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.

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.

Oclusão da artéria central da retina em paciente com poliangeíte microscópica / Central retinal artery occlusion in patient with microscopic polyangiitis

RESUMO A poliangeíte microscópica é uma vasculite necrotizante sistêmica que acomete arteríolas, capilares e vênulas, mas também pode atingir pequenas e médias artérias. É considerada uma doença rara, idiopática e autoimune. Diversas anormalidades oculares e sistêmicas estão associadas às oclusões arteriais retinianas. Dentre as doenças vasculares do colágeno, a literatura cita como possíveis causas de obstrução das artérias retinianas o lúpus eritematoso sistêmico, a poliarterite nodosa, a arterite de células gigantes, a granulomatose de Wegener e a granulomatose linfóide de Liebow. Até o presente momento, não se encontrou na literatura relatos da associação de casos de oclusão arterial retinana associados à PAM. Os autores relatam o caso de um paciente com poliangeíte microscópica que apresentou comprometimento renal importante e oclusão da artéria central da retina unilateral. Atenta-se para a inclusão de pesquisa da PAM, através do p-ANCA, na avaliação de possível origem sistêmica em pacientes acometidos por oclusão arterial retiniana.

ABSTRACT The microscopic polyangiitis is a systemic necrotizing vasculitis that affects arterioles, capillaries and venules, but can also reach small and medium-sized arteries. It is considered a rare disease, idiopathic in nature but clearly autoimmune. Several ocular and systemic abnormalities are associated with retinal arterial occlusions. Among the collagen vascular diseases, the literature cited as possible causes of retinal artery obstruction lupus erythematosus, polyarteritis nodosa, giant cell arteritis, Wegener’s granulomatosis and lymphoid Liebow. Until now, there were no reports in the literature of the association of cases of arterial occlusion retinana associated with PAM. The authors report a case of a 53 years old patient diagnosed with microscopic polyangiitis who presented with important renal artery occlusion and associated unilateral central retinal artery occlusion. An extended systemic evaluation of patients presenting with central retinal artery occlusion should include research of PAM through analysis op p-ANCA.

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.

An aetiological & clinicopathological study on cutaneous vasculitis.

Background & objectives: Cutaneous vasculitis has protean clinical manifestations. It may be idiopathic or associated with a spectrum of conditions such as infections, drugs, etc. Skin is involved in both small vessel vasculitis (SVV) and medium vessel vasculitis (MVV). Overlapping features are seen between SVV and MVV. The histopathological features may not always relate with the clinical lesions. The aim of the present study was to evaluate the aetiological factors and clinicopathological association in patients with cutaneous vasculitis. Methods: In this cross-sectional study, detailed history and clinical examination were done on patients with biopsy proven cutaneous vasculitis. Two skin biopsies were taken from each patient for routine histopathology and direct immunofluorescence. Results: Of the 61 patients studied, hypersensitivity vasculitis (HSV) [23 (37.7%)] and Henoch Schonlein purpura (HSP) [16 (26.2%)] were the two most common forms. Systemic involvement was seen in 32 (52.45%) patients. Drugs were implicated in 12 (19.7%) cases, infections in 7 (11.4%) and connective tissue disorders in 4 (6.5%) cases. Histologically SVV was the most common pattern, seen in all the clinically diagnosed patients with SVV (47), and in 12 of the 14 clinically diagnosed patients with MVV. Direct immunofluorescence showed positivity for at least one immunoreactant in 62 per cent of the patients and the most common deposit was C3 followed by IgG, IgA and IgM. Interpretation & conclusions: Majority of our patients with cutaneous vasculitis were idiopathic. Histologically, SVV was seen in most of our patients. No association was seen between history of drug intake and tissue eosinophilia and also between histologically severe vasculitis and clinical severity. The presence of immunoreactant IgA was not specific for HSP.

Características generales de 29 pacientes con vasculitis de pequeños vasos / General characteristics of 29 patients with small vessel vasculitis

El objetivo de esta serie fue describir las características generales y manifestaciones clínicas de pacientes con vasculitis de pequeños vasos que concurrieron al servicio de autoinmunidad de un hospital de la comunidad y compararlas con la literatura. Se revisaron de manera retrospectiva las historias clínicas archivadas bajo el rótulo de vasculitis en un período de 16 años. Se seleccionaron aquellos pacientes que cumplieran criterios diagnósticos de vasculitis de pequeños vasos. Se extrajeron los datos de interés y se constató la supervivencia mediante contacto telefónico. Posteriormente se realizó una búsqueda bibliográfica y se compararon los resultados. Se incluyeron 13 pacientes con granulomatosis de Wegener, 6 con síndrome de Churg Strauss y 10 con poliangeítis microscópica. El 55% (16) fueron menores de 55 años al diagnóstico y hubo predominio del sexo femenino (2.6:1). La demora diagnóstica fue mayor a un año en el 46% de los casos. Los sistemas más frecuentemente afectados fueron respiratorio y otorrinolaringológico. El 79% presentó anticuerpos anti-citoplasma de neutrófilos (ANCA) positivos. La mortalidad fue del 24% (7/29). Al comparar las características de los pacientes incluidos en esta serie con lo descripto en la literatura, se hallaron diferencias en cuanto a la forma de presentación, sistemas comprometidos y porcentaje de pacientes ANCA positivos; además se observó que el resultado negativo de este marcador parece asociarse con mayor demora diagnóstica y en consecuencia peor pronóstico, lo que remarca su importancia como herramienta adicional no invasiva al momento del diagnóstico.

The objective of this series was to describe the general characteristics and clinical manifestations of patients with small vessel vasculitis who were assisted in the autoimmunity department of a community public hospital and to compare the results with the literature. Clinical records under the label of vasculitis in a period of 16 years were reviewed in a retrospective way. All patients selected fulfilled diagnostic criteria of small vessel vasculitis. The data were extracted and the analysis of survival was completed by phone. Later a bibliographical search was carried out and the results were compared. Thirteen patients with Wegener's granulomatosis, 6 with Churg-Strauss syndrome and 10 with microscopic polyangiitis were included. Fifty five percent (16) were under 55 years old when diagnosis was made and male/female ratio was 2.6 to 1. The diagnostic delay was over a year in 46% of the cases. Respiratory and ear-nose-throat were the most frequently affected systems. Anti-neutrophil cytoplasmic antibodies were present in 79% of patients. Overall mortality was 24% (7/29). There were several differences between the results of our series and the literature: the presentation form, affected systems and percentage of patients with anti-neutrophil cytoplasmic antibodies. Greater diagnostic delay and worse prognosis were observed in anti-neutrophil cytoplasmic antibody negative patients. Special attention should be given to these antibodies since they constitute a significant tool at the time of diagnosis.