Primary Vasculitis in Childhood: GPA and MPA in Childhood

Abstract

Childhood onset anti-neutrophilic cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a rare group of primary systemic vasculitides affecting medium and small blood vessels. AAV includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and renal limited ANCA vasculitis. These disorders are associated with severe clinical manifestations, frequent relapses and a high cumulative morbidity, and often present with multisystem involvement. Renal involvement is common in the pediatric age group, characterized by pauci-immune necrotizing and crescentic glomerulonephritis which frequently progresses to chronic kidney disease in adulthood. ANCAs against proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO) (MPO-ANCA) remain the hallmark of AAV and are integral to the disease pathogenesis. Newer understanding of neutrophil extracellular traps and complement activation have provided better insights into disease pathogenesis. A pediatric vasculitis working group has developed and validated childhood vasculitis classification criteria and disease activity and damage scores. No specific pediatric treatment recommendations exist due to rare nature of the illness in pediatric population. Smaller case series have been published on the efficacy of adult treatment regimens in pediatric patients. The prognosis often remains guarded with frequent relapses and a high cumulative morbidity. The aim of this article is to provide a comprehensive review on pediatric AAV with a focus on recent observations regarding epidemiology, disease pathogenesis, treatment, and prognosis.

Clinical and Pathophysiological Insights Into Immunological Mediated Glomerular Diseases in Childhood

“…This feature might be shared with EGPA, but is rarely seen with MPA. Involvement of the upper respiratory tract (rhinitis, sinusitis, nasal crust, epistaxis, otitis media, sensorineural or conductive hearing loss) precludes the diagnosis of MPA (164). Subglottic tracheal stenosis is a severe complication and that occurs 5 times more frequently in pediatric patients than in adults (163).…”

“…Lower respiratory tract involvement is a shared feature in all AAV subtypes (cough, wheezing, hemoptysis, and bronchial stenosis). Catastrophic pulmonary hemorrhage may also occur in up to 42% patients in MPA (164). Eosinophilic granulomatosis with polyangiitis predominantly affects the airways, less frequently the skin, heart, gastrointestinal tract, or nervous system.…”

“…Renal involvement in AAV is common. In MPA, it is present in 94-100% of patients at onset (164), whereas GPA renal involvement has been noted in 50-100% of children at onset (163). To date, no pediatric case report has described renal injury in EGPA (25,160).…”

“…High levels of MPO and PR3 are noted on the surface of primed circulating neutrophils, where they are most exposed to the action of autoantibodies (164). Regardless of the trigger, a series of events occurs leading to B cell dysregulation which, in association with an imbalance between helper and effector T cells, leads to ANCA production and neutrophil activation with consequent tissue damage and vessel inflammation.…”

Optic neuritis in a teenage girl with granulomatosis with polyangiitis

“…Occasionally disease can start as fulminant form. 3 Inflammation can affect different parts of the eye and manifest with scleritis, ulcerative keratitis, occlusive retinal periarteritis and uveitis. Regarding the ocular adnexa, nasolacrimal duct obstruction can occur and lead to dacryocystitis, or inflammation can occur in the orbital tissue in the form of orbital pseudotumor.…”