Concomitant giant cell aortitis, thoracic aortic aneurysm, and aortic arch syndrome: Occurrence in a patient and significance

Authors


Introduction

Giant cell arteritis (GCA) is the most common vasculitis in populations with predominantly northern European ancestry, with an annual incidence of as high as 15–33 cases per 100,000 persons over the age of 50 years (1–4). GCA primarily affects medium-sized and large arteries. Although the temporal arteries or other cranial arteries were classically thought to be involved in GCA (hence the name temporal arteritis), the aorta with any of its primary or secondary branches can be affected by this inflammatory vasculopathy (5–8).

GCA has been associated with aortic aneurysm and aortic dissection. In a population-based study examining the incidence of aortic aneurysm and dissection in 96 patients with GCA, Evans et al (9) found that patients with GCA were 17.3 times more likely to develop a thoracic aortic aneurysm and 2.4 times more likely to develop an abdominal aortic aneurysm compared with the general population. GCA has also been associated with the development of large artery stenosis (10–15), including aortic arch syndrome, which is characterized by narrowing of the lumen of the proximal branches of the aorta. This can lead to intermittent claudication in the arms if subclavian, axillary, or brachial arteries are critically narrowed, or it can lead to ischemic neurologic symptoms (like transitory ischemic attacks or stroke) if the cranial arteries are critically narrowed.

It has been thought that aortic arch syndrome and aortic aneurysm (or dissection) due to GCA generally do not occur together in the same patient, but that these are manifestations of distinct, mutually exclusive disease entities (9, 13, 14, 16). The occurrence of concomitant giant cell aortitis, aortic aneurysm, and aortic arch syndrome has not been well acknowledged in the literature.

Case report

A 75-year-old, healthy-appearing women was incidentally noted to have a cardiac murmur and was diagnosed with an asymptomatic ascending thoracic aortic aneurysm with associated mild to moderate aortic regurgitation confirmed by computerized tomography and echocardiography at an outside clinic 2 years prior to presentation. This was found to gradually enlarge with time, and when the diameter of the ascending thoracic aorta had increased to 6.8 cm (see Figure 1), she was referred for thoracic aortic aneurysm repair. The aneurysm resulted in only mild mediastinal widening on plain chest radiography. Coronary angiography revealed normal coronary arteries.

Figure 1.

Computerized tomography of the chest demonstrating aneurysmal dilatation of the ascending aorta with a maximum diameter of 6.8 cm.

The patient underwent aortic root and aortic valve replacement surgery (aortic valve and conduit SynerGraft—an allograft from which the cellular components are removed, leaving the tissue's collagen matrix intact). The aneurysm was found to be markedly thick-walled with a cobblestone appearance on the surface, suggestive of a vasculitic process, macroscopically distinct from a usual atherosclerotic aneurysm. The aneurysm was widest in the midsection of the ascending thoracic aorta. It extended into the proximal arch and narrowed in the midarch. The native annulus and the distal aorta were sufficiently healthy to allow for hemiarch repair. Histopathology of the ascending aortic aneurysm showed severe chronic fibrosing periaortitis with focal giant cell aortitis (Figures 2 and 3).

Figure 2.

Cross-sectional view of the entire aortic wall of the ascending aortic aneurysm, demonstrating chronic fibrosing periaortitis and focal giant cell aortitis (the lumen of the aorta is on the right side). Top: hematoxylin and eosin stain; Bottom: Verhoeff van Gieson stain (magnification ×7.2).

Figure 3.

Top left: Destruction of the internal elastic membrane and the architecture of the inner media with giant cell (Verhoeff van Gieson stain, 25× magnification). Top right: Giant cells stained with hematoxylin and eosin (50× magnification). Bottom left: Adventitia demonstrating mononuclear cell infiltration and chronic fibrosis (hematoxylin and eosin stain, 25× magnification). Bottom right: Mononuclear cell infiltration (hematoxylin and eosin stain, magnification ×100).

