Abstract
ObjectivesThe Systemic Capillary Leak Syndrome (SCLS) is a rare and potentially fatal disorder resembling systemic anaphylaxis that is characterized by transient episodes of hypotensive shock and peripheral edema. The pathogenesis of SCLS is unknown, and triggers for attacks are apparent only in a minority of patients. We introduce a clinical algorithm for the diagnosis of SCLS, and we investigated potential serum biomarkers of acute SCLS episodes.MethodsWe analyzed serum cytokines in a cohort of 35 patients with an established diagnosis of SCLS and characterized the effects of SCLS sera on endothelial cell function. We investigated the cellular source(s) of CXCL10, a chemokine that was significantly elevated in both basal and acute SCLS sera, by flow cytometry.ResultsSeveral cytokines were elevated in acute SCLS sera compared to baseline or sera from healthy controls, including CXCL10, CCL2, IL-1β, IL-6, IL-8, IL-12 and TNFα. The majority of acute sera failed to activate endothelial cells as assessed by surface adhesion marker expression. Monocytes appear to be the major source of serum CXCL10, and the percentage of CXLC10+ monocytes in response to IFNγ stimulation was increased in SCLS subjects compared to controls.ConclusionsThe presence of proinflammatory cytokines in acute SCLS sera suggests that inflammation or infection may have a role in triggering episodes. The enhanced capacity of monocytes from SCLS patients to produce CXCL10 suggests a new therapeutic avenue for SCLS.
Highlights
The Systemic Capillary Leak Syndrome (SCLS) is a life-threatening disorder that occurs sporadically, typically in middle-aged Caucasians [1,2]
Using samples from our () 23-patient cohort, we reported previously that sera from SCLS patients during acute disease intervals uniformly induced hyperpermeability of human microvascular endothelial cell (HMVEC) monolayers due to disruption of endothelial adherens junctions and actin stress fiber formation [4]
Complement factor 1 esterase inhibitor (C1 INH) levels and function should be evaluated in all patients with suspected SCLS to rule out hereditary or acquired angioedema
Summary
The Systemic Capillary Leak Syndrome (SCLS) is a life-threatening disorder that occurs sporadically, typically in middle-aged Caucasians [1,2]. SCLS resembles, and is often erroneously diagnosed as, more common disorders such as sepsis, angioedema, and systemic anaphylaxis. Because no specific biomarkers or pathognomonic clinical sign(s) of SCLS exist currently, the triad of transient hypotension, hemoconcentration, and serum hypoalbuminemia in the absence of underlying causes is sufficient to establish the diagnosis [2,5,6]. There is no specific treatment for acute SCLS other than hemodynamic support with intravenous fluids and vasopressors. Drugs such as theophylline, β2-adrenergic agonists, and most recently, imatinib, have been used as prophylactic agents to promote vascular integrity in SCLS [6]. Based on anecdotal evidence accumulated over several years, it has become apparent that monthly intravenous immunoglobulin (IVIG, 2 g/kg) infusions have severely curtailed attacks in a majority of patients who receive this therapy indefinitely [6,7,8]
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