Case 1
A previously healthy 6-month-old girl presented a three-day history of high-grade fever, irritability and vomiting. Upon admission, myoclonic movements of both hands, oral aphthae, and conjunctival erythema in the right eye were noticed. Due to clinical suspicion of encephalitis, a lumbar puncture was performed which showed pleocytosis with WBC count 141 mm3, 75% monocytes, 15% PMN, glucose 73 mg/dL, protein 181mg/dL and LDH 50 U/L. Complete blood count revealed WBC 14,350/mm3 (75% PMN, 20.6% lymphocytes), Hb 9.7g/dL, platelets 110,000/mm3, CRP 10mg/dL, procalcitonin 7.5ng/mL, UA showed leukocyturia. The patient received treatment with cefotaxime and vancomycin. High fever persisted with vomiting and generalized erythematous rash. COVID-19 was suspected, a CT of the chest showed right lung apical consolidation and subsegmental atelectasis with subsegmental pneumonic foci in the left lung (Figure 1A). Subsequent laboratory tests showed WBC 29,900/mm3, PMN 23,390/mm3(78%), lymphocytes 6,010/mm3, Hb 10.2g/dL, platelets 107,000/mm3, CRP 16.7mg/dL, ESR 37mm/hr, procalcitonin 46.3 ng/mL, albumin 1.9 g/dL, D-dimer 3.49 mg/mL, NT-proBNP 2.916 pg, Troponin I <10 pg/mL, fibrinogen 125 mg/dL, with positive IgG and negative nasopharyngeal RT-PCR for SARS-CoV-2. The diagnosis of MIS-C was made and treatment with IVIG (2g/kg), three boluses of methylprednisolone (30 mg/kg/dose) and enoxaparin (1 mg/kg/dose) was started. The echocardiogram reported LVEF 59%, mild mitral and tricuspid regurgitation, with mild pericardial effusion, with normal coronary arteries.
On day 9 he presented increased respiratory effort, continuous fever, hypotension and lactic acidosis. The CT scan showed an increase in bilateral pulmonary infiltrate (Fig. 2), hepatomegaly and splenomegaly of 4 cm below the costal border. Laboratory test showed WBC 47,720/mm3, PMN 41,800/mm3(87.5%), lymphocytes 4,990/mm3, Hb 11g/dL, platelets 89,000/mm3, CRP 13 mg/dL, albumin 3.1g/dL, AST 271 U/L, ALT 351 U/L, total bilirubin 0.61 mg/dL, indirect bilirubin 0.15mg/dL, D-dimer 6.36 mcg/mL, NT-proBNP 12.347 pg, ferritin 2.204 ng/mL, fibrinogen 105 mg/dL, negative blood cultures. A second dose of IVIG (2g/kg) and three consecutive methylprednisolone pulses were administered.
Due to the presence of persistent fever, hyperferritinemia, anemia and thrombocytopenia, hypofibrinogenemia, elevated transaminases, a bone marrow aspiration was performed with evidence of four hemophagocytic cells (figure 2), HScore was 243. The patient received dexamethasone 10 mg/m2/day and cyclosporine-A (3 mg/kg/day). After 72 hours the IL-6 level was 63.1 pg/mL and the patient received tocilizumab 12mg/kg/day and a second dose after 12 hrs. Clinical improvement was observed within 24 to 36 hours with normalization of fever, respiratory failure, and inflammatory biomarkers. On follow-up, all medications were suspended and a new bone marrow aspiration was performed at day 28 of presentation, with no evidence of hemophagocytosis (Figure 2C).