title: Isoform D of vascular endothelial growth factor in systemic capillary leak syndrome: a case report.
abstract: BACKGROUND
  Systemic capillary leak syndrome is a rare condition characterized by episodic attacks of hypovolemia due to systemic capillary hyperpermeability, which results in profound hypotension and edema. Although the implication of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 has been suggested, the pathogenesis of systemic capillary leak syndrome remains unclear. In this report, we describe a case of systemic capillary leak syndrome in which serum isoform D of vascular endothelial growth factor was elevated. To the best of our knowledge, this is the first reported case of systemic capillary leak syndrome in which isoform D of vascular endothelial growth factor is suggested as the plausible biomarker.
  
  
  METHODS
  A 41-year-old Japanese man was transferred to our emergency department. He was hypotensive, tachycardic, and edematous over the trunk and all four limbs. He received aggressive intravenous fluid therapy and underwent fasciotomy of the right forearm to prevent muscle necrosis. A diagnosis of systemic capillary leak syndrome was suspected. The presence of serum monoclonal immunoglobulin G and κ light chain supported this diagnosis. Prevention of hypotensive crises was unsuccessfully attempted with theophylline, intravenous immunoglobulin, high-dose dexamethasone, bortezomib, melphalan, and prednisolone; however, the patient's attacks dramatically disappeared after the introduction of thalidomide. The serum of the patient was stored soon after the onset of hypotensive crisis and analyzed to profile possible mediators responsible for the capillary leak. The concentration of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 were all within normal ranges. Meanwhile, we found that isoform D of vascular endothelial growth factor was elevated, which was normalized after the introduction of thalidomide.
  
  
  CONCLUSIONS
  In our patient, isoform D of vascular endothelial growth factor (instead of vascular endothelial growth factor) may have been a causative factor of hypotensive crises, since isoform D contributes to vascular endothelial growth factor receptor-2 signaling, which is the major mediator of the permeability-enhancing effects of vascular endothelial growth factor. We suggest the measurement of isoform D of vascular endothelial growth factor in patients with systemic capillary leak syndrome in whose serum vascular endothelial growth factor is not elevated.
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Soushi
authors.initials: S
authors.lastname: Ibata
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Kohichi
authors.initials: K
authors.lastname: Takada
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Tatekoshi
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Hashimoto
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kamihara
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Jomen
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Horiguchi
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ono
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Murase
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iyama
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Miyanishi
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Rishu
authors.initials: R
authors.lastname: Takimoto
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kobune
authors.affiliation: Department of Medical Oncology and Hematology, School of Medicine, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo, Japan. jkato@sapmed.ac.jp.
authors.forename: Junji
authors.initials: J
authors.lastname: Kato
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers; D019559:Capillary Leak Syndrome / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007022:Hypotension / Q000150:complications / Q000188:drug therapy; D008297:Male; D020033:Protein Isoforms / Q000097:blood; D013792:Thalidomide / Q000627:therapeutic use*; D042643:Vascular Endothelial Growth Factor D / Q000009:adverse effects* / Q000097:blood*
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D020033:Protein Isoforms; D042643:Vascular Endothelial Growth Factor D; D013792:Thalidomide