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Systemic Capillary Leak Syndrome

What Is It, Causes, Symptoms, Diagnosis, and More

Author:Lily Guo

Editors:Alyssa Haag,Ian Mannarino, MD, MBA,Kelsey LaFayette, DNP, RN

Illustrator:Jessica Reynolds, MS

Copyeditor:Sadia Zaman, MBBS, BSc


What is systemic capillary leak syndrome?

Systemic capillary leak syndrome (SCLS), also known as Clarkson disease, is a rare disorder in which considerable amounts of plasma and proteins leak from capillaries into surrounding tissue, muscle, and body cavities. As a result, there is a sharp drop in blood pressure - potentially resulting in hypovolemic shock - hypoalbuminemia, and thickened blood due to a decrease in plasma volume (i.e., hemoconcentration). If left untreated, organ failure and death can occur. The frequency of attacks can range from several a year to a single occurrence in a lifetime. The average age of onset is 45 years of age with the sexes affected equally. Of note, there have only been approximately 250 cases reported in medical literature to date. 

Enlarged illustration of capillary with injured walls leaking fluid.

What causes systemic capillary leak syndrome?

The cause of systemic capillary leak syndrome is often unknown (idiopathic SCLS), however, it is thought to be an abnormal response of the immune system to an infection or illness. Attacks of capillary leak syndrome may be triggered by upper respiratory tract infections or through intense physical exertion. It has recently been discovered that COVID-19 can induce this disorder in those who have never had an attack, as well as induce recurring episodes in those who have previously experienced SCLS. 

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What are the signs and symptoms of systemic capillary leak syndrome?

The signs and symptoms of systemic capillary leak syndrome vary from person-to-person. The clinical presentation usually consists of three phases: prodromal phase, status phase, and recovery. During the prodromal phase, there are non-specific symptoms, including irritability, fatigue, abdominal pain, nausea, muscle aches, increased thirst, and sudden increases in body weight. Symptoms such as fever, chills, rash, or signs of infection may or may not be present. This phase typically lasts one to two days. The status phase follows and is characterized by general swelling; significantly low blood pressure; fluid build-up in the lungs and around the heart; diminished urine output; and preserved consciousness. Other complications of this stage may include rhabdomyolysis, which is the breakdown of muscle tissue causing release of proteins and electrolytes into the blood, and compartment syndrome of the extremities. Compartment syndrome is a rare and painful condition that occurs when a build-up of pressure around the muscle leads to decreased blood flow and potential loss of the affected limb. During recovery, which usually takes place between the fifth and seventh day, blood pressure normalizes, urine output normalizes, swelling reduces and the individual loses weight.

These characteristic features often vary, with some people experiencing more symptoms than others, and they can range from mild to severe. Over time, as fluid leaks out from the bloodstream, organs may be starved of adequate blood flow. For example, the kidneys, brain, and liver may be deprived of oxygen and other critical nutrients they need for normal function. If left untreated, kidney failure, lung failure, heart failure, and stroke can occur. 

How is systemic capillary leak syndrome diagnosed?

Diagnosis of systemic capillary leak syndrome is based on the clinical history, examination, and other laboratory tests. Specifically, if an individual experiences recurring episodes, a blood test may reveal monoclonal gammopathy (i.e., an abnormal immunoglobulin protein) that is indicative of SCLS. Furthermore, other conditions need to be excluded before systemic capillary leak syndrome can be diagnosed, especially since the condition resembles septic shock (a severe reaction to widespread infection) and anaphylactic shock (a severe allergic reaction). 

How is systemic capillary leak syndrome treated?

There is currently no known cure, so treatment of systemic capillary leak syndrome is focused on managing and stabilizing the symptoms during an episode, and preventing future episodes and complications. Given the serious nature of the disorder, treatment usually occurs in an intensive care unit. During an episode, treatment involves stabilizing the airway, administering medications, providing hydration, and delivering oxygen therapy. Intravenous fluids are often administered. After a variable number of days, the vascular permeability spontaneously improves, and the blood pressure stabilizes. There are prophylactic treatments that can help prevent future episodes, including monthly infusions of intravenous immunoglobulin (IVIG). Those who do not improve with IVIG or who cannot tolerate the therapy may have success with theophylline and terbutaline, which are oral medications designed to treat asthma.

What are the most important facts to know about systemic capillary leak syndrome?

Systemic capillary leak syndrome (SCLS) is a rare disease that involves the leaking of massive amounts of plasma and protein through capillaries, leading to hypovolemic shock, which deprives major organs of oxygen and nutrients if not treated rapidly. Currently, the cause(s) of SCLS are unknown, however it is thought that it is an immune response to infection or illness. In the days leading up to a SCLS attack, the individual may feel fatigue, nausea and abdominal pain. They are also likely to experience swelling and weight gain as a result of capillary leakage. Long-term complications include lung, kidney, and heart failure. Diagnosis relies on clinical examination and laboratory testing. Finally, treatment is focused on managing symptoms and administering IVIG as prophylactic therapy. 

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Resources for research and reference

Atkinson J. P., Waldmann T. A., Stein S. F., et al. (1977). Systemic capillary leak syndrome and monoclonal IgG gammopathy; studies in a sixth patient and a review of the literature. Medicine (Baltimore), 56: 225-239. DOI: 10.1097/00005792-197705000-00004

Durand Bechu, M., Rouget, A., Recher, C., Azoulay, E., & Bounes, V. (2016). A Systemic Capillary Leak Syndrome (Clarkson Syndrome) in a Patient with Chronic Lymphocytic Leukemia: A Case Report in an Out-of-Hospital Setting. Case reports in emergency medicine, 2016, 5347039. DOI:10.1155/2016/5347039

Kapoor, P., Greipp, P. T., Schaefer, E. W., Mandrekar, S. J., Kamal, A. H., Gonzalez-Paz, N. C., Kumar, S., & Greipp, P. R. (2010). Idiopathic systemic capillary leak syndrome (Clarkson's disease): the Mayo clinic experience. Mayo Clinic proceedings, 85(10): 905–912. DOI: 10.4065/mcp.2010.0159

Mayo Clinic (2021, October 29). Systemic capillary leak syndrome. In Mayo Clinic. Retrieved November 15, 2021, from https://www.mayoclinic.org/diseases-conditions/systemic-capillary-leak-syndrome/symptoms-causes/syc-20378147. 

Pineton de Chambrun, M., Constantin, J. M., Mathian, A., Quemeneur, C., Lepere, V., Combes, A., Luyt, C. E., & Amoura, Z. (2021). Clarkson's Disease Episode or Secondary Systemic Capillary Leak-Syndrome: That Is the Question!. Chest, 159(1): 441. DOI: 10.1016/j.chest.2020.07.084

U.S. Department of Health and Human Services. (2021, November 8). Systemic capillary leak syndrome. In Genetic and Rare Diseases Information Center. Retrieved November 15, 2021, from https://rarediseases.info.nih.gov/diseases/1084/systemic-capillary-leak-syndrome.