Ultrasound findings and specific intrinsic blood volume expansion therapy for neonatal capillary leak syndrome: report from a multicenter prospective self-control study.

OBJECTIVE: Capillary leak syndrome (CLS) is characterized by severe systemic edema without specific treatment, resulting in a high mortality rate. This study investigated whether there is organ edema in neonatal CLS patients and specific treatment strategies to improve patient prognosis. METHODS: Thirty-seven newborns diagnosed with CLS were included in this study. (1) Routine point-of-care ultrasound (POCUS) was used to identify whether the patients had visceral edema or fluid collection. (2) All patients were treated with 3% NaCl intravenously, and the clinical manifestations, laboratory indices and outcomes were compared before and after treatment. RESULTS: (1) Diffuse severe edema was found in 92.0% of the patients. (2) The POCUS examination revealed that CLS patients exhibited significant visceral edema in addition to diffuse severe edema, which included pulmonary edema in 67.6%, cerebral edema in 37.8%, severe intestinal edema in 24.3%, severe myocardial edema in 8.1%, pericardial effusion in 5.4%, pleural effusion in 29.7% and peritoneal effusion in 18.9%. Two patients (5.45%) had only myocardial edema without other manifestations. (3) Before and after the intravenous injection of 3% NaCl, there were no significant differences in the serum sodium or potassium levels of CLS patients, while the hemoglobin and hematocrit levels were significantly lower after treatment (p < 0.01). Her plasma ALB concentration and arterial pressure returned to normal levels after the treatment was completed. (4) All the patients survived, and no side effects or complications were observed during or after treatment with 3% NaCl. CONCLUSIONS: (1) In addition to diffuse severe edema, visceral edema and effusion are common and important clinical manifestations of neonatal CLS and need to be detected by routine POCUS. (2) The intravenous injection of 3% NaCl is a safe, effective and specific treatment strategy for neonatal CLS, with a survival rate of 100% and no adverse effects.

A case of chronic systemic capillary leak syndrome (SCLS) exacerbated during SARS-CoV2 infection.

Systemic capillary leak syndrome (SCLS) is a very rare and lethal disease characterized by hemoconcentration and hypoalbuminemia caused by reversible plasma extravasation. The underlying cause for SCLS remains largely unknown and acute treatment has remained mainly supportive. Prophylaxis with intravenous immunoglobulin (IVIG) has been shown to successfully prevent further episodes in affected patients. We reported a case of SCLS in a patient who presented to our hospital with COVID-19 and developed profound shock.

Persistent endoleak after endovascular exclusion of an aortocaval fistula, producing renal insufficiency.

This report presents a case of type II endoleak after endovascular exclusion of a primary aortocaval fistula, producing renal vein hypertension and renal insufficiency. A 74-year-old patient presented with acute renal insufficiency, hematuria, lower limb edema, and weight gain. The abdominal CT scan revealed an abdominal aortic aneurysm and an aortocaval fistula. An endograft was deployed but type II endoleak was present and persisted after surgical ligation of the inferior mesenteric artery and subsequent unsuccessful attempt of coil-embolization. The patients renal function continued to be impaired. Surgical ligation of aortocaval communication with preservation of the endograft was performed, resulting in restored renal function.

Myocardial edema in paroxysmal permeability disorders: The paradigm of Clarkson's disease.

PURPOSE: Paroxysmal Permeability Disorders (PPDs) comprise a variety of diseases characterized by recurrent and transitory increase of endothelial permeability. Idiopathic Systemic Capillary Leak Syndrome (ISCLS) is a rare PPD that leads to an abrupt massive shift of fluids and proteins from the intravascular to the interstitial compartment. In some cases, tissue edema may involve the myocardium, but its role in the development of shock has not been elucidated so far. MATERIALS AND METHODS: Assessment of cardiac involvement during ten life-threatening ISCLS episodes admitted to ICU. RESULTS: Transthoracic echocardiographic examination was performed in eight episodes, whereas a poor acoustic window prevented cardiac ultrasound assessment in two episodes. Myocardial edema was detected by echocardiography in eight episodes and marked pericardial effusion in one-episode. Cardiac magnetic resonance showed diffuse myocardial edema in another episode. In one case, myocardial edema caused fulminant left ventricular dysfunction, which required extracorporeal life support. The mean septum thickness was higher during the shock phase compared to the recovery phase [15.5 mm (13.1-21 mm) vs. 9.9 mm (9-11.3 mm), p = .0003]. Myocardial edema resolved within 72 h. CONCLUSIONS: During early phases of ISCLS, myocardial edema commonly occurs and can induce transient myocardial dysfunction, potentially contributing to the pathogenesis of shock.

