Systemic capillary leak syndrome (ORPHA:188)
Systemic capillary leak syndrome (SCLS) is a severe systemic disease due to increased capillary permeability, characterized by episodes of hypotension, edema and hypovolemia.
Epidemiology
SCLS has been reported in less than 150 cases since its first description in 1960.
Clinical description
Mean age of onset is 45 and pediatric or geriatric cases are rare. The disease is characterized by alternance of crises and quiescent phases. Delay between crises is a few weeks to several years. They have been reported following infection, mostly of the upper airways, during perimenstrual or post-partum periods and, more rarely, after intense physical effort. They last days or weeks, can be of variable severity, from grade 1 (hypotension responding to oral hydration) to grade 4 (fatal attacks), and have a 3-step evolution. Crises may start with prodromes such as generalized weakness, fatigue, myalgias, orthostatic hypotension, possible digestive (diarrea, abdominal pain) and ENT (rhinorrhea, cough) manifestations, occasional fever and weight gain. The leak phase follows with oliguria, arterial hypotension and rapid development of edema of the face or the upper limbs but sparing the lungs. Hypotension may lead to hypovolemic shock with preserved consciousness. In the post-leak phase, massive edema resorption leads to polyuria and weight loss. Biological features are a characteristic association of hemoconcentration with hypoalbuminemia without albuminuria, hyperleukocytosis and a proteinemia drop in the 350-750 kDa range. Chronic cases have been reported with a continuous generalized edema, visceral effusions, hypotension and hemoconcentration being more subtle. Complications may occur in acute and post-leak phases: in the former, they include compartment syndrome with rhabdomyolysis, cardiac arrythmias, thrombosis, pancreatitis, pericarditis (see this term), seizures, cerebral edema or thickening of the myocardium. Rhabdomyolysis and fatal pericarditis may also occur in the post-leak phase, but cardiovascular overload is more frequent. Fatal acute lung edema has also been reported at this stage. Renal failure may result from hypoperfusion-induced acute tubular necrosis and rhabdomyolysis.
Etiology
SCLS is caused by capillary hyperpermeability of unknown etiology. Several physiopathological hypotheses have been considered such as an inflammation-mediated mechanism or a damage of the capillary endothelium by the monoclonal gammopathy.
Diagnostic methods
Diagnosis is based on physical and biological examination, recurrence of crises, association of hemoconcentration with hypoalbuminemia being strong indicators. The presence of an anomalous monoclonal immunoglobulin termed paraprotein is suggestive but not diagnostic.
Differential diagnosis
Differential diagnosis includes sepsis, anaphylaxis, any other cause of capillary leakage and inferior vena cavainterruption (see this term). Chronic cases might be misdiagnosed as Gleich syndrome, venous stasis, protein-losing enteropathy and nephrotic syndrome.
Management and treatment
There is no curative treatment, thus management is symptomatic and prophylactic. Intravenous fluids administration is not recommended as it fails to increase arterial pressure and worsens edema, furthermore it increases the risk of vascular overload in the post-leak phase. Oral electrolyte-containing fluids can reduce the attack severity if taken early, thus patient education to detect early signs of prodrome is crucial. Beta-adrenergic agonists (terbutaline) and phosphodiesterase inhibitors (theophylline) have shown good results in few cases but have serious side effects; intra-venous immunoglobulines are a promising prophylactic strategy.
Prognosis
Despite progress in diagnosis and management that has prolonged the survival of patients, prognosis remains poor as mortality reaches 30-40% after 10 years.

                            Last update: 
                            November 2012


                            - Expert reviewer(s): 
                            Pr Zahir AMOURA