Capillary leak syndrome

Capillary leak syndrome
Classification and external resources
DiseasesDB	34090
MeSH	D019559

Capillary leak syndrome (usually Systemic Capillary Leak Syndrome, SCLS or Clarkson’s Disease) 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 (low blood pressure), 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.

History

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]

Symptoms

Most patients report having a runny nose and/or other flu-like symptoms, or else gastro-intestinal disorders (diarrhea or vomiting), or a general weakness or pain in their limbs, but others get no particular or consistent warning signs ahead of their episode. They subsequently develop thirst and lightheadedness and the following measurable conditions:^[2][3]

• hemoconcentration;
• low blood pressure (hypotension);
• hypoalbuminemia; and
• partial or generalized edema.

Treatment

An episode of SCLS usually consists of two distinct phases:^[2][3]

The capillary leak phase

The initial stage is the capillary leak phase, lasting from 1 to 4 days. The most common clinical features are fatigue; lightheadedness up to and including syncope (fainting); limb, abdominal or generalized pain; facial or other edema; dyspnea; and hypotension that results in circulatory shock and potentially in cardiopulmonary collapse and other organ distress or damage. Acute renal failure is a risk due to acute tubular necrosis consequent to hypovolemia and rhabdomyolysis.

The loss of fluid out of the capillaries has similar effects on the circulation as dehydration, slowing both the flow of oxygen delivered to tissues and organs as well as the output of urine. Urgent medical attention in this phase consists of fluid resuscitation efforts, mainly the intravenous administration of saline solution plus hetastarch or albumin and colloids (to increase the remaining blood flow to vital organs like the kidneys), as well as glucocorticoids (steroids like methylprednisolone, to reduce or stop the capillary leak). However, it is important to avoid overly aggressive intravenous fluid administration during this leak phase, because it may cause massive swelling of the extremities and thus serious collateral damage because of induced compartment syndromes.

The recruitment phase

The second stage features the reabsorption of the initially extravasated fluid and usually lasts from 1 to 3 days. Intravascular fluid overload leads to polyuria and can cause flash pulmonary edema with possibly fatal consequences. The severity of the problem depends on to the quantity of fluid supplied in the initial phase, the damage that may have been sustained by the kidneys, and the promptness with which diuretics are administered to help the patient discharge the accumulated fluids quickly.

The prevention of episodes of SCLS has involved two approaches. The first has long been identified with the Mayo Clinic and it recommends treatment with beta agonists such as theophylline, terbutaline and montelukast sodium.^[4] The second, more recent approach pioneered in France involves monthly intravenous infusions of intravenous immunoglobulin (IVIG), and the case-report evidence is encouraging.^[5][6][7]

A recent review of clinical experience with 28 European SCLS patients suggests that either prophylactic treatment may reduce the frequency and severity of attacks and may improve survival.^[8]

Prognosis

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%.^[2][3] 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.^[8] 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.

See also

• Anasarca
• Urticarial syndromes

References

1. ^ Clarkson, Bayard; Thompson, David; Horwith, Melvin; Luckey, E.Hugh (1960). "Cyclical edema and shock due to increased capillary permeability". The American Journal of Medicine 29 (2): 193–216. doi:10.1016/0002-9343(60)90018-8. PMID 13693909. 
2. ^ ^{a b c d} Druey, Kirk M.; Greipp, Philip R. (2010). "Narrative Review: Clarkson Disease-Systemic Capillary Leak Syndrome". Annals of Internal Medicine 153 (2): 90–8. doi:10.1059/0003-4819-153-2-201007200-00005. PMC 3017349. PMID 20643990. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3017349. 
3. ^ ^{a b c d} Kapoor, Prashant; Greipp, Patricia T.; Schaefer, Eric W.; Mandrekar, Sumithra J.; Kamal, Arif H.; Gonzalez-Paz, Natalia C.; Kumar, Shaji; Greipp, Philip R. (2010). "Idiopathic Systemic Capillary Leak Syndrome (Clarkson's Disease): The Mayo Clinic Experience". Mayo Clinic Proceedings 85 (10): 905–12. doi:10.4065/mcp.2010.0159. PMC 2947962. PMID 20634497. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2947962. 
4. ^ Droder, RM; Kyle, RA; Greipp, PR (1992). "Control of systemic capillary leak syndrome with aminophylline and terbutaline". The American journal of medicine 92 (5): 523–6. doi:10.1016/0002-9343(92)90749-2. PMID 1580299. 
5. ^ Lambert, Marc; Launay, David; Hachulla, Eric; Morell-Dubois, Sandrine; Soland, Vincent; Queyrel, Viviane; Fourrier, François; Hatron, Pierre-Yves (2008). "High-dose intravenous immunoglobulins dramatically reverse systemic capillary leak syndrome". Critical Care Medicine 36 (7): 2184–7. doi:10.1097/CCM.0b013e31817d7c71. PMID 18552679. 
6. ^ Abgueguen, Pierre; Chennebault, Jean Marie; Pichard, Eric (2010). "Immunoglobulins for Treatment of Systemic Capillary Leak Syndrome". The American Journal of Medicine 123 (6): e3–4. doi:10.1016/j.amjmed.2009.09.034. PMID 20569743. 
7. ^ Zipponi, Manuel; Eugster, Roland; Birrenbach, Tanja (2011). "High-dose intravenous immunoglobulins: A promising therapeutic approach for idiopathic systemic capillary leak syndrome". BMJ Case Reports 2011. doi:10.1136/bcr.12.2010.3599. http://casereports.bmj.com/content/2011/bcr.12.2010.3599.abstract. 
8. ^ ^{a b} Gousseff, Marie; Arnaud, Laurent; Lambert, Marc; Hot, Arnaud; Hamidou, Mohamed; Duhaut, Pierre; Papo, Thomas; Soubrier, Martin et al. (2011). "The Systemic Capillary Leak Syndrome: A Case Series of 28 Patients From a European Registry". Annals of Internal Medicine 154 (7): 464–71. doi:10.1059/0003-4819-154-7-201104050-00004. PMID 21464348. 

External links

• Mayo Clinic overview, diagnosis and treatment information.
• Druey, Kirk M.; Greipp, Philip R. (2010). "Narrative Review: Clarkson Disease-Systemic Capillary Leak Syndrome". Annals of Internal Medicine 153 (2): 90–8. doi:10.1059/0003-4819-153-2-201007200-00005. PMC 3017349. PMID 20643990. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3017349. 
• ClinicalTrials.gov NCT00936325 Studies in the Pathogenesis of Systemic Capillary Leak Syndrome
• National Organization for Rare Disorders.
• Systemic Capillary Leak Syndrome Community
• Overview (2003) at Orphanet
• Article from the Washington Post about the disease and its virtual community.
• Article from the Pittsburgh Post Gazette about the disease and an upcoming TV episode covering it
• Alternative health group trying to compile personal health success stories