Polyarteritis Nodosa (PAN)

Meet the patient

A 54-year-old man lands on the medical take with three weeks of fevers, eight kilograms gone, and a left foot that has been dragging for four days. On the round he is holding his abdomen and admits the pain is worst twenty minutes after he eats — he has stopped eating to avoid it. His blood pressure, normal six months ago, is now 168 over 104. The urine dip, run twice, is completely bland.[1][5]

On the skin of his shins you find a net-like livedo and two tender peasized lumps along the course of the posterior tibial artery. He winces when you examine the testis, and a quick neuro check shows a right wrist drop he had not mentioned. The chest is clear. ANCA, sent yesterday, is negative.[1][5]

Two questions are now live on the ward round, and the whole topic exists to answer them: is this PAN or is this MPA? (the bland urine and the negative ANCA are doing the heavy lifting) and is there hepatitis B driving it? (because the answer rewrites the prescription). Hold those two forks and every section below slots into place.[1][3]

What PAN actually is — and the name on the statue

PAN is the archetype of the medium-vessel vasculitides, and it is one of the oldest names in medicine. Kussmaul and Maier coined periarteritis nodosa in 1866 after autopsy on a young tailor studded with nodular arterial lesions — the first systemic vasculitis ever described.[3]

The 2012 Revised International Chapel Hill Consensus Conference (CHCC) Nomenclature defines PAN as a necrotising arteritis of medium or small muscular arteries without glomerulonephritis and without ANCA. Read that definition as three deliberate negatives — those exclusions are exactly what separate PAN from the ANCA-associated vasculitides.[3]

Etymology for viva gold: periarteritis means inflammation around an artery; nodosa means nodular. The nodules Kussmaul felt were aneurysms beaded along an artery like a rosary — which is why the angiographic equivalent, a century later, is still called the rosary sign. One finding, two ways of seeing it.[3]

The clinical skill in PAN is three simultaneous recognitions. First, recognise the medium-vessel pattern — ischaemic end-organ damage from stenosis, thrombosis or aneurysm, not the capillaritis pattern of glomerulonephritis and pulmonary haemorrhage. Second, recognise the two defining negatives — bland urine and a negative ANCA. Third, recognise HBV-PAN, because its treatment is completely different from idiopathic disease.[1]

Untreated PAN was once uniformly fatal — five-year survival in the pre-steroid era was about 13 percent. With modern treatment it now exceeds 80 percent. Yet it remains rare and easily missed, because its presentation overlaps infection, malignancy and the more common AAV, and its hallmark — microaneurysms — is invisible unless you specifically go looking with visceral angiography.[2]

The three cardinal negatives — and the table every examiner wants

PAN is defined by what it spares, not what it hits. Memorise the three negatives as a single unit, because they are the diagnostic cornerstone: no glomerulonephritis (the urine is bland), no ANCA, and no lung involvement. All three fall straight out of the vessel size — PAN lives in arteries, not in the capillary beds of the glomerular tuft or the alveolar wall.[1][3]

Because the kidney is involved at the interlobar and arcuate arteries at the renal hilum, PAN gives you renovascular hypertension, renal infarction and ischaemic nephropathy — but the glomerulus is structurally untouched, so the dipstick stays clean. An active urinary sediment in suspected PAN is the single loudest red flag to abandon the diagnosis and look instead at MPA, anti-GBM disease, IgA nephritis or lupus.[1][3]

The face-off that decides every viva is PAN against microscopic polyangiitis. The discriminator is one line: medium vessel, bland urine, no ANCA, lungs clear — that is PAN; small vessel, active sediment, ANCA-positive, lungs bleeding — that is MPA.[1][3]

The two forms — one common, one that needs different drugs

PAN splits on two axes: vessel size (which defines it) and trigger (which dictates treatment). The fork that earns marks is idiopathic versus HBV-associated — they share a name and almost nothing else therapeutically.[1][3]

