Pediatric vasculitis is uncommon in children, with incidence rates reported between 12 to 53 cases per 100,000 individuals under 17 years of age [1-5]. However, despite its rarity, pediatric vasculitis exhibits significant heterogeneity. Therefore, evaluating incidence rates by specific underlying cause, rather than overall rates, provides a more accurate picture. These rates also vary depending on the population studied. However, globally, HSP is the most prevalent primary vasculitis in children, while KD is more common in Korea, Japan, and other Asian regions. In Korea, the average incidence rate of KD among children under 5 years was 196.9 per 100,000 individuals during 2015 to 2017, ranking second globally after Japan [1]. However, interestingly, stringent nonpharmacological interventions implemented worldwide during the COVID-19 pandemic, including Korea, have been associated with a significant decrease in KD incidence [6]. In Korea, KD rates declined by 40% post-pandemic compared with pre-pandemic levels. This suggests a link between environmental factors, such as infections, and the occurrence of childhood vasculitis [7]. Regarding HSP, a Korean study utilizing the national insurance database reported an incidence rate of 55.9 per 100,000 children under 18 years, exceeding the 14~20 (29.9) per 100,000 incidence rate reported internationally [2]. In contrast, other vasculitis like polyarteritis nodosa (PAN), are extremely rare, with an incidence less than 1 per 100,000 individuals [8,9]. Similarly, Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and Takayasu arteritis (TA) are rarely observed in children, with reported incidence rates ranging from 1 to 6.3 per million and 1 to 2.6 per millionpopulation, respectively [10-13].

Similar to adults, the primary classification system for childhood vasculitis categorizes patients based on the size of the affected vessels. The most commonly used classification criteria for vasculitis, approved at the 1994 Chapel Hill Consensus Conference, endorsed by the American College of Rheumatology (ACR) [14], faced limitations. Designed primarily for adult vasculitis, these criteria excluded common childhood conditions such as KD and HSP. Consequently, many pediatric vasculitis cases remained unclassified using these criteria. Therefore, in 2005, the European League against Rheumatism (EULAR) and the Pediatric Rheumatology European Society (PReS) proposed classification criteria specifically for primary vasculitis in children under 18 years [15]. These were further revised in 2008 through a collaboration with the EULAR, PReS, and the Paediatric Rheumatology International Trials Organization (PRINTO), improving sensitivity for four specific diseases (HSP, Wegener's granulomatosis, childhood PAN, and TA) (Table 1) [16].

The second Chapel Hill Consensus Conference held in 2012 provided the most recent nomenclature and extensive framework for vasculitis classification, including specific disease definitions [17]. The Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) plan was established to collect data on patients with vasculitis and develop enhanced classification criteria for adults with vasculitis. This led to the revision, approval, and publication of ACR/EULAR criteria for AAV subtypes, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) in 2022 [18-20]. These MPA criteria mark the first categorical system for this disease; however, their applicability to children remains to be evaluated.

The diagnosis of primary vasculitis in children can be challenging due to its highly variable clinical manifestations. These variables depend on factors such as the location and severity of inflammation, extent of vascular damage, and resultant hemodynamic changes. Therefore, vasculitis should be considered as a differential diagnosis in children presenting with unexplained systemic inflammation or multi-organ involvement. Table 2 summarizes the features suggestive of vasculitis. Additionally, distinguishing between primary vasculitis and other conditions that exhibit similar symptoms, or secondary vasculitis, is necessary (Table 3) [21,22].

To diagnose suspected vasculitis, a detailed medical history, physical examination, and basic laboratory tests are essential. The medical history should include recent infections, medications, and detailed family history. Physical examination involves measuring blood pressure in the extremities, auscultating vascular bruits, and assessing peripheral pulses. Additionally, examining for tender nodules, purpura, ulcers, or livedo reticularis on the skin, and performing a neurological evaluation for peripheral neuropathy are warranted.

Laboratory investigations typically include a complete blood count, erythrocyte sedimentation rate, C-reactive protein level, liver function tests, blood urea nitrogen level, creatinine level, and urinalysis to assess renal and hepatic involvement. Depending on the suspected vasculitis type, autoimmune antibody tests (antinuclear antibodies, ANCA) and complement levels may be performed. While tissue biopsy or characteristic vascular abnormalities on imaging studies, such as CT angiography and magnetic resonance angiography, are gold standards for confirmation, particularly when medium- or large-vessel vasculitis is suspected, specific clinical features may be sufficient for diagnosing certain vasculitis syndromes, such as KD, HSP, and GPA (Table 1) [23].

The principles of treatment for primary vasculitis in children prioritizes distinguishing it from similar conditions (Table 3). Treatment plans are then tailored based on disease activity, severity, and a risk-benefit analysis. As pediatric vasculitis treatment adheres to specific guidelines for each vasculitis type, this review emphasizes KD and HSP management. KD and HSP, the most common causes of primary vasculitis in children, may exhibit self-limiting clinical courses. Effective treatment strategies have been proposed based on an understanding of the characteristic clinical courses and potential long-term complications.

