Paediatric anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis: an update on renal management

Abstract

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of disorders characterized by necrotizing inflammation of the small to medium vessels in association with autoantibodies against the cytoplasmic region of the neutrophil. Included in this definition are granulomatosis with polyangiitis (GPA, formerly known as Wegener’s granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (formerly known as Churg–Strauss syndrome). AAV are chronic, often relapsing diseases that can be organ or life threatening. Despite immunosuppression, the morbidity and mortality remain high. Renal involvement contributes significantly to the morbidity with high numbers of patients progressing to end-stage kidney disease. Current therapies have enabled improvements in renal function in the short term, but evidence for long-term protection is lacking. In MPA, renal involvement is common at presentation (90%) and often follows a more severe course than that seen in paediatric GPA. Renal biopsy remains the ‘gold standard’ in diagnosing ANCA-associated glomerulonephritis. While GPA and MPA are considered separate entities, the two are managed identically. Current treatment regimens are extrapolated from adult studies, although it is encouraging to see recruitment of paediatric patients to recent vasculitis trials. Traditionally more severe disease has been managed with the ‘gold standard’ treatment of glucocorticoids and cyclophosphamide, with remission rates achieved of between 70 and 100%. Other agents employed in remission induction include anti-tumor necrosis factor-alpha therapy and mycophenolate mofetil. Recently, however, increasing consideration is being given to rituximab as a therapy for children in severe or relapsing disease, particularly for those at risk for glucocorticoid or cyclophosphamide toxicity. Removal of circulating ANCA through plasma exchange is a short-term measure reserved for severe or refractory disease. Maintenance therapy usually involves azathioprine. The aim of this article is to provide a comprehensive review of paediatric AAV, with a focus on renal manifestations, and to highlight the recent advances made in therapeutic management.

Seronegative granulomatosis with polyangiitis presenting with multiple cranial nerve palsies

“…The CHCC 2012 defined this disease as necrotizing granulomatous inflammation and necrotizing vasculitis of small to medium‐sized vessels . The presence of anti‐neutrophil cytoplasmic antibody (ANCA), an autoimmune antibody, is adjunctive for its diagnosis …”

“…Without treatment, the expected patient survival is about 1 year after diagnosis and shorter for delayed diagnosis; however, the 5‐year survival rate increases to up to 80% with treatment. Therefore, early diagnosis with subsequent adequate treatment is critical for better prognosis …”

“…2 The presence of anti-neutrophil cytoplasmic antibody (ANCA), an autoimmune antibody, is adjunctive for its diagnosis. [3][4][5][6][7] GPA can manifest with variable symptoms and a wide range of severities in either an acute or chronic course, but renal and respiratory systems are commonly involved as the first clinical manifestations. In the kidneys, rapidly progressive glomerulonephritis (RPGN) occurs, leading to chronic renal failure, while the respiratory system manifestations involve the upper airways, trachea and lungs.…”

“…Therefore, early diagnosis with subsequent adequate treatment is critical for better prognosis. 3 There have been case reports of GPA with multiple involvement of the nervous system. 3,18,19 We report a case of GPA, focusing on the peculiar symptoms and diagnostic pitfalls, as it is a rare entity in which the initial manifestation of neurological deficits and ACNA negativity are very unusual.…”

“…3 There have been case reports of GPA with multiple involvement of the nervous system. 3,18,19 We report a case of GPA, focusing on the peculiar symptoms and diagnostic pitfalls, as it is a rare entity in which the initial manifestation of neurological deficits and ACNA negativity are very unusual. This study abides by the World Medical Association Declaration of Helsinki recommendations and was approved by the Institutional Review Board of Seoul National University Hospital (IRB No.…”