Takayasu's Arteritis

Background

This vasculitis is also known as aortic arch syndrome and pulseless disease. It is rare and commonly occurs in young women affecting larger arteries, commonly the aortic arch. It may lead to thrombosis and narrowing of the lumen of arteries feeding the extremities, hence the term pulseless disease. It does not affect the superficial vessels of the skin. In advanced cases, there may be secondary skin changes including erythema nodosum, pyodermatous ulcers, and urticaria.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Prognosis and Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

SYNONYMS Pulseless disease

GEOGRAPHY

MEXICO

Immunogenetics and clinical aspects of Takayasu's arteritis patients in a Mexican Mestizo population.

Vargas-Alarcon G, Flores-Dominguez C, Hernandez-Pacheco G, Zuniga J, Gamboa R, Soto ME, Granados J, Reyes PA.

Department of Physiology, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico.

Clin Exp Rheumatol 2001 Jul-Aug;19(4):439-43 Abstract quote
OBJECTIVE: The aim of the present work was to study the association between HLA alleles and Takayasu's arteritis in Mexican Mestizo patients.

METHODS: The study included 26 Mexican Mestizo patients with Takayasu's arteritis and 99 healthy unrelated individuals. HLA-A, -B and -DR alleles were determined by polymerase chain reaction PCR-SSP

RESULTS: Increased gene frequencies were demonstrated for HLA-B15(p=0.009,pC=0.020,OR=3.24,EF=11.9%) and HLA-B52 (p=0.008, pC=0.027, OR=5.16, EF=7.7%), and a decreased frequency for the HLA-A24 allele in patients compared to normal controls (p=0.035, pC=NS, PF=11.1%). When HLA typing was correlated to clinicalfeatures in 24 cases, wefound an increasedfrequencies of HLA-DR14 in patients with systemic arterial hypertension (p=0.005, pC=0.004, OR=24.6, EF=38.3%) and HLA-A2 on patients with pulmonary involvement (p=0.034, pC=0.036, OR=3.67, EF=40.4%) when compared to patients without these clinical manifestations.

CONCLUSION: These data confirm HLA-B52 as a relevant susceptibility allele for Takayasu's arteritis and suggest that HLA-B15 could be important as a marker of the disease in Mexican patients. Other class I and/or class II alleles could also be relevant as markers for the clinical features present in these patients.

DISEASE ASSOCIATIONS CHARACTERIZATION

CROHN'S DISEASE

Takayasu's arteritis and Crohn's disease: an unusual association. Report on two cases.

Biagi P, Castro R, Campanella G, Parisi G, Gobbini AR, Vedovini G.

Department of Internal Medicine, Tuscan Region, Local Health Unit ASL 7, Abbadia S. Salvatore (SI), Italy.
Dig Liver Dis 2001 Aug-Sep;33(6):487-91 Abstract quote
Two cases of Takayasu's arteritis associated with Crohn's disease of the colon are described, both of which occurring in young female patients.

In the first case, the vasculitic process was widespread, involving the aortic arch, the abdominal aorta, the renal arteries and the left iliac artery, similar to the angiographic "Indian" pattern. The second case presented a typical "Japanese" aortic arch involvement. In the first patient, Crohn's disease appeared to have been present prior to Takayasu's arteritis, vice versa in the second case; steroid treatment, assigned for both diseases might, however, have modified their natural evolution.

The association is rare. Moreover, the coexistence of two immune-mediated diseases in the same subject is unusual as they are generally considered to be independent. Hypotheses concerning their possible inter-relationship are advanced.

SARCOIDOSIS

Concurrence of sarcoidosis and aortitis: case report and review of the literature.

Weiler V, Redtenbacher S, Bancher C, Fischer MB, Smolen JS.

Second Department of Internal Medicine, Centre for the Rheumatic Diseases, Lainz Hospital, Vienna, Austria.

Ann Rheum Dis 2000 Nov;59(11):850-3 Abstract quote
Takayasu arteritis (TA) is a rare manifestation of systemic large vessel vasculitis which affects predominantly the aorta and its main branches, but often remains unrecognised owing to delayed diagnosis and non-characteristic clinical features. Sarcoidosis, too, is a systemic inflammatory disease which can affect virtually any organ system. Reports about the coincidence of both diseases have appeared. The case presented here is characterised by a significant time lag between detection of TA and appearance of clinical signs of sarcoidosis.

The woman, now 39 years old, had erythema nodosum, circumscript alopecia, and recurrent uveitis, which dated back to 1980 and was attributed to sarcoidosis. At least 12 years later aortic valve insufficiency with progressive cardiac failure developed. Histology performed at the time of aortic valve prosthesis in 1997 disclosed a diagnosis of TA, which was confined to the aortic root. Incidentally, sarcoidosis was diagnosed in adjacent lymph nodes. A thorough check up failed to detect further manifestations of TA; thus, possibly, the patients had aortitis similar to, but not identical with, TA.Several related cases previously reported are discussed, suggesting that both diseases may be inherently related as they are characterised by certain non-specific, immunoinflammatory abnormalities.

This case report suggests that the prevalence of TA, or related forms of arteritis, may be higher than expected and should be considered, especially in younger patients with non-characteristic cardiovascular symptoms and suspected systemic inflammatory disease. Moreover, the association with sarcoidosis in this and other previously described cases suggests that the two diseases may be related and that TA or TA-like vasculitis may even be a complication of sarcoidosis.

PATHOGENESIS CHARACTERIZATION

ANTI-ENDOTHELIAL CELL ANTIBODIES

Complement and cell mediated cytotoxicity by antiendothelial cell antibodies in Takayasu's arteritis.
Tripathy NK, Upadhyaya S, Sinha N, Nityanand S.

Department of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
J Rheumatol 2001 Apr;28(4):805-8 Abstract quote
OBJECTIVE: To study complement and cell mediated cytotoxicity by antiendothelial cell antibodies (AECA) in Takayasu's arteritis (TA).

METHODS: Complement dependent cytotoxicity (CDC) and antibody dependent cellular cytotoxicity (ADCC) of AECA positive/negative TA sera were investigated by colorimetric MTT and 51Cr release assays, respectively, using human umbilical vein endothelial cells (HUVEC) as targets.

RESULTS: Seven of 12 (58%) sera positive for IgG and/or IgM AECA exhibited CDC in comparison to none of the 13 AECA negative sera (p = 0.0052). The median value of CDC of the AECA positive group was 14% (range 13-21%) and that of the AECA negative group was 1% (p = 0.0012). Interleukin 1beta (10 U/ml) treatment of HUVEC resulted in enhancement in CDC of 6 of the 7 AECA positive cytotoxic sera, the median enhancement being 17% (range 7-29%). Tumor necrosis factor-alpha (100 U/ml) treatment of the targets resulted in a median enhancement by 36% (range 25-55%) in the CDC of 3 of these 7 sera. No sera exhibited ADCC at any of the effector:target ratios tested (10:1 to 100:1).

CONCLUSION: AECA in TA mediate CDC against endothelial cells and may have a pathogenic role in the perpetuation of vascular damage in this disease

HLA

Mapping of the HLA-linked genes controlling the susceptibility to Takayasu's arteritis.

Kimura A, Ota M, Katsuyama Y, Ohbuchi N, Takahashi M, Kobayashi Y, Inoko H, Numano F.

Department of Molecular Pathogenesis, Division of Adult Diseases, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, 101-0062, Tokyo, Japan.
Int J Cardiol 2000 Aug 31;75 Suppl 1:S105-10; discussion S111-2 Abstract quote
To further define the HLA-linked genes controlling the susceptibility to Takayasu's arteritis, polymorphisms in five microsatellites around the HLA-B and MICA genes, C1-2-A, MIB, C1-4-1, C1-2-5, and C1-3-1, were investigated in 91 Japanese patients with Takayasu's arteritis and 248 healthy Japanese controls.

It was found that allele 238 of C1-2-A [60.4% in patients vs. 29.8% in controls, odds ratio (OR)=3.59, P(c)<0.000004], allele 332 of MIB (22.0% vs. 6. 1%, OR=4.32, P(c)<0.0003), allele 208 of C1-2-5 (47.3% vs. 24.6%, OR=2.75, P(c)=0.001), and allele 291 of C1-3-1 (62.6% vs. 44.8%, OR=2.07, P(c)<0.02) were significantly associated with the disease.

