Polyarteritis Nodosa Workup

Updated: Jan 12, 2016
  • Author: Dana Jacobs-Kosmin, MD, FACP; Chief Editor: Herbert S Diamond, MD  more...
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Workup

Approach Considerations

Evidence of peripheral neuropathy should be sought carefully with history and electromyography (EMG), since it is a common complication of polyarteritis nodosa (PAN), being found in as many as 60% of patients. Mononeuritis multiplex is the most common form of PAN neuropathy, but other forms can be present.

Many neurologic and systemic disorders can present with headache. Pathologic headaches are often difficult to differentiate from benign headaches solely on clinical grounds. Severe, persistent headaches, with or without neurologic deficit, warrant complete neurologic evaluation, including brain-imaging studies.

Even though stroke is a late complication in many cases of PAN, it certainly can occur early. PAN and other vasculitic diseases should be considered in many patients with stroke with multiple foci or a combination of hemorrhage and infarction.

Electroencephalography (EEG) may show nonspecific findings of generalized slow wave activity during periods of encephalopathy or toxic delirium.

Laboratory studies

Laboratory findings in PAN are nonspecific but can help to establish the systemic nature of the disease. Findings include the following:

  • Elevated erythrocyte sedimentation rate (ESR) and/or C-reactive protein - These markers may be useful in evaluating some patients for active disease but do not correlate with activity in all patients [5]
  • Leukocytosis, normochromic anemia, or thrombocytosis
  • Hepatitis B surface antigen and hepatitic C serologies
  • Elevated creatinine level
  • Mild proteinuria
  • Elevated levels of liver enzymes
  • Hypergammaglobulinemia - Found in 30% of patients with PAN

Cryoglobulins, circulating immune complexes, and decreased levels of serum complement (ie, C3, C4) may be observed in patients with HBV-related PAN but are otherwise uncharacteristic of idiopathic PAN.

Cerebrospinal fluid findings often are usually normal in PAN, but polymorphonuclear pleocytosis can be seen when meningeal signs are present.

ANCA testing is rarely positive in PAN. If ANCA testing is positive, the tests more commonly show a perinuclear (rather than cytoplasmic) pattern and antibodies to proteinase-3 and myeloperoxidase will be negative. [5] Antinuclear antibodies and rheumatoid factor are generally negative, but low positive titers may be detected. [5]

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Imaging Studies

Angiography

Angiography should be considered if clinically involved tissue is inaccessible. Conventional angiography is preferred. Computed tomography angiography or magnetic resonance angiography are not as sensitive for smaller abnormalities but can reveal larger aneurysms and stenoses. [17, 47]

Positive findings include aneurysms and stenoses of medium-sized vessels. (Note that these findings are not pathognomonic for PAN but rarely occur in MPA). [17]

Aneurysms are most commonly found in the kidney, liver, and mesenteric arteries, and their presence is associated with more severe and extensive disease.

Angiography has a higher yield in cases with evidence of intra-abdominal involvement, including clinical symptoms or signs and laboratory abnormalities of liver or renal function.

For images and discussion, see Imaging in Polyarteritis Nodosa

Other studies

Arteriograms reveal microaneurysms in the small- and medium-sized arteries of the kidneys and abdominal viscera.

Computed tomography (CT) scanning and magnetic resonance imaging (MRI) of the GI tract may show nonspecific abnormal findings, including bowel wall thickening, mesenteric vascular engorgement, ascites, bowel obstruction, or diffuse mucosal fold thickening. For PAN with CNS involvement, new techniques, including susceptibility for blood, diffusion, and perfusion-weighted images, make MRI a very powerful modality for differentiating intracranial hemorrhage from potentially reversible ischemia (since PAN lesions are typically irreversible and progressive).

Electromyography (EMG) and nerve conduction studies (NCS) can be useful in revealing axonal nerve involvement and identifying asymmetry in nerve involvement. EMG/NCS can be used to guide a nerve biopsy, if necessary. [17, 40]

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Biopsy

When possible, a biopsy sample of involved, accessible tissue should be collected to aid in the diagnosis. The most accessible tissue sites for biopsy include the skin, sural nerve, testes, and skeletal muscle. The results of a retrospective study suggest muscle biopsy may be helpful for the diagnosis of systemic vasculitides, even in the absence of myalgias or creatine kinase level elevation. [48] Kidney biopsy carries a risk of aneurysmal rupture and bleeding.

Biopsies should be performed correctly to allow for adequate sampling of medium-sized arteries. Biopsy samples of skin nodules or ulcers should be collected at the edges and include deep dermis and subcutaneous fat. [5] In addition, nearby central ulcer areas, including subcutaneous tissue, should be included to increase diagnostic yield. [49]

Biopsy of small arteries from the abdominal viscera in conjunction with arteriography facilitates identification of the vasculitis.

Combined nerve and muscle biopsy is preferred. Biopsy of the sural nerve should be full-thickness to include epineural vessels. [40]

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Histologic Findings

Histology reveals a focal necrotizing arteritis of generally mixed cellular infiltrate within the vessel wall. Nerve biopsy characteristically reveals axonal degeneration and fiber loss. Segmental demyelination may also be seen. [40]

When an inflammatory infiltrate is present around a vessel wall without necrotizing changes, features on nerve biopsy that strongly suggest angiopathic nerve injury include Wallerian degeneration and fiber loss in part of a fascicle, perineural necrosis, and neoangiogenesis around the epineurium or perineurium. [40] An occlusion of a muscular artery and leukocytic infiltrate is seen in the slide below.

Polyarteritis nodosa (PAN) is characterized by fib Polyarteritis nodosa (PAN) is characterized by fibrinoid necrosis of the arterial wall with a leukocytic infiltrate. In this slide, a large, pale occlusion of a muscular artery can be seen. Within this collagenous tissue is a leukocytic infiltrate, which is the hallmark of PAN. Courtesy of Urbana Atlas of Pathology.

Despite a general recommendation to avoid kidney biopsy owing to a risk of aneurysmal rupture and bleeding, renal biopsy abnormalities in PAN patients have been described. Biopsies from 15 patients with PAN with no or mild renal involvement at study entry only showed abnormalities in one patient. This patient, with HBV-related PAN, had renal vasculitis and membranoproliferative glomerulonephritis (MPGN). [50]

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Staging

The Birmingham Vasculitis Activity Score and disease extent index have been validated to assess the level of disease activity in children with vasculitis, including PAN. [51]

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