For KD, intravenous immunoglobulin (IVIG) at a dose of 2 g/kg and aspirin (30~50 mg/kg/day or 80~100 mg/kg/day) during the acute phase are the primary treatments used to reduce the risk of cardiovascular complications, such as coronary artery aneurysms [24]. Persistent or recurrent fever after IVIG may necessitate re-administration of IVIG or steroids. Infliximab, a tumor necrosis factor (TNF) inhibitor, may be used for patients unresponsive to these treatments [24]. Following the febrile phase, low-dose aspirin (3~5 mg/kg/day) is administered, exerting an antiplatelet effect by inhibiting thromboxane A2 and prostacyclin synthesis. If echocardiography at around 6 to 8 weeks shows no coronary artery aneurysms, low-dose aspirin may be discontinued [25].

Most patients with HSP receive symptomatic treatment. Graduated therapy is commonly used based on the clinical presentation, with nonsteroidal anti-inflammatory drugs (NSAIDs) for patients with joint and/or abdominal pain. Steroids are used for patients with severe abdominal pain that interferes with their oral intake and those unresponsive to NSAID or complications like nephritis [26]. Patients with HSP nephritis who do not respond to glucocorticoids may be candidates for other immunosuppressive therapies, such as cyclophosphamide, mycophenolate mofetil, or rituximab [27].

For primary vasculitides other than KD and HSP, symptoms are often chronic or recurrent, necessitating the use of steroids as the mainstay of treatment to maintain remission. Although steroids alone may be sufficient for mild cases, more severe cases often require combination therapy with cyclophosphamide. Patients with various pediatric systemic vasculitides refractory to conventional therapy or experiencing frequent relapses, consideration may benefit from other immunosuppressive agents, such as methotrexate and azathioprine, and biologics (e.g., TNF inhibitors, rituximab, and tocilizumab) [28].

The prognosis of primary vasculitis in pediatric patients depends on several factors: the underlying cause, disease severity, involvement of major organs, treatment response, and treatment-related complications. KD and HSP, the predominant types, typically exhibit spontaneous recovery with a favorable prognosis as long-term complications are infrequent. Instead, for other forms of primary vasculitides, effective immunosuppressive therapies have improved survival and remission rates. In 2008, a systematic review encompassing both adult and pediatric populations reported 5-year survival rates for various types of systemic vasculitis: GPA (approximately 75%), MPA (45%~75%), EGPA (68%~100%), HSP (75% in adult-onset, higher in pediatric-onset), medium-vessel vasculitis including PAN (75%~80%), KD (>99% at 5 years), and TA (70%~93%) [29].

In KD, long-term morbidity depends on the severity of coronary artery involvement. Data analysis was conducted on demographic characteristics, clinical manifestations, treatment modalities, and coronary complications of KD between 2015 and 2017 [1]. The study identified 15,378 KD cases over 3 years, with 17.1% exhibiting coronary artery dilatation (18.2% in 2015, 17.7% in 2016, and 15.1% in 2017) and 1.7% developing coronary aneurysms. Among these, giant coronary aneurysms (internal diameter >8 mm) developed in 19 (0.17%) patients. Among patients who were unresponsive to initial IVIG therapy, the rate of coronary artery dilatation was 27.2%, with an incidence of giant aneurysms of 0.27%. Two fatalities were recorded during the study period: one due to multi-organ failure at 15 months and the other due to hepatic encephalopathy at 83 months.

HSP typically exhibits a favorable prognosis [30-33], with spontaneous resolution observed in the majority of cases within weeks to months. However, a minority of patients may experience complications such as renal involvement or disease recurrence, underscoring the importance of long-term monitoring and individualized management strategies to optimize patient outcomes. Recurrences of HSP occur in approximately one-third of patients and are notably more prevalent in slightly older children (aged over 8 years), particularly in those exhibiting nephritis, acute inflammation, or having undergone steroid treatment [26,31,33-35]. Kidney involvement, observed in around 20 to 54 percent of pediatric HSP cases [31,36,37], tends to be more prominent among older children and adults [38-40]. Short-term kidney outcomes for HSP are generally favorable, with complete recovery documented in 94 percent of children and 89 percent of adults, typically within an average period of 18 months [41]. However, long-term consequences of HSP nephritis can lead to chronic kidney disease, accounting for 1%~2% of end-stage kidney disease cases [42].

A meta-analysis of nine case-control studies involving 969 HSP nephritis patients identified clinical risk factors for CKD, including older age at disease onset, low glomerular filtration rate, and an initial presentation with nephrotic or nephritic-nephrotic syndrome, all of which were associated with unfavorable kidney outcomes [43]. Conversely, a presentation characterized by hematuria and mild proteinuria, with or without hematuria, tended to correlate with more favorable outcomes.

In a retrospective cohort study conducted in Italy involving 208 children aged 0 to 18 years who met the criteria for HSP [44], treatment outcomes were examined. NSAIDs were administered to sixty-seven percent of patients, while corticosteroids were given to 62 patients. The use of corticosteroids was primarily due to renal dysfunction (13% of the cohort), persistent skin lesions (9%), severe abdominal pain (5%), or scrotal involvement (2%). Only 2 patients required immunosuppressive therapy (azathioprine and cyclophosphamide), one due to persistent proteinuria and the other due to non-response to corticosteroid therapy. Both patients demonstrated a positive response to immunosuppressive drugs and experienced favorable outcomes. No severe infections or adverse reactions were reported during treatment.