The 2012 Chapel Hill classification seats PAN in the medium-vessel vasculitis group beside Kawasaki disease, and strips it of every small-vessel feature. A patient with glomerulonephritis, pulmonary capillaritis, or a positive ANCA does not have PAN — reclassify as MPA or another AAV. The older 1990 ACR criteria predate the separation of MPA and are no longer reliable; the 2021 ACR/Vasculitis Foundation criteria recognise PAN as a distinct medium-vessel entity, weighting visceral angiography for it and ANCA-positivity and glomerulonephritis against it.[1]

How common, who, and what lights the fuse

PAN is rare. Annual incidence is about 2 to 9 per million, prevalence about 30 per million, and incidence has fallen over three decades as universal HBV vaccination shrank the HBV-PAN share — leaving the idiopathic form dominant in modern practice.[1][2]

Peak onset is 40 to 60 years with a 2 to 1 male predominance, and no strong racial or geographic pattern; the historical over-representation of HBV-endemic regions has faded with vaccination. Recognised triggers drive the secondary workup.[1][6]

• Hepatitis B — the classical association. Historically up to 30 to 50 percent of PAN was HBV-driven; with vaccination this has fallen to under 10 percent.
• Hepatitis C — a rare cause of true PAN; HCV more often causes mixed cryoglobulinaemic vasculitis, which is a separate small-vessel entity.
• Hairy cell leukaemia — the most cited haematological association; suspect a malignancy in atypical or refractory disease.
• DADA2 — now a distinct genetic differential, not idiopathic PAN.[1][6]

The mechanism in four moves — immune complex to rosary sign

PAN is driven by immune-complex deposition in the walls of medium muscular arteries. Walk the cascade in four moves and you will never confuse the mechanism with pauci-immune AAV.[1][6]

1. Immune complexes land and fire complement. In idiopathic disease the antigen is unknown; in HBV-PAN the complexes are HBV-antigen with anti-HBV, often mixed with cryoglobulins. Classical-pathway activation gives a low serum complement in HBV-PAN.
2. Neutrophils invade the full wall. C5a and C3a recruit neutrophils and macrophages through intima, media and adventitia, producing transmural fibrinoid necrosis.
3. The elastic lamina ruptures and aneurysms form. Neutrophil proteases and reactive oxygen species fragment the internal elastic lamina and weaken the media, throwing the microaneurysms (the nodosa) alternating with segmental stenoses — angiographically the beaded rosary sign.
4. The vessel thromboses, ruptures, or scars. Thrombosis infarcts downstream territory, rupture bleeds (renal, hepatic, mesenteric), and healing fibrosis leaves permanent segmental narrowing — the chronic ischaemic phenotype.[1][6]

The two defining negatives fall straight out of this anatomy. Because PAN involves arteries rather than arterioles, capillaries or venules, it spares the glomerulus (bland urine) and spares the lungs (no capillaritis, no alveolar haemorrhage). In HBV-PAN the antigen is known, which is precisely why the goal of therapy is HBV clearance by antivirals and removal of complexes by plasma exchange rather than indefinite immunosuppression.[1][6]

The clinical picture — NODULES on the ward round

PAN is a multi-system disease with a subacute onset over weeks to months, and no single pathognomonic feature. The diagnostic skill is recognising the medium-vessel pattern across territories — constitutional plus organ-specific — because the combination, not any one sign, makes the call.[1]

Constitutional features come first and mislead longest. Fever, malaise, fatigue and weight loss are present in most patients and mimic infection, malignancy or endocarditis. Weight loss may reach 10 percent of body weight and is compounded by post-prandial pain the patient avoids by not eating — sitophobia.[1]

Atypical presentations earn their own shelf because they are the ones that bite: cutaneous PAN (skin-only, benign but relapsing); mononeuritis multiplex as the sole feature (every workup must screen vasculitis — HBV, ANCA, cryoglobulins, ESR and CRP); explosive HBV-PAN within months of acute HBV; and recurrent stroke or PAN-like disease in a child or young adult — think DADA2 and reach for anti-TNF, not steroids.[7][8]

