Granulomatosis con poliangeítis. A propósito de un caso

La granulomatosis con poliangeítis es una vasculitis sistémica, necrosante y granulomatosa que afecta el tracto respiratorio superior e inferior y los riñones. Se presenta el caso de una paciente blanca, de 59 años de edad, hipertensa y fumadora inveterada, que ingresó por presentar síntomas constitucionales, orinas turbias y hemáticas, así como creatininemia elevada con valor previo normal. Con impresión diagnóstica inicial de infección del tracto urinario se indica antibioticoterapia. Después del tercer día de iniciado el tratamiento, mejoraron los síntomas constitucionales y, de forma progresiva, comenzó con manifestaciones multiorgánicas (renal, respiratoria, cutánea y musculoesquelética) sugestivas de vasculitis sistémica. Como elementos significativos, en exámenes complementarios se detectaron azoados y reactantes de fase aguda aumentados, sedimento urinario activo, imagen nodular en vértice pulmonar derecho y microhemorragias multifocales en ambos campos pulmonares, detectados mediante tomografía computarizada y c-ANCA altamente positivo. Se indicó tratamiento inmunosupresor y citotóxico potente, obteniéndose control inicial de las manifestaciones graves de la enfermedad. Evolutivamente desarrolló complicaciones propias de la entidad y secundarias al tratamiento médico, que la hicieron tributaria de terapia de sustitución renal, falleciendo a los dos años de recibir hemodiálisis iterada. El cuadro clínico, unido a los estudios imagenológicos e inmunológicos (c-ANCA), fueron elementos claves para realizar el diagnóstico.

Granulomatosis with polyangiitis is a systemic, necrotizing, granulomatous vasculitis that affects the upper and lower respiratory tract and kidneys. The case of a 59-year-old white female patient, who is hypertensive and inveterate smoker, is presented; she was admitted for presenting constitutional symptoms, turbid and bloody urine, as well as elevated creatininemia with a normal previous value. With the initial diagnostic impression of urinary tract infection, antibiotic therapy was indicated. After the third day of starting treatment the constitutional symptoms improved, and progressively began with multiorgan manifestations (renal, respiratory, skin and musculoskeletal) suggestive of systemic vasculitis. As significant elements, complementary examinations detected increased nitrogen and acute phase reactants, active urinary sediment, nodular image in the right lung apex and multifocal microhemorrhages in both lung fields through computed tomography, and highly positive c-ANCA. Potent immunosuppressive and cytotoxic treatment was indicated, obtaining initial control of severe manifestations of the disease. Evolutionarily she developed complications specific to the entity and secondary to medical treatment which made her subject to renal replacement therapy, dying two years after receiving iterated hemodialysis. The clinical characteristics, together with the imaging and immunological studies (c-ANCA) were key elements to make the diagnosis.

Criterios broncoscópicos, laboratoriales y anatomopatológicos de enfermedad de la vía aérea en pacientes diagnosticados con granulomatosis con poliangitis / Bronchoscopic, laboratory and anatomopathological criteria for airway disease in patients diagnosed with granulomatosis with polyangiitis

Introducción: los pacientes con granulomatosis con poliangitis (GPA) pueden presentar compromiso de la vía aérea superior (VAS) o inferior (VAI). Objetivos: describimos las manifestaciones endoscópicas de las vías respiratorias, los hallazgos histológicos y los anticuerpos anticitoplasma de neutrófilos (ANCA) en un grupo de pacientes con GPA. Métodos: estudio retrospectivo de historias clínicas de pacientes con GPA sometidos a broncoscopia entre 2012 y 2019. Se analizaron hallazgos de la vía aérea, biopsias y ANCA. Resultados: se incluyeron 40 pacientes, con una edad media de 46,92±17,61 años, predominantemente del sexo femenino (67,5%). Se observó afectación de la vía aérea en el 90% (n=36). El C-ANCA fue reactivo en el 63,9%, P-ANCA en el 25%, ANCA doblemente reactivo en el 8,33% y no reactivo en el 20%. Los hallazgos comunes en la vía aérea superior (VS) fueron sinusitis crónica (41,7%), destrucción del tabique nasal (16,7%); y en la vía aérea inferior (AI): estenosis traqueobronquial (38,9%), traqueobronquitis (25%). Los hallazgos más frecuentes de las biopsias broncoscópicas fueron proceso inflamatorio polimorfonuclear (61,9%) y necrosis geográfica (47,6%). Conclusión: la vía aérea está comprometida hasta en un 90% de los pacientes con GPA. ANCA no reactivos no descartan esta posibilidad. La sinusitis crónica y los procesos fibroestenóticos traqueobronquiales fueron los hallazgos endoscópicos más comunes. La vasculitis en biopsias se encontró en una minoría de casos.