The patient recovered well from surgery. At subsequent rheumatology service consultation, she had no symptoms suggestive of giant cell arteritis, including headaches, scalp tenderness, visual disturbance, jaw claudication, joint pain or stiffness, proximal muscle pain or stiffness, or extremity claudication. She had no constitutional symptoms, although she had been dieting during the several months prior to surgery and had lost 17 pounds. She had a history of controlled hypertension. An atrophic right kidney measuring 5.4 cm and a left kidney measuring 11.2 cm in length were detected on renal sonography 2 weeks prior to surgery, and renal function was essentially normal (serum creatinine was 1.0 mg/dl; normal range up to 0.9). Physical examination revealed normal temporal arteries with normal pulses, and no tenderness or nodularities. There was a questionably diminished left radial artery pulse, but the patient had multiple recent cannulations of the left radial artery. The systolic blood pressure was 140/62 in the right arm and 120/60 in the left arm. Pedal pulses were normal. There were no bruits over the entire aorta; the subclavian, axillary, and brachial arteries; or the cervical arteries. Heart sounds were normal. The lungs were clear. The sternotomy wound was healing well. There was no synovitis, and only minimal changes of degenerative arthritis in both hands. The residual physical examination was essentially normal.

Because an inflammatory condition had not been expected, no markers of inflammation had been obtained preoperatively. The C-reactive protein (CRP) measured on the third postoperative day was 21.9 mg/dl (normal range 0.02–0.80), and the erythrocyte sedimentation rate (ESR) was 45 mm/hour, which increased to 60 mm/hour 11 days after surgery. The preoperative hemoglobin was 10.7 gm/dl. Syphilis serology was negative. Magnetic resonance imaging (MRI) and angiography (MRA) with and without gadolinium performed 8 days after surgery showed postoperative changes and circumferential aortic wall thickening of the mid- and distal descending thoracic aorta measuring 4 mm, possibly on the basis of inflammation due to GCA. There was long tapered narrowing of both subclavian arteries with high-grade stenoses of the proximal left subclavian artery as well as the left subclavian-axillary junction (Figure 4). The proximal right subclavian artery was mildly stenotic, and the left common carotid artery was narrowed at its origin. The right renal artery was severely stenosed or occluded. The right kidney measured 7.1 cm in length, and the left kidney 11.7 cm. The celiac artery had a high-grade stenosis, and the inferior mesenteric artery was stenotic as well. Carotid ultrasound obtained postoperatively showed no significant stenosis of the cervical arteries, and vertebral artery flow was anterograde bilaterally.

Figure 4.

Magnetic resonance angiography demonstrating high grade stenosis in the left subclavian artery proximally, stenosis in the region of the left subclavian-axillary junction, and mild long segment narrowing of the proximal right subclavian artery.

Based on the histopathologic and angiographic findings, a diagnosis of active GCA affecting both the aorta and the subclavian/axillary arteries was made.

Eleven days following surgery, treatment with prednisone at 60 mg every day was started with a subsequent slow tapering course. At 1-month followup, on a prednisone dose of 40 mg every day, the patient was doing well. Blood pressures in both arms were now symmetric, as were the radial pulses. Although no preoperative markers of inflammation were available as reference points for followup of disease activity, the CRP had almost normalized at 0.816 mg/dl (normal range 0.02–0.80), and the ESR was normal at 5 mm/hour.

Discussion

This is the first detailed case report of concomitant giant cell aortitis, thoracic aortic aneurysm, and aortic arch syndrome in the literature for the past 3 decades. Our patient had both asymptomatic thoracic aortic aneurysm and subclavian artery stenosis in the setting of GCA. This case may be a rare exception to the general rule that aortic aneurysm (or dissection) and aortic arch syndrome due to GCA do not occur together in the same patient (9, 13, 14, 16), or may reflect lack of recognition of both conditions occurring simultaneously. None of a series of 41 patients with GCA and thoracic aortic aneurysm (16) and none of 11 patients with thoracic aortic aneurysm of 96 patients with GCA in a population-based study (9) had aortic arch syndrome. Similarly, none of 74 patients with subclavian/axillary artery GCA of a referral population was reported to have an aortic aneurysm (13).

Review of the literature reveals only a few cases with similar findings, with none reported since 1975. In 1941, Sproul (5) described a case of GCA with diffuse aortic dilation and stenosis of all the main arterial branches, including the subclavian arteries. Oestberg (17), in a series of 13 autopsies of patients with GCA, reported 1 case with marked widening of the thoracic aorta, thoracic aortic rupture, stenosis of arm arteries by history, and intimal thickening of arm arteries on autopsy. GCA was documented both in the thoracic aorta and the respective arm arteries. In the same series, an additional case with marked dilation of the proximal aorta and intimal thickening of the proximal arm arteries was reported, as well as a case with slight widening of the proximal aorta and stenoses of arm arteries, with histopathologic demonstration of GCA in the affected areas. Klein et al (14) briefly describe 1 patient (of 34 patients with large-artery involvement) from a consecutive series of 248 patients with GCA who had both a thoracic aortic aneurysm with dissection and left subclavian and axillary giant cell artery arteritis with associated stenoses.

