Performance of the 2017 American College of Rheumatology/European League Against Rheumatism Provisional Classification Criteria for Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in a Peruvian Tertiary Care Center.

AIM: To validate the new classification criteria for antineutrophil cytoplasmic antibody-associated vasculitis in a real-life Peruvian cohort of antineutrophil cytoplasmic antibody-associated vasculitis patients. METHODS: We reviewed medical records from a Peruvian tertiary care center from January 1990 to December 2019. Antineutrophil cytoplasmic antibody-associated vasculitis was diagnosed based on the 1990 American College of Rheumatology (ACR) criteria, the 2012 Chapel Hill Consensus Conference definitions, the European Medicines Agency (EMEA) algorithm, and the clinical acumen of the treating rheumatologists. We classified all patients using the "former criteria" (the 1990 ACR criteria for granulomatosis with polyangiitis [GPA] and eosinophilic GPA [EGPA] and the 1994 Chapel Hill Consensus Conference definition for microscopic polyangiitis [MPA]), the EMEA algorithm, and the "new criteria" (the 2017 ACR/European League Against Rheumatism Provisional Criteria). The level of agreement (using Cohen κ) was calculated using the clinical diagnosis as the criterion standard. RESULTS: We identified 212 patients, 12 of whom were excluded. One hundred fifty-four (77%) had MPA, 41 (20.5%) GPA, and 5 (2.5%) EGPA. The new criteria performed well for MPA (κ = 0.713) and EGPA (κ = 0.659), whereas the EMEA algorithm performed well for GPA (κ = 0.938). In the overall population, the new criteria showed better agreement (κ = 0.653) than the EMEA algorithm (κ = 0.506) and the former criteria (κ = 0.305). CONCLUSIONS: The 2017 ACR/European League Against Rheumatism Provisional Criteria showed better agreement for the clinical diagnosis of all the patients overall and had the best performance for MPA and EGPA. The EMEA algorithm had the best performance for GPA.

Survival in ANCA-Associated Vasculitides in a Peruvian Center: 28 Years of Experience.

AIM: The aim of this study was to identify demographic and clinical risk factors for mortality in patients with antineutrophil cytoplasmic antibodies-associated vasculitides (AAVs) in a Peruvian tertiary referral hospital. METHODS: Medical records of patients with AAV according to classification criteria or diagnosed by an experienced rheumatologist, covering the period between January 1990 and December 2018, were reviewed. Granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited vasculitis were included. Potential predictors of mortality were demographic factors, clinical manifestations, antineutrophil cytoplasmic antibodies status, diagnosis, disease categorization, the 2009 Five Factor Score (FFS), and treatment. Cox regression models were used to determine the risk factors for mortality. Univariable and multivariable analyses using a backward selection method were performed. RESULTS: One hundred ninety-six patients were included; female-to-male ratio was 2:1. The median (interquartile range) age at diagnosis and follow-up were 60.0 (51.0-68.0) and 4.8 (1.3-11.6) years, respectively. One hundred forty-eight patients (75.5%) had microscopic polyangiitis, 37 (18.9%) granulomatosis with polyangiitis, 5 (2.6%) eosinophilic granulomatosis with polyangiitis, and 6 (3.0%) renal-limited vasculitis. Overall survival rates at 1, 5, and 10 years were 83.4%, 68.2%, and 51.7%, respectively. Ocular involvement was protective (hazards ratio [HR], 0.36; 95% confidence interval [CI], 0.17-0.74; p = 0.006), whereas renal (HR, 2.09; 95% CI, 1.33-3.28; p = 0.001) and lung involvement (HR, 2.07; 95% CI, 1.31-3.28; p = 0.002) and the 2009 FFSs were predictive of mortality (2009 FFS = 1: HR, 2.46; 95% CI, 1.50-4.04; p < 0.001; 2009 FFS = 2: HR, 3.07; 95% CI, 1.54-6.10; p = 0.001; 2009 FFS = 3: HR, 13.29; 95% CI, 3.69-47.88; p < 0.001). CONCLUSIONS: Ocular involvement was protective, whereas 2009 FFS ≥ 1 and renal and lung involvement were predictive factors of mortality in Peruvian AAV patients.

Demographic and Clinical Features of ANCA-Associated Vasculitides in a Peruvian Tertiary Center.