The case report of capillary leakage syndrome secondary to malignant hypertension.

INTRODUCTION: Capillary leak syndrome (CLS) is characterized by hypoproteinemia, diffused pitting edema, noncardiogenic pulmonary edema, and hypotension. By far, there are no related reports of CLS secondary to malignant hypertension (MHT). A 33-year-old male was admitted to our hospital with the diagnosis of CLS on the background of MHT. PATIENT CONCERNS: A 33-year-old male was admitted with a 6-day history of worsening dyspnea, chest distress, and diffused pitting edema accompanied by very high blood pressure (200/145 mm Hg). DIAGNOSES: The tests and examinations showed hypoalbuminemia (26.7 g/L), pulmonary edema, and normal heart function. However, the expected massive proteinuria was absent (1.5 g/24 h). After diuretic and other antihypertensive therapy, the blood pressure reduced gradually; meanwhile, the symptoms of dyspnea and chest distress were improved quickly, and edema in his legs was also reduced. It is surprising that there was no change of pulmonary edema signs on imaging scan, and hypoalbuminemia remained with only mild proteinuria. Thus, our provisional diagnosis of this patient was CLS secondary to MHT. INTERVENTIONS AND OUTCOMES: We administered intravenous immunoglobulin, sulodexide, and renin-angiotensin system inhibitor to the patient for repairing vascular endothelium and improving the function of vascular endothelium. Before discharge, the patient's edema disappeared and the chest X-ray turned to normal. The level of serum albumin also increased to 35.1 g/L along with the overall improvement. Finally, the renal biopsy revealed malignant hypertensive glomerulosclerosis. All these clinical manifestations were consistent with CLS caused by MHT. LESSONS: Up to now, there has been no case report of CLS caused by MHT. We should pay more attention to CLS induced by MHT, try to diagnose it as soon as possible, and give prompt treatment to CLS and primary disease.

Severe capillary leak syndrome with cardiac arrest triggered by influenza virus infection.

Systemic capillary leak syndrome (SCLS), also known as Clarkson syndrome, is a rare disease with potential fatal outcome. The clinical picture involves leakage of fluid and protein from the bloodstream into peripheral tissues, resulting in hypoalbuminaemia, elevated haematocrit, oedema and hypotension. The spectrum of the symptoms ranges from discrete swelling/oedema of extremities to fulminant cardiogenic shock. We present a case with a 52-year-old man diagnosed with SCLS after being resuscitated from cardiac arrest, which was complicated by compartment syndrome. The severe episode of capillary leak was potentially triggered by influenza virus infection. With the benefit of hindsight, he presented with symptoms of SCLS 2 years prior the major acute episode. Here we describe this case and review some aspects of the literature on SCLS, with particular focus on the pathogenesis, treatment/prophylaxis and long-term physical and psychological complications.

A p190BRhoGAP mutation and prolonged RhoB activation in fatal systemic capillary leak syndrome.

We describe a fatal case of pediatric systemic capillary leak (Clarkson's disease) associated with a point mutation in p190BRhoGAP. Dermal microvascular endothelial cells (ECs) isolated from this patient form monolayers with similar levels and distribution of junctional proteins and transendothelial electrical resistance compared with normal human dermal microvascular ECs. However, patient-derived ECs demonstrate a greater increase in permeability and impaired recovery of barrier function in response to tumor necrosis factor (TNF) compared with normal donor EC cultures. TNF transiently activates RhoB in ECs coincident with developing leak, and inactivation of RhoB correlates with barrier recovery. The mutation in p190BRhoGAP impairs RhoB inactivation, and the mutant phenotype of patient-derived ECs is replicated by siRNA knockdown of p190BRhoGAP in normal ECs. These data suggest a previously unknown function for p190BRhoGAP in control of capillary EC barrier function that may also be important in acquired systemic capillary leak associated with critical illness in humans.

Multimodality imaging of blood-brain barrier impairment during epileptogenesis.

