To the Editors:
A 10-month-old boy presented with a fever >38°C and was diagnosed with coronavirus disease 2019 (COVID-19). After his fever subsided, he developed vomiting and diarrhea, with somnolence tendency, pallor, and peripheral coldness. On day 7, his pulse rate was 178 bpm, blood pressure was 95/51 mmHg, and oxygen saturation of the peripheral arteries was 94% with room air. He was in a state of hypovolemic pre-shock and required a supplemental 5-L/min oxygen mask and fluid resuscitation. Echocardiography revealed decreased intravascular volume and pericardial effusion. The arterial blood gas test revealed the following: pH, 7.241; pCO2, 31.9 mmHg; glucose, 104 mg/dL; lactate, 1.1 mmol/L, HCO3− 13.2 mEq/L; albumin-adjusted anion gap, 13 mmol/L. A white blood cell count of 20,570/mm3 (lymphocytes, 55.8%), hemoglobin level of 9.8 g/dL, platelet count of 10.8 × 104/μL, a total protein level of 1.4 g/dL, albumin level of 0.8 g/dL, C-reactive protein level of 0.9 mg/dL, and immunoglobulin G level of 31 mg/dL were indicative of marked hypoalbuminemia and hypogammaglobulinemia. He was transferred to our department. Thoracoabdominal radiograph showed pleural effusion and intestinal wall edema. Computed tomography revealed pleural effusion and ascites (Figure 1A). He received supplemental fluids with albumin, fresh-frozen plasma, sodium bicarbonate, and dopamine to maintain blood pressure and hematologic colloid osmolality. However, the thoracoabdominal effusions associated with infusions increased. We diagnosed COVID-19-associated vasculitis and administered pulse therapy with methylprednisolone and continuous renal replacement therapy (CRRT). However, various treatments were unsuccessful, and the patient died 14 hours after admission to the intensive care unit (Figure 1B). Based on his clinical course, we finally diagnosed severe systemic capillary leak syndrome (SCLS).
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FIGURE 1.: Clinical course of the patient. (A) The thoracoabdominal radiograph (a) shows pleural effusion and intestinal wall edema, and computed tomography (b) reveals massive pleural effusion and ascites. (B) The left vertical axis of the graph represents the fluid balance (mL). The right vertical axis represents the heart rate (/min) and blood pressure (mmHg). The horizontal axis depicts hospital hours. The solid line indicates the change in blood pressure. The dashed line indicates the change in heart rate. The bars under the graph represent the entire clinical course with treatments. HDC, hydrocortisone; mPSL pulse, methylprednisolone pulse therapy; FFP, fresh frozen plasma.
Due to the lack of specific diagnostic SCLS, its identification remains challenging. Pediatric SCLS is often preceded by an acute, mostly viral intercurrent illness and can be misdiagnosed as septic shock.1 As it is potentially fatal and likely underdiagnosed, the differential diagnosis should be considered in patients presenting with fluid-refractory hypovolemic or distributive shock, even if they do not meet the classic triad of hypotension, hemoconcentration, and hypoalbuminemia1,2 as in this case.
The management of acute SCLS requires careful monitoring to assess oxygenation, volume status, tissue perfusion, and blood pressure. In acute pharmacologic treatment, corticosteroids, intravenous immunoglobulin, and TNF-α antagonists have been used to treat acute idiopathic SCLS2,3; however, the effectiveness of these interventions during the acute phase is controversial in children.4,5 In the present case, because of the dramatic deterioration of the condition, our patient received rapid administration of methylprednisolone pulse therapy; however, his symptoms did not improve. The causal relationship between COVID-19 and SCLS pathophysiology has not been fully elucidated to establish treatment in the acute phase, and further research is required.
This is the first reported case of COVID-19 associated with SCLS in a pediatric patient. Because of its rare presentation, SCLS is underrecognized and should be considered in the differential diagnosis when an unexplained hypovolemic shock is observed. Further, pediatricians should be aware that COVID-19 associated with SCLS can be fatal pathophysiology while evaluating and treating such patients.
ACKNOWLEDGMENTS
We appreciate our patient and his parents for allowing us to present this case report.
REFERENCES
1. Bozzini MA, Milani GP, Bianchetti MG, et al. Idiopathic systemic capillary leak syndrome (Clarkson syndrome) in childhood: systematic literature review. Eur J Pediatr. 2018;117:1149–1154.
2. Gousseff M, Arnaud L, Lambert M, et al.; Capillary Leak Syndrome Registry. The systemic capillary leak syndrome: a case series of 28 patients from a European registry. Ann Intern Med. 2011;154:464–471.
3. Zipponi M, Eugster R, Birrenbach T. High-dose intravenous immunoglobulins: a promising therapeutic approach for idiopathic systemic capillary leak syndrome. BMJ Case Rep. 2011;2011:bcr1220103599.
4. Sion-Sarid R, Lerman-Sagie T, Blumkin L, et al. Neurologic involvement in a child with systemic capillary leak syndrome. Pediatrics. 2010;125:e687–e692.
5. Iwasa T, Ohashi H, Kihira K, et al. 10-year-old girl with life-threatening idiopathic systemic capillary leak syndrome: a case report. BMC Pediatr. 2014;14:137.
