Polyarteritis nodosa



Introduction
Epidemiology
Pathophysiology
Clinical features
Investigations
Differential diagnosis
Management
Complications


Introduction

Polyarteritis nodosa (PAN) is a vasculitis affecting medium-sized arteries with necrotizing inflammation leading to aneurysm formation. PAN is more common in middle-aged men and is associated with hepatitis B infection.

Epidemiology

  • Incidence: 3.00 cases per 100,000 person-years
  • Peak incidence: 40-50 years
  • Sex ratio: 1:1
Condition Relative
incidence
Infective endocarditis1.67
Polyarteritis nodosa1
Granulomatosis with polyangiitis0.33
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Pathophysiology

There are different subsets of PAN when it comes to the pathophysiology of the disease.
  • Some subsets, including hepatitis B-associated PAN, have the role of immune complexes, although the mechanism, by which these immune complexes affect vessels, is unknown.
  • In other subsets, immune complexes play a lesser role in pathogenesis of the disease.

The inflammation of vessel leads to intimal thickening and weakening of vessels, causing aneurysm formation, which can cause significant bleeding (e.g., rectal bleeding).

The intimal thickening and narrowing can also cause infarctions in various organs, the most commonly involved organ is kidney.

Clinical features

Features
  • fever, malaise, arthralgia
  • weight loss
  • hypertension
  • mononeuritis multiplex, sensorimotor polyneuropathy
  • testicular pain
  • livedo reticularis
  • haematuria, renal failure
  • perinuclear-antineutrophil cytoplasmic antibodies (ANCA) are found in around 20% of patients with 'classic' PAN
  • hepatitis B serology positive in 30% of patients

© Image used on license from DermNet NZ
Livedo reticularis

Investigations

Various tests can be performed to diagnose or to ascertain the extent of polyarteritis nodosa (PAN):
  • Laboratory testing: There is no diagnostic laboratory test for PAN. Basic laboratory tests help ascertain the extent of involvement of different organs. They include:
    • Liver function tests
    • Hepatitis B and C serologies
    • Creatinine kinase
    • Serum creatinine
    • Urine analysis
    • Acute phase proteins (ESR and C reactive protein are significantly elevated, though they are neither sensitive nor specific for the diagnosis)
  • Chest radiography may be obtained to exclude other forms of vasculitis, which have greater involvement in the lungs.
  • Biopsy is performed on a clinically affected organ to confirm the diagnosis.
  • Imaging:
    • Arteriography (mesenteric or renal) can be used as an alternative to biopsy to confirm the diagnosis (to minimise bleeding risk). It can reveal aneurysms and irregular constrictions in the vessels.
    • Computed tomography/Magnetic resonance imaging can demonstrate wedge shaped renal infarctions, which are less specific than microaneurysms showed on arteriography.

Differential diagnosis

PAN is a multisystemic illness, and hence various diseases can be considered in differentials for PAN. They include infectious processes as well as other forms of vasculitis.
  • Infectious causes include HBV and HCV, which can also cause secondary PAN that can be differentiated on biopsy.
    • Fever, murmur, or associated weight loss can also be caused by infective endocarditis, which should be subsequently ruled out by blood cultures and echocardiogram.
  • Atherosclerosis can also cause infarctions in various organs, causing similar symptoms, with similar age of onset as PAN. They can be both differentiated on histology.
  • Hypercoagulable states
    • Antiphospholipid syndrome may present with a history of multiple abortions, although uterine involvement may also be seen with PAN in some patients.
    • Purpuric lesions can mimic those of thrombotic thrombocytopenic purpura
  • Vasospastic disorders
  • Other multisystem inflammatory disorders
    • Sarcoidosis, also a multisystemic illness and a diagnosis of exclusion
  • Malignancy
    • Lymphoma and leukaemia can be diagnosed with bone marrow biopsy.

Management

The treatment of polyarteritis nodosa (PAN) depends on the severity of illness:
  • Mild disease with constitutional symptoms but no end-organ damage:
    • Oral prednisone (1mg/kg body weight).
  • Mild disease but resistant to or intolerant to of required dose of glucocorticoids:
    • Addition of azathioprine or methotrexate to a tolerable dose of glucocorticoids. Methotrexate should be avoided in patients with renal disease or hepatitis.
  • Moderate to severe disease, with evidence of end-organ damage:
    • High-dose glucocorticoids and cyclophosphamide, followed by azathioprine or methotrexate for remission maintenance.
  • In patients with mild PAN and associated hepatitis B or C infection, it is advised to treat initially with antivirals only, and not to give any immunosuppressants. However, patients with severe hepatitis virus-associated PAN may be benefited from short term glucocorticoids or plasma exchange until antiviral therapy becomes effective.

Complications

Clinical manifestations of PAN, in the order of decreasing frequency, include:
  • Systemic symptoms
  • Neuropathy
    • Mononeuritis multiplex, polyneuropathy
  • Arthralgias and/or myalgias
  • Cutaneous
    • Livedo reticularis, purpura, ulcers
  • Renal disease
    • Elevated creatinine, hematuria, glomerulonephritis
  • Gastrointestinal symptoms
  • New-onset hypertension
  • Respiratory manifestations
  • Stroke
  • Cardiomyopathy, pericarditis
  • Peripheral vascular disease
    • Claudication, ischemia, necrosis

Here are important things to keep in mind regarding the morbidity and mortality of PAN.
  • There is a substantial rate of relapse with PAN, which requires monitoring disease for an indefinite period.
  • Untreated PAN has a five-year survival rate of 13% as compared to 80% in the case of treated PAN.
  • HBV-associated PAN has a poorer prognosis than non-HBV-associated PAN.
  • Major causes of death include renal failure and mesenteric, cardiac and cerebral infarctions. Aneurysms can cause life-threatening bleeding.