PMC8107285_01
Time series of various examinations (A) White blood cell (WBC) differential count; Patient's feet upon examination (right panel: edematous, left panel: recovery). Both white blood cell and eosinophil counts reached their peak on day 7. (B) Investigations: Lactate dehydrogenase was slightly elevated in the initial stage, but soon normalized. The reference range for LDH is 110-220 IU/L. Other investigations were within normal range through the course of illness.
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Physical examination revealed striking, non-pitting edema of both lower legs and feet ( Figure 1A ). Initial laboratory findings were as follows: white blood cell count was 1.82x104/muL, and it increased to 1.91x104/muL with 68.6% eosinophils later (eosinophil count was as high as 1.31x104/muL) ( Figure 1A ). Serum lactate dehydrogenase was slightly elevated ( Figure 1B ). Table 1 ). There was no evidence of anemia, hypoalbuminemia, or thyroid dysfunction ( Figure 1B ).
Body impedance analysis and cytokines/chemokines (A) The ratio of extracellular water to total body water (ECW/TBW). Lower extremity, especially left leg showed the most severe edema. The normal range for ECW/TBW for edema is less than 0.39. (B) Time series of body weight and fluid volume in each part remained unchanged throughout the course of illness. (C) Cytokines and chemokines known to be involved in NEAE. IL-5, interleukin-5; TARC, thymus-and activation-regulated chemokine; CCL, C-C motif chemokine ligand; TNF-alpha, tumor necrosis factor-alpha; VEGF-A, vascular endothelial growth factor-A. (D) Cytokines and chemokines newly reported to be involved in NEAE. MCP-4, monocyte chemoattractant protein-4.
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The high ratio of extracellular water to total body water (ECW/TBW) in the trunk and lower limbs, especially on the left side, concurred with the finding of edema (  Figure 2A ). Although the total amount of body water and intra- and extra-cellular water remained unchanged ( Figure 2B ), bioimpedance analysis revealed edema of the trunk and lower legs. Figure 2C ). Furthermore, we found the relationship between monocyte chemotactic protein-4/CCL-13 (MCP-4/CCL-13), eotaxin-1/CCL-11, and regulated on activation, normal T expressed and secreted/CCL-5 (RANTES/CCL-5), and the extent of disease ( Figure 2D ).