Polyarteritis nodosa

Last updated 28 Mar 2026 · Vasculitis

Polyarteritis Nodosa

Polyarteritis nodosa (PAN) is a systemic necrotising vasculitis of medium-sized arteries, characterised by focal, segmental inflammation leading to aneurysm formation, thrombosis, and end-organ ischaemia. PAN spares small vessels (capillaries, venules, arterioles) and is ANCA-negative, distinguishing it from ANCA-associated vasculitides. It is associated with hepatitis B virus (HBV) infection in a significant proportion of cases. PAN predominantly affects the kidneys, gastrointestinal tract, peripheral nerves, skin, and musculoskeletal system. It is a rare but potentially life-threatening condition requiring prompt immunosuppression.

Australian Context

PAN is rare in Australia with an estimated incidence of 2–9 per million per year. Since the introduction of universal HBV vaccination in Australia in 1999, HBV-associated PAN has declined significantly. Idiopathic PAN (without HBV) now constitutes the majority of cases. PAN may also be associated with hairy cell leukaemia and other haematological malignancies. Diagnosis requires exclusion of ANCA-associated vasculitis and infectious causes (HBV, HIV) before initiating immunosuppression.

Pathophysiology

Necrotising Vasculitis

PAN is characterised by segmental, transmural necrotising inflammation of medium-sized muscular arteries. All layers of the arterial wall (intima, media, adventitia) are affected, with fibrinoid necrosis, neutrophil infiltration, and destruction of the internal elastic lamina. Healing lesions show granulomatous features and fibrosis. Aneurysmal dilation occurs at sites of arterial wall weakness. Occlusion from thrombosis and intimal proliferation causes distal ischaemia.

HBV-Associated PAN

HBV surface antigen-antibody immune complex deposition in arterial walls triggers complement activation and neutrophil recruitment, causing vasculitis indistinguishable from idiopathic PAN. HBV-associated PAN typically occurs within the first 6 months of HBV infection and is treated with antiviral therapy alongside short-course immunosuppression, rather than prolonged immunosuppression alone.

Clinical Presentation

Constitutional Features

Fever, weight loss, fatigue, and malaise are almost universal. Myalgia and arthralgia are common. Constitutional symptoms may precede organ-specific features by weeks to months, contributing to diagnostic delay.

Organ-Specific Manifestations

Peripheral nervous system (70%): Mononeuritis multiplex — asymmetric, painful peripheral neuropathy affecting multiple individual nerve territories sequentially (e.g., foot drop from peroneal nerve, wrist drop from radial nerve)
Renal (40%): Renovascular hypertension from renal artery aneurysms, renal infarction, renal impairment (note: PAN does NOT cause glomerulonephritis — haematuria/proteinuria suggests alternative diagnosis)
Gastrointestinal (30–50%): Mesenteric ischaemia causing severe abdominal pain, bowel infarction, perforation, or bleeding — a surgical emergency
Skin (50%): Livedo reticularis, palpable purpura, skin ulceration, cutaneous nodules (subcutaneous aneurysms)
Testicular (20%): Testicular pain from testicular artery involvement — an important diagnostic clue in men
Cardiac (rare): Coronary arteritis causing myocardial infarction; pericarditis

Investigations

Essential
ANCA (c-ANCA/PR3, p-ANCA/MPO)
Must be NEGATIVE in PAN. Positive ANCA indicates AAV (GPA, MPA, EGPA) — a different diagnosis requiring different treatment. ANCA-negativity is a diagnostic requirement for PAN.
Essential
Hepatitis B Serology (HBsAg, HBcAb, HBV DNA)
Mandatory in all suspected PAN. HBV-associated PAN requires antiviral therapy as cornerstone of treatment rather than prolonged immunosuppression. HBsAg-positive PAN treated differently.
Essential
ESR and CRP
Markedly elevated. Used for treatment monitoring. Normal ESR/CRP does not exclude PAN in established disease.
Essential
CT Angiography (Mesenteric and Renal Arteries)
Demonstrates characteristic saccular microaneurysms at arterial bifurcations (mesenteric, renal, hepatic arteries) — pathognomonic of PAN. Also assesses for bowel ischaemia, renal infarction.
Available
Nerve Conduction Studies / EMG
Confirm mononeuritis multiplex pattern — axonal, asymmetric, multifocal. Guides biopsy site selection. Serial studies monitor recovery.
Referral
Tissue Biopsy (Sural Nerve, Skin, Testis, Muscle)
Histological confirmation of medium-vessel necrotising vasculitis. Sural nerve biopsy preferred when mononeuritis multiplex is present. Skin biopsy for cutaneous nodules.

