Characteristics and Prognosis of Microscopic Polyangiitis Patients with Diffuse Alveolar Hemorrhage and Interstitial Lung Disease / 中国医学科学杂志(英文版)

Objective To evaluate the clinical characteristics and prognostic predictors of patients with diffuse alveolar hemorrhage (DAH) and/or interstitial lung disease (ILD) secondary to microscopic polyangiitis (MPA) in a Chinese general hospital. Methods We retrospectively reviewed the medical records of MPA patients admitted to internal medicine departments between the year 2002 and 2012. The patients were divided into the ILD, DAH, DAH combined with ILD (DAHILD), and no pulmonary involvement (NPI) groups according to pulmonary involvement patterns. The clinical characteristics at diagnosis were analyzed. The risk factors associated with short-term death and long-term death were identified with Logistic regression and Cox analysis.Results Of 193 newly diagnosed MPA patients, 181 patients were enrolled in the research, of which 19 had DAH alone, 96 had ILD alone, 18 had DAH and DAH concurrently, and 48 had NPI. The median of serum creatine level in the DAH group was 449 μmol/L, significantly higher than that in the ILD group (123 μmol/L, Nemenyi = -35.215, P = 0.045) and DAHILD group (359 μmol/L, Nemenyi = -43.609, P = 0.007). The median follow-up time was 67 (range: 1-199) months. Patients in the ILD group were older than those in the DAH group (median: 69 years vs. 57 years, Nemenyi = 43.853, P= 0.005). The patients with both DAH and ILD had combined features of the two subtypes, and the highest mortality (72.2% at the end of follow-up). The elevated white blood cell count was a risk factor for short-term death (OR = 1.103, 95%CI: 1.008-1.207, P = 0.032 for one month; OR = 1.103, 95%CI: 1.026-1.186, P = 0.008 for one year). Old age (HR= 1.044, 95%CI: 1.023-1.066, P < 0.001), cardiovascular system involvement (HR = 2.093, 95%CI: 1.195-3.665, P = 0.010), poor renal function (HR = 1.001, 95%CI: 1.000-1.002, P = 0.032) were risk factors for long-term death. Pulmonary infections (38/54) were the leading causes of death, especially for the patients with ILD. Besides, 49 patients suffered from pulmonary infections in the first year after diagnosis. Conclusions MPA patients who presented with different pulmonary involvement patterns have completely different clinical features. These subtypes probably have different pathogenesis and should be studied separately.

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

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

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

Eficácia e segurança de Rituximabe comparado a outras drogas no tratamento de vasculites sistêmicas: revisão rápida de evidências / Efficacy and safety of Rituximab compared to other drugs in the treatment of systemic vasculitides: rapid response review of evidence

Objetivo: descrever as evidências disponíveis na literatura científica sobre eficácia e segurança do rituximabe comparado a diferentes tratamentos. Materiais e métodos: é uma revisão rápida de evidências científicas para tomada de decisão informada por evidências em políticas e práticas de saúde. Conclusão: o Rituximabe tem eficácia e segurança similares à da Ciclofosfamida, para terapia de indução de remissão e para manutenção da remissão e, para pacientes com doença recidivante, o Rituximabe é mais eficaz que a Ciclofosfamida para manter a remissão. Para terapia de manutenção, Rituximabe é mais eficaz que Azatioprina, com perfil de segurança similar. Diferentes regimes de dosagem do Rituximabe tem eficácia e segurança similar para terapia de manutenção. O Infliximabe parece ser superior ao Rituximabe nos desfechos de eficácia (indução e manutenção da remissão).

Objective: to describe the evidence available in the scientific literature on the efficacy and safety of rituximab compared to different treatments. Materials and Methods: is a rapid review of scientific evidence for evidence-informed decision making in health policy and practice. Conclusion: Rituximab has similar efficacy and safety to Cyclophosphamide, for remission induction therapy and for maintenance of remission, and for patients with relapsing disease, Rituximab is more effective than Cyclophosphamide in maintaining remission. For maintenance therapy, Rituximab is more effective than Azathioprine, with a similar safety profile. Different dosing regimens of Rituximab have similar efficacy and safety for maintenance therapy. Infliximab appears to be superior to Rituximab in efficacy outcomes (induction and maintenance of remission).

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.

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

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

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

Manifestaciones imagenológicas pulmonares y abdominales de las vasculitis primarias / Imaging of Pulmonary and Abdominal Manifestations of Primary Vasculitis

Las vasculitis son un grupo de enfermedades que consisten en la inflamación dentro y alrededor de la pared de los vasos sanguíneos, lo que produce necrosis, y su extensión depende del tamaño y ubicación del vaso afectado. Se pueden manifestar en cualquier órgano, por lo que se consideran enfermedades sistémicas. Las vasculitis primarias son patologías poco comunes y difíciles de diagnosticar, porque sus signos y síntomas son inespecíficos y pueden confundirse con muchas otras patologías ­como enfermedades infecciosas, neoplásicas o del tejido conjuntivo­. Por esta razón, para su diagnóstico es importante combinar los hallazgos clínicos, radiológicos, de estudios histopatológicos y de laboratorio. Esta revisión se enfocará en el papel de los hallazgos imagenológicos en el diagnóstico y monitoreo de las manifestaciones pulmonares y abdominales de las vasculitis más frecuentes.

Vasculitis are a group of diseases that are characterized by the presence of inflammation in and around the wall of the blood vessels. This produces necrosis and inflammation where the extension of the injury depends on the size and location of the affected vessel. They can have manifestations in any organ, so they are considered systemic diseases. Primary vasculitis are uncommon pathologies and difficult to diagnose because its signs and symptoms are nonspecific and are easily confused with many other disease processes such as infectious, neoplastic or connective tissue. Because of this, it is important to combine clinical, radiological, histopathological and laboratory findings to achieve a correct diagnosis. In this review, we will focus on the role of imaging findings on the diagnosis and monitoring for pulmonary and abdominal manifestations of the most frequent vasculitis.

Microscopic polyangiitis and antiphospholipid syndrome. An uncommon association / Poliangitis microscópica y síndrome antifosfolípido. Una asociación infrecuente

ABSTRACT Antiphospholipid syndrome is frequently associated with systemic lupus erythematosus and other autoimmune diseases. However, coexistence with primary vasculitis has been poorly reported. The case is presented of a 67-year-old patient with a history of recurrent abortion and chronic pulmonary thromboembolism who was admitted due to haemopty sis. At the initial evaluation, a massive alveolar haemorrhage and glomerulonephritis were diagnosed. The results of the antibodies were positive for ANCA with P-type pattern, anti-myeloperoxidase antibodies, and antiphospholipid antibodies (anti-β2 IgG glycoprotein 1 and lupus anticoagulant). Diagnosis of ANCA positive vasculitis-type microscopic polyangiitis was made in association with antiphospholipid syndrome. Given the clinical context, it was decided to initiate intravenous methylprednisolone in pulses for 3 consecutive days, fol lowed by oral prednisone, and as maintenance therapy, rituximab and anticoagulation with warfarin were instituted. The clinical evolution of the patient was satisfactory, with symp tom control being achieved, as well as a significant improvement of renal and pulmonary function, with a decrease in the Birmingham vasculitis activity score (BVAS).

RESUMEN El síndrome antifosfolípido se asocia frecuentemente con lupus eritematoso sistémico y otras enfermedades autoinmunes. Sin embargo, la coexistencia con vasculitis primaria ha sido poco reportada. Se presenta el caso de una paciente de 67 arios de edad con historia de aborto recurrente y tromboembolismo pulmonar crónico, quien es admitida para estudio de hemoptisis. A la evaluación inicial se diagnosticó una hemorragia alveolar masiva y glomerulonefritis. El resultado de los anticuerpos fue positivo para anticuerpos anticitoplasma de neutrófilos (ANCA) con patrón tipo perinuclear, anticuerpos anti-mieloperoxidasa y anticuerpos antifosfolípidos (anti (32 glicoproteína 1 IgG y anticoagulante lúpico), configurándose el diagnóstico de vasculitis asociada a ANCA de tipo poliangitis microscópica en asociación con síndrome antifosfolípido. Dado el contexto clínico, se decidió iniciar metilprednisolona intravenosa en pulsos por 3 días consecutivos, seguida de prednisona oral, y como terapia de mantenimiento se instauró rituximab y anticoagulación con warfarina. La evolución clínica de la paciente fue satisfactoria, alcanzando control de síntomas e importante mejoría de la función renal y pulmonar, con disminución del score BVAS.

