ABSTRACT
Introduction: Objectives: Methods: Results: A four-months old infant was referred for fever for two days and dyspnea. He had bilateral conjunctival hyperemia;bilateral cervical lymphadenopathy;truncal exanthem;perineal erythema;dry cough;normal cardiac, thoracic, and abdominal examination. Nasopharyngeal swab was negative for SARS-CoV-2. His routine analysis showed: Hb 9,9 g/dl;leukocytes 12000/mm3 (neutrophils 60%;lymphocytes 13%);platelets 430000/mm3;CRP 19 mg/dl (normal values < 0,5 mg/dl);ESR 94;Serum Amyloid A 1430 mg/l;ferritin 883 ng/ml. His chest X-ray showed an interstitial pattern. His first echocardiographic evaluation only showed a minimal pericardial effusion, and normal coronary arteries. The patient received two consecutive intravenous infusions of immunoglobulins (2 g/kg), associated with 2 mg/kg/day methylprednisolone, with consequent apyrexia and reduction of CRP (4,5 mg/dl). He also started 3 mg/kg/day aspirin. After two days from the second infusion, fever reappeared together with coronary dilatation: diameter was 2,4 mm for LCA (z-score 3,16);2,4 mm for LAD (z-score 4,49);2,5 mm for RCA (z-score 4,13). Exams showed CRP 6,57 mg/dl;leukocytes 62860/mm3 (73% neutrophils);platelets 1532000/mm3. The child then received Intravenous pulses of 30 mg/kg/day methylprednisolone in three consecutive days, and started 4 mg/kg/day anakinra. The pulses were followed by apyrexia, with CRP 6,54 mg/dl. Four days later CRP was 8,96 mg/dl, so anakinra was interrupted, and 5 mg/kg infliximab was started. Echocardiogram showed rapidly evolving giant coronary aneurysms: diameter was 6 mm for LCA (z-score 15,79);6,5 mm for LAD (z-score 16,41);5 mm for RCA (z-score 11,72). Due to the rapid evolution of aneurysms and an elevated z-score (> 10), 1 mg/kg/dose enoxaparin was started, according to the Kawasaki disease guidelines of the American Heart Association (AHA) (Circulation, 2017). The patient also started ECG, troponin and BNP monitoring. Three days later, the coronary arteries showed further dilatation. Seven days after infliximab infusion, RCA developed a rosary bead - like pattern. There was a gradual improvement of general clinical conditions with reduction of inflammatory markers (negative CRP, ESR 22, leukocytes 28580/mm3, platelets 800000/mm3 after ten days from infliximab infusion), so steroid tapering was started. Because of an increased thromboembolic risk (due to thrombocytosis and to the accelerated blood flow in stenotic coronary traits), clopidogrel 0,5 mg/kg/day was added, according to AHA guidelines. Thirty days after symptom onset, also LDA developed a rosary bead - like pattern. CRP was 1,27 mg/dl and ESR was 37. The patient was then transferred to Pediatric Cardiac Surgery, started 5 mg/kg/day cyclosporin and, after further coronary dilatation (LDA 11 mm;RCA 9 mm), 3 mg/kg/day propranolol and warfarin. A CT angiogram confirmed the aneurysms, and excluded any aortic dilatations. Epiaortic vessels were spared. An increase of cyclosporin dose to 8 mg/kg/day was followed by stabilization of coronary aneurysms. Conclusion: The extreme refractariety of coronary disease, despite aggressive therapy and biologics, is rather clear. The rapid evolution could be explained, though only in part, by a few risk factors such as age below 12 months and elevated CRP. These factors are well known, even though they are not mentioned in guidelines. ed.
ABSTRACT
Introduction: Several clinical conditions can manifest with fever and a maculopapular rash in paediatric age. Although some presentations are benign, others may be medical emergencies, which demand a prompt diagnosis and treatment. Some of the more common causes of fever and maculopapular rash include infectious diseases (Sars-CoV-2, Parvovirus B19;Coxsackie;Epstein-Barr virus infection, Mycoplasma Pneumoniae, etc), hypersensitivity reactions, Autoinflammatory syndromes, vasculitis, Kawasaki disease (KD), autoimmune diseases. Objectives: In the COVID-19 pandemic era these symptoms need a well-organized hospital strategy to rapidly exclude Sars-CoV-2 infection and to distinguish severe and rapidly developing patients. Methods: We evaluated the medical records of children admitted to a paediatric tertiary centre in the years 2020-202, excluding children with suspected or documented COVID-19 infection. Results: We retrospectively identified 21 patients (13M;9F), age: 0.7- 12 years, admitted with the diagnosis of fever and rash and with a definite diagnosis. 10 children had a documented infection (2 Mycoplasma;2 Parvovirus;5 EBV;1 Adenovirus);3 patients had a KD;4 had an autoimmune disease;3 had an Autoinflammatory syndrome, 1 a vasculitis;1 had a Macrophage Activation Syndrome (MAS). Distribution of the rash, a persistent/vanishing rash, the associated lymphadenopathy did not contribute to the differential diagnosis. Haemoglobin levels were significantly lower in KD (8.3- 11.2). CRP was significantly higher in KD (3.23-34) vs autoimmune diseases and Autoinflammatory syndromes. The other laboratory parameters did not contribute to the differential diagnosis, otherwise reached by specific IgM and PCR. In children with clinical signs of suspicion of Autoinflammatory syndromes, the genetic approach permitted to reach the treat-to-target. Conclusion: The numerous viral skin diseases that affect children present a diagnostic challenge to the clinicianIn some situations, viral rash may be difficult to clinically differentiate from nonviral diseases;extensive laboratory evaluation isolates the virus. Otherwise, autoimmune diseases must be excluded and, in this suspicion, the alert must be high to promptly diagnose a MAS. A most severe presentation can hide the first attack of an Autoinflammatory syndrome: hence, the genetic study of these condition is a milestone in the differential diagnosis and avoid a diagnostic delay.