Combined analyses of polymorphisms in the HLA-B and MICA genes with those in the microsatellites suggest that there are two different disease-susceptible loci for Takayasu's arteritis; one is mapped near the C1-2-A locus and the other is more closely linked to the HLA-B gene than to the MICA gene, because there are at least two different disease-associated HLA-B haplotypes, HLA-B*52 and -B*39.2 haplotypes, in which the disease-associated C1-2-A allele is shared in common.

PLATELET SENSISTIVITY

Enhanced platelet sensitivity to prostacyclin in patients in an active stage of Takayasu arteritis.

Watanabe T, Kishi Y, Numano F, Isobe M.

Department of Cardiovascular Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Thromb Res 2001 Oct 15;104(2):77-83 Abstract quote
Patients in an active stage of Takayasu arteritis are often complicated with thrombosis in the affected vessels.

We investigated whether alteration of platelet sensitivity to prostacyclin is involved in platelet function in these patients. Twelve female patients in an active stage (48.3+/-11.8 years, mean+/-S.D.), diagnosed clinically by a persistently elevated erythrocyte sedimentation rate (>40 mm/h) with typical symptoms, along with 10 gender- and age-matched patients in an inactive stage and 12 control subjects were enrolled. Half-maximal concentration (EC(50)) for platelet aggregation to collagen was determined in the presence and absence of 1 nM iloprost, a stable prostacyclin analog. Sensitivity of platelets to prostacyclin was quantified by the ratio of EC(50) (R) in the presence of iloprost to that in its absence. Patients in an active stage exhibited enhanced platelet aggregation, as demonstrated by significantly lower EC(50) to collagen and increased plasma thromboxane B(2) concentration. However, R values in these patients were significantly higher (4.00+/-1.05; P<.001) than those in the inactive patients or controls (2.58+/-0.62 and 2.43+/-0.68, respectively), suggesting enhanced sensitivity to prostacyclin in patients with active disease. Plasma 6-keto-PGF1 alpha levels were lower in the active patients than those in other groups of subjects.

We conclude that platelets in an active stage of TA may be sensitive not only to collagen but also to prostacyclin. The increase in sensitivity of the platelets to prostacyclin could be a compensatory mechanism against a decrease in the prostanoid production, presumably associated with endothelial dysfunction.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

Follow-up electron beam CT for the management of early phase Takayasu arteritis.

Paul JF, Fiessinger JN, Sapoval M, Hernigou A, Mousseaux E, Emmerich J, Piette JC.

Service de Radiologie, Hopital Marie Lannelongue, Le Plessis-Robinson, Paris, France.
J Comput Assist Tomogr 2001 Nov-Dec;25(6):924-31 Abstract quote
PURPOSE: The purpose of this work was to assess typical findings of Takayasu arteritis on serial CT examinations following therapy.

METHOD: Serial CT studies were performed on 16 patients with early phase Takayasu arteritis. Mural or luminal changes of the aorta on successive CT scans were compared with clinical data.

RESULTS: Vascular lesions progressed during follow-up in 6 of 16 patients. In one patient, progression of lesions was symptomatic. In the other five of six patients with worsening lesions, vascular progression occurred without new clinical symptoms and was first identified on CT scans. One of these five had dilatation of the ascending aorta and required aortic repair. Four others had progression of stenotic vascular lesions leading to changes in medical treatment only or in combination with either surgery or angioplasty. For two of them, CT examinations showed decreased mural lesions after changes in medical treatment.

CONCLUSION: CT examinations performed in treated patients with Takayasu arteritis demonstrate either regression, stabilization, or progression of vascular lesions. Serial CT examinations may thus be useful for evaluating response to treatment.

The role of radiology in the diagnosis and management of Takayasu's arteritis.

Angeli E, Vanzulli A, Venturini M, Zoccai GB, Del Maschio A.

Department of Diagnostic Radiology, Scientific Institute S.Raffaele Hospital, Vita-Salute University, Milan, Italy.
J Nephrol 2001 Nov-Dec;14(6):514-24 Abstract quote
In the last years new computer-based imaging techniques, like color Doppler sonography, Computed Tomography, and Magnetic Resonance, have allowed a non-invasive approach to vascular diseases, partially replacing angiography, and increasing the role of radiology in the diagnosis and management of many chronic diseases, such as Takayasu's arteritis.

Simultaneous evaluation of luminal and vascular wall changes may now allow a simpler diagnosis of this condition also in its early phase and the effective therapy monitoring. Application of new procedures of interventional radiolgy provides a safer and more conservative correction of late steno-occlusive complications.

Familiarity with the different imaging features of Takayasu arteritis will permit a more accurate clinical diagnosis and management of this insidious disorder.

ULTRASOUND

A novel use of ultrasound in pulseless electrical activity: the diagnosis of an acute abdominal aortic aneurysm rupture.

Hendrickson RG, Dean AJ, Costantino TG.

Department of Emergency Medicine, Medical College of Pennsylvania/Hahnemann University, Philadelphia, Pennsylvania 19129, USA.
J Emerg Med 2001 Aug;21(2):141-4 Abstract quote
We report a case of a patient who presented to the Emergency Department with pulseless electrical activity.

A rapid diagnosis of ruptured abdominal aortic aneurysm was made by Emergency Medicine bedside ultrasonography. On arrival, the patient was without palpable pulses and bradycardic. Therapy with epinephrine, fluids, and atropine was initiated.

A bedside ultrasound was immediately performed and revealed coordinated cardiac motion with empty ventricles. A rapid search for signs of blood loss in the abdomen revealed a large abdominal aortic aneurysm. Pulses were restored with fluid, blood, and epinephrine and surgical intervention was begun within 30 min of patient arrival.

VENTILATION-PERFUSION SCAN

Ventilation-perfusion lung scan for the detection of pulmonary involvement in Takayasu's arteritis.

Castellani M, Vanoli M, Cali G, Bacchiani G, Origgi L, Reschini E, Scorza R, Gerundini P.

Department of Nuclear Medicine, Ospedale Maggiore, Pad. Granelli, Via F. Sforza 35, 20122 Milan, Italy.

Eur J Nucl Med 2001 Dec;28(12):1801-5 Abstract quote
The aim of study was to analyse ventilation and perfusion (V/Q) lung scan findings in a series of Italian patients with Takayasu's arteritis.

Eighteen consecutive patients underwent V/Q lung planar scintigraphy and single-photon emission tomography (SPET). Before perfusion scan acquisition was started, a first-pass study with (99m)Tc-macroaggregates of albumin was performed to assess the right ventricular ejection fraction (RVEF). All patients had normal chest X-rays and were symptom free at the time of the investigation. They also underwent echocardiography to evaluate pulmonary artery pressure and in 13 patients respiratory function tests were performed. In four patients, perfusion lung scan was repeated after 1 year. In 10/18 patients (55.5%), 43 unmatched lobar, segmental or subsegmental perfusion defects were found on planar images; ventilation scintigraphy was normal in all cases. On SPET images, 55 defects were found; no defects were found with SPET in the remaining patients who had normal planar images.

All patients had normal RVEF and 5/13 patients had mild restrictive-obstructive lung disease. The pulmonary artery pressure was increased in two patients with perfusion defects. In the four patients who had repeat scintigraphy, all defects remained unchanged. The prevalence of lung perfusion abnormalities observed in Italian patients with Takayasu's arteritis is within the range of values reported in other countries, and V/Q planar scintigraphy is sufficient for the screening of patients.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

Occlusive thromboaortopathy (Takayasu disease): clinical and angiographic features and a brief review of literature.

Sheikhzadeh A, Tettenborn I, Noohi F, Eftekharzadeh M, Schnabel A.

Medical School and Cardiovascular Medical and Research Center, Heart Hospital, Teheran, Iran.

Angiology 2002 Jan-Feb;53(1):29-40 Abstract quote
The aim of this study was to evaluate the diagnostic criteria and angiographic classifications of Takayasu arteritis by presenting the clinical, angiographic, and prognostic findings and a prospective follow-up of 78 patients. Occlusive thromboaortopathy or Takayasu arteritis is a large vessel vasculitis. The disease is systemic with an autoimmune and genetic etiology.

