- 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.
- fever, malaise, arthralgia
- weight loss
- 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
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- 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.
- 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.
- Infectious causes include HBV and HCV, which can also cause secondary PAN that can be differentiated on biopsy.
- 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
- Lymphoma and leukaemia can be diagnosed with bone marrow biopsy.
- 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.
- Systemic symptoms
- Mononeuritis multiplex, polyneuropathy
- Arthralgias and/or myalgias
- Livedo reticularis, purpura, ulcers
- Renal disease
- Elevated creatinine, hematuria, glomerulonephritis
- Gastrointestinal symptoms
- Abdominal pain, rectal bleeding
- New-onset hypertension
- Respiratory manifestations
- 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.