Takayasu Arteritis

Tools



Abbreviation: Takayasu arteritis – TA, Giant cell arteritis – GCA, Middle cerebral artery – MCA, Magnetic resonance angiogram – MRA, Magnetic resonance imaging – MRI, Computed tomography – CT

Abstract

Takayasu arteritis (TA) is a rare disease that affects primarily adolescent girls and young women. We report occurrence of Takayasu arteritis in a 25 year old afro-american female. Clinical presentation of this patient was classic with unequal pulses, difference in blood pressure in both arms and magnetic resonance angiography (MRA) findings suggestive of large vessel occlusion. Patient had 3/6 criteria, based on American College of Rheumatology (ACR) Classification for TA and was treated with intravenous Methylprednisolone. TA is very difficult to differentiate from Giant cell arteritis (GCA) on the basis of imaging. Age helps in distinguishing between TA and GCA.

The Case

A 25-year-old afro-american female with no significant past medical history presented to the ER with resolved episode of right sided weakness which lasted for 15 minutes. Computed tomography (CT) scan of the head showed a possible left middle cerebral artery thrombus. Patient was admitted for observation. Patient denied headache, loss of consciousness, fall, trauma to head, history of miscarriages or deep vein thrombosis. Neurology was consulted. Later in the evening, patient was noted to have right facial droop, repeat CT-head was normal. Systemic anticoagulation was started, but clinical condition deteriorated as patient had difficulty speaking the very next morning.

On physical examination, the patient was comfortable and was not in any distress. She was afebrile with a regular pulse rate of 78 beats per minute – unequal radial pulses, blood pressure of 100/80 mm Hg – difficult to auscultate on right arm approximately 80/60 mm Hg, and respiratory rate of 17 breaths per minute. Left carotid artery pulse was non-palpable. Neurological examination indicated right facial droop, intact sensation, normal 2+reflexes. The patient could follow commands but could not speak. Gait was normal. Motor power was 5/5 in all limbs.

The initial workup included complete blood cell count (CBC), basic metabolic panel, coagulation profile, sedimentation rate, C-reactive protein, urine drug screen, sickle cell profile. All lab results were within normal limits. MRI of the brain was suggestive of left middle cerebral artery infarct. Lower extremity Doppler was negative for deep vein thrombosis. Transthoracic echocardiogram with bubble study and holter monitoring were normal. Rheumatology team was consulted. Blood work up for dsDNA, ANA, C-ANCA, P-ANCA, Anticardiolipin Ab, Factor V leiden, was negative. Carotid Doppler revealed absence of flow in left common carotid artery with minimal flow in left internal carotid artery. MRA – neck was suggestive of left common carotid artery occlusion, right subclavian occlusion, tight stenosis of right common carotid artery and collateral flow to the left internal carotid artery via muscular branches of thyrocervical trunk and left vertebral artery. MRA – Chest was suggestive of normal aortic arch and large vessels with no evidence of stenosis, thrombus, aneurysm or dissection.

Based on physical findings and MRA – neck findings, Rheumatology team had high suspicion for Takayasu arteritis and recommended Intravenous Methylprednisolone 60 mg every 12 hourly. Patient showed favorable improvement in response to steroids, was discharged with oral prednisone, 50 mg every 12 hourly with taper of 10% every week.

Figure 1. CT-Brain showing thrombosis of the sylvan branch of middle cerebral artery.
Figure 1. CT-Brain showing thrombosis of the sylvan branch of middle cerebral artery.
Figure 2. MRA-Brain. Arrow A pointing right subclavian artery occlusion. Arrow B,C pointing hypertrophied right and left vertebral arteries respectively.
Figure 2. MRA-Brain. Arrow A pointing right subclavian artery occlusion. Arrow B,C pointing hypertrophied right and left vertebral arteries respectively.
Figure 3. MRA-Neck. Arrow A pointing occlusion of the right subclavian artery, Arrow B pointing occlusion of the left common carotid artery. Arrow C pointing attenuated and irregular right internal carotid artery.
Figure 3. MRA-Neck. Arrow A pointing occlusion of the right subclavian artery, Arrow B pointing occlusion of the left common carotid artery. Arrow C pointing attenuated and irregular right internal carotid artery.

