Rapidly progressive edema in a 3-year-old male

CASE DESCRIPTION

A 3-year-old male with a recent diagnosis of nephrotic syndrome (NS) presented with recurrence of proteinuria and rapidly progressive periorbital edema. When first diagnosed 2 weeks earlier, he required admission for albumin and Lasix therapy. Poor access and edema necessitated placement of a peripherally inserted central catheter (PICC) for 3 days. He had initially responded well to steroids but had steroid-induced hyperglycemia. On this assessment, he was found to have a serum albumin of 20 g/L, significant proteinuria (2.9 g/mmol of Cr), and influenza A positivity. Throughout the assessment he became progressively unwell and was admitted for further observation. The patient was afebrile but had a mild cough.

Approximately 6 hours after admission, the paediatric intensive care team was consulted for significant tachycardia, poor perfusion, increased work of breathing with desaturations, a low-grade fever, and lethargy. On examination, he had significant neck swelling, periorbital edema, and circumoral cyanosis. He was rapidly given intravenous antibiotics and albumin. Over the next hour, his work of breathing increased and he developed stridor. Given his rapid progression, anesthesia and ENT were consulted and the patient was taken to the operating room for intubation. An urgent CT scan of his head and chest was then obtained.

Discussion

Chest CT scan with contrast revealed a completely occluded superior vena cava (SVC) with a thrombus extending from the innominate veins into the right atrium. He was taken urgently to the operating room for median sternotomy and surgical thrombectomy.

NS is a podocytopathy with resultant proteinuria, hypoalbuminemia, and edema. This leads to elevated serum cholesterol and loss of immunoglobulins and clotting factors in the urine. NS is not a benign condition and comes with significant sequelae if not monitored and treated appropriately. Infection is the leading cause of morbidity in children with NS. This is related to the loss of immunoglobulins in urine, and immunosuppressive medications. Acute kidney injury is also a significant cause of morbidity in patients with NS. This is secondary to intravascular depletion due to low oncotic pressure and third spacing of fluid. Dyslipidemia is characteristic of NS and is related to albumin loss in the urine and dysregulated lipid metabolism.

Venous thromboembolism (VTE) is another sequela of NS, occurring in up to 3% of cases (1), and is associated with significant morbidity. The most common locations of VTE in NS include the cerebral venous sinuses, pulmonary vasculature, and renal veins. Clot formation in NS is usually secondary to low effective circulating volume and the loss of antithrombotic factors in the urine. Additionally, the placement of central venous catheters compounds the risk of VTE (1); and indeed, our patient required a PICC line when first admitted for albumin and furosemide therapy.

There are just a few rare reports of paediatric patients with NS who developed thrombosis of the SVC, but only one which appears to have clearly lead to SVC syndrome (2). SVC syndrome is characterized by obstruction of venous return from the SVC, resulting in congestion of the cerebral venous system, a decrease in preload, significant exaggeration of collateral venous circulation, and swelling of the head, face, or neck. SVC syndrome is a medical emergency and can lead to airway obstruction with stridor and shortness of breath. SVC syndrome is most commonly caused by a tumour or mass compressing the vasculature. However, VTE is also a cause of the SVC syndrome and was the cause of our patient’s deterioration.

Intraoperatively, it was noted the thrombus was a mixture of both old and new clot, and it was postulated the initial placement of a PICC line during his first admission led to a clot at the level of the right atrium. It was once he began to relapse and was intravascularly depleted and thrombogenic that this clot grew to completely obstruct the SVC, despite no longer having a PICC.

Postoperatively, he was stable, but still had nephrotic range proteinuria. He was maintained on hydrocortisone shortly after the procedure at equivalent dosing to prednisone at 60 mg/m² and soon began to show signs of remission. He was discharged on prednisone therapy, enoxaparin, and insulin and was well at his most recent clinic appointment.

This case illustrates a relatively common complication of NS in an uncommon location, and the dangers associated with PICC lines in patients with NS. The perfect combination of infection-induced relapse, intravascular depletion, increased thrombogenicity, and central line placement led our patient to develop an SVC thrombus leading to SVC syndrome. Patients with NS should be assessed for VTE, and if there is a high index of clinical suspicion, they should be screened. Prophylaxis for VTE in NS is under debate; however, at the present time, it is not formally recommended.

CLINICAL PEARLS

1. NS is not a benign condition, and VTE is an important complication.

2. Consider SVC syndrome in patients with NS when the swelling in the face and neck is out of keeping with the swelling elsewhere in the body.

3. We caution clinicians on the risks of central catheter insertion in patients with NS.