The complete clinical and angiographic manifestations are reported for 78 cases based on diagnostic criteria of the American College of Rheumatology with a mean 6 +/- 3.2 years follow-up. The mean age was 34.7 and female:male ratio was 3.6:1. According to National Institute of Health criteria, 61.5% of patients were in the acute phase of disease with systemic symptoms such as fever, weight loss, malaise, and elevated C-reactive protein levels. Immunologic markers, such as antinuclear antibody and antineutrophil cytoplasmic antibodies, were negative. The tuberculin test result was positive in 47%. Vascular bruit was present in 89%. Almost all patients had stenoses, occlusions, or aneurysmatic changes of the aorta and its main branches. Hypertension was detected in 58% and left ventricular hypertrophy was initially present in 22 (28%) patients. The angiographic manifestations were classified as type I, cervicobrachial type with 20 cases (25.6%); type II, thoracoabdominal type with 13 cases (16.6%); type III, peripheral type with 10 cases (12.8%); and type IV, generalized type with 35 cases (44.8%). The coronary arteries were involved in 6 cases, pulmonary arteries in 11 initially 5 in follow-up (16 cases), and renal arteries in 28 cases, respectively. A good correlation of the clinical manifestations and the prognosis was observed. During follow-up, five patients suffered from myocardial infarction, six had cerebrovascular accident, seven patients underwent aortic valve replacement, and six patients died (mortality rate, 7.6%). The specificity and sensitivity of diagnostic criteria were 94% and 76%, respectively.

In contrast to ours and Nasu's classification in the new classification of Numano, some angiographic types and subtypes of Takayasu arteritis are not present in our patients.

VARIANTS

ACUTE MYOCARDIAL INFARCTION

Mixed aneurysmal and obstructive coronary artery disease causing acute myocardial infarction in a young woman with Takayasu's arteritis.

Al-Hulaimi N, Al-Saileek A, Ahmed T, Al-Zaibag M, Pai RG, El-Widaa H.

Department of Cardiac Sciences, King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia.
Can J Cardiol 2001 May;17(5):602-5 Abstract quote
Takayasu's disease is a chronic inflammatory pathology of the aorta and its main branches.

The present report describes a rare presentation of the disease in a young woman who presented with anterior myocardial infarction, and was subsequently found to have mixed aneurysmal and obstructive coronary artery disease involving the left anterior descending artery and its diagonal branches. Issues surrounding the management of coronary artery disease in this patient are discussed.

CAROTID ARTERY

Carotid artery involvement in Takayasu's arteritis: evaluation of the activity by ultrasonography.

Park SH, Chung JW, Lee JW, Han MH, Park JH.

Department of Radiology, Seoul National University College of Medicine, Institute of Radiation Medicine, Korea.

J Ultrasound Med 2001 Apr;20(4):371-8 Abstract quote
The purpose of this study was to investigate the ultrasonographic criteria for determining the activity of carotid lesions in Takayasu's arteritis.

In 10 consecutive patients, common carotid arteries with active lesions (n = 8) and inactive lesions (n = 9) were included in the study. The activity of the carotid lesions was determined on the basis of clinical and laboratory findings and computed tomographic scans. Special focus was placed on thickness and echogenicity of the involved arterial wall and outer diameter of the involved arterial segment. All 17 common carotid arteries evaluated showed segmental or diffuse circumferential thickening of the involved wall. The wall thickness was 2.5 to 5.0 mm (mean +/- SD, 3.3 +/- 0.8 mm) in active lesions and 1.1 to 2.0 mm (mean, 1.6 +/- 0.4 mm) in inactive lesions. The outer diameter of the involved segment was 7.0 to 15.0 mm (mean, 10.0 +/- 2.4 mm) in active lesions and 4.9 to 9.5 mm (mean, 6.8 +/- 1.4 mm) in inactive lesions. Active lesions showed hyperechogenicity in the full thickness of the involved wall (n = 6) or concentric triple layers with a hyperechoic middle layer (n = 2). Inactive lesions showed hyperechogenicity (n = 7) or isoechogenicity (n = 2) of the involved wall. One active lesion showed intramural arteries.

Although precise measurement to tenths of a millimeter is impossible with the transducer used, prominent wall thickening with a maintained outer diameter in the common carotid artery suggests an active lesion, whereas mild wall thickening with a decreased outer diameter suggests an inactive lesion. Triple layers of a thickened wall with intramural arteries can be an ultrasonographic finding of an active lesion.

PEDIATRIC

Study of Takayasu's arteritis in children: clinical profile and management.

Muranjan MN, Bavdekar SB, More V, Deshmukh H, Tripathi M, Vaswani R.

Department of Paediatrics, Seth G. S. Medical College and K.E.M. Hospital Parel, Mumbai- 400 012, India.

J Postgrad Med 2000 Jan-Mar;46(1):3-8 Abstract quote
AIMS: To study clinical features, pattern of involvement and treatment modalities of Takayasu's arteritis (TA) in children.

MATERIAL AND METHODS: Retrospective analysis of hospital records of children admitted over a period of 4.5 years.

RESULTS: 17 patients in the age group of 5 to 11 years (M: F = 1.1: 1) were diagnosed to have TA on the basis of Ishikawa's criteria. One child was diagnosed post-mortem. The commonest presenting features were hypertension (64. 7%), congestive cardiac failure (47%), weak or absent peripheral pulses, cardiomyopathy (41.1% each) and cardiac valvular affection (35.2%). Retinopathy, hypertensive encephalopathy and abdominal bruits were uncommon. None presented in the prepulseless phase. No patient had an active tuberculous lesion, although Mantoux or BCG test was positive in 6 (35.2%). The predominant pattern of angiographic affection was Type II (52.9%). Nephrotic syndrome and portal cavernoma seen in one patient each were incidental associations. Anti-hypertensive drugs, oral steroids and drugs to control congestive heart failure were the mainstays of medical management. Antitubercular therapy was started in six patients. Angioplasty was attempted in 15 cases and proved to be partially beneficial in six. Three patients who failed to respond to medical management had to undergo surgical procedures, either bypass, nephrectomy or both. In-hospital mortality was 11.7%.

CONCLUSIONS: Patients of TA in this study presented acutely in the pulseless phase, with hypertension and its complications. Type II involvement was the commonest pattern. Anti-hypertensive agents and steroids along with angioplasty were partially successful in controlling symptoms in 35.2%. Surgical procedures were reserved for a minority with poor response to drugs and angioplasty.

RESPIRATORY FAILURE

Takayasu's arteritis presenting with bilateral parenchymal consolidations and severe respiratory failure.

Cilli A, Ozdemir T, Ogus C.

Department of Respiratory Medicine, University of Akdeniz, Antalya, Turkey.
Respiration 2001;68(6):628-30 Abstract quote
This is a report of an unusual case of Takayasu's arteritis presenting with bilateral parenchymal infiltrations and severe respiratory failure caused by pulmonary hemorrhage.

The patient was initially diagnosed and treated as protracted pneumonia. After the diagnosis of Takayasu's arteritis, she was successfully treated with high-fractioned oxygen and corticosteroid therapy.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL

VARIANTS

SKIN

Takayasu arteritis and cutaneous necrotizing vasculitis.

Skaria AM, Ruffieux P, Piletta P, Chavaz P, Saurat JH, Borradori L.

Department of Dermatology, University Medical Hospital, DHURDV, Geneva, Switzerland.
Dermatology 2000;200(2):139-43 Abstract quote
Takayasu arteritis (TA) is an inflammatory arteriopathy involving predominantly the aorta and its main branches. The disease evolves in two phases: a first, nonspecific inflammatory stage and a late 'pulseless' stage, in which complications related to arterial stenosis and aneurysm formation predominate.

In both phases, skin manifestations, such as inflammatory nodules, erythema-nodosum- and pyoderma-gangrenosum-like ulcers, have been described. We report 2 patients with TA, who had cutaneous necrotizing vasculitis as presenting manifestation of the disease. A review of the literature revealed 8 similar cases. TA does not only involve large arteries, but also small blood vessels. The observation that in TA the inflammatory process of the large arteries affects regions of the walls supplied by the vasa vasorum, the anatomy of which bears resemblance to the cutaneous vessel system, suggests that primary involvement of small vessels contributes to the development of the clinicopathological features of TA.

