Does Takayasu arteritis differ between children and adolescents? Insights from a Russian multicenter cohort

Table 1 Demographic and baseline characteristics of the total cohort and stratified by age group (< 10 years vs ≥ 10 years), n (%)

Characteristic	Total cohort (n = 79)	< 10 years (n = 25)	≥ 10 years (n = 54)	P value
Age at onset, years, median (IQR)	11.0 (8.0-14.0)	7.0 (5.0-8.5)	13.0 (11.0-14.0)	< 0.001
Female sex	62 (78.5)	15 (60.0)	47 (87.0)	0.016
Diagnostic delay, months, median (IQR)	8.0 (2.0-17.5)	10.0 (2,0-24.0)	7.0 (2.0-12.0)	0.209
Follow-up duration, months, mean ± SD	28.0 ± 22.0	35.8 ± 28.4	24.6 ± 19.6	0.088
Surgical intervention at diagnosis	12 (15.2)	8 (32.0)	4 (7.4)	0.008
ITAS.A at onset, mean ± SD	11.0 ± 4.6	8.9 ± 4.3	12.0 ± 4.4	0.005
ITAS 2010 at onset, median (IQR)	7.0 (5.0-12.5)	5.0 (3.0-8.0)	7.0 (5.0-9.0)	0.061
ESR at onset, mm/hour, mean ± SD	47.8 ± 24.9	37.5 ± 19.5	52.7 ± 25.8	0.012
CRP at onset, mg/L, median (IQR)	35.5 (11.8-90.2)	17.0 (5.0-36.0)	47.0 (15.0-100.2)	0.003

IQR: Interquartile range; ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein.

Table 2 Clinical manifestations at disease onset in the total cohort and stratified by age group (< 10 years vs ≥ 10 years), n (%)

Parameter	Total cohort (n = 79)	Total cohort (n = 79), %, 95%CI	< 10 years	≥ 10 years	P value
Malaise	67	84.8, 75.0-91.9	18 (72.0)	49 (90.7)	0.044
Fever	43	54.4, 42.8-65.7	10 (40.0)	33 (61.1)	0.080
Headache	37	46.8, 35.5-58.4	11 (44.0)	26 (48.1)	0.731
Arthralgia	21	26.6, 17.3-37.7	4 (16.0)	17 (31.5)	0.179
Arthritis	5	6.3, 2.1-14.2	0 (0.0)	5 (9.3)	0.173
Weight loss	20	25.3, 16.2-36.4	4 (16.0)	16 (29/6)	0.269
Myalgia	14	17.7, 10.0-27.9	4 (16.0)	10 (18.5)	1.000
Abdominal pain	14	17.7, 10.0-27.9	6 (24.0)	8 (14.8)	0.353
Limb claudication	21	26.6, 17.3-37.7	10 (40.0)	11 (20.4)	0.099
Limb numbness	13	16.5, 9.1-26.5	4 (16.0)	9 (16.7)	1.000
Diminished/absent pulse	25	31.6, 21.6-43.1	8 (32.0)	17 (31.5)	1.000
Vascular bruits	43	54.4, 42.8-65.7	11 (44.0)	32 (59.3)	0.205
Blood pressure difference between extremeties ≥ 10 mmHg	22	27.8, 18.3-39.1	7 (28.0)	15 (27.8)	1.000
Carotidynia	11	13.9, 7.2-23.5	2 (8.0)	9 (16.7)	0.487
Arterial hypertension	28	35.4, 25.0-47.0	9 (36.0)	19 (35.2)	1.000
Vascular pain	21	26.6, 17.3-37.7	5 (20.0)	16 (29.6)	0.424
Epistaxis	4	5.1, 1.4-12.5	3 (12.0)	1 (1.9)	0.091
Lymphadenopathy	7	8.9, 3.6-17.4	1 (4.0)	6 (11.1)	0.422
Hearing loss	1	1.3, 0.0-6.9	0 (0.0)	1 (1.9)	1.000
Nausea	4	5.1, 1.4-12.5	0 (0.0)	3 (5.6)	1.000
Syncope	8	10.1, 4.5-19.0	3 (12.0)	5 (9.3)	0.703
Dizziness	8	10.1, 4.5-19.0	1 (4.0)	7 (13.0)	0.424
Visual impairment	4	5.1, 1.4-12.5	0 (0.0)	4 (7.4)	0.302

Table 3 Frequency of vascular involvement at disease onset in the total cohort and stratified by age group (< 10 years vs ≥ 10 years), n (%)

