Takayasu arteritis (TA) is a chronic granulomatous large-vessel vasculitis primarily affecting the aorta and its major branches, with potential involvement of the pulmonary and coronary arteries. Although traditionally described in young adult women, pediatric-onset disease represents a distinct and particularly challenging clinical entity characterized by diagnostic delay, heterogeneous presentation, and a high risk of irreversible vascular damage at diagnosis [1].

The current classification framework most widely applied in children derives from the EULAR/PRINTO/PRES Ankara 2008 criteria, which require angiographic abnormalities of the aorta or its main branches plus at least one supporting clinical feature such as pulse deficit, blood pressure discrepancy, bruits, hypertension, or elevated acute-phase reactants [1]. Importantly, these criteria rely on imaging-confirmed vascular involvement, underscoring the central role of imaging in diagnosis.

Epidemiological data in children are limited but suggest that pediatric TA is rare, with reported annual incidence rates as low as 0.4 cases per million children in certain European populations [2]. Despite its rarity, TA represents the most common large-vessel vasculitis in childhood [2]. The principal clinical difficulty lies not in frequency but in recognition: early disease often manifests with nonspecific systemic inflammation—including prolonged fever, fatigue, weight loss, and elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)—while classical vascular signs frequently emerge only after structural arterial damage has occurred.

Diagnostic delay in pediatric TA is well documented and clinically consequential. In a tertiary UK cohort, the median time to diagnosis was reported as 17 months, with hypertension present in approximately 73% of patients at diagnosis, suggesting that many cases are identified only after hemodynamically significant vascular involvement has developed [3]. More recent cohorts indicate that diagnostic delay may vary substantially depending on access to subspecialty care; a contemporary retrospective study evaluating childhood Takayasu arteritis and polyarteritis nodosa reported a median diagnostic delay of 13 weeks, though delays remained strongly associated with systemic inflammatory presentations and absence of overt vascular findings [4]. Systematic reviews further highlight the heterogeneity of reported delays and emphasize that laboratory biomarkers lack sufficient sensitivity and specificity to reliably distinguish active disease from other inflammatory conditions [5].

Imaging therefore plays a decisive role not only in classification but also in early detection. Conventional structural imaging modalities—including magnetic resonance angiography (MRA) and computed tomography angiography (CTA)—are designed to detect luminal stenosis, occlusion, aneurysm formation, or mural thickening. However, these findings may be absent during the early inflammatory phase, when vascular wall inflammation precedes measurable luminal compromise. Updated EULAR recommendations for imaging in large-vessel vasculitis (2023 update) endorse MRI/MRA as the preferred modality for Takayasu arteritis while recognizing that fluorodeoxyglucose positron emission tomography (FDG-PET), CT, or ultrasound may provide complementary information depending on clinical context [6].

FDG-PET/CT offers functional imaging by detecting increased glucose metabolism within inflamed vessel walls and may identify active disease before structural abnormalities become apparent. A systematic review and meta-analysis evaluating FDG-PET/CT in large-vessel vasculitis demonstrated pooled sensitivity of approximately 77% and specificity of 71% for detecting active disease, although heterogeneity in methodology and interpretation was noted [7]. Recent nuclear medicine literature further emphasizes standardized acquisition protocols and careful interpretation to distinguish inflammatory uptake from atherosclerotic or physiologic patterns [8].

We report the case of a 12-year-old male presenting with persistent systemic inflammation and sustained elevation of acute-phase reactants in whom initial contrast-enhanced MRA of the aorta and its major branches did not reveal definitive structural abnormalities. Despite negative structural imaging, clinical suspicion for large-vessel vasculitis remained high. Serial FDG-PET/CT ultimately demonstrated metabolically active large-vessel inflammation, establishing the diagnosis of Takayasu arteritis in its early inflammatory phase. Using this case as a framework, we provide a comprehensive and practice-oriented review of pediatric Takayasu arteritis, focusing on early diagnostic pitfalls, limitations of laboratory markers, comparative imaging strategies, and a pragmatic algorithm for cases with persistent inflammatory activity and inconclusive initial studies.