Knowledge of the skin manifestations associated with TA remains important for its diagnosis and prompt instauration of life-saving treatment.

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSTIC FACTORS

Takayasu arteritis. Treatment and prognosis in a university center in Brazil.

Sato EI, Lima DN, Espirito Santo B, Hata F.

Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil.
Int J Cardiol 2000 Aug 31;75 Suppl 1:S163-6 Abstract quote
The aim of this study was to evaluate the treatment and evolution of TA patients in a University Center in Brazil.

This is a retrospective and descriptive study, that included all patients with TAs who attended the out-patient clinic at the Universidade Federal de Sao Palo, between 1993 and 1998. Twenty-four patients were women and 22 where white. The median age at the time of diagnosis was 27 yo. Full arteriography was performed in 28 patients and carotid duplex ultrasound plus computed tomography of aorta was done in two patients. Type I was found in 4, type II-a and type II in one case each, the type IV in 4 cases and the type V in 20 patients. Regarding the treatment only three patients with quiescent disease did not receive any medications. Twenty-seven patients (90%) received prednisone and only ten of these patients achieved disease control. Forth-eight percent of patients who received prednisone showed some side effects. Twelve patients received methotrexate associated to prednisone and 58% of them had a good response. Two patients who did not control disease activity with prednisone plus methotrexate received cyclophosphamide without good results. Some surgical procedure was performed in ten TA patients. Three patients died during the follow-up.

This study showed that the majority of TA patients attended at a University Center needed association of prednisone and methotrexate to control disease activity, 30% needed some surgical procedures and that may be a cause of death in a young patient.

TREATMENT Corticosteroids and/or methotrexate

BETA-BLOCKER

Usefulness of beta blocker therapy in patients with Takayasu arteritis and moderate or severe aortic regurgitation.

Moncada GA, Hashimoto Y, Kobayashi Y, Maruyama Y, Numano F.

Third Department of Internal Medicine, Tokyo Medical and Dental University, School of Medicine, Japan.

Jpn Heart J 2000 May;41(3):325-37 Abstract quote
The objective of the present study was to evaluate the benefit of beta-blocker therapy for patients with Takayasu arteritis complicated by moderate or severe aortic regurgitation. Clinical and echocardiographic evaluation was performed in 20 Japanese women in a follow-up period of 7.0 +/- 2.0 years.

The patients were divided into 2 groups: Group A (n=10) patients who did not receive beta-blockers, and Group B (n=10) patients treated with long-term (5.1 +/- 1.6 years) therapeutic doses of beta-blockers. Left ventricular wall thickness increased significantly in all Takayasu patients who did not receive beta-blockers. Consequently, a remarkable increment in left ventricular mass took place (232 +/- 59 to 361 +/- 79 g; p < 0.005). In the same group, progressive worsening of the symptoms, with no reduction in the percent fractional shortening, was observed in 2 patients, while reduction of this last index was present in 1 asymptomatic patient. On the other hand, among the patients who were treated with beta-blockers, left ventricular mass still increased in 6 cases, while it clearly decreased in the other 4 cases (290 +/- 171 to 284 +/- 61 g; NS). The increment in wall thickness or left ventricular mass observed among patients with beta-blocker therapy was clearly less than the one registered among those who had not received beta-blockers. Furthermore, no worsening of the symptoms and/or left ventricular performance was observed during the follow-up period for patients receiving beta-blockers.

We conclude that beta-blocker therapy can slow and even reverse the progression of left ventricular hypertrophy in patients with Takayasu arteritis complicated by moderate or severe aortic regurgitation. The mechanism still needs to be elucidated. We believe an effective reduction in the excessive afterload imposed on the left ventricle to be most likely responsible, but cardiac beta-receptor up-regulation might also be involved. Deterioration of the clinical status and/or impairment of left ventricular function were not associated with beta-blocker therapy in our patients.

Therefore, these agents can be used safely alone or in addition to standard anti-hypertensive therapy when attempting to reduce excessive afterload, in spite of the presence of severe aortic regurgitation.

LEFLUNOMIDE

Beneficial effects of leflunomide in glucocorticoid- and methotrexate-resistant Takayasu's arteritis.

Haberhauer G, Kittl EM, Dunky A, Feyertag J, Bauer K.
Clin Exp Rheumatol 2001 Jul-Aug;19(4):477-8

NITRIC OXIDE

Nitric oxide and molsidomine in the management of pulmonary hypertension in Takayasu's arteritis.

Lee SD, Kim DS, Shim TS, Lim CM, Koh Y, Kim WS, Kim WD.

Department of Internal Medicine, Asan Medical Center, College of Medicine, Ulsan University, Seoul, Korea.
Chest 2001 Jan;119(1):302-7 Abstract quote
We present three patients with pulmonary hypertension in Takayasu's arteritis who showed long-term favorable response, clinically and hemodynamically, to nitric oxide donor molsidomine.

In these patients, nitric oxide inhalation was effective in reducing pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). Molsidomine (single dose of 4 mg p.o.) was also effective in reducing PAP and PVR, but nifedipine was not. With molsidomine, 4 mg tid, dyspnea, exercise capacity, and hemodynamic parameters were improved.

These favorable responses have lasted during the 3-month follow-up period in all patients.

SURGERY

Surgical experience of the thoracic aortic aneurysm due to Takayasu's arteritis.
Sasaki S, Kubota S, Kunihara T, Shiiya N, Yasuda K.

Department of Cardiovascular Surgery, Hokkaido University School of Medicine, N-14, W-5, Kita-ku, 0608648, Sapporo, Japan.
Int J Cardiol 2000 Aug 31;75 Suppl 1:S129-34 Abstract quote
We have treated 10 patients with thoracic aortic aneurysms due to Takayasu's arteritis during the last 15 years and presented surgical results. In the surgical treatment of thoracic aortic aneurysm due to Takayasu's arteritis, therapeutic strategy is different from that for atherosclerotic aneurysm and should be determined by the location and the extent of aneurysmal lesions and the degree of inflammation.

Palliative procedure, which was taken to reduce surgical risk, has failed to prevent the recurrence of aneurysmal formation or to minimize surgical risk in the later period. Radical surgical treatment for thoracic aortic aneurysms is highly recommended if technically possible.

Penoperative steroid therapy to control the degree of inflammation, appropriate strategy for multiple or extensive lesions and progress in the organ protection method that enabled radical treatment, all these will contribute to the improvement of surgical results.

Carotid artery reconstruction for Takayasu's arteritis the necessity of all-autogenous-vein graft policy and development of a new operation.

Tada Y, Kamiya K, Shindo S, Miyata T, Koyama H, Sato O, Ariizumi K.

Second Department of Surgery, Yamanashi Medical University, Japan.
Int Angiol 2000 Sep;19(3):242-9 Abstract quote
BACKGROUND: We have adopted an all-autogenous-vein-graft policy in carotid reconstruction for Takayasu arteritis, namely an ascendo-right carotid and right subclavian (axillary) arteries bypass using a pantaloon vein graft for patients all of whose arch branches are occluded, and an extra-anatomical bypass from the right subclavian artery for patients whose brachiocephalic artery is the only arch branch that remains patent. This report is to elaborate on these operations and to assess the long-term outcome.

METHODS: Six patients were operated on according to this policy; (5 women, 1 man, age range: 14 to 59 years (mean: 30). The indications for surgery were severe cerebral ischaemia that significantly interfered with their daily lives. The pantaloon vein graft bypass was performed in four patients, and an extra-anatomical bypass in two. The specific management protocol to prevent the "postbypass hyperperfusion syndrome" and cerebral oedema included a shunt procedure to the internal carotid artery using one limb of the pantaloon vein graft, induced hypotension just before the completion of the carotid reconstruction and the administration of a glycerine-fructose solution.

RESULTS: Cerebral ischaemic symptoms disappeared in all patients. All but one, who died of a ruptured thoraco-abdominal aneurysm on the 35th postoperative month, are living a normal life with a patent graft. No suture line complications have as yet been encountered (follow-up: 10 to 205 months, mean: 126 months).

