Undifferentiated Shock: A Case of Idiopathic Capillary Leak Syndrome

ABSTRACT

Systemic capillary leak syndrome (SCLS or Clarkson's disease) is a rare condition characterized by episodes of vascular hyperpermeability. The extravasation of plasma to the interstitial space results in hemoconcentration, hypoalbuminemia, hypovolemia and compartment syndrome of the extremities. The disease can be idiopathic or secondary to causes including viral infections or chemotherapeutic toxicity. We present a fatal case of idiopathic SCLS which rapidly deteriorated to multiple organ failure despite initial improvement with methylene blue. A 57-year-old male presented for worsening back pain over one month. He described a flulike illness 2 weeks prior. Testing for respiratory viruses including SARS-CoV-2 was negative. He received intravenous crystalloid fluids acutely developed respiratory distress and hypotension requiring emergent intubation and initiation of norepinephrine infusion. CT angiography of the chest demonstrated pulmonary edema. Early during his hospitalization urine output ceased and body weight increased by 10 kg, developing tense anasarca. Hematocrit concentrated from 42.7 to 54.4%. Serum albumin dropped from 4.6 to 2.5 g/dL. C1 esterase inhibitor level and IgM were normal. Ferritin was elevated at 2515 ng/ml. He received cefepime and vancomycin, though infectious workup returned unremarkable. Continuous renal replacement therapy and stress dose steroids were initiated. Vasopressor requirement worsened until he was on three vasopressors at one point. Given the constellation of hemoconcentration, hypoalbuminemia, and shock a diagnosis was made of idiopathic SCLS. Treatment was started with methylene blue, montelukast, and the β-adrenergic agonist terbutaline. Blood pressure improved and patient came off pressors and lactate improved from 13 to 4. However, he later developed rising creatine kinase continued to climb to >40,000 U/L. He developed rhabdomyolysis with concern for compartment syndrome of the extremities due to third spacing of fluids. Orthopedic surgery was consulted;but did not believe a fasciotomy was indicated due to rapid decline. Lactic acidosis rose to 18 mmol/L. His family decided to transition to comfort measures. He passed with family at bedside on Day 4 of hospitalization. There are fewer than 500 cases of SCLS reported since initial discovery in 1960. Given the overlap in presentation with common causes of plasma leakage such as sepsis, it is likely that many cases are unrecognized. Patients are often mismanaged;development of severe hypovolemia despite fluids and compartment syndrome is overlooked. This case builds on our evolving recognition of this disease, and the potential for the use of methylene blue to help acute exacerbations of the disease.