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Background
The incidence of anti-glomerular basement membrane (GBM) disease and ANCA-associated vasculitis (AAV) is less than 2 in million and 20 in million per year, respectively. When they occurred together, it is called “double positive disease” which occurred in more than what is expected by chance alone. Both may present with life-threatening conditions including rapidly progressive glomerulonephritis (RPGN) and alveolar haemorrhage with very poor prognosis if left untreated. The dual positivity might influence the onset and the course of the disease as well as the treatment plan, the initial presentation might be aggressive as seen in patients with anti-GBM disease, and histological evidence of chronicity and tendency to relapse as seen in AAV. Management including trying to clear the antibodies by PE and decrease the production of new antibodies by immunosuppression. Unlike anti-GBM disease, double positivity has a high risk for relapse so maintenance immunosuppression is required.
Case presentation
A 59 year old gentleman, presented with fever, hemoptysis, decreasing urine output and lower limb edema of 2 weeks with rapidly deteriorating renal function. Not on any long-term medication.
Examination (Table 1)
Discussion
Up to one third of cases of anti-GBM disease will have ANCA, usually P-ANCA, and up to 5% of patient with AAV will have anti-GBM antibodies. The severe presentation for patients with double positive antibodies suggest that anti-GBM disease is the major pathology in early disease, however, the features of older age at presentation and chronicity found in renal biopsies suggest that AAV is also being a part of the equation. Kidney biopsy is crucial for confirming the diagnosis and for its prognostic value.Positive anti-GBM antibodies are assumed to be pathogenic especially in the context of RPGN. The lack of linear deposition in the biopsy, as seen in our case, although not common, was seen in experimental models, demonstrated that anti-GBM antibodies can synergise with ANCA to enhance GN, without the manifestation of linear anti-GBM staining. As per KDIGO guidelines PE is recommended and treatment should be started if the diagnosis is suspected even before confirming the diagnosis as delaying in treatment carries a poor prognosis, PE should be continued until the anti-GBM antibodies are no longer detectable. Maintenance immunosuppression is needed as double-positive disease showed higher rate of relapse compared to anti-GBM disease.
Double positivity for both ANCA and anti-GBM antibodies should be considered in patients with either antibody as it may change in the management. Patients have a mixed disease phenotype, necessitating aggressive early treatment for anti-GBM disease, and maintenance immunosuppression and observation for risk of relapse for AAV.