Insult-associated blood-brain barrier leakage is strongly suggested to be a key step during epileptogenesis. In this study, we used three non-invasive translational imaging modalities, i.e. positron emission tomography, single photon emission computed tomography, and magnetic resonance imaging, to evaluate BBB leakage after an epileptogenic brain insult. Sprague-Dawley rats were scanned during early epileptogenesis initiated by status epilepticus. Positron emission tomography and single photon emission computed tomography scans were performed using the novel tracer [68Ga]DTPA or [99mTc]DTPA, respectively. Magnetic resonance imaging included T2 and post-contrast T1 sequence after infusion of Gd-DTPA, gadobutrol, or Gd-albumin. All modalities revealed increased blood-brain barrier permeability 48 h post status epilepticus, mainly in epileptogenesis-associated brain regions like hippocampus, piriform cortex, thalamus, or amygdala. In hippocampus, Gd-DTPA-enhanced T1 magnetic resonance imaging signal was increased by 199%, [68Ga]DTPA positron emission tomography by 37%, and [99mTc]DTPA single photon emission computed tomography by 56%. Imaging results were substantiated by histological detection of albumin extravasation. Comparison with quantitative positron emission tomography and single photon emission computed tomography shows that magnetic resonance imaging sequences successfully amplify the signal from a moderate amount of extravasated DTPA molecules, enabling sensitive detection of blood-brain barrier disturbance in epileptogenesis. Imaging of the disturbed blood-brain barrier will give further pathophysiologic insights, will help to stratify anti-epileptogenic treatment targeting blood-brain barrier integrity, and may serve as a prognostic biomarker.

A possible role for IL-17 in Clarkson's disease.

INTRODUCTION: Systemic capillary leak syndrome (SCLS) is a rare disease characterized by recurrent episodes and a triad of "leak attacks": hypovolemic shock, generalized edema, hemoconcentration and paradoxical hypoalbuminemia. CASE STUDY AND DISCUSSION: Here we report a case of pediatric idiopathic SCLS with an episode of cough and fever followed two days later by myalgia, livedo, acrocyanosis, and five days later by edema, tachycardia, hypotension, and generalized tonic-clonic seizure. Moreover, we provide evidence for an LPS-induced overproduction of interferon-gamma and interleukin-17 by the patient's peripheral blood mononuclear cells one year after the attack. CONCLUSION: This observation suggests the involvement of IL-17 in the pathogenesis of this disease.

Acute pulmonary capillary leak syndrome during elective surgery under general anesthesia.

A 75-year-old previously healthy man presented for elective resection of rectal cancer under general anesthesia. Six days before the operation, he had a high-grade fever, and elevated leukocyte count and C-reactive protein concentration, but this was resolved by an intravenous antibiotic. His condition was well controlled before the operation. Soon after the operation started, severe hypoxemia emerged, with low arterial pressure. Fiberoptic bronchoscopy demonstrated a massive amount of plasma-like edema fluid; the total amount of suctioned fluid was approximately 800 ml at the end of the surgery. This acute pulmonary edema appeared to be due to increased permeability rather than pulmonary congestion as indicated by chest radiography, pulmonary artery occlusion pressure, echocardiogram, and the protein-rich edema fluid. Elevated concentrations of the proinflammatory cytokines, interleukin (IL)-6 and IL-8, in both plasma and the pulmonary edema fluid, suggested a possible role of systemic and pulmonary inflammation in the development of this acute pulmonary capillary leak. According to the "two-hit" hypothesis, the bacterial infection preceding the operation may have primed the immune cells, and the following surgical stress may have then triggered rapid progression of acute respiratory distress syndrome. We should keep in mind that, especially following sepsis, sudden massive pulmonary capillary leak can occur during elective surgery, even though the patient's condition is well controlled.

Decreased hepatic uptake of gallium-67 citrate in haemophagocytic syndrome occurring concomitantly with capillary leak syndrome.

We describe a 4-year-old girl with haemophagocytic syndrome (HPS) in whom hepatic gallium-67 citrate (Ga-67) uptake was suppressed when the disease was in its acute phase and returned to normal when the disease was in remission. The prominent clinical feature of this case was the occurrence of systemic capillary leak syndrome (CLS). Because extravasation of plasma proteins may be the result of vascular endothelial injury in CLS, loss of hepatic Ga-67 uptake may reflect insult to the hepatic sinusoidal endothelium. This case suggests a possible role of sinusoidal endothelial cells in the mechanism of hepatic Ga-67 uptake and indicates the need for further study of Ga-67 uptake in patients with HPS.