Capillary leak syndrome

Capillary leak syndrome (also known as systemic capillary leak syndrome, SCLS, or Clarkson’s disease) is an extremely 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 (Ht up to 80-85%);
• low blood pressure (hypotension);
• hypoalbuminemia;
• partial or generalized edema;
• possible MGUS.

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 3 days, during which up to 70% of total plasma volume may invade cavities in the trunk and extremities.^[2] 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.^[2][3] Acute renal failure is a risk due to acute tubular necrosis consequent to hypovolemia and rhabdomyolysis.^[2][3]

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).^[2] 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.^[3]

The recruitment phase

The second stage features the reabsorption of the initially extravasated fluid and it usually lasts just as long as the leak phase. Intravascular fluid overload leads to polyuria and can cause flash pulmonary edema, with possibly fatal consequences.^[2][3] 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.^[2]

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 terbutaline, phosphodiesterase inhibitor theophylline and leukotriene receptor antagonists montelukast sodium.^[4] The second, more recent approach pioneered in France involves monthly intravenous infusions of intravenous immunoglobulin (IVIG), and the growing case-report evidence is encouraging.^[5][6][7][8]

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.^[9]

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.^[9] 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.

References

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 (inactive 2015-01-11). PMC 3017349. PMID 20643990. 
• Clinical trial number NCT00936325 for "Studies in the Pathogenesis of Systemic Capillary Leak Syndrome" at ClinicalTrials.gov
• National Organization for Rare Disorders.
• Systemic Capillary Leak Syndrome Community
• Overview (2003) at Orphanet