The long tapered narrowing of the subclavian arteries on MRA in our patient were most likely due to GCA, and not simply to atherosclerosis (18). We only had indirect evidence for active GCA in the subclavian arteries due to the normalization of initially asymmetric systolic blood pressure readings after 1 month of high-dose prednisone therapy. Positron emission tomography (PET) scan could have helped in assessing disease activity of GCA in the subclavian arteries (19–22), but currently this is still a research tool and needs to be further validated in prospective studies. In our patient, interpretation of PET scan results would have been confounded by the postoperative changes.

Large-artery stenosis related to active GCA usually responds to corticosteroid therapy (14), with resolution of intermittent claudication and normalization of previously absent pulses or blood pressures, although there have not been any controlled trials of treatment of large-artery stenosis in GCA. The true incidence of large-artery stenosis in GCA is unknown and has not been addressed in any strictly population-based study.

In our judgment, the finding of giant cell aortitis on surgical pathology was not coincidental, but causally related to the pathogenesis of the thoracic aortic aneurysm. Although the causality between giant cell aortitis and the development of aortic aneurysm and large-artery stenosis in this patient cannot be proven, we believe that circumstantial evidence and epidemiologic studies (9, 14) support the relationship.

This case raises several questions beyond that of concomitant aortic aneurysm and aortic arch syndrome in the setting of giant cell arteritis. How frequent is asymptomatic giant cell aortitis? Is this causally related to the development of aortic aneurysm formation? Is immunosuppressive therapy indicated when this is coincidentally found at the time of surgery for aortic aneurysm?

A large retrospective autopsy study of 20,591 people from Malmo, Sweden (23) revealed an incidence of arteritis in 7% of aortic aneurysms (30 of 443) and 15% of thoracic aortic aneurysms (13 of 85). In a more recent retrospective study of 1,204 surgical pathologic specimens of the aorta (1,064 of which were obtained at surgery for aortic aneurysm) (24), idiopathic aortitis was found to be present in 4.3%, usually affecting the thoracic aorta. These inflammatory changes were histopathologically distinguished from an additional 3.4% showing inflammation related to atheromatous changes. The authors did not explain in detail how this distinction was made. Thirty-six patients (3.0%) had aortitis that was not related to a known prior systemic disease, and giant cells were present in 16 of these (1.3%). None of these patients had clinical features of GCA prior to surgery. No information is provided about preoperative inflammatory serum markers (ESR, CRP). Followup information is incomplete. Some of these patients were treated with corticosteroids in an uncontrolled, nonstandardized way. None of 11 patients treated with corticosteroids and followed for a mean of 35.5 months developed new aneurysms, whereas 6 of 25 patients who did not receive corticosteroid therapy and were followed for a mean of 41.2 months developed new aneurysms.

The pivotal question of whether a patient with an incidental finding of isolated “asymptomatic” giant cell aortitis presenting as aortic aneurysm should be treated with immunosuppressive therapy remains unanswered. As Rojo-Leyva et al (24) point out, the risk of developing a new aortic aneurysm following detection of idiopathic aortitis in a surgical specimen remains unknown. It is also uncertain whether immunosuppressive therapy may be able to prevent aneurysm formation related to progressive aortitis, although ample indirect evidence suggests that this is likely the case (9).

When clues of ongoing active large-artery GCA are detected (e.g., persistently elevated inflammatory markers, intermittent extremity claudication responding to corticosteroid therapy, abnormal PET scan, suspicious aortic wall thickening in other locations on MRI), initial high-dose corticosteroid therapy in a way that is used in treatment of classic GCA would appear to be indicated. However, there are no data from controlled trials available to support this opinion.

In conclusion, this case report of a patient with concomitant giant cell aortitis, thoracic aortic aneurysm, and aortic arch syndrome is evidence that large artery aneurysm and stenosis can occur in the same patient, and counters the conventional wisdom that thoracic aortic aneurysm and aortic arch syndrome are distinct, mutually exclusive manifestations of GCA that do not occur together in the same patient (9, 13, 14, 16). We propose that patients with GCA and either thoracic aortic aneurysm or aortic arch syndrome/large-artery stenosis should also be monitored carefully for possible development of the respective other kind of large-artery involvement of GCA. Patients with active disease should be treated in an attempt to prevent the development of and complications related to large artery disease.

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