The Coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) have been variably associated with thromboembolic events (TEs) in children. The aim of our study was ...to assess the prevalence of TEs in children hospitalized during a five-year period in a tertiary pediatric hospital, particularly in patients with COVID-19 and MIS-C. Overall, 38 patients were discharged with the diagnosis of TE: 20 in the pre-pandemic and 18 in the pandemic period. The prevalence of TEs was the same (0.08%) in the pre-pandemic and pandemic periods. The occurrence of TEs was higher in patients with COVID-19 or MIS-C (6/517, 1.16%) when compared to children without these conditions in the pandemic and in the pre-pandemic periods. The prevalence of TEs in children with MIS-C was significantly higher than the prevalence in patients with COVID-19. Five out of six of the patients with COVID-19 or MIS-C developing a TE had at least one predisposing factor to thrombosis. In conclusion, our study shows an increased prevalence of TEs in children hospitalized with COVID-19 or MIS-C, if compared to children without COVID-19 or MIS-C in the pandemic period and in the pre-pandemic period. The prevalence of TEs was significantly higher in patients with MIS-C.
Few data are currently available for Kawasaki disease (KD) below 12 months especially in Caucasians. This study aims to analyze clinical and laboratory features of KD among an Italian cohort of ...infants.
A retrospective chart review of KD children aged less than 1 year at time of disease onset between January 2008-December 2017 was performed. Clinical data, laboratory parameters, instrumental findings, treatment and outcome were collected in a customized database.
Among 113 KD patients, 32 (28.3%) were younger than 1 year. Nineteen patients aged below 6 months, and three below 3 months. The median age was 5.7 ± 2.7 months. The mean time to diagnosis was 7 ± 3 days and was longer in the incomplete forms (8 ± 4 vs 6 ± 1 days). Conjunctival injection was present in 26 patients (81.2%); rash in 25 (78.1%); extremity changes in 18 (56.2%); mucosal changes in 13 (40.6%,) and lymphadenopathy only in 7 (21.8%). Mucosal changes were the least common features in incomplete forms (18.2%). Twenty-two patients (68.7%) had incomplete KD. Nineteen (59.4%) had cardiac involvement, of whom 13 (59.0%) had incomplete form. ESR, PCR and platelet values were higher in complete KD; especially, ESR resulted significantly higher in complete forms (80 ± 25.7 mm/h vs 50 ± 28.6 mm/h; p = 0.01). Conversely, AST level was statistically significant higher in patients with incomplete forms (95.4 ± 132.7 UI/L vs 29.8 ± 13.2 UI/L; p = 0.03). All patients received IVIG. Response was reported in 26/32 patients; 6 cases needed a second dose of IVIG and one required a dose of anakinra.
In our cohort, incomplete disease was commonly found, resulting in delayed diagnoses and poor cardiac prognosis. Infants with incomplete KD seem to have a more severe disease and a greater predilection for coronary involvement than those with complete KD. AST was significantly higher in incomplete forms, thus AST levels might be a new finding in incomplete forms' diagnosis. Eventually, we highlight a higher resistance to IVIG treatment. To our knowledge this is the first study involving an Italian cohort of patients with KD below 12 months.
COVID-19 and multisystem inflammatory syndrome in children (MIS-C) have been associated with a higher incidence of hypercoagulability and thromboembolic events (TEs), even in children, leading to ...relevant morbidity, and mortality. However, our understanding of such complications in childhood is limited. To better understand the incidence, clinical manifestations, risk factors, and management of COVID-19 and MIS-C-related TEs in children, a review of the current literature and a brief update on pathophysiology are given. Sixty-two studies, describing 138 patients with TEs associated with COVID-19 or MIS-C, were included. The overall number of TEs was 157, as 16 patients developed multiple TEs: venous TEs represented the majority (54%), followed by arterial thrombosis (38%, mainly represented by arterial ischemic stroke-AIS), and intracardiac thrombosis (ICT) (8%). Within the venous TEs group, pulmonary embolism (PE) was the most frequent, followed by deep venous thrombosis, central venous sinus thrombosis, and splanchnic venous thrombosis. Notably, 10 patients had multiple types of venous TEs, and four had both venous and arterial thrombosis including a newborn. Most of them (79 cases,57%) had at least one predisposing condition, being obesity the most frequent (21%), especially in patients with PE, followed by malignancy (9%). In 35% of cases, no data about the outcome were available About one-third of cases recovered, 12% improved at discharge or follow-up, and 6% had persistent neurological
sequelae.
The mortality rate was 12%, with death due to comorbidities in most cases. Most fatalities occurred in patients with arterial thrombosis. Pediatricians should be aware of this life-threatening possibility facing children with SARS-CoV-2 infection or its multisystemic inflammatory complication, who abruptly develop neurological or respiratory impairment. A prompt intensive care is essential to avoid severe sequelae or even exitus.
Clinical Data of Neonatal Systemic Thrombosis Saracco, Paola, MD, PhD; Bagna, Rossana, MD, PhD; Gentilomo, Chiara, MD, PhD ...
