Capillary leak syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: M. Hassan, M.B.B.S

Capillary leak syndrome is a rare medical condition characterized by self-reversing episodes during which the endothelial cells which line the capillaries are thought to separate for a few days, allowing for a leakage of fluid from the circulatory system to the interstitial space, resulting in a dangerous hypotension, hemoconcentration, and hypoalbuminemia. It is a life-threatening illness because each episode has the potential to cause damage to, or the failure of, vital organs due to limited perfusion. It is often misdiagnosed as polycythemia, polycythemia vera or sepsis.

The syndrome was first described by B. Clarkson in 1960, after whom it was later informally named. Beyond numerous case reports published since then, two comprehensive reviews of clinical and research experience were published in 2010.

The pathogenesis of capillary leak syndrome remain unclear, however, cytokines, vascular endothelial growth factor (VEGF), leukotrienes, and complement play an important role. During each episode of hyperpermeability of the vasculature, there is an increase of interleukin 2 receptor-positive peripheral blood M-cell count, as well as apoptosis of the endothelial cells.

Capillary leak syndrome may be a result of various diseases, and an adverse effect of numerous drugs.

Conditions associated with capillary leak syndrome include sepsis, engraftment syndrome, differentiation syndrome, ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune disease, snakebite envenomation, and ricin poisoning.

Drugs associated with capillary leak syndrome include Acitretin, Aldesleukin, Denileukin diftitox, Filgastrim, Oprelvekin, Sargramostim, tbo-filgrastim, gemcitabine, and monoclonal antibodies.

As capillary leak syndrome has overlapping clinical and laboratory findings with various other conditions, it should be considered as the diagnosis of exclusion. Some common ones include Adrenal insufficiency, Anaphylaxis, Carcinoid Syndrome, Chronic Heart Failure, Enteropathy, Gleich syndrome, Hereditary angioedema, Inferior vena cava syndrome, Mastocytosis, Nephrotic syndrome, Ovarian hyperstimulation syndrome, Pancreatitis, Pheochromocytoma, Primary amyloidosis, Sepsis and Toxic shock syndrome. Some other conditions that should be considered as a differential diagnosis include Differentiation syndrome, Engraftment syndrome, Hemophagocytic lymphohistiocytosis, Viral hemorrhagic fevers, Snakebite envenomation, Ricin poisoning, as well as multiple autoimmune conditions.

Between 1960 to 2006, hundred cases of systemic capillary leak syndrome were reported in the world literature.

Capillary leak syndrome has been described in children, however, it is sporadic and is diagnosed most often in previously healthy, middle-aged, Caucasian adults (median age ± S.D.: 45 ± 15 yrs; age range 5 months to 74 years).

Based of 107 cases of capillary leak syndrome where information was available, 57% of the individuals were male.

Independent risk factors for capillary leak syndrome in neonates include respiratory distress syndrome, sepsis, cold injury syndrome, and hyperglycemia. Condition with monoclonal or M protein detected in the blood as well as autoimmune diseases are risk factors for the development of capillary leak syndrome. Because of the rarity of the disease there are pending investigations pertaining to the underlying cause.

Capillary leak syndrome may present as an acute or chronic phase. The acute phase can be further subdivided into the capillary leak phase and the recruitment of interstitial fluid.

Capillary leak syndrome is associated with the following complications compartment syndrome, pulmonary edema, end-organ damage leading to multiorgan failure, arrhythmias, pericardial effusion, myocardial edema, pancreatitis, acute deep venous thrombosis, acute renal failure, rhabdomyolysis, pleural effusion, and acute ischemic stroke.

Mortality is reported in 21% of the 57 cases described. However, better management of this condition has recently led to lower mortality. Prognosis can be determined according to the SCLS Severity Scale which describes the condition according to grades.

History and Symptoms | Physical Examination | Laboratory Findings | Other Diagnostic Studies

Medical Therapy | Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: M. Hassan, M.B.B.S

Capillary leak syndrome was first described by B. Clarkson in 1960, and was named after him.

