A previously healthy 10-month-old African infant developed high-grade fever and emesis with a subsequent widespread urticarial rash and bilateral non-secretive conjunctivitis.
He was admitted to our tertiary care hospital after 4 days of persistent fever. At the physical examination, the infant presented marked irritability with tense, wide and bulging anterior fontanelle, shallow breathing and a widespread macular erythematous rash on trunk and limbs. Brain ultrasounds did not detect intracranial bleeding or meningitis signs. Blood tests evidenced a remarkable increase of inflammatory markers [C-reactive protein (CRP) 32.08 mg/dl, procalcitonin (PCT) 97.7 ng/ml], neutrophilic leucocytosis, NT-pro-BNP (92,230 pg/ml) and D-dimer (2547 ug/l FEU) elevation, and a high ferritin value (810 ng/ml). SARS-CoV-2 IgG antibodies were positive, while RT-PCR for SARS-CoV-2 on nasopharyngeal swab was negative. Echocardiography evidenced slight coronary arteries dilatation and hyperkinetic left ventricle, with normal systolic function. Empiric antibiotic and antiviral treatment was started. Clinical and laboratory findings suggested a PIMS-TS diagnosis. Therefore, a single 2 g/kg dose of intravenous immunoglobulin (IVIG) was administered, followed by intravenous continuous infusion of anakinra (10 mg/kg qd). Moreover, a prophylactic antithrombotic therapy with enoxaparine at 100 UI/kg qd was started because of D-dimer elevation and initial coronary arteries dilatation, according to American College of Rheumatology clinical guidelines for PIMS-TS.
Despite this prompt intervention, 24 h after admission, a neurological deterioration was observed with drowsiness alternating with extreme irritability. Brain computed tomography (CT) reported an initial cerebral oedema, with meningeal and cerebral herniation from the anterior fontanelle. The patient continued to get worse and severe hypotension rapidly occurred requiring the admission to the intensive care unit (ICU), hemodynamic support with amines and mechanical ventilation. In order to treat cerebral oedema, dexamethasone and mannitol were administered intravenously. Subsequent cardiological evaluation described increased coronary arteries ectasia.
On day 7 from admission, a new fever rise, and a leucocytosis rebound occurred during the slow tapering of anakinra, therefore, the immunomodulatory regimen was re-intensified. A second 2 g/kg dose of IVIG followed by three boluses of methylprednisolone was administered.
After the maximization of treatment, patient's clinical conditions gradually improved. He was weaned from ventilation, sedation and vasoactive support. Antibiotics and antiviral therapy were discontinued since all infectious tests resulted negative (aerobic and anaerobic bacteria and fungal blood cultures; Cytomegalovirus, Epstein-Barr virus, Adenovirus, Neisseria meningitidis, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Streptococcus agalactiae, Haemophilus influentiae, Human Herpesvirus-6, Human Herpesvirus-7, Enterovirus, Herpes Simplex virus-1, Herpes Simplex virus-2, Parvovirus on blood samples by real-time polymerase chain reaction (RT-PCR); QuantiFERON for the detection of Mycobacterium tuberculosis).
On day 10, the boy was back at his neurological baseline, with a normal anterior fontanelle. He was persistently afebrile, and the rash completely disappeared. Inflammation indexes slowly decreased, and the patient was moved to the paediatric ward. Dexamethasone regimen was suspended. Two weeks after the admission, the baby presented peeling of the extremities and remarkable thrombocytosis. Right coronary artery (RCA) demonstrated a residual deep aneurismatic remodelling (+5.5 SD). Anti-platelet therapy was started, while enoxaparin was discontinued. Anakinra was slowly tapered and shifted to subcutaneous administration, with no fever relapse.
Brain magnetic resonance imaging (MRI), performed on day 14, showed periventricular hyperintensities without restricted diffusion (Figure 1). Slight cerebral and cerebellar trophism reduction was observed, with mild peri encephalic subarachnoid spaces enlargement. Angiography, venography and post-contrast scan were normal.
Coronary arteries dilatation regressed at its normal size (proximal RCA: +2.2 DS; common trunk of left coronary artery +2 DS; proximal anterior interventricular coronary artery: +1.32 DS; circumflex branch of left coronary artery +1.2 DS) within 2 weeks after its peak (Figure 2). As regards neurological status, the infant presented a regular development without sequelae.