The bedside round — nerve, gut, kidney, skin, testis

A focused multi-system examination is mandatory at first contact and every follow-up, because PAN's territory is arterial and the organs map the vessel distribution.[1][5]

General and vitals. Check blood pressure in both arms — renovascular hypertension is common and may be the first clue — plus temperature, weight, and a search for fever patterns and cachexia.[1]

Skin. Examine the lower limbs and trunk in daylight for livedo reticularis (net-like, blanchable), tender subcutaneous nodules along arteries (palpate the course of the sural, posterior tibial, radial and ulnar arteries — these are the nodosa and the best biopsy targets), ulcers, digital infarcts and gangrene.[1]

Neurological — the most important bedside domain. Test ankle and foot dorsiflexion (peroneal nerve — foot drop), wrist and finger extension (radial, ulnar, median — wrist drop), and sensation in named peripheral-nerve territories. Mononeuritis multiplex — an asymmetric, painful, sensorimotor neuropathy in two or more individual nerves — is the single most characteristic finding and reflects nerve infarction. Add a cranial-nerve and cerebellar screen; CNS disease is uncommon but real.[5]

Abdomen and genitalia. Look for tenderness out of proportion to findings (early mesenteric ischaemia), distension and peritonism (infarction or perforation — a surgical emergency). Auscultate for renal, aortic and mesenteric bruits. Perform a testicular examination for epididymal tenderness — characteristic of PAN and routinely forgotten.[1][5]

Cardiovascular and eyes. Heart sounds (pericarditis, failure), murmurs (endocarditis is a key mimic), peripheral pulses and bruits, signs of hypertensive or ischaemic cardiac failure. Fundoscopy for hypertensive retinopathy — the kidney in PAN is renovascular, so the eye often shows the consequences.[1]

Investigations — angiography first, biopsy if you can reach it

A staged workup confirms the vasculitis, defines the vessel size, excludes mimics, screens for HBV and sets the treatment intensity. Three non-negotiables: ANCA is negative, the urinalysis is bland, and visceral angiography plus tissue biopsy are the two confirmatory tests.[1]

First-line bloods. FBC (normocytic anaemia of chronic disease, leucocytosis, thrombocytosis as acute-phase responses — eosinophilia points AWAY from PAN toward EGPA); ESR and CRP (markedly elevated but non-specific); U and E plus creatinine (renal impairment); LFTs (hepatitic in HBV-PAN, low albumin in active inflammation); CK (myositis); glucose and lipids (cardiovascular risk).[1]

Urinalysis and microscopy — the single most important bedside test. In PAN the urine is bland: no proteinuria, no haematuria, no red-cell casts. An active sediment mandates reconsideration — MPA, anti-GBM, IgA nephritis, lupus. Send a protein-to-creatinine ratio; significant proteinuria in suspected PAN points to a glomerular disease.[1][3]

Immunology — the discriminating panel. ANCA is NEGATIVE on both indirect immunofluorescence and PR3 or MPO ELISA; a positive ANCA means reconsider MPA, GPA or EGPA. Add ANA, rheumatoid factor and anti-dsDNA to exclude lupus or overlap. Complement (C3, C4) is normal or LOW in HBV-PAN (immune-complex consumption; C4 selectively low if cryoglobulins are present). Send cryoglobulins (kept warm) if HBV or HCV is suspected, anti-GBM if a pulmonary-renal overlap is on the cards, and serum electrophoresis to screen for paraproteinaemia and the hairy-cell association.[1]

Infection screen — mandatory in every case. HBV serology (HBsAg, anti-HBc, anti-HBs) changes the prescription, so it cannot be skipped. Add HCV and HIV antibodies and an HBV DNA viral load if HBsAg is positive. Missing HBV commits the patient to the wrong regimen.[1]

