A previously healthy 16-month-old male child was transferred to our hospital for continuous high-grade fever associated with erythematous and target-like rash (Figure 1) 5 days after the beginning of fever.
At the local hospital, on clinical examination neurological symptoms such as irritability and lethargy were noted; blood examinations showed leukocytosis with neutrophilia (white blood cell count: 21,000/muL) and elevated procalcitonin (PCT: 15.6 ng/mL; n.v: normal values < 0.5) and C-reactive protein (CRP: 8.9 mg/L; n.v: normal values < 5) levels. Intravenous (IV) fluids and ceftriaxone had been immediately administered for suspected meningococcemia.
On admission to our unit, a body temperature of 39.6 C was recorded. The boy appeared extremely irritable, and physical examination demonstrated an erythematous eruption with round lesions characterized by polycyclic contours covering the limbs and the abdomen with many targeted lesions involving the abdomen, the arms, and the face. Bilateral erythema and edema of palms and soles were also described (Figure 1). His mother reported the beginning of the rash 2 days after the onset of fever. Initially, erythematous-purpuric lesions on the limbs were noted, spreading confluently later to the inferior abdomen, where some peripheral targeted lesions were also present. Similar well-delineated, target-like lesions appeared in the upper abdomen quadrants and subsequently on his face and arms.
Cervical lymph nodes were not swollen on clinical evaluation. The physical examination showed a strawberry tongue and intense pharyngeal hyperemia, although the conjunctiva and the lips appeared normal.
The peripheral blood test exhibited leukocytosis (white blood cell count, 11,660 cells/muL, with 82.6% neutrophils), thrombocytosis (platelets 777,000 cells/muL), and increased fibrinogen (772 mg/dL, n.v: normal values < 500) and d-dimer (13,030 ng/mL, n.v: normal values 200-400) with partial thromboplastin time and activated partial thromboplastin time values in the normal range. Marked elevated levels of CRP (98 mg/L; n.v: normal values < 0.5) and PCT (54 ng/mL; n.v: normal values < 0.5) were seen.
Lumbar puncture was performed and cerebrospinal fluid (CSF) analysis was normal. The antibiotic therapy (ceftriaxone) was continued, and acyclovir was prescribed until results of microbiological analyses in the CSF were available.
Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses for detection of cytomegalovirus (CMV), Epstein-Barr virus (EBV), polyomavirus JC, enterovirus, herpes simplex virus, human herpesvirus type 6 (HHV-6), and varicella zoster virus genome in CSF came back negative. RT-PCR analyses for detection of the enterovirus genome in stool and pharyngeal swabs gave negative results. Suspecting a viral infection, serological tests for adenovirus, EBV, CMV, coxsackievirus, influenza A and B, human parainfluenza virus, and parvovirus B19 were performed and came back negative too. The urinary examination revealed sterile pyuria and mild proteinuria. CSF, blood, and pharyngeal swab cultures were also negative.
On the second day of hospitalization, we documented sudden-onset drowsiness with progressive lethargy. Brain computed tomography (CT) was performed, giving a negative result. The infant developed tachycardia, systolic hypotension (60/50 mm Hg), oliguria, and mild dyspnea, with cold extremities a few hours later.
An initial echocardiographic examination revealed first-degree mitral valve regurgitation and left ventricular hypokinesia with pericardial effusion (3 mm in thickness). Hyperechogenic coronary arteries with a normal size were also documented. Ejection fraction (EF) was estimated to be 35-40%. A chest X-ray revealed a small retrocardiac consolidation.
The development of hypotension, despite massive IV fluids resuscitation, associated with the neurological deterioration of the child required inotropic support (dobutamine infusion) given until the second dose of IV immunoglobulin (IVIG) was administered and continuous monitoring in the intensive care unit.
On the second day, suspecting KD shock syndrome (KDSS), a first dose of IVIG was administered (2 g/kg) but not effective on the fever spikes. On the same day, oral aspirin was given in an anti-inflammatory dose (100 mg/kg per day for 3 days then at a dose of 30 mg/kg per day).
Abdominal ultrasound demonstrated a hydropic gallbladder and mild ascitic effusion surrounding the liver and in the pelvis. On the fourth day, a second dose of IVIG was prescribed with clinical improvement and effect on the fever spikes.
Hypotension regressed after 1 day of dobutamine infusion. EF increased after the first dose of immunoglobulins and further after the second dose.
Interestingly, the rash was initially mitigated by the first dose of IVIG, but the second was more effective with simultaneous blanching in the areas concerned. Echocardiographic examination on the 6th day revealed exclusively residual and persistent hyperechogenicity of the coronary arteries.
Blood tests showed a decreased hemoglobin level (from 11 to 7.6 g/dL) requiring blood transfusion.
Serum immunoglobulin levels were normal. Albumin (ALB) was decreased (total protein: 61 g/L, reference range: 57-80 g/L; ALB: 27 g/L, reference range: 37-51 g/L); total bilirubin (TBIL) (TBIL: 0.2 mg/dL; reference range: 0.3-1.2 mg/dL), alanine aminotransferase, and aspartate aminotransferase were normal. Other blood biochemical tests, including glucose, triglycerides, and calcium were all within reference limits. Renal function and electrolytes were normal; the myocardial enzyme spectrum was also normal, but an increased level of N-terminal prohormone brain natriuretic peptide was evidenced (26,696 pg/mL, n.v: normal values < 150), confirming an ongoing cardiac dysfunction.
The throat culture, anti-streptolysin O, and anti-DNase B came back negative; therefore, the hypothesis of streptococcal infection was discarded.
Brain magnetic resonance imaging (MRI) was performed 1 week later after the admission to rule out a neurological disease, showing hyperintensities in diffusion and T2-weighted imaging at the level of the anterior perforated substance and hypothalamus, with proton density reduction only in the anterior commissure (Figures 2, 3). Radiologists had suggested an underlying inflammatory/postinfectious process (related to HHV-6 virus), a hypothesis not supported by diagnostic tests (Figures 2, 3). A retropharyngeal abscess (diameter: 10 x 15 mm) with phlogistic involvement of the next longus colli muscle was also described on brain MRI scans, likewise previously reported in KD in literature.
To rule out a vasculitic rash complement levels, antineutrophil cytoplasmic antibody, antinuclear antibody, and anticardiolipin antibody tests were studied and came back normal, such as C3 and C4 levels.
Brain MRI without lesions in the white matter and multifocal involvement, CSF negative results without pleocytosis, and absent history of past infection/vaccination and/or demyelinating disorders led us to exclude acute disseminated encephalomyelitis. The patient has been followed for 12 months without any neurological and/or cardiac complications as confirmed by subsequent brain and cardiac MRI. Pituitary disorders were excluded.