Capillary leak syndrome
Encyclopedia
Capillary leak syndrome (usually Systemic Capillary Leak Syndrome, SCLS or Clarkson’s Disease) is a 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
.
was first described by B. Clarkson in 1960, 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.
(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. Acute renal failure is a risk due to acute tubular necrosis consequent to hypovolemia
and rhabdomyolysis
.
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). 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
.
and can cause flash pulmonary edema
with possibly fatal consequences. 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.
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 theophylline
, terbutaline
and montelukast sodium. The second, more recent approach pioneered in France involves monthly intravenous infusions of intravenous immunoglobulin
(IVIG), and the case-report evidence is encouraging.
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.
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
Circulatory system
The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
to the interstitial space, resulting in a dangerous hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
(low blood pressure), hemoconcentration, and hypoalbuminemia
Hypoalbuminemia
Hypoalbuminemia is a medical condition where levels of albumin in blood serum are abnormally low. It is a specific form of hypoproteinemia.Albumin is a major protein in the human body, making up about 60% of total human plasma protein by mass...
. 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
Perfusion
In physiology, perfusion is the process of nutritive delivery of arterial blood to a capillary bed in the biological tissue. The word is derived from the French verb "perfuser" meaning to "pour over or through."...
. It is often misdiagnosed as polycythemia
Polycythemia
Polycythemia is a disease state in which the proportion of blood volume that is occupied by red blood cells increases...
, polycythemia vera
Polycythemia vera
Polycythemia vera is a blood disorder in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets. Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the...
or sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
.
History
The syndromeSyndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
was first described by B. Clarkson in 1960, 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.
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:- hemoconcentration;
- low blood pressure (hypotensionHypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
); - hypoalbuminemiaHypoalbuminemiaHypoalbuminemia is a medical condition where levels of albumin in blood serum are abnormally low. It is a specific form of hypoproteinemia.Albumin is a major protein in the human body, making up about 60% of total human plasma protein by mass...
; and - partial or generalized edemaEdemaEdema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
.
The capillary leak phase
The initial stage is the capillary leak phase, lasting from 1 to 4 days. The most common clinical features are fatigue; lightheadedness up to and including syncopeSyncope (medicine)
Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...
(fainting); limb, abdominal or generalized pain; facial or other edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
; dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
; and hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
that results in circulatory shock and potentially in cardiopulmonary collapse and other organ distress or damage. Acute renal failure is a risk due to acute tubular necrosis consequent to hypovolemia
Hypovolemia
In physiology and medicine, hypovolemia is a state of decreased blood volume; more specifically, decrease in volume of blood plasma...
and rhabdomyolysis
Rhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
.
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
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
. Urgent medical attention in this phase consists of fluid resuscitation efforts, mainly the intravenous administration of saline solution
Saline (medicine)
In medicine, saline is a general term referring to a sterile solution of sodium chloride in water but is only sterile when it is to be placed intravenously, otherwise, a saline solution is a salt water solution...
plus hetastarch or albumin
Albumin
Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
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). 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
Compartment syndrome
Compartment syndrome is a limb threatening and life threatening condition, defined as the compression of nerves, blood vessels, and muscle inside a closed space within the body . This leads to tissue death from lack of oxygenation due to the blood vessels being compressed by the raised pressure...
.
The recruitment phase
The second stage features the reabsorption of the initially extravasated fluid and usually lasts from 1 to 3 days. Intravascular fluid overload leads to polyuriaPolyuria
Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...
and can cause flash pulmonary edema
Pulmonary edema
Pulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...
with possibly fatal consequences. 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.
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 theophylline
Theophylline
Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...
, terbutaline
Terbutaline
Terbutaline is a β2-adrenergic receptor agonist.Terbutaline is currently on the World Anti-Doping Agency's list of prohibited drugs for Olympic athletes, except when administered by inhalation and a Therapeutic Use Exemption has been obtained in advance.Terbutaline is currently used to delay...
and montelukast sodium. The second, more recent approach pioneered in France involves monthly intravenous infusions of intravenous immunoglobulin
Intravenous immunoglobulin
Intravenous immunoglobulin is a blood product administered intravenously. It contains the pooled IgG extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months...
(IVIG), and the case-report evidence is encouraging.
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.
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%. 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. 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.External links
- Mayo Clinic overview, diagnosis and treatment information.
- National Organization for Rare Disorders.
- Systemic Capillary Leak Syndrome Community
- Overview (2003) at OrphanetOrphanetOrphanet is a European website providing information about orphan drugs and rare diseases. It contains content both for physicians and for patients. Its administrative office is in Paris. The organisation also publishes the open-access online journal Orphanet Journal of Rare Diseases.-External...
- Article from the Washington Post about the disease and its virtual community.
- Article from the Pittsburgh Post Gazette about the disease and an upcoming TV episode covering it
- Alternative health group trying to compile personal health success stories