Chinar Rahmattulla

Renal function and ear, nose, throat involvement in anti-neutrophil cytoplasmic antibody-associated vasculitis: prospective data from the European Vasculitis Society clinical trials

OBJECTIVE We investigated whether ENT involvement is associated with renal biopsy findings and renal function in patients with ANCA-associated vasculitis (AAV). METHODS Newly diagnosed AAV patients derived from three international, multicentre trials were included. To investigate an association between ENT involvement and estimated glomerular filtration rate (eGFR) at diagnosis and 5-year follow-up, we performed multivariable regression analyses including clinical and histopathological parameters. To investigate whether our findings are specific to ENT involvement, we performed comparable analyses between eGFR and other early disease manifestations (arthralgia/arthritis, cutaneous and lung involvement). RESULTS One hundred and eighty-five of the 414 patients had ENT involvement. The mean presenting eGFR of patients with and without ENT involvement was 39.16 and 23.88 ml/min/1.73 m(2), respectively (P < 0.001). Mean eGFR increased by 6.76 ml/min/1.73 m(2) with each added ENT symptom (P = 0.007). Patients with ENT involvement had less interstitial fibrosis and tubular atrophy and a prognostically more favourable histopathological class on renal biopsy examination. Multivariable regression analyses correcting for clinical and histopathological parameters showed that ENT involvement is associated with both baseline and 5-year follow-up eGFR. There were no associations between baseline and 5-year follow-up eGFR and arthralgia/arthritis, cutaneous or lung involvement, suggesting that our findings are specific to ENT involvement. CONCLUSION The presence of ENT involvement in AAV patients is associated with prognostically favourable renal biopsy findings and better renal function. These results indicate that there may be different phenotypes of AAV defined by ENT involvement.

Incidence of Malignancies in Patients With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis Diagnosed Between 1991 and 2013

To investigate the incidence of malignancies during longitudinal followup of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV), and to examine the effect of immunosuppressive therapy on malignancy risk in these patients.

Acute coronary syndrome with a totally occluded culprit artery: relation of the ST injury vector with ST-elevation and non-ST elevation ECGs

BACKGROUND In acute coronary syndrome (ACS), ST-segment elevation (STE), often associated with a completely occluded culprit artery, is an important ECG criterion for primary percutaneous coronary intervention (PCI). However, several studies showed that in ACS a completely occluded culprit artery can also occur with a non-ST-elevation (NSTE) ECG. In order to elucidate reasons for this discrepancy we examined ST injury vector orientation and magnitude in ACS patients with and without STE, all admitted for primary PCI and having a completely occluded culprit artery. METHODS We studied the ECGs of 300 ACS patients (214/86 STE/NSTE; 228/72 single/multivessel disease) who had a completely occluded culprit artery during angiography prior to primary PCI. The J+60 injury vector orientation and magnitude were computed from Frank XYZ leads derived from the 10-s standard 12-lead ECG. RESULTS Demographic and anthropomorphic characteristics of the STE and NSTE patients did not differ. STE patients had a higher rate of right coronary artery occlusions, and a lower rate of left circumflex occlusions than NSTE patients (43 vs. 31%, and 13 vs. 22%, respectively; P<0.05). Injury vector elevation and magnitude were larger in STE than in NSTE patients (32° ± 37° vs. 6° ± 39°, and 304 ± 145 μV vs. 134 ± 72 μV, respectively; P<0.0001). CONCLUSION STE criteria favor certain injury vector directions and larger injury vector magnitudes. Obviously, several ACS patients with complete culprit artery occlusions requiring primary PCI do not fulfill these criteria. Our study suggests that STE-NSTE-based ACS stratification needs further enhancement.

Histopathological classification of antineutrophil cytoplasmic antibody-associated glomerulonephritis: an update.

Purpose of review This review discusses the findings of studies validating the histopathological classification of antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, which was devised in 2010 by an international working group of pathologists and nephrologists in collaboration with the European Vasculitis Society. Recent findings So far, eight studies have validated the histopathological classification of ANCA-associated glomerulonephritis. The studies came from Japan, China, Australia, the United States, the Netherlands, and Turkey. These validation studies confirmed that the histopathological classification of ANCA-associated glomerulonephritis is of predictive value for renal outcome. This was especially the case for patients with either a focal or sclerotic-class renal biopsy, whereas the crescentic and mixed classes showed different results in the validation studies. These differences could be due to differences in patient populations or therapy, inter-rater reliability and lack of inclusion of tubulointerstitial lesions in the classification. Therapy is known to influence renal outcome, but due to the retrospective design of the to-date performed validation studies, this parameter could not be fully accounted for in these validation studies. Inter-rater reliability among three histopathologists was investigated in one study and was moderate. Summary The histopathological classification of ANCA-associated glomerulonephritis predicts renal outcome during follow-up, especially in patients with a focal or sclerotic-class renal biopsy. A large international validation study is currently being performed. Video Abstract http://links.lww.com/CONH/A6

Incidence of malignancies in patients diagnosed with ANCA‐associated vasculitis between 1991 and 2013

To investigate the incidence of malignancies during longitudinal followup of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV), and to examine the effect of immunosuppressive therapy on malignancy risk in these patients.