Discussion

“Wreathlike appearance of blood vessels in the back of the eye” was a peculiar description by Dr. Mikito Takayasu, who presented the first case of TA in 1908. The diagnostic criteria include female with an age between 10- 40 years at disease onset; how-ever, TA can start later in life, particularly in Asians. 1  Incidence rates are higher in Asia especially in Japan with occurrence estimated at 150 cases per year. 2  The reported incidence in the United States is 2.6 per million per year. 3  TA can occur in all races and geographic regions, but South American countries have been recognized as areas of relatively high incidence. 1

The pathogenesis is poorly understood. Takayasu arteritis is a granulomatous polyarteritis. The adventitia is characterized by striking thickening, often with intense perivascular infiltrates around the vasa vasorum. Granuloma formation and giant cells are found predominantly in the media of the large elastic arteries. The medial elastic smooth-muscle cell layer is destroyed in a centripetal direction and replaced by fibrotic tissue, providing the conditions for vessel-wall dilatation and aneurysm formation. Smooth tapering, narrowing, or complete occlusion of the vascular lumen results from proliferation of the intima, occasionally with thrombosis. 4  In view of the systemic features of the syndrome, microbial infections have been implicated, but no conclusive evidence for infectious organisms has been provided. In aortic-wall lesions, CD8 T cells have been identified as a major cell type distinguishing the vascular infiltrates in TA from those in giant cell arteritis. Cytotoxic capabilities of tissue-infiltrating CD8 T cells, mediated by release of the pore-forming enzymes perforin and granzyme B, have been suspected to contribute to damage of smooth-muscle cells. 5  Involvement of CD8 T-cell mediated cytolytic tissue injury has been observed in selected HLA class I molecules, specifically HLA-B52, which are over-represented in people with TA. 6  The focus of lymphocytic infiltrates on the adventitia and accumulation of T cells around vasa vasorum make it less likely that the macroendothelium has major involvement in the pathogenesis of TA.

Clinicians divide TA into two phases: Systemic and Occlusive. Patients may have features of both phases at the same time. In the early or systemic phase of TA, clinical features include fatigue, low grade fever, weight loss and lethargy. As the disease progresses into the occlusive phase, vascular involvement and insufficiency become apparent due to dilatation, narrowing and occlusion of the main vessels like the aorta and its branches. 7  These may include pain in limbs, claudication, dizziness upon standing up, headaches, and visual disturbances. Lung involvement is a rare presenting feature but involvement of the pulmonary arteries has been reported. 8

According to “The American College of Rheumatology 1990 Classification criteria for Takayasu arteritis”, patient will be diagnosed as TA if they fulfill at least three out of six criteria. The presence of any three or more criteria yields a sensitivity of 90% and a specificity of 97.8%. 3

ACR Criteria for Classification of Takayasu Arteris

  1. Age at disease onset < or equal to 40 years
  2. Claudication of extremities – especially Upper Extremities
  3. Decreased Brachial artery pulse
  4. Blood pressure difference > 10mm Hg (systolic) between arms
  5. Bruit over subclavian arteries or aorta
  6. Arteriogram abnormality

A combination of vasoocclusive disease and systemic inflammation in a young female should raise immediate suspicion for TA. Diagnosis is confirmed by vascular imaging; tissue rarely is available. Angiography provides the best information about the vessel lumen and can be combined with angioplasty, if indicated. A complete aortic arteriography can help determine the distribution and degree of involvement. Noninvasive vascular imaging techniques with CT, MRI, and magnetic resonance angiography can help estimate the extent of wall inflammation. 9  Laboratory tests i.e. sedimentation rate, C-reactive protein are not helpful in diagnosis and reports have suggested that these tests are no longer reliable as marker for disease activity in a sizeable number of patients. 10  In an NIH cohort, 50% of patients had active, progressive disease, despite non-elevated acute-phase reactants. 4

The differential Diagnosis of TA includes infection (tuberculosis, mycoses, syphilis), congenital collagen disorders (Ehlers-Danlos, Marfan’s syndrome), Fibrous Dysplasias (FD), and acquired idiopathic inflammatory diseases (other Vasculitides, Sarcoidosis, and Spondyloarthropathies). Imaging is very useful in differentiating most of the possible diagnoses except for giant cell arterititis. Giant cell arteritis like TA involves large arteries showing granulomatous vasculitis on histologic examination. Distinction can be made based on the age of the patient and distribution of lesions. 11 12

