AUTOINFLAMMATORY DISEASES IN HEMATOLOGY FROM DIAGNOSIS TO TREATMENT

AUTOINFLAMMATORY_DISEASES_IN_HEMATOLOGY_FROM_DIAGNOSIS_TO_TREATMENTkapak

SYSTEMIC CAPILLARY LEAK SYNDROME (CLARKSON’S DISEASE)

Ece Vural

Yüksek İhtisas University, Faculty of Medicine, Department of Hematology, Ankara, Türkiye

Vural E. Systemic Capillary Leak Syndrome (Clarkson’s Disease). In: Kurt Yüksel M, editor. Autoinflammatory Diseases in Hematology from Diagnosis to Treatment. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.123-132.

ABSTRACT

Capillary Leak Syndrome (CLS) is a clinical entity that consists of three episodes due to an increase in capillary permeability: severe hypotension, hypoalbuminemia, and hemoconcentration. Pathophysiology of CLS is characterized by generalized hyperpermeability of proteins and hypercytokinemia. Monoclonal proteins, such as IgG kappa light chain monoclonal gammopathy of undetermined significance (MGUS), also play a major role in pathophysiology. VEGF and angiopoietin-2 play significant roles in maintaining endothelial permeability. CLS acute attacks consist of three phases: prodromal symptoms, fluid extravasation phase, and recovery phase. Prodromal symptoms include flu-like symptoms, fever, abdominal pain, irritability, myalgia and may be triggered by menstruation or excessive physical activity. The extravasation phase typically starts after the prodromal phase, with hypotension, hemoconcentration, and hypoalbuminemia. The recovery phase may occur rapidly, and administering intravenous fluid therapy to patients with hypovolemia may increase the risk of pulmonary edema. CLS is a rare condition with no definitive diagnostic criteria. Serum immunofixation, protein electrophoresis, levels of immunoglobulin, and free light chains should be assessed. Differential diagnosis includes all diseases that can cause shock, such as severe sepsis, septic shock, toxic shock syndrome, anaphylaxis due to medication or other factors, systemic mastocytosis, hereditary angioedema, hemophagocytic lymphohistiocytosis, and various medications. Hemoconcentration can identify CLS from other types of hemodynamic instability. There is no specific treatment for CLS but stabilizing the patient’s volume status is crucial. Factors causing respiratory distress may include pulmonary edema, hyperpnea to compensate for lactic acidosis due to hypovolemia, or respiratory system failure due to central nervous system hypoperfusion. The stabilization of respiration is also lifesaving. Pharmacological treatments include intravenous immunoglobulin (IVIG), terbutaline, intravenous aminophylline, tumor necrosis factor alpha antagonist infliximab, and vascular endothelial growth factor inhibitor bevacizumab. However, the definitive benefits of these treatments have not been demonstrated. It is important to recognize the disease and to exhibit appropriate approaches at the right stage.

Keywords: Capillary leak syndrome with monoclonal gammopathy; Blood protein electrophoresis; Cytokines

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