Severity Assessment

MILD

Limited Disease

Constitutional symptoms, peripheral neuropathy only, no vital organ involvement. FFS = 0

Prednisolone 1 mg/kg/day alone; close monitoring for escalation

MODERATE

Organ Involvement

Renal impairment, GI ischaemia (non-surgical), cardiac involvement. FFS = 1

High-dose corticosteroids + cyclophosphamide; consider IV pulse methylprednisolone

SEVERE

Life/Organ-Threatening

Bowel infarction, renal failure, mesenteric crisis, coronary involvement. FFS ≥ 2

IV methylprednisolone + cyclophosphamide; urgent surgical review for GI complications

The Five Factor Score (FFS) predicts mortality in PAN: each of the following scores 1 point: proteinuria >1g/day, renal insufficiency (creatinine >140 µmol/L), cardiomyopathy, severe GI involvement, CNS involvement. FFS ≥ 2 indicates high-risk disease requiring aggressive immunosuppression.

Treatment Strategy

Idiopathic PAN

High-dose prednisolone 1 mg/kg/day (max 60–80 mg/day) is the foundation of treatment. For mild disease (FFS = 0), corticosteroids alone may be sufficient. For moderate-severe disease (FFS ≥ 1), add cyclophosphamide (15 mg/kg IV pulse every 2–3 weeks × 6 pulses, or oral 2 mg/kg/day). After remission induction (typically 3–6 months), transition to maintenance with azathioprine or methotrexate. Rituximab is used for refractory cases.

HBV-Associated PAN

Antiviral therapy is the cornerstone: tenofovir (300 mg/day) or entecavir (0.5 mg/day) — start immediately. Short-course corticosteroids (prednisolone 1 mg/kg/day for 2–4 weeks, then rapid taper) to control acute inflammation. Plasma exchange (7–10 sessions) to remove immune complexes. Long-term antiviral therapy maintained until HBsAg seroconversion. Prolonged immunosuppression avoided as it promotes viral replication.

Steroid Taper

Taper prednisolone over 12–18 months guided by clinical response and inflammatory markers. Bone protection mandatory. Relapse during taper is common — return to last effective dose and reassess adequacy of steroid-sparing agent.

Directed Therapy

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Cyclophosphamide

Endoxan® · Alkylating Agent · Induction

Adult DoseIV pulse: 15 mg/kg (max 1.2 g) every 2–3 weeks × 6 pulses

Paediatric500–750 mg/m² IV per pulse; specialist dosing

RouteIV pulse (preferred) or oral

Duration3–6 months induction

Renal Adj.Reduce dose if eGFR <30; monitor closely

Hepatic Adj.Caution in hepatic impairment

PBS Status✓ PBS Listed

💊

Tenofovir Disoproxil

Viread® · Antiviral · HBV-associated PAN

Adult Dose300 mg once daily

PaediatricWeight-based; specialist dosing for children ≥2 years

RouteOral

FrequencyOnce daily

DurationUntil HBsAg seroconversion (may be years)

Renal Adj.Reduce dose if eGFR <50; switch to tenofovir alafenamide if eGFR <30

Hepatic Adj.No adjustment required (excreted renally)

PBS StatusPBS Authority Required

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Azathioprine

Imuran® · Antimetabolite · Maintenance

Adult Dose2 mg/kg/day (max 200 mg/day)

RouteOral

Duration18–24 months minimum

Renal Adj.Reduce dose with renal impairment; check TPMT

PBS Status✓ PBS Listed

Acute Management

Acute Mesenteric Ischaemia

Abdominal PAN may present as an acute abdomen from mesenteric ischaemia, bowel infarction, or perforation — a surgical emergency. Urgent CT angiography to characterise mesenteric vasculitis and aneurysms. Immediate surgical consultation. Start IV methylprednisolone 500–1000 mg/day × 3 days alongside surgical management. Antihypertensives for hypertensive crisis. Avoid vasopressors where possible due to ischaemic risk.

Mononeuritis Multiplex

Rapid progressive mononeuritis multiplex may cause severe disability. Start high-dose corticosteroids immediately. Add cyclophosphamide for moderate-severe neuropathy. Physiotherapy and occupational therapy essential during recovery phase. Nerve recovery is slow (months to years) — early intervention prevents permanent deficit.

Hypertensive Crisis

Renovascular hypertension in PAN may be severe and difficult to control. Use calcium channel blockers (amlodipine) or labetalol IV for acute control. ACE inhibitors require caution with bilateral renal artery aneurysms. Monitor renal function closely. Control of vasculitis activity is essential for long-term blood pressure management.

