Capillary leak syndrome

Overview

Capillary Leak Syndrome (CLS), also known as systemic capillary leak syndrome (SCLS) or Clarkson’s disease, is a rare and potentially life-threatening condition characterized by sudden and severe episodes of plasma leakage from the blood vessels into surrounding tissues. This results in low blood pressure, hemoconcentration (increased concentration of red blood cells), and hypoalbuminemia (low albumin levels). During an episode, the body experiences rapid fluid shifts, which can lead to shock, organ failure, or even death if not treated promptly.

Causes

The exact cause of capillary leak syndrome is unknown, especially in idiopathic cases (primary CLS). However, various factors have been associated with triggering or mimicking the syndrome. These include:

• Idiopathic (primary CLS): Often associated with monoclonal gammopathy (an abnormal protein in the blood)

• Secondary CLS: Occurs in association with other conditions, such as:

  • Severe infections (e.g., sepsis, COVID-19)

  • Cancer or chemotherapy

  • Autoimmune disorders

  • Snake bites or certain toxins

• Drug reactions: Some medications, including interleukin-2 therapy, can cause CLS-like episodes

Symptoms

CLS is characterized by recurring attacks that occur in phases. Each episode has three stages:

• Prodromal phase: Flu-like symptoms such as fatigue, nausea, muscle aches, and mild swelling

• Leak phase: Lasts several hours and includes:

  • Sudden drop in blood pressure (hypotension)

  • Swelling of limbs, face, or abdomen (edema)

  • Hemoconcentration and thickened blood

  • Decreased urine output

  • Lightheadedness or fainting

• Recovery phase: Reabsorption of fluids into the bloodstream, which can lead to fluid overload, pulmonary edema, or cardiac stress

Between episodes, individuals are usually symptom-free.

Diagnosis

Diagnosing CLS can be challenging due to its rarity and overlap with other conditions. The diagnosis is based on clinical presentation, lab findings, and exclusion of other causes. Key diagnostic features include:

• Triad of symptoms during episodes:

  • Hypotension

  • Hemoconcentration (elevated hematocrit)

  • Hypoalbuminemia (low serum albumin)

• Exclusion of sepsis, anaphylaxis, and other shock causes

• Monoclonal gammopathy detection: Blood tests may reveal an abnormal monoclonal protein in primary CLS cases

• Imaging: Chest X-rays or ultrasound to assess for fluid accumulation

Treatment

There is no cure for CLS, but treatment focuses on managing acute episodes and preventing recurrence. Management includes:

• Acute phase treatment:

  • Intravenous fluids (cautiously administered)

  • Vasopressors to maintain blood pressure

  • Monitoring for kidney failure or organ dysfunction

• Medications for prevention:

  • Theophylline and terbutaline: Bronchodilators that stabilize capillary membranes

  • IVIG (intravenous immunoglobulin): Shown to reduce frequency and severity of attacks in some patients

• Supportive care: Includes oxygen, electrolyte monitoring, and management of complications like fluid overload

Prognosis

The prognosis for individuals with Capillary Leak Syndrome depends on the severity of episodes and how early treatment is initiated. Without treatment, severe episodes can lead to shock, multi-organ failure, and death. With appropriate emergency management and preventative therapy, many patients can reduce the frequency and intensity of attacks. However, CLS remains a chronic and potentially life-threatening condition that requires lifelong monitoring and care. Regular follow-ups with immunology or hematology specialists are often necessary for optimal management.