Takayasu Arteritis in Children: Preliminary Experience with Cyclophosphamide Induction and Corticosteroids Followed by Methotrexate

doi:10.1016/j.jpeds.2006.10.059

The Journal of Pediatrics

Volume 150, Issue 1, January 2007, Pages 72-76

https://doi.org/10.1016/j.jpeds.2006.10.059 Get rights and content

Objective

To review the results of our treatment protocol in the last 7 years.

Study design

Six patients (4 girls, 2 boys) with an age range of 12 to 17 years were diagnosed with Takayasu arteritis (TA) during this period. Patients were allocated to receive (1) oral steroids and methotrexate (MTX) (12.5 mg/m²/week) if they had disease limited to one side of the diaphragm only without pulmonary disease involvement (two patients); and (2) oral steroids and oral cyclophosphamide (CYC) (maximum total dose 150 mg/kg) followed by oral MTX for maintenance as above if the disease was more widespread (four patients).

Results

One patient died of pulmonary vasculitis during the first month of therapy. The remaining three patients with involvement of both the thoracic and abdominal aorta and branches received the second protocol for 12 to 18 months. All entered remission. Aortic bypass, aortorenal bypass, balloon dilatation, and unilateral nephrectomy were performed in these patients.

Conclusions

The presented single-center experience suggests that CYC induction and corticosteroids followed by MTX is an effective and safe treatment for childhood TA.

Section snippets

Diagnosis

From 1998 to 2005 we have followed six patients (4 female, 2 male; all Turkish) with TA in our unit. All patients met the criteria of the American College of Rheumatology for TA and the recently introduced pediatric criteria.4, 5 Two were siblings (patients 1 and 5).

Features at Pesentation

Clinical features of the patients are summarized in the Table. The mean age at the onset the first symptom(s) was 12 years (10–15 years). Headache was present in two patients; abdominal pain and arthralgia/arthritis was present in

Results

Four patients were eligible for treatment with the second approach (prednisolone, CYC, and MTX). One patient (patient 2) died of pulmonary vasculitis during the first month of therapy. The remaining three (patients 1, 3, and 4), with involvement of both the thoracic and abdominal aorta and branches, received steroids with oral CYC for 12 weeks followed by weekly MTX for 12 to 18 months. Two patients (patients 5 and 6) had vasculitis of the abdominal aorta and renal artery, and they received

Discussion

TA is one of the interesting vasculitides, with its age at onset, distribution of vascular involvement, and the type of vessel destruction it displays. It is not a self-limited vasculitis such as Henoch Schönlein purpura or Kawasaki disease; thus, it requires prolonged treatment. The high relapse rate also necessitates extended treatment. Serial angiographic studies have shown that new lesions can be found in 61% of patients even when the disease is thought to be in remission.¹

The delay in

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The adverse events for biologic drugs were similar to what has been reported for other conditions treated with these therapies (infections, infusion reactions and cancer). Severe complications occurred with CYX, which was only used in patients with severe disease [14,15]. Long-term observational studies show that 5–10% of TAK patients have disease refractory to several drugs [7,8].
Takayasu's Arteritis (TAK) affects mostly young women and causes significant morbidity. Most patients are refractory to glucocorticoids (GC) or relapse when GC doses are reduced. The objective of this study is to summarize the literature pertaining to the effectiveness of non-GC drugs for the treatment of TAK.
MEDLINE and Embase were searched for English-language studies of TAK patients with a sample size >5. Studies were included if the effectiveness of non-GC drugs for the treatment of TAK was reported. Random effects meta-analyses of various effect measures were performed.
Of the 915 studies identified by the search, 14 of small molecule immunosuppressants (IS) and 25 of biologic therapies were included. Studies had a high risk of bias. Pooled remission rates were similar for both categories of non-GC drugs: 58% (95% CI: 40–74%) and 64% (95% CI: 56–72%), respectively. The relapse rate was 54% (95% CI: 39–68%) for IS therapies and 31% (95% CI: 22–41%) for biologics. Both significantly decreased GC doses and acute phase reactants. Observational studies suggested that anti-TNF agents were more effective than IS at maintaining remission. Randomized-controlled trials (RCTs) of biologics were of small sample size: abatacept was not effective and the trial of tocilizumab was underpowered to detect a difference in time to relapse versus placebo. Serious adverse events were uncommon.
Non-GC agents were moderately effective in inducing remission in TAK, but relapse rates were high. Larger, better designed studies are required to determine the optimal treatment regimen for TAK.
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Our aim was to describe our experience with tocilizumab (interleukin 6 receptor antagonist) treatment in children with Takayasu arteritis and to review previous studies regarding tocilizumab use in Takayasu arteritis patients.
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Our small series suggests that tocilizumab may be a promising alternative for Takayasu arteritis treatment. Long-term controlled studies are warranted to provide better evidence for tocilizumab treatment in childhood Takayasu arteritis.

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Original articleTakayasu Arteritis in Children: Preliminary Experience with Cyclophosphamide Induction and Corticosteroids Followed by Methotrexate

Objective

Study design

Results

Conclusions

Section snippets

Diagnosis

Features at Pesentation

Results

Discussion

Rheum Dis Clin North Am

Arch Pediatr

Takayasu arteritis

Ann Intern Med

Advances in medical and surgical treatment of Takayasu arteritis

Curr Opin Rheumatol

The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis

Arthritis Rheum

EULAR/PRES Endorsed Consensus Criteria for the Classification of Childhood Vasculitides

Ann Rheum Dis

Takayasu’s arteritis and tuberculosis: a case report

Clin Rheumatol

Takayasu’s arteritis: a study of 104 Italian patients

Arthritis Rheum

Original article
Takayasu Arteritis in Children: Preliminary Experience with Cyclophosphamide Induction and Corticosteroids Followed by Methotrexate