Elsevier

Clinical Immunology

Volume 211, February 2020, 108325
Clinical Immunology

Childhood GPA, EGPA, and MPA

https://doi.org/10.1016/j.clim.2019.108325Get rights and content

Abstract

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a term used to describe rare primary systemic vasculitides affecting small and medium-sized blood vessels. AAV diseases which include Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA), Microscopic Polyangiitis (MPA) and renal limited ANCA vasculitis. These multisystemic disorders involve upper and lower respiratory tract and kidneys associated with organ damage and long term sequelae. Newer understanding of pathogenesis in AAV have paved the way for clinical research with different biologic therapies. In spite of the paucity of clinical trials in pediatric AAV, the long-term survival of patients with AAV has improved dramatically. International collaborations will help to conduct clinical trials in pediatric AAV and help in better understanding of remission rates, relapse rates, and other outcomes. This article aims to provide a comprehensive review of pediatric AAV with a focus on epidemiology, disease pathogenesis, treatment trials, and prognosis.

Section snippets

Background

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) represents a family of disorders resulting in primary inflammation of the blood vessel wall. These are multisystemic diseases characterized by necrotizing arteritis with few or no immune deposits in small to medium-sized arteries. These disorders comprise granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and renal limited ANCA vasculitis [1]. In most

Epidemiology

ANCA associated vasculitis is a rare in the pediatric population. Childhood primary vasculitis overall is diagnosed in 3% of all children referred to some US pediatric rheumatology clinics [2]. The overall incidence of AAV is 10 to 20 new cases per million per annum in most parts of the world [3,4]. The annual incidence and prevalence of AAV vary according to latitude in both the southern and northern hemispheres [5]. Childhood AAV has a higher female preponderance. In childhood, the disease is

Etiopathogenesis

The pathogenesis of AAV remains unclear. They are recognized as primary systemic vasculitis of small blood vessels with the presence of ANCAs in the serum. Patients with GPA are typically positive for PR3-ANCAs (proteinase 3 also called as myeloblastin), MPA are positive for MPO-ANCAs (myeloperoxidase) and 50% of patients with EGPA are positive for MPO-ANCAs [1].

Genome-wide association studies (GWAS) have identified the strongest associations with AAV with major histocompatibility complex class

Classification

There is considerable overlap among different forms of vasculitis. The 1990 American College of Rheumatology (ACR) classification criteria included GPA and EGPA, but not MPA [32,33]. Pediatric vasculitis classification criteria were published in 2010 and were endorsed by EULAR, the Pediatric Rheumatology European Society, and Pediatric Rheumatology International Trial Organization (EULAR/PRINTO/PReS) [34] (Table 1). These criteria for GPA in addition to the previous clinical descriptions of ACR

GPA

GPA usually occurs as a triad involving the upper and lower respiratory tract with renal involvement. Though a clinical triad is common, patients can present with either localized granulomatous disease with a chronic course or as an acute small vessel vasculitis characterized by the pulmonary-renal syndrome, in addition to other acute and chronic presentations and combinations. A recent meta-analysis identified upper respiratory tract involvement as the most frequent manifestation, followed by

Disease activity and damage assessments

The Pediatric Vasculitis Activity Score (PVAS) is scored 0–63, based on presence or absence of clinical item attributable to active vasculitis after exclusion of other causes such as infection. A higher PVAS score indicates higher disease activity. It was published in 2012 by redefining the Birmingham Vasculitis Activity Score (BVAS) components and adding eight pediatric items in cutaneous, cardiovascular and abdominal sections [56]. This activity scoring is a validated tool in pediatrics

Treatment

The therapeutic approach and management strategies in pediatric AAV are extrapolated from adult studies [60,61]. In spite of the paucity of pediatric-specific AAV guidelines, incorporating the adult evidence-based treatment suggestions for AAV has led to a drastically improved long term morbidity and mortality. Recently, pediatric specific treatment guidelines in AAV have been published as a part of European initiative Single Hub and Access point for pediatric Rheumatology in Europe (SHARE

Outcome/prognosis

Pediatric AAV is associated with a higher relapse rate, more accrued damage and longer maintenance therapy than adult AAVs. A recent study from the French Vasculitis Study Group Registry compared the differences between childhood-onset and matched adult-onset controls. They identified that children had a higher incidence of initial GPA-associated ischemic abdominal pain and nasal cartilage damage and the relapse rate was much higher (24.5 vs. 18.7 flares per 100 patient-years). The study also

Conclusion

Pediatric AAV is a rare systemic vasculitis of childhood with severe complications associated with significant organ damage. In spite of the paucity of treatment data in the pediatric literature, significant progress has been made in the long term management and outcomes. A collaborative effort is needed to conduct larger multicentre studies to better delineate the treatment options and prognosis of these patients. Future biomarker and genetic studies will guide the pediatric rheumatologist in

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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