Vessel	Total cohort (n = 79)	Total cohort (n = 79), %, 95%CI	< 10 years (n = 25)	≥ 10 years (n = 54)	P value
Brachiocephalic trunk	20	25.3, 16.2-36.4	6 (24.0)	14 (25.9)	1.000
Left common carotid artery	41	51.9, 40.4-63.3	11 (44.0)	30 (55.6)	0.339
Right common carotid artery	29	36.7, 26.1-48.3	7 (28.0)	22 (40.7)	0.323
Left subclavian artery	33	41.8, 30.8-53.4	9 (36.0)	24 (44.4)	0.479
Right subclavian artery	13	16.5, 9.1-26.5	3 (12.0)	10 (18.5)	0.536
Axillary artery	1	1.3, 0.0-6.9	0 (0.0)	1 (1.9)	1.000
Left vertebral artery	14	17.7, 10.0-27.9	4 (16.0)	10 (18.5)	1.000
Right vertebral artery	4	5.1, 1.4-12.5	2 (8.0)	2 (3.7)	0.587
Ascending aorta	17	21.5, 1.4-12.5	6 (24.0)	11 (20.4)	0.772
Aortic arch	15	19.0, 11.0-29.4	7 (28.0)	8 (14.8)	0.219
Descending aorta	29	36.7, 26.1-48.3	11 (44.0)	18 (33.3)	0.453
Abdominal aorta	41	51.9, 40.4-63.3	15 (60.0)	26 (48.1)	0.327
Celiac trunk	26	32.9, 22.7-44.4	8 (32.0)	18 (33.3)	1.000
Superior mesenteric artery	21	26.6, 17.3-37.7	7 (28.0)	14 (25.9)	1.000
Left renal artery	24	30.4, 20.5-41.8	9 (36.0)	15 (27.8)	0.600
Right renal artery	20	25.3, 16.2-36.4	8 (32.0)	12 (22.2)	0.409
Splenic artery	2	2.5, 0.3-8.8	1 (4.0)	1 (1.9)	0.536
Iliac arteries	8	10.1, 4.5-19.0	3 (12.0)	5 (9.3)	0.703
Coronary arteries	2	2.5, 0.3-8.8	1 (4.0)	1 (1.9)	0.536
Pulmonary trunk	3	3.8, 0.8-10.7	1 (4.0)	2 (3.7)	1.000
Femoral arteries	5	6.3, 2.1-14.2	2 (8.0)	3 (5.6)	0.849

Table 4 Association between age of Takayasu arteritis onset and surgical treatment

Parameter	Value	95%CI	P value
Spearman’s correlation (age of onset and number of surgeries)	ρ = -0.316	-	0.012
Linear regression: Change in age of onset per one surgery	β = -1.3 years	-2.1 to -0.5	0.002
Linear regression model fit (R2)	0.24	-	0.002

ρ: Spearman’s correlation coefficient; β: Linear regression coefficient; CI: Confidence interval. All shown associations are statistically significant (P < 0.05).

Table 5 Baseline characteristics of patients included in and excluded from outcome analysis

Parameter	Outcome analysis (n = 62)	Excluded (n = 17)	P value
Disease duration, months, median	49.00 [26.00; 65.00]	9.50 [3.25; 15.25]	< 0.001
Time from first symptoms to diagnosis, months, median	7.00 [2.00; 20.00]	9.50 [2.25; 14.25]	0.930
Follow-up duration after diagnosis, months, median	30.00 [19.50; 44.25]	1.00 [1.00; 2.00]	< 0.001
Age at onset, years, median	11.00 [9.00; 14.00]	11.00 [8.00; 13.00]	0.647
ITAS2010 at onset, median	7.00 [5.00; 9.00]	5.00 [4.00; 7.00]	0.173
ITAS.A at onset, median	11.00 [9.00; 14.00]	7.00 [5.00; 11.00]	0.015
CRP at onset, mg/L, median	40.00 [15.73; 99.25]	4.90 [1.23; 36.75]	0.001
ESR at onset, mm/hour	50.90 (22.06)	36.56 (31.49)	0.040
bDMARD use	38 (61.3)	2 (11.8)	0.001
Female sex	51 (82.3)	11 (64.7)	0.197
Surgical intervention at diagnosis	7 (11.3)	4 (23.5)	0.131

Data are presented as median (interquartile range), mean (SD), or n (%). IQR: Interquartile range; bDMARD: Biologic disease-modifying antirheumatic drugs; ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein.

Table 6 Logistic regression model for the prediction of biologic disease-modifying antirheumatic drugs prescription

Parameter	Value
Model characteristics	Model characteristics
Number of patients (n)	78
Nagelkerke R2, %	12.3
Model P value	0.006
Predictor: Follow-up duration (per 1 month)	Predictor: Follow-up duration (per 1 month)
Odds ratio	1.030
95%CI	1.007-1.052
P value	0.010
Equation	Equation
Logit function (Z)	Z = -0.802 + 0.029 × follow-up (months)
Predicted probability (P)	P = 1/(1 + e-z)
Discriminatory performance	Discriminatory performance
Area under the curve	0.704
95%CI	0.589-0.820
P value	0.002
Optimal cut-off (Youden index)	0.396
Sensitivity at cut-off, %	89.7
Specificity at cut-off, %	46.2
Additional predictors assessed	Additional predictors assessed
Other baseline clinical/laboratory parameters	No statistically significant associations identified

CI: Confidence interval.

Table 7 Clinical characteristics of three deceased patients

Parameter	Patient 1	Patient 2	Patient 3
Sex	Male	Male	Female
Age at onset, years	5	11	8
TA type (Hata et al[25])	IIb	IV	V
ITAS2010/ITAS.A at diagnosis	11/14	4/6	6/12
Follow-up, months	57	4	88
Time from onset to surgery, months	57	3	12
Surgery reason	Bilateral critical renal artery stenosis	Bilateral critical renal artery stenosis	Bilateral critical renal artery stenosis, abdominal aorta stenosis
Cause of death	Multi-organ failure, sepsis	Multi-organ failure, sepsis	Rupture of aortic anastomotic aneurysm
bDMARDs	Yes	No	Yes

TA: Takayasu arteritis; bDMARDs: Biologic disease-modifying antirheumatic drugs.