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Polyarteritis Nodosa (PAN)

BASICS

  • Definition: ANCA-negative necrotizing arteritis of medium-sized muscular arteries (occasionally small arteries). Arterioles, capillaries, and venules are spared.
  • Involved Systems: GI, peripheral and central nervous system, genitourinary, skin, cardiovascular. Rarely glomerulonephritis or pulmonary capillaritis.
  • Clinical Presentation: Depends on organ involvement—mesenteric ischemia, hypertension, mononeuritis multiplex, skin lesions (purpura, nodules, livedo reticularis), and more.
  • Renal Involvement: HTN, mild proteinuria with/without azotemia.
  • Subtypes: Classic (idiopathic/generalized) PAN, HBV-associated PAN, Cutaneous PAN (limited to skin), Microscopic polyangiitis now considered separate/ANCA-associated.

EPIDEMIOLOGY

  • Incidence: 0–1.6 per million per year; rare
  • Prevalence: Up to 31 cases/million
  • Age: Mean diagnosis at 50 years; increases with age
  • Sex: Male predominance

ETIOLOGY & PATHOPHYSIOLOGY

  • Pathology: Segmental, transmural necrotizing inflammation of medium/small arteries → intimal proliferation, thrombosis, ischemia, aneurysm formation (especially at vessel bifurcations).
  • HBV-associated PAN: Immune complex deposition and complement activation from hepatitis B viral antigens.
  • Idiopathic cases: Most are idiopathic, ~20% linked to hepatitis B/C.
  • Genetics: ADA2 mutations in familial PAN.
  • Cutaneous PAN: Usually benign, skin-limited.

RISK FACTORS

  • Infection: Hepatitis B (strongly with classic PAN), hepatitis C (less with cutaneous PAN)
  • Others: Hairy cell leukemia, medications (minocycline, amphetamines, interferon), rare after HBV vaccination, CMV infection

ASSOCIATED CONDITIONS

  • Hepatitis B (classic PAN)
  • Hepatitis C (cutaneous PAN)
  • Hairy cell leukemia

DIAGNOSIS

  • No formal criteria—diagnosis is clinical with confirmatory biopsy/angiography.
  • Suspect PAN with:
  • Acute/fulminant multisystem disease
  • Vasculitic skin rash + neuropathy
  • Recent-onset HTN with systemic symptoms
  • Unexplained neuropathy with systemic symptoms
  • Hepatitis B + multisystem disease

History

  • Constitutional: fever, weight loss, malaise
  • Myalgia/arthralgia, focal weakness/numbness, GI (abdominal pain, bleeding), rash, altered mental status, testicular pain

Physical Exam

  • Neuro: Mononeuritis multiplex, peripheral neuropathy
  • Renal: Hypertension
  • Skin: Purpura, urticaria, nodules, livedo, ulcers, Raynaud (rare)
  • GI: Acute abdomen, rebound/guarding
  • CNS: Seizures, altered mental status
  • Cardiac: CHF, MI, S3, pericarditis (rare)
  • GU: Testicular/epididymal tenderness
  • Musculoskeletal: Arthritis (lower extremity large joints)

Differential Diagnosis

  • Other vasculitides: GPA, MPA, Churg-Strauss (EGPA), HSP, SLE, Goodpasture, drug-induced
  • Buerger disease, embolic/thrombotic disease, Ehlers-Danlos, infections

Diagnostic Tests & Interpretation

  • Labs:
  • Nonspecific: ↑ ESR/CRP, anemia of chronic disease, thrombocytosis, mild proteinuria, ↑ creatinine/BUN
  • Serology: Hepatitis B surface Ag (+ in 10–50%), hepatitis C Ab/RNA, ANCA/anti-PR3/anti-MPO (negative in classic PAN), rheumatoid factor may be +
  • Urinalysis: Proteinuria/hematuria, but no active sediment/cellular casts
  • ANA, cryoglobulins, complement levels
  • Imaging:
  • Angiography (CT/MR): Microaneurysms, beading at vessel bifurcations
  • Biopsy: Necrotizing inflammation with fibrinoid necrosis of medium/small arteries, segmental, often at bifurcations. No granulomas; veins/pulmonary arteries are spared.
  • Electrodiagnostics: For neuropathy; sural nerve or skin biopsy (edges of ulcer, deep dermis/SC fat) may help

TREATMENT

General Measures

  • Aggressive HTN control to prevent end-organ damage

Medication

  • Severe/Life-Threatening:
  • High-dose steroids (prednisone 1 mg/kg/day, or IV methylprednisolone 0.5–1 g/day × 3 days → PO prednisone with slow taper)
  • PLUS IV cyclophosphamide (0.6 g/m2 every 2 wks × 3, then monthly for 4–12 mo)
  • Plasma exchange considered for severe, refractory, or rapidly progressive disease
  • Less Severe:
  • Steroids alone ± azathioprine, methotrexate, mycophenolate mofetil, or hydroxychloroquine
  • Cutaneous PAN: NSAIDs, dapsone, colchicine
  • HBV-PAN: Antivirals, short-term steroids, plasma exchange
  • Refractory: Tocilizumab, infliximab, rituximab (anecdotal)
  • DADA2-associated: TNF inhibitors

Other Therapies

  • Prophylaxis for Pneumocystis jiroveci in patients on cyclophosphamide (TMP-SMX preferred)

COMPLEMENTARY/ALTERNATIVE

  • Physical therapy for neuropathy/muscle involvement

ONGOING CARE

  • Follow-Up: Monitor for relapse (clinical, labs: CBC, creatinine, UA, ESR/CRP)
  • Imaging: Repeat vascular imaging if GI involvement and now asymptomatic
  • Monitor for: Immunosuppressant complications (bladder malignancy, osteoporosis, infection)
  • Scoring: Five Factor Score (FFS) to predict mortality/guide therapy (age, renal insufficiency, cardiac/GI involvement)

DIET

  • Low-salt (for HTN)
  • Mediterranean diet (cardiovascular protection)
  • Calcium/vitamin D for patients on steroids

PROGNOSIS

  • Untreated: Poor
  • Treated: 5-year survival 75–80% with immunosuppression
  • Poorer prognosis: proteinuria, renal/GI/CNS/cardiac involvement, age >65

ICD-10

  • M30.0 Polyarteritis nodosa
  • M30.1 Polyarteritis with lung involvement [Churg-Strauss]
  • M30.8 Other conditions related to polyarteritis nodosa

CLINICAL PEARLS

  • PAN: Necrotizing vasculitis of medium/small arteries, spares veins and pulmonary arteries, no granulomas.
  • Clinical features depend on target organ(s) involved.
  • Always check hepatitis B and C serologies.
  • Classic PAN: ANCA-negative.
  • Biopsy: Deep dermis/SC fat at ulcer edges yields best results.
  • Revised Five Factor Score (FFS) helps guide prognosis and therapy.
  • Immunosuppression is mainstay of treatment; choice depends on disease extent/severity.