Page 66 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

42 David S. Younger

Insight into the rigorous management of PCNSV has been forthcoming in the French
COVAC? cohort [196] that showed sustained therapeutic response during three years of
followup and overall mortality and relapse rates of 6% and 27% respectively with
corticosteroids and cyclophosphamide as first-line therapy. One retrospective analysis [197]
found that cyclophosphamide conferred little benefit over azathioprine in patients with GAB
so treated and in fact, increased the risk for potentially fatal side effects. Nonetheless, failure
to respond or progress on corticosteroids, azathioprine or cyclophosphamide suggests an
alternative diagnosis rather than a refractory disease [193].

Idiopathic Aortitis-IgG4-Related Disorders

In 1972, an unusual form of inflammatory aortic disease or aortitis came to light in the
surgical literature with far-reaching implications for concepts of autoimmunity. Walker and
colleagues [198] noted that 10% of 217 patients presenting with abdominal aneurysms at
Manchester Royal Infirmary between 1958 and 1969 for resection showed excessive
thickening of aneurysm walls and perianeurysmal adhesions at operation. Subsequent
histological examination of the walls of the aneurysms showed extensive active chronic
inflammatory changes including plasma-cell infiltration.

The clinical features of patients with inflammatory aneurysms differed from those with
atherosclerotic disease due to generally younger age by a decade, lower incidence of rupture,
lack of claudication of intermittent the limbs and presence of peripheral pulses, less likelihood
of unusual presenting features, elevated ESR, and lack of calcification on preoperative
abdominal Rojo-Leyva and colleagues [199] noted idiopathic aortitis in 43% of 1,204 aortic
specimens gathered over a period of 20 years. In 96% of the patients with idiopathic aortitis
patients and aneurysm formation, aortitis was present only in the thoracic aorta. In 2001,
Hamano and colleagues [200] noted a high concentrations of IgG4 associated with sclerosing
pancreatitis characterized by obstructive jaundice, infrequent attacks of abdominal pain,
irregular narrowing of the pancreatic duct, sonolucent swelling of the parenchyma,
lymphoplasmacytic infiltration, fibrosis, and a favorable response to corticosteroid treatment.
One year later, Hamano and coworkers [201] noted the association of sclerosing pancreatitis
with raised concentrations of IgG4 among those with concomitant hydronephrosis that caused
ureteral masses later diagnosed as retroperitoneal fibrosis (RPF).

Histologic examination of ureteral and pancreatic tissues revealed abundant tissue
infiltration by IgG4-bearing plasma cells. In the same year, 2008, three important
observations were made. First, Sakata and colleagues [202] concluded that inflammatory
abdominal aortic aneurysm (IAAA) was related to IgG4 sclerosing disease. Second,
Kasashima and colleagues [203] concluded that IAAA was an IgG-RD together with RPF.
Third, Ito and colleagues [204] described a patient with IAAA, hydronephrosis caused by
RPF and high levels of IgG4, in whom treatment with corticosteroids led to clinical
improvement and reduction in IgG4 levels. Histological inspection of the aortic wall
specimen showed lymphocytoplasmacytic infiltration. Immunohistochemical analysis of the
tissue showed IgG4 positive plasma cells. The findings suggested that IAAA had an
etiopathogenesis similar to autoimmune pancreatitis and that some cases of IAAA and RPF
could be aortic and periaortic lesions of an IgG4-RD. One year later in 2009, Khosroshahi
and colleagues [205] described thoracic aortitis due to IgG4-RD with marked elevation of the

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