Clinical course and prognostic factors of childhood Takayasu's arteritis: over 15-year comprehensive analysis of 101 patients

Luyun Fan, Huimin Zhang, Jun Cai, Lirui Yang, Bin Liu, Dongmei Wei, Jiachen Yu, Jiali Fan, Lei Song, Wenjun Ma, Xianliang Zhou, Haiying Wu, Ying Lou, Luyun Fan, Huimin Zhang, Jun Cai, Lirui Yang, Bin Liu, Dongmei Wei, Jiachen Yu, Jiali Fan, Lei Song, Wenjun Ma, Xianliang Zhou, Haiying Wu, Ying Lou

Abstract

Background: Childhood Takayasu's arteritis (c-TA) is scarcely reported but is characterized by devastating morbidity and mortality. This study aims to investigate the clinical course of c-TA and prognostic factors associated with rehospitalization and events including vascular complications, flares, and death.

Methods: An ambispective study of 101 c-TA patients satisfying the American College of Rheumatology (ACR) criteria and/or the European League against Rheumatism (EULAR)/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS) criteria was conducted from January 2002 to December 2017. Data on demographic, clinical, laboratory, imaging, and therapeutic features were collected. Event-free survival, complication-free survival, flare-free survival, rehospitalization-free survival, and associated prognostic factors were assessed by Kaplan-Meier survival curve and propensity score analysis.

Results: The median age at c-TA onset was 14 (interquartile range (IQR) 12-16) years and 76.2% were female. Hypertension (70.3%), blood pressure discrepancy (55.4%), bruits (51.5%), and pulse deficits (37.6%) were core presentations. Major vascular involvement included the renal artery (62.4%), abdominal aorta (42.6%), subclavian artery (43.6%), and carotid artery (42.6%). Glucocorticoids (78.2%), antihypertensive drugs (72.3%), antiplatelet agents (72.3%), and revascularization (57.4%) were made up the majority administered. At a median 2.4 (IQR 0.7-6.1) years of follow-up, events, rehospitalization, vascular complications, flares and death were observed in 44.6%, 37.6%, 44.6%, 26.7%, and 3%, respectively. The 5-year event-free survival, rehospitalization-free survival, vascular complication-free survival, and flare-free survival were 42.8%, 55.8%, 45.9%, and 62.3%, respectively. Body mass index (BMI) (hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.30-0.81, p = 0.005), stroke (HR = 7.37, 95% CI 2.35-23.1, p = 0.001), and revascularization (HR = 0.51, 95% CI 0.27-0.94, p = 0.032) were independent prognostic predictors of events. Predictors for rehospitalization include age at admission (HR = 0.81, 95% CI 0.69-0.94, p = 0.006), renal artery involvement (HR = 0.49, 95% CI 0.25-0.96, p = 0.037), and elevated C-reactive protein (CRP; HR = 2.50, 95% CI 1.24-5.00, p = 0.01). BMI level (p = 0.024) and renal artery involvement (p = 0.015) were also associated with vascular complications, while revascularization (p = 0.002) independently correlated with re-flares.

Conclusions: This large ambispective study of c-TA revealed an early 3% mortality at the first year and around 50% morbidity within 5 years after diagnosis. Hypertension, renal artery involvement, and revascularization based on anti-inflammation, antihypertension, and antiplatelet medications dominated c-TA with indications for optimistic prognosis. Patients with initial lower BMI level, a younger age at admission, stroke, and elevated CRP have a high risk of poor outcomes, requiring close c-TA monitoring and more aggressive management.

Trial registration: NCT03199183 , unique protocol ID: 2016-ZX43. June 26, 2017.

