Capillary leak syndrome: etiologies, pathophysiology, and management

Abstract

In various human diseases, an increase in capillary permeability to proteins leads to the loss of protein-rich fluid from the intravascular to the interstitial space. Although sepsis is the disease most commonly associated with this phenomenon, many other diseases can lead to a "sepsis-like" syndrome with manifestations of diffuse pitting edema, exudative serous cavity effusions, noncardiogenic pulmonary edema, hypotension, and, in some cases, hypovolemic shock with multiple-organ failure. The term capillary leak syndrome has been used to describe this constellation of disease manifestations associated with an increased capillary permeability to proteins. Diseases other than sepsis that can result in capillary leak syndrome include the idiopathic systemic capillary leak syndrome or Clarkson's disease, engraftment syndrome, differentiation syndrome, the ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune diseases, snakebite envenomation, and ricin poisoning. Drugs including some interleukins, some monoclonal antibodies, and gemcitabine can also cause capillary leak syndrome. Acute kidney injury is commonly seen in all of these diseases. In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome; hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury. The purpose of this article is to discuss the diseases other than sepsis that produce capillary leak and review their collective pathophysiology and treatment.

Chemotherapy‐induced skin toxicity and capillary leak syndrome

“…2 Factors associated with the development of CLS include sepsis, acute renal failure, adverse drug reactions, autoimmune and hematologic diseases, and post hematopoietic stem cell transplant (HSCT), but it may also be idiopathic. [3][4][5] Oncologic medications have also been identified as provoking factors of CLS. Drugs including denileukin diftitox, 6,7 gemcitabine, 8 imatinib, 9 and oxaliplatin 10 have been implicated.…”

Quantification of total dinutuximab concentrations in neuroblastoma patients with liquid chromatography tandem mass spectrometry

“…However, patients on Unituxin will continue to receive this formulation. DNX-β can be given without co-administration of interleukin-2, which induces inflammatory side effects [28]. These two drugs contain the same peptide sequences, only glycosylation differences can occur due to the different cell lines used.…”

Acute kidney injury caused by decompression illness successfully treated with hyperbaric oxygen therapy and temporary dialysis

“…CLS could be caused by increased vascular permeability resulting from endothelial injuries caused by gas bubbles and causes hemoconcentration [11]. AKI is commonly observed in patients with CLS, and appropriate fluid management is an essential part of the treatment [12]. The Hct increases significantly after diving, and this increase is weakly correlated to the maximum depth of the dive [13].…”