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22. ANCA-ASSOCIATED VASCULITIS IN CHILDREN OF ASIA
Bugubaeva Makhabat Mitalipovna.
Masthan Hisham Khan.
(1, HOD Clinical disciplines-2, Associate professor, International Medical Faculty, Osh State University, Osh, Kyrgyzstan.)
2, Student, International Medical Faculty, Osh State University, Osh, Kyrgyzstan.)
ABSTRACT
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of autoimmune disorders characterized by inflammation of small- to medium-sized blood vessels. Although AAV is relatively rare in children, it presents unique diagnostic and therapeutic challenges, particularly across Asia, where genetic, environmental, and socioeconomic factors influence disease prevalence and clinical course.
INTRODUCTION
ANCA-associated vasculitis encompasses three main clinicopathological entities: Granulomatosis with Polyangiitis (GPA), Microscopic Polyangiitis (MPA), and Eosinophilic Granulomatosis with Polyangiitis (EGPA). These conditions are characterized by necrotizing inflammation of small blood vessels and the presence of circulating ANCAs directed against myeloperoxidase (MPO) or proteinase 3 (PR3).
Although AAV is well-documented in adults, pediatric cases remain underreported, especially in Asia.
Children in Asia with AAV often exhibit overlapping clinical features, leading to diagnostic delays. The disease may present with nonspecific symptoms such as fever, malaise, and arthralgia before evolving into more severe organ involvement, including renal and respiratory manifestations. In recent years, multicenter studies from countries like Japan, China, India, and South Korea have contributed valuable data highlighting regional differences in prevalence and presentation.
TYPES AND PATHOPHYSIOLOGY
The pathogenesis of AAV in children involves complex interactions between genetic susceptibility, environmental triggers, and immune dysregulation. The two principal autoantibodies implicated—anti-MPO and anti-PR3—play central roles in activating neutrophils and promoting vascular injury. When activated, neutrophils release reactive oxygen species and proteolytic enzymes that damage endothelial cells, leading to necrotizing inflammation and Fibrinoid necrosis of vessel walls.
1. Granulomatosis with Polyangiitis (GPA): Characterized by necrotizing granulomatous inflammation affecting the upper and lower respiratory tracts and kidneys. PR3-ANCA positivity is more common in GPA.
2. Microscopic Polyangiitis (MPA): Features necrotizing vasculitis without granulomatous inflammation and is frequently MPO-ANCA positive. Renal involvement and pulmonary capillarity are typical.
3. Eosinophilic Granulomatosis with Polyangiitis (EGPA): Rare in children, EGPA involves asthma, peripheral eosinophilia, and systemic vasculitis. It is associated with MPO-ANCA in approximately 40% of cases.
In Asia, MPO-ANCA–positive vasculitis predominates, contrasting with Western populations where PR3-ANCA is more frequent. Genetic polymorphisms in HLA- DPB1, PTPN22, and CTLA4 have been linked to AAV susceptibility in Asian populations. Additionally, environmental exposures such as infections and silica may contribute to disease onset.
CLINICAL FEATURES IN ASIAN CHILDREN
Pediatric AAV in Asia often manifests differently compared to Western counterparts. Data from Japanese and Chinese cohorts indicate that renal and pulmonary involvement are predominant, whereas ENT and neurological features are less common. Studies from India and Southeast Asia reveal a similar trend, emphasizing rapidly progressive glomerulonephritis as a frequent initial presentation.
Renal involvement is a major determinant of prognosis. Children often present with hematuria, proteinuria, hypertension, and renal failure. Histological examination typically demonstrates pauci-immune necrotizing crescentic glomerulonephritis.
Pulmonary manifestations include cough, dyspnea, pulmonary hemorrhage, and nodular infiltrates on imaging. Diffuse alveolar hemorrhage, though rare, may be
life-threatening.
Systemic features such as fever, fatigue, arthralgia, and skin purpura frequently precede major organ involvement.
Neurological and gastrointestinal symptoms are less common but may occur in severe systemic forms.
The disease course in Asian children tends to be more aggressive, possibly due to delayed recognition or limited access to specialized care. Despite this, early initiation of immunosuppressive therapy markedly improves long-term outcomes.
DIAGNOSIS AND MANAGEMENT
Diagnosis of AAV in children relies on a combination of clinical evaluation, serologic testing, and tissue biopsy. Detection of ANCA by indirect immunofluorescence and ELISA for PR3 or MPO specificity remains the cornerstone of diagnosis. However, negative ANCA tests do not exclude disease, particularly in early or limited forms.
Laboratory findings include elevated ESR, CRP, and serum creatinine levels. Urinalysis frequently reveals red cell casts and proteinuria. Radiological imaging of the chest may show nodules, infiltrates, or cavitary lesions. Biopsy of affected tissues
—especially kidney or skin—confirms necrotizing vasculitis and excludes mimicking conditions such as lupus or infection.
Management strategies combine induction and maintenance phases.
- Induction therapy typically involves corticosteroids with cyclophosphamide or rituximab. Pediatric trials have demonstrated the efficacy of rituximab as an alternative to cytotoxic agents, especially in relapsing or refractory disease.
- Maintenance therapy utilizes azathioprine, mycophenolate mofetil, or methotrexate to prevent relapse.
- Adjunctive treatments include plasmapheresis in severe renal or pulmonary disease and prophylaxis for Pneumocystis jirovecii infection.
- Supportive care addressing blood pressure control, renal protection, and vaccination remains integral.
Recently, biologic agents targeting B cells (e.g., rituximab) or complement pathways (e.g., avacopan, a C5a receptor antagonist) have expanded therapeutic options.
However, their accessibility and cost remain limiting factors in many Asian regions.
DISCUSSION
AAV in Asian children is emerging as a significant concern within pediatric rheumatology and nephrology. Although incidence remains lower than in adults, improved recognition has led to increased reporting across Asia. Studies indicate that MPO-ANCA–dominant disease patterns and higher rates of renal involvement distinguish Asian cohorts from Western populations. This may reflect underlying genetic predispositions and differing environmental exposures.
Delayed diagnosis remains a major issue due to nonspecific early symptoms and limited pediatric expertise in rare autoimmune vasculitis. Initiatives such as regional vasculitis registries and multicenter collaborations are vital to improve epidemiological understanding. The Japanese Pediatric Rheumatology Association and Chinese Pediatric Nephrology Society have taken steps toward establishing such databases.
Long-term outcomes depend on early diagnosis, control of inflammation, and prevention of relapses. Complications from chronic steroid use and immunosuppression, including growth retardation and infection, are significant challenges. Transition care into adolescence also requires structured follow-up to ensure adherence and minimize morbidity.
Psychological support and family education are equally essential. Chronic illness management in children can impact schooling, social life, and emotional well-being. Health education programs tailored to cultural contexts in Asia may improve coping and adherence to therapy.
With growing availability of targeted biologic therapies, future research in Asia must address cost-effective access and pharmacogenetic variations that may influence drug response. Strengthening pediatric training and awareness, alongside early referral pathways, will continue to improve outcomes in ANCA-associated vasculitis among Asian children.
CONCLUSION
ANCA-associated vasculitis in children across Asia presents unique epidemiological and clinical characteristics. MPO-ANCA predominance, renal involvement, and variable access to diagnostic and therapeutic facilities remain demining challenges. Prompt recognition, appropriate immunosuppressive therapy, and long-term multidisciplinary care are key to improving survival and quality of life. Strengthened regional registries, increased awareness among pediatricians, and equitable access to modern therapies.
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