Research Progress on Capillary Leak Syndrome Associated with Hematopoietic Stem Cell Transplantation--Review / 中国实验血液学杂志

Capillary leak syndrome (CLS) is a clinical syndrome characterized by impairment of vascular endothelial barrier function, increased vascular permeability, and reversible systemic edema. It is one of the early fatal complications after hematopoietic stem cell transplantation. So far, the exact pathogenesis of CLS has not been elucidated, and the diagnostic criteria and treatment methods have not been unified. At present, it is believed that the fundamental cause of CLS is hypercytokinemia, and the core factor is high permeability of vascular endothelial cells. According to the clinical manifestations, the natural course of CLS can be divided into prodrome, leakage and recovery stages. As far as treatment is concerned, symptomatic and supportive treatment is dominant according to different characteristics of each stage. In this review, the pathogenesis, clinical manifestations, diagnosis and treatment of hematopoietic stem cell transplant-associated CLS were briefly summarized.

Clinical analysis of secondary hemophagocytic lymphohistiocytosis complicated with capillary leak syndrome / 中华血液学杂志

Objective: To investigate the clinical characteristics of secondary hemophagocytic lymphohistiocytosis (sHLH) complicated with capillary leak syndrome (CLS) . Methods: The clinical and laboratory data of 87 sHLH patients, who were treated in our hospital between January 2015 and December 2017, were retrospectively analyzed. Depending on whether they were complicated with CLS, 21 sHLH patients were classified as the CLS-sHLH group, while 66 were classified as the non-CLS-sHLH group. The differences of clinical manifestations, laboratory tests, treatment and prognosis between the two groups were compared. Results: There was no significant difference in the etiology of sHLH between the CLS-sHLH group and the non-CLS-sHLH group (P>0.05) . The neutrophil, fibrinogen and albumin levels in the CLS-sHLH group were lower than those in the non-CLS-sHLH group, while the triacylglycerol levels were higher than those in the non-CLS-sHLH group (P<0.05) . Varying degrees of edema, weight gain, hypotension, hypoproteinemia, oliguria and multiple serous effusions were observed in the CLS-sHLH group. Among them, there were 15 patients that CLS get improved, and the medial time of improvement was 7 (5-14) days. The other 6 patients did not get remission, while they died within 6-30 days. The median overall survival of the CLS-sHLH group was lower than that of the non-CLS-sHLH group (75 days vs not reached, P=0.031) . Conclusions: There may be no correlation between the cause of sHLH and the occurrence of CLS. Severity of neutropenia, fibrinogen and albumin levels, and triglyceride levels may be accompanied for sHLH patients complicated with CLS. Patients with sHLH who complicated with CLS have a poor prognosis. Active treatment of HLH and its primary disease, reasonable fluid replacement and oxygen supply are crucial, which can effectively control disease progression.

How relevant are vascular endothelial growth factor and intercellular adhesion molecule in the systemic capillary leak syndrome of psoriasis?

Abstract: Psoriasis is a chronic disease, characterized by erythematous scaly lesions, presented in eight different forms: plaques, guttate, pustular, erythrodermic, inverse, nail and scalp psoriasis, and psoriatic arthritis. Its development depends on genetic factors, external stimulus and immune response alteration.1 Proinflammatory cytokines such as TNF-alpha, IL-12 and 23 may also be involved. In the worst cases, systemic complications linked to endothelial alterations may occur. A literature review was conducted for a better understanding of what roles VEGF (vascular endothelial growth factor) and ICAM-1 (intercellular adhesion molecule) have, among other cytokines, in systemic capillary leak syndrome, involved in erythrodermic and pustular psoriasis, the most unstable forms of the disease.