Comparison of Radiological and Histological Findings of Lung Parenchyma in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

PURPOSE: The present study investigated chest computed tomography (CT) patterns and lung histological features, as well as the consistency between radiological and histological features among patients with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic GPA (EGPA). MATERIALS AND METHODS: The medical records of 74 antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients with radiological lung parenchymal lesions were reviewed along with the histological results for 28 of them. Chest CT patterns were divided according 12 items mostly suggested by radiologists and histological features were divided according to necrotising granuloma, necrotising vasculitis, eosinophilic infiltration, and hemosiderin laden macrophages as defined by a pathologist. RESULTS: The mean age was 57.1 years (22 men). The most common clinical manifestation other than lung manifestation was renal manifestation (62.2%), and the most common chest CT pattern was lung involvement of vasculitis (35.1%). In MPA patients, the major histological features were hemosiderin-laden macrophages in the alveolar space and vasculitis. In GPA patients, the major histological features were necrotizing vasculitis and necrotizing granuloma, while in EGPA patients, the major histological feature was only necrotising vasculitis. The consistency rate in GPA patients was the highest (100%), followed by that in MPA patients (66.7%) and EGPA patients (50.0%). CONCLUSION: When lung involvement of AAV is suspected on chest CT, lung biopsy should be recommended for the proper classification of AAV, due to the discordance rate between radiological and histological findings in MPA and EGPA patients, but not GPA patients.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in Korea: A Narrative Review

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a group of systemic necrotising vasculitides, which often involve small vessels, and which lead to few or no immune deposits in affected organs. According to clinical manifestations and pathological features, AAV is classified into three variants: microscopic polyangiitis, granulomatosis with polyangiitis (GPA), and eosinophilic GPA. The American College of Rheumatology 1990 criteria contributed to the classification of AAV, although currently the algorithm suggested by the European Medicines Agency in 2007 and the Chapel Hill Consensus Conference Nomenclature of Vasculitides proposed in 2012 have encouraged physicians to classify AAV patients properly. So far, there have been noticeable advancements in studies on the pathophysiology of AAV and the classification criteria for AAV in Western countries. However, studies analysing clinical features of Korean patients with AAV have only been conducted and reported since 2000. One year-, 5 year-, and 10 year-cumulative patient survival rates are reported as 96.1, 94.8, and 92.8%. Furthermore, initial vasculitis activity, prognostic factor score, age and specific organ-involvement have been found to be associated with either all-cause mortality or poor disease course. The rate of serious infection is 28.6%, and 1 year-, 5 year- and 10 year-cumulative hospitalised infection free survival rates range from 85.1% to 72.7%. The overall standardised incidence ratio of cancer in AAV patients was deemed 1.43 compared to the general Korean population.

Classification of Antineutrophil Cytoplasmic Antibody-associated Vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of systemic vasculitides, that are characterized by inflammation in the small vessels, ranging from capillaries to arterioles or venules. AAV is divided into three variants based on the clinical manifestations and histological findings such as microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA). MPA often induces rapid progressive necrotising glomerulonephritis, and occasionally induces diffuse alveolar hemorrhage. In contrast, GPA preferentially affects the respiratory tracts from the bronchus to the nasal cavity. GPA can also involve the kidneys, but the frequency of renal involvement is less than MPA. EGPA is based on allergic components such as asthma, peripheral eosinophilia, migratory eosinophilic pneumonia and eosinophil infiltration. Since 1982, when the association between ANCA and systemic vasculitis was first reported, several classification criteria for AAV have been proposed. This review describes the classification criteria for and nomenclature of AAV from the 1990 American College of Rheumatology (ACR) classification criteria to the 2012 revised Chapel Hill consensus conference (CHCC) nomenclature of Vasculitides. New classification trials for AAV such as AAV based on the ANCA-types (myeloperoxidase-ANCA vasculitis, proteinase 3-ANCA vasculitis and ANCA negative vasculitis) and the ACR/European League Against Rheumatism (EULAR) 2017 provisional classification criteria for GPA were also introduced. In addition, the histopathological classification of ANCA-associated glomerulonephritis and the revised 2017 international consensus on testing of ANCAs in GPA and MPA are also discussed.