Visceral angiography — the radiological hallmark. CT, MR or conventional mesenteric and renal angiography reveals the pathognomonic findings: multiple microaneurysms 1 to 5 mm and a beaded (rosary sign) irregular outline of the renal, mesenteric and hepatic arteries, distributed at branch points. Conventional digital subtraction angiography has the highest spatial resolution when CT or MR is equivocal.[1][6]

Tissue biopsy — the gold standard. Biopsy an involved organ with the highest yield and lowest risk: a skin nodule in cutaneous disease, sural nerve plus adjacent muscle when neuropathy leads (combined nerve-muscle biopsy raises yield), testis when epididymo-orchitis is present, gut resected at surgery for perforation or infarction, or kidney targeting perirenal tissue rather than the glomerulus. Histology at the acute stage shows transmural medium-vessel vasculitis with fibrinoid necrosis, disruption of the internal elastic lamina and a mixed infiltrate; older lesions heal with fibrosis and intimal hyperplasia. Skip lesions are common — a negative biopsy never excludes PAN.[1]

Nerve conduction and EMG localise mononeuritis multiplex (axonal, asymmetric, in named-nerve distribution), confirm the pattern, and guide the choice of nerve to biopsy — a clinically affected nerve with an absent sensory action potential, plus adjacent muscle.[5]

Other imaging. Chest X-ray (the lungs should be clear — infiltrates or haemorrhage point away from PAN); CT abdomen and pelvis for organomegaly, infarcts and haemorrhage; echocardiogram for cardiac involvement and to exclude endocarditis, the key mimic.[1]

The classic trap: a standard renal biopsy in suspected PAN. PAN lives at the renal hilum in the interlobar and arcuate arteries; a percutaneous biopsy samples the glomerulus, which PAN spares, and comes back normal or non-specific. Biopsy an involved organ you can reach — skin, nerve-muscle, testis — or go straight to angiography.[1][6]

The treatment fork — steroids versus antivirals

Treatment is stratified by HBV status and severity. The pivotal fork — and a favourite examiner question — is idiopathic versus HBV-associated: the former gets corticosteroids plus cyclophosphamide for severe disease; the latter gets antivirals and plasma exchange to clear HBV, not long-term immunosuppression.[1][2][6]

Idiopathic PAN

Corticosteroids are the cornerstone. Start oral prednisolone 1 mg/kg/day (maximum 60 to 80 mg) immediately for confirmed PAN; for severe or organ-threatening disease (severe mononeuritis multiplex, cardiac, gut, renal) begin with IV methylprednisolone 500 to 1000 mg daily for 3 days then convert to oral prednisolone 1 mg/kg/day. A rapid clinical and biochemical response — falling ESR and CRP, stabilising renal function, improving neuropathy — is characteristic.[1]

Add cyclophosphamide for severe disease. The French Vasculitis Study Group approach uses cyclophosphamide 15 mg/kg IV every 2 weeks for 6 doses (then every 3 weeks), or oral 2 mg/kg/day (maximum 200 mg/day) for 3 to 6 months, with dose reduction for age over 65 and for renal impairment. Indications: severe neuropathy, gut, cardiac, renal or CNS involvement, or steroid-refractory disease. After induction, switch to a safer maintenance agent.[1]

Maintenance and refractory disease. After cyclophosphamide induction use azathioprine 2 mg/kg/day or methotrexate 20 to 25 mg once weekly (with folate) for 18 to 24 months. Rituximab (375 mg per square metre weekly for 4 doses, or 1 g two weeks apart) is used in refractory, relapsing or cyclophosphamide-intolerant PAN; the evidence is extrapolated from AAV, but B-cell depletion is rational given the immune-complex pathogenesis.[1]

