Polyarteritis Nodosa

Description

Polyarteritis nodosa (PAN) is a systemic necrotising inflammation of small and medium-sized arteries that spares the smallest blood vessels such as arterioles, venules, and capillaries. It typically leads to aneurysm formation and consequent rupture, leading to organ infarction or haemorrhage.

Pathogenesis

The pathogenesis of PAN is not entirely clear, but it involves an inflammatory response in the walls of affected arteries. This response leads to the destruction of the arterial wall, causing aneurysm formation, vessel occlusion, and subsequent ischaemia in the supplied tissues. Though not yet entirely understood, PAN is thought to involve an aberrant immune response.

It most commonly affects vessels of the mesentery, pancreas, and testes, but lesions may also occur in the hepatic, coronary, uterine, cerebral, adrenal, and renal arteries. It does not usually involve the lung.

Epidemiology, Risk Factors & Associations

• PAN is a rare disease with a prevalence estimated to be around 31 cases per million.
• Seen in people of European descent.
• Incidence increases with age, peaking in the 5th-6th decade of life.
• Men are more affected than women, with a male-to-female ratio of 2:1.
• Associated with Hepatitis B infection (30% of HBV patients), with a notable percentage of PAN cases (~10%) having an active or recent Hepatitis B infection.

Clinical Features

Typically, the onset of PAN is insidious, with initial symptoms being nonspecific, such as malaise, weight loss, and fever. May present with Lenk’s triad of acute flank pain, flank mass, and hypovolemic shock. As the disease progresses, symptoms reflect the organs supplied by the affected arteries:

• Renal involvement: Presents in 60-70% of patients, typically manifesting as hypertension and renal impairment
• Neurological involvement: Occurs in up to 70% of cases, presenting as mononeuritis multiplex, stroke, or other neurological issues
• Gastrointestinal involvement: Occurs in approximately half of the patients, with symptoms including abdominal pain, gastrointestinal bleeding, and perforation
• Musculoskeletal involvement: Myalgia and arthralgia can occur but are less common manifestations.

Complications

• Organ infarction
• Aneurysm rupture leading to haemorrhage
• Organ failure
• Spontaneous subcapsular or perirenal hemorrhage (Wunderlich Syndrome): Majority of cases due to neoplasm (angiomyolipoma or renal cell carcinoma), with PAN being the third most common cause.

Pathological Features

Histopathology

• Frequently causes destruction of the media and internal elastic lamina
• Fibrinoid necrosis with polymorphonuclear infiltration.
• Segmental transmural necrotising inflammation with leukocytoclastic vasculitis.
• Fibrous thickening of the arterial wall.
• Lumen stenosis and aneurysmal dilation.

Serology

• Not typically associated with P-ANCA (Perinuclear Anti-Neutrophil Cytoplasmic Antibodies) unlike other small-vessel vasculitides – although may be present in a minority of cases.

Radiological Features

General Features

• Angiography is the key imaging technique for PAN.
• Microaneurysms are the most characteristic angiographic feature.
• Renal artery involvement may be seen as multiple small aneurysms and areas of stenosis.
• Aneurysms can occur at bifurcation points in the arteries.

Kidneys

• Microaneurysms (2 – 5 mm) of interlobar or arcuate renal arteries most common
• Spontaneous perirenal or subcapsular hemorrhage
• Striated nephrogram and renal infarcts

Grading and Staging

There is no specific grading and staging system for PAN. The Birmingham Vasculitis Activity Score (BVAS) is a validated tool used for assessing disease activity in systemic vasculitides including PAN.

Differential Diagnosis

• Microscopic polyangiitis: Involves small vessels (arterioles, venules, capillaries) in addition to medium-sized arteries, and is typically P-ANCA positive.
• Granulomatosis with polyangiitis: Typically PR3-ANCA positive, and involves the respiratory tract with granuloma formation. Most common renal manifestation is glomerulonephritis. Rare: Solitary or multiple renal pseudotumor, ureter stricture, prostatitis, epididymoorchitis
• Churg-Strauss syndrome: Associated with asthma and eosinophilia.
• Takayasu arteritis: Rare stenosis, wall thickening of renal artery. Predominantly women < 40 years of Asian descent.

Management

• High-dose corticosteroids are the initial treatment for inducing remission in PAN.
• Immunosuppressive agents such as cyclophosphamide are used in severe disease or if the patient fails to respond to steroids.
• For PAN associated with Hepatitis B, antiviral therapy should be added.
• Plasma exchange might be used for severe or refractory cases.

This disease is a medical emergency and requires immediate attention. Early diagnosis and treatment are crucial in improving survival rates. It should be managed by a rheumatologist or immunologist, often in conjunction with other specialists depending on the organs involved.