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Kidney International Jul 2017In 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.... (Review)
Review
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.
Topics: Acute Kidney Injury; Animals; Capillaries; Capillary Leak Syndrome; Capillary Permeability; Diagnosis, Differential; Fluid Therapy; Hemodynamics; Humans; Plasma Substitutes; Pleural Effusion; Predictive Value of Tests; Risk Factors; Sepsis; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome
PubMed: 28318633
DOI: 10.1016/j.kint.2016.11.029 -
British Journal of Clinical Pharmacology Aug 2021Many drugs are responsible, through different mechanisms, for peripheral oedema. Severity is highly variable, ranging from slight oedema of the lower limbs to anasarca... (Review)
Review
Many drugs are responsible, through different mechanisms, for peripheral oedema. Severity is highly variable, ranging from slight oedema of the lower limbs to anasarca pictures as in the capillary leak syndrome. Although most often noninflammatory and bilateral, some drugs are associated with peripheral oedema that is readily erythematous (eg, pemetrexed) or unilateral (eg, sirolimus). Thus, drug-induced peripheral oedema is underrecognized and misdiagnosed, frequently leading to a prescribing cascade. Four main mechanisms are involved, namely precapillary arteriolar vasodilation (vasodilatory oedema), sodium/water retention (renal oedema), lymphatic insufficiency (lymphedema) and increased capillary permeability (permeability oedema). The underlying mechanism has significant impact on treatment efficacy. The purpose of this review is to provide a comprehensive analysis of the main causative drugs by illustrating each pathophysiological mechanism and their management through an example of a drug.
Topics: Edema; Heart Failure; Humans; Lymphedema; Pharmaceutical Preparations; Vasodilation
PubMed: 33506982
DOI: 10.1111/bcp.14752 -
Biology of Blood and Marrow... Apr 2019Chimeric antigen receptor (CAR)-modified T cells (CAR-Ts) targeting CD19 have resulted in unprecedented durable remissions for patients with relapsed and refractory B... (Review)
Review
Chimeric antigen receptor (CAR)-modified T cells (CAR-Ts) targeting CD19 have resulted in unprecedented durable remissions for patients with relapsed and refractory B cell malignancies. Cytokine release syndrome (CRS), resulting from rapid immune activation induced by CAR-Ts, is the most significant treatment-related toxicity. CRS initially manifests with fever and can progress to life-threatening capillary leak with hypoxia and hypotension. The clinical signs of CRS correlate with T cell activation and high levels of cytokines including IL-6. Tocilizumab, an anti-IL-6 receptor antagonist, is the standard for CRS management, but optimal timing of administration is unclear. The development of a supportive infrastructure by treatment centers is important to maintain safe administration as access expands. Collaborative efforts are underway to harmonize the definition and grading of CRS to allow for better interpretation of toxicities across CAR-T products and clinical trials and allow for informed management algorithms.
Topics: Cell- and Tissue-Based Therapy; Cytokine Release Syndrome; Humans; Receptors, Chimeric Antigen
PubMed: 30586620
DOI: 10.1016/j.bbmt.2018.12.756 -
Kidney International Reports May 2022The term capillary leak syndrome (CLS) describes the manifestations associated with an increased capillary permeability to proteins leading to an escape of plasma from... (Review)
Review
The term capillary leak syndrome (CLS) describes the manifestations associated with an increased capillary permeability to proteins leading to an escape of plasma from the blood circulatory system to surrounding tissues, muscle, organs, or body cavities. This results clinically in the typical triad of hypotension, edema, and elevated hematocrit. The more severe cases of CLS may present with cardiovascular collapse, shock, and death. The most classic form of this pathology is represented by the idiopathic systemic CLS (SCLS) also called Clarkson's disease, but capillary leaks are also described as adverse drug reactions foremost among which are anticancer drugs. This review will focus on oncologic drugs such as gemcitabine, therapeutic growth factors or cytokines, and monoclonal antibodies (mAbs) that appear now as the strongest candidates for anticancer drug-induced CLS.
PubMed: 35570987
DOI: 10.1016/j.ekir.2022.02.014 -
Case Reports in Oncology 2023Capillary leak syndrome is a rare life-threatening disorder of acute endothelial hyperpermeability. It consists of initial fluid extravasation resulting in hypotension,...
