Childhood-onset granulomatosis with polyangiitis and microscopic polyangiitis: systematic review and meta-analysis

Abstract

BackgroundThe data from cohorts of childhood-onset granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) remain scarce and heterogeneous. We aimed to analyse the features at presentation, therapeutic approaches and the disease course of these rare diseases.MethodsElectronic searches of Medline and the Cochrane Central Register of Controlled trials database were conducted. We also checked the reference lists of the studies included and other systematic reviews, to identify additional reports. We included all cohorts, cross-sectional studies or registries reporting features at presentation or outcomes in patients with a diagnosis of childhood-onset GPA or MPA (age <18 years). The pooled prevalence of clinical manifestations at presentation, ANCA and induction therapies for GPA and MPA was calculated.ResultsWe reviewed 570 full texts and identified 14 studies on GPA and 8 on MPA. Childhood-onset GPA and MPA occurred predominantly in female subjects during adolescence. For GPA, ear-nose-throat (ENT) disease (pooled prevalence 82 % [95 % CI 78–87]), constitutional symptoms (73 % [95 % CI 55–88]), renal (65 % [95 % CI 49–79]), and lower respiratory tract (61 % [95 % CI 48–74]) manifestations were the most frequently reported at presentation. Renal disease was a hallmark of MPA (94 % [95 % CI 89–97]). ANCA were detected in >90 % of children with GPA or MPA. Combined corticosteroids and cyclophosphamide was the most frequently used first remission-inducing treatment for GPA (76 % [95 % CI 69–82]) and MPA (62 % [95 % CI 20–96]). Relapses occurred more frequently in GPA (67–100 %) than in MPA (25–50 %). The leading causes of death were the disease itself, and infections.ConclusionsChildhood-onset MPA and GPA remain severe diseases with frequent relapses and a high cumulative morbidity. Survival and disease-free survival need to be improved.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0523-y) contains supplementary material, which is available to authorized users.

Lung involvement in childhood onset granulomatosis with polyangiitis

“…This characteristic triad is frequently associated with systemic symptoms (73%) [18]. Although the main aim of this review is to present lung involvement in GPA, upper airway disease is briefly summarized below in the next paragraph, as it affects respiratory findings in patients with GPA.…”

“…Sinonasal disease is a common presenting feature of GPA in children, which should be distinguished from infectious or allergic rhinitis or rhinosinusitis [18, 24, 32]. Longstanding disease can damage nasal cartilage, leading to septal perforation and saddle-nose deformity.…”

Granulomatosis with Polyangiitis (Wegener's Granulomatosis): Evolving Concepts in Treatment

“…GPA in children is rare, and exhibits some differences from adult cases. [27][28][29][30][31] Renal involvement is less common in childhood cases (53-83%), [24][25][26][27]29 whereas laryngeal/tracheal and bronchial involvement is more common in children (>30%). 25,26,32,33 In a meta-analysis of 14 studies of childhood GPA, most common features included (þ) ANCA (> 90%) and involvement of ears/ nose/throat (ENT) (82%), constitutional (73%), kidneys (65%), and/or lower respiratory tract (61%).…”

“…Relapses occurred in 67 to 100% of children. 29 Treatment of GPA in children is variable internationally, with a greater use of rituximab in the United States and greater use of cytotoxic agents (principally cyclophosphamide [CYC]) in other countries. 34…”

Neuroimaging in Pediatric Autoimmune Diseases

“…Peripheral or cranial neuropathies may occur in up to 40% of patients. 121 CNS manifestations may occur in up to 24% of children, 122,123 including headache, encephalopathy, seizures, and stroke. eGPA is a small vessel necrotizing granulomatous vasculitis associated with both anti-PR3 and anti-MPO ANCA, and accompanied by asthma and hypereosinophilia.…”