Childhood Polyarteritis Nodosa

Childhood polyarteritis nodosa (CPAN) is a rare and often fatal disease that affects small and medium arteries. Previously, it had been referred to as infantile polyarteritis nodosa (IPAN). The use of the term infantile is too restrictive, as infancy connotes age 1 year or younger. Polyarteritis has been described worldwide, although vasculitic diseases tend to be more common in individuals of Asian descent.

Clinically, CPAN often is part of the spectrum of Kawasaki disease (KD). However, it was described nearly 130 years ago. CPAN with aneurysmal involvement of major coronary arteries and KD are clinically and pathologically indistinguishable. Indeed, the major distinction between KD and CPAN is that the diagnosis of KD is based entirely on clinical criteria, while the diagnosis of CPAN is based on histologic findings. This article explores the similarities and differences between these entities with the focus on the current understanding of CPAN.

The Viennese pathologist Karl von Rokitansky is credited with the first description of polyarteritis nodosa (PAN) in 1852. The drawing that accompanied his original description of PAN clearly showed multiple aneurysms of varying size in the mesenteric artery of the index case. In 1866, Kussmaul and Maier reported the case of a 27-year-old man who, over a period of approximately 2 months, developed a multisystem disease characterized by fever, myalgias, abdominal pain, mononeuritis multiplex, and proteinuria. A few days before his death he developed palpable subcutaneous nodules. At autopsy, nodules involving the coronary, gastric, renal, splenic, mesenteric, hepatic, bronchial, and phrenic arteries were obvious.

Microscopic studies demonstrated that the intima of the affected arteries was completely intact and that the media and adventitia were severely inflamed and disrupted. For these reasons, Kussmaul and Maier termed this condition periarteritis nodosa. Their paper included a drawing of their patient's heart showing numerous coronary artery aneurysms. The first case of CPAN reported in the English-language literature may be that of a 7-year-old boy who, in 1870, died of "scarlet fever" at St. Bartholomew Hospital in London. Samuel Gee noted that 3 coronary artery aneurysms were present at autopsy and were filled with fresh thrombi.

More recently, Sarah Long suggested that perhaps one of the first documented cases of KD in the United States was that of a 9-month-old infant reported as 1 in a series of 5 cases of Stevens-Johnson syndrome in the Journal of Pediatrics in 1949. The infant had fever, irritability, cervical adenopathy, a polymorphous rash, and conjunctival suffusion. Cardiac arrest supervened, and, at autopsy, hemopericardium secondary to a ruptured coronary artery aneurysm was discovered. This author submits that this infant had CPAN. Other similar case reports appeared in Europe and the United States in the late 19th and early 20th centuries.

Much has been written in the past 2 decades with regard to the classification of the systemic vasculitides. In an attempt to put PAN into proper perspective, the classification promulgated by an international consensus conference held in Chapel Hill, NC, and published in 1994 ^[1] is included here. Large-vessel vasculitis includes giant cell (temporal) arteritis and Takayasu arteritis. Medium-vessel vasculitis includes PAN and KD. Small-vessel vasculitis includes Wegener granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis (microscopic polyarteritis), Henoch-Schönlein purpura, essential cryoglobulinemic purpura, and cutaneous leukocytoclastic angiitis.

Frequency

United States

The incidence and prevalence of childhood polyarteritis nodosa (CPAN) is not known, perhaps because of problems with the nosology of vasculitis syndromes, the rarity of the condition, and the lack of reported cases. The incidence of classic Kawasaki disease (KD) seems to be decreasing in the United States, as well as worldwide, with atypical or forme fruste cases becoming more common.

International

The incidence, prevalence, and distribution of childhood polyarteritis nodosa (CPAN) are not known.

A population-based study from southern Sweden reported that the annual incidence for polyarteritis nodosa was 0.7 per million children. ^[2]

Mortality/Morbidity

Adult polyarteritis nodosa (PAN) is an often fatal disease. Before the modern treatment era, the 5-year mortality was approximately 90%. The disease course is highly variable in individual patients. Some may have rapidly progressive disease, leading to death in days or weeks, whereas others may have more subacute disease. Other patients experience waxing and waning of symptoms, leading to chronic disability. In still others, the disease apparently remits with little or no treatment.

Childhood polyarteritis nodosa (CPAN) is perhaps more variable; however, rapidly progressive cases involving the coronary arteries may be highly lethal. With the widespread recognition of Kawasaki disease (KD) and its effective treatment, CPAN has almost disappeared. Most cases of isolated coronary arteritis observed today are considered incorrectly (in the author's opinion) to be atypical KD.

Race

Sufficient worldwide data are lacking, but individuals of Asian descent appear to have a disproportionately high incidence of vasculitis.

Sex

Males are affected more commonly than females, with a male-to-female ratio approaching 2:1.

Age

Polyarteritis nodosa (PAN) most often affects persons aged 40-60 years, although all ages are represented. By definition, childhood polyarteritis nodosa (CPAN) refers to cases occurring in childhood.