Definition and epidemiology
Polyarteritis nodosa (PAN) is a necrotising vasculitis of small- and medium-sized arteries with aneurysm formation and segmental, focal involvement that spares the smallest vessels (no glomerulonephritis, no capillaritis). It is rare in childhood, with a roughly equal sex distribution and a mean onset around 9 years. Two principal phenotypes are recognised: systemic PAN and the milder, skin-limited cutaneous PAN, the latter often relapsing and frequently post-streptococcal.
A critical modern caveat: monogenic mimics — particularly DADA2 (deficiency of adenosine deaminase 2) — can present as early-onset PAN-like vasculitis with livedo, strokes, and immunodeficiency. Hepatitis B-associated PAN, historically common, is now rare where vaccination is widespread.
Clinical features
PAN is a multisystem disease driven by ischaemia. Constitutional symptoms (fever, weight loss, malaise) are near-universal. Organ-specific features include:
- Skin — livedo reticularis, tender subcutaneous nodules, palpable purpura, digital ischaemia, ulceration.
- Musculoskeletal — severe myalgia, arthralgia/arthritis.
- Neurological — mononeuritis multiplex (a hallmark), focal deficits, seizures, stroke.
- Renal — renovascular hypertension and infarcts (vascular, not glomerular).
- Gastrointestinal — colicky pain, bleeding, mesenteric ischaemia, bowel perforation.
- Cardiac — myocardial ischaemia, hypertension.
Cutaneous PAN is confined to skin, muscle, and joints with no progressive visceral involvement.
Diagnosis
There is no single confirmatory test. Diagnosis rests on a compatible clinical picture plus histology (necrotising arteritis of medium/small vessels) OR angiographic abnormalities (aneurysms, stenoses, occlusions) of medium-sized arteries — one of which is mandatory under the validated EULAR/PRINTO/PRES (Ankara 2008) criteria. Supportive items include skin involvement, myalgia/muscle tenderness, hypertension, peripheral neuropathy, and renal involvement. The criteria perform at ~89.6% sensitivity and ~99.6% specificity. ANCA is characteristically negative — a positive ANCA should redirect toward ANCA-associated vasculitis. Always screen for hepatitis B and, in early-onset or familial disease, ADA2 activity/gene testing.
See the full criteria: Pediatric-Onset Polyarteritis Nodosa
Red flags
- Acute abdomen, GI bleeding — mesenteric ischaemia or bowel perforation
- New focal neurology, stroke, or mononeuritis multiplex
- Accelerated/renovascular hypertension
- Digital or limb ischaemia
- Early-onset, familial disease, or recurrent stroke — investigate DADA2 before/around immunosuppression
- Positive ANCA, pulmonary haemorrhage, or glomerulonephritis — reconsider the diagnosis
Management overview
Treatment is risk-stratified by disease severity and organ involvement (drug classes/strategy only):
- Systemic PAN — remission induction with high-dose corticosteroids plus a cytotoxic/immunosuppressive agent (classically cyclophosphamide for severe/organ-threatening disease), followed by maintenance with a steroid-sparing immunosuppressant (e.g. azathioprine or methotrexate). Refractory disease may warrant biologic therapy.
- Cutaneous PAN — milder; often controlled with corticosteroids and a steroid-sparing agent; penicillin prophylaxis is used where a streptococcal trigger is identified.
- HBV-associated PAN — combine short-course steroids with antiviral therapy and plasma exchange rather than prolonged immunosuppression.
- DADA2 — fundamentally different: anti-TNF agents are the cornerstone (they prevent strokes); avoid relying on conventional vasculitis immunosuppression alone, and consider HSCT in severe haematological phenotypes.
Manage hypertension aggressively, provide thrombosis risk assessment, and follow per SHARE recommendations with pediatric rheumatology. Prognosis has improved markedly with modern therapy, though relapse is common.
References
- Ozen S, et al. EULAR/PRINTO/PRES Ankara 2008 criteria, Part II. Ann Rheum Dis. 2010;69:798-806.
- de Graeff N, et al. SHARE recommendations for rare paediatric vasculitides. Rheumatology. 2019;58:656-671.
- Nelson Textbook of Pediatrics, 21st ed.
Decision support for qualified clinicians only — verify against current primary guidelines and your clinical judgement.