Association of anti-neutrophil cytoplasmic antibodies with the disease activity in patients with systemic lupus erythematosus / 实用医学杂志

Objective To investigate the clinical significance of ANCA in the disease activity of patients with SLE.Methods A total of 1 025 SLE patients were recruited and were divided into inactive and active groups according to SLEDAI score.Demographic characteristics,clinical symptoms,autoantibodies,routine laboratory tests and renal pathology were also recorded and compared between the two groups.Results All patients were divided into inactive group(n = 750)and active group(n = 250).The occurrence of renal,pulmonary,cutaneous,arthritis manifestations were significantly higher than those of the inactive group(all P<0.05).All patients were tested for ANCA,and the most common pattern being perinuclear or p-ANCA,the percentage of p-ANCA seroposi-tive increased greatly with the increased disease activity(P<0.05).The autoantibodies were further analyzed between the two groups,25 patients had reactivity to MPO,but no patient had reactivity to PR3.Also,there were significant differences in anti-dsDNA antibody,anti-nucleosome antibody between the two groups(P<0.05).In the active group,patients with p-ANCA seropositive exhibited higher serum beta-2-microglobulin(β2-MG),titers of anti-dsDNA antibody,SLEDAI scores,lower albumin,C3,and C4 levels(P<0.05).Meanwhile,p-ANCA was associated with IL-6,which increased significantly with the increase of SLEDAI score.In addition,patients with p-ANCA seropositive had more occurrence of lupus nephritis,but it had no association with the renal pathology.Conclusion The appearance of p-ANCA in SLE patients indicated more severe disease activity status.

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.

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)

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.

Head and neck manifestations of granulomatosis with polyangiitis: a retrospective analysis of 19 patients and review of the literature

Introduction: Granulomatosis with Polyangiitis (GPA) is a small vessel vasculitis characterized by a necrositing granulomatous inflammation of the upper and lower respiratory tracts and focal/proliferative glomerulonephritis. In more than 70% of the cases, the presenting symptoms are head and neck manifestations that are often misdiagnosed as infectious or allergic in etiology. Objective: The present study provides an analysis of head and neckmanifestations in a series of patients diagnosed with GPA. It also evaluates their medical and surgical treatment and provides a review of the relevant literature. Methods: A retrospective analysis of 19 patients diagnosed with GPA at a public tertiary care hospital between 2006 and 2017 was performed. Results: A total of 19 patients were included in the present study, and 16 of them presented head and neck manifestations. Sinonasal symptoms were the most common, affecting 56% of the patients, followed by laryngotracheal (31.25%) and ear (25%) symptoms. In 7 patients, sinonasal symptoms were the first manifestation of the disease (43.75%). Four patients underwent surgery at some stage of the disease. Conclusions: Head and neck involvement is common in GPA and may stand for the first or the onlymanifestation of the disease. The otolaryngologists play a central role in the diagnosis and long-term treatment of these patients, and they have to keep this pathology in mind when treating patients with ENT symptoms that do not respond as expected to the treatment (AU)

Key advances in the clinical studies of ANCA-associated vasculitis / 医学研究生学报

Anti-neutrophil cytoplasmic antibodies( ANCA)-associated vasculitis ( AAV) has various clinical symptoms, thus various treatment schemes were used in clinics.To date, there has been no validated diagnostic criteria or treatment guideline for AAV.There are three aspects to be considered when assessing the treatment with AAV patients:staging of disease, distinction between disease activity and chronic damages, and quality of life ( QOL) .This review focuses on the latest classification of vasculitis, the rela-tion between disease stages and its severity, the importance of distinguishing active diseases from permanent damages, the therapeutic choices and the management of complications.

Approach to the patient with propylthiouracil induced anti-neutrophil cytoplasmic antibodies positive vasculitis / 中华内分泌代谢杂志

[Summary] Propylthiouracil-induced anti-neutrophil cytoplasmic antibodies ( ANCA ) positive vasculitis ( APV) is an autoimmune diseases with multi-system damage. Its basic pathological lesions are characterized by necrotizing vasculitis. We present a case of propylthiouracil-induced APV, with regard to its pathogenesis, clinical manifestation, diagnosis, treatment, and outcomes for futher understanding this disease.