Numerous case reports on capillary leak syndrome are published since then.

Between 1960 to 2006, a hundred cases of capillary leak syndrome were reported in the world literature, and additional 26 cases were published since 2006.

The syndrome was first described by B. Clarkson in 1960,^[1] after whom it was later informally named. Beyond numerous case reports published since then, two comprehensive reviews of clinical and research experience were published in 2010.^[2][3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: M. Hassan, M.B.B.S

The pathogenesis of capillary leak syndrome remain unclear, however, cytokines, vascular endothelial growth factor (VEGF), leukotrienes, and complement play an important role. During each episode of hyperpermeability of the vasculature, there is an increase of interleukin 2 receptor-positive peripheral blood M-cell count, as well as apoptosis of the endothelial cells.

Capillary leak syndrome also known as Clarkson’s disease and spontaneous periodic edema is a life threatening condition characterized by recurrent episodes of hypovolemic shock, hemoconcentration, and hypoalbuminemia, occurring in the absence of albuminuria.

The pathogenesis of capillary leak syndrome remain unclear, however, cytokines, vascular endothelial growth factor (VEGF), leukotrienes, and complement play an important role. During each episode of hyperpermeability of the vasculature, there is an increase of interleukin 2 receptor-positive peripheral blood M-cell count. The exact cause of hyperpermeability remains unknown, and protein up to 900 kDa can extravasate from the intravascular to interstitial space. During the hyperpermeability episode, endothelial cells undergo apoptosis, which is characterized by endothelial microvascular body and bleb formation. ^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: M. Hassan, M.B.B.S

Capillary leak syndrome may be a result of various diseases, and an adverse effect of numerous drugs.

Conditions associated with capillary leak syndrome include sepsis, engraftment syndrome, differentiation syndrome, ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune disease, snakebite envenomation, and ricin poisoning.

Drugs associated with capillary leak syndrome include Acitretin, Aldesleukin, Denileukin diftitox, Filgastrim, Oprelvekin, Sargramostim, tbo-filgrastim, gemcitabine, and monoclonal antibodies.

1. Sepsis
2. Engraftment syndrome
3. Differentiation syndrome
4. Ovarian hyperstimulation syndrome
5. Hemophagocytic lymphohistiocytosis
6. Viral hemorrhagic fevers
7. Autoimmune disease
8. Snakebite envenomation
9. Ricin poisoning

• Acitretin
• Aldesleukin
• Denileukin diftitox
• Filgastrim
• Oprelvekin
• Sargramostim
• Tbo-filgrastim
• Gemcitabine
• Monoclonal antibodies

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: M. Hassan, M.B.B.S

As capillary leak syndrome has overlapping clinical and laboratory findings with various other conditions, it should be considered as the diagnosis of exclusion. Some common ones include Adrenal insufficiency, Anaphylaxis, Carcinoid Syndrome, Chronic Heart Failure, Enteropathy, Gleich syndrome, Hereditary angioedema, Inferior vena cava syndrome, Mastocytosis, Nephrotic syndrome, Ovarian hyperstimulation syndrome, Pancreatitis, Pheochromocytoma, Primary amyloidosis, Sepsis and Toxic shock syndrome. Some other conditions that should be considered as a differential diagnosis include Differentiation syndrome, Engraftment syndrome, Hemophagocytic lymphohistiocytosis, Viral hemorrhagic fevers, Snakebite envenomation, Ricin poisoning, as well as multiple autoimmune conditions.

Due to overlapping clinical and laboratory findings of capillary leak syndrome with other conditions, it is considered as the diagnosis of exclusion. SCLS should be differentiated from many possible differential diagnoses many of which may have overlapping symptoms such as hypotension, flushing and hypoalbuminemia with resultant edema. Such conditions include Adrenal insufficiency, Anaphylaxis, Carcinoid Syndrome, Chronic Heart Failure, Enteropathy, Gleich syndrome, Hereditary angioedema, Inferior vena cava syndrome, Mastocytosis, Nephrotic syndrome, Ovarian hyperstimulation syndrome, Pancreatitis, Pheochromocytoma, Primary amyloidosis, Sepsis and Toxic shock syndrome.^[1][2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: M. Hassan, M.B.B.S

From 1960 to 2006, a hundred cases were reported of capillary leak syndrome. Apart from children it has been diagnosed in healthy, middle-aged, Caucasian adults with the median age ± S.D.: 45 ± 15 yrs. From 107 cases that were reported, 57% of those were males.