A previously healthy 12-year-old male was referred for evaluation of persistent systemic inflammation of unclear origin. The clinical course began approximately six weeks prior with intermittent low-grade fever, progressive fatigue, decreased physical endurance, and unintentional weight loss. There was no initial history of limb claudication, chest pain, focal neurological deficits, or visual disturbances. Physical examination at first evaluation revealed no pulse deficits or audible bruits, and peripheral pulses were symmetrical. Blood pressure measurements were within the upper-normal range for age.

Initial laboratory studies demonstrated marked systemic inflammation, with erythrocyte sedimentation rate (ESR) persistently elevated between 65 and 85 mm/h and C-reactive protein (CRP) levels ranging from 5 to 7 mg/dL. Mild normocytic anemia was present (hemoglobin 10.8 g/dL), while leukocyte and platelet counts remained within normal limits. Renal and hepatic function tests were unremarkable. Extensive infectious evaluation—including blood cultures, viral serologies, tuberculosis screening, and inflammatory infectious markers—was negative. Autoimmune testing, including antinuclear antibodies, anti-double-stranded DNA antibodies, antineutrophil cytoplasmic antibodies, and complement levels, did not reveal evidence of systemic autoimmune disease.

Differential diagnoses included occult infection (such as tuberculosis or endocarditis), malignancy—particularly lymphoma—and systemic inflammatory conditions such as systemic juvenile idiopathic arthritis. These were considered unlikely given negative microbiological studies, absence of suggestive imaging findings, and lack of disease-specific clinical or laboratory features.

Given the persistence of inflammatory markers and constitutional symptoms without an identifiable source, large-vessel vasculitis was considered in the differential diagnosis. Contrast-enhanced magnetic resonance angiography (MRA) of the thoracic and abdominal aorta and its major branches was performed to assess for structural vascular abnormalities. The study did not demonstrate significant luminal stenosis, aneurysmal changes, or clear mural thickening. No angiographic abnormalities meeting classification criteria for Takayasu arteritis were identified. At this stage, structural imaging was considered nondiagnostic.

Due to ongoing inflammation and absence of a definitive diagnosis, a short empirical course of systemic glucocorticoids was initiated (oral prednisone at approximately X mg/kg/day for X days). The initial FDG-PET/CT was performed shortly after this exposure. The patient experienced transient improvement in constitutional symptoms and partial reduction in CRP levels; however, inflammatory markers rebounded upon tapering, and systemic symptoms recurred. This steroid-responsive but relapsing pattern strengthened suspicion of an underlying immune-mediated inflammatory process and raised the possibility that prior glucocorticoid exposure could have influenced early metabolic imaging findings.

In light of sustained inflammatory activity and nondiagnostic structural imaging, ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) was obtained to evaluate for occult malignancy or metabolically active inflammatory disease. FDG-PET/CT interpretation was based on visual grading comparing vascular uptake to hepatic uptake. The initial PET/CT study (Figure 1) demonstrated vascular uptake not exceeding liver background (visual grade ≤ 2), and was therefore considered nondiagnostic. No definitive evidence of active large-vessel vasculitis was established at that time. This result illustrated the potential limitation of single-time-point metabolic imaging in early inflammatory-phase disease, particularly in the context of recent glucocorticoid exposure.

Over the subsequent weeks, the patient continued to demonstrate persistent elevation of ESR and CRP, along with recurrent fatigue and intermittent fever. Serial blood pressure measurements began to reveal mild systolic hypertension, raising concern for evolving vascular involvement despite previously negative imaging. The coexistence of sustained inflammatory markers, partial glucocorticoid responsiveness with relapse upon taper, newly emerging hypertension, and absence of an alternative diagnosis created a clinically significant discordance between laboratory findings and imaging studies.

Recognizing that early Takayasu arteritis may manifest with active vascular inflammation prior to the development of detectable luminal changes, and that metabolic activity may evolve over time, repeat FDG-PET/CT was performed several weeks after steroid tapering and in the context of persistent inflammatory activity. The follow-up study (Figure 2) demonstrated increased FDG uptake greater than hepatic activity (visual grade ≥ 3) along the thoracic and abdominal aorta as well as the proximal segments of the subclavian and carotid arteries. The distribution and intensity of vascular hypermetabolism were consistent with active large-vessel vasculitis.

