Idiopathic Systemic Capillary Leak Syndrome - Causes, Symptoms, Diagnosis, and Treatment

Introduction

Idiopathic systemic capillary leak syndrome (ISCLS), commonly referred to as Clarkson's disease or Clarkson syndrome, is a rare and possibly fatal ailment. Systemic capillary leak syndrome (SCLS) is an uncommon condition marked by sudden, severe episodes that cause a rapid reduction in blood pressure due to fluid leaks from capillaries, which are tiny blood vessels. Attacks frequently last for several days and need urgent attention. Sometimes they pose a threat to life. The condition is uncommon in youngsters and affects adults most frequently.

What Are the Causes of Idiopathic Systemic Capillary Leak Syndrome?

Although the cause of SCLS is unknown, there does not appear to be an inherited tendency to develop the disorder. More than half of the patient’s blood samples had monoclonal or M proteins. M protein levels are often low. Plasma cells in the bone marrow make the M protein. It is uncertain what part the M protein plays in sudden attacks. There are a variety of potential causes for the M protein synthesis in SCLS patients, one of which is an autoimmune process where the immune system unintentionally targets the body. Recently, it has been hypothesized that a blood component released during the acute attack may harm capillary lining cells.

What Are the Symptoms of Idiopathic Systemic Capillary Leak Syndrome?

The symptoms of idiopathic systemic capillary leak syndrome are:

• Leukocytosis (an abnormal elevation in the blood's leukocyte (white blood cells) count).

• Abdominal pain.

• Constitutional symptom (a sign or symptom of an illness that may have an impact on a person's overall health or condition and indicates a systemic or general influence).

• Diarrhea.

• Fatigue.

• Hypotension (low blood pressure).

• Myalgia (muscle pain).

• Pancreatitis (inflammation of the pancreas).

• Rhinorrhea (runny nose).

• Weight loss.

• Abnormality of renal tubules.

• Arrhythmia (abnormal heart rate).

• Cardiorespiratory arrest.

• Cough.

• Multiple myeloma (a type of plasma cell tumor).

• Myocarditis (inflammation of heart muscle).

• Oliguria (low urine output).

• Pericarditis (outer covering of the heart inflammation).

• Renal failure.

How Is Idiopathic Systemic Capillary Leak Syndrome Diagnosed?

Low blood pressure, elevated hematocrit, and low blood protein levels (hypoalbuminemia) are three factors that can be used to diagnose SCLS. These three characteristics, however, do not prove SCLS beyond a reasonable doubt. In order to rule out alternative possible causes for the symptoms, including infection and a lack of C-1 esterase (a protein found in the blood) inhibitors, more tests must be performed.

Several important test findings are crucial for confirming the diagnosis. A quick and severe capillary leak results in hypoalbuminemia (a sudden and profound reduction in serum albumin levels) and a sharp rise in hemoglobin and hematocrit levels. There is no actual increase in the red blood cells that are measured for hemoglobin and hematocrit. Instead, the loss of fluid causes the blood to become more concentrated. The presence of this hemoconcentration, a defining characteristic of the illness, is necessary for making the diagnosis. Some individuals receive the incorrect diagnosis of polycythemia, a disorder in which the hematocrit is elevated as a result of excessive red blood cell synthesis in the marrow. Although it is advisable to look for an M protein, the absence does not rule out the diagnosis.

How Is Idiopathic Systemic Capillary Leak Syndrome Treated?

SCLS is currently incurable. The goal of treatment is to avoid attacks by utilizing substances that reduce capillary leakage and interfere with hormones like cytokines that cause the leakage. Once an attack has started, the focus of treatment shifts to supportive care, with a focus on managing blood pressure to maintain blood flow to important organs and avoiding exaggerated edema and fluid retention.

1. Acute Attacks: It is important to understand that an acute attack comprises two phases before treating a fully established SCLS episode.

• Resuscitation Phase: The first stage, known as the resuscitation phase, frequently lasts several days and is intended to stop capillary leaks and keep blood pressure stable. At that time, swelling is brought on by capillary albumin, and fluid leaks into the tissue spaces. The slowing of the blood's ability to deliver oxygen to tissues due to dehydration is a similar effect of fluid loss on the body's circulation. As the blood pressure drops, red blood cells begin to gather.

  • Although intravenous fluid replacement is frequently necessary due to its propensity to penetrate into tissues, it should be kept to a minimum.

  • Even though the blood pressure is still low, it is essential to avoid administering intravenous fluids too aggressively because this could cause severe swelling in the extremities that would necessitate surgical decompression.

  • To relieve the compressive pressure from the trapped fluids and promote blood flow to and from the extremities, the skin of the arm or leg is cut during this surgery. Extra intravenous fluids may also lead to fluid buildup around and in the lungs and other important organs.

  • The objective during the acute phase is not to try to maintain normal blood pressure or urine flow but rather to maintain the blood pressure at just sufficiently high levels to prevent long-term harm to vital organs while sparing the patient the risks of excessive fluid administration. To maintain this delicate equilibrium in an intensive care unit, measurement of central venous or arterial pressure is frequently required. It is possible to utilize intravenous albumin and colloid. Maintaining fluid loss is crucial because persistently low blood pressure might harm crucial organs like the kidneys.

• Recruiting Phase: Due to the resorption of albumin and fluids from the tissues, the second phase of therapy is frequently referred to as the recruiting phase. At this point, the greatest danger is fluid overload; the capillary leak has diminished. Diuretics could be needed if there is a fluid overload problem. To lessen the capillary leak during the acute attack, glucocorticoids (steroids) are frequently administered, especially early in the recruiting phase. However, their effectiveness is unknown. The administration of albumin and colloids, along with intravenous fluids, may temporarily improve blood flow to important organs like the kidneys.

2. Maintenance Therapy: To lessen the frequency and severity of acute attacks, maintenance therapy is administered. SCLS is now managed with intravenous immunoglobulin administration once a month for an unlimited amount of time. In patients with SCLS with monoclonal gammopathy, IVIG (intravenous immunoglobulin) for prevention has been proven to greatly increase survival; however, it is also very successful in treating SCLS without monoclonal gammopathy.

3. Secondary Medication: Theophylline and Terbutaline may be used in conjunction as secondary medicines. These are taken by mouth. Regular blood tests must be used to determine the therapeutic range for Theophylline levels. Leukotriene inhibitors, such as Montelukast, may be beneficial for patients who cannot tolerate these medications. An ACE (angiotensin-converting enzyme) inhibitor like Lisinopril may occasionally be helpful. These additional drugs' function is questionable.

Conclusion

Idiopathic systemic capillary leak syndrome (ISCLS) is a fatal and extremely rare disorder. Due to the paucity of medical knowledge and the rarity of this ailment, the diagnosis is frequently missed. The diagnosis of ISCLS requires a high degree of suspicion, particularly when the patient exhibits recurring bouts of unexplained hypotension (low blood pressure), hemoconcentration (concentration of cellular elements of the blood), and hypoalbuminemia (low serum albumin level).