Polyarteritis nodosa

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

PAN affects muscular arteries while sparing arterioles, capillaries and venules. This anatomical level explains organ infarction, microaneurysms and renovascular hypertension and the absence of classic glomerular casts and alveolar haemorrhage. Symptoms are often painful and patchy: livedo and nodules, postprandial abdominal pain, testicular pain, myalgia and abrupt deficits in individual peripheral nerves. Examine skin, pulses, pressures, abdomen, testes where indicated and a detailed neurological map.

Baseline tests measure consequences and causes rather than confirm disease: FBC, inflammatory markers, renal and liver function, urine, CK, hepatitis B and C, HIV and blood cultures when febrile. ANCA helps identify an alternative. CTA or MRA maps renal, mesenteric, hepatic and other arterial lesions; catheter angiography shows fine microaneurysms and allows intervention. Angiographic irregularity is not unique, so integrate age, atherosclerosis and non-inflammatory arteriopathies.

Tissue is preferred when an accessible affected site exists. Deep skin, nerve-muscle or testicular biopsy may show segmental transmural necrotising arteritis. Biopsy and angiography are complementary, and treatment may begin before either in bowel or cardiac threat. Mesenteric ischaemia needs surgical review; glucocorticoid cannot revive necrotic bowel. Renal hypertension needs cautious control because perfusion may depend on stenosed vessels.

Idiopathic severe PAN uses glucocorticoid and cyclophosphamide. HBV-associated PAN is mechanistically different: antiviral suppression removes antigen drive, a short steroid course controls acute inflammation and plasma exchange may remove immune complexes. Prolonged conventional immunosuppression can worsen viraemia. Maintenance after idiopathic remission is individualised, while HBV response follows viral and vascular outcomes.

Key points

PAN is necrotising vasculitis of muscular medium and small arteries, producing renal-vascular, gastrointestinal, skin, nerve, muscle and testicular ischaemia without primary glomerulonephritis or pulmonary capillaritis.
Look for fever, weight loss, livedo, tender nodules, ulcers, myalgia, mononeuritis multiplex, severe hypertension, abdominal pain after meals, GI bleeding and testicular pain.
Urinalysis is often bland or shows non-glomerular abnormalities; red-cell casts or pulmonary haemorrhage should redirect toward AAV, anti-GBM or immune-complex disease.
Test HBsAg, anti-HBc and HBV DNA early because HBV-associated PAN needs antiviral-led specialist treatment and limited rather than prolonged immunosuppression.
Use CTA or MRA to identify renal, mesenteric and hepatic stenoses, occlusions, infarcts and microaneurysms; catheter angiography is the anatomical reference when intervention or high-resolution assessment is required.
Biopsy accessible symptomatic skin, muscle, nerve or testis when safe, seeking transmural necrotising arteritis and avoiding blind sampling of unaffected tissue.
Severe idiopathic PAN receives high-dose glucocorticoid plus cyclophosphamide; non-severe disease may use glucocorticoid with another steroid-sparing agent under specialist care.
HBV-PAN treatment combines potent antiviral therapy, a short glucocorticoid course and often plasma exchange in expert care, avoiding prolonged immunosuppression that sustains viral replication.
Manage mesenteric infarction, aneurysm rupture, coronary disease and critical limb ischaemia with surgical, interventional and vascular teams in parallel.
ANCA testing is usually negative and not a diagnostic criterion; diagnosis rests on the medium-artery phenotype, imaging or biopsy and exclusion of infection and mimics.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Idiopathic immune vasculitis

Most modern cases have no identified trigger and involve immune-mediated necrotising inflammation of medium and small muscular arteries without capillary disease.

Hepatitis B association

HBV immune complexes can cause a distinct, often severe PAN phenotype; prevalence has fallen with vaccination, blood safety and antiviral treatment.

Genetic and secondary mimics

Deficiency of adenosine deaminase 2, hairy-cell leukaemia and selected infections can produce PAN-like vasculopathy and require cause-specific treatment.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Transmural arterial necrosis
Segmental neutrophilic inflammation destroys muscular arterial walls, causing luminal thrombosis, stenosis and weakening without primary glomerular capillaritis.
2
Microaneurysm formation
Wall destruction at branch points produces aneurysms that can rupture, while healing lesions create irregular narrowing and infarction.
3
Patchy organ ischaemia
Renal, mesenteric, nerve, skin, muscle, coronary and testicular arterial occlusion causes painful multifocal infarction with lesions of different ages.
4
Medium-vessel boundary
Pulmonary capillaritis and glomerulonephritis are not typical, helping separate PAN from MPA and other ANCA-associated small-vessel vasculitis.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Skin medium-vessel pattern

Livedo racemosa, painful subcutaneous nodules, deep ulcers and digital ischaemia indicate dermal or subcutaneous arterial injury.

Mesenteric ischaemiaRed flag

Postprandial or severe acute abdominal pain, bleeding and peritonism signals bowel arterial injury and possible infarction.