These findings, in conjunction with persistent systemic inflammation and evolving clinical features, established the diagnosis of Takayasu arteritis in its inflammatory phase. Although initial imaging did not fulfill EULAR/PRINTO/PRES classification criteria due to absence of angiographic abnormalities, the diagnosis was ultimately made based on integrated clinical, laboratory, and metabolic imaging findings, highlighting the distinction between clinical diagnosis and classification frameworks.

High-dose intravenous methylprednisolone pulses were administered, followed by oral glucocorticoid therapy. Given the risk of disease progression and the need to limit cumulative steroid exposure, methotrexate was initiated as steroid-sparing immunosuppressive therapy. Low-dose aspirin was introduced for vascular protection, and antihypertensive therapy was implemented to control blood pressure.

Within eight weeks of treatment initiation, the patient demonstrated complete resolution of constitutional symptoms, normalization of inflammatory markers, and stabilization of blood pressure. Clinical remission was achieved, and structured imaging surveillance was planned to monitor disease activity and prevent structural vascular progression.

This case illustrates the diagnostic complexity of pediatric Takayasu arteritis in its early inflammatory phase and underscores the importance of serial metabolic imaging when structural studies are initially inconclusive. In selected pediatric cases with persistent clinical suspicion, the diagnostic yield of repeat FDG-PET/CT may outweigh potential risks related to radiation exposure, particularly when early diagnosis can prevent irreversible vascular damage.

Table 1.Key characteristics of Takayasu arteritis in pediatric patients.

Figure 1.Initial FDG-PET/CT at first diagnostic evaluation.

Schematic representation adapted from FDG-PET/CT imaging obtained during the initial diagnostic workup, showing absence of significant ¹⁸F-fluorodeoxyglucose uptake along the aorta and its major branches. This finding illustrates the limited sensitivity of early single-time-point imaging in pediatric Takayasu arteritis despite ongoing systemic inflammation.

Figure 2.Follow-up FDG-PET/CT revealing active large-vessel vasculitis.

Adapted schematic representation of follow-up FDG-PET/CT demonstrating increased metabolic uptake along the carotid, subclavian, and aortic segments, consistent with active large-vessel vasculitis. Serial imaging was pivotal in establishing the diagnosis of Takayasu arteritis after initially negative studies.

Pediatric Takayasu arteritis represents a diagnostic challenge driven not only by its rarity but by its pathophysiologic timing. Children frequently present during the early inflammatory phase, when systemic manifestations and elevated acute-phase reactants precede overt structural vascular abnormalities. In this context, reliance on single time-point structural imaging may result in false reassurance and diagnostic delay.

This case illustrates the critical importance of maintaining a high index of suspicion in children with persistent unexplained systemic inflammation, steroid-responsive but relapsing disease, and emerging vascular features such as hypertension. The absence of luminal abnormalities on initial MRA did not exclude active large-vessel vasculitis. Serial FDG-PET/CT imaging ultimately demonstrated metabolically active vascular inflammation, thereby unmasking disease during its inflammatory phase and allowing timely initiation of targeted immunosuppressive therapy.

Early recognition and integration of clinical, laboratory, and complementary imaging findings are essential to prevent progression toward irreversible vascular remodeling. A pragmatic diagnostic approach incorporating structural and metabolic imaging, particularly in cases of clinicoradiologic discordance, may reduce diagnostic delay and improve long-term outcomes in pediatric Takayasu arteritis.

1) Persistent systemic inflammation in children without an identifiable cause should prompt consideration of large-vessel vasculitis, even in the absence of classic vascular signs.

2) A negative structural imaging study (MRA or CTA) does not exclude early inflammatory-phase Takayasu arteritis.

3) Steroid-responsive but relapsing inflammatory patterns may signal underlying immune-mediated vascular disease.

4) Emerging or unexplained hypertension in a child with systemic inflammation is a critical red flag for possible renal artery involvement.

5) FDG-PET/CT provides functional assessment of vascular inflammation and may detect disease activity before structural luminal changes are apparent.

6) Serial imaging should be considered when clinicobiochemical activity persists despite nondiagnostic initial studies.

7) Early steroid-sparing immunosuppression and structured longitudinal monitoring are essential to prevent irreversible vascular damage.

This study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Written informed consent for publication was obtained from the patient’s legal guardians, and ethics committee approval was obtained/waived according to local regulations.