Risk factors for capillary leak syndrome in children with hematological malignancies / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the risk factors for capillary leak syndrome (CLS) in children with malignant hematologic diseases.</p><p><b>METHODS</b>Thirty children with hematological malignancies complicated with CLS were analyzed with multiple logistic regression analysis.</p><p><b>RESULTS</b>At the test level of 0.05, hypoxemia and septicemia were found to significantly correlate with CLS in these children, and the number of white blood cells before CLS and severe bone marrow suppression were near the test level.</p><p><b>CONCLUSION</b>Hypoxemia and septicemia are risk factors for CLS in children with malignant hematologic diseases.</p>

Será choque séptico? Um caso raro de choque distributivo / Is this septic shock? A rare case of distributive shock

Os autores apresentam um caso raro de choque em doente sem antecedentes pessoais significativos, admitido na unidade de terapia intensiva por suspeita de choque séptico. Inicialmente, foi tratado com fluidoterapia sem melhoria, tendo sido aventada a hipótese de síndrome de hiperpermeabilidade capilar, após confirmação de hipoalbulinemia paradoxal grave, hipotensão e hemoconcentração exuberante - tríade característica da doença. Os autores discutiram o diagnóstico diferencial e ainda realizaram uma revisão do diagnóstico e do tratamento da doença.

The authors report a rare case of shock in a patient without significant clinical history, admitted to the intensive care unit for suspected septic shock. The patient was initially treated with fluid therapy without improvement. A hypothesis of systemic capillary leak syndrome was postulated following the confirmation of severe hypoalbuminemia, hypotension, and hemoconcentration - a combination of three symptoms typical of the disease. The authors discussed the differential diagnosis and also conducted a review of the diagnosis and treatment of the disease.

Fluid resuscitation in a patient with severe hypovolemic shock and severe pulmonary capillary leak / 南方医科大学学报

A male patient undergoing extracorporeal ultrasound lithotripsy developed the symptoms of dyspnea, low blood pressure, palpitations, chest tightness, and sweating, and a clinical diagnosis of pulmonary capillary leak and hypovolemic shock was made. Pulse indicator continuous cardiac output (PiCCO) technique was used for resuscitation according to the measurements of extravascular lung water index (EVLWI) and global end-diastolic volume index (GEDI). The patient showed low levels of cardiac output (CO) and GEDI with a peak EVLWI of 32 ml/kg and profuse pink and thin sputum overflow from the trachea. The high ventilator support parameters failed to correct low oxygen saturation. Restricted fluid infusion was used to reduce pulmonary edema. Colloidal solution was given when GEDI was below 500 ml/m(2), and the volume and fluid infusion rate were reduced for a GEDI higher than 500 ml/m(2). Pulmonary edema was gradually reduced after the treatments with improvement of lactic acid level and liver and kidney functions. Vasopressors were withdrawn 6 days later, mechanical ventilation was discontinued 10 days later, and tracheal intubation was removed 25 days later, after which the patient was discharged. In the treatment of the patient, PiCCO monitoring played an important role.

A Case of Systemic Capillary Leak Syndrome Presenting as Septic Shock / 대한내과학회지

Systemic capillary leak syndrome is a rare disease characterized by life-threatening attacks of reversible plasma extravasation and vascular collapse accompanied by hypotension, hemoconcentration, and hypoalbuminemia. A 36-year-old woman was admitted to this hospital with a fever, along with symptoms consistent with an upper respiratory tract infection and hypotension. Initial laboratory tests revealed several abnormal findings, including an elevated leukocyte count and hematocrit, hypoalbuminemia, and acute renal failure. Here, we report a case of successful treatment of systemic capillary leak syndrome, which can be difficult to distinguish from septic shock.

Systemic capillary leak syndrome under general anesthesia: a case report / 대한마취과학회지

Systemic capillary leak syndrome (SCLS) is very rare and lethal disease and only 150 cases have been reported after the first publication of its report in 1960 by Clarkson. SCLS is characterized by hemoconcentation and hypoalbuminemia caused by reversible plasma extravasation. Its mechanism is unknown, but transient dysfunction of the endothelium is the most suspected cause and trigger of this event may cause immunologic disarrangement. After recovery of endothelial function, fluid injected during the shock period is redistributed and can cause severe pulmonary edema. SCLS should be considered in patients with acute and severe hypotension with hemoconcentration and hypoalbuminemia without obvious cardiac dysfunction. Especially we should take into account the possibility of SCLS if fluid replacement does not work or the shock state is aggravated despite aggressive fluid resuscitation and vasopressor administration. SCLS itself is a very rare disease; furthermore, SCLS that develops during well-controlled surgery is even more rare. So we report this case with review of the literature.