Introduction: patients with granulomatosis with polyangiitis (GPA) may present upper airway (UA) and lower airway (LA) involvement. Objectives: we describe the endoscopic manifestations of the airways, histological findings from biopsied tissue and antineutrophilic cytoplasm antibody (ANCA) in a group of patients with GPA. Methods: retrospective study of medical records of patients with GPA undergoing bronchoscopy between 2012 and 2019. Airway findings, results of biopsies performed and ANCA results were analyzed. Results: 40 patients were included, with a mean age of 46.92±17.61 years and predominantly female (67.5%). Airway involvement was observed in 90% (n=36). The C-ANCA was reactive in 63.9%, P-ANCA in 25%, doubly reactive ANCA in 8.33% and non-reactive in 20%. The findings in upper airway (UA) were: chronic sinusitis (41.7%), destruction of the nasal septum (16.7%); and in lower airway (LA) were: tracheobronchial stenosis (38.9%) and tracheobronchitis (25%). The pathological findings most common of bronchoscopic biopsies were: polymorphonuclear inflammatory process (61.9%) and geographic necrosis (47.6%). Conclusion: the airway is involved in up to 90% of patients with GPA. Non-reactive ANCA does not rule out this possibility. Chronic sinusitis and tracheobronchial fibrostenotic processes were the most common endoscopic findings. Vasculitis in biopsies was found in a minority of cases.

Clinical profile and management of granulomatosis with polyangiitis–associated scleritis from a tertiary care hospital in South India

Purpose: To describe the clinical features and management of patients with scleritis associated with granulomatosis with polyangiitis (GPA) at a tertiary eye care center in South India. Methods: The clinical profile and management of patients presenting to a tertiary eye care center in South India with scleritis secondary to GPA from 2003 to 2021 were analyzed retrospectively. Scleritis was classified into anterior diffuse, nodular, and necrotizing scleritis with inflammation according to Watson and Hayreh’s classification. Demographic characteristics, clinical features, anti?neutrophil cytoplasmic antibody (ANCA) positivity, treatment response, ocular complications, and status at the last follow?up were analyzed. Statistical analysis of data was performed using Microsoft Excel 2019. Results: Nineteen eyes of 17 patients (15 cytoplasmic staining ANCA [c?ANCA], two p?ANCA positive) were included. Fifteen eyes had necrotizing scleritis, two had diffuse anterior scleritis, and two had nodular scleritis. Remission was induced using a combination of steroids and cyclophosphamide or rituximab. Maintenance therapy was instituted using tapering steroids and immunosuppressants like cyclophosphamide, mycophenolate mofetil, methotrexate, or rituximab. Three eyes required a scleral patch graft. Fourteen patients had good anatomical and visual outcomes, and three were lost to follow?up. Conclusion: GPA is a rare disease, while it is the most common ANCA?associated vasculitis with scleritis. As scleritis may be the presenting sign of the disease, ophthalmologists must be aware of the various features suggestive of GPA. GPA?associated scleritis can have a good prognosis when diagnosed promptly and managed aggressively in the acute stage, and remission is maintained with adequate systemic immunosuppression.