Steroid taper. Once remission is achieved (typically 4 to 8 weeks), taper slowly — about 10 percent every 1 to 2 weeks down to 20 mg, then 2.5 mg every 2 to 4 weeks to 10 mg, then 1 mg every 1 to 2 months — guided by symptoms, ESR and CRP, and organ function. The tapering window is 12 to 24 months.[1]

HBV-associated PAN

The principle is clearance of HBV with antivirals and plasma exchange, plus a short steroid course to dampen the early inflammatory phase — NOT long-term immunosuppression. The Guillevin and French Vasculitis Study Group regimen runs like this:[1][5]

• Antiviral therapy — entecavir 0.5 to 1.0 mg orally once daily (1 mg in decompensated liver disease or lamivudine resistance) or tenofovir disoproxil fumarate 300 mg once daily (or tenofovir alafenamide 25 mg once daily). These potent nucleoside or nucleotide analogues suppress HBV replication and clear the circulating complexes driving the vasculitis. Treat with hepatology.
• Plasma exchange (PLEX) — typically 3 exchanges per week for the first 2 to 3 weeks, then progressively less frequent (1 to 2 per week for several weeks), exchanging one plasma volume per session, replaced with 4 to 5 percent human albumin (fresh-frozen plasma for bleeding risk or pre-procedure). PLEX removes circulating HBV-antigen-antibody complexes and cryoglobulins.
• Short-course corticosteroids — prednisolone 1 mg/kg/day for 1 to 2 weeks to control early inflammation, then rapidly tapered and stopped as the antiviral and PLEX take effect. The aim is to avoid prolonged immunosuppression, which impairs HBV clearance.[1][5]

HBV-PAN is usually monophasic and rarely relapses once HBV is cleared; HBeAg seroconversion correlates with vasculitis remission. Universal HBV vaccination has made it uncommon in countries with infant programmes.[1]

The classic trap: HBV-PAN meets cyclophosphamide. Cyclophosphamide suppresses the immune response that is trying to clear HBV, so it prolongs viraemia and worsens the vasculitis. Always screen HBsAg before the first dose — the HBV-positive patient needs antivirals and plasma exchange, not a cytotoxic.[1]

Cutaneous-limited PAN

Skin-only PAN (livedo, nodules, ulcers, no systemic involvement) is treated with prednisolone 0.5 to 1 mg/kg/day tapered over weeks to months, with colchicine 0.6 mg twice daily, dapsone 50 to 100 mg/day (check G6PD first), or methotrexate as steroid-sparing agents for relapsing disease. Local wound care for ulcers and surveillance for systemic spread (clinical review, ESR and CRP, urinalysis) are essential.[1]

The resuscitation moves you cannot hesitate on

PAN rarely presents with the seconds-count emergency of an AAV pulmonary-renal syndrome — it spares the lungs and the glomerulus — but several life- or organ-threatening presentations need immediate inpatient care.[1][6]

• Mesenteric ischaemia with infarction or perforation — acute severe abdominal pain with peritonism, lactic acidosis, pneumatosis on imaging. Urgent surgical review, broad-spectrum antibiotics, fluid resuscitation, and laparotomy or laparoscopy for resection; immunosuppression is withheld or reduced peri-operatively.
• Malignant hypertension or hypertensive emergency (renovascular) — IV labetalol or nicardipine infusion to lower mean arterial pressure by no more than 25 percent in the first hour, then gradual control; monitor for end-organ damage.
• Severe mononeuritis multiplex with rapid functional loss (bilateral foot or wrist drop, falling function) — begin urgent high-dose corticosteroids (IV methylprednisolone pulses) to abort further nerve infarction.
• Microaneurysm rupture with renal, hepatic or mesenteric haemorrhage — resuscitation, transfusion, and interventional radiology for selective arterial embolisation.
• Fulminant HBV-PAN — expedite the diagnosis and begin antiviral therapy plus plasma exchange without delay.[1][6]

