Identifying relevant determinants of in-hospital time to diagnosis for ANCA-associated vasculitis patients

OBJECTIVES: Diagnosing patients with ANCA-associated vasculitis (AAV) can be challenging owing to its rarity and complexity. Diagnostic delay can have severe consequences, such as chronic organ damage or even death. Given that few studies have addressed diagnostic pathways to identify opportunities to improve, we performed a clinical audit to evaluate the diagnostic phase. METHODS: This retrospective, observational study of electronic medical records data in hospitals focused on diagnostic procedures during the first assessment until diagnosis. RESULTS: We included 230 AAV patients from nine hospitals. First assessments were mainly performed by a specialist in internal medicine (52%), pulmonology (14%), ENT (13%) or rheumatology (10%). The overall median time to diagnosis was 13 [interquartile range: 2–49] days, and in patients primarily examined by a specialist in internal medicine it was 6 [1–25] days, rheumatology 14 [4–45] days, pulmonology 15 [5–70] days and ENT 57 [16–176] days (P = 0.004). Twenty-two of 31 (71%) patients primarily assessed by a specialist in ENT had non-generalized disease, of whom 14 (64%) had ENT-limited activity. Two hundred and nineteen biopsies were performed in 187 patients (81%). Histopathological support for AAV was observed in 86% of kidney biopsies, 64% of lung biopsies and 34% of ENT biopsies. CONCLUSION: In The Netherlands, AAV is diagnosed and managed predominantly by internal medicine specialists. Diagnostic delay was associated with non-generalized disease and ENT involvement at presentation. Additionally, ENT biopsies had a low diagnostic yield, in contrast to kidney and lung biopsies. Awareness of this should lead to more frequent consideration of AAV and early referral for a multidisciplinary approach when AAV is suspected

Glomerular hematuria:an atypical presentation of anti-glomerular basement membrane nephritis

BACKGROUND: Urologic diseases can cause hematuria, but dysmorphic erythrocytes directs to a glomerular disease. The latter might occur isolated or in the presence of systemic complaints, proteinuria or kidney failure. These factors determine the differential diagnosis that ranges from an innocent IgA nephropathy to a fatal anti-glomerular basement membrane (GBM) nephritis.CASE: A 30-year old patient attended the outpatient clinic because of glomerular hematuria and normal kidney function with working diagnosis IgA nephropathy. Three months later he presented to the emergency department with a severe acute kidney injury duo to an anti-GBM nephritis. In retrospect, the anti-GBM titer was already high during the outpatient clinic phase, but due to the preserved kidney function, anti-GBM nephritis was not added to the differential diagnosis.CONCLUSION: Glomerular hematuria with a preserved kidney function could in a rare instance be caused by a subclinical anti-GBM nephritis. Follow-up of the kidney function and comprehensive laboratory testing - or even a kidney biopsy - could potentially lead to an early diagnosis of anti-GBM nephritis.</p

ExploriNg DUrable Remission with Rituximab in ANCA-associatEd vasculitis (ENDURRANCE trial): protocol for a randomised controlled trial

Introduction Both rituximab (RTX) and cyclophosphamide (CYC) are effectively used in combination with steroids as remission induction therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Several studies have shown that the effect on achieving (clinical) remission, frequency and severity of relapses is equivalent for both therapies, but there is accumulating data that the long-term safety profile of RTX might outperform CYC. Combination of RTX with low-dose CYC (LD-CYC) has been investigated in only a few uncontrolled cohort studies, in which clinical remission and a favourable immunological state with low relapse rates was quickly achieved. In this randomised controlled trial, we aim to investigate whether the combination treatment (RTX+LD CYC) is superior in comparison to standard care with RTX only.Methods and analysis This study is an open-label, multicentre, 1:1 randomised, prospective study for patients with AAV with generalised disease, defined as involvement of major organs, that is, kidneys, lungs, heart and nervous system. In total, 100 patients will be randomised 1:1 to receive either remission induction therapy with standard of care (RTX) or combination treatment (RTX+LD CYC) in addition to steroids and both arms are followed by maintenance with RTX retreatments (tailored to B-cell and ANCA status). Our primary outcome is the number of retreatments needed to maintain clinical remission over 2 years. Secondary outcomes are relevant clinical endpoints, safety, quality of life and immunological responses.Ethics and dissemination This study has received approval of the Medical Ethics Committee of the Leiden University Medical Center (P18.216, NL67515.058.18, date: 7 March 2019). The results of this trial (positive and negative) will be submitted for publication in relevant peer-reviewed publications and the key findings presented at national and international conferences