Page 817 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Small- and Medium-Vessel Primary Vasculitis

Raashid Ahmed Luqmani, Ana Águeda, Lorraine O’Neill

Small- and medium-vessel vasculitides are characterized by EPIDEMIOLOGY
inflammation of the blood vessel wall resulting in end organ
failure or irreversible tissue damage and necrosis. In some cases, Despite improvement in our understanding of the epidemiology
this is relatively trivial and may lead to minor inconvenience for of the systemic vasculitides, patients are often not diagnosed as
the patient. However, in many forms of vasculitis, the conse- having vasculitis for extended periods. The discovery of antibodies
quences of rapid onset of ischemia and occlusion of blood vessels to neutrophil cytoplasm (ANCA) and their association with
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are devastating, leading to organ failure and death. small-vessel vasculitis has improved recognition. Greater aware-
The distinction between small- and medium-vessel vasculitis ness of vasculitis may be a factor that explains an apparent increase
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entities is arbitrary, with three main patterns of vasculitis: small, in incidence from 1.5/million/year to 6.1/million per year. The
medium, and large. Although there is merit in this classification, incidence of ANCA-associated vasculitides (AAV) is 10–20 new
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there are different patterns of involvement for patients with cases per million per annum. In southern Europe, the number
predominantly small-vessel involvement (characterized by capil- of cases of MPA is greater than those of GPA.
laritis) compared with, but overlapping with, patients with MPA is also more common than GPA in Japan. ANCA directed
medium-vessel involvement typified by small arteriolar inflam- against myeloperoxidase is the predominant antibody detected
mation. For example, in the kidney, small-vessel involvement in patients with AAV in Japan, whereas autoantibodies directed
leads to inflammation of glomeruli (glomerulonephritis); by against proteinase 3 (PR3) are rarely seen in Japanese patients
contrast, medium-vessel inflammation of renal arterioles results but are the most frequent ANCA antibody in patients in northern
in infarction of the kidney with tissue loss. Therefore patterns Europe.
of disease are well recognized, with typical dominance of kidney, The epidemiology of EPGA is less well understood compared
lung, and upper airway involvement in patients with granulo- with other forms of AAV. EGPA is characterized by an elevated
matosis with polyangiitis (GPA), previously termed Wegener’s eosinophil count in patients with late-onset asthma. Around
granulomatosis. In microscopic polyangiitis (MPA), there is lack 50% of cases have ANCA, usually directed against myeloperoxi-
of upper airway involvement but significant renal and lung dase. EGPA is less common than either GPA or MPA, with an
involvement. Finally, in eosinophilic glomerulonephritis with incidence of around 0.6/million per annum. There is a potential
polyangiitis (EGPA), previously termed Churg-Strauss syndrome, overlap condition called hypereosinophilic syndrome (HES), and
the pattern of clinical involvement is dominated by upper and it is not clear whether some cases of HES are really cases of
lower airway disease combined with neurological (peripheral EGPA, or vice versa. Indeed, if patients are ANCA negative,
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nerve) features. These three entities are grouped together by distinguishing the two conditions can be challenging. Further-
their association with the presence of antineutrophil cytoplasmic more, because bronchospasm is a key feature of EGPA, it is
antibody (ANCA) in most, but not all, cases. possible that some cases of asthma, an extremely common
In patients with polyarteritis nodosa (PAN), one of the main condition, may, in fact, represent mild forms of EGPA. This has
forms of medium-vessel vasculitis, the most characteristic findings been brought more to light in cases of drug-induced EGPA,
are bowel ischemia or infarction and peripheral neuropathy. In specifically in the setting of the use of montelukast, a leukotriene
a childhood onset form of medium-vessel vasculitis (Kawasaki inhibitor, as a treatment for moderate to severe asthma. It has
disease [KD]), the clinical features are diverse and include been suggested that these patients probably had underlying EGPA,
mucocutaneous inflammation and systemic upset with fever, which had previously been suppressed with systemic glucocor-
and in 2–4% of cases, there is coronary artery dilatation and/or ticoids, but when these were withdrawn, features of EGPA became
aneurysm development, which can potentially rupture, leading more apparent.
to fatal consequences. 1 AAV typically affects older individuals in their 60s or 70s but
The diversity of different forms of vasculitis with overlapping can occur at any age. Most patients survive their initial illness
features suggests that the underlying mechanisms are varied, as a result of effective immunotherapy, and therefore the preva-
but some pathways are likely to be shared. This is reflected in lence of these diseases is growing. In southern Sweden, estimates
treatment approaches, which, with some exceptions, are often of prevalence are 160 per million (95% confidence interval [CI]
very similar across diseases. 114–206) for GPA, 94 (58–129) for MPA, 31 (11–52) for PAN,

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