CONCLUSIONS: Carotid vein bypass for Takayasu arteritis, particularly, the pantaloon vein graft bypass is recommended for those of whom all aortic arch branches are occluded, resulting in severe brain ischaemia. Perioperative blood pressure control is important for prevention of the hyperperfusion syndrome.

Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.

Commonly Used Terms

Vasculitis-See term.

Internet Links

Last Updated 4/16/2002

PATHOGENESIS	CHARACTERIZATION
ANTI-ENDOTHELIAL CELL ANTIBODIES
Complement and cell mediated cytotoxicity by antiendothelial cell antibodies in Takayasu's arteritis. Tripathy NK, Upadhyaya S, Sinha N, Nityanand S. Department of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India	J Rheumatol 2001 Apr;28(4):805-8 Abstract quote OBJECTIVE: To study complement and cell mediated cytotoxicity by antiendothelial cell antibodies (AECA) in Takayasu's arteritis (TA). METHODS: Complement dependent cytotoxicity (CDC) and antibody dependent cellular cytotoxicity (ADCC) of AECA positive/negative TA sera were investigated by colorimetric MTT and 51Cr release assays, respectively, using human umbilical vein endothelial cells (HUVEC) as targets. RESULTS: Seven of 12 (58%) sera positive for IgG and/or IgM AECA exhibited CDC in comparison to none of the 13 AECA negative sera (p = 0.0052). The median value of CDC of the AECA positive group was 14% (range 13-21%) and that of the AECA negative group was 1% (p = 0.0012). Interleukin 1beta (10 U/ml) treatment of HUVEC resulted in enhancement in CDC of 6 of the 7 AECA positive cytotoxic sera, the median enhancement being 17% (range 7-29%). Tumor necrosis factor-alpha (100 U/ml) treatment of the targets resulted in a median enhancement by 36% (range 25-55%) in the CDC of 3 of these 7 sera. No sera exhibited ADCC at any of the effector:target ratios tested (10:1 to 100:1). CONCLUSION: AECA in TA mediate CDC against endothelial cells and may have a pathogenic role in the perpetuation of vascular damage in this disease
HLA
Mapping of the HLA-linked genes controlling the susceptibility to Takayasu's arteritis. Kimura A, Ota M, Katsuyama Y, Ohbuchi N, Takahashi M, Kobayashi Y, Inoko H, Numano F. Department of Molecular Pathogenesis, Division of Adult Diseases, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, 101-0062, Tokyo, Japan.	Int J Cardiol 2000 Aug 31;75 Suppl 1:S105-10; discussion S111-2 Abstract quote To further define the HLA-linked genes controlling the susceptibility to Takayasu's arteritis, polymorphisms in five microsatellites around the HLA-B and MICA genes, C1-2-A, MIB, C1-4-1, C1-2-5, and C1-3-1, were investigated in 91 Japanese patients with Takayasu's arteritis and 248 healthy Japanese controls. It was found that allele 238 of C1-2-A [60.4% in patients vs. 29.8% in controls, odds ratio (OR)=3.59, P(c)<0.000004], allele 332 of MIB (22.0% vs. 6. 1%, OR=4.32, P(c)<0.0003), allele 208 of C1-2-5 (47.3% vs. 24.6%, OR=2.75, P(c)=0.001), and allele 291 of C1-3-1 (62.6% vs. 44.8%, OR=2.07, P(c)<0.02) were significantly associated with the disease. Combined analyses of polymorphisms in the HLA-B and MICA genes with those in the microsatellites suggest that there are two different disease-susceptible loci for Takayasu's arteritis; one is mapped near the C1-2-A locus and the other is more closely linked to the HLA-B gene than to the MICA gene, because there are at least two different disease-associated HLA-B haplotypes, HLA-B52 and -B39.2 haplotypes, in which the disease-associated C1-2-A allele is shared in common.
PLATELET SENSISTIVITY
Enhanced platelet sensitivity to prostacyclin in patients in an active stage of Takayasu arteritis. Watanabe T, Kishi Y, Numano F, Isobe M. Department of Cardiovascular Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.	Thromb Res 2001 Oct 15;104(2):77-83 Abstract quote Patients in an active stage of Takayasu arteritis are often complicated with thrombosis in the affected vessels. We investigated whether alteration of platelet sensitivity to prostacyclin is involved in platelet function in these patients. Twelve female patients in an active stage (48.3+/-11.8 years, mean+/-S.D.), diagnosed clinically by a persistently elevated erythrocyte sedimentation rate (>40 mm/h) with typical symptoms, along with 10 gender- and age-matched patients in an inactive stage and 12 control subjects were enrolled. Half-maximal concentration (EC(50)) for platelet aggregation to collagen was determined in the presence and absence of 1 nM iloprost, a stable prostacyclin analog. Sensitivity of platelets to prostacyclin was quantified by the ratio of EC(50) (R) in the presence of iloprost to that in its absence. Patients in an active stage exhibited enhanced platelet aggregation, as demonstrated by significantly lower EC(50) to collagen and increased plasma thromboxane B(2) concentration. However, R values in these patients were significantly higher (4.00+/-1.05; P<.001) than those in the inactive patients or controls (2.58+/-0.62 and 2.43+/-0.68, respectively), suggesting enhanced sensitivity to prostacyclin in patients with active disease. Plasma 6-keto-PGF1 alpha levels were lower in the active patients than those in other groups of subjects. We conclude that platelets in an active stage of TA may be sensitive not only to collagen but also to prostacyclin. The increase in sensitivity of the platelets to prostacyclin could be a compensatory mechanism against a decrease in the prostanoid production, presumably associated with endothelial dysfunction.

