Systemic Capillary Leak Syndrome Details

Expanded Description

Systemic Capillary Leak Syndrome (SCLS) is an exceedingly rare, life- and limb-threatening disorder characterized by acute and severe recurrent attacks featuring a rapid fall in blood pressure due to the temporary leak of plasma out of the blood circulatory system.

The episodes often last several days and require emergency and intensive care in a hospital setting. Identification and management of these episodes has improved in recent years and thus the survival rate has increased, but sometimes they still prove fatal depending on what medications are administered in what sequence and dosage, and depending on how the vital organs can cope (particularly the heart, lungs and kidney). SCLS is very rare in children and there is no evidence of it being hereditary.

Prevalence

1000.0 ( Cases ) [Source]

Causes

Systemic Capillary Leak Syndrome (SCLS) is idiopathic, and thus at present there are no known causes. Probably a mid-life gene mutation takes place that renders those affected vulnerable (possibly immune-deficient in some way) to these curiously self-reversing capillary leaks..

Disorder Symptoms

Many patients report having a runny nose, flu-like symptoms, gastro-intestinal disorders, a general weakness or pain in their limbs, or swelling in the face or hands and feet, but others get no particular or consistent warning signs.

Name	Description
Swelling	swelling
Myalgia	Myalgia is muscle pain
Rhinorrhea	Rhinorrhea is a runny nose
Dizziness	Dizziness
Lightheadedness	Lightheadedness
Hypotension	Hypotension is abnormally low blood pressure
Hemoconcentration	Hemoconcentration is the decrease of the fluid content of the blood, with increased concentration of formed elements
Hypoalbuminemia	Hypoalbuminemia is low levels of protein in the blood
Nausea	Nausea
Excessive thirst	Excessive thirst
Generalized edema	Generalized edema
Decline in clinical picture	Clinical picture declines rapidly within hours
Cold limbs and sweating	Cold limbs and sweating
Rapid swelling and compartment syndrome	Rapid swelling of all limbs with development of compartment syndrome, especially during IV fluid administration
Decreased urine output	Decreased urine output
Vomiting	Usually caused by severe nausea
Intestinal cramps	Cramps
Diarrhea	Frequent loose stools
Fatigue	Extreme loss of energy

Diagnosis

Systemic Capillary Leak Syndrome is diagnosed based on symptoms and the presence of an unusual protein called a Monoclonal Gammopathy of Unknown Significance (MGUS) in most patients. Symptoms for diagnosis are hypotension, hemoconcentration, hypoalbuminemia and the presence of the MGUS.

Diagnostic Tests

• Elevated hemoglobin due to hemoconcentration (can be > 20 gm/dl).

• Decreased serum albumin.

• Increase in creatine kinase (CPK) levels, with marked edema and compartment syndrome.

• Although creatinine may increase, overt renal failure is not common.

• Chest X-ray may show fluid retention, but lungs are relatively spared except as a result of overaggressive hydration.

Name
Lab test for hemoconcentration
Portable, instantaneous test for hemoconcentration

Disorder Treatments

• Methylprednisolone 125 mg IV STAT, repeated as needed.

• Judicious use of IVF boluses and drips to keep CVP above zero.

• Phenylephrine or Norepinephrine for hypotension, early institution.

• 50 ml of 25% albumin, repeated as needed.

• Continuous CVP monitoring, stat and serial lab work including CPK and lactate.

• Immediate Orthopedics consult and compartment pressure measurement; early, preventive limb fasciotomies if compartment pressures or CPK high.

• Venous Doppler for DVT, may need full anticoagulation.

Treatment of a fully developed SCLS episode requires recognition that there are two phases. The first phase, which often lasts a couple of days, is called the resuscitation phase because the dual aim of ER/ICU treatment is to stop or control the capillary leak and to raise the patient’s blood pressure from near zero.

In this initial phase, an albumin and fluid leak from the capillaries into the tissue spaces causes swelling, especially into the extremities rather than the abdomen or organs (such as the lungs). The blood pressure falls and the red cells concentrate. This loss of fluid has similar effects on the circulation as dehydration, slowing both the flow of oxygen carrying blood to tissues and the output of urine.

Glucocorticoids (steroids like methylprednisolone) are recommended to reduce or stop the capillary leak, and albumin and colloids usually help to increase the remaining blood flow to vital organs like the kidneys. Keeping up with the fluid loss is important because sustained low blood pressure can damage vital organs such as the kidneys.