AIM: The aim of this study was to identify the demographic and clinical features of patients with ANCA-associated vasculitides (AAVs) in a Peruvian tertiary referral hospital. METHODS: Medical records of patients with AAV according to classification criteria or diagnosed by an experienced rheumatologist, and covering the period between January 1990 and December 2019, were reviewed. Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and renal-limited vasculitis (RLV) were included. Demographic factors (age at diagnosis, sex), disease duration, clinical manifestations (per organ involvement), creatinine level at diagnosis (milligram per deciliter), ANCA status, diagnosis, 2009 Five Factor Score, disease categorization, and treatment were recorded. RESULTS: Two hundred twelve patients were included. Their female-to-male ratio was 1.9:1 (139 [65.6%]/73 [34.4%]), and their mean (SD) age at diagnosis was 59.2 (12.5) years. One hundred fifty-eight patients (74.5%) had MPA, 42 (19.8%) GPA, 7 (3.3%) RLV, and 5 (2.4%) EGPA. Neurological, lung, and renal involvements were the most frequently affected systems. Myeloperoxidase preferentially occurred in MPA (82.5%), whereas proteinase 3 did occur in GPA (79.5%). Microscopic polyangiitis patients were older (61.1 [11.5] years). Female sex predominated in MPA and RLV (2.4:1 and 6:1, respectively), but the opposite was the case for EGPA (1:4). Ear-nose-throat and ocular involvement were more frequent in GPA (both p's < 0.001), and neurological and cardiovascular involvement were more frequent in EGPA (p < 0.001 and p = 0.002, respectively). CONCLUSIONS: This is one of the largest series of AAV patients in Latin America. Overall, female sex predominated. Microscopic polyangiitis was the most frequent AAV, and myeloperoxidase-ANCA was the most frequent antibody in Peruvian AAV population.

Different epidemiologic profiles of systemic vasculitis between Brazil and Peru-preliminary results in two referral centers from both countries.

Little is known about the epidemiology of systemic vasculitis in South American countries. The aim of this study is to compare the prevalence of systemic vasculitides in two vasculitis referral centers from Brazil and Peru. A cross-sectional study was performed and all patients above 18 years of age, with at least 6 months of follow-up and who met classification or diagnosis criteria for the most common forms of vasculitis, were included. A total of 562 patients with systemic vasculitis were analyzed, 345 (61.4%) from Brazil and 217 (38.6%) from Peru. The frequency of Behçet's disease (37.9% vs. 1.8%; p < 0.0001), Takayasu arteritis (TAK) (25.2% vs. 6.9%; p < 0.0001), and giant cell arteritis (9.8% vs. 0.9%; p < 0.0001) was higher in the Brazilian center than the Peruvian one. On the other hand, the frequency of microscopic polyangiitis (MPA) (67.3% vs. 2.8%; p < 0.0001) and renal-limited vasculitis (2.8% vs. 0.0%; p = 0.009) was higher in the Peruvian center. No differences were found concerning other forms of vasculitis. At diagnosis, Brazilian patients with TAK, granulomatosis with polyangiitis, and MPA were younger than Peruvian patients. Epidemiologic differences in the frequency of systemic vasculitis are observed between a vasculitis referral center from Brazil and another from Peru. Key Points • Significant differences are observed regarding the epidemiologic profile of systemic vasculitis between Brazil and Peru. • MPA is the predominant form of vasculitis in Peru while BD and TAK are the most frequent forms of vasculitis in Brazil. • The age at diagnosis of TAK, MPA, and GPA was lower in Brazilian patients than in Peruvian patients.

Comparison of an interferon-gamma assay with tuberculin skin testing for detection of tuberculosis (TB) infection in patients with rheumatoid arthritis in a TB-endemic population.

OBJECTIVE: Tuberculosis (TB) in patients with rheumatoid arthritis (RA) undergoing treatment with anti-tumor necrosis factor (TNF) agents is commonly the result of reactivation of latent TB infection (LTBI); detection and treatment of LTBI is essential before treatment with anti-TNF agents. We reported previously that the tuberculin skin test (TST) is inaccurate for diagnosis of LTBI in patients with RA. Here, we compare the prevalence of LTBI in RA patients and matched controls according to positive TST and QuantiFeron-TB Gold In-Tube version (QFT) results and determine their agreement. METHODS: A cross-sectional study of 101 RA patients and 93 controls was conducted in Lima, Perú, where the prevalence of LTBI in the general population has been estimated to be 68%. Blood was drawn for QFT assay followed by TST using 2-TU of RT 23 purified protein derivative. TST was deemed positive at >or= 5 mm for RA patients and >or= 10 mm for controls. RESULTS: There were no significant differences between RA patients and controls for age, sex, bacillus Calmette-Guérin vaccination, or history of or contact with TB. 88% of patients had active RA disease and 2 (1.9%) patients had indeterminate QFT results. The number of subjects testing positive with the QuantiFeron assay was comparable between patients and controls (44.6% vs 59.1%, respectively), whereas the TST detected significantly less LTBI among RA patients (26.7%) than controls (65.6%). Thus, the rate of LTBI in RA patients represented 75% and 41% of the rate in their controls using QFT or TST, respectively (p = 0.008). Poor agreement between TST and QFT was seen in RA patients, but in controls, good agreement was observed between these tests. CONCLUSION: In a TB-endemic population, the QuantiFeron-TB Gold In-Tube assay seemed to be a more accurate test for detection of LTBI in RA patients compared with the TST, and may potentially improve the targeting of prophylactic therapy before treatment with anti-TNF agents.

