Kirk M. Druey, MD; Philip R. Greipp, MD
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.
Classic acute prodromal symptoms, which can last hours to days, may precede the rapid development of hemoconcentration and hypovolemia, although symptoms may occasionally develop rapidly in the absence of a prodrome. Hypoalbuminemia and edema due to fluid and protein extravasation characterize the leak phase, which lasts for several days in the classic acute syndrome. The postleak phase comprises restoration of capillary barrier function with recruitment of fluids into the intravascular space and diuresis. Complications associated with each phase are listed. DVT = deep venous thrombosis; SCLS = systemic capillary leak syndrome.
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Dept. of Occup. Safety & Hlth., Tampere, Finland
July 20, 2010
Proteoglycans and leakage of protein
The extremely interesting review on the systemic capillary leakage of circulating macromolecules (1) raises the possibility of capillary dysfunction(s).
An analogous more common case is the renal proteinuria. It is thought that the heparan sulfate proteoglycan of the glomerular basement membrane is one of the key elements to retain red blood cells and plasma protein in the circulation. This may be achieved by the negative net charge of the proteoglycans which repel cells and other protein species.
Urinary proteoglycan analysis indeed shows that their synthesis and excretion is changed in asymptomatic proteinuria (2). Based on this, one wonders whether similar changes occur also in the generalized leakage syndrome
1 Druey KM, Greipp PR. Narrative review: The systemic capillary leak syndrome. Ann Int Med 2010; 153: 90-98
2 Savolainen H. A sensitive method for the analysis of urinary proteoglycans. Biochem Int 1992; 28: 475-479
Bert A. Govig
August 19, 2010
Moving beyond anecdotes in the Systemic Capillary Leak Syndrome
SCLS can be a dramatic, perplexing and terrifying disease to treat, particularly in its initial presentation. We have repeatedly treated a patient with recurrent SCLS and consulted by telephone on another patient. We thank Drs Druey and Greipp for raising awareness of this rare syndrome, and would like to compliment their excellent review with our anecdotal experience and three comments:
1. We agree with their observation that the SCLS is distinct from sepsis in its weak response to vasopressors, and its associated polycythemia and severe hypoalbuminemia, but these findings are more obvious in retrospect, and the clinical features of hypotension, tachycardia and elevated white blood cell count should trigger a septic work up and empiric broad spectrum antibiotics in most newly presenting cases of SCLS.
2. We also agree that aggressive volume administration is a two edged sword that palliates the first phase of the disease and complicates the second phase, particularly if there is oliguria. We favor hydroxyethyl starch (or similar large molecule colloids) as a colloid agent for the theoretical reason that its molecular weight (264 kD) is much larger than albumin and it may be more contained to the vascular space. Our patient received 10 liters of crystalloid in the initial 24 hours of her diagnostic presentation and suffered a bilateral lower extremity compartment syndrome. In her subsequent 15 admissions she received on average 730 ml. of hydroxyethyl starch and 5 liters of crystalloid in the first 24 hours, and suffered no major symptoms of volume overload.
3. The evidence base for the prevention of recurrences is extremely thin. This is, in part, because of the rarity of the disease, and the fact that it may remit for long periods. Our patient had an undiagnosed and self limited episode in 2004, a dramatic life threatening presentation in 2006 (which prompted preventative treatment with theophylline and terbutaline), and then fourteen episodes in the first 8 months of 2008 (mean and median remission times of 18 and 9 days). She was then started on IV Ig 1g/Kg x 2 days q 4 weeks, and experienced one episode thirteen days after the first treatment, and none in the subsequent 23 months. It is tempting but naive to draw conclusions from such anecdotal experience, and an international patient registry would be of great use in determining the natural history of this disease and its treatments.
Ragheb A Assaly
University of Toledo
December 4, 2010
Acute right axis deviation in SCLS
In their recent Narrative Review: The Systemic Capillary Leak Syndrome (SCLS) Druey, and Greipp, (1) did not discuss a clinical characteristic common to both our patients and others with SCLS (2). The development of acute right-axis deviation during the acute attacks that resolved with the resolution of the attack. Jacox et al (3) also described this finding. In our patients, pulmonary emboli were ruled out, as was acute pulmonary hypertension due to either left myocardial dysfunction or hypoxia. Instead, we suggest that the acute right-axis deviation (in the absence of pulmonary emboli and hypoxia) is secondary to the notable increase in Pulmonary Vascular Resistance (PVR). This mechanism was proposed by Lister et al (4) following the acute and dramatic rise in hematocrit that also raises blood viscosity.
1) Kirk M. Druey, MD, and Philip R. Greipp, MD, Narrative Review: The Systemic Capillary Leak Syndrome Ann Intern Med. 2010; 153:90-98.
2)Assaly R, Olson D, Hammersley J, Fan PS, Liu J, Shapiro JI, et al. Initial evidence of endothelial cell apoptosis as a mechanism of systemic capillary leak syndrome. Chest. 2001; 120:1301-8.
3) Jacox RF, Waterhouse C, Tobin R. Periodic disease associated with muscle destruction. Am J Med 1973; 55:105-110
4)Lister G, Hellenbrand WE, Kleinman CS, et al. Physiologic effects of increasing hemoglobin concentration in left to right shunting in infants with ventricular septal defects. N Engl J Med 1982; 306:502-506
Druey KM, Greipp PR. Narrative Review: The Systemic Capillary Leak Syndrome. Ann Intern Med. 2010;153:90-98. doi: 10.7326/0003-4819-153-2-201007200-00005
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Published: Ann Intern Med. 2010;153(2):90-98.
Infectious Disease, Multi-Organ Failure and Sepsis, Pulmonary/Critical Care, Venous Thromboembolism.
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