Even though blood pressure readings may reach and remain at very low levels, it is important to avoid overly aggressive intravenous fluid administration causing massive swelling of the extremities. The goal of saline and vasopressors administered should NOT be to restore a “normal” blood pressure (or urine flow), but to maintain it at a minimal level sufficient to avoid permanent damage to vital organs.

Measurement of central venous or arterial pressure in an ICU setting is often necessary to achieve this delicate balance. When too much fluid is administered, the result is excessive swelling, and the patient may well require surgical decompression of the limbs. In this procedure, known as a fasciotomy, the skin of the arms and/or legs is incised to release the compressive pressure the retained fluid is having on blood flow to and from the extremities.

The second phase of the treatment is known as the recruitment phase, when fluids and albumin are reabsorbed from the tissues during at least a couple of days. In this phase, the capillary leak has ended and the main threat is fluid overload. If intravenous fluids were given in excess, they usually cause an accumulation of fluid in the lungs and around other vital organs. Most of the patient deaths happen during this recruitment phase so it is important that diuretics be administered to help patients discharge all the fluid previously given — and to keep them from backing up, especially into the lungs.

As concerns episode prevention, two approaches have been tried: β2-agonists like theophylline and terbutaline, and a prophylaxis with IVIG infusions. In recent years, more and more patients have been migrated from the former to the latter in Canada, Europe, and the United States, because IVIG therapy apparently leads to superior results — no episodes or fewer and lighter episodes than compared to no therapy or the other therapies — and does not have as many adverse side effects as does treatment with β2-agonists like theophylline and terbutaline. For further details on the use of IVIG, see the following insert and discussion of Prognosis.

Name
IVIG monthly infusions

Prognosis

The prognosis is uncertain and depends on (a) how well episodes are managed, in terms of preventing permanent damage to vital organs and extremities; and (b) the ability to prevent episodes altogether.

There are two main treatments to prevent episodes of SCLS. The first can be called the Mayo Clinic’s approach of a preventive therapy with theophylline (or aminophylline) and terbutaline tablets taken on a daily basis. However, these medications, meant to reduce endothelial hyperpermeability, have very unpleasant side effects, and often prove ineffective, providing partial and transient improvement.

The second can be called the French preventive regimen, which involves monthly infusions of immunoglobulins (IVIG). There is growing evidence that IVIG (2 gr/kg per month, administered over two consecutive days) has worked for many patients in Europe for over five years now, and is proving mostly successful among patients who have tried it in North America in the past couple of years, suggesting that SCLS may be caused by some kind of acquired immunological deficiency.

Tips for Living with the Disorder

Name	Description
Medical help	Find yourself a compassionate physician, preferably a specialist in internal medicine or hematology affiliated with a major university hospital, willing to do his/her homework on this rare disorder (namely, read the literature and follow the instructions), and willing to consult with the few SCLS experts available: in the United States, Dr. Mark S. Pecker, Professor of Clinical Medicine; Weill Cornell Medical College, New York, NY, tel. 212-746-2210, email mpecker@med.cornell.edu ; in Europe, Prof. Zahir Amoura, Département de Médecine Interne, Hôpital de la Pitié-Salpêtrière, Bd. de l’Hôpital 83, Paris 13e, tél. 0033 1 42 17 80 81, email : zahir.amoura@psl.aphp.fr
Clinical Study Volunteer	Patients who have been diagnosed as having SCLS and who are at least 16 years old are wanted for participation in the only scientific study of the illness taking place anywhere in the world: at the National Institutes of Health in Bethesda, MD, right outside Washington DC. You must have a documented medical history including at least one acute episode of SCLS or else continuous symptoms of periodic hemoconcentration, hypotension and protein leakage. Have your primary doctor contact Ms. Laura Wisch at wischl@niaid.nih.gov , tel. 301-594-1192, before sending in the requisite letter of referral with your medical history and laboratory studies to the lead clinical investigator, Dr. Kirk Druey, kdruey@niaid.nih.gov, tel. 301-435-8875. Once accepted into the clinical research study, you will be invited to come to NIH and spend about 4 days there for the purpose of being examined, donating blood, and being subjected to various tests (e.g., clinical digital photography of your blood vessels). Depending on circumstances, you probably will have time off to do sightseeing in the capital area during your stay at NIH. Those who wish to be greeted in person during their stay by this community’s Expert, please contact aporzeca@american.edu