Systemic capillary leak syndrome (Clarkson's disease) during elective pylorus-preserving pancreaticoduodenectomy: case report

Systemic capillary leak syndrome (SCLS), also called Clarkson's disease is rare and life-threatening disorder of unknown etiology, which is a characteristic triad of hypovolemic shock, hemoconcentration, and hypoalbuminemia. Unexplained capillary leakage from the intravascular to the interstitial space, which has been estimated up to 70% of the intravascular volume, is the proposed mechanism. Because the pathogenesis is unknown, it is diagnosed clinically after exclusion of other diseases that cause systemic capillary leak and no efficacious pharmacological treatment has been clearly established. The mortality rate ranges from 30% to 76%. In Korea, four cases of SCLS (5 cases in adult and 1 case in child) were reported by 2012. We describe a case of severe SCLS that suddenly occurred and rapidly progressed during pylorus preserving pancreaticoduodenectomy and review the literature.

Clinical risk factors for capillary leak syndrome in children with sepsis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features of capillary leak syndrome (CLS) in children with sepsis, and to analyze its risk factors.</p><p><b>METHODS</b>Clinical data of 384 children with sepsis was studied retrospectively. They included 304 cases of general sepsis, 54 cases of severe sepsis and 26 cases of septic shock, and were divided into non-CLS (n=356) and CLS groups (n=28). Univariate analysis was performed for each of the following variables: sex, age, malnutrition, anemia, coagulation disorders, white blood cell count, C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, blood glucose, lactic acid, Pediatric Risk of Mortality (PRISM) III score, pediatric critical illness score (PICS), severe sepsis and number of failed organs≥3. The statistically significant variables (as independent variables) were subjected to multivariate logistic regression analysis.</p><p><b>RESULTS</b>The incidence rate of CLS in children with septic shock, severe sepsis and general sepsis were 42.3%, 20.1% and 1.3%, respectively, with significant differences among them (P<0.01). There were significant differences in anemia, coagulation disorders, CRP, PCT>2 ng/mL, TNF, IL-1, IL-6, blood glucose, lactic acid, PRISM III score, PICS and number of failed organs≥3 between the non-CLS and CLS groups (P<0.05). Severe sepsis/shock and PRISM III score were the independent risk factors for CLS in children with sepsis.</p><p><b>CONCLUSIONS</b>The severity of sepsis and PRISM III score are positively correlated with the incidence of CLS in children with sepsis. Early monitoring of such factors as infection markers and blood glucose in children with severe sepsis and high PRISM III score may contribute to early diagnosis and effective intervention, thus reducing the mortality from CLS in children with sepsis.</p>

Manifestaciones sistémicas del dengue / Systemic manifestations of dengue

Introducción: el dengue es una infección que puede afectar múltiples órganos.Objetivo: determinar la afectación multisistémica por dengue. Metodología: estudio observacional, descriptivo, prospectivo realizado en sujetos adultos con dengue grave con signos de alarma internados en el Hospital Nacional entre diciembre 2012 y mayo 2013. La infección debía estar confirmada con antígeno NS1 y/o serología IgM (+). Resultados: se encontró 10,1% de hepatitis, 85,6% de transaminitis, 48% con relación CPKmb/CPK total >5%, 22,5% de alteraciones electrocardiográficas, 70,4% con proteinuria de 24 hs elevada y 9,3% con proteinuria en rango nefrótico. Conclusiones: la afectación multisistémica es frecuente, generalmente pasa desapercibida y en general es autolimitada aunque se requieren más estudios para evaluar la evolución a largo plazo en estos casos.

Introduction: dengue is an infection that could affect multiple organs. Objective: to determine the multisystem involvement of dengue. Methodology: observational, descriptive, prospective study conducted in adult subjects with severe and warning signs of dengue admitted to the National Hospital between December 2012 and May 2013. Infection should be confirmed with NS1 antigen and / or IgM serology (+). Results: we found 10.1% of hepatitis, 85.6% of transaminitis the relation CPKmb / total CPK > 5% in 48%, electrocardiographic alterations in 22.5%, elevated proteinuria in 70.4% and nephrotic proteinuria in 9.3%. Conclusions: multisystemic involvement is frecuent, usually asymptomatic and generally self-limited although more studies are needed to evaluate the long-term outcome in these cases.