Capillary leak syndrome is a rare life-threatening disorder of acute endothelial hyperpermeability. It consists of initial fluid extravasation resulting in hypotension, hypoalbuminemia, and hemoconcentration, followed by noncardiogenic pulmonary edema from rapid fluid remobilization into intravascular compartment. Drug-induced etiology is an important diagnostic consideration in cancer patients, particularly with use of antimetabolites, immunostimulants, and monoclonal antibodies. Sorafenib-mediated capillary leak syndrome has never been reported. Here, we present the case of a 29-year-old female patient with a desmoid tumor of the thigh, who was admitted for acute hypoxic respiratory failure after recent initiation of sorafenib. She was found to have extensive pulmonary edema, bilateral pleural effusions, and hemoconcentration, all of which stabilized on supportive care with noninvasive mechanical ventilation and intravenous diuresis. Her infectious and cardiac work-up were negative. Given the temporal relationship between sorafenib use and symptom onset as well as a lack of an alternative etiology of her findings, patient was deemed to have sorafenib-induced acute capillary leak syndrome. Importantly, she did not become hypotensive prior to or during this hospitalization. To our knowledge, we reported for the first time an atypical presentation of acute capillary leak syndrome due to sorafenib use without hemodynamic instability.
PubMed: 37900814
DOI: 10.1159/000533957 -
Zhongguo Dang Dai Er Ke Za Zhi =... Oct 2020Neonatal capillary leak syndrome is a clinical syndrome with definite etiology or predisposing factors and has the manifestations of hypotension, hemoconcentration,...
Neonatal capillary leak syndrome is a clinical syndrome with definite etiology or predisposing factors and has the manifestations of hypotension, hemoconcentration, hypoproteinemia, and systemic edema. This disease often has critical conditions and may lead to multiple organ failure and even death. There are still controversies over the diagnosis and treatment of this disease. This article summarizes the recent advances in the diagnosis and treatment of neonatal capillary leak syndrome, in order to improve the diagnosis and treatment of this disease among clinicians.
Topics: Capillary Leak Syndrome; Edema; Humans; Hypoproteinemia; Multiple Organ Failure
PubMed: 33059800
DOI: 10.7499/j.issn.1008-8830.2004033 -
The New England Journal of Medicine Sep 2010Preclinical and preliminary clinical data indicate that ch14.18, a monoclonal antibody against the tumor-associated disialoganglioside GD2, has activity against... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Preclinical and preliminary clinical data indicate that ch14.18, a monoclonal antibody against the tumor-associated disialoganglioside GD2, has activity against neuroblastoma and that such activity is enhanced when ch14.18 is combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2. We conducted a study to determine whether adding ch14.18, GM-CSF, and interleukin-2 to standard isotretinoin therapy after intensive multimodal therapy would improve outcomes in high-risk neuroblastoma.
METHODS
Patients with high-risk neuroblastoma who had a response to induction therapy and stem-cell transplantation were randomly assigned, in a 1:1 ratio, to receive standard therapy (six cycles of isotretinoin) or immunotherapy (six cycles of isotretinoin and five concomitant cycles of ch14.18 in combination with alternating GM-CSF and interleukin-2). Event-free survival and overall survival were compared between the immunotherapy group and the standard-therapy group, on an intention-to-treat basis.
RESULTS
A total of 226 eligible patients were randomly assigned to a treatment group. In the immunotherapy group, a total of 52% of patients had pain of grade 3, 4, or 5, and 23% and 25% of patients had capillary leak syndrome and hypersensitivity reactions, respectively. With 61% of the number of expected events observed, the study met the criteria for early stopping owing to efficacy. The median duration of follow-up was 2.1 years. Immunotherapy was superior to standard therapy with regard to rates of event-free survival (66±5% vs. 46±5% at 2 years, P=0.01) and overall survival (86±4% vs. 75±5% at 2 years, P=0.02 without adjustment for interim analyses).
CONCLUSIONS
Immunotherapy with ch14.18, GM-CSF, and interleukin-2 was associated with a significantly improved outcome as compared with standard therapy in patients with high-risk neuroblastoma. (Funded by the National Institutes of Health and the Food and Drug Administration; ClinicalTrials.gov number, NCT00026312.)
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Child; Child, Preschool; Combined Modality Therapy; Drug Therapy, Combination; Gangliosides; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy; Infant; Intention to Treat Analysis; Interleukin-2; Isotretinoin; Neuroblastoma; Stem Cell Transplantation; Survival Analysis
PubMed: 20879881
DOI: 10.1056/NEJMoa0911123 -
BMJ Case Reports Oct 2023We report an interesting case of pericardial effusion associated with idiopathic systemic capillary leak syndrome (ISCLS) following administration of SARS-CoV-2 vaccine....
We report an interesting case of pericardial effusion associated with idiopathic systemic capillary leak syndrome (ISCLS) following administration of SARS-CoV-2 vaccine. This patient initially presented with dyspnoea and chest pain, with non-pitting oedema and clear lung fields. The diagnosis of ISCLS was made based on the clinical syndrome and laboratory evidence of polycythaemia and hypoalbuminaemia. An enlarging pericardial effusion was diagnosed on transthoracic echocardiogram. Daily point-of-care ultrasound (POCUS)-guided volume management and serial transthoracic echocardiograms contributed to avoidance of refractory shock, cardiac tamponade and critical care admission.
Topics: Humans; Capillary Leak Syndrome; Cardiac Tamponade; COVID-19; COVID-19 Vaccines; Pericardial Effusion
PubMed: 37813549
DOI: 10.1136/bcr-2023-256527 -
Biomedicines Sep 2022Capillary leak syndrome is an under-diagnosed condition leading to serious hypoalbuminemia with diffuse edema, pulmonary edema, severe hypotension, and possibly death.... (Review)
Review
Capillary leak syndrome is an under-diagnosed condition leading to serious hypoalbuminemia with diffuse edema, pulmonary edema, severe hypotension, and possibly death. Sepsis leading to hemophagocytic lymphohistiocytosis (HLH) is a major risk factor; however, capillary hyper-permeability is the core underlying pathophysiological mechanism. Endothelial dysfunction plays a major role in cardiometabolic disease through insulin resistance, lipotoxicity, and, eventually, oxidative stress and chronic inflammation. We review the literature concerning the aforementioned mechanisms as well-established risk factors for adverse COVID-19 outcomes. We especially focus on data regarding the underlying endothelial effects of SARS-CoV-2 infection, including direct damage and increased vascular leakage through a hyper-inflammatory cascade and diminished nitric oxide bioavailability. Interestingly, an increased incidence of hypoalbuminemia has been observed in patients with severe COVID-19, especially those with underlying cardiometabolic disease. Importantly, low albumin levels present a strong, positive association with poor disease outcomes. Therefore, in this review article, we highlight the important role of cardiovascular risk factors on endothelium integrity and the possible link of endothelial damage in the hypoalbuminemia-associated adverse prognosis of COVID-19 patients.
PubMed: 36289641
DOI: 10.3390/biomedicines10102379 -
Indian Journal of Critical Care... Oct 2017Capillary leak syndrome is a unique complication that follows Russell's viper envenomation. This syndrome has a very high fatality rate and is characterized by parotid... (Review)
Review
Capillary leak syndrome is a unique complication that follows Russell's viper envenomation. This syndrome has a very high fatality rate and is characterized by parotid swelling, chemosis, periorbital edema, hypotension, albuminuria, hypoalbuminemia, and hemoconcentration. This syndrome is frequently recognized from the southern parts of India, especially from the state of Kerala. It has been postulated that a vascular apoptosis inducing component of Russell's viper venom that is not neutralized by the commercially available anti-snake venom (ASV) is responsible for this complication as it occurs even after adequate doses of ASV administration in most cases. Acute kidney injury often requiring dialysis is invariably present in all patients because of reduced renal perfusion and ischemic acute tubular necrosis as a result of hypotension. Management mainly involves aggressive fluid resuscitation to maintain adequate tissue perfusion. There are no other proven effective treatment modalities, except a few reports of successful treatment with plasmapheresis. Methylprednisolone pulse therapy, terbutaline, aminophylline, and intravenous immunoglobulin are other treatment modalities tried.
PubMed: 29142382
DOI: 10.4103/ijccm.IJCCM_41_17