• Between 1960 to 2006, hundred cases of systemic capillary leak syndrome were reported in the world literature.
• Capillary leak syndrome has been described in children, however, it is sporadic and is diagnosed most often in previously healthy, middle-aged, Caucasian adults (median age ± S.D.: 45 ± 15 yrs; age range 5 months to 74 years).
• Based of 107 cases of capillary leak syndrome where information was available, 57% of the individuals were male.^[1]

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: M. Hassan, M.B.B.S

Independent risk factors for capillary leak syndrome in neonates include respiratory distress syndrome, sepsis, cold injury syndrome, and hyperglycemia. Condition with monoclonal or M protein detected in the blood as well as autoimmune diseases are risk factors for the development of capillary leak syndrome. Because of the rarity of the disease there are pending investigations pertaining to the underlying cause.

Independent risk factors for capillary leak syndrome in neonates include respiratory distress syndrome, sepsis, cold injury syndrome, and hyperglycemia.^[1] Conditions with monoclonal or M protein detected in the blood are associated with capillary leak syndrome. In addition, autoimmune disease are also an important risk factor for the development of capillary leak syndrome in adults.^[2] Due to the rare occurances of the disease, the underlying causes are still largely unknown and continue to be investigated.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: M. Hassan, M.B.B.S

Capillary leak syndrome may present as an acute or chronic phase. The acute phase can be further subdivided into the capillary leak phase and the recruitment of interstitial fluid.

Capillary leak syndrome is associated with the following complications Compartment syndrome, Pulmonary edema, end-organ damage leading to multiorgan failure, Arrhythmias, Pericardial effusion, Myocardial edema, Pancreatitis, acute deep venous thrombosis, acute renal failure, Rhabdomyolysis, Pleural effusion, and acute ischemic stroke.

Mortality is reported in 21% of the 57 cases described. However, better management of this condition has recently led to lower mortality. Prognosis can be determined according to the SCLS Severity Scale which describes the condition according to grades.

Capillary leak syndrome may present as an acute or chronic phase. The acute phase is further subdivided into the Capillary Leak Phase and Recruitment of the Interstitial Fluid.^[1]

The initial phase is the capillary leak phase, lasting from 1 to 4 days. Clinical features are abdominal pain, nausea, generalized edema and hypotension that may result in cardiopulmonary collapse. Acute renal failure is due to acute tubular necrosis consequent to hypovolemia and rhabdomyolysis.

The second phase results in the recruitment of the initially extravasated fluid. Intravascular overload with polyuria and pulmonary edema often occur. Edema may be more severe due to massive fluid supply in the initial phase. It’s necessary to monitor the patient in order to switch to depletion treatment with diuretics or hemofiltration.

The chronic subtype poses difficulty when diagnosing cases. Affected individuals often develop persistent but irregular generalized edema that progresses over time. Pleural and pericardial effusion may also be evident.^[2]

Most common complications of capillary leak syndrome include the following:^[4][5]

Mortality is reported in 21% of the 57 cases described. However, better management of this condition has recently led to lower mortality. Prognosis can be determined according to the SCLS Severity Scale which describes the condition according to grades.^[3]

In the Mayo Clinic’s experience, the median survival of 25 patients that were followed over 30 years (counting only SCLS-related deaths) was approximately 15 years, and their 5-year survival rate was 76%. In European experience, the 5-year post-diagnosis survival rate was 85% in 23 patients who had received prophylactic treatment and 20% in 5 patients who had not. However, better identification and management of this condition appears to be resulting in lower mortality and improving survival and quality-of-life results as of late.^[6]

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