their target organs the lungs are involved in 85% of cases. Many entities are part of the differential diagnosis, including pulmonary tuberculosis. We present the case of a 54 years old man, diagnosed as Wegener's disease in 1996 which begins in August 2007 with cough, hemoptysis, progressive dyspnea on effort and serial sputum positive for AFB and then starts TB treatment. Subsequent bronchoalveolar fluids resulted negative for AFB. The patient evolved with impaired renal function, palpable purpura and positive anti-neutrophil cytoplasm antibodies cytoplasmic pattern (c-ANCA), interpreted as Wegener's disease relapse. He started hemodialysis and immunosuppressive therapy and tuberculosis treatment was stopped. One month after discharge was readmitted with a similar picture with serial sputum positive for AFB.

Acro-osteolysis and mononeuritis multiplex as a presenting symptom of systemic angiitis of Wegener's type.

Wegener's granulomatosis is a multisystem disorder involving small- and medium-sized vessels, leading to granuloma formation and involvement of upper and lower respiratory tract with or without glomerulonephritis. However, limited forms of angiitis and granulomatosis of the Wegener's type with oligosymptomatic and atypical site involvement are known to occur. We present here a rare case of limited form of angiitis and granulomatosis of Wegener's type who presented sequentially with spontaneous resorption of digits with acro-osteolysis and mononeuritis multiplex over a period of 10 months. His vasculitic workup revealed high proteinase 3 antibodies (c-ANCA) titers and an almost asymptomatic lung involvement, detected on high-resolution computed tomography of chest. The patient was aggressively treated with immunosuppressive therapy, following which he showed good improvement.

Vasculitis syndrome: an approach.

Vasculitides are clinical syndromes characterized by vessel wall inflammation and resultant organ damage. Pathogenesis involves autoimmune reactions from type I to type IV. Vasculitis may be primary or secondary to infective and connective tissue disorders. The extent of damage may involve multiple organ systems or may remain limited to skin only. As the vasculitic syndromes display a multitude of variable presentations, there can be no uniform laid out guidelines or evaluation scale for the diagnosis of these conditions. High degree of suspicion, a detailed history regarding onset of disease and course of illness, meticulous physical examination, and appropriate laboratory tests to determine organ systems involved and the extent of involvement, lead to the diagnosis of specific syndrome. Anti-neutrophil cytoplasmic antibodies (ANCA), urinalysis, organ-specific biopsy and arteriography are the main diagnostic modalities for the diagnosis of vasculitis.

Avaliaçäo dos métodos de identificaçäo do anticorpo anticitoplasma de neutrófilo (ANCA) / A critical evaluation of methods for the detection of anti-neutrophil cytoplasmatic antibodies (ANCA) subtypes

A literatura referente ao anticorpo anticitoplasma de neutrófilo (ANCA) chama atençäo para a grande importância deste no diagnóstico e monitoramento clínico de várias entidades que têm em comum um processo inflamatório do vaso, do rim e ou do pulmäo; entretanto, ainda se faz necessário uma análise crítica referente aos métodos utilizados para sua identificaçäo e caracterizaçäo. Neste estudo analisamos os três métodos mais utilizados na detecçäo e caracterizaçäo do ANCA, com objetivo de caracterizar o mais específico, sensível e econômico. Os métodos säo: imunofluorescência indireta (IFI), utilizando com substrato neutrófilos humanos, enzima imunoensaio (ELISA) para proteinase 3 (PR3) e "western blot", a partir de extrato semipurificado de neutrófilos humanos. Utilizamos o soro de 139 pacientes portadores de doenças autoimunes, infecciosas e vasculites e o soro de 10 indivíduos sadios que serviram de controle negativo. A concordância de resultados entre os três métodos utilizados permite concluir que a IFI representa um bom teste de triagem na detecçäo do ANCA, por tratar-se de um método mais econômico, entretanto menos específico. O ELISA e o "western blot" apresentaram-se mais específicos e sensíveis, porém de alto custo, sendo indicados quando a caracterizaçäo do ANCA fizer-se necessária.

Diagnostic Role of Anti-Saccharomyces cerevisiae and Antineutrophil Cytoplasmic Autoantibodies in Pediatric Inflammatory Bowel Disease / 대한소화기학회지

BACKGROUND/AIMS: Combined measurement of perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) and anti-Saccharomyces cereviseae mannan antibodies (ASCA) has recently been suggested as a valuable diagnostic approach to inflammatory bowel disease (IBD) in the pediatric age group. The aim of this study was to test the accuracy of the assay using pANCA and ASCA in diagnosing pediatric ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Sera were collected from 25 patients with IBD (17 with CD, 8 with UC) and 32 healthy controls. The levels of pANCA and ASCA were determined by using a standard indirect immunofluorescence technique on ethanol-fixed granulocytes and an ELISA assay, respectively. RESULTS: In patients with UC, the sensitivity, specificity, and positive predictive value of the pANCA test were 38%, 88%, and 60%, respectively. Such values were not changed significantly in the case of positive pANCA and negative ASCA. The sensitivity, specificity, and positive predictive value of ASCA test in diagnosing CD were 71%, 88%, and 92%, respectively. The combination of pANCA negative and ASCA positive was not significant. CONCLUSIONS: ASCA and pANCA assays are highly disease specific for CD and UC, respectively. These serological tests can assist clinicians in diagnosing and categorizing patients with IBD and may be useful in making therapeutic decisions.

Antineutrophil cytoplasmic antibody (ANCA) and rapidly progressive crescentic glomerulonephritis in Thai population.

The impact of vasculitis as a cause of primary rapidly progressive crescentic glomerulonephritis (RPGN) was examined in patients with Thai ethnic by antineutrophil cytoplasmic antibody (ANCA) test. Thirty patients found in a six years study period were included. Patients' mean age was 34.8+/-16.4 years. Mean crescent score was 86.2+/-22.9%. ANCA proved positive in fifteen patients. This helps to differentiate vasculitis associated (ANCA positive) from nonvasculitis (ANCA negative) RPGN. Incidence of immune complex type RPGN (46.6%) is higher than the Caucasians while the incidence of antiglomerular basement membrane antibody (anti-GBM disease) is much lower. More vasculitis patients were treated with cyclophosphamide (n = 11) than the nonvasculitis group (n = 2). Mean renal survival time of ANCA and non-ANCA associated patients were 26.69 and 14.16 months, respectively. Renal survival of all patients is significantly worse if associated with a high entry creatinine (>6 mg/dl). Our results show that vasculitis associated RPGN is not an uncommon disease in the Thai population and can be recognized initially by ANCA test.

Massa intracardíaca em provável caso de granulomatose de Wegener / Wegener's granulomatosis in a patient with intracardiac mass

A granulomatose de Wegener, doença conhecida há aproximadamente 65 anos, continua sendo um dilema para a classe médica, talvez pelo seu polimorfismo clínico, talvez pela carência de métodos diagnósticos. Seu diagnóstico laboratorial repousa no binômio: dosagem do anticorpo anti-neutrófilo em sua fração citoplasmática (ANCA-c) e na obtenção de material para análise anatomopatológica. Descrevemos aqui, o caso de um paciente, em cuja evolução clínica pôde ser observada todo aspecto proteiforme desta doença, chamado atenção para o envolvimento cardíaco. Este último considerado por muitos como pouco usual, manifestou-se clinicamente sob a forma de miocardite, pericardite e de uma massa intracardíaca.

A possible defective estimation of antineutrophil cytoplasmic antibodies in systemic lupus erythematosus due ot the coexistence of periodontitis: preliminary observations

The objectives of this study is to determine if periodontitis-related ANCA hinder the accurate estimation of this kind of autoantibodies in systemic lupus erythematosus (SLE), due to the frequent coexistence of SLE and periodontitis, and the high incidence of antineutrophil cytoplasmic antibodies (ANCA) in this periodontal condition. Thirty SLE, thirty periodontitis lacking systemic involvement patients, and twenty healthy controls were utilized in this study. The periodontal condition and the presence of ANCA in sera of all individuals was carefully evaluated. For ANCA determination an EIA essay was utilized, directed to a neutrophil granular extract and six neutrophil granule proteins. Sixty percent of SLE patients had periodontitis, and sixty-five percent were ANCA positive. Eighty three percent of all ANCA cases were coexisting with periodontitis. A significant association (p > 0.005) between periodontitis and ANCA was found (Chi Square Test). Fifty percent of the patients with periodontitis lacking systemic involvement were ANCA positive. The results obtained in this study suggest that the figures of ANCA previously reported for SLE, might be overestimated due to the inadvertent presence of periodontitis

Anticuerpos anticitoplasma de neutrófilo: ficción o realidad?

Los anticuerpos anticitoplasma de neutrófilo (Antineutrophil cytoplasmic antibodies -ANCA-) se han descrito en asociación con la Granulomatosis de Wegener (GW), la Poliarteritis Nodosa Micrscópica (PNM), la Glomerulonefritis (GN) focal y segmentaria con formación de medias lunas y el sindrome de Kawasaki (SK). Están dirigidos contra la proteinasa 3, la mieloperoxidasa (MPO) y la elastasa, enzimas presentes en los gránulos primarios o azurófilos de los neutrófilos. La mayoría de ellos son anticuerpos de la clase de IgG, aun cuando se han descrito ANCA de la clase de IgM e IgA. La Inmunofluorescencia Indirecta (IFI) es el método standard utilizado para su detección. El hallazgo de ANCA es importante como ayuda diagnóstica en el estudio de cierta vasculitis, y los anticuerpos tipo ANCA parecen jugar un papel importante en la patogénesis de estas enfermedades