Description

• Polyarteritis nodosa (PAN) is a necrotizing vasculitis that typically affects medium-sized arteries, with occasional involvement of small-sized arteries.
• Systemic symptoms are prominent at presentation.
• Most common organ involvement: GI tract, peripheral nervous system (sensory and motor), kidney, skin, testes/epididymis, cardiac, CNS
• Most common features of PAN include mesenteric ischemia-related symptoms, renal involvement, mononeuritis multiplex, and purpuric skin lesions.
• Renal disease in PAN usually manifests as hypertension (HTN) and mild proteinuria with/without azotemia.
• PAN formerly encompassed several distinct entities (classic PAN, microscopic PAN, cutaneous PAN). With the advent of antineutrophilic antibody (ANCA) testing, it is now apparent that microscopic PAN may not be related to the other 2 pathophysiologically (1):
  • Patients with classic PAN (now commonly referred to as PAN) are typically ANCA negative.
  • In contrast, patients with microscopic PAN have ANCAs directed against myeloperoxidase (MPO) and generally involvement of small arterioles (as opposed to medium-sized arteries). This disease is also known as microscopic polyangiitis and is now classified as one of the ANCA-associated vasculitides.
  • Cutaneous (or limited) PAN is a disease in which patients have largely cutaneous and neurologic manifestations with characteristic histopathologic features but few systemic features. ANCA positivity is variable.
• Synonym(s): Periarteritis; Panarteritis; Necrotizing arteritis

Epidemiology

• Predominant age: Peak onset is in the 5th–6th decade, but all ages can be affected.
• Predominant sex: Male > Female (2.5:1)

Prevalence
Rare: 31 cases/1 million adults in one study

Risk Factors

Hepatitis B infection >> hepatitis C infection (cutaneous PAN)

Genetics
Unknown

Pathophysiology

• Segmental, transmural, necrotizing inflammation of medium and small muscular arteries, with subsequent intimal proliferation at the sites of inflammation, thrombosis, and ischemia of the organ/tissue supplied by the affected arteries. Aneurysm formation is prominent.
• Most frequent sites for inflammatory lesions: Bifurcations of vessels
• Disease mechanism in hepatitis B-related PAN: Direct injury to the vessel due to viral replication or secondary to deposition of immune complexes, with consequent activation of the complement cascade leading to an inflammatory response

Etiology

• Most cases are idiopathic; 20% are related to hepatitis B or C infection.
• The cause is unknown but immune-complex mediation has been postulated.
• In patients with PAN and hepatitis B, studies have shown immune complexes containing the hepatitis B antigen in involved vessel walls.

Commonly Associated Conditions

• Hepatitis B (strong association with classic PAN)
• Hepatitis C (less strongly linked to cutaneous PAN)
• Hairy cell leukemia
• 27 case reports of systemic PAN following hepatitis B vaccination (2)
• Case reports of various drugs, such as amphetamines, minocycline, and interferon