[Pattern of serum cytokines in patients with rheumatoid artritis according to PPD reactivity]. / Patrón de citocinas séricas en pacientes con artritis reumatoide de acuerdo a su reactividad al PPD.

INTRODUCTION: We demonstrated, in a recently published study, far more PPD negative reactivity among patients who had RA (70%) than among controls (30%). To evaluate the hypothesis that different response to PPD in RA patients is associated with different profiles of serum cytokines, we compared the serum levels of IL-2, IL-4, IL-6, IL-10, TNF alpha and IFN gamma from PPD negative and PPD positive RA patients. We also evaluated any correlations between serum cytokines and RA activity. MATERIAL AND METHODS: Forty RA patients and 21 controls were enrolled. Those with an induration < 5mm were considered as negative and those with ≥ 5mm as positive PPD. Disease activity was calculated using DAS28. Plasma levels of cytokines were determined using the multiplex BD TM Cytometric Bead Array Kit Assay. RESULTS: Of the RA patients, 27 (67.5%) had negative reaction to PPD and 13 (32.5%) a positive reaction to PPD. There was no statistical difference in sex profile, age or activity index between both negative and positive PPD RA patients. There was no significant difference in all the cytokines measured between PPD positive and PPD negative RA patients. Index activity show a positive correlation with IFN gamma (r = 0.433; p = 0.005) and IL-6 (r = 0.325; p = 0.041) in RA patients. CONCLUSIONS: Positive and negative tuberculin RA patients seem to show a similar cytokine serum profile.

Riesgo de enfermedad tuberculosa en pacientes con artritis reumatoide / Tuberculosis risk in patients with rheumatoid arthritis

Antecedentes: Los estudios sobre riesgo de enfermedad tuberculosa (ET) en artritis reumatoide (AR) en pacientes no usuarios de terapia biológica son controversiales. Objetivo: Evaluar AR como factor de riesgo independiente para ET. Diseño: Estudio de cohortes no concurrente. Lugar: Red asistencial Hospital Guillermo Almenara Irigoyen, Lima-Perú, hospital docente. Participantes: Pacientes con AR no usuarios de terapia biológica. Intervenciones: Una cohorte de pacientes con AR no usuarios de terapia biológica (cumplimiento de criterios 1987 del ACR) fue pareada por edad y género con una cohorte control (pacientes con trastornos no inmunológicos). Se realizó una entrevista personal. El seguimiento para la cohorte AR se inició en el diagnostico de AR y culminó en el momento de la entrevista o en el diagnóstico de ET (los controles fueron seguidos el mismo periodo de tiempo). Se calculó la densidad de incidencia (DI) para ET en cada cohorte y el riesgo relativo (RR). La probabilidad de ET de acuerdo al tiempo de enfermedad fue comparada mediante curvas de Kaplan Meier. Se aplicó un modelo de Cox para ajustar drogas y patologías predisponentes (hazard ratio -HR). Principales medidas de resultados: Enfermedad tuberculosa en pacientes con artritis reumatoide. Resultados: La cohorte AR y los controles (667 y 664 pacientes, respectivamente) tuvieron 6 940,75 y 6 666,53 personas-año de seguimiento. La edad al diagnóstico...

