Current adult AAV criteria better at classifying the disease in children
Study researchers propose that they be universally adopted for pediatric patients
Written by |
Updated criteria for classifying ANCA-associated vasculitis (AAV) in adults better discriminate between the AAV types granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in children than the current pediatric classification criteria.
That’s according to a study comparing classification results of 574 children between the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria, designed for adults, and the older pediatric-adapted European Medicines Agency (Ped-EMA) classification algorithm, which includes the Ankara criteria for pediatric GPA.
“We propose that the ACR/EULAR classification criteria for both GPA and MPA should be universally adopted for children,” researchers wrote. “Using the same classification system for both GPA and MPA and grouping patients into discriminated … [groups] will better enable comparative research of AAV subtypes both in children, and between children and adults.”
The study, “Effective performance of the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for Antineutrophil-Cytoplasmic-Antibody-Associated Vasculitis in Pediatric Patients: an ARChiVe Study,” was published in Arthritis & Rheumatology.
Adult-based criteria before 2022 often misclassified children with GPA
In AAV, self-reactive antibodies mistakenly target immune cells called neutrophils, causing inflammation and damage to small blood vessels in several organs, resulting in symptoms.
Depending on certain features, such as the affected organs, AAV can be classified into three main types: GPA, MPA, and eosinophilic granulomatosis with polyangiitis (EGPA), the rarest form. Adult-based classification criteria before 2022 often misclassified children with GPA and lacked clear rules for MPA, leading to overlap and confusion.
The Ankara criteria for pediatric GPA aimed to address these issues and were combined with the Ped-EMA algorithm used to classify MPA, but this system “did not establish mutually exclusive [groups] of GPA and MPA,” the researchers wrote.
In 2022, the ACR/EULAR classification criteria made it possible to more clearly separate GPA from MPA, reducing overlap between AAV types. They also added specific criteria for diagnosing MPA, making classification more consistent. However, because these criteria were developed using data from adult patients, they may not fully reflect features that are more specific to children.
More children classified as either GPA or MPA using ACR/EULAR criteria
To understand how the newer 2022 ACR/EULAR classification criteria compare with the older Ped-EMA algorithm, including Ankara criteria, researchers reviewed data from 574 children and adolescents from ARChiVe, an international registry of childhood vasculitis (blood vessel inflammation).
Each participant had an initial diagnosis from their doctors, which was then confirmed using computer-based classification criteria.
When comparing the two systems, more children were classified as either GPA or MPA using the ACR/EULAR criteria (396) than using the Ankara/Ped-EMA criteria (360).
Fewer participants were classified as GPA alone with the ACR/EULAR criteria (261 vs. 288 patients), but nearly twice as many were classified as MPA (135 vs. 72 children). Also, fewer children were classified as both GPA and MPA (12% vs. 28%).
“There were too few patients with EGPA for further analysis,” the team wrote.
Of the 330 children diagnosed with GPA by their doctors, 261 (79%) were also classified as GPA using the ACR/EULAR classification criteria, and 288 (87.3%) using the Ankara criteria for pediatric GPA. For MPA, the corresponding figures were 87 (diagnosed), 135, and 72. Some children were classified as both GPA and MPA according to the ACR/EULAR classification criteria (36 patients), indicating overlap.
The 2022 ACR/EULAR classification criteria for AAV perform at least as well as previous pediatric criteria and provide categorical MPA criteria where none existed previously; the criteria for GPA and MPA now specifically differentiate each other, with more differences between them in the frequencies of clinical features.
For GPA, the ACR/EULAR classification criteria had a sensitivity of 74.5% and a specificity of 93.9%, which was higher than the 72.1% sensitivity and the 79.5% specificity of the Ankara criteria. Sensitivity refers to how well a test correctly identifies people who truly have a disease, while specificity refers to how well it excludes those who do not.
About half of the children with GPA (49.9%) were classified consistently across systems, but agreement for MPA was much lower (11.5%), which “signals the need for clearer categorical criteria,” the researchers wrote.
“Using [a doctor’s diagnosis] as a comparative reference standard, our assessment indicates that ACR/EULAR criteria outperform Ankara/Ped-EMA criteria when applied to our large pediatric [group of patients],” they added.
In children with GPA, patterns of ear-nose-throat disease, lung disease, and kidney disease were generally similar across systems. In those with MPA, organ involvement differed more depending on the system used. For example, the ACR/EULAR classification criteria identified less skin and mucous membrane involvement but more chest and ear, nose, and throat involvement.
“The 2022 ACR/EULAR classification criteria for AAV perform at least as well as previous pediatric criteria and provide categorical MPA criteria where none existed previously; the criteria for GPA and MPA now specifically differentiate each other, with more differences between them in the frequencies of clinical features,” the researchers wrote.
Using the same classification system for pediatric and adult patients “will provide a foundation for future data-driven revisions to classification criteria across the lifespan,” they concluded.