Renovascular disease

Abrupt severe hypertension, renal infarct pain and kidney dysfunction with relatively bland urine supports renal-artery involvement.

Mononeuritis multiplexRed flag

Painful asymmetric sensory loss followed by foot or wrist drop reflects sequential nerve-artery infarction.

Testicular involvement

Acute or subacute testicular pain after torsion and infection assessment can provide a distinctive medium-vessel clue.

Red flags requiring action

Severe pain out of proportion, guarding, lactate rise or GI bleeding may indicate mesenteric infarction or perforation and requires immediate surgical and vascular imaging.
Abrupt hypertension, AKI or flank pain suggests renal-artery ischaemia or infarction; glomerular casts instead argue against classic PAN.
New foot or wrist drop with painful asymmetric deficits indicates nerve infarction and needs urgent disease control.
Chest pain, troponin rise, arrhythmia or heart failure may indicate coronary arteritis and requires acute cardiology.
HBsAg positivity changes treatment toward antiviral and specialist immune-complex management rather than prolonged conventional immunosuppression alone.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
FBC, CRP or ESR, renal, liver, CK and urinalysisFirst step
Why
Assess inflammation, ischaemic organ injury and whether urine suggests a small-vessel glomerulonephritis alternative.
Interpretation and limitations
Severe pressure with bland urine supports renovascular disease; casts, marked protein or lung haemorrhage argues against classic PAN.
02
HBV, HCV and HIV testing
Why
Identify infection-associated vasculitis that changes immune and antiviral treatment.
Interpretation and limitations
Use HBsAg, anti-HBc and HBV DNA with hepatology; active HBV cannot be treated as idiopathic PAN.
03
CTA or MRA abdomen and renal arteries
Why
Map stenoses, occlusions, infarcts and aneurysms in symptomatic medium-vessel territories.
Interpretation and limitations
Multifocal branch-point lesions support PAN but atherosclerosis, FMD and segmental arterial mediolysis require radiological distinction.
04
Catheter angiography
Why
Provide high-resolution anatomy and enable embolisation or other intervention for threatened organs or bleeding.
Interpretation and limitations
This is the anatomical reference when non-invasive imaging is inadequate, but contrast, access and embolic risks require specialist selection.
05
Deep skin or nerve-muscle biopsy
Why
Confirm necrotising medium-artery inflammation and exclude infection, cholesterol emboli or another vasculopathy.
Interpretation and limitations
Target an active symptomatic site; superficial punch or blind muscle biopsy may miss patchy deeper arteries.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

ANCA-associated vasculitis

Glomerular haematuria, pulmonary capillaritis, PR3 or MPO ANCA and small-vessel biopsy findings favour GPA or MPA rather than classic PAN.

Atherosclerotic or embolic disease

Cholesterol emboli, atrial emboli, non-occlusive mesenteric ischaemia and systemic atherosclerosis cause arterial organ injury through non-inflammatory mechanisms.

Infective endocarditis

Fever, embolic infarcts, aneurysm, renal abnormality and low complement may reflect endocarditis and would worsen with uncritical immunosuppression.

Other medium-vessel disorders

Segmental arterial mediolysis, fibromuscular dysplasia, Takayasu disease and DADA2 can produce stenosis, aneurysm and infarction with different demographics and histology.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First-line confirmationDefine the medium-vessel phenotypeFirst stepFirst linePainful skin, nerve, renal-vascular, bowel or testicular features suggest PAN.

1Assess organ threat and map pulses, pressure, skin, nerve, abdominal and testicular findings, urine and cardiopulmonary absence or presence.
2Test hepatitis and infection, obtain CTA or MRA of involved territories and select accessible deep tissue for biopsy.
3Use catheter angiography when fine anatomy or embolisation is required and do not delay surgery for suspected bowel necrosis.

02Severe idiopathic inductionCombine glucocorticoid and cyclophosphamideMesenteric, cardiac, renal, neurological or limb disease threatens organ function and HBV is excluded.

1Give intravenous methylprednisolone for critical disease then high-dose oral prednisolone with a planned taper and prophylaxis.
2Add intravenous cyclophosphamide adjusted for age and kidney function and coordinate vascular, surgical and renal source control.
3Measure organ recovery directly and transition to a safer maintenance agent after remission and an adequate induction course.

03HBV-associated pathwayRemove viral antigen driveActive hepatitis B infection accompanies a compatible PAN phenotype.

1Involve hepatology and start a high-potency nucleos(t)ide antiviral such as tenofovir or entecavir selected for renal, pregnancy and resistance factors.
2Use only a short specialist glucocorticoid course for immediate vascular inflammation and consider plasma exchange for severe immune-complex disease.
3Track HBV DNA, liver safety and vascular response and avoid prolonged cyclophosphamide unless exceptional expert circumstances justify it.

04Ischaemic complicationRestore flow and remove necrotic tissueImaging or examination shows bowel, coronary, renal, limb or bleeding aneurysm complication.