A Case of Chronic Renal Failure Associated with Systemic Capillary Leak Syndrome / 영남의대학술지

Systemic capillary leak syndrome (SCLS) is an unusual entity characterized by hypovolemic shock, hemoconcentration, and hypo-albuminemia associated with paraproteinemia as a result of marked capillary hyperpermeability. Complications of this syndrome can include compartment syndromes, pulmonary edema, thrombosis, and acute kidney injury. This paper reports a case of severe SCLS accompanied by acute tubular necrosis caused by hypoperfusion and myoglobinuria secondary to rhabdomyolysis, which resulted in chronic kidney disease that necessitated hemodialysis. However, there have been rare data of residual end-organ damage after acute attacks in Korea. Therefore, this paper reports a case of complicated SCLS enough to hemodialysis and that developed into chronic kidney disease.

Síndrome de extravasamento capilar sistêmico / Systemic capillary leak syndrome

A síndrome de extravasamento capilar sistêmico é rara e causada por aumento da permeabilidade capilar. Várias etiologias estão envolvidas. No nosso serviço de Dermatologia, a principal é a psoríase instável. Diversos tratamentos são usados e muitos ainda estão em estudo. Nosso objetivo foi apresentar esta situação clínica potencialmente fatal que ocorre em nossa especialidade.

The systemic capillary leak syndrome is rare and caused by increased capillary permeability. Several etiologies are involved. In our Department of Dermatology the main one is unstable psoriasis. Several treatments are used and many are still under study. Our objective was to present this potentially fatal medical condition that occurs in our specialty.

Risk factors for capillary leak syndrome in neonates / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the risk factors for capillary leak syndrome (CLS) in neonates.</p><p><b>METHODS</b>The clinical data of 52 neonates with CLS (case group) were retrospectively reviewed. Fifty hospitalized neonates without CLS were used as the control group. The possible factors for the development of CLS were identified by univariate analysis. The independent risk factors for CLS were determined by multivariate logistic regression analysis.</p><p><b>RESULTS</b>The univariate analysis showed that the incidences of hyperglycemia, respiratory distress syndrome (RDS), sepsis and cold injury syndrome in the case group were significantly higher than those in the control group (P<0.05). The logistic regression analysis showed that sepsis (OR=5.004, P=0.001), RDS (OR=3.880, P=0.013) and cold injury syndrome (OR=3.207, P=0.023) were the independent risk factors for the development of CLS.</p><p><b>CONCLUSIONS</b>RDS, sepsis and cold injury syndrome are independent risk factors for CLS in neonates. Hyperglycemia may be associated with the development of CLS.</p>

Status epilepticus and capillary leak syndrome in a neonate related to perinatal hypoxic-ischemic encephalopathy.

Hypoxic-ischemic cerebral injury that occurs during the perinatal period is one of the most commonly recognized cause of long-term neurological deficit in children, often referred to as cerebral palsy. We describe a case with capillary leak syndrome and seizures to co-morbid status epilepticus related to perinatal hypoxicischemic encephalopathy in newborn period.

Recurrent Systemic Capillary Leak Syndrome Responding to the Corticosteroid Therapy / 대한신장학회지

Systemic capillary leak syndrome (SCLS) is a rare devastating condition that is caused by unexplained marked capillary hyperpermeability, resulting in hypovolemic shock, hemoconcentration, and hypoproteinemia. Most patients have prodromal symptoms such as non-specific gastrointestinal symptoms, myalgia, or dizziness. In the current case, we observed the patient with recurrent SCLS show perivascular lymphocytic infiltration on skin biopsy and eosinophilic infiltrates on random biopsies from duodenum to colon. This finding might be due to distinct eosinophilic enterocolitis or secondary to SCLS. However, there has been rare data for the prevention of the recurrent attack of SCLS, although the mortality is high. Therefore, we report a case of frequently relapsing SCLS responding to the corticosteroid therapy.