Hidronefrosis como manifestación inusual y distractora en el diagnóstico de una vasculitis ANCA positiva. A propósito de un caso / Hydronephrosis as an unusual and distracting manifestation in the diagnosis of ANCA-positive vasculitis. About a case

La nefropatía obstructiva se considera una manifestación inusual en las vasculitis ANCA. Se presenta el caso de un masculino de 38 años, con granulomatosis con poliangitis e hidronefrosis unilateral, y revisión de la literatura. Masculino de 38 años, sano, quien consulta por cuadro subagudo de odinofagia, síntomas constitucionales y lesión renal aguda anúrica. Inicialmente con hallazgo de hidronefrosis izquierda, manejado como nefropatía obstructiva, que eventualmente desarrolla hemorragia alveolar difusa, distrés respiratorio y fallece debido a un síndrome de distrés respiratorio agudo severo refractario asociado a su granulomatosis con poliangitis. La nefropatía obstructiva es una manifestación inusual de las vasculitis ANCA asociadas. Es importante la sospecha diagnóstica en estos cuadros multisistémicos para no dilatar el tratamiento inmunosupresor conjunto con el resto de las terapias requeridas.

Obstructive nephropathy is considered an unusual presentation in ANCA-associated vasculitis. The following case describes a 38-year-old male with granulomatosis with polyangiitis and unilateral hydronephrosis, as well as a literature review. A 38-year-old male with an unremarkable medical background presents with a 3-week history of odynophagia, constitutional symptoms and anuric kidney injury. Initially managed as an obstructive nephropathy due to a left hydronephrosis finding, the patient eventually develops a diffuse alveolar hemorrhage, acute respiratory distress and perishes due to granulomatosis with polyangiitis. Obstructive nephropathy is an unusual manifestation of ANCA-associated vasculitis. Diagnostic suspicion is important in these multisystem pictures so as not to delay immunosuppressive treatment together with the rest of the required therapies.

Organizing Pneumonia in A Patient Double-Positive for ANCA and Anti-GBM Antibodies: A Case Report / 中国医学科学杂志(英文版)

Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose

Abstract Objective: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. Methods: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). Results: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05-0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05-0.88, p = 0.034). After six months (D69-D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. Conclusion: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).

Measurement of superoxide dismutase: clinical usefulness for patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Abstract Objective To investigate the clinical usefulness of serum superoxide dismutase (SOD) measurement in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods In this single-center retrospective study, demographic data, serum SOD levels, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), the Birmingham Vasculitis Activity Score (BVAS), ANCA, organ involvement, and outcomes were analyzed for 152 AAV patients hospitalized in the Second Affiliated Hospital of Chongqing Medical University. Meanwhile, the serum SOD levels of 150 healthy people were collected as the control group. Results Compared to the healthy control group, serum SOD levels of the AAV group were significantly lower (P < 0.001). SOD levels of AAV patients were negatively correlated to ESR, CRP, and BVAS (ESR rho = − 0.367, P < 0.001; CRP rho = − 0.590, P < 0.001; BVAS rho = − 0.488, P < 0.001). SOD levels for the MPO-ANCA group were significantly lower than the PR3-ANCA group (P = 0.045). SOD levels for the pulmonary involvement group and the renal involvement group were significantly lower than those for the non-pulmonary involvement group and the non-renal involvement group (P = 0.006; P < 0.001, respectively). SOD levels in the death group were significantly lower than the survival group (P = 0.001). Conclusions In AAV patients, low SOD levels might indicate disease associated oxidative stress. SOD levels in AAV patients were decreased with inflammation, suggesting that SOD levels could potentially be a surrogate marker for disease activity. SOD levels in AAV patients were closely related to ANCA serology, pulmonary involvement, and renal involvement, with low SOD levels an important indicator of a poor prognosis for AAV patients.

Improvement of indirect immunofluorescence technique to detect antineutrophil cytoplasmic antibodies and its impact on test positivity rate

