Real-World Biomarkers for Pediatric Takayasu Arteritis

Abstract

Childhood-onset Takayasu arteritis (TA) is a rare, heterogeneous disease with limited diagnostic markers. Our objective was to identify and classify all candidates for biomarkers of TA diagnosis in children reported in the literature. A systematic literature review (PRISMA) of MEDLINE, EMBASE, Wiley Cochrane Library, ClinicalTrias.gov, and WHO ICTRP for articles related to TA in the pediatric age group between January 2000 and August 2023 was performed. Data on demographics, clinical features, laboratory measurements, diagnostic imaging, and genetic analysis were extracted. We identified 2026 potential articles, of which 52 studies (81% case series) met inclusion criteria. A total of 1067 TA patients were included with a peak onset between 10 and 15 years. Childhood-onset TA predominantly presented with cardiovascular, constitutional, and neurological symptoms. Laboratory parameters exhibited a low sensitivity and specificity. Imaging predominantly revealed involvement of the abdominal aorta and renal arteries, with magnetic resonance angiography (MRA) being the preferred imaging modality. Our review confirms the heterogeneous presentation of childhood-onset TA, posing significant challenges to recognition and timely diagnosis. Collaborative, multinational efforts are essential to better understand the natural course of childhood-onset TA and to identify accurate biomarkers to enhance diagnosis and disease management, ultimately improving patient outcomes.

Keywords: Takayasu arteritis; biomarkers; childhood vasculitis; diagnosis; disease activity; pediatrics; review.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.

Figure 2

Demographics at presentation. (a) Age at symptom onset (years) [15,16,17,18,19,21,23,26,28,29,30,32,35,37,40,41,42,43,44,45,47,48]; (b) age at diagnosis (years) [14,18,20,21,22,24,25,27,30,31,33,38,40,46,47,48,49,50,51,52,53,54]; (c) time between symptom onset and diagnosis (months) [14,15,16,21,22,25,29,31,32,33,37,40,41,44,45,46,47,48,49,51,55]. Mean values are displayed in red, and median values are displayed in blue. Vertical lines represent the interquartile range (IQR), while the beginning and ending points of the horizontal lines indicate the minimum and maximum values.

Figure 3

Most frequently (≥25%) described symptoms at presentation, divided according to different subcategories. Green: cardiovascular symptoms; orange: general symptoms; blue: neurological symptoms; yellow: respiratory symptoms; grey: musculoskeletal symptoms.

Figure 4

Inflammatory parameters at presentation. (a) CRP (mg/dL) [15,19,20,21,23,24,28,29,31,40,42,46,47,49,50,51,53]; (b) ESR (mm/h) [15,16,18,19,20,21,23,24,25,28,29,31,35,37,40,42,44,46,47,49,50,51,53]. Mean values are displayed in red and median values are displayed in blue. Vertical lines represent the interquartile range (IQR), while the beginning and ending points of the horizontal lines indicate the minimum and maximum values. The dashed line represents the upper limit of normal (CRP 0.5 mg/dL, ESR 20 mm/h).

Figure 5

Angiographic classification of affected vessels. (a) Numano classification; (b) Lupi–Herrera classification.

Figure 6

Most frequently (>5%) involved arteries in childhood-onset TA.

Figure 7

Summary of diagnostic biomarkers in childhood-onset TA based on current systematic review. Clinical evaluation includes most frequently (≥25%) described symptoms at presentation (ocular, gastro-intestinal, renal, and dermatological involvement (italic) is described but less common (<25%).