Narrative review: the systemic capillary leak syndrome Abstract: The systemic capillary leak syndrome (SCLS) is a rare disease of reversible plasma extravasation and vascular collapse accompanied by hemoconcentration and hypoalbuminemia. Its cause is unknown, although it is believed to be a manifestation of transient endothelial dysfunction due to endothelial contraction, apoptosis, injury, or a combination of these. Fewer than 150 cases of SCLS have been reported, but the condition is probably underrecognized because of its nonspecific symptoms and signs and high mortality rate. Patients experience shock and massive edema, often after a nonspecific prodrome of weakness, fatigue, and myalgias, and are at risk for ischemia-induced organ failure, rhabdomyolysis and muscle compartment syndromes, and venous thromboembolism. Shock and edema reverse almost as quickly as they begin, at which time patients are at risk for death from flash pulmonary edema during rapid fluid remobilization. Diagnosis is made clinically and by exclusion of other diseases that cause similar symptoms and signs, most notably sepsis, anaphylaxis, and angioedema. Acute episodes are treated with vasopressor therapy and judicious fluid replacement, possibly with colloid solutions for their osmotic effects, to prevent the sequelae of underperfusion. Between episodes, patients may be treated with theophylline and terbutaline, which clinical experience suggests may reduce the severity and frequency of acute episodes. Prognosis is uncertain, but patients who survive an initial severe SCLS episode are estimated to have a 10-year survival rate greater than 70%. Much remains to be learned about SCLS, and clinicians should consider the diagnosis in patients with unexplained edema, increased hematocrit, and hypotension.

Idiopathic Systemic Capillary Leak Syndrome (Clarkson’s Disease): The Mayo Clinic Experience Abstract: Of the 34 patients whose records were reviewed, 25 fulfilled all diagnostic criteria for SCLS. The median age at diagnosis of SCLS was 44 years. Median follow-up of surviving patients was 4.9 years, and median time to diagnosis from symptom onset was 1.1 years (interquartile range, 0.5-4.1 years). Flulike illness or myalgia was reported by 14 patients (56%) at onset of an acute attack of SCLS, and rhabdomyolysis developed in 9 patients (36%). Patients with a greater decrease in albumin level had a higher likelihood of developing rhabdomyolysis (P=.03). Monoclonal gammopathy, predominantly of the IgG-kappa type, was found in 19 patients (76%). The progression rate to multiple myeloma was 0.7% per person-year of follow-up. The overall response rate to the different therapies was 76%, and 24% of patients sustained durable (>2 years) complete remission. The estimated 5-year overall survival rate was 76% (95% confidence interval, 59%-97%). In conclusion, SCLS, a rare disease that occurs in those of middle age, is usually diagnosed after a considerable delay from onset of symptoms. The degree of albumin decrement during an attack correlates with development of rhabdomyolysis. A reduction in the frequency and/or the severity of attacks was seen in nearly three-fourths of patients who were offered empiric therapies. The rate of progression to multiple myeloma appears to be comparable to that of monoclonal gammopathy of undetermined significance.

High-Dose Intravenous Immunoglobulins Dramatically Reverse Systemic Capillary Leak Syndrome. Abstract: The objective of this study was to report the dramatic improvement of patients with systemic capillary leak syndrome obtained with high-dose intravenous immunoglobulins. Systemic capillary leak syndrome is a rare and life-threatening disorder characterized by hypotension that can lead to shock, weight gain, hypoalbuminemia, and elevated hematocrit secondary to unexplained episodic capillary fluid extravasation into the interstitial space. Because its cause is unknown, systemic capillary leak syndrome treatment has remained largely supportive. Intravenous immunoglobulins administration to a patient with refractory systemic capillary leak syndrome yielded dramatic improvement. The patient is still alive 11 yrs after systemic capillary leak syndrome diagnosis and receives intravenous immunoglobulins monthly. Later, based on that result, intravenous immunoglobulins were successfully given to two other patients during the acute phase of systemic capillary leak syndrome. Both are still alive 8 and 1.5 yrs after receiving intravenous immunoglobulins at the onset of each flare. In conclusion, intravenous immunoglobulins were effective against systemic capillary leak syndrome symptoms in three patients, but their exact mechanism remains unknown. Their immunomodulatory effect merits further investigation.

