Importance of Serum Ferritin Level for Early Diagnosis and Differentiation in Patients with Kawasaki Disease with Macrophage Activation Syndrome

Abstract

We aimed to evaluate the utility of the serum ferritin level as an early screening test of Kawasaki disease with macrophage activation syndrome (KD-MAS). We analyzed the serum ferritin levels on the first day of admission and the clinical progress of patients diagnosed with complete or incomplete KD. Of the 158 patients, 5 were diagnosed with KD-MAS. Conjunctival injection was significantly more frequent in KD group (p = 0.035), although there were no significant differences in other clinical features. On the first day of admission, the serum ferritin level in the KD-MAS group was >500 ng/mL, which was higher than that in the KD group (p = 0.001). In the KD-MAS group, total bilirubin, triglyceride, and lactate dehydrogenase (LDH) were significantly higher, and erythrocyte sedimentation rate (ESR), total protein, albumin, and fibrinogen were significantly lower than the KD group (p < 0.05). Four patients were diagnosed with MAS within 7 days after admission, and 4 (80%) patients with KD-MAS survived. In conclusion, carrying out an early ferritin screening test is important in patients with principal clinical features that may suspect KD. We propose to include ferritin level in the primary laboratory test to differentiate between KD with and without MAS early.

Serum ferritin as a crucial biomarker in the diagnosis and prognosis of intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease: A systematic review and meta-analysis

“…In general, the minimum value of DOR is 0, and the maximum value is infinity; a higher value of DOR suggests a better discriminatory test performance ( 46 ). All these results suggested that SF might be suitable as a potential biomarker for diagnosing KD, which is consistent with conclusions from other studies ( 20 , 47 ). Ferritin is an acute-phase reactant that is utilized in clinical practice as a serum biomarker ( 37 ), which regulates the homeostasis of serum iron, and elevated ferritin concentration signifies high levels of stored iron ( 48 ).…”

Under-Recognized Macrophage Activation Syndrome in Refractory Kawasaki Disease: A Wolf in Sheep’s Clothing

“…In fact, the incidence of MAS was reported to be 4.8% (3/63) in KD shock syndrome [ 24 ] and 3.2% (8/247) in incomplete KD [ 14 ], both of which have more severe clinical manifestations than typical KD. In this study, the incidence of MAS in refractory KD was 6.3%, which is similar to that found in previous studies by Roh et al [ 20 ] and Qiu et al [ 21 ] ( Table 3 ). The reported incidence of MAS is 7.0–13.0% in children with sJIA and 0.9–4.6% in children with SLE [ 9 , 25 ].…”

“…These risk factors are useful for predicting IVIG resistance, but they are not useful for distinguishing refractory KD and MAS because they are found in both refractory KD and MAS patients [ 12 , 18 ]. The mortality rate of MAS in patients with KD was reported to be 13–25% [ 13 , 20 ]. To not overlook MAS, it is necessary to consider the possibility of developing MAS in patients with KD, especially those with risk factors for IVIG resistance.…”

“…Pilania et al [ 19 ] have highlighted that the application of MAS screening to patients with KD was determined by physician experience rather than by clinical severity. Given the low incidence of MAS in KD (0.4–1.9%), it may be not necessary to include MAS screening in routine laboratory tests for KD [ 20 ]. However, given the relatively high incidence of MAS in refractory KD (6.3–7.0%), it is worthwhile to include MAS screening in routine laboratory tests for refractory KD.…”

“… MAS, macrophage activation syndrome; KD, Kawasaki disease; IVIG, intravenous immunoglobulin. a The incidence of MAS in KD is exceptionally high, probably because subjects with severe clinical manifestations and who were tested for serum ferritin levels were included in their prospective study [ 20 ]. b The number of patients with refractory KD was calculated using the average proportion of refractory KD (i.e., 15% of total KD [ 1 ]) in studies that did not represent the number of patients with refractory KD.…”