Corticosteroids remain the therapy of choice for management of TA. Dosage of 40-60 mg of prednisone daily may be necessary to sufficiently control vascular and systemic inflammation. Prednisone doses are tapered as clinically indicated and tolerated, usually by 5mg/day every 2 weeks, until a maintenance dose of 10mg/day is reached. Low-dose aspirin or other antiplatelet agents should complement corticosteroid therapy. Methotraxate, given in weekly doses of up to 25 mg, has shown some promise in sparing steroids. 13  Overall, cytotoxic agents do not have impressive therapeutic benefit in this inflammatory vasculopathy. Anti-tumor necrosis factor may be a useful therapy in patients with difficult to treat Takayasu arteritis. 14  Bypass grafts and angioplastic management has gained importance in the management of irreversible TA. In cases with disease refractory to glucocorticoids recommendations are to give trials of mycophenolate, methotrexate, or leflunamide and cyclophosphamide as the last source for those who have no improvement. 15 16

Vascular involvement tends to be progressive, although short term prognosis is favorable. Long-term follow- up of almost 1,000 Japanese patients found stable clinical conditions in two-thirds and serious complications in only 25%. Acceleration of atherosclerotic disease is a critical factor in long-term outcome. 1 17

References

  1. Numano F. Differences in clinical presentation and outcome in different countries for Takayasu’s arteritis. Curr Opin Rheumatol 1997; 9:12-15.

  2. Koide K. Takayasu arteritis in Japan. Heart Vessels 1992; 7: 48.

  3. Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH, Edworthy SM, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis & Rheumatism. 1990; 33:1129-34.

  4. Kerr GS, Hallahan CW, Giordano J, Leavitt RY, Fauci AS, Rottem M, Hoffman GS. Takayasu arteritis. Ann Intern Med 1994; 120: 919-929.

  5. Seko Y. Takayasu arteritis: insights into immunopathology, Jpn Heart J 2000; 41:15-26.

  6. Kimura A, Kitamura H, Date Y, Numano F. Comprehensive analysis of HLA genes in Takayasu arteritis in Japan. Int J Cardiol 1996; 54:S61-S69.

  7. Kerr GS. Takayasu arteritis. Rheum Dis Clin North Am 1995; 21:1041-1058.

  8. Nakabayashi K, Kurata N, Nangi N, Miyake H, Nagasawa T. Pulmonary artery involvement as first manifestation in three cases of Takayasu arteritis. International Journal of Cardiology.1996; 54 Suppl:S177-83.

  9. Tso E, Flamm SD, White RD, Schvartzman PR, Mascha E, Hoffman GS.Takayasu arteritis: utility and limitations of magnetic resonance imaging in diagnosis and treatment. Arthritis & Rheumatism.2002; 46:1634-42.

  10. David Hellmann, M.D. Takayasu arteritis. American college of Physicians 1998; Edition 11. http://vasculitis.med.jhu.edu/typesof/takayasu.html

  11. Hunder GG. Giant cell arteritis in polymyalgia rheumatica. American Journal of Medicine. 1997; 102:514-6.

  12. Michel BA, Arend WP, Hunder GG. Clinical differentiation between giant cell (temporal) arteritis and Takayasu’s arteritis. Journal of Rheumatology. 1996; 23:106-11.

  13. Langford CA, Sneller MC, Hoffman GS. Methotrexate use in systemic vasculitis.Rheum Dis Clin North Am 1997; 23:841-853.

  14. Hoffman GS, Merkel PA, Brasington RD, Lenschow DJ, Liang P. Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis. Arthritis Rheum. 2004; 50: 2296-2304.

  15. Mevorach D, Leibowitz G, Brezis M, Raz E. Induction of remission in a patient with Takayasu’s arteritis by low dose pulses of methotrexate. Ann Rheum Dis 1992; 51:904-05.

  16. Diana E, Schieppati A, Remuzzi G. Mycophenolate mofetil for the treatment of Takayasu arteritis: report of three cases. Ann Intern Med 1999; 130:422-26.

  17. Seyahi E, Ugurlu S, Cumali R, Balci H, Seyahi N, Yurdakul S, et al.Atherosclerosis in Takayasu arteritis. Annals of the Rheumatic Diseases. 2006; 65:1202-7.