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
Follow-up electron beam CT for the management of early phase Takayasu arteritis. Paul JF, Fiessinger JN, Sapoval M, Hernigou A, Mousseaux E, Emmerich J, Piette JC. Service de Radiologie, Hopital Marie Lannelongue, Le Plessis-Robinson, Paris, France.	J Comput Assist Tomogr 2001 Nov-Dec;25(6):924-31 Abstract quote PURPOSE: The purpose of this work was to assess typical findings of Takayasu arteritis on serial CT examinations following therapy. METHOD: Serial CT studies were performed on 16 patients with early phase Takayasu arteritis. Mural or luminal changes of the aorta on successive CT scans were compared with clinical data. RESULTS: Vascular lesions progressed during follow-up in 6 of 16 patients. In one patient, progression of lesions was symptomatic. In the other five of six patients with worsening lesions, vascular progression occurred without new clinical symptoms and was first identified on CT scans. One of these five had dilatation of the ascending aorta and required aortic repair. Four others had progression of stenotic vascular lesions leading to changes in medical treatment only or in combination with either surgery or angioplasty. For two of them, CT examinations showed decreased mural lesions after changes in medical treatment. CONCLUSION: CT examinations performed in treated patients with Takayasu arteritis demonstrate either regression, stabilization, or progression of vascular lesions. Serial CT examinations may thus be useful for evaluating response to treatment.
The role of radiology in the diagnosis and management of Takayasu's arteritis. Angeli E, Vanzulli A, Venturini M, Zoccai GB, Del Maschio A. Department of Diagnostic Radiology, Scientific Institute S.Raffaele Hospital, Vita-Salute University, Milan, Italy.	J Nephrol 2001 Nov-Dec;14(6):514-24 Abstract quote In the last years new computer-based imaging techniques, like color Doppler sonography, Computed Tomography, and Magnetic Resonance, have allowed a non-invasive approach to vascular diseases, partially replacing angiography, and increasing the role of radiology in the diagnosis and management of many chronic diseases, such as Takayasu's arteritis. Simultaneous evaluation of luminal and vascular wall changes may now allow a simpler diagnosis of this condition also in its early phase and the effective therapy monitoring. Application of new procedures of interventional radiolgy provides a safer and more conservative correction of late steno-occlusive complications. Familiarity with the different imaging features of Takayasu arteritis will permit a more accurate clinical diagnosis and management of this insidious disorder.
ULTRASOUND
A novel use of ultrasound in pulseless electrical activity: the diagnosis of an acute abdominal aortic aneurysm rupture. Hendrickson RG, Dean AJ, Costantino TG. Department of Emergency Medicine, Medical College of Pennsylvania/Hahnemann University, Philadelphia, Pennsylvania 19129, USA.	J Emerg Med 2001 Aug;21(2):141-4 Abstract quote We report a case of a patient who presented to the Emergency Department with pulseless electrical activity. A rapid diagnosis of ruptured abdominal aortic aneurysm was made by Emergency Medicine bedside ultrasonography. On arrival, the patient was without palpable pulses and bradycardic. Therapy with epinephrine, fluids, and atropine was initiated. A bedside ultrasound was immediately performed and revealed coordinated cardiac motion with empty ventricles. A rapid search for signs of blood loss in the abdomen revealed a large abdominal aortic aneurysm. Pulses were restored with fluid, blood, and epinephrine and surgical intervention was begun within 30 min of patient arrival.
VENTILATION-PERFUSION SCAN
Ventilation-perfusion lung scan for the detection of pulmonary involvement in Takayasu's arteritis. Castellani M, Vanoli M, Cali G, Bacchiani G, Origgi L, Reschini E, Scorza R, Gerundini P. Department of Nuclear Medicine, Ospedale Maggiore, Pad. Granelli, Via F. Sforza 35, 20122 Milan, Italy.	Eur J Nucl Med 2001 Dec;28(12):1801-5 Abstract quote The aim of study was to analyse ventilation and perfusion (V/Q) lung scan findings in a series of Italian patients with Takayasu's arteritis. Eighteen consecutive patients underwent V/Q lung planar scintigraphy and single-photon emission tomography (SPET). Before perfusion scan acquisition was started, a first-pass study with (99m)Tc-macroaggregates of albumin was performed to assess the right ventricular ejection fraction (RVEF). All patients had normal chest X-rays and were symptom free at the time of the investigation. They also underwent echocardiography to evaluate pulmonary artery pressure and in 13 patients respiratory function tests were performed. In four patients, perfusion lung scan was repeated after 1 year. In 10/18 patients (55.5%), 43 unmatched lobar, segmental or subsegmental perfusion defects were found on planar images; ventilation scintigraphy was normal in all cases. On SPET images, 55 defects were found; no defects were found with SPET in the remaining patients who had normal planar images. All patients had normal RVEF and 5/13 patients had mild restrictive-obstructive lung disease. The pulmonary artery pressure was increased in two patients with perfusion defects. In the four patients who had repeat scintigraphy, all defects remained unchanged. The prevalence of lung perfusion abnormalities observed in Italian patients with Takayasu's arteritis is within the range of values reported in other countries, and V/Q planar scintigraphy is sufficient for the screening of patients.

