ANCA and anti-glomerular basement membrane double-positive patients: A systematic review of the literature

Double-positive patients (DPP) exhibiting anti-glomerular basement membrane (GBM) and anti-neutrophil cytoplasmic antibodies (ANCAs) belong to an entity that is newly and poorly described, mainly in short series. We aimed to better characterize the epidemiological features, clinical presentation and therapeutic outcomes of these patients through a systematic review. We performed a systematic review of English-, German-, Spanish- and French-written publications from February 1987 to March 2020 reporting cases of DPP using the following databases: PubMed, Scielo, ScienceDirect, Google Scholar, The Cochrane Library, Open Grey, The Grey Literature Report, Clinicaltrials.gov and International Clinical Trial Registry Platform of the World Health Organization. In total, 538 DPP were identified from 90 articles. Their clinical presentations were often severe, and the majority exhibited acute kidney failure (91.8%) with a median initial serum creatinine level of 873 μmol/L; 50.7% had alveolar haemorrhage. Other manifestations were present in 30.3% of DPP, mainly ear, nose, throat and articular manifestations. ANCAs were predominantly directed against MPO (n = 377/523; 72.1%) compared to PR3 (n = 107/523; 20.5%), with rare cases of triple positivity (n = 15/538; 2.9%). Although most patients received initial immunosuppressive therapy (n = 285/317; 89.9%), the one-year overall, renal and relapse-free survival rates were 64.8%, 38.7% and 71.1%, respectively. DPP are associated with the characteristics of two eponymous vasculitis types, responsible for a poor overall and renal prognosis. Thus, simultaneous testing of both antibodies and systematic renal biopsy should be recommended in every patient with rapidly progressive glomerulonephritis to recognize this difficult-to-treat and rare disease.