1Resuscitate, provide analgesia and antibiotics for perforation or sepsis and involve vascular, interventional and surgical teams immediately.
2Use embolisation, revascularisation, bowel resection or other source control according to anatomy while immune treatment proceeds.
3After survival, manage nutrition, neuropathy, pressure, kidney function and recurrence with interval imaging tailored to the lesion.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Rapid control of necrotising arterial inflammation, combined with cyclophosphamide for severe idiopathic disease.

Prednisolone for severe PAN

Use 1 mg/kg orally once daily, commonly up to 60 mg/day, after intravenous methylprednisolone 500 mg–1 g daily for three days when an organ is critically threatened; taper with remission induction.

Assess infection and HBV before prolonged therapy, monitor glucose, pressure, mood, eyes and bone, and provide prophylaxis according to total immune risk.

Induces remission in severe non-HBV PAN with major gastrointestinal, renal, neurological, cardiac or limb disease.

Intravenous cyclophosphamide

A specialist pulse course may give 15 mg/kg intravenously at baseline, after two weeks and after four weeks, then continue at three-week intervals with age-, kidney- and cytopenia-based reductions.

Monitor FBC, urine and infection and provide antiemetic and bladder protection. Discuss infertility preservation, teratogenicity, cumulative bladder cancer and later malignancy.

Suppresses HBV replication and removes the antigen source driving immune-complex vascular disease.

Entecavir for HBV-associated PAN

For nucleoside-naive adults with compensated liver disease use 0.5 mg orally once daily with or without food, adjusting the interval for renal impairment under hepatology guidance; resistance or decompensation needs a different regimen.

Confirm HIV status before monotherapy, monitor HBV DNA and liver flare, and never stop without hepatology because severe post-treatment hepatitis can occur. Use effective contraception; avoid in pregnancy unless clearly necessary, prefer a better-established pregnancy antiviral when appropriate, and stop breast-feeding during entecavir treatment.

Steroid-sparing maintenance option after cyclophosphamide when ongoing relapse prevention is required.

Azathioprine maintenance

After remission in idiopathic disease, start 25–50 mg orally daily after TPMT assessment and increase toward 1.5–2 mg/kg/day under specialist monitoring.

Monitor FBC, liver and renal function, infection and pancreatitis; allopurinol or febuxostat interactions require expert dose adjustment or avoidance.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Bowel infarction and perforation

Mesenteric thrombosis or aneurysm rupture causes necrosis, bleeding, perforation, sepsis and death without rapid surgery and disease control.

Renal vascular hypertension

Renal infarcts and artery stenoses activate renin, causing severe hypertension, kidney dysfunction and cardiovascular injury without glomerulonephritis.

Neuropathy and limb disability

Vasa-nervorum infarction causes mononeuritis multiplex, chronic neuropathic pain, foot drop, muscle wasting and persistent functional impairment.

Aneurysm rupture and treatment harm

Renal, mesenteric or hepatic aneurysm rupture combines with infection, infertility, malignancy, diabetes and osteoporosis from intensive treatment.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During severe disease follow abdominal signs, lactate, haemoglobin, pressure, kidney function, pulses, skin and neurological deficits at organ-appropriate frequency.
Repeat vascular imaging for known aneurysm, stenosis or infarct according to size, site, intervention and symptoms rather than one universal schedule.
In HBV disease track HBV DNA, ALT, renal safety and adherence with hepatology and avoid unsupervised antiviral withdrawal.
Record cyclophosphamide cumulative dose, blood counts, fertility, bladder symptoms and malignancy risk and taper glucocorticoid deliberately.
Provide rehabilitation and orthotics for neuropathy and monitor neuropathic pain, falls, nutrition and bowel recovery.
Reassess diagnosis if glomerular urine, pulmonary haemorrhage or ANCA-associated features emerge.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

The spared glomerulus is a clue

Renal disease in PAN is arterial infarction and hypertension; glomerular casts point toward a small-vessel alternative.

Lung capillaritis is atypical

Asthma, haemorrhage or diffuse lung capillary disease should prompt EGPA, MPA, infection or another diagnosis.

Angiography sees consequences

Microaneurysms and irregular stenoses support PAN but are not histology and occur in non-inflammatory arteriopathies.

HBV changes the logic

Removing viral antigen and immune complexes matters more than prolonged nonspecific suppression, which can increase replication.

Steroid cannot rescue infarcted bowel

Surgery and revascularisation proceed alongside immune treatment whenever tissue viability is lost.

11Common pitfallsFrequent interpretation and management errors.

01
Calling glomerulonephritis PAN despite red-cell casts and pulmonary capillaritis.
02
Failing to test hepatitis B before cyclophosphamide and prolonged glucocorticoid.
03
Interpreting every angiographic irregularity as vasculitis without considering atherosclerosis, FMD and arterial mediolysis.
04
Using a superficial biopsy that does not sample medium arteries.
05
Delaying surgical assessment of severe abdominal pain while waiting for immune tests.
06
Treating HBV-PAN with prolonged immunosuppression without potent antiviral therapy.