10-year-old girl with life-threatening idiopathic systemic capillary leak syndrome: a case report
© Iwasa et al.; licensee BioMed Central Ltd. 2014
Received: 27 June 2013
Accepted: 23 May 2014
Published: 31 May 2014
Idiopathic systemic capillary leak syndrome (ISCLS) is a rare disorder, characterized by episodic life-threatening hypotension, hypoalbuminemia, and hemoconcentration.
A 10-year-old girl presented with abdominal pain, vomiting, diarrhea, fever and developed generalized edema a day after admission. Clinical and laboratory findings were consistent with ISCLS. She received aggressive fluid replacement, methylprednisolone pulse (30 mg/kg/day), high-dose intravenous immunoglobulin (IVIG, 2 g/kg/day) and plasma exchange in acute phase. She received fasciotomy of bilateral lower extremities as she developed complications of compartment syndrome. Since there were two episodes of ISCLS attacks, theophylline and terbutaline were initiated for prevention of attacks and then the remission is currently maintained. Because of high fatality rate in ISCLS, prompt diagnosis and intervention are very important.
We describe here, a rare case of pediatric ISCLS. ISCLS should be considered as a differential diagnosis, when the patient presents with unexplained or sudden hypovolemic shock. Reports on pediatrics ISCLS are very few, and accumulation of similar case reports is needed.
KeywordsIdiopathic systemic capillary leak syndrome Vascular endothelial damage Methylprednisolone pulse Theophylline Terbutaline
Idiopathic Systemic Capillary Leak Syndrome (ISCLS), also known as Clarkson’s disease, is a very rare disorder, characterized by recurrent episodes of severe hypotension, hypoalbuminemia and hemoconcentration . Attacks of ISCLS demonstrate three phases: (1) prodrome, (2) hypovolemia with weight gain and (3) hypervolemia with fluid overload and polyuria often complicated by pulmonary edema. Compartment syndrome, leading to rhabdomyolysis is a serious complication of ISCLS .
Laboratory data on admission
41 × 103/μL
(3.9-6.60 × 103/μL)
7.99 × 106/μL
(4.08-4.81 × 106/μL)
25.7 × 104/μL
(18.0-36.5 × 104/μL)
Culture (Blood, Urine, Stool): (−)
Only 10 cases of ISCLS in children have been reported to date [3–11]. These attacks occurred at ages ranging from 5 months to 8 years. Most of the cases were severe or fatal. All patients in reports were previously healthy and only one had a family history of ISCLS. ISCLS should be included in the differential diagnosis of sudden hypovolemic shock with general edema (anaphylaxis, C1-esterase inhibitor deficiency, nephrotic syndrome). Pathogenesis and pathophysiology of ISCLS are relatively unknown. Reports suggest that VEGF and angiopoietin 2 (Ang2) contribute to endothelial contraction and might be associated with pathogenesis . Elevated levels of cytokines and chemical mediators (G-CSF, IL-6, IL-8 and monocyte chemotactic protein-1: MCP-1) were reported in some cases . G-CSF and VGEF levels might be a used as biomarkers for the severity and for monitoring the clinical course in ISCLS [14, 15]. In the present case, G-CSF was elevated, but VEGF was normal in plasma. Surprisingly, VEGF in ascites was elevated. There was a case report that did not show increase of VEGF in plasma as the present case, but the reason is unknown . Further investigations of various biomarkers, which might play an important role, are needed for clarify the pathophysiology of ISCLS. Although there are no established therapies in acute phase, corticosteroids and IVIG has been used to treat ISCLS attacks [8, 17]. Recently, it has been reported that a patient with ISCLS after stem cell transplantation was received anti-VEGF antibody bevacizumab despite low serum VEGF level, and improved within 48 hours . In pediatric case, the tumor necrosis factor alpha (TNF-α) antagonist infliximab was administered when serum TNF-α was increased, and clinical course was developed dramatically . In present case, methylprednisolone and IVIG could not improve symptoms and the effect of these treatments was limited. Therefore, appropriate fluid management in acute phase is most important. Prophylactic treatment with theophylline and terbutaline as well as IVIG has been shown to reduce frequency and severity of ISCLS attacks, which could be effective in the present case [8, 18].
In conclusion, ISCLS should be considered in the differential diagnosis when unexplained hypovolemic shock is observed. The diagnostic evaluation should be performed concurrently with initial fluid management. Immediate intervention should be started because ISCLS has a high fatality rate.
Written informed consent was obtained from the patient’s parents for publication of this Case report and any accompanying images. A copy of the written consents is available for review by the Editor of this journal.
Idiopathic systemic capillary leak syndrome
Granulocyte colony-stimulating factor
Vascular endothelial growth factor
Monocyte chemotactic protein-1
Tumor necrosis factor alpha.
We thank Professor Hiroshi Imai in Department of Emergency and Critical Care Center for his assistance with the management of this patient.
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- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/14/137/prepub
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