The indirect immunofluorescence (IIF) technique for antineutrophil cytoplasmic antibodies (ANCA) detection is subject to substantial differences across laboratories. This study aimed to assess the impact of improvements in the IIF-ANCA technique on the positivity rate of ANCA tests. A cross-sectional study was performed with serum samples from patients with ANCA-associated vasculitis (AAV), autoimmune hepatitis (AIH), and ulcerative colitis (UC). A paired analysis was performed for IIF-ANCA results using the traditional method and a modified protocol after a series of specific adjustments in the technique based on the protocol of IIF-ANCA test performed at a nation-wide private laboratory in Brazil. ANCA specificity was assessed by ELISA for anti-proteinase 3 (PR3) and anti-myeloperoxidase (MPO) antibodies. Sixty-one patients were evaluated. The positivity rate of IIF-ANCA tests at disease presentation performed at the University reference laboratory was 32.3% in AAV, AIH, and UC patients, whereas the positivity rates of IIF-ANCA and ELISA tests in other laboratories were 75.0 and 72.7%, respectively. After modifications in the IIF-ANCA technique, there was a significant increase in the positivity rate (14.8 vs 34.3%; P=0.0002) and in median titers [1/40 (1/30-1/160) vs 1/80 (1/40-1/80); P=0.0003] in AAV, AIH, and UC patients. UC had the highest increment in positive results from 5.3 to 36.8%. There was poor agreement between MPO- or PR3-ANCA and both IIF-ANCA techniques. In conclusion, modifications in the IIF-ANCA protocol led to a significant improvement in its positivity rate and titers.

Three years follow-up report of two diffuse connective tissue disease cases caused by SARS-CoV-2 infection / 中国热带医学

@#Abstract: To report on two patients with Coronavirus Disease 2019 (COVID-19) combined with diffuse connective tissue disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection followed for nearly 3 years, in order to understand the long-term effects on the patients' immune system. Both patients were male, aged 81-82 years, and were hospitalized with fever on January 29, 2020 and February 10, 2020, respectively. Both were diagnosed with COVID-19 after positive SARS-CoV-2 polymerase chain reaction (PCR) tests. After receiving anti-infection treatment, cough suppressants, ex‐pectorants, and symptomatic supportive treatment, their body temperature returned to normal and two consecutive PCR tests were negative for SARS-CoV-2, and they were discharged from hospital. However, due to recurring fevers and varying degrees of rheumatic disease-related symptoms, both patients were readmitted to the hospital, indicating the presence of positive auto‐ antibodies and organ involvement. One patient recovered from COVID-19 with recurrent fever, joint pain, muscle aches and subcutaneous nodules, and was subsequently diagnosed with undifferentiated connective tissue disease. The other patient developed recurrent fever, mouth ulcers and rash after recovery from COVID-19 and was subsequently diagnosed with anti neutro phil cytoplasm antibody (ANCA)-associated vasculitis (AAV). The patient was treated with glucocorticoids and immunosuppres sive drugs and the symptoms resolved rapidly and subsequent laboratory and imaging examinations showed stable condition. However, due to self-termination of medication, their symptoms quickly relapsed, and further treatment with glucocorticoids and immunosuppressive agents resulted in sustained stability of their condition. The erythrocyte sedimentation rate and hyper‐sensitive C-reactive protein remained within normal limits, and lung CT scans showed stable lesions with partial absorption.SARS-CoV-2 infection may have long-term effects on patients' immune systems, leading to abnormal immune responses and diffuse connective tissue disease. This suggests that regular follow-up observation of immune system-related diseases may be necessary for elderly patients with COVID-19.

ANCA vasculitis and membranoproliferative glomerulonephritis associated with Sjögren's syndrome: Case report and literature review

ANCA-associated vasculitis may occur concomitantly with primary Sjögren's syndrome (SS) or arise during its evolution. We present the case of a patient who underwent dry symptoms, a positive Schirmer test and an SS-compatible autoimmunity profile and, simultaneously, deterioration of renal function, anaemia, and dyspnoea, requiring renal biopsy and fibro-bronchoscopy. Complementary studies documented acute necrotizing glomerulonephritis with extracapillary proliferation, and membranoproliferative pattern with immune complex deposition. Bronchoalveolar lavage was compatible with alveolar haemorrhage. Kidney lung syndrome secondary to ANCA vasculitis was diagnosed and treatment with steroid and intravenous cyclophosphamide with clinical and paraclinical improvement was instituted. Mixed renal involvement found in this case is uncommon in patients with SS, and treatment changes significantly, hence the importance of differential diagnosis and reporting in the literature.

