Prognostic impact of vascular leakage in acute Kawasaki disease.
BACKGROUND
Increased microvascular permeability is an initial step of Kawasaki disease (KD). We reported that vascular endothelial growth factor (VEGF) might play a role in the vascular leakage of KD. In fatal KD, plasma leakage was extensively documented at VEGF-positive microvessels. Increases in vascular leakage cause hypoalbuminemia and noncardiogenic edema. However, the prognostic impact of vascular leakage in KD remains unclear.


RESULTS
We compared 76 patients who became afebrile within 5 days after starting intravenous gamma globulin (IVGG) (2 g/kg over 5 days) (IVGG-responsive) with 27 patients who did not respond (IVGG-resistant). Baseline levels of serum VEGF and albumin were similar between the groups. After IVGG, VEGF levels increased (P<0.0001) and albumin levels decreased (P<0.00001) in both groups. However, the IVGG-resistant group had higher VEGF levels (P=0.029) and severe hypoalbuminemia (P<0.00001) compared with the IVGG-responsive group. Coronary aneurysms were documented in 12 patients from the IVGG-resistant group but not in the IVGG-responsive group. Then IVGG-resistant patients were divided into 2 subgroups according to the presence (n=12) or absence (n=15) of coronary aneurysms. There was no difference between subgroups in age, sex, laboratory data including albumin, and retreated doses of IVGG. However, body weight gain after IVGG was documented in patients who subsequently developed coronary aneurysms (P=0.003) but not in those who did not (P=0.967).


CONCLUSIONS
These results suggest that vascular leakage may be a key feature of KD pathophysiology. The present study may provide better insights into the pathogenesis and treatment of patients resistant to IVGG in acute KD.
Terai
Masaru
M
Department of Pediatrics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan. terai@med.m.chiba-u.ac.jp
Honda
Takafumi
T
Yasukawa
Kumi
K
Higashi
Kouji
K
Hamada
Hiromichi
H
Kohno
Yoichi
Y
D000208:Acute Disease; D001835:Body Weight / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003323:Coronary Aneurysm / Q000209:etiology; D004351:Drug Resistance; D004487:Edema / Q000209:etiology; D016228:Endothelial Growth Factors / Q000097:blood; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008222:Lymphokines / Q000097:blood; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology*; D011379:Prognosis; D012709:Serum Albumin / Q000032:analysis / Q000627:therapeutic use; D013256:Steroids / Q000627:therapeutic use; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D016756:Immunoglobulins, Intravenous; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012709:Serum Albumin; D013256:Steroids; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors