Case Presentation: A 76-year-old male with systemic capillary leak syndrome (SCLS) and monoclonal gammopathy of undetermined significance (MGUS) presented with syncope. On the day of presentation, he was sitting on his bed when he developed lightheadedness followed by approximately 2 seconds of unwitnessed loss of consciousness. He denied head trauma, chest pain, shortness of breath, or recent medication changes.At presentation, he was afebrile, hypotensive (78/59 mmHg), with otherwise normal vital signs. His exam was unremarkable. Labs showed low serum bicarbonate, and albumin (2.1 g/dL; reference range [RR] 3.4-5 g/dL); elevated lactate; urinalysis with moderate leukocyte esterase, white blood cells (>182/HPF), many bacteria, and hyaline casts (32/HPF); and normal CBC and CMP. Head and cervical spine CT showed no acute injury.He received 3 L IV crystalloid, albumin 50 g IV x2, and dexamethasone 12 mg IV with improvement in his blood pressure to 95/67 mmHg. An arterial line was placed, and he was admitted to intensive care. In addition to continuous IV fluids, he started terbutaline, theophylline, and cetirizine. Hemoglobin peaked at 18.5 g/dL (RR 12.9-16.5 g/dL) and albumin decreased to 1.8 g/dL. Urine culture grew >100k cfu/mL multidrug resistant Escherichia coli and ertapenem was started. Adrenal insufficiency (AI) was ruled out by normal cortisol stimulation test. With these measures, his blood pressure, hemoglobin, and albumin normalized. He was diagnosed with an acute exacerbation of SCLC triggered by a urinary tract infection. He transitioned to oral antibiotics, received IV immunoglobin (IVIG), and discharged home.
Discussion: SCLS, or Clarkson’s disease, is rare (260 cases globally) and marked by sudden hypotension, hemoconcentration, and hypoalbuminemia. Acute exacerbations begin with a ‘leak phase,’ where fluid shifts from plasma to extravascular spaces, followed by a ‘post-leak’ phase that restores intravascular volume. The exact pathophysiology is unclear, but one theory suggests oxidative apoptosis of endothelial cells leads to injury and increased vascular permeability.1-3 Triggers remain poorly understood, though viral infections and inflammation may play a role, with recent studies linking severe attacks to SARS-CoV-2.1-2,4-5Symptoms of acute SCLS include presyncope, syncope, edema, pain, nausea, and vomiting; signs include hypotension, hemoconcentration (often confused with polycythemia vera), hypoalbuminemia, and extravascular fluid accumulation. Complications can involve multiple organ dysfunction, compartment syndrome, and deep vein thrombosis. Proper recognition of SCLS is crucial to differentiate it from other conditions like hereditary angioedema, adrenal insufficiency, sepsis, and congestive heart failure. Misdiagnosis can increase patient morbidity.Treatment for acute SCLS involves intravenous fluids and corticosteroids.1-2 Prophylactic monthly IVIG can reduce attack frequency and severity, enhancing survival.6-7 Other preventive options include agents like theophylline and terbutaline to protect against endothelial damage.2,6-8
Conclusions: Understanding systemic capillary leak syndrome (SCLS) is crucial for hospitalist physicians, as timely recognition and appropriate management of this rare condition can significantly reduce patient morbidity and prevent misdiagnosis in cases of acute hypotension and edema.