Residency · Residency · Medicine Pediatrics

Vasculitis in Children and Adults

Overview

Vasculitis is inflammation of blood vessels, classified by vessel size (Chapel Hill Consensus Conference) Pediatric vasculitis differs significantly from adult vasculitis in etiology, distribution, and prognosis. Kawasaki disease and IgA vasculitis (Henoch-Schonlein purpura) dominate in children. ANCA-associated vasculitis and giant cell arteritis dominate in adults. The Med-Peds physician must recognize overlap syndromes and age-specific management.

Classification by Vessel Size

Large Vessel

Takayasu arteritis: aorta and branches; predominantly young women (10-40 years); can present in childhood. Giant cell arteritis (GCA): temporal and cranial arteries; almost exclusively >50 years.

Medium Vessel

Kawasaki disease: coronary arteries predominantly; children <5 years. Polyarteritis nodosa (PAN): medium muscular arteries; can affect any age but more common in adults.

Small Vessel (ANCA-Associated)

Granulomatosis with polyangiitis (GPA, formerly Wegener): upper/lower respiratory tract, kidneys. Microscopic polyangiitis (MPA): kidneys, lungs. Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss): asthma, eosinophilia, vasculitis.

Small Vessel (Immune Complex)

IgA vasculitis (Henoch-Schonlein purpura): predominantly children. Cryoglobulinemic vasculitis: adults, HCV-associated. Anti-GBM disease (Goodpasture): lungs and kidneys.

<image>Vessel size classification of vasculitides showing large, medium, and small vessel involvement with corresponding diseases and their age distribution from pediatric through adult populations</image>

Kawasaki Disease

Epidemiology

Leading cause of acquired heart disease in children in developed countries; Peak age: 6 months to 5 years (80% of cases <5 years); Higher incidence in Asian populations (Japan: 300/100,000 vs US: 25/100,000); Male predominance (1.5:1); Seasonal variation with winter-spring peaks.

Diagnostic Criteria (Classic Kawasaki)

Fever >= 5 days PLUS >= 4 of 5 clinical criteria: Bilateral non-exudative conjunctival injection (limbic-sparing) Changes in lips/oral mucosa: erythema, cracking, strawberry tongue. Polymorphous rash (maculopapular, erythema multiforme-like, NOT vesicular) Extremity changes: edema, erythema of palms/soles; later: periungual desquamation (day 10-21) Cervical lymphadenopathy >= 1.5 cm (least common criterion)

Incomplete Kawasaki Disease

Fever >= 5 days with 2-3 clinical criteria, especially in infants <6 months. Infants are at highest risk for coronary complications and most likely to have incomplete presentation. AHA algorithm: if CRP >= 30 mg/L and/or ESR >= 40, obtain supplementary lab criteria (albumin <3, anemia, elevated ALT, platelets >450K after day 7, WBC >15K, urine WBC >= 10/HPF) If >= 3 supplementary criteria: treat as Kawasaki disease. Echocardiogram findings can confirm diagnosis even if clinical criteria incomplete.

Cardiac Complications

Coronary artery aneurysms: 25% of untreated cases; 4-5% with timely IVIG treatment. Risk factors for aneurysms: delayed treatment, IVIG resistance, age <1 year or >9 years, male sex. Classification: small (<5 mm), medium (5-8 mm), giant (>8 mm); giant aneurysms have worst prognosis. Other cardiac: myocarditis, pericarditis, valvular regurgitation, coronary stenosis and thrombosis (late)

Treatment

IVIG 2 g/kg single infusion within first 10 days of illness (ideally day 5-7) Aspirin: high-dose (80-100 mg/kg/day) during acute phase in some protocols; moderate/low dose (3-5 mg/kg/day) until 6-8 weeks post-onset if no coronary changes. IVIG-resistant (persistent/recurrent fever >36 hours after first IVIG): second IVIG dose; if still resistant, consider IV methylprednisolone, infliximab (anti-TNF), or cyclosporine. Coronary aneurysm management: long-term aspirin (small aneurysm); aspirin + anticoagulation for moderate-giant aneurysms; serial echocardiograms; cardiac catheterization/stress testing for giant aneurysms.

Long-Term Surveillance

No coronary changes: echocardiogram at 2 weeks, 6-8 weeks; no long-term follow-up needed per AHA. Coronary aneurysms: lifelong follow-up; frequency and testing based on aneurysm classification (Z-score) Coronary CT angiography or MRI for long-term surveillance (replacing invasive angiography) Patients with giant aneurysms need assessment for stenosis, thrombosis; may need intervention (PCI or CABG)

<image>Echocardiographic and coronary angiographic images showing normal coronary arteries, small coronary artery dilation, medium aneurysm, and giant coronary artery aneurysm in Kawasaki disease with Z-score classification</image>

IgA Vasculitis (Henoch-Schonlein Purpura)

Epidemiology

Most common systemic vasculitis in children (peak age 3-10 years); Incidence: 10-20 per 100,000 children/year; Can occur in adults (less common, more severe); Often preceded by upper respiratory infection (post-streptococcal in some).