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
Occlusive thromboaortopathy (Takayasu disease): clinical and angiographic features and a brief review of literature. Sheikhzadeh A, Tettenborn I, Noohi F, Eftekharzadeh M, Schnabel A. Medical School and Cardiovascular Medical and Research Center, Heart Hospital, Teheran, Iran.	Angiology 2002 Jan-Feb;53(1):29-40 Abstract quote The aim of this study was to evaluate the diagnostic criteria and angiographic classifications of Takayasu arteritis by presenting the clinical, angiographic, and prognostic findings and a prospective follow-up of 78 patients. Occlusive thromboaortopathy or Takayasu arteritis is a large vessel vasculitis. The disease is systemic with an autoimmune and genetic etiology. The complete clinical and angiographic manifestations are reported for 78 cases based on diagnostic criteria of the American College of Rheumatology with a mean 6 +/- 3.2 years follow-up. The mean age was 34.7 and female:male ratio was 3.6:1. According to National Institute of Health criteria, 61.5% of patients were in the acute phase of disease with systemic symptoms such as fever, weight loss, malaise, and elevated C-reactive protein levels. Immunologic markers, such as antinuclear antibody and antineutrophil cytoplasmic antibodies, were negative. The tuberculin test result was positive in 47%. Vascular bruit was present in 89%. Almost all patients had stenoses, occlusions, or aneurysmatic changes of the aorta and its main branches. Hypertension was detected in 58% and left ventricular hypertrophy was initially present in 22 (28%) patients. The angiographic manifestations were classified as type I, cervicobrachial type with 20 cases (25.6%); type II, thoracoabdominal type with 13 cases (16.6%); type III, peripheral type with 10 cases (12.8%); and type IV, generalized type with 35 cases (44.8%). The coronary arteries were involved in 6 cases, pulmonary arteries in 11 initially 5 in follow-up (16 cases), and renal arteries in 28 cases, respectively. A good correlation of the clinical manifestations and the prognosis was observed. During follow-up, five patients suffered from myocardial infarction, six had cerebrovascular accident, seven patients underwent aortic valve replacement, and six patients died (mortality rate, 7.6%). The specificity and sensitivity of diagnostic criteria were 94% and 76%, respectively. In contrast to ours and Nasu's classification in the new classification of Numano, some angiographic types and subtypes of Takayasu arteritis are not present in our patients.
VARIANTS
ACUTE MYOCARDIAL INFARCTION
Mixed aneurysmal and obstructive coronary artery disease causing acute myocardial infarction in a young woman with Takayasu's arteritis. Al-Hulaimi N, Al-Saileek A, Ahmed T, Al-Zaibag M, Pai RG, El-Widaa H. Department of Cardiac Sciences, King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia.	Can J Cardiol 2001 May;17(5):602-5 Abstract quote Takayasu's disease is a chronic inflammatory pathology of the aorta and its main branches. The present report describes a rare presentation of the disease in a young woman who presented with anterior myocardial infarction, and was subsequently found to have mixed aneurysmal and obstructive coronary artery disease involving the left anterior descending artery and its diagonal branches. Issues surrounding the management of coronary artery disease in this patient are discussed.
CAROTID ARTERY
Carotid artery involvement in Takayasu's arteritis: evaluation of the activity by ultrasonography. Park SH, Chung JW, Lee JW, Han MH, Park JH. Department of Radiology, Seoul National University College of Medicine, Institute of Radiation Medicine, Korea.	J Ultrasound Med 2001 Apr;20(4):371-8 Abstract quote The purpose of this study was to investigate the ultrasonographic criteria for determining the activity of carotid lesions in Takayasu's arteritis. In 10 consecutive patients, common carotid arteries with active lesions (n = 8) and inactive lesions (n = 9) were included in the study. The activity of the carotid lesions was determined on the basis of clinical and laboratory findings and computed tomographic scans. Special focus was placed on thickness and echogenicity of the involved arterial wall and outer diameter of the involved arterial segment. All 17 common carotid arteries evaluated showed segmental or diffuse circumferential thickening of the involved wall. The wall thickness was 2.5 to 5.0 mm (mean +/- SD, 3.3 +/- 0.8 mm) in active lesions and 1.1 to 2.0 mm (mean, 1.6 +/- 0.4 mm) in inactive lesions. The outer diameter of the involved segment was 7.0 to 15.0 mm (mean, 10.0 +/- 2.4 mm) in active lesions and 4.9 to 9.5 mm (mean, 6.8 +/- 1.4 mm) in inactive lesions. Active lesions showed hyperechogenicity in the full thickness of the involved wall (n = 6) or concentric triple layers with a hyperechoic middle layer (n = 2). Inactive lesions showed hyperechogenicity (n = 7) or isoechogenicity (n = 2) of the involved wall. One active lesion showed intramural arteries. Although precise measurement to tenths of a millimeter is impossible with the transducer used, prominent wall thickening with a maintained outer diameter in the common carotid artery suggests an active lesion, whereas mild wall thickening with a decreased outer diameter suggests an inactive lesion. Triple layers of a thickened wall with intramural arteries can be an ultrasonographic finding of an active lesion.
PEDIATRIC
Study of Takayasu's arteritis in children: clinical profile and management. Muranjan MN, Bavdekar SB, More V, Deshmukh H, Tripathi M, Vaswani R. Department of Paediatrics, Seth G. S. Medical College and K.E.M. Hospital Parel, Mumbai- 400 012, India.	J Postgrad Med 2000 Jan-Mar;46(1):3-8 Abstract quote AIMS: To study clinical features, pattern of involvement and treatment modalities of Takayasu's arteritis (TA) in children. MATERIAL AND METHODS: Retrospective analysis of hospital records of children admitted over a period of 4.5 years. RESULTS: 17 patients in the age group of 5 to 11 years (M: F = 1.1: 1) were diagnosed to have TA on the basis of Ishikawa's criteria. One child was diagnosed post-mortem. The commonest presenting features were hypertension (64. 7%), congestive cardiac failure (47%), weak or absent peripheral pulses, cardiomyopathy (41.1% each) and cardiac valvular affection (35.2%). Retinopathy, hypertensive encephalopathy and abdominal bruits were uncommon. None presented in the prepulseless phase. No patient had an active tuberculous lesion, although Mantoux or BCG test was positive in 6 (35.2%). The predominant pattern of angiographic affection was Type II (52.9%). Nephrotic syndrome and portal cavernoma seen in one patient each were incidental associations. Anti-hypertensive drugs, oral steroids and drugs to control congestive heart failure were the mainstays of medical management. Antitubercular therapy was started in six patients. Angioplasty was attempted in 15 cases and proved to be partially beneficial in six. Three patients who failed to respond to medical management had to undergo surgical procedures, either bypass, nephrectomy or both. In-hospital mortality was 11.7%. CONCLUSIONS: Patients of TA in this study presented acutely in the pulseless phase, with hypertension and its complications. Type II involvement was the commonest pattern. Anti-hypertensive agents and steroids along with angioplasty were partially successful in controlling symptoms in 35.2%. Surgical procedures were reserved for a minority with poor response to drugs and angioplasty.
RESPIRATORY FAILURE
Takayasu's arteritis presenting with bilateral parenchymal consolidations and severe respiratory failure. Cilli A, Ozdemir T, Ogus C. Department of Respiratory Medicine, University of Akdeniz, Antalya, Turkey.	Respiration 2001;68(6):628-30 Abstract quote This is a report of an unusual case of Takayasu's arteritis presenting with bilateral parenchymal infiltrations and severe respiratory failure caused by pulmonary hemorrhage. The patient was initially diagnosed and treated as protracted pneumonia. After the diagnosis of Takayasu's arteritis, she was successfully treated with high-fractioned oxygen and corticosteroid therapy.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
Takayasu arteritis. Treatment and prognosis in a university center in Brazil. Sato EI, Lima DN, Espirito Santo B, Hata F. Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil.	Int J Cardiol 2000 Aug 31;75 Suppl 1:S163-6 Abstract quote The aim of this study was to evaluate the treatment and evolution of TA patients in a University Center in Brazil. This is a retrospective and descriptive study, that included all patients with TAs who attended the out-patient clinic at the Universidade Federal de Sao Palo, between 1993 and 1998. Twenty-four patients were women and 22 where white. The median age at the time of diagnosis was 27 yo. Full arteriography was performed in 28 patients and carotid duplex ultrasound plus computed tomography of aorta was done in two patients. Type I was found in 4, type II-a and type II in one case each, the type IV in 4 cases and the type V in 20 patients. Regarding the treatment only three patients with quiescent disease did not receive any medications. Twenty-seven patients (90%) received prednisone and only ten of these patients achieved disease control. Forth-eight percent of patients who received prednisone showed some side effects. Twelve patients received methotrexate associated to prednisone and 58% of them had a good response. Two patients who did not control disease activity with prednisone plus methotrexate received cyclophosphamide without good results. Some surgical procedure was performed in ten TA patients. Three patients died during the follow-up. This study showed that the majority of TA patients attended at a University Center needed association of prednisone and methotrexate to control disease activity, 30% needed some surgical procedures and that may be a cause of death in a young patient.
TREATMENT	Corticosteroids and/or methotrexate
BETA-BLOCKER
Usefulness of beta blocker therapy in patients with Takayasu arteritis and moderate or severe aortic regurgitation. Moncada GA, Hashimoto Y, Kobayashi Y, Maruyama Y, Numano F. Third Department of Internal Medicine, Tokyo Medical and Dental University, School of Medicine, Japan.	Jpn Heart J 2000 May;41(3):325-37 Abstract quote The objective of the present study was to evaluate the benefit of beta-blocker therapy for patients with Takayasu arteritis complicated by moderate or severe aortic regurgitation. Clinical and echocardiographic evaluation was performed in 20 Japanese women in a follow-up period of 7.0 +/- 2.0 years. The patients were divided into 2 groups: Group A (n=10) patients who did not receive beta-blockers, and Group B (n=10) patients treated with long-term (5.1 +/- 1.6 years) therapeutic doses of beta-blockers. Left ventricular wall thickness increased significantly in all Takayasu patients who did not receive beta-blockers. Consequently, a remarkable increment in left ventricular mass took place (232 +/- 59 to 361 +/- 79 g; p < 0.005). In the same group, progressive worsening of the symptoms, with no reduction in the percent fractional shortening, was observed in 2 patients, while reduction of this last index was present in 1 asymptomatic patient. On the other hand, among the patients who were treated with beta-blockers, left ventricular mass still increased in 6 cases, while it clearly decreased in the other 4 cases (290 +/- 171 to 284 +/- 61 g; NS). The increment in wall thickness or left ventricular mass observed among patients with beta-blocker therapy was clearly less than the one registered among those who had not received beta-blockers. Furthermore, no worsening of the symptoms and/or left ventricular performance was observed during the follow-up period for patients receiving beta-blockers. We conclude that beta-blocker therapy can slow and even reverse the progression of left ventricular hypertrophy in patients with Takayasu arteritis complicated by moderate or severe aortic regurgitation. The mechanism still needs to be elucidated. We believe an effective reduction in the excessive afterload imposed on the left ventricle to be most likely responsible, but cardiac beta-receptor up-regulation might also be involved. Deterioration of the clinical status and/or impairment of left ventricular function were not associated with beta-blocker therapy in our patients. Therefore, these agents can be used safely alone or in addition to standard anti-hypertensive therapy when attempting to reduce excessive afterload, in spite of the presence of severe aortic regurgitation.
LEFLUNOMIDE
Beneficial effects of leflunomide in glucocorticoid- and methotrexate-resistant Takayasu's arteritis. Haberhauer G, Kittl EM, Dunky A, Feyertag J, Bauer K.	Clin Exp Rheumatol 2001 Jul-Aug;19(4):477-8
NITRIC OXIDE
Nitric oxide and molsidomine in the management of pulmonary hypertension in Takayasu's arteritis. Lee SD, Kim DS, Shim TS, Lim CM, Koh Y, Kim WS, Kim WD. Department of Internal Medicine, Asan Medical Center, College of Medicine, Ulsan University, Seoul, Korea.	Chest 2001 Jan;119(1):302-7 Abstract quote We present three patients with pulmonary hypertension in Takayasu's arteritis who showed long-term favorable response, clinically and hemodynamically, to nitric oxide donor molsidomine. In these patients, nitric oxide inhalation was effective in reducing pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). Molsidomine (single dose of 4 mg p.o.) was also effective in reducing PAP and PVR, but nifedipine was not. With molsidomine, 4 mg tid, dyspnea, exercise capacity, and hemodynamic parameters were improved. These favorable responses have lasted during the 3-month follow-up period in all patients.
SURGERY
Surgical experience of the thoracic aortic aneurysm due to Takayasu's arteritis. Sasaki S, Kubota S, Kunihara T, Shiiya N, Yasuda K. Department of Cardiovascular Surgery, Hokkaido University School of Medicine, N-14, W-5, Kita-ku, 0608648, Sapporo, Japan.	Int J Cardiol 2000 Aug 31;75 Suppl 1:S129-34 Abstract quote We have treated 10 patients with thoracic aortic aneurysms due to Takayasu's arteritis during the last 15 years and presented surgical results. In the surgical treatment of thoracic aortic aneurysm due to Takayasu's arteritis, therapeutic strategy is different from that for atherosclerotic aneurysm and should be determined by the location and the extent of aneurysmal lesions and the degree of inflammation. Palliative procedure, which was taken to reduce surgical risk, has failed to prevent the recurrence of aneurysmal formation or to minimize surgical risk in the later period. Radical surgical treatment for thoracic aortic aneurysms is highly recommended if technically possible. Penoperative steroid therapy to control the degree of inflammation, appropriate strategy for multiple or extensive lesions and progress in the organ protection method that enabled radical treatment, all these will contribute to the improvement of surgical results.
Carotid artery reconstruction for Takayasu's arteritis the necessity of all-autogenous-vein graft policy and development of a new operation. Tada Y, Kamiya K, Shindo S, Miyata T, Koyama H, Sato O, Ariizumi K. Second Department of Surgery, Yamanashi Medical University, Japan.	Int Angiol 2000 Sep;19(3):242-9 Abstract quote BACKGROUND: We have adopted an all-autogenous-vein-graft policy in carotid reconstruction for Takayasu arteritis, namely an ascendo-right carotid and right subclavian (axillary) arteries bypass using a pantaloon vein graft for patients all of whose arch branches are occluded, and an extra-anatomical bypass from the right subclavian artery for patients whose brachiocephalic artery is the only arch branch that remains patent. This report is to elaborate on these operations and to assess the long-term outcome. METHODS: Six patients were operated on according to this policy; (5 women, 1 man, age range: 14 to 59 years (mean: 30). The indications for surgery were severe cerebral ischaemia that significantly interfered with their daily lives. The pantaloon vein graft bypass was performed in four patients, and an extra-anatomical bypass in two. The specific management protocol to prevent the "postbypass hyperperfusion syndrome" and cerebral oedema included a shunt procedure to the internal carotid artery using one limb of the pantaloon vein graft, induced hypotension just before the completion of the carotid reconstruction and the administration of a glycerine-fructose solution. RESULTS: Cerebral ischaemic symptoms disappeared in all patients. All but one, who died of a ruptured thoraco-abdominal aneurysm on the 35th postoperative month, are living a normal life with a patent graft. No suture line complications have as yet been encountered (follow-up: 10 to 205 months, mean: 126 months). CONCLUSIONS: Carotid vein bypass for Takayasu arteritis, particularly, the pantaloon vein graft bypass is recommended for those of whom all aortic arch branches are occluded, resulting in severe brain ischaemia. Perioperative blood pressure control is important for prevention of the hyperperfusion syndrome.

