NORD gratefully acknowledges Philip R. Greipp, MD, Professor of Medicine and Laboratory Medicine and Pathology at the Mayo Clinic College of Medicine for creating this report.
Systemic capillary leak syndrome (SCLS) is a rare acquired disorder characterized by acute and severe recurrent attacks associated with a rapid fall in blood pressure. Attacks often last several days and require emergency care. They are sometimes fatal. SCLS occurs most often in adults and the disease is very rare in children. SCLS is not hereditary.
Symptoms of systemic capillary leak syndrome classically involve a brief warning, which can include nasal congestion and cough that can be mistaken for a viral upper respiratory infection. Patients develop malaise, nausea, lightheadedness, a faint feeling, abdominal pain headache and swelling of the extremities. There is a characteristic absence of fever, chills, rash, or signs of infection. Overt prostration and fainting may occur.
Disappearance of the syndrome is rare. Such remissions may be spontaneous or they may follow treatment. Disappearance of SCLS may be more common in children than adults.
A chronic form of SCLS has been reported that is manifest by swelling of the extremities and sometimes fluid accumulation around the heart and lungs. The characteristic increase in hemoglobin and hematocrit and decrease in albumin occur due to loss of fluid in the tissues. Low blood volume with decrease in blood pressure or shock are uncommon in the chronic form. These patients may respond to glucocorticoids, diuretics, and aminophylline.
More than one half of patients have a monoclonal or M protein detected in the blood. The level of M protein is usually low. The M protein is produced by what usually amount to small numbers of plasma cells in the marrow. The M protein itself does not appear to cause the attacks. Many possible explanations have been offered including an autoimmune mechanism. Recently it has been suggested that capillary lining cells may be damaged by a factor in the blood, which is produced during the acute attack. SCLS has been recognized in a range of racial backgrounds and nationalities. Although the cause of SCLS is not yet known, there appears to be no genetic predisposition to the disease.
There are less than 100 patients reported in the world literature since its first description in 1960 by Clarkson. SCLS seems to occur more often in males and older adults. The disease may be more frequent than the literature suggests because the diagnosis is often missed or delayed. SCLS may be mistaken for a severe infection such as septic shock or toxic shock syndrome. Some features such as the swelling may lead one to suspect heart failure or kidney disease. C-1 esterase inhibitor deficiency syndrome may present with a type of recurring edema called angioedema and is often thought of in patients presenting with SCLS. In some cases the hemoconcentration and resulting high hematocrit and hemoglobin level have been mistaken for polycythemia.
Patients present with a classic combination of hypotension or shock accompanied b. hemoconcentration, and hypoalbuminemia. To confirm the diagnosis several key laboratory features are critical. The sudden and profound capillary leak causes a sharp decrease in serum albumin level (hypoalbuminemia) and a similarly sharp increase in the level of hemoglobin and hematocrit. The red blood cells which contribute to measurements of hemoglobin and hematocrit are not actually increased. Rather the blood becomes concentrated due to the loss of fluid. This hemoconcentration is a classic feature of the syndrome and proof of hemoconcentration is essential for the diagnosis. Some patients are mistakenly diagnosed as having polycythemia, a condition in which the hematocrit is increased due to excessive marrow production of red blood cells.
In order to make a diagnosis of SCLS one should rule out infection and C-1 esterase inhibitor deficiency by laboratory studies. A search for an M protein should be undertaken but the absence of an M protein does not exclude the diagnosis.
Treatment is directed at prevention of attacks using agents aimed at decreasing capillary leakage and aimed at interfering with hormone like cytokines that induce the leakage. Once an attack is underway, treatment is directed toward controlling blood pressure to maintain blood flow to vital organs as well as preventing excessive swelling and fluid accumulation.
Treatment of a fully developed SCLS episode requires recognition that there are two phases of the acute attack. The first phase, which often lasts several days is called the resuscitation phase aimed at controlling the capillary leak and maintaining blood pressure. In that phase an albumin and fluid leak from the capillaries into the tissue spaces causes swelling. This loss of fluid has similar effects on the circulation as dehydration, slowing the flow of oxygen carrying blood to tissues. The blood pressure falls and the red cells concentrate. Intravenous fluid replacement is usually required. In most cases intravenous fluids must be administered immediately and in high-volume in order to prevent excessive drops in blood pressure. Intravenous albumin and colloid may be used. Keeping up with the fluid loss is important because sustained low blood pressure can damage vital organs such as the kidneys.
The second phase of the treatment is sometimes called the recruitment phase as fluids and albumin are reabsorbed from the tissues. In this phase the capillary leak has abated and the main threat is fluid overload. Even though the blood pressure may still be low, it is important to avoid overly aggressive intravenous fluid administration causing massive swelling of the extremities requiring surgical decompression. In this procedure the skin of the arm or leg is incised to release the compressive pressure the retained fluid is having on blood flow to and from the extremities. Excessive intravenous fluids may also cause accumulation of fluid in the lungs and around other vital organs. Many of the deaths happen during this recruitment phase. The goal during the acute phase is NOT to attempt to maintain absolutely normal blood pressure or urine flow but to maintain the blood pressure at just sufficiently high enough levels to avoid permanent damage to vital organs yet spare the patient from the risks of excess fluid administration. Measurement of central venous or arterial pressure in an intensive care unit is often necessary to achieve this delicate balance. Diuretics may be required for excess fluid overload.
Glucocorticoids (steroids) are often used during the acute attack especially early in the recruitment phase in an attempt to reduce the capillary leak. Albumin and colloids administered with the intravenous fluids may have temporary benefit to increase blood flow to vital organs like the kidneys.
Maintenance therapy is given in an attempt to reduce the frequency and severity of the acute attacks. The most commonly used medications are a combination of theophylline and terbutaline. These are administered by mouth. The level of theophylline must be maintained in the therapeutic range at a means of regular blood tests. Patients who do not tolerate these drugs may benefit by leukotriene inhibitors such as Singulair. Occasionally an ACE inhibitor such as lisinopril may be of benefit. The role of glucocorticoids, chemotherapy, thalidomide, and intravenous immunoglobulin is as yet unproven.
The National Institute of Allergy and Infectious Diseases (NIAID) is sponsoring a study to investigate mechanisms that may cause systemic capillary leak syndrome. Patients between 16 and 65 years of age who have been diagnosed with SCLS are eligible. The following link provides details:
For more information, please contact:
Patient Recruitment and Public Liaison Office
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
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Assaly, R, Olson, D, Hammersley, J; Fan, P; Liu, J, Shapiro, JI Bashar Kahaleh, M. Initial Evidence of Endothelial Cell Apoptosis as a Mechanism of Systemic Capillary Leak Syndrome. Chest. 2001; 120:1301-1308
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Talasczka A, Rondeau E, Dutel JL, Wechsler B, Piette JC. Systemic capillary leak syndrome: report on 13 patients with special focus on course and treatment. Am J Med. 1997;103: 514-519
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