La vasculitis asociada con anticuerpos anticitoplasma de neutrófilos-ANCA puede presentarse concomitantemente con síndrome de Sjögren primario o surgir durante su evolución. Se presenta el caso de una paciente que cursó con síntomas secos, test de Schirmer positivo, perfil de autoinmunidad compatible con síndrome de Sjögren y, de forma simultánea, deterioro de la función renal, anemia y disnea, por lo que requirió biopsia renal y fibrobroncoscopia. Los estudios complementarios documentaron glomerulonefritis aguda necrosante con proliferación extracapilar y patrón membranoproliferativo con depósito de complejos inmunes. El lavado broncoalveolar fue compatible con hemorragia alveolar. Se hizo diagnóstico de síndrome de pulmón-rinón secundario a vasculitis ANCA y se instauró tratamiento con esteroide y ciclofosfamida intravenosa, con mejoría clínica y paraclínica. El compromiso renal mixto encontrado en este caso es infrecuente en pacientes con SS, y el tratamiento cambia ostensiblemente, de ahí la importancia del diagnóstico diferencial y el reporte en la literatura.

Role of Immunohistochemistry and serology in subclassifying the Inflammatory Bowel Disease cases diagnosed as Inflammatory Bowel Diseases-unclassified on colonic biopsies

Background: Inflammatory bowel diseases (IBDs) mainly consist of Crohn's Disease (CD) and Ulcerative Colitis (UC). These two categories have overlapping histopathological features and sometimes it is difficult to diagnose them into distinct category and such biopsies are categorised as Inflammatory Bowel Disease (IBD-U). Recently, there has been an increase in interest to discover new biomarkers of IBD to differentiate UC and CD and predict their prognosis. Method: In the present study, 273 non-neoplastic colonic biopsies with clinicoendoscopic features of IBD were studied and categorized into UC (88; 32.3%) and CD (03; 1.1%) but a major chunk remained in category of IBD-U (182; 66.6%). 161 (58.9%) of these biopsies were then subjected to IHC for RB protein and ?-catenin and Serology for pANCA and ASCA was done in only 85 (31.13%) of these selected cases for identification of UC and CD on colonic biopsies. Result: 161 biopsies that were subjected to IHC analysis included 57 cases of UC, 03 cases of CD, and rest 101 cases of IBD-U. Out of 101 cases of IBD-U, 87 (86.13%) cases were reclassified as UC (61; 60.3%) and CD (14; 13.86%) on the basis of results of IHC and Serology. Conclusion: The two major tools IHC for ?-catenin and RB protein and the assay of serum ASCA and p-ANCA along with proper history and clinical presentation can act as a good adjunct to conventional H and E in subclassifying cases of IBD-U into UC and CD.

Granulomatosis with polyangiitis: A case report of early systemic fulminant presentation

Granulomatosis with polyangiitis is a systemic vasculitis that affects medium and small vessels, with high expression of anti-neutrophil cytoplasmic autoantibody. A case is pre sented on a patient with an initial compromise of the lower airway, who did not respond to management, required intensive care unit management, and died due to severe diffuse alveolar hemorrhage. His definitive diagnosis was established with a clinical autopsy. Gran-ulomatosis with polyangiitis is a disease with different ways of presentation, and can have fatal outcomes if it is not diagnosed early.

La granulomatosis con poliangeítis es un tipo de vasculitis que afecta a vasos de mediano y pequeño calibre de manera sistémica, con una alta expresión de anticuerpos contra el citoplasma del neutrófilo. Se presenta el caso de un paciente con un compromiso inicial de la vía área inferior, que no respondió al tratamiento y requirió manejo en unidad de cuidados intensivos. Finalmente, falleció por una hemorragia alveolar difusa severa. Su diagnóstico definitivo se estableció con una autopsia clínica. La granulomatosis con poliangeítis tiene diferentes formas de presentación y puede tener desenlaces fatales si no se diagnostica a tiempo.