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Prognosis and Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Pulseless disease
GEOGRAPHY
MEXICO
Immunogenetics and clinical aspects of Takayasu's arteritis patients in a Mexican Mestizo population. Vargas-Alarcon G, Flores-Dominguez C, Hernandez-Pacheco G, Zuniga J, Gamboa R, Soto ME, Granados J, Reyes PA. Department of Physiology, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico.	Clin Exp Rheumatol 2001 Jul-Aug;19(4):439-43 Abstract quote OBJECTIVE: The aim of the present work was to study the association between HLA alleles and Takayasu's arteritis in Mexican Mestizo patients. METHODS: The study included 26 Mexican Mestizo patients with Takayasu's arteritis and 99 healthy unrelated individuals. HLA-A, -B and -DR alleles were determined by polymerase chain reaction PCR-SSP RESULTS: Increased gene frequencies were demonstrated for HLA-B15(p=0.009,pC=0.020,OR=3.24,EF=11.9%) and HLA-B52 (p=0.008, pC=0.027, OR=5.16, EF=7.7%), and a decreased frequency for the HLA-A24 allele in patients compared to normal controls (p=0.035, pC=NS, PF=11.1%). When HLA typing was correlated to clinicalfeatures in 24 cases, wefound an increasedfrequencies of HLA-DR14 in patients with systemic arterial hypertension (p=0.005, pC=0.004, OR=24.6, EF=38.3%) and HLA-A2 on patients with pulmonary involvement (p=0.034, pC=0.036, OR=3.67, EF=40.4%) when compared to patients without these clinical manifestations. CONCLUSION: These data confirm HLA-B52 as a relevant susceptibility allele for Takayasu's arteritis and suggest that HLA-B15 could be important as a marker of the disease in Mexican patients. Other class I and/or class II alleles could also be relevant as markers for the clinical features present in these patients.

DISEASE ASSOCIATIONS	CHARACTERIZATION
CROHN'S DISEASE
Takayasu's arteritis and Crohn's disease: an unusual association. Report on two cases. Biagi P, Castro R, Campanella G, Parisi G, Gobbini AR, Vedovini G. Department of Internal Medicine, Tuscan Region, Local Health Unit ASL 7, Abbadia S. Salvatore (SI), Italy.	Dig Liver Dis 2001 Aug-Sep;33(6):487-91 Abstract quote Two cases of Takayasu's arteritis associated with Crohn's disease of the colon are described, both of which occurring in young female patients. In the first case, the vasculitic process was widespread, involving the aortic arch, the abdominal aorta, the renal arteries and the left iliac artery, similar to the angiographic "Indian" pattern. The second case presented a typical "Japanese" aortic arch involvement. In the first patient, Crohn's disease appeared to have been present prior to Takayasu's arteritis, vice versa in the second case; steroid treatment, assigned for both diseases might, however, have modified their natural evolution. The association is rare. Moreover, the coexistence of two immune-mediated diseases in the same subject is unusual as they are generally considered to be independent. Hypotheses concerning their possible inter-relationship are advanced.
SARCOIDOSIS
Concurrence of sarcoidosis and aortitis: case report and review of the literature. Weiler V, Redtenbacher S, Bancher C, Fischer MB, Smolen JS. Second Department of Internal Medicine, Centre for the Rheumatic Diseases, Lainz Hospital, Vienna, Austria.	Ann Rheum Dis 2000 Nov;59(11):850-3 Abstract quote Takayasu arteritis (TA) is a rare manifestation of systemic large vessel vasculitis which affects predominantly the aorta and its main branches, but often remains unrecognised owing to delayed diagnosis and non-characteristic clinical features. Sarcoidosis, too, is a systemic inflammatory disease which can affect virtually any organ system. Reports about the coincidence of both diseases have appeared. The case presented here is characterised by a significant time lag between detection of TA and appearance of clinical signs of sarcoidosis. The woman, now 39 years old, had erythema nodosum, circumscript alopecia, and recurrent uveitis, which dated back to 1980 and was attributed to sarcoidosis. At least 12 years later aortic valve insufficiency with progressive cardiac failure developed. Histology performed at the time of aortic valve prosthesis in 1997 disclosed a diagnosis of TA, which was confined to the aortic root. Incidentally, sarcoidosis was diagnosed in adjacent lymph nodes. A thorough check up failed to detect further manifestations of TA; thus, possibly, the patients had aortitis similar to, but not identical with, TA.Several related cases previously reported are discussed, suggesting that both diseases may be inherently related as they are characterised by certain non-specific, immunoinflammatory abnormalities. This case report suggests that the prevalence of TA, or related forms of arteritis, may be higher than expected and should be considered, especially in younger patients with non-characteristic cardiovascular symptoms and suspected systemic inflammatory disease. Moreover, the association with sarcoidosis in this and other previously described cases suggests that the two diseases may be related and that TA or TA-like vasculitis may even be a complication of sarcoidosis.

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Takayasu arteritis and cutaneous necrotizing vasculitis. Skaria AM, Ruffieux P, Piletta P, Chavaz P, Saurat JH, Borradori L. Department of Dermatology, University Medical Hospital, DHURDV, Geneva, Switzerland.	Dermatology 2000;200(2):139-43 Abstract quote Takayasu arteritis (TA) is an inflammatory arteriopathy involving predominantly the aorta and its main branches. The disease evolves in two phases: a first, nonspecific inflammatory stage and a late 'pulseless' stage, in which complications related to arterial stenosis and aneurysm formation predominate. In both phases, skin manifestations, such as inflammatory nodules, erythema-nodosum- and pyoderma-gangrenosum-like ulcers, have been described. We report 2 patients with TA, who had cutaneous necrotizing vasculitis as presenting manifestation of the disease. A review of the literature revealed 8 similar cases. TA does not only involve large arteries, but also small blood vessels. The observation that in TA the inflammatory process of the large arteries affects regions of the walls supplied by the vasa vasorum, the anatomy of which bears resemblance to the cutaneous vessel system, suggests that primary involvement of small vessels contributes to the development of the clinicopathological features of TA. Knowledge of the skin manifestations associated with TA remains important for its diagnosis and prompt instauration of life-saving treatment.