Keywords: Children; Prognostic factor; Takayasu arteritis.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the Institutional Ethics Committee of Fuwai Hospital (No. 2016–842); the need for consent was waived for the retrospective study from January 2002 to January 2017 with de-identified data.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Event-free survival, complication-free survival, flare-free survival, and rehospitalization-free survival
Fig. 2
Fig. 2
Prognostic factors of c-TA in multivariable Cox regression analysis. BMI body mass index, CI confidence interval, CRP C-reactive protein, HR hazard ratio

References

    1. Watanabe Y, Miyata T, Tanemoto K. Current clinical features of new patients with Takayasu arteritis observed from cross-country research in Japan: age and sex specificity. Circulation. 2015;132:1701–1709. doi: 10.1161/CIRCULATIONAHA.114.012547.
    1. Mukhtyar C, Guillevin L, Cid MC, Dasgupta B, de Groot K, Gross W, et al. EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2009;68:318–323. doi: 10.1136/ard.2008.088351.
    1. 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. doi: 10.1002/art.20300.
    1. Brunner J, Feldman BM, Tyrrell PN, Kuemmerle-Deschner JB, Zimmerhackl LB, Gassner I, et al. Takayasu arteritis in children and adolescents. Rheumatology. 2010;49:1806–1814. doi: 10.1093/rheumatology/keq167.
    1. Eleftheriou D, Varnier G, Dolezalova P, McMahon AM, Al-Obaidi M, Brogan PA, et al. Takayasu arteritis in childhood: retrospective experience from a tertiary referral centre in the United Kingdom. Arthritis Res Ther. 2015;17:36. doi: 10.1186/s13075-015-0545-1.
    1. Goel R, Kumar TS, Danda D, Joseph G, Jeyaseelan V, Surin AK, et al. Childhood-onset Takayasu arteritis—experience from a tertiary care center in South India. J Rheumatol. 2014;41:1183–1189. doi: 10.3899/jrheum.131117.
    1. Misra DP, Aggarwal A, Lawrence A, Agarwal V, Misra R. Pediatric-onset Takayasu's arteritis: clinical features and short-term outcome. Rheumatol Int. 2015;35:1701–1706. doi: 10.1007/s00296-015-3272-7.
    1. Aeschlimann FA, Eng SWM, Sheikh S, Laxer RM, Hebert D, Yeung RS, et al. Childhood Takayasu arteritis: disease course and response to therapy. Arthritis Res Ther. 2017;19:255. doi: 10.1186/s13075-017-1452-4.
    1. Feng Y, Tang X, Liu M, Zhou J, Zhao X, Li Q. Clinical study of children with Takayasu arteritis: a retrospective study from a single center in China. Pediatr Rheumatol Online J. 2017;15:29. doi: 10.1186/s12969-017-0164-2.
    1. 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 Rheum. 1990;33:1129–1134. doi: 10.1002/art.1780330811.
    1. Ozen S, Pistorio A, Iusan S, Bakkaloglu A, Herlin T, Brik R, et al. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: final classification criteria. Ann Rheum Dis. 2010;69:798–806. doi: 10.1136/ard.2009.116657.
    1. Peng M, Ji W, Jiang X, Dong H, Zou Y, Song L, et al. Selective stent placement versus balloon angioplasty for renovascular hypertension caused by Takayasu arteritis: two-year results. Int J Cardiol. 2016;205:117–123. doi: 10.1016/j.ijcard.2015.12.006.
    1. Che W, Xiong H, Jiang X, Dong H, Zou Y, Yang Y, et al. Stenting for middle aortic syndrome caused by Takayasu arteritis-immediate and long-term outcomes. Catheter Cardiovasc Interv. 2018;91:623–631. doi: 10.1002/ccd.27492.
    1. Fan L, Zhang H, Cai J, Ma W, Song L, Ying L. Middle aortic syndrome because of pediatric Takayasu arteritis admitted as acute heart failure: clinical course and therapeutic strategies. J Hypertens. 2018;36:2118–2119. doi: 10.1097/HJH.0000000000001847.