Poliangiite microscópica com síndrome pulmão-rim: relato de caso e revisão de literatura / Microscopic polyangiitis with lung-kidney syndrome: case report and literature review

A poliangiite microscópica (PAM) é uma vasculite necrosante sistêmica pauci-imune associada ao anticorpo anticitoplasma de neutrófilos (ANCA) com preferência de pequenos vasos. Relato do caso: Relatamos o caso de uma paciente do sexo feminino, 54 anos, que apresentou quadro de poliartrite migratória em punhos, joelhos e tornozelos associada à rigidez matinal progressiva, com histórico de "rash" malar, fotossensibilidade e alopecia. Progrediu ao longo do ano de 2017 com deterioração da função renal e hemorragia pulmonar, necessitando de cuidados intensivos. A biópsia renal sugeriu padrão compatível com glomerulonefrite pauci-imune e o diagnóstico de poliangiite microscópica foi aventado. Realizou pulsoterapia com metilprednisolona e ciclofosfamida, além de plasmaférese, recebendo alta após estabilização do quadro clínico. Importância do problema: O presente caso ilustra uma complicação incomum e de elevada morbimortalidade da PAM. A negatividade do ANCA dificultou o diagnóstico, sendo necessária a realização de biópsia renal com confirmação diagnóstica. A síndrome pulmão-rim apresenta evolução potencialmente fatal se não instituído precocemente o tratamento. (AU)

Microscopic polyangiitis (MPA) is a pauci-immune systemic necrotizing vasculitis associated with neutrophil anti-cytoplasmic antibody (ANCA) with a preference for small vessels. Case report: We report the case of a 54-year-old woman, who presented migratory polyarthritis in wrists, knees and ankles associated with progressive morning stiffness, with history of malar "rash", photosensitivity and alopecia. It progressed throughout the year of 2017 with deterioration of renal function and pulmonary hemorrhage, requiring intensive care. Renal biopsy suggested a pattern compatible with pauci-immune glomerulonephritis and the diagnosis of microscopic polyangiitis was suggested. She underwent pulse therapy with methylprednisolone and cyclophosphamide, in addition to plasmapheresis, being discharged from hospital after stabilization of the clinical condition. Importance of the issue: The present case reveals an uncommon and high morbimortality complication of MPA. The negativity of the ANCA made diagnosis difficult, and a renal biopsy was necessary to confirm diagnosis. Lung-kidney syndrome is potentially fatal if the treatment is not instituted early. (AU)

Tratamiento exitoso de poliangeítis microscópica con compromiso grave del sistema nervioso central y renal en una paciente anciana / Successful treatment of microscopic polyangiitis with severe compromise of central nervous system and renal in a very elderly patient

RESUMEN El compromiso neurológico del sistema nervioso central (SNC) en las vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos (ANCAS, del inglés anti-neutrophil cytoplasmic autoantibodies) es raro y potencialmente catastrófico. El estándar de tratamiento ha sido la ciclofosfamida con pulsos de esteroides, sin embargo, este esquema no tiene evidencia fuerte para el compromiso del sistema nervioso central y no está exento de efectos adversos graves sobre todo en la población anciana. En los últimos años, ha aparecido el rituximab como terapia alternativa a la ciclofosfamida para inducir la remisión en este tipo de vasculitis, no obstante, su uso con compromiso neurológico grave también ha sido anecdótico. Se presenta el caso de una paciente de 84 años de edad con poliangeítis microscópica y compromiso neurológico y renal grave, tratada con rituximab evolucionando favorablemente alcanzando la remisión de la enfermedad.

SUMMARY The neurological involvement of the central nervous system (CNS) in vasculitis associated with ANCAS is rare and potentially catastrophic. The standard treatment is cyclophosphamide with pulses of steroids; however, this scheme has no strong evidence for central nervous system involvement and is not free of serious adverse effects especially in the elderly population. In recent year's rituximab has appeared as an alternative therapy to cyclophosphamide to induce remission in this type of vasculitis, however its use with severe neurological involvement has also been anecdotal. We present the case of 84-year-old patient who presented a microscopic polyangiitis with severe neurological and renal involvement, treated with rituximab with a favorable evolution in reaching remission of the disease.

ANCA associated vasculitis in patients from Saudi Arabia

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

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

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

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

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

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

A case of microscopic polyangiitis presenting with acute spinal subdural hemorrhage

This report describes a case of a 62-year-old woman with microscopic polyangiitis (MPA) who developed acute spinal subdural hemorrhage. MPA was confirmed by positive autoantibodies to myeloperoxidase and focal segmental necrotizing and pauci-immune crescentic glomerulonephritis on renal biopsy. She did not recover from paraplegia due to acute spinal subdural hemorrhage, despite decompression operation and aggressive immunosuppression. Although spontaneous spinal hemorrhage in MPA patients is very rare, the prognosis for such patients is poor. Considering the possibility of ongoing vasculitis activity in extra-renal organs, clinicians should be very cautious to attenuate the strength of immunosuppressant drugs, even in patients with chronic or irreversible renal pathology.

