Page 818 - Clinical Immunology_ Principles and Practice ( PDFDrive )

790 Part SIX Systemic Immune Diseases

TABLE 58.1 Diagnosis, Incidence and Prevalence in KD, PaN, aaV and
Leukocytoclastic Vasculitis
Diagnosis Incidence Prevalence references/ reviews
KD For children <5 years old: Not applicable
2431/million (Japan) Makino N, et al., 2015 96
1131 per million (Korea)
690 per million (Taiwan)
36–185/million (Italy)
PAN 3.6/million adults 2.6–14/million adults Nesher G, et al., 2016 5
Mohammad AJ, et al., 2007 4
ANCA-associated vasculitides 9.5–16/million/year (Germany) 149/million Reinhold-Keller E, et al., 2005 10
22.6/million (Japan) Herlyn K, et al., 2014 11
21.8/million (UK) Fujimoto S, et al., 2011 94
Leukocytoclastic vasculitis 45/million (equal male and female; increased No data Arora A, et al., 2014 7
incidence with age)
AAV, ANCA-associated vasculitis; ANCA, antineutrophil cytoplasmic antibody; KD, Kawasaki disease; PAN, polyarteritis nodosa.

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and 14 (0.3-27) for EGPA. However, these are based on a relatively 210.5/100 000 children, in contrast to the rate for Caucasian
small population size and are higher than those reported from children in Hawaii of 13.7/100 000, similar to the rate of 12.0/100
a Spanish series, where the prevalence of all forms of AAV was 000 among Caucasian children in continental United States. 6
under 45/million. Leukocytoclastic skin vasculitis is one of the more common
The two main forms of medium-vessel vasculitis are PAN forms of small vessel vasculitis occurring with an annual incidence
7
and KD. PAN is extremely rare. There is very wide misconception of about 45/million (Table 58.1). Less than a third is found in
among many physicians that PAN is the most common form of association with immunoglobulin A (Henoch-Schönlein purpura
vasculitis, and this is partly encouraged by the older literature, [HSP], or IgA vasculitis). IgA vasculitis is very common in children
which refers to all forms of vasculitis as PAN (initially called and is usually self-limiting; annual incidence is 100–200/million
8
periarteritis nodosa and subsequently polyarteritis nodosa). In children ≤17 years of age. By contrast, this is a much less common
fact, the majority of patients with so-called PAN probably did disease in adults (around 13/million/year).
not have this disease but were more likely suffering from one of Cryoglobulinemic vasculitis is strongly associated with hepatitis
the forms of small-vessel vasculitis, particularly MPA and GPA. C, and its epidemiology is likely to mirror the prevalence of the
PAN has been associated with infection, especially hepatitis B hepatitis C virus (HCV). However, there are no published incidence
and hepatitis C. The epidemiology of hepatitis B has been and prevalence figures for cryoglobulinemic vasculitis itself.
transformed by effective immunization; as a result of this, hepatitis
B associated with PAN is now an extremely rare disease. Recent PATHOGENESIS OF AAV
figures suggest an incidence of PAN of 0.6–3.6/million adults. 5
KD is most common in children under the age of 5 years but The Pathogenic Role of ANCA in GPA and MPA
can occur in older children and young adults, in which case it There is some evidence that ANCA play a significant role in the
is more difficult to diagnose because it is not suspected. In a pathogenesis of GPA, MPA, and EGPA. Based on the immuno-
recent Italian study of children under the age of 14 years, the fluorescence pattern, different forms of ANCA can be distin-
incidence rate was 17.6/100 000 children under the age of 5 guished, but only two are of direct clinical relevance: cytoplasmic
years, with a slight increase in reported cases during spring and c-ANCA (corresponding to antibodies directed against PR3)
winter compared with other times of the year. This is a slightly and perinuclear p-ANCA (predominantly corresponding to
higher incidence rate than previously reported by other studies antibodies directed against myeloperoxidase [MPO]). p-ANCA
in Europe with a range of 3.6–15.2/100 000 children under the can also be directed against other antigens, including bactericidal/
age of 5 years. Earlier figures from a large-scale study from the permeability-increasing (BPI) protein, lactoferrin, human
United States of over 6000 children admitted to hospital because neutrophil elastase (HNE), cathepsin G, and azurocidin, but
of KD suggested that the peak age of onset was 1 year, and their clinical significance is not well characterized. Although
children under the age of 2 years accounted for over a third of ANCAs are associated with vasculitis, titers are not reliable for
all cases. The under-5-year incidence was reported as 8.1 per monitoring disease status because there is no clear relationship
100 000 children in 1988, rising to 18.5 per 100 000 children in with remission or relapse.
1997, similar to the recent Italian experience. Males were more Transfer of MPO-ANCA in humans (maternal–fetal route)
commonly affected than females (approximately 60% males); and animal models (necrotizing pauciimmune glomerulonephritis
there was no obvious seasonal variation. In a recent nationwide after passive transfer of purified antibody or splenocytes from
hospital survey in Japan, however, the incidence rates for KD MPO-deficient mice immunized with purified murine MPO)
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during 2011 and 2012 were over 2400 cases per million children has resulted in features typical of MPA. By contrast, the
under the age of 5 years. The higher incidence of KD in patients pathogenicity of antiPR3 antibodies is less well established. In
of Japanese ethnicity appears to be independent of their geo- one animal model of autoimmune-prone nonobese diabetic
graphical location. In fact, during 1996–2006, the average annual (NOD) mice, immunization with recombinant mouse PR3
incidence of KD in Japanese American children in Hawaii was (rmPR3) in complete Freund’s adjuvant (CFA) had no clinical