Page 45 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

Overview of Primary and Secondary Vasculitides 21

Reproduced from reference [4], with permission.

Figure 2. This small muscular artery from muscle is from a patient with polyarteritis nodosa. In the
third, or proliferative, phase illustrated here, chronic inflammatory cells replace the neutrophils of the
second phase; there is evidence of necrosis of the media (arrows), early intimal proliferation
(arrowheads), and fibrosis. The lumen is almost completely occluded. Ultimately, in the healing phase,
this process is replaced by dense, organized connective tissue (stain, hematoxylin and eosin; original
magnification, ×250).

The classification criteria for cPAN requires histological evidence of necrotizing
vasculitis in medium-or small-sized arteries or angiographic abnormalities demonstrating
aneurysm formation or vascular occlusions, as a mandatory criterion, plus two of five features
among them myalgia, skin involvement, hypertension, neuropathy, or abnormal urinalysis or
impaired renal function [6], with disease manifestations ranging from a benign cutaneous
form with clinical, laboratory and molecular characteristics of Familial Mediterranean Fever
[27, 28] to severe disseminated multisystem disease. Ozen and colleagues [29] studied 110
children of mean age 9 years, from twenty-one pediatric centers worldwide diagnosed with
cPAN dividing them into four groups including systemic PAN (57%), cutaneous PAN (30%),
and classic PAN with hepatitis B surface antigen (HBsAg) (4.6%). Children with serological
and microbiologic evidence of preceding streptococcal infection have also been described
[30]. The FVSG study [26] allowed for a comparison of diagnostic modalities in adult PAN.

Only 6 of 47 sera so tested manifested a positive ANCA finding by immunofluourescent
testing (IFT) and enzyme linked immunosorbant assay (ELISA) techniques, rendering it
helpful in support of PAN especially when negative to differentiate it from AAV and MPA.
Cutaneous nerve biopsy performed in 129 patients, including 108 with peripheral neuropathy
and 21 without peripheral neuropathy, showed typical vasculitic lesions respectively in 83%
and 81%, compared to muscle biopsy that revealed vasculitis respectively in 68% and 60% of
patients. Angiography showed renal and gastrointestinal microaneurysms or stenosis
respectively in 66% and 57% of patients. Patients with HB virus (HBV)-related PAN had
more frequent peripheral neuropathy, abdominal pain, cardiomyopathy, orchitis, and
hypertension than those with non-HBV-related PAN, with respective five-year relapse-free
survival rates of 59% and 67% in scheduled therapeutic regimens depending upon
involvement in clinical trials, or according to the standard of care at the time of diagnosis,
among them glucocorticoids and cyclophosphamide [31, 32]. The predictors of a poor
prognosis were age >65 years, hypertension, and gastrointestinal involvement, and cutaneous
manifestations or non-HBV-related PAN had higher rates of relapse.

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