The level and clinical significance of serum anti-lysosomal associated membrane protein-2 antibody in patients with anti-neutrophil cytoplasmic antibodies-associated vasculitis / 中华风湿病学杂志

Objective To explore the clinical.significance of serum anti-lysosomal associated membrane protein-2 (LAMP-2) antibody in the pathogenesis of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AASV) by investigating the relationship of its levels and AASV.Methods Sera from twenty patients with AASV and twenty healthy controls were collected.Serum anti-LAMP-2 antibody was detected using commercial enzyme linked immunosorbent assay (ELISA) kits.Anti-LAMP-2 antibody levels between the two groups were assessed using the t test,the correlation between anti-LAMP-2 antibody levels and erythrocyte sedimentation rate (ESR),C-reactive protein (CRP) was assessed by Spearman's rank correlation test,the correlation between anti-LAMP-2 antibody levels and the Birmingham vasculitis activity score(BVAS),hemoglobin (Hb),albumin (Alb) was assessed by Pearson's rank correlation test.Results ① The serum level of anti-LAMP-2 antibody in patients with AASV [(3714±1446) pg/ml] was higher than that in the healthy controls [(174±43) pg/ml] (t=10.94,P＜0.05).The serum level of Hb [(99±30) g/L] and Alb [(27±5) g/L]in patients with AASV was lower than that in healthy controls [(138±14) g/L,(44±3) g/L] (t=5.27,t=13.04,P＞0.05).② The level of anti-LAMP-2 antibody in AASV was positively correlated with BVAS (r=0.669 9,P＜0.05),and was not found elevated compared with ESR,CRP,Hb and Alb (P＞0.05).Conclusion ① AntiLAMP-2 antibody is involved in the pathogenesis of AASV.② Anti-LAMP-2 antibody is correlated with the activity of AASV,it may be an indicator of AASV disease activity.

Treatment and diagnosis of anti-neutrophil cytoplasmic antibodies-associated vasculitis / 中国小儿急救医学

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) includes granulomatosis with polyangiitis,microscopic polyangiitis,eosinophilic granulomatosis with polyangiitis,which are known for this name because the common involvement of ANCA in the serum.New revise have been made in the Chapel Hill consensus conference 2012 about the nomenclature and definition of vasculitides,including the AAV.AAV can be misdiagnosed and delay diagnosed very easily for the variety and lack of specificity of clinical manifestations,and a early diagnosis and timely treatment is the key for a better prognosis.

A Case of Rifampin-Induced Crescentic Glomerulonephritis / 대한내과학회지

A 56-year-old male with pulmonary tuberculosis was admitted to our hospital for evaluation of generalized edema. He began antituberculosis treatment with rifampin, isoniazid, ethambutol, and pyrazinamide. He experienced abnormal increments in weight and serum creatinine after 6 weeks. All serological findings, including anti-neutrophil cytoplasmic antibodies (ANCA), were negative. Rifampin was stopped because it might have caused the increase in creatinine. Renal biopsy was consistent with pauci-immune crescentic glomerulonephritis (CrGN). His renal function was improved by high-dose steroid treatment. Rifampin-induced, ANCA-negative pauci-immune CrGN is very rare; most cases of rifampin-induced acute renal failure are due to acute tubulointerstitial nephritis. We present here a case of rifampin-induced CrGN and pulmonary tuberculosis successfully treated with high-dose steroids and antituberculosis medications, excluding rifampin.

A Case of Rifampin-Induced Crescentic Glomerulonephritis / 대한내과학회지

A 56-year-old male with pulmonary tuberculosis was admitted to our hospital for evaluation of generalized edema. He began antituberculosis treatment with rifampin, isoniazid, ethambutol, and pyrazinamide. He experienced abnormal increments in weight and serum creatinine after 6 weeks. All serological findings, including anti-neutrophil cytoplasmic antibodies (ANCA), were negative. Rifampin was stopped because it might have caused the increase in creatinine. Renal biopsy was consistent with pauci-immune crescentic glomerulonephritis (CrGN). His renal function was improved by high-dose steroid treatment. Rifampin-induced, ANCA-negative pauci-immune CrGN is very rare; most cases of rifampin-induced acute renal failure are due to acute tubulointerstitial nephritis. We present here a case of rifampin-induced CrGN and pulmonary tuberculosis successfully treated with high-dose steroids and antituberculosis medications, excluding rifampin.

Contribution of immunofluorescence to identification and characterization of antineutrophil cytoplasmic antibodies in inflammatory bowel disease.

We evaluated the combined use of different fixatives for the identification of atypical perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) in patients with inflammatory bowel diseases (IBD) by indirect immunofluorescence (IIF). Sera from 59 ulcerative colitis (UC) and 37 Crohn’s disease (CD) patients, and from 64 healthy controls were studied. The IIF on ethanol-, formalin-, and methanol-fixed neutrophils was used for the detection of ANCA. Enzyme linked immunosorbant assay (ELISA) was performed to identify the antigens recognized by ANCA. ANCAs were present in 35 of 59 (59.3%) UC patients and in 10 of 37 (27.02%) CD patients. Atypical p-ANCA positivity was strongly associated with UC disease (44.1% in UC vs. 8.1% in CD; p=0.0002). The combined application of different fixatives contributed to make easy the differentiation between typical p-ANCA and atypical p-ANCA. Atypical p-ANCA determination appears to be a useful parameter for the distinction between UC and CD.

