What are the clinical presentation and treatment options for polyarteritis nodosa in pediatric patients?

Clinical Presentation of Polyarteritis Nodosa in Children

Pediatric polyarteritis nodosa (PAN) presents as a severe systemic inflammatory disease with insidious onset, most commonly manifesting with musculoskeletal symptoms (myalgia and arthralgia/arthritis in 83-87% of cases), skin involvement (88-93%), and constitutional symptoms including fever (87%) and weight loss. 1, 2, 3

Major Clinical Features

Musculoskeletal and Constitutional Manifestations

• Myalgia occurs in 83% of pediatric patients and represents a major diagnostic criterion 2
• Arthralgia or arthritis affects 87% of children, significantly more common than in adults (59%) 3
• Fever is present in 87% of cases at presentation 2
• Weight loss occurs in approximately 20% of pediatric patients, less frequently than in adults (59%) 3

Cutaneous Involvement

• Skin manifestations occur in 88-93% of pediatric PAN patients, including skin nodules and livedo reticularis 4, 2, 3
• Deep skin biopsy showing necrotizing vasculitis confirms diagnosis in 80% of cases (40 of 50 children) 2

Renal Manifestations

• Renal involvement occurs in 19-20% of pediatric patients, significantly less common than in adults (50%) 1, 2, 3
• Renal involvement has the greatest adverse effect on outcome and mortality 1
• Hypertension may accompany renal disease 1

Gastrointestinal Involvement

• Severe gastrointestinal involvement occurs in 10% of pediatric patients at presentation 2
• Abdominal pain, vomiting, and diarrhea may progress to intestinal ischemia requiring emergency surgical intervention 5
• Mesenteric ischemia can occur due to involvement of mesenteric vessels 4
• Severe GI involvement is associated with increased risk of disease relapse (P = 0.031) 2

Neurologic Manifestations

• Peripheral neuropathy occurs in 10% of children at presentation 1, 2
• Central nervous system involvement is documented in 10% of cases 1
• Neurologic involvement is less common in children (40%) compared to adults (59%) 3

Other Organ Systems

• Cardiac involvement may occur 1
• Pulmonary involvement is documented but less common 1

Diagnostic Criteria for Pediatric PAN

The presence of five of twelve criteria, including at least one major criterion (musculoskeletal or renal involvement), is highly suggestive of PAN and was present in 97% of pediatric patients. 1

Major Criteria (Must Have ≥1)

• Musculoskeletal involvement 1
• Renal involvement 1

Minor Criteria (Need Total of 5 Including Major)

• Cutaneous findings 1
• Gastrointestinal involvement 1
• Peripheral neuropathy 1
• Central nervous system involvement 1
• Hypertension 1
• Cardiac involvement 1
• Lung involvement 1
• Constitutional symptoms 1
• Presence of acute-phase reactants 1
• Presence of hepatitis B surface antigen 1

Disease Activity and Severity

The median Paediatric Vasculitis Activity Score (PVAS) at presentation is 9 of 63 (range 4-24), indicating moderate to severe disease activity. 2

Diagnostic Imaging Findings

Selective visceral arteriography suggests PAN in 96% of pediatric patients, revealing saccular or fusiform aneurysms and stenotic lesions in mesenteric, hepatic, and renal arteries. 4, 2

Angiography at diagnosis is performed less frequently in children (33%) compared to adults (82%), likely reflecting the more benign presentation in pediatric cases. 3

Clinical Course and Prognosis

Pediatric PAN has a more benign course than adult-onset disease, with less renal and neurologic involvement, shorter duration of induction treatment required, and lower mortality rates (0% vs 13.6% in adults). 3

The overall mortality rate in pediatric PAN is 4-16%, with renal involvement being the strongest predictor of poor outcome. 1, 2

Disease relapse occurs in 35% of pediatric patients, with severe gastrointestinal involvement being the primary risk factor for relapse. 2

Treatment Implications Based on Presentation

For newly diagnosed active, severe pediatric PAN, initiate treatment with cyclophosphamide and high-dose glucocorticoids immediately. 6, 4

Intravenous pulse glucocorticoids are preferred over high-dose oral glucocorticoids for severe disease in pediatric patients, as pulse therapy has a favorable side-effect profile and is not more strongly associated with infections or other morbidities. 6

Treatment should be initiated promptly in patients meeting five diagnostic criteria, especially those with renal involvement, while diagnostic procedures are being carried out. 1

Higher cumulative doses of cyclophosphamide are associated with lower risk of relapse (P = 0.005), while longer time to induce remission is also protective (P = 0.022). 2