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Idiopathic systemic capillary leak syndrome

Rajesh Aneja, MD, FAAP
Section Editor
Scott Manaker, MD, PhD
Deputy Editor
Geraldine Finlay, MD


Idiopathic systemic capillary leak syndrome (ISCLS) is a rare disorder characterized by episodes of severe hypotension, hypoalbuminemia, and hemoconcentration [1,2]. During "attacks" of ISCLS, profound derangements of the vascular endothelium develop, resulting in leakage of plasma and proteins into the interstitial compartment [1,2]. Episodes vary in severity and frequency and may be fatal. ISCLS was first described by Clarkson in 1960 and is variably referred to as Clarkson's disease or syndrome [1].


Approximately 150 cases of idiopathic systemic capillary leak syndrome (ISCLS) have been reported worldwide [3,4]. These have been diagnosed primarily in middle-aged adults, although cases in children as young as five months old have been reported [5-9]. There is no apparent gender predilection.


The cause(s) of idiopathic systemic capillary leak syndrome (ISCLS) is not known, although there is an associated monoclonal gammopathy in many patients. Several theories of pathogenesis have been proposed and are discussed in this section. It is helpful first to review mechanisms of capillary leakage in other diseases.

Mechanisms of capillary leakage — The vascular endothelium is a semi-permeable barrier that controls the passage of fluid and macromolecules between the intravascular and interstitial spaces. Dysfunction of this barrier leads to leakage, with loss of intravascular fluid and protein into the interstitial compartment. Cells and platelets are generally retained within the vasculature, resulting in elevations in white blood cell, red blood cell, and platelet counts. The resulting intravascular fluid depletion can cause hypotension and impair the delivery of oxygen to the tissues. Severe capillary leakage can result in hypotension and shock.

There are many known causes of capillary leak, which can be categorized as follows:

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Literature review current through: Nov 2017. | This topic last updated: May 20, 2016.
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