Narrative Review: The Systemic Capillary Leak Syndrome

Abstract

In 1960, Dr. Bayard Clarkson described a patient experiencing sporadic episodes of hypovolemia, hypotension, and edema. Plasma during the acute attack induced a “shock”-like syndrome when given systemically in rats. The unusual and enigmatic “Systemic Capillary Leak Syndrome” (SCLS) named for Dr. Clarkson is of unknown etiology and is characterized by transient, severe, reversible hemoconcentration and hypoalbuminemia due to leakage of fluids and macromolecules (up to 900 kDa) into tissues (1). Fewer than 150 cases of SCLS have been reported since 1960, but the nonspecific presenting symptoms and signs and high mortality rate may have resulted in under-recognition of this disorder. Given the substantial overlap of SCLS with other “shock” syndromes, including sepsis, anaphylaxis, and angioedema, clinicians should consider this diagnosis in patients with unexplained edema, increased hematocrit, and hypotension.

Idiopathic Systemic Capillary Leak Syndrome in Children

“…By contrast, 75% to 95% of adults with classic acute SCLS have monoclonal gammopathy of undetermined significance. 2,3 Our current and limited understanding of SCLS pathogenesis is that endothelial contraction and adhesive junction remodelling lead to capillary hyperpermeability and subsequent plasma extravasation. 14,15 Although the high prevalence of monoclonal gammopathy of undetermined significance in adult cases raises the possibility of a paraprotein/autoantibody-mediated mechanism, we and others [14][15][16] have been unable to demonstrate a direct pathogenic function of the monoclonal IgG in SCLS.…”

“…Since then, only 200 to 300 similar cases of what was later termed the "systemic capillary leak syndrome" (SCLS) have been reported. 2,3 Most of the documented subjects are adults, who experience recurrent episodes of severe hypotensive shock due to extravasation of plasma fluid and proteins into the interstitium, resulting in hemoconcentration, hypoalbuminemia, hyponatremia, and severe generalized edema. SCLS is associated with substantial morbidity and mortality, with a 5-year overall survival of 73% to 76%.…”

Idiopathic Systemic Capillary Leak Syndrome Preceding Diagnosis of Infiltrating Lobular Carcinoma of the Breast With Quiescence During Neoadjuvant Chemotherapy

“…[1][2][3][4][5][6] The shock that patients with SCLS experience, with associated hemoconcentration and hypoalbuminemia, is caused by sudden, massive leakage of proteins and serum into the extravascular space. 1,7 Plasma proteins up to 200 kDa or, in some cases, 900 kDa escape the capillary bed, resulting in an intravascular loss of up to 70% of plasma volume.…”

“…1,13,14 Use of numerous investigational drugs has been reported with variable outcomes. 6,[15][16][17][18][19][20] Traditional prophylactic therapies, theophylline/aminophylline and terbutaline, have been reported to achieve durable success, 3,6,9,21 despite a lack of understanding of their mode of action. Spironolactone, hydrocortisone, progesterone, and dexamethasone all appear to protect against endothelial cell apoptosis in response to serum deprivation, 22 whereas albumin inhibits endothelial cell apoptosis when there is intact endothelial cell adhesion, 23 suggesting that these therapies have potential benefit.…”

Systemic Capillary Leak Syndrome Caused by Granulocyte Colony-Stimulating Factor

“…Moreover, increased levels of G-CSF have been reported after infusions of IL-2, IL-4, IL-6, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor as well as after allogeneic hematopoietic stem cell transplantation (1,2,5). Therefore, in some SCLS, G-CSF might be useful biomarker for the severity of attacks in SCLS, but not in all cases.…”