Risk factors for capillary leak syndrome in children with tetralogy after operation / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To determine risk factors of capillary leak syndrome(CLS) in children with tetralogy after operation.</p><p><b>METHODS</b>Clinical data were retrospectively collected and analyzed from 32 tetralogy cases with CLS and 50 cases without CLS(control group), who received operation under cardiopulmonary bypass (CBP) in our hospital from October 2002 to December 2006. Risk factors with statistical significance were screened with univariate logistic regression analysis, independent risk factors of CLS were determined with multivariate logistic regression analysis. Postoperative outcome was compared between CLS group and control group.</p><p><b>RESULT</b>Logistic analysis showed that the risk factors for CLS were age(OR=6.783), duration of CBP(OR=4.756)and MGoon index (OR=3.826). There were statistical differences in injection of colloid, time of inotropic drugs and ventilation between CLS and control groups(P<0.01). Eight CLS cases underwent peritoneal dialysis and 2 CLS cases died.</p><p><b>CONCLUSION</b>The risk factors of CLS in children with tetralogy after CBP are age, duration of CBP and MGoon index.</p>

Two Cases of Systemic Capillary Leak Syndrome that were Treated with Pentastarch

Systemic capillary leak syndrome (SCLS) is a condition that's caused by the shift of fluid and protein from the intravascular space to the interstitial space as a result of repetitive episodes of capillary hyperpermeability. The pathogenesis of SCLS is still unclear, but there's recently been a report showing this syndrome in association with monoclonal gammopathy. This syndrome can be a fatal disease because cardiovascular collapse can occur in the initial capillary leak phase. Although theophylline, diuretics, terbutaline, steroids, calcium antagonist, Ginkgo biloba extracts and plasmapheresis have been suggested as medication, none of them have been proven to be effective. Considering that this disease is self-limiting, conservative treatment in the acute phase is believed to be very important. Because hypoalbuminemia is very a common manifestation of SCLS, Pentastarch, which has a higher molecular weight than albumin, could be efficient to prevent cardiovascular collapse. We used 10% Pentastarch during the acute SCLS attacks of 2 patients and the patients both showed a dramatic response. Pentastarch may be helpful to treat SCLS in its initial capillary leak phase by the elevating blood pressure, and this might contribute to somewhat decreasing the acute mortality of SCLS.

Síndrome de fuga capilar después de desviación cardiopulmonar en niños / Capillary leakage syndrome after cardiopulmonary bypass in children

El síndrome de fuga capilar se puede observar en pacientes con cardiopatías congénitas a los que se realiza una derivación cardiopulmonar. Está asociado a un significativo aumento de la morbilidad en el postoperatorio inmediato. Investigamos, mediante análisis univariado y multivariado, los factores preoperatorios y perioperatorios relacionados con la aparición del síndrome de fuga capilar, y también determinamos las características de la evolución del síndrome en lo referente a la duración de la ventilación mecánica, estadía en la unidad de cuidados intensivos y la mortalidad. Se realizó un estudio prospectivo que incluyó a 123 pacientes en edades comprendidas entre los 10 días y los 16 años, quienes fueron operados bajo circulación extracorpórea en el Servicio de Cirugía Cardiovascular del Hospital Universitario ®William Soler¼ durante 2001. En las primeras 48 h, 22 pacientes desarrollaron síndrome de fuga capilar, para una incidencia del 17,89 por ciento. Los pacientes que presentaron síndrome de fuga capilar estuvieron mayor tiempo en ventilación mecánica (259 h contra 29,9 h), tuvieron mayor estadía en la sala de cuidados intensivos (13 días contra 2 días) y mayor mortalidad (50 por ciento contra 9,9 por ciento) en comparación con el grupo control. El tiempo de derivación cardiopulmonar prolongado fue identificado como factor de riesgo independiente para la aparición del síndrome de fuga capilar. Este grupo de pacientes presentó mayor morbilidad y mortalidad

A Case of Drug Induced Interstitial Pneumonitis by Gemcitabine / 결핵

Gemcitabine is an effective newly developed chemotherapeutic agent, which is increasingly being used to treat non-small cell lung, ovarian and breast cancers. Pulmonary toxicity is usually self-limiting mild dyspnea, bronchospasm, but severe pulmonary toxicity is rarely reported. Herein, we report drug induced interstitial lung disease associated with gemcitabine treatment. High resolution computerized tomogram (HRCT) showed an increased ground glass opacity and thickened septal lines. The patient showed a rapid good response with prednisolone treatment.