Polyarteritis Nodosa Classification

Polyarteritis nodosa (PAN) is a necrotizing vasculitis predominantly affecting medium-sized arteries without granulomatous inflammation, glomerulonephritis, or ANCA positivity. It most commonly involves the skin (livedo, ulcers, nodules), peripheral nerves (mononeuritis multiplex), kidneys (renovascular hypertension), gastrointestinal tract, and testes. PAN is now distinguished from ANCA-associated vasculitis (AAV), which it was historically confused with. Up to 30% of PAN cases are associated with hepatitis B virus (HBV) infection.

ANCA (anti-neutrophil cytoplasmic antibodies) - particularly MPO-ANCA and PR3-ANCA - are the hallmark of ANCA-associated vasculitides (GPA, MPA, EGPA). PAN is defined by the absence of ANCA. If ANCA is positive, the diagnosis favors MPA or another AAV even if clinical features overlap with PAN. The 2022 ACR/EULAR classification framework separates the vasculitides partly by ANCA status: PAN is ANCA-negative medium-vessel vasculitis, while MPA is ANCA-positive small-vessel vasculitis.

The angiographic criterion (3 points - the highest weighted item) requires demonstration of aneurysms or occlusions in medium-sized arteries on imaging. This can be seen on conventional angiography (the historical gold standard), CTA, or MRA. Classic findings include multiple microaneurysms at vessel bifurcations in the renal, mesenteric, hepatic, and celiac arteries. The finding must not be attributable to atherosclerosis, fibromuscular dysplasia, or other non-inflammatory causes. This criterion is highly specific for PAN when present alongside other features.

Livedo reticularis is a physiologic or reactive blotchy, lace-like, mottled purplish discoloration of skin that disappears with warming - it has a regular, unbroken net pattern and is common in young women. Livedo racemosa is pathologic: it has an irregular, broken net pattern that does not disappear with warming, reflecting true cutaneous vascular disease. In PAN and antiphospholipid syndrome, livedo racemosa indicates medium-vessel disease of the skin. The 2022 criteria count both livedo racemosa and livedo reticularis when they occur in the context of vasculitis.

Hepatitis B-associated PAN (HBV-PAN) accounts for approximately 7-36% of PAN cases globally, though its prevalence has declined with universal HBV vaccination. It is thought to result from immune complex deposition causing vasculitis. Clinically, HBV-PAN may be more severe, with higher rates of mononeuritis multiplex, hypertension, and abdominal involvement. Treatment differs: HBV-PAN is treated with antiviral therapy (tenofovir or entecavir) combined with a short course of corticosteroids and sometimes plasma exchange, rather than long-term immunosuppression, to avoid enhancing viral replication.

No - this is a key distinguishing feature. PAN affects medium-sized arteries and does not cause glomerulonephritis. Renal involvement in PAN is due to renal artery vasculitis causing renovascular hypertension, renal infarction, or microaneurysms - not glomerular disease. In contrast, MPA and GPA commonly cause pauci-immune glomerulonephritis. If a patient has glomerulonephritis, the diagnosis is unlikely to be PAN and should prompt workup for ANCA-associated vasculitis, cryoglobulinemic vasculitis, or other immune complex-mediated vasculitides.

In the 2022 ACR/EULAR validation study, the PAN criteria (score ≥5) demonstrated sensitivity of 92.3% and specificity of 99.0% against other vasculitides in a cohort of patients with an established diagnosis of vasculitis. These criteria replaced the 1990 ACR PAN criteria and were developed as part of a coordinated classification exercise covering nine different vasculitis types, including AAV, IgA vasculitis, cryoglobulinemic vasculitis, and giant cell arteritis.