Background: Studies on tuberculosis (TB) risk in patients with rheumatoid arthritis (RA) non-users of biological therapy show contradictory results. Objetives: To determine RA as independent risk factor for TB. Design: Non concurrent cohort study. Setting: Guillermo Almenara Asistential Net, Lima-Peru, a teaching hospital. Participants: Biological therapy non-users RA patients. Interventions: RA patients fulfilled the ARA 1987 diagnosis criteria and were biological therapy non-users. Control group was paired by age and sex to RA patients. Patients in control groups had non immunological disorders. Clinical information was completed by interviews. RA patients follow-up was started at the time of diagnosis and ended at the time of interview and/or TB diagnosis. Density incidence (DI) was found for each cohort and TB relative risk (RR) was calculated. To evaluate time length to TB evolution a Kaplan Meier curve was graphed and compared both groups with log-rank test. Drugs and predisposing TB pathologies were analyzed. Main outcome measures: Tuberculosis in patients with rheumatoid arthritis. Results: Six hundred and seventy six out of 808 RA patients and 664 controls qualified for inclusion criteriaÆs. RA and control groups reached 6 940,75 and 6 666,53 follow-up patients-year, respectively. RA cohort mean age was 46,65 at RA diagnosis. Only 29,7 per cent of RA patients had a positive tuberculin reaction. Fifteen TB cases were identified in the RA cohort and 8 at the control group, yielding a mean DI of 216,1/100 000 and 122,1/ 100 000 patients-year respectively. TB RR was 1,8 (IC 95 per cent=0,8- 4,2), and after adjusting drugs and co-morbidity the HR was 1,69 (IC 95 per cent =0,26-10,93). Statistically significant difference was not found with Kaplan Meier curves comparison (p=0,19). Conclusions: We did not find a higher risk of rheumatoid arthritis patients to develop tuberculosis.

Patrón de citocinas séricas en pacientes con artritis reumatoide de acuerdo a su reactividad al PPD / Pattern of serum cytokines in patients with rheumatoid artritis according to PPD reactivity

Introducción: En un reciente estudio, se demostró una alta reactividad negativa al PPD o tuberculina en pacientes con artritis reumatoide (AR), (70%) comparado con controles (30%). Para determinar si esta alta reactividad negativa al PPD está asociada con un determinado patrón de citocinas, se compararon las concentraciones séricas de interleucina (IL)-2, IL-4, IL-6, IL-10, factor de necrosis tumoral (TNF)-a e interferón (IFN)-g en pacientes con AR con reactividad positiva y negativa al PPD. Se analizó también la correlación entre las citocinas y la actividad de la AR. Material y métodos: Se estudiaron 40 pacientes con AR y 21 individuos sanos. Se consideró reactividad positiva al PPD a una induración e 5mm y reactividad negativa cuando es < 5 mm. La actividad de la AR se determinó según el DAS28. Las citocinas se determinaron por citometría de flujo utilizando el Kit Multiplex Cytometric Bead Array. Resultados: De los pacientes con AR, 27 (67,5%) presentaron reactividad negativa al PPD y 13 (32,5%) reactividad positiva al PPD, similares en edad, sexo femenino y enfermedad activa. No se encontraron diferencias significativas en las citocinas entre los grupos con PPD positivo y PPD negativo. El IFN-g (r = 0,433; p = 0,005) y la IL-6 (r = 0,325; p = 0,041) fueron las únicas que mostraron correlación positiva con la actividad de la enfermedad. Conclusiones: No parece que haya diferencias en el patrón de citocinas séricas en los pacientes con reactividad negativa y positiva al PPD(AU)

Introduction: We demonstrated, in a recently published study, far more PPD negative reactivity among patients who had RA (70%) than among controls (30%). To evaluate the hypothesis that different response to PPD in RA patients is associated with different profiles of serum cytokines, we compared the serum levels of IL-2, IL-4, IL-6, IL-10, TNF alpha and IFN gamma from PPD negative and PPD positive RA patients. We also evaluated any correlations between serum cytokines and RA activity. Material and methods: Forty RA patients and 21 controls were enrolled.Those with an induration < 5mm were considered as negative and those with e 5mm as positive PPD. Disease activity was calculated using DAS28. Plasma levels of cytokines were determined using the multiplex BD TM Cytometric Bead Array Kit Assay. Results: Of the RA patients, 27 (67.5%) had negative reaction to PPD and 13 (32.5%) a positive reaction to PPD. There was no statistical difference in sex profile, age or activity index between both negative and positive PPD RA patients. There was no significant difference in all the cytokines measured between PPD positive and PPD negative RA patients. Index activity show a positive correlation with IFN gamma (r = 0.433; p = 0.005) and IL-6 (r = 0.325; p = 0.041) in RA patients. Conclusions: Positive and negative tuberculin RA patients seem to show a similar cytokine serum profile(AU)