C-Reactive Protein to Serum Albumin Ratio Is an Independent Predictor of All-Cause Mortality in Patients with ANCA-Associated Vasculitis

PURPOSE: We investigated whether C-reactive protein (CRP) to serum albumin ratio (CAR) could be an independent predictor of all-cause mortality in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 170 patients with AAV. We collected clinical and laboratory data. We also examined AAV-related and traditional risk factors of all-cause mortality. To assess the hazard ratios of variables, we performed univariable and multivariable Cox hazard model analyses. RESULTS: The mean age was 55.0 years and 53 patients (31.2%) were male among 170 patients with AAV (88 microscopic polyangiitis, 43 granulomatosis with polyangiitis, and 39 eosinophilic granulomatosis with polyangiitis). ANCA was detected in 129 patients (75.9%). The initial mean CRP and serum albumin were 41.1 (mg/L) and 3.6 (g/dL), and the mean CAR at diagnosis was 14.8. The most common risk factor of mortality was hypertension (42.4%), followed by chronic kidney disease ≥stage 3 (25.9%). Fourteen patients (8.2%) died during the mean follow-up of 56.7 months. In both multivariable Cox hazard model analyses, CAR at diagnosis was identified as an independent predictor of all-cause of mortality comparable to diabetes mellitus (DM). Moreover, patients with CAR ≥10.35 and having DM exhibited a higher frequency of all-cause mortality than those without. CONCLUSION: CAR at diagnosis can be an independent predictor of all-cause mortality, comparable to DM, the conventional risk factor of mortality.

Delta Neutrophil Index Is Associated with Vasculitis Activity and Risk of Relapse in ANCA-Associated Vasculitis

PURPOSE: Delta neutrophil index (DNI) represents the immature granulocytes count associated with neutrophil-consumption. We investigated whether DNI might be associated with Birmingham vasculitis activity score (BVAS) at diagnosis and could predict relapse during the follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). MATERIALS AND METHODS: We reviewed the medical records of 97 patients having DNI results. Twenty patients had granulomatosis with polyangiitis (GPA), 58 had microscopic polyangiitis (MPA), and 19 had eosinophilic GPA (EGPA). We collected clinical and laboratory data including BVAS, five factor score (FFS), and DNI. The correlation coefficient and cumulative relapse free survival rate were obtained. The optimal cut-off of DNI was extrapolated by calculating the area under the receiver operator characteristic curve. RESULTS: DNI was significantly related to cross-sectional BVAS. Furthermore, among continuous variables, only DNI could reflect BVAS of GPA and MPA, but not EGPA. Severe AAV was defined as BVAS ≥20 (the highest quartile). At diagnosis, patients having DNI ≥0.65% had a significantly higher risk of severe GPA and MPA than those having not (relative risk 4.255) at diagnosis. During the follow-up, DNI ≥0.65% could predict the higher relapse rate. CONCLUSION: DNI could reflect BVAS at diagnosis and furthermore, DNI ≥0.65% could not only identify severe AAV at diagnosis, but also predict relapse during the follow-up in patients with GPA and MPA.

Presentación atípica de la poliangeítis microscópica con compomiso renal, pulmonar, dermatológico y del sistema nervioso central / Atypical presentation of microscopic polyangiitis with renal, pulmonary, dermatological and central nervous system involvement

La poliangeítis microscópica (PAM) es una vasculitis autoinmune caracterizada por la inflamación de los vasos sanguíneos de pequeño calibre y la presencia de anticuerpos anticitoplasma de neutrófilos (ANCA). Clínicamente se caracteriza por presentar glomerulonefritis y capilaritis pulmonar aunque la afectación de la piel, los nervios y el tracto gastrointestinal no es infrecuente. Presentamos el caso de un paciente de 17 años con manifestaciones atípicas dadas por glomerulonefritis pauci-inmune, hemorragia pulmonar, vasculitis leucocitoclásica cutánea y hemorragia cerebral. Además revisamos las características histológicas y radiológicas.