Factor reumatoide en vasculitis ANCA asociadas / Rheumatoid factor in ANCA associated vasculitis

Introducción: las pruebas de factor reumatoide (FR) se utilizan principalmente para el diagnóstico de artritis reumatoidea (AR), sin embargo, también pueden estar presentes en otras enfermedades. Su significado clínico en contexto de vasculitis ANCA asociadas (VAA) todavía es incierto. El objetivo de este estudio fue establecer el significado clínico y pronóstico del FR en pacientes con VAA. Materiales y métodos: se realizó un estudio observacional, retrospectivo. Se evaluaron pacientes con diagnóstico de VAA (granulomatosis con poliangitis -GPA-, poliangitis microscópica -PAM- y granulomatosis eosinofílica con poliangitis -GEPA-), mayores de 18 años, con FR solicitado antes del inicio del tratamiento. Se recolectaron los siguientes datos: edad, sexo, tipo de VAA, duración de la enfermedad, tratamiento, órganos afectados, Birmingham Vasculitis Activity Score (BVAS), Five Factor Score (FFS), eritrosedimentación, proteína C reactiva, requerimiento de diálisis, asistencia respiratoria mecánica, mortalidad y causa de muerte. Se calculó el odds ratio (OR) y su intervalo de confianza del 95% (IC 95%) para determinar la fuerza de asociación entre las variables. Resultados: incluimos 32 pacientes en los que encontramos 31,2% de FR positivo. Comparados con aquellos con FR negativo, no hubo diferencias significativas con respecto a manifestaciones clínicas, ni actividad de la enfermedad medida por el BVAS y reactantes de fase aguda. La presencia de factor reumatoide se asoció a menor ingreso a diálisis (OR 0.14 IC 0,02-0,8; p=0,02) y mortalidad (p=0,04). No hubo diferencias significativas con respecto al FFS. Conclusiones: en nuestro estudio la presencia de FR en pacientes con vasculitis ANCA se asoció a menor requerimiento de diálisis y menor mortalidad. Estos hallazgos no se correlacionaron estadísticamente con el FFS. No se encontró asociación entre la presencia de FR y el compromiso de órgano, actividad de la enfermedad, ni requerimiento de asistencia respiratoria mecánica.

Introduction: rheumatoid factor tests are mainly used for the diagnosis of rheumatoid arthritis (RA); however, it may also be present in other diseases. Its clinical significance in the context of ANCA associated vasculitis (AAV) is still uncertain. The objective was to establish the clinical and prognostic significance of RF in patients with AAV. Materials and methods: a retrospective observational study was carried out. Patients with a diagnosis of AAV (GPA, MAP and AGEP) over 18 years of age with RF requested before the start of treatment were evaluated. The following data were collected: age, sex, type of AAV, disease duration, treatment, affected organs, Birmingham Vasculitis Activity Score (BVAS), Five Factor Score (FFS), erythrocyte sedimentation rate, C-reactive protein, dialysis requirement, attendance mechanical ventilation, mortality and cause of death. The odds ratio (OR) and its 95% confidence interval (95%CI) were calculated to determine the strength of association between variables. Results: we included 32 patients in whom we found 31.2% positive RF. Compared to those with negative RF, there were no significant differences with respect to clinical manifestations, nor disease activity measured by BVAS and acute phase reactants. The presence of the rheumatoid factor was associated with lower admission to dialysis (OR 0.14 CI 0.02-0.8 p=0.02) and mortality (p=0.04). There were no significant differences with respect to FFS. Conclusions: in our study, the presence of RF in patients with ANCA vasculitis was associated with a lower requirement for dialysis and lower mortality. These findings were not statistically correlated with the FFS. No association was found between the presence of RF and organ involvement, disease activity, or mechanical ventilation requirement.