A supportive bundle applies across all of these: analgesia, fluid and electrolyte correction, gastric protection, Pneumocystis jirovecii prophylaxis (cotrimoxazole 480 mg or 960 mg daily, or an alternative if allergic) whenever high-dose steroids or cyclophosphamide are started, bone protection (calcium, vitamin D, bisphosphonate where indicated), and vaccination (influenza, pneumococcal, COVID-19, hepatitis B if non-immune — ideally before immunosuppression; avoid live vaccines during it).[1]

The labelling trap: MPA is not PAN. A patient with neuropathy plus renal disease is MPA, not PAN, the moment the urine is active or the ANCA is positive. Reach for rituximab or cyclophosphamide for pauci-immune disease — but the diagnosis must be right first, because PAN and MPA diverge on long-term strategy.[1][3]

The mimic that changes everything — DADA2

DADA2 (deficiency of adenosine deaminase 2) is a monogenic PAN-mimic that needs completely different drugs, and forgetting it is a named exam trap. Autosomal recessive loss-of-function mutations in ADA2 (CECR1) on chromosome 22q11 present in childhood with livedoid rash, PAN-like medium-vessel vasculitis, recurrent ischaemic and haemorrhagic strokes, immunodeficiency with recurrent infections, haematological disease (pure red cell aplasia, neutropenia), and hepatosplenomegaly.[7][8]

Treat DADA2 with anti-TNF (etanercept), NOT corticosteroids, and reserve haematopoietic stem cell transplant for severe haematological disease. Exclude DADA2 in any child, adolescent or young adult with PAN-like disease or unexplained stroke — the treatment is life-changing and steroids do not work.[7][8]

Everyone forgets: DADA2 in the young stroke patient. A teenager with livedo, PAN-like vasculitis and recurrent stroke is not idiopathic PAN — it is a single-gene disease, and the right drug is etanercept. Send ADA2 sequencing before the first cycle of cyclophosphamide.[7][8]

Other named subtypes and associations round out the shelf: hairy-cell-leukaemia-associated PAN (treat the leukaemia with cladribine and the vasculitis often remits); juvenile PAN (rare, weight-based dosing, exclude DADA2, minimise steroid exposure for growth and bone); and pregnancy (plan conception in remission, avoid cyclophosphamide, methotrexate and mycophenolate, use azathioprine maintenance, prednisolone at the lowest effective dose, multidisciplinary care).[1]

How patients die — disease and drugs

PAN's complications arise from end-organ ischaemia (the disease) and treatment toxicity (the drugs).[1][6]

Disease complications — mononeuritis multiplex with residual foot or wrist drop, sensory deficit and chronic neuropathic pain; mesenteric ischaemia, gut infarction and perforation (the leading cause of mortality in severe PAN); ischaemic pancreatitis; renovascular hypertension and chronic kidney disease (not glomerulonephritis); coronary arteritis, infarction and cardiac failure, especially in HBV-PAN; cerebral vasculitis and stroke; microaneurysm rupture with renal, hepatic or mesenteric haemorrhage; and digital gangrene needing amputation.[1][6]

Treatment complications — glucocorticoids (diabetes, osteoporosis, infection, hypertension, cataracts, adrenal suppression, mood change); cyclophosphamide (infection, haemorrhagic cystitis — maintain hydration, consider mesna — bone-marrow suppression, infertility with fertility preservation offered, late bladder and myelodysplastic malignancy); plasma exchange (catheter infection, hypotension, citrate-induced hypocalcaemia and bleeding, venous-access complications); and rituximab (infusion reactions, late-onset neutropenia, hypogammaglobulinaemia, HBV reactivation — screen and antiviral-prophylax).[1]

Supportive care that prevents harm — tight antihypertensive control for renovascular hypertension (ACE inhibitor or ARB with renal function and potassium monitoring, calcium-channel blocker); neuropathy rehabilitation with physiotherapy, ankle-foot orthosis for foot drop, and neuropathic agents (amitriptyline, gabapentin, pregabalin); PJP prophylaxis with cotrimoxazole 480 mg or 960 mg daily throughout high-dose steroids or cyclophosphamide; bone protection; gastric protection; vaccination; and monitoring with BVAS, ESR and CRP, renal function, blood pressure, and follow-up angiography in selected cases.[1]