Clinical Features

Palpable purpura: non-thrombocytopenic, gravity-dependent (buttocks, lower extremities); must be present for diagnosis. Arthritis/arthralgia: large joints (knees, ankles); transient, non-destructive. Abdominal pain: colicky, from bowel wall edema and hemorrhage; can precede rash; risk of intussusception (ileoileal, not ileocecal as in idiopathic) Renal involvement: hematuria, proteinuria; IgA nephropathy is the same histologic entity; ranges from microscopic hematuria to nephrotic/nephritic syndrome.

Diagnosis

Clinical diagnosis in classic presentation. Labs: normal platelets (distinguishes from ITP), normal coagulation studies, elevated IgA in ~50%. Skin biopsy (if needed): leukocytoclastic vasculitis with IgA deposition on immunofluorescence. Renal biopsy: IgA mesangial deposits (indistinguishable from IgA nephropathy); indications — nephrotic-range proteinuria, renal insufficiency, >50% crescents.

Management

Most cases are self-limited (4-6 weeks); supportive care. NSAIDs for joint and abdominal pain. Corticosteroids: may reduce abdominal pain duration but do NOT prevent nephritis per RCTs; consider for severe GI involvement or testicular involvement. Renal disease: ACE inhibitor for proteinuria; corticosteroids + immunosuppression (MMF, cyclophosphamide) for severe nephritis with crescents. Monitoring: urinalysis weekly during acute phase, then monthly for 6 months; long-term follow-up for blood pressure and proteinuria.

Prognosis

Children: excellent overall; <5% develop significant renal disease; recurrence in 30-40%. Adults: worse prognosis; higher rates of nephritis and chronic renal disease.

ANCA-Associated Vasculitis (AAV)

Granulomatosis with Polyangiitis (GPA)

Adults: most common in 40-65 years; sinusitis, pulmonary nodules/cavitary lesions, glomerulonephritis (pauci-immune) Children: rare but can occur; similar clinical features; more likely to have subglottic stenosis. ANCA: c-ANCA / anti-PR3 positive (~90%) Classic triad: upper airway, lower airway, renal disease. Diagnosis: ANCA serology + tissue biopsy (granulomatous inflammation, vasculitis) Treatment: induction with rituximab or cyclophosphamide + glucocorticoids; maintenance with rituximab or azathioprine. Avacopan (complement C5a receptor inhibitor): approved for adult GPA/MPA as glucocorticoid-sparing agent.

Microscopic Polyangiitis (MPA)

Rapidly progressive glomerulonephritis + pulmonary hemorrhage (pulmonary-renal syndrome) ANCA: p-ANCA / anti-MPO positive; No granulomas (unlike GPA); Treatment: same as GPA.

EGPA (Churg-Strauss)

Asthma (adult-onset, severe) + eosinophilia (>1,500 or >10%) + vasculitis. Phases: allergic (asthma, rhinitis), eosinophilic (tissue infiltration), vasculitic. ANCA positive in ~40% (p-ANCA/anti-MPO) Cardiac involvement (cardiomyopathy, coronary vasculitis) is the leading cause of death. Treatment: glucocorticoids; mepolizumab (anti-IL-5) approved for EGPA; cyclophosphamide or rituximab for severe disease. Benralizumab (anti-IL-5R): also showing efficacy in EGPA.

<image>Clinical manifestations of ANCA-associated vasculitis showing organ involvement patterns for GPA, MPA, and EGPA with corresponding ANCA serologies and key distinguishing features</image>

Clinical Pearls

Kawasaki disease should be considered in ANY child with fever >= 5 days without clear source, especially infants — incomplete KD is most dangerous because of delayed treatment. The coronary artery Z-score (adjusted for body surface area) is more important than absolute size for risk stratification in Kawasaki disease. IgA vasculitis with preceding abdominal pain and NO rash can be confused with surgical abdomen — always check for purpura on buttocks and legs. In adults with palpable purpura and renal disease, IgA vasculitis occurs but is less common than ANCA-associated vasculitis — biopsy is essential. Never give aspirin to children for any other indication due to Reye syndrome risk — Kawasaki disease is the notable exception. ANCA testing should be part of the workup for any patient with glomerulonephritis, pulmonary hemorrhage, or sinusitis with destructive features. Takayasu arteritis in adolescent girls presenting with hypertension, limb claudication, and absent pulses is often delayed in diagnosis — check blood pressure in all four extremities.

References

• McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: AHA Scientific Statement. Circulation. 2017;135(17):e927-e999.
• Ozen S, Marks SD, Brogan P, et al. EULAR/PRINTO/PRES Criteria for Henoch-Schonlein Purpura, Childhood Polyarteritis Nodosa, Childhood Wegener Granulomatosis, and Childhood Takayasu Arteritis. Ann Rheum Dis. 2010;69(5):798-806.
• Chung SA, Langford CA, Maz M, et al. 2021 ACR/VF Guideline for the Management of ANCA-Associated Vasculitis. Arthritis Care Res. 2021;73(8):1088-1105.
• Jayne DRW, Merkel PA, Schall TJ, et al. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med. 2021;384(7):599-609.

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