Studies in the Pathogenesis of Systemic Capillary Leak Syndrome

Background:

• Systemic Capillary Leak Syndrome (SCLS) is a disorder of unknown cause characterized by episodes of life-threatening drop in blood pressure and leakage of fluids into tissues. The outcome from an episode of SCLS may be mild and resolve on its own, or may be severe and result in death. Although SCLS likely involves abnormalities in the cells lining blood vessels, the specific cause(s) of this disorder are not known.
• The treatment of choice for an acute SCLS episode is intravenous fluids and drugs such as norepinephrine (adrenaline), which are given to keep blood pressure at a level that will maintain vital organ function. This may be followed by a course of intravenous steroids and IVIG. Currently, there is no cure, but IVIG has been effective in diminishing the frequency and/or intensity of SCLS episodes when given regularly, as long-term effective preventive therapy for many patients who experience recurrent episodes of SCLS.
• This protocol is focused on understanding what causes SCLS with the hope that research findings will lead to the design of safe and more effective treatments. Objectives: \- To investigate mechanisms that may cause Systemic Capillary Leak Syndrome. Eligibility:
• Patients between 16 and older who have been diagnosed with SCLS. Patients who have been diagnosed with SCLS and are between the ages of 7 and 16 may participate off-site, by sending specimens to the NIH. Patients 16 and older who have been diagnosed with SCLS and cannot travel to the NIH may also participate off-site.
• Patients must have a documented history of at least one episode of SCLS with all three of the following documented on at least one occasion: low blood volume, low blood pressure without cause, and evidence of protein leakage during the episode. A letter of a referral from a treating physician is also required. Design:
• Patients seen on site will be evaluated at the National Institutes of Health (NIH) for approximately 4 to 5 days on an inpatient basis, and will undergo the following procedures:
• Medical history and physical examination.
• Blood samples for evaluation and research purposes, as well as possible genetic testing.
• Apheresis procedure, if needed, to obtain a larger volume of blood cells for research.
• Bone marrow biopsy, if medically indicated.
• Other medically indicated tests, such as skin tests to check for possible allergic reactions.
• Patients who have a capillary leak episode while at NIH will be treated with the standard of care for treating SCLS.
• Patients will be discharged from the protocol 1 year after the NIH visit.
• Patients participating off-site will be asked to collect and send specimens (such as blood) to the NIH for research purposes and evaluation.
• Unaffected Biological relatives of SCLS patients and Unrelated Normal Volunteers may also enroll on the study. Relatives and Normal Volunteers may be asked to provide research samples for the study, such as skin biopsy and research blood specimens.