Role of the vectorcardiogram-derived spatial QRS-T angle in diagnosing left ventricular hypertrophy

INTRODUCTION Current criteria for electrocardiographic (ECG) diagnosis of left ventricular hypertrophy (LVH) have a low diagnostic accuracy. Addition of demographic, anthropomorphic, and additional ECG variables may improve accuracy. As hypertrophy affects action potential morphology and intraventricular conduction, QRS prolongation and T-wave morphology may occur and become manifest in the vectorcardiographic variables spatial QRS-T angle (SA) and spatial ventricular gradient. In this study, we attempted to improve the diagnostic accuracy for LVH by using a combination of demographic, anthropomorphic, ECG, and vectorcardiographic variables. METHODS The study group (n = 196) was divided in 4 subgroups with, on one hand, echocardiographically diagnosed LVH or a normal echocardiogram and, on the other hand, with any of the conventional ECG signs for LVH or with normal ECGs. Each subgroup was randomly split into halves, yielding 2 equally-sized (n = 98) data sets A and B. Age, sex, height, weight, body mass index, body surface area (BSA), frontal QRS axis, QRS duration, QT duration, maximal QRS vector magnitude, SA, and ventricular gradient magnitude and orientation were univariate studied by receiver operating characteristic analysis and were used to build a stepwise linear discriminant model using P < .05 as entry and P > .10 as removal criterion. The discriminant model was built in set A (model A) and tested on set B. Stability checks were done by building a discriminant model on set B and testing on set A and by cross-validation analysis in the complete study group. RESULTS The discriminant model equation was D = 5.130 × BSA - 0.014 × SA - 8.74, wherein D greater than or equal to 0 predicts a normal echocardiogram and D less than 0 predicts LVH. The diagnostic accuracy (79%) was better than the diagnostic accuracy of conventional ECG criteria for LVH (57%). CONCLUSION The combination of BSA and SA yields a diagnostic accuracy of LVH that is superior to that of the conventional ECG criteria.

Incidence of Malignancy Prior to Antineutrophil Cytoplasmic Antibody–associated Vasculitis Compared to the General Population

Objective. Previous studies have reported an increased malignancy risk preceding antineutrophil cytoplasmic antibody–associated vasculitis (AAV), suggesting common pathogenic pathways in these 2 entities. However, the study results were conflicting and often limited to patients with granulomatosis with polyangiitis (GPA). Here, we study the malignancy risk prior to AAV diagnosis [either GPA or microscopic polyangiitis (MPA)] to elaborate on the putative association between malignancy and AAV. Methods. A total of 203 patients were selected for the current study. Malignancies prior to AAV diagnosis were identified using a nationwide pathology database, and their occurrence was verified by reviewing the medical files of 145 patients (71.4%). The malignancy incidence was compared to the general population by calculation of standardized incidence ratios (SIR), matching for sex, age, and time period. SIR were calculated for 2 intervals: < 2 years and ≥ 2 years prior to AAV diagnosis. Separate analyses were performed for GPA and MPA. Results. The overall risk for malignancy prior to AAV diagnosis was similar to that of the general population (SIR 0.96, 95% CI 0.55–1.57), as was true when risks were analyzed by malignancy type, including skin, bladder, kidney, lung, stomach, rectum, and uterus (SIR ranged from 1.64 to 4.14). We found no significant difference in malignancy risk between patients with GPA and MPA. Conclusion. Our findings do not support the hypothesis that preceding malignancies and AAV have a causal relationship or shared pathogenic pathways.

FRI0455 Renal Function in Anca-Associated Vasculitis is Associated with ENT Involvement

Background It has been suggested that ear, nose, and throat (ENT) involvement in ANCA-associated vasculitis (AAV) may carry the advantage of earlier recognition of the disease. Alternatively, differences in histological findings between patients with MPO-ANCA and PR3-ANCA might represent different routes in the pathogenesis of vasculitic disease in these subsets of patients. Objectives This study investigates whether ENT involvement in AAV is associated with better renal function and histopathology than AAV without ENT involvement. Methods Newly diagnosed AAV patients with renal involvement from three international, multicentre trials were included. Multivariable analysis correcting for age, ANCA-serotype, tubulitis, interstitial infiltrate, interstitial fibrosis and tubular atrophy (IFTA), and the histopathological class in the classification of ANCA-associated glomerulonephritis (AAGN) investigated an association between ENT involvement and estimated glomerular filtration rate (eGFR). To investigate whether our findings are specific to ENT involvement, we repeated the multivariable analysis with cutaneous involvement, lung involvement, and arthralgia/arthritis as possible eGFR determinants. Results Of the 414 patients included in this study, 185 patients had ENT involvement. Patients with ENT involvement had a better eGFR compared to patients without ENT involvement. Mean (SD) presenting eGFR of patients with and without ENT involvement was 39.2 (33.1) and 23.9 (20.1) mL/min/1.73 m2, respectively (p<0.001). Moreover, average eGFR increased by 6.7 (95% CI 1.7 – 11.6) mL/min/1.73 m2 with each additional ENT symptom present (p<0.008). Patients with ENT involvement also had less interstitial fibrosis and tubular atrophy in their renal biopsy (p<0.001) and a prognostically more favourable class in the histopathological classification of AAGN (p=0.044). Multivariable linear regression analysis to investigate associations with eGFR showed that, in addition to ENT involvement (β=9.0, p=0.004), age (β=-0.5, p<0.001), tubulitis (β=-8.1, p=0.001), interstitial infiltrate (β=-8.1, p<0.001), IFTA (β=-7.9, p=0.002), and the histopathological classification of AAGN (β=-6.5, p<0.001) were each independently associated with eGFR. A pre-specified sensitivity analysis including only PR3-ANCA positive patients showed that also in this subgroup of patients ENT involvement is positively associated with better eGFR. No influence on eGFR was observed with cutaneous involvement, lung involvement, or arthralgia/arthritis, suggesting that our findings are specific to ENT involvement. Conclusions ENT involvement in AAV patients with renal disease is associated with better renal function and a prognostically more favorable renal biopsy. These findings are indicative of different phenotypes of AAV defined by ENT involvement. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1745