Immunoglobulins for Treatment of Systemic Capillary Leak Syndrome Abstract: A 43-year-old white woman in France diagnosed with SCLS was put on the recommended combination of Theophylline plus Terbutaline, but she nevertheless had 10 episodes of severe capillary leak during 2001-mid-2007, necessitating intensive care unit admission for her last 3 episodes. She was then put on IVIG administered every 6 weeks, and this yielded a dramatic improvement such that she has had no more episodes and has returned to her normal lifestyle.

The Mayo Clinic’s summary of the diagnosis and treatment of SCLS. From the Treatment section:
During an episode of systemic capillary leak syndrome, fluids are administered intravenously to maintain the patient’s blood pressure and to prevent damage to vital organs such as the kidneys, heart and brain. The amount of fluid must be carefully controlled. An attempt to normalize blood pressure through aggressive fluid administration can cause destructive swelling of the body’s extremities and overload the kidneys and lungs when the body needs to eliminate the excess fluids after the episode passes.

Glucocorticoids (steroids) are often injected during an acute capillary leak syndrome attack to reduce or stop the capillary leak. This is sometimes successful. Fluid pressure in muscles may be monitored. Emergency surgery may be needed to relieve pressure and minimize damage to muscles and nerves in the arms and legs.

Once the capillary walls stop leaking and fluids start to be reabsorbed, patients are usually given diuretics to speed up elimination of the fluids before they accumulate in the lungs and other vital organs, which can be a fatal complication.

Patients who avoid organ and limb damage in a capillary leak syndrome episode tend to recover their health after several days, once the capillary walls return to normal and the accumulated fluid is expelled from the body through urination.

Although no cure has been found for systemic capillary leak syndrome, the frequency and/or severity of episodes is often reduced by having patients take certain asthma medications: theophylline and terbutaline. Patients also may benefit from intravenous treatment with immunoglobulin or by taking thalidomide.

Patients may also be prescribed corticosteroid pills such as prednisone to be taken at the first sign of symptoms of another capillary leak.

This article from The Washington Post newspaper tells the story of how this SCLS virtual community was created, the story of its founder and, more generally, of this fantastic RareShare site.

The Systemic Capillary Leak Syndrome: A Case Series of 28 Patients From a European Registry. Abstract: The article describes the clinical characteristics, laboratory findings, treatments, and outcomes of patients with SCLS who were not previously reported in the literature. These European patients with SCLS were treated and monitored from the start of 1997 until end-July 2010. Survival rates were 89% at 1 year and 73% at 5 years; instances of death were directly related to SCLS attacks in 6 cases (75% of total). Treatments of various kinds increased the chances of survival: Five years after diagnosis, survival rates were 85% in 23 patients who had received a treatment and just 20% in 5 patients who had not. The authors provide additional evidence that a prophylactic treatment with IVIG tends to reduce the frequency and severity of attacks, and may improve the survival of patients with SCLS.

High-dose intravenous immunoglobulins: A promising therapeutic approach for idiopathic systemic capillary leak syndrome. Abstract: The article reports the case of a 40-year-old woman with chronic SCLS treated in Berne, Switzerland, with high-dose intravenous immunoglobulins (IVIG) after a prophylactic therapy with theophylline and terbutaline (T&T) was poorly tolerated and failed to decrease the frequency and severity of the attacks. During the 5 years she was on T&T the patient suffered from about 20 similar episodes of mild to moderate shock, often requiring hospital re-admission and supportive therapy. So far, 10 months of prophylactic therapy with IVIG (2gr/kg/month) have resulted in an impressive reduction of intensity and frequency of attacks, confirming the finding of other case studies.

Comment on The Systemic Capillary Leak Syndrome. Abstract: The authors report on 2 additional patients from the United States with SCLS in whom prophylaxis with terbutaline and theophylline failed, but who had no further episodes after the initiation of IVIG therapy. There are additional published reports of successful prophylaxis with IVIG cited, and the authors are also aware of yet another case. Given the present state of knowledge and despite the high cost, the authors strongly believe that IVIG is the optimal prophylaxis and should be the initial choice to prevent attacks in patients with SCLS.

The 5-Minute ICU Consult Entry on SCLS Abstract: The entry on SCLS appears on pages 256-257 of the 2012 edition of this new guide containing more than 200 entries covering all aspects of adult critical care. The 2-page protocol includes the basics, diagnosis, treatment, and ongoing care of patients with SCLS.