A 62-year-old woman from Mumbai with a 6-month history of progressive dyspnea, orthopnea, and lower-limb edema presents to the hospital. She reports a 2-month prodrome of fever, arthralgias, and weight loss. On examination, blood pressure is 148/92 mmHg, JVP is elevated, and she has a palpable nodule over the right ulnar nerve. Laboratory findings: ESR 95 mm/h, CRP 18 mg/dL, hemoglobin 9.2 g/dL, serum creatinine 2.1 mg/dL, and urinalysis shows proteinuria (3.5 g/24 h) with dysmorphic RBCs. Serum hepatitis B surface antigen is positive. Echocardiography reveals a dilated right ventricle with moderate tricuspid regurgitation. What is the most likely diagnosis?

Explanation

## Diagnosis: Polyarteritis Nodosa (PAN) ### Clinical Presentation Alignment **Key Point:** Polyarteritis nodosa is a medium-vessel vasculitis that classically presents with systemic inflammation, peripheral neuropathy, renal disease, and hepatitis B association. The patient's presentation is characteristic of PAN: - **Systemic inflammation:** fever, weight loss, elevated ESR/CRP - **Peripheral neuropathy:** palpable nodule over ulnar nerve indicates mononeuritis multiplex (vasculitis of vasa nervorum) - **Renal involvement:** proteinuria and dysmorphic RBCs from renal artery vasculitis and infarction (NOT glomerulonephritis) - **Cardiac involvement:** right heart failure with tricuspid regurgitation from pulmonary artery involvement or secondary pulmonary hypertension - **Hepatitis B seropositivity:** present in 5–10% of PAN cases; HBsAg-positive PAN has worse prognosis - **Anemia:** from chronic inflammation and possible GI bleeding (PAN causes mesenteric vasculitis) ### Pathophysiology of Medium-Vessel Vasculitis ```mermaid flowchart TD A[Polyarteritis Nodosa]:::outcome --> B[Medium-vessel vasculitis] B --> C[Necrotizing inflammation<br/>of muscular arteries] C --> D[Segmental involvement<br/>with sparing] D --> E[Peripheral nerves<br/>mononeuritis multiplex] D --> F[Renal arteries<br/>infarction, NOT GN] D --> G[Coronary arteries<br/>aneurysm, MI] D --> H[Mesenteric arteries<br/>ischemia, perforation] E --> I[Palpable nodules<br/>along nerves] F --> J[Proteinuria,<br/>hematuria] ``` ### Distinguishing Features of PAN | Feature | PAN | MPA | GPA | EGPA | |---------|-----|-----|-----|------| | **Vessel size** | Medium | Small | Small–medium | Small | | **Glomerulonephritis** | NO (renal infarction) | YES (pauci-immune) | YES (pauci-immune) | YES (IgA) | | **Pulmonary involvement** | NO | YES (alveolar hemorrhage) | YES (nodules, hemorrhage) | YES (asthma, infiltrates) | | **Mononeuritis multiplex** | YES (classic) | Rare | Rare | Rare | | **Hepatitis B** | 5–10% | NO | NO | NO | | **ANCA** | Negative | MPO-ANCA+ | PR3-ANCA+ | MPO-ANCA+ | | **Renal biopsy** | Arterial necrosis | Pauci-immune GN | Pauci-immune GN | IgA GN | **High-Yield:** PAN spares the lungs and glomeruli (no primary GN); renal involvement is from renal artery vasculitis causing infarction, not immune complex deposition. ### Diagnosis - **Angiography:** "beads-on-string" appearance from alternating stenosis and aneurysm of medium arteries (hepatic, renal, mesenteric) - **Nerve/muscle biopsy:** vasculitis of vasa nervorum - **Serology:** ANCA negative (distinguishes from ANCA-associated vasculitides) - **Hepatitis B serology:** positive in subset; HBsAg-positive PAN requires antiviral therapy **Clinical Pearl:** Mononeuritis multiplex (asymmetric peripheral neuropathy affecting individual nerves) is a hallmark of PAN and distinguishes it from other vasculitides, which typically cause symmetric polyneuropathy or no neuropathy. ### Management - **Corticosteroids:** prednisolone 1 mg/kg/day - **Immunosuppression:** cyclophosphamide or azathioprine for severe disease - **HBsAg-positive PAN:** add lamivudine or other antivirals - **Prognosis:** 5-year survival ~80% with treatment; worse in HBsAg-positive cases [cite:Robbins 10e Ch 11]