Meta-analysis of the effectiveness of rituximab and cyclophosphamide combined with azathioprine in the treatment of anti-neutrophil cytoplasmic antibodies-related vasculitis / 中华风湿病学杂志

Objective:To evaluate the effectiveness and safety of rituximab (RTX) and cyclophosphamide/azathioprine (CYC/AZA) in the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis (AAV).Methods:After setting up the search strategy, the inclusion and screening criteria of the literature were determined, the Pubmed, Cochrane Library, Embase, China Biomedical Literature Database, CNKI, Wanfang Database, Weipu Database were searched for RTX and CYC/AZA treatment for AAV. For randomized controlled studies, in which the experimental group was RTX for AAV, and the control group was CYC/AZA for AAV were included. The retrieval time span was from January 2000 to June 2021, and the data obtained were analyzed using Revman 5.3 software.Results:A total of 9 articles and 4 studies were included, with a total of 384 patients, including 203 cases in the experimental group and 181 cases in the control group. In the treatment of AAV, the difference in the remission rate of RTX and CYC/AZA treatment of AAV was statistically significant, and the remission rate of the RTX group was higher [ OR(95% CI)=1.58(1.03, 2.40), P=0.03]. For the remission rates of different types of AAV, RTX and CYC/AZA were benefit for the treatment of granulomatous vasculitis, microscopic polyangiitis, eosinophilic granulomatous vasculitis, there was no statistically significant difference in the remission rate of patients with protease 3-related vasculitis and myeloperoxidase-related vasculitis. The incidence of granulocytopenia in the RTX group was significantly lower than that in the CYC/AZA group, and RTX treatment could reduce the incidence of other serious adverse reactions. Conclusion:For the remission induction therapy, RTX is not inferior to CYC for all subtypes of AAV. In the maintenance treatment phase, RTX has a higher remission rate and a lower recurrence rate. During the entire treatment process, patients who were treated with RTX had a higher long-term remission rate than patients who were not treated with RTX. RTX can effectively reduce the occurrence of adverse reactions such as neutropenia.

Cardiopulmonary arrest due to bronchoscopy-induced Takotsubo syndrome in a patient with antineutrophil cytoplasmic autoantibody-associated lung disease: a case report / Journal of Rural Medicine

Objective: Cardiac arrest (CA) has been observed in some patients with Takotsubo syndrome (TTS), most of whom had CA at the initial presentation of TTS. The objective of this report was to discuss the factors underlying the onset of this syndrome.Case presentation: A 72-year-old woman with refractory antineutrophil cytoplasmic autoantibody-associated lung disease was referred to our hospital. Twenty minutes after bronchoscopic examination, cardiopulmonary arrest suddenly occurred. Resuscitation immediately resumed her heartbeat and spontaneous breathing. Subsequent 12-lead electrocardiography, echocardiography, and left ventricular angiography revealed TTS.Conclusion: This case indicates that bronchoscopy can cause severe TTS, especially in patients with systemic inflammation.

Vasculitis y vasculopatía con compromiso cutáneo, nasal y pulmonar inducida por consumo de cocaína-levamisol / Vasculitis and vasculopathy with cutaneous, nasal and pulmonary involvementinduced by cocaine-levamisole use

Resumen La cocaína pura y la contaminada con levamisol producen múltiples dermatosis, siendo las más frecuentes las lesiones destructivas de línea media y las vasculitis similares a las ANCA. Las bases fisiopatológicas de estas manifestaciones se sustentan en el daño vascular secundario a vasculitis y/o vasculopatía, originado por ambas sustancias y en muchos casos se puede encontrar solapamiento de las formas clínicas, lo que puede llevar a diagnósticos erróneos. Los patrones de positividad de los auto anticuerpos, el patrón de las lesiones cutáneas y el contexto social, serán claves en el abordaje y tratamiento adecuado de estos pacientes.

Abstract Pure cocaine and contaminated cocaine with levamisole produce multiple cutaneous and systemic manifestations, being midline destructive lesions and ANCA-like vasculitis the most frequent ones. The pathophysiological bases of these manifestations are based on secondary vascular damage to vasculitis and/or vasculopathy caused by both substances and in many cases it may be found an overlapping of the clinical forms, which might lead to erroneous diagnoses. The patterns of positivity of the autoantibodies, the pattern of skin lesions and the social context of the patient will be key in the proper approach and management of these patients. The following case describes a patient with cutaneous, nasal and pulmonary manifestations due to cocaine / levamisole consumption. Also, a review of the literature is carried out.

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.