Monitoring and Follow-up

Disease Activity Monitoring

BVAS (Birmingham Vasculitis Activity Score) at each visit. ESR and CRP every 4–6 weeks initially, then 3-monthly when stable. Urinalysis and renal function at every visit — new haematuria or proteinuria suggests alternative diagnosis or complication. Peripheral nerve examination to track mononeuritis recovery. Blood pressure monitoring at every visit.

HBV Monitoring

HBV DNA quantification every 3 months on antiviral therapy. HBsAg and HBsAb every 6 months — target HBsAg clearance (seroconversion). LFTs monthly initially, then 3-monthly. Liver ultrasound annually for HCC surveillance in patients with HBV-associated PAN (particularly those with cirrhosis).

Vascular Imaging

CT angiography at 6–12 months after treatment to assess aneurysm evolution (resolution, persistence, or new formation). Annual imaging recommended in patients with known aneurysms. MR angiography as radiation-sparing alternative for younger patients requiring repeated imaging.

Special Populations

🤰 Pregnancy

CyclophosphamideCONTRAINDICATED in pregnancy — severely teratogenic. Switch to azathioprine before conception. Ensure contraception during and for 3 months after cyclophosphamide use.

HBV AntiviralsTenofovir is safe in pregnancy and is the preferred antiviral for HBV during pregnancy. Continued antiviral therapy throughout pregnancy and postpartum important to prevent perinatal HBV transmission.

Disease ActivityPAN in pregnancy is rare. Aim for remission before conception. Hypertension management critical. Multidisciplinary care with rheumatology, hepatology (if HBV-related), and obstetrics essential.

🛡️ Hairy Cell Leukaemia-Associated PAN

AssociationPAN is strongly associated with hairy cell leukaemia (HCL). PAN may be the presenting feature of occult HCL. Screen with blood film, bone marrow biopsy if hairy cell leukaemia is suspected.

TreatmentTreating the underlying HCL with cladribine often leads to resolution of the associated vasculitis. Coordinate management with haematology.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Hepatitis B infection has historically been highly prevalent in some Aboriginal and Torres Strait Islander communities, though universal infant vaccination since 1990 and targeted catch-up programs have significantly reduced prevalence. Chronic HBV infection in older Aboriginal and Torres Strait Islander adults may predispose to HBV-associated PAN. This possibility must be actively considered when PAN is diagnosed in this population, as treatment differs fundamentally from idiopathic PAN.

HBV Screening

HBV serology (HBsAg, HBcAb, HBsAb) should be performed in all Aboriginal and Torres Strait Islander patients with suspected PAN. HBV prevalence remains higher in remote communities among older adults who may not have received childhood vaccination. Identify and treat underlying HBV infection as a priority.

Diagnostic Access

CT angiography for microaneurysm detection and nerve conduction studies for mononeuritis characterisation may not be available locally. Arrange urgent patient transport to metropolitan or regional centres for definitive diagnosis. Telehealth rheumatology review to guide investigation prioritisation.

Treatment Coordination

Cyclophosphamide-based immunosuppression requires intensive monitoring and specialist supervision. Shared care arrangements, community nursing support, and telehealth monitoring should be established to enable safe treatment in or near the patient's community where possible.

Antimicrobial Stewardship

HBV and Immunosuppression

Hepatitis B screening and antiviral prophylaxis are critical in PAN management. Reactivation of occult HBV (HBsAg-negative but HBcAb-positive) can occur during immunosuppression — prophylactic antiviral therapy (tenofovir or entecavir) should be considered in HBcAb-positive patients commencing cyclophosphamide or high-dose corticosteroids.

HBsAg-positive patients: antiviral therapy is the primary treatment; avoid prolonged immunosuppression
HBcAb-positive, HBsAg-negative: prophylactic antiviral therapy recommended during immunosuppression; monitor HBV DNA 3-monthly
PJP prophylaxis (trimethoprim-sulfamethoxazole 160/800 mg three times weekly) for patients on cyclophosphamide + high-dose steroids >4 weeks
TB screening (IGRA) required before biologic therapy (rituximab)
Withhold immunosuppression during significant active bacterial infections

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Critical: Never use prolonged immunosuppression alone for HBV-associated PAN without antiviral therapy — corticosteroids and cyclophosphamide promote HBV replication and can cause fatal hepatitis flare.

References

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Australian Rheumatology Association. Vasculitis Management Guidelines. Sydney: ARA; 2023.
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