Page 224 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

200 Loic Guillevin

Introduction

In 1852, Carl von Rokitansky, Professor of Pathology at the University of Vienna
described polyarteritis nodosa (PAN) in a 23-year-old man with a 5-day history of fever and
diarrhea [1]; Küssmaul and Maier [2] rediscovered the disorder in 1866. Within decades,
PAN was one of the most frequent vasculitides which became progressively less common in
developed countries as a consequence of the eradication and treatment of one of its most
frequent causes [3], hepatitis B virus (HBV) infection. This chapter reviews the classification
criteria, epidemiology, main clinicopathologic features, etiopathogenesis, treatment and
outcome of PAN.

Classification and Diagnostic Criteria

In 1990, the American College of Rheumatology (ACR) (Table 1) established criteria for
the classification of PAN [4], and although frequently cited, it did not distinguish between
PAN and microscopic polyangiitis (MPA). These two disorders were initially considered
different forms of the same disease because of similar main clinical manifestations. However
the two entities were clearly distinguished by the 2012 Revised Chapel Hill Consensus
Conference (CHCC) Nomenclature [5], defining PAN as a necrotizing arteritis of medium- or
small-sized arteries without glomerulonephritis, vasculitis in arterioles, capillaries or venules;
and absent anti-neutrophil cytoplasmic antibodies (ANCA). While both disorders involve the
kidneys such as glomerulonephritis in MPA and vascular nephropathy in PAN, the former is
associated lung capillaritis while the latter has at most subclinical lung involvement.
Moreover, the two disorders may be difficult to discern when nephropathy and lung
capillaritis are absent, and especially when tissue biopsy does not distinguish involved vessel
types or size. The 2012 Revised CHCC Nomenclature classifies PAN in the category of
medium-sized vessel vasculitis (MVV), and vasculitis associated with a probable etiology
when associated with HBV infection. ANCA serology, so noted in the majority of patients
with MPA and other small-sized–vessel vasculitides (SVV) including granulomatosis with
polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA), is virtually
never detected in PAN. Accordingly, a positive ANCA serology excludes the diagnosis in a
given patient. Table 2 lists clinical criteria useful in the diagnosis of PAN [6].

Epidemiology

PAN affects all racial and ethnic groups with an estimated annual incidence in the general
population 4.6 per 1,000,000 inhabitants in England [7], to 9.0 per 1,000,000 inhabitants in
Olmsted County, Minnesota, to 77 per 1,000,000 inhabitants in a hepatitis B-hyperendemic
Alaskan Eskimo population [8]. In a German study [9], the incidence of PAN was 0.3 to 0.4
per 1,000,000 inhabitants depending on the year and part of the country. A comparison of the
incidence of PAN among two European areas of Lugo, Spain, and Norwich, United Kingdom
(UK) found insignificant incidence differences of 6.2 and 9.7 and 1,000,000 inhabitants [10,

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