Hematoma esofágico como manifestación atípica de Vasculitis ANCA asociada: Reporte de un caso / Esophageal hematoma as an atypical manifestation of associated ANCA Vasculitis: Report of a case

Las Vasculitis ANCA pueden causar lesiones diversas a lo largo del tracto gastrointestinal pero la afectación esofágica es infrecuente. Dentro del espectro de lesiones que pueden aparecer un hematoma esofágico no es una mención habitual en la bibliografía. Presentamos el caso de una mujer de 67 años con diagnóstico de vasculitis ANCA asociada (VAA) y hematemesis. Consideramos que el hematoma esofágico es una manifestación atípica de una enfermedad infrecuente. La prevalencia real de este tipo de manifestaciones atípicas es desconocida ya sea por su carácter infrecuente o por la baja tasa de reportes, por lo que creemos es de utilidad la publicación de este tipo de manifestaciones.

ANCA associated vasculitis (AAV) can cause various injuries along the gastrointestinal tract, but esophageal involvement is rare. Within the spectrum of lesions that may occur an esophageal hematoma is not a common mention in the literature. We present the case of a 67-year-old woman diagnosed with AAV and hematemesis. We consider the esophageal hematoma to be an atypical manifestation of a rare disease. The actual prevalence of this type of atypical manifestations is unknown, either due to its infrequent nature or the low reporting rate, so we believe that the publication of this type of manifestations is useful.

Granulomatosis eosinofílica con poliangeitis: presentación inusual de una enfermedad rara en la edad pediátrica / Eosinophilic granulomatosis with polyangiitis: unusual presentation of a rare disease in pediatric age

La granulomatosis eosinofílica con poliangitis (GEPA), es un trastorno poco frecuente en la edad pediátrica, representando menos de un 2% de las vasculitis en pediatría. Su etiología es desconocida y de difícil diagnóstico debido a la variabilidad en su cuadro clínico. Los pacientes presentan como rasgo característico antecedentes de asma, rinitis alérgica y eosinofilia en sangre periférica. A nivel microscópico es una vasculitis necrosante que afecta a vasos de pequeño a mediano calibre, presencia de granulomas y eosinofilia extravascular. La GEPA es una vasculitis asociada a la presencia de anticuerpos anticitoplasma de neutrófilo (ANCA), su positividad en niños sólo se encuentran en menos del 40% de los casos. Presentamos el caso de una escolar de 8 años con cuadros respiratorios recurrentes asociados a eosinofilia superior al 10%, manifestaciones cutáneas importantes, esofagitis eosinofílica y polineuropatía, finalmente diagnosticado con GEPA-ANCA-PR3 (ANCA específico para proteinasa 3).

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disorder in pediatric age, accounting for less than 2% of vasculitis in pediatrics. Its etiology is unknown and difficult to diagnose due to the variability in its clinical picture. Patients have a history of asthma, allergic rhinitis and eosinophilia in peripheral blood as a characteristic feature. Microscopically, necrotizing vasculitis that affects small to medium-caliber vessels, the presence of granulomas and extravascular eosinophilia. GEPA is a vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA), its positivity in children is only found in less than 40% of cases. We present the case of an 8-year-old schoolgirl with recurrent respiratory symptoms associated with eosinophilia greater than 10%, important skin manifestations, eosinophilic esophagitis and polyneuropathy, finally diagnosed with GEPA-ANCA-PR3 (specific ANCA for proteinase 3).

Burkholderia sepsis mimicking flare of ANCA-associated vasculitis: A rare presentation

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune condition that primarily targets smallto medium sized vessels in multiple organ systems, with sinonasal, pulmonary and renal involvement being common.The present case study discusses a known case of ANCA associated vasculitis, type 2 diabetes and hypertension, whopresented with altered sensorium and weakness of the left side of the body. Few months before the onset of symptoms,the patient received rituximab injection for treating cutaneous panniculitis and high pANCA titers. MRI of brain and CECTof chest were suggestive of vasculitis and blood culture showed the growth of Burkholderia cepacia. She was treated withbroad spectrum antibiotics and other supportive treatment. Despite all the efforts including ionotropic and ventilatorsupports, the patient succumbed to the infection.