Page 837 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Large-Vessel Vasculitides

Cornelia M. Weyand

Most tissues have compensatory mechanisms that allow them monitoring. Excellent progress has been made in unraveling the
to sustain the damaging effects of acute and chronic inflammation, pathogenesis of GCA, and this will inevitably lead to improve-
but medium and large arteries are organs without redundancy ments in diagnosis, long-term management, and broadening of
and limited regenerative capacity. Life is unsustainable unless the therapeutic armamentarium.
the major arteries have uncompromised function. Accordingly,
inflammatory damage to such arterial vessels leads to severe EPIDEMIOLOGY
clinical consequences, immediately posing a threat for the loss
of function of vital organs. When affected by inflammation, the GCA may be a very old disease, as suggested by historic evidence
aorta and its branches have two possible response patterns: (i) that more than 1000 years ago removal of the temporal artery
Inflammatory destruction of the vessel wall leads to dilatation, was recommended by a physician in Baghdad. In 1932, Horton
aneurysm formation, and rupture. Alternatively, the wall layers et al. at the Mayo Clinic in Minnesota recognized that GCA was
dissect. (ii) The inflammation initiates a maladaptive response an inflammatory vasculopathy when they found dense inflam-
to injury, resulting in luminal occlusion, disruption of blood mation in the temporal arteries of two patients who were systemi-
supply, and ischemic damage of dependent organ structures. cally ill and had severe headaches. The first reports of TA, or
In contrast to other vasculopathies, especially those related “pulseless disease,” in young women surfaced in Japan in the
to atherosclerosis, vasculitides of the larger blood vessels are nineteenth century. The syndrome was named after Dr. Takayasu,
almost always associated with a syndrome of intense systemic an ophthalmologist, who, in 1905, described peculiar optic fundus
1
inflammation. Recent evidence has challenged the traditional abnormalities caused by ischemia-driven collateral formation.
3,4
view that systemic inflammation represents a spillover of inflam- The strongest risk factor for GCA, TA, and PMR is age.
matory mediators from the vasculitic lesions. Instead, systemic GCA and PMR are essentially absent in individuals <50 years
activation of the innate immune system appears to be a pinnacle of age, and their incidence climbs continuously during the seventh
event that initiates the processes leading to vessel wall inflam- and eighth decades of life. TA is almost exclusively diagnosed
mation. The coincidence of malaise, fever, wasting, and myalgias, in individuals <40 years of age, with peak incidence during the
with signs of ischemia caused by vascular failure, remains a critical second and third decades of life. Women are affected more often
clue for the physician when diagnosing and treating large-vessel by all three syndromes compared with men, with a 2 : 1 ratio in
vasculitides (LVVs). PMR and GCA and a 9 : 1 ratio in TA. 3,5
The two major forms of LVVs are giant-cell arteritis (GCA) Marked geographical variations in the incidence and prevalence
and Takayasu arteritis (TA). In addition, aortitis can infrequently of GCA, TA, and PMR have given rise to speculations about
be seen in other diseases, such as infections, connective tissue environmental exposures as key factors in disease pathogenesis.
diseases, sarcoidosis, and inflammatory bowel disease (IBD), and GCA is the most frequent vasculitis in the Western world, with
occasionally is diagnosed as an idiopathic syndrome. Polymyalgia yearly incidence rates reaching 10–20 cases per 100 000 persons
3
rheumatica (PMR) is a condition closely related to GCA; it occurs >50 years of age. In general, PMR is diagnosed three- to fourfold
in the same patient population and often precedes or follows more frequently, with a prevalence of up to 1 case per 133
2
2
the clinical diagnosis of GCA. Patients with PMR do not have individuals >50 of age. Iceland, Norway, Sweden, and Denmark
typical vascular lesions; consequently, PMR is not classified as are high-risk areas; higher incidence rates are also seen in
a vasculitis. However, patients with PMR do have a systemic Scandinavian immigrant populations in the United States. The
inflammatory syndrome indistinguishable from GCA, and about risk is significantly lower in Hispanics and African Americans.
10% of patients with PMR eventually progress to full-blown Although TA can afflict all races, a predilection exists for individu-
vasculitis. Similarities in the vascular lesions of GCA and TA als of Asian and Central and South American origins. Japan,
have been interpreted as revealing parallels in immunopatho- Thailand, India, Turkey, and nations in Central and South
genesis. Whether similarities in histomorphology and tissue Americas are considered high-incidence regions. TA is a rare
targeting reflect similarities in underlying molecular defects disease with an annual incidence of 1–2 cases/million. The typical
remains unclear. Whether the systemic inflammatory reactions patient is a female in her 20s to 30s. In middle-aged men and
accompanying GCA, TA, and PMR have disease-specific elements women, it can be challenging to differentiate TA from rapidly
also remains unanswered, but this has opened the possibility of progressing atherosclerotic disease, especially as both disease
developing biomarkers that are urgently needed for clinical processes may coexist. 6

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