    1. Saadoun D, Lambert M, Mirault T, Resche-Rigon M, Koskas F, Cluzel P, et al. Retrospective analysis of surgery versus endovascular intervention in Takayasu arteritis: a multicenter experience. Circulation. 2012;125:813–819. doi: 10.1161/CIRCULATIONAHA.111.058032.
    1. Hata A, Noda M, Moriwaki R, Numano F. Angiographic findings of Takayasu arteritis: new classification. Int J Cardiol. 1996;54(Suppl):S155–S163. doi: 10.1016/S0167-5273(96)02813-6.
    1. Kerr GS, Hallahan CW, Giordano J, Leavitt RY, Fauci AS, Rottem M, et al. Takayasu arteritis. Ann Int Med. 1994;120:919–929. doi: 10.7326/0003-4819-120-11-199406010-00004.
    1. Comarmond C, Biard L, Lambert M, Mekinian A, Ferfar Y, Kahn JE, et al. Long-term outcomes and prognostic factors of complications in Takayasu arteritis: a multicenter study of 318 patients. Circulation. 2017;136:1114–1122. doi: 10.1161/CIRCULATIONAHA.116.027094.
    1. Liu Q, Dang A, Lv N, Wang X, Zheng D. Anaemia and low body mass index are associated with increased cardiovascular disease in patients with Takayasu arteritis. Clin Exp Rheumatol. 2016;34:S16–S20.
    1. Goel R, Danda D, Joseph G, Ravindran R, Kumar S, Jayaseelan V, et al. Long-term outcome of 251 patients with Takayasu arteritis on combination immunosuppressant therapy: single centre experience from a large tertiary care teaching hospital in Southern India. Semin Arthritis Rheum. 2018;47:718–726. doi: 10.1016/j.semarthrit.2017.09.014.
    1. Rumman RK, Matsuda-Abedini M, Langlois V, Radhakrishnan S, Lorenzo AJ, Amaral J, et al. Management and outcomes of childhood renal artery stenosis and middle aortic syndrome. Am J Hypertens. 2018;31:687–695. doi: 10.1093/ajh/hpy014.
    1. Green R, Gu X, Kline-Rogers E, Froehlich J, Mace P, Gray B, et al. Differences between the pediatric and adult presentation of fibromuscular dysplasia: results from the US Registry. Pediatr Nephro. 2016;31:641–650. doi: 10.1007/s00467-015-3234-z.
    1. de Souza AW, Machado NP, Pereira VM, Arraes AE, Reis Neto ET, Mariz HA, et al. Antiplatelet therapy for the prevention of arterial ischemic events in takayasu arteritis. Circ J. 2010;74:1236–1241. doi: 10.1253/circj.CJ-09-0905.
    1. Miyata T, Sato O, Koyama H, Shigematsu H, Tada Y. Long-term survival after surgical treatment of patients with Takayasu’s arteritis. Circulation. 2003;108:1474–1480. doi: 10.1161/01.CIR.0000089089.42153.5E.
    1. Hong S, Ghang B, Kim YG, Lee CK, Yoo B. Long-term outcomes of renal artery involvement in Takayasu arteritis. J Rheumatol. 2017;44:466–472. doi: 10.3899/jrheum.160974.
    1. Ladapo TA, Gajjar P, McCulloch M, Scott C, Numanoglu A, Nourse P. Impact of revascularization on hypertension in children with Takayasu's arteritis-induced renal artery stenosis: a 21-year review. Pediatr Nephrol. 2015;30:1289–1295. doi: 10.1007/s00467-015-3049-y.
    1. Wang X, Dang A, Lv N, Cheng N, Cheng X, Yang Y, et al. Long-term outcomes of coronary artery bypass grafting versus percutaneous coronary intervention for Takayasu arteritis patients with coronary artery involvement. Semin Arthritis Rheum. 2017;47:247–252. doi: 10.1016/j.semarthrit.2017.03.009.
    1. Couture P, Chazal T, Rosso C, Haroche J, Leger A, Hervier B, et al. Cerebrovascular events in Takayasu arteritis: a multicenter case-controlled study. J Neurol. 2018;265:757–763. doi: 10.1007/s00415-018-8744-8.
    1. Jung JH, Lee YH, Song GG, Jeong HS, Kim JH, Choi SJ, et al. Endovascular versus open surgical intervention in patients with Takayasu's arteritis: a meta-analysis. Eur J Vasc Endovasc Surg. 2018;55:888–899. doi: 10.1016/j.ejvs.2018.02.030.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel