Polyarteritis Nodosa
Necrotising vasculitis of medium-sized arteries with characteristic microaneurysm formation. Distinguished from ANCA-associated vasculitis by the absence of glomerulonephritis and ANCA negativity. Historically associated with hepatitis B, though idiopathic cases are now more common.
Key Facts
PAN is a medium-vessel vasculitis characterised by necrotising arteritis with microaneurysm formation on angiography ANCA negative and no glomerulonephritis (unlike AAV); distinguishing features from MPA Hepatitis B association: historically ~30%; now <10% due to vaccination; HBsAg-positive PAN treated with antivirals + plasma exchange Mesenteric angiography: shows microaneurysms (beaded appearance), stenoses, and occlusions – diagnostic Clinical features: systemic (fever, weight loss), skin (livedo, nodules, ulcers), peripheral neuropathy (mononeuritis multiplex, 70%), GI (mesenteric ischaemia), renal (hypertension from renal artery involvement) Treatment: prednisolone ± cyclophosphamide for severe disease (FFS ≥1); HBV-related: antivirals + plasma exchange + short steroids Rare: incidence ~2-9 per million/year; M:F slight male predominance
Overview
Key Facts
PAN is becoming rarer as hepatitis B prevalence decreases. It is distinguished from AAV by medium-vessel involvement without glomerulonephritis.
Epidemiology
- Incidence: ~2-9 per million/year (declining)
- Peak age: 40-60; slight male predominance
- Declining incidence due to HBV vaccination
Pathophysiology
- Necrotising inflammation of medium-sized arteries (segmental, at vessel bifurcations)
- Transmural inflammation with fibrinoid necrosis → microaneurysm formation
- Vessel occlusion → tissue ischaemia and infarction
- NO venous involvement, NO granulomata, NO small-vessel involvement
Clinical Presentation
Constitutional (>90%)
- Fever, malaise, weight loss, myalgia, arthralgia
Neurological (70%)
- Mononeuritis multiplex: most common manifestation; foot drop, wrist drop
- Peripheral neuropathy (sensorimotor)
Skin (50%)
- Livedo reticularis, subcutaneous nodules
- Skin ulcers, digital gangrene
- Purpura (non-palpable, unlike small-vessel vasculitis)
GI (50%)
- Abdominal pain (mesenteric ischaemia)
- GI bleeding, perforation, cholecystitis
- Mesenteric vasculitis is the most serious visceral manifestation
Renal
- Renal artery involvement → renovascular hypertension, renal infarction
- NO glomerulonephritis (key distinction from AAV)
Cardiac
- Coronary arteritis → MI
- Pericarditis, heart failure
Testicular
- Orchitis (~20% of males): testicular pain and swelling
Red Flags
- Abdominal pain → mesenteric ischaemia → surgical emergency if infarction
- Severe hypertension → renal artery involvement
- Testicular pain → consider PAN
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| MPA | ANCA positive, GN, small vessel | ANCA, urine |
| GPA | Upper airway, ANCA positive, GN | ANCA |
| SLE vasculitis | ANA/dsDNA positive, multi-system | Immunology |
| Cholesterol emboli | Post-catheterisation, blue toes, eosinophilia | Biopsy |
| Infective endocarditis | Murmur, embolic phenomena | Blood cultures, echo |
Diagnosis / Investigation
Bloods
- ANCA: negative (essential for diagnosis)
- HBsAg: hepatitis B screen (positive in <10% now)
- CRP/ESR: elevated
- FBC: anaemia, leucocytosis, thrombocytosis
- U&Es: renal function (may show renovascular hypertension)
Angiography
- Mesenteric or renal angiography: microaneurysms, stenoses, occlusions at vessel bifurcations (diagnostic)
- CT angiography or MR angiography: less sensitive but non-invasive alternatives
Biopsy
- Tissue biopsy (skin, sural nerve, muscle, testis): transmural necrotising vasculitis of medium arteries, fibrinoid necrosis
- No granulomata, no venous involvement
Urinalysis
- No active sediment (no GN); may show proteinuria from renovascular disease
Management
Idiopathic PAN
FFS = 0:
- Prednisolone 1mg/kg/day alone; taper over 12-18 months
FFS ≥1 (cardiac, GI, renal, CNS):
- Prednisolone + IV cyclophosphamide induction
- Azathioprine maintenance
HBV-Associated PAN
- Short course prednisolone (2-4 weeks only)
- Antiviral therapy: entecavir or tenofovir (aim for HBV seroconversion)
- Plasma exchange: to remove immune complexes
- Prolonged immunosuppression avoided (risk of HBV reactivation)
Supportive
- Antihypertensives for renovascular hypertension
- Neuropathic pain management
- Surgical intervention for bowel ischaemia/infarction
Referral
- All PAN → rheumatology
- Mesenteric ischaemia → surgery
- HBV-positive → hepatology
Prognosis
- 5-year survival: 80-90% with treatment
- Untreated: ~50% mortality at 1 year (historical)
- FFS score predicts outcome (higher = worse)
- HBV-related PAN: antiviral-induced seroconversion can lead to complete remission
- Relapse: less common than AAV (~10-20%)
- Mononeuritis multiplex: may cause permanent neuropathy despite treatment
Other Relevant Information
PAN vs MPA
| Feature | PAN | MPA |
|---|---|---|
| Vessel size | Medium | Small |
| ANCA | Negative | Positive (MPO 70%) |
| GN | No | Yes (crescentic) |
| Angiography | Microaneurysms | Normal |
| HBV association | Yes (historically) | No |
| Pulmonary | Rare | DAH common |
Five-Factor Score (FFS) for PAN
| Factor | Significance |
|---|---|
| Cardiac | Poor prognosis |
| GI | Poor prognosis |
| Renal (creatinine >141) | Poor prognosis |
| Proteinuria >1g/day | Poor prognosis |
| CNS | Poor prognosis |