A Case of Pulmonary Adenocarcinoma Developed on a Previous Lesion from Microscopic Polyangiitis / 대한신장학회지

This report examines a patient with pulmonary adenocarcinoma that developed on a previous lesion from microscopic polyangiitis. A 59-year-old woman had been diagnosed with microscopic polyangiitis in October of 1988 based on her clinical symptoms and serological tests, which were positive for anti-neutrophil cytoplasmic antibodies. Her glomerulonephritis had been well controlled with low-dose prednisolone. She presented in October of 2005 with vague chest discomfort and dyspnea on exertion. Physical examination was unremarkable. A non-contrast computed tomography (CT) scan of the chest showed patch ground-glass opacity at the right lower lobe of the lung. Because we did not believe the lesion to be a definite malignancy, we decided to follow up with chest images over a short interval. During the 18 months following the images, the lesion did not change. However, the opacity of the lesion increased slightly over the last two months, and a non-contrast CT scan of the chest was therefore performed. A CT scan showed persistent ground-glass opacity with a slightly solid portion. To diagnose the previous finding and possibly to provide treatment, a right lower lobectomy of the lung via video-assisted thoracoscopic surgery was performed. The pathologic review of the resected lung revealed an adenocarcinoma, stage pT1N0. After one year, fluorodeoxyglucose positron emission tomography was performed, and no evidence of a recurrent malignancy was found.

Diagnóstico de granulomatosis de Wegener en pacientes con enfermedades oculares inflamatorias / Diagnosis of Wegener's granulomatosis in patients with ocular inflamatory disease

Objetivo. Informar las manifestaciones oftalmológicas en pacientes con granulomatosis de Wegener (GW). Método. Se revisó la base de datos del Instituto de Oftalmología Conde de Valenciana. Se recolectó la exploración oftalmológica completa, los exámenes de laboratorio y de gabinete, el tratamiento y la evolución. Resultados. Se incluyeron 11 pacientes con GW (18 ojos). Siete pacientes masculinos y 4 femeninos con edad promedio de 43.7 años (28-55). Tres habían tenido diagnóstico previo de GW y los 8 restantes se diagnosticaron en nuestro departamento. Siete presentaron cuadros bilaterales y 4 unilaterales. Las formas de presentación clínica fueron escleritis necrosante con queratitis ulcerativa periférica (QUP) (7/18), escleritis difusa (3/18), escleritis nodular (1/18), uveítis anterior no granulomatosa (1/18), neuropatía óptica isquémica (1/18), neuropatía óptica retrobulbar (1/18), desprendimiento de retina seroso (2/18) y dacriocistitis (2/18). De los 18 ojos, la capacidad visual final fue mejor o igual a 20/40 en 13, 20/400 en 3, cuenta dedos a 30cm o no-percepción de luz en 1. Actualmente 7 pacientes se encuentran en fase inactiva. Conclusiones. Las manifestaciones oftalmológicas más frecuentes en pacientes con GW fueron: escleritis necrosante y QUP. En la mayoría, la GW se diagnosticó después de las manifestaciones oftalmológicas, sin embargo, todos presentaron síntomas sistémicos u oftalmológicos previos.

OBJECTIVE: Report the ophthalmologic manifestations among patients with Wegener 's Granulomatosis (WG). METHOD: We reviewed the database of the Instituto de Oftalmologia Fundación Conde de Valenciana in order to collect information regarding complete ophthalmic examination, laboratory and cabinet tests, treatment, and disease progression. RESULTS: We included 11 patients with WG (18 eyes). Seven men and four women, mean age 43.7 years (range = 28-55). Three patients had a prior diagnosis of WG and the remaining eight patients were diagnosed by our study team. Seven subjects developed a bilateral affection and four had unilateral involvement. The clinical presentation was necrotizing scleritis with peripheral ulcerative keratitis (PUK) (7/18), diffuse scleritis (3/18), nodular scleritis (1/18), non-granulomatous uveitis (1/18), optic ischemic neuropathy (1/18), retrobulbar neuritis (1/18), serous retinal detachment (2/18), and dacryocystitis (2/18). Final visual acuity was better or equal to 20/40 (13/18), 20/400 (3/18), finger-counting or no-perception of light in 1/18. Currently, seven patients are symptom free. CONCLUSIONS: The most frequent ophthalmic manifestations among our patients with WG were: necrotizing scleritis and PUK. In most cases, WG was diagnosed after ophthalmic manifestations; however, all patients displayed prior systemic or ocular symptoms.