Prognosis — the Five-Factor Score

Five-year survival is approximately 80 percent with modern treatment, against 13 percent untreated. Outcome is stratified by the Five-Factor Score (FFS, 2009 revision) — the prognostic instrument for the systemic necrotising vasculitides (PAN, MPA, GPA, EGPA).[4]

HBV-associated PAN is usually monophasic and rarely relapses once HBV is cleared, with HBeAg seroconversion correlating with remission. Idiopathic PAN can relapse and needs maintenance immunosuppression with long-term cardiovascular and renal surveillance — residual renovascular hypertension is common and an independent cardiovascular risk factor. Cutaneous-limited PAN has an excellent prognosis but relapses frequently.[1]

Disposition: admit for organ-threatening or suspected surgical disease (mesenteric ischaemia or perforation, severe neuropathy, malignant hypertension, microaneurysm rupture, fulminant HBV-PAN); manage stable disease as an outpatient under combined rheumatology, nephrology, neurology and hepatology (for HBV-PAN) care. Follow-up is lifelong for cardiovascular risk, renal surveillance and relapse detection.[1][4]

Special populations

• HBV-associated PAN — treat with antivirals plus plasma exchange plus short corticosteroids to clear HBV; engage hepatology early; now uncommon due to universal HBV vaccination.
• DADA2 (paediatric or young-adult PAN) — anti-TNF (etanercept), NOT steroids; HSCT for severe haematological disease; genetic counselling (autosomal recessive); screen siblings.
• Hairy cell leukaemia-associated PAN — treat the underlying malignancy (cladribine); the vasculitis often resolves with haematological remission.
• Pregnancy — plan conception during remission; avoid cyclophosphamide, methotrexate and mycophenolate (teratogenic); azathioprine maintenance; prednisolone at lowest effective dose; multidisciplinary maternal-foetal medicine and rheumatology care.
• Children (juvenile PAN) — rare; weight-based dosing; DADA2 must be excluded; growth, fertility and bone concerns with chronic steroids — minimise exposure.
• Elderly — more renal and mesenteric disease; poorer tolerance of cyclophosphamide and high-dose steroids; favour steroid-sparing strategies and lower thresholds for plasma exchange; age over 65 is an FFS point.
• Renal impairment — dose-adjust cyclophosphamide; rituximab dosing is unaffected by renal function; consider plasma exchange for severe disease.
• Immunosuppressed patients — screen for latent TB, HBV, HCV and HIV before induction; antiviral prophylaxis for HBsAg-positive or anti-HBc-positive patients throughout therapy and for 12 months after rituximab; PJP prophylaxis; vaccinate (avoid live vaccines).[1][7][8]

Evidence, guidelines, regional notes

The guidelines that govern PAN management. The 2022 EULAR recommendations for primary medium- and small-vessel vasculitis and the 2021 ACR and Vasculitis Foundation classification criteria are the contemporary reference standards. The French Vasculitis Study Group algorithms underpin the FFS stratification and the HBV-PAN regimen. HBV vaccination is the single most effective public-health measure against HBV-PAN — its prevalence has fallen dramatically wherever universal infant vaccination runs.[1][2]

The PAN run-down

The mantra: medium muscular arteries, bland urine, no ANCA, lungs spared — and screen HBsAg before you touch the cyclophosphamide.[1][2]

Consultant confession: the first time a registrar showed me foot drop, haematuria and a positive MPO-ANCA labelled as PAN with renal involvement, I learned that the urine had already told the whole story. It was MPA. The medium-vessel versus small-vessel split is the one question that separates the right drug from the wrong one — and the dipstick answers it for free.[1][5]

Ward-round test — four stems, a minute each