Takayasu arteritis usually occurs among females 40 years of age and younger, including children, but is rare during infancy. Because clinical manifestations are not specific, TA is difficult to diagnose. We studied 10 infants diagnosed with TA, most of whom were initially diagnosed with an infection or incomplete Kawasaki disease and were treated with anti-infective therapy and gamma globulin. However, with uncontrollable fever and inflammation and observation of coronary artery involvement, TA was considered as a diagnosis in these cases and was confirmed with further laboratory testing and vascular imaging. There are few reports of treatment results in the scientific literature, especially treatment of infantile TA, which is rare globally, making our treatment results useful for clinicians and researchers.
TA is usually chronic with either a linear course or a remitting-relapsing course. The inflammatory process causes thickening of arteries with narrowing or occlusion of the lumen. Glucocorticoids are the mainstay of treatment. Because glucocorticoids alone do not always achieve and maintain remission, approximately half of TA patients require immunosuppressive agents[4, 6–9]. In contrast with childhood TA, vascular involvement is highly variable in infants and carries a worse prognosis, requiring high-dose, long-duration GC use. Unfortunately, glucocorticoids significantly affect growth and development of infants – a side effect that cannot be ignored. For example, in our study, one infant was treated with glucocorticoids for 7 months, affecting growth and development and necessitating consideration of alternative therapy.
Clinical manifestations of TA are nonspecific in infants and children. Fever and inflammation are the most common manifestations; the abdominal aorta is the most commonly involved vessel[10–16]. In our series, eight (80%) cases had fever as the first symptom and most prominent clinical manifestation. Laboratory analyses showed increased leukocytes and inflammatory indexes. Vascular imaging showed that large and medium arteries were involved. The most commonly-involved arteries were carotid arteries, abdominal aortas and coronary arteries (9 cases, 90%). Thoracic aortas and subclavian aortas (8 cases, 80%), renal arteries (7 cases, 70%), axillary arteries, pulmonary arteries and descending aortas (6 cases, 60%), and superior mesenteric arteries (4 cases, 40%) were also commonly involved. All 10 infants were in active disease states at the time of diagnosis, with widespread vascular involvement, suggesting that the infants’ conditions were serious and had poor prognoses.
Tumor necrosis factor alpha (TNF-α) is implicated in TA inflammation. IFX is a TNF-α inhibitor that has direct cytotoxicity and induces apoptosis of immune cells. IFX is reported to have significant effectiveness in refractory TA that is resistant to glucocorticoids and immunosuppressants[8, 9, 17–20]. Our observations showed that IFX is also effective for treatment of TA in infants. Five of our cases were treated with IFX alone and five were treated with IFX combined with GC. We found that temperatures rapidly normalized, inflammatory indexes decreased, and vascular lesions gradually improved with IFX therapy. Additionally, IFX enabled a reduction in dose or discontinuation of GC. In cases 1-8, vascular lesions treated with IFX in the early stage began to resolve within 1.5-3 months. Most of the affected arteries recovered within 13 months, but some remained stenotic, with intimal thickening and uneven lumens that which did not resolve. In Case 9, some vascular lesions worsened during GC and MTX treatment, but the vascular lesions gradually recovered after initiating IFX. In Case 10, the coronary arteries and abdominal aorta improved, but other vascular lesions did not improve during three months of combination GC and tocilizumab therapy. Some vascular lesions gradually recovered after initiating IFX. In 6 infants with hypertension, blood pressure returned to normal after 3-8 months of IFX treatment, showing that treatment with IFX could lead to inactive disease status. IFX was effective, beneficial, and well-tolerated in all 10 TA infants. In Case 9, growth and development lagged behind normal growth and development, but after stopping glucocorticoids and starting IFX, growth and development improved.
Our study showed that IFX has a good safety profile for use in infants. During IFX treatment, only 1 infant had an allergic reaction, which was during the eighth infusion; other infusions were not associated with adverse events. No severe infections were diagnosed during treatment, consistent with previous reports[10, 13, 20] . Early application of IFX in cases 1-8 had no impact on growth and development.
Our study had limitations. Our case series had only 10 infants, and the follow-up time was relatively short. Therefore, studies of long-term effectiveness and safety of IFX for infantile TA need to include more infants and have longer follow-up times.