Microscopic polyangiitis (MPA) is an autoimmune antineutrophil cytoplasmic antibody-associated (ANCA) small-vessel vasculitis. It is clinically characterized by glomerulonephritis and pulmonary capillaritis, however, skin, nerve and gastrointestinal tract involvement is also relatively common. A case is presented in a 17-year-old male patient with atypical manifestations, such as, pauci-immune glomerulonephritis, alveolar hemorrhage, cutaneous leukocytoclastic vasculitis and cerebral hemorrhage. MPA histologic and radiologic features were also reviewed.

Severe microscopic polyangiitis with unilateral vocal cord paralysis as initial manifestation / Parálisis unilateral de cuerda vocal como manifestación inicial de poliangitis microscópica grave

Abstract Case Description: A 16 year-old female who presented with initial ear, nose and throat manifestations who later progressed to severe renal disease, requiring hemodialysis after 11 months of unique laryngeal involvement. Clinical Findings: Unilateral vocal cord paralysis without other symptoms or signs, but with positive perinuclear anti-neutrophil cytoplasmic antibodies (ANCA) and anti-myeloperoxidase autoantibodies, followed an unfavorable course months later with rapidly progressive glomerulonephritis. Renal biopsy confirmed an ANCA-associated vasculitis. She was diagnosed with microscopic polyangiitis. Treatment and Outcome: High-dose glucocorticoids, intravenous cyclophosphamide, plasma exchange and finally, hemodialysis and renal transplantation. Clinical Relevance: In contrast to granulomatosis with polyangiitis (Wegener), ear, nose and throat manifestations in microscopic polyangiitis are uncommon, while involvement of the lungs and kidneys are usual. We present a case with an isolated rare involvement, which progressed to severe disease. This atypical case warns about laryngeal symptoms as initial manifestation of an anti-myeloperoxidase positive systemic vasculitides, and emphasizes the relevance of close observation when unexplained isolated conditions with accompanying evidence of autoimmunity, in this case high levels of specific autoantibodies, are present.

Resumen Descripción del caso: Una mujer de 16 años se presentó inicialmente con manifestaciones otorrinolaringológicas y posteriormente progresó hacia enfermedad renal grave, requiriendo hemodiálisis después de 11 meses de tener exclusivamente afección laríngea. Hallazgos clínicos: parálisis de cuerda vocal unilateral sin otros síntomas ni signos, pero con autoanticuerpos anticitoplasma de neutrófilo (ANCA) con patrón perinuclear y especificidad contra mieloperoxidasa, siguiendo un curso desfavorable meses después con desarrollo de glomerulonefritis rápidamente progresiva. La biopsia renal confirmó una vasculitis asociada con ANCA (VAA). Se diagnosticó entonces como poliangitis microscópica. Tratamiento y desenlace: Glucocorticoides a dosis altas, ciclofosfamida endovenosa, recambio plasmático y finalmente, hemodiálisis y transplante renal. Relevancia clínica: en contraste con la granulomatosis con poliangitis (Wegener), las manifestaciones otorrinolaringológicas en poliangitis microscópica son poco comunes, mientras que la afección pulmonar y renal es común. Presentamos un caso con afección inusual aislaea, que progresó a enfermedad grave. Este caso atípico enfatiza sobre los síntomas laríngeos como manifestación inicial de una vasculitis antimieloperoxidasa positiva, y subraya la relevancia de una estrecha observación cuando condiciones aisladas inexplicables, que como en este caso se acompañan de evidencia de autoinmunidad manifestado por presencia de niveles altos de autoanticuerpos, se presentan para su atención.

Long-Term Functional Outcome of Peripheral Neuropathy in Microscopic Polyangiitis with Poor Prognostic Factors: 3-Year Clinical Follow-up

Microscopic polyangiitis (MPA) is a systemic small vessel vasculitis with few or no immune deposits and no granulomatous inflammation. Peripheral neuropathy occurs in approximately 20%–30% of patients with MPA. We report a case of a 66-year-old woman who presented with paresthesia and motor weakness of the extremities and rapidly progressive glomerulonephritis. She was later diagnosed with MPA based on the findings of positive perinuclear antineutrophil cytoplasmic antibody along with findings on kidney biopsy. Nerve conduction study showed symmetric sensorimotor polyneuropathy. We followed the patient for 3 years, and she showed good functional outcome after immune-modulating therapy although Five-Factor Score more than 2 at diagnosis.