The Journal of pediatrics,
04/2016, Volume:
171
Journal Article
Peer reviewed
Objective To evaluate clinical data and associated risk conditions of noncerebral systemic venous thromboembolism (VT), arterial thromboembolism (AT), and intracardiac thromboembolism (ICT) in ...neonates. Study design Data analysis of first systemic thromboembolism occurring in 75 live neonates (0-28 days), enrolled in the Italian Registry of Pediatric Thrombosis from neonatology centers between January 2007 and July 2013. Results Among 75 events, 41 (55%) were VT, 22 (29%) AT, and 12 (16%) ICT; males represented 65%, and 71% were preterm. In 19 (25%), thromboembolism was diagnosed on the first day of life. In this “early onset” group, prenatal-associated risk conditions (maternal/placental disease) were reported in 70% and inherited thrombophilia in 33%. Postnatal risk factors were present in 73%; infections and central vascular catheters in 56% and 54% VT, respectively, and in 67% ICT vs 27% AT (<.05). Overall mortality rate was 15% and significant thromboembolism-related sequelae were reported in 16% of discharged patients. Conclusions This report from the Registro Italiano Trombosi Infantili, although limited by representing an uncontrolled case series, can be used to develop future clinical trials on appropriate management and prevention of neonatal thrombosis, focusing on obstetrical surveillance and monitoring of critically ill neonates with vascular access. A thrombosis risk prediction rule specific for the neonatal population should be developed through prospective controlled studies.
Vitamin C deficiency is anecdotal in developed countries, mainly associated with underling clinical morbidities as autism or neurological impairment. Chronic insufficient dietary supply is ...responsible for vascular fragility and impaired bone formation, resulting in gingival bleeding, petechial lesions, articular and bone pain or limb swelling. Children may present anorexia, irritability, failure to thrive, limping or refusal to walk. Accordingly, pediatric scurvy is frequently misdiagnosed with osteomyelitis, septic arthritis, bone and soft tissue tumor, leukemia, bleeding disorders, and rheumatologic conditions. We report the case of a 3-years old child developing scurvy as consequence of strict selective diet; extensive and invasive investigations were undertaken before the correct diagnosis was considered. Despite being considered a rare condition, scurvy still exists nowadays, even in children with no apparent risk factors living in wealthy families. The increasing popularity of dietary restriction for children, especially those with allergies, may potentially enhance the occurrence of scurvy in apparently healthy children. Appropriate dietary anamnesis is fundamental in order to highlight potential nutritional deficit and to avoid unnecessary invasive diagnostic procedures. Patients without considerable risk factors may benefit from psychological support in order to investigate possible eating disorders.
Multisystem Inflammatory Syndrome in Children (MIS-C) is a systemic hyperinflammatory disorder that is associated with a hypercoagulable state and a higher risk of thrombotic events (TEs). We report ...the case of a 9-year-old MIS-C patient with a severe course who developed a massive pulmonary embolism that was successfully treated with heparin. A literature review of previous TEs in MIS-C patients was conducted (60 MIS-C cases from 37 studies). At least one risk factor for thrombosis was observed in 91.7% of patients. The most frequently observed risk factors were pediatric intensive care unit hospitalization (61.7%), central venous catheter (36.7%), age >12 years (36.7%), left ventricular ejection fraction <35% (28.3%), D-dimer >5 times the upper limit of normal values (71.9%), mechanical ventilation (23.3%), obesity (23.3%), and extracorporeal membrane oxygenation (15%). TEs may concurrently affect multiple vessels, including both arterial and venous. Arterial thrombosis was more frequent, mainly affecting the cerebral and pulmonary vascular systems. Despite antithrombotic prophylaxis, 40% of MIS-C patients developed TEs. Over one-third of patients presented persistent focal neurological signs, and ten patients died, half of whom died because of TEs. TEs are severe and life-threatening complications of MIS-C. In case with thrombosis risk factors, appropriate thromboprophylaxis should be promptly administered. Despite proper prophylactic therapy, TEs may occur, leading in some cases to permanent disability or death.
Central venous catheters (CVCs) represent one of the main risk factors for venous thrombotic events (VTEs) in children.
We studied the Italian Registry of Pediatric Thrombosis (RITI) with regard to ...systemic radiologically confirmed CVC-related VTEs (CVC-VTEs) occurred during 6.5 years in children aged 29 days to 18 years.
A total of 78 CVC-VTEs were included, which occurred in 76 patients (40/76, 53% males). CVC-VTEs comprised 67 non-cardiac VTEs (86%) and 11 intracardiac thrombotic events (ICTEs) (14%); the median age at onset was 19 and 17 months, respectively. The most frequent reason for CVC insertion was supportive therapy. The catheters were placed percutaneously in 85% of cases (56/66) and surgically in the remaining 15% (10/66). Peripherally inserted central catheters (PICCs) were used in 47% (31/66) cases, partially implanted catheters in 42% (28/66), non-implantable catheters in 7% (5/66), and totally implanted catheters (Port) in 2% (1/66). CVC-VTEs were symptomatic in 77% of cases (60/78), while in the remaining 23%, they were incidentally detected on the imaging performed for the underlying condition. The median time between CVC insertion and the onset of symptoms was 10 days in non-cardiac VTEs and 39 days in ICTEs. Doppler ultrasound was the diagnostic technique most frequently used. The venous compartment most frequently affected was the veins of the lower extremities (52%, 43/73). Anti-thrombotic treatment was administered in 96% of CVC-VTEs (75/78). About 2.6% (2/76) of patients experienced a second thrombotic event. At discharge, post-thrombotic syndrome was reported in 13.5% (5/37) events with available data, CVC replacement in 10.8% (4/47), and ischemic necrosis with toe finger amputation in 2.7% (1/37). Three patients died due to an underlying condition; no CVC-VTE-related deaths were reported.
We have carried out a registry-based study on CVC-VTEs in the children in Italy, providing the data that may help improve the detection and management of this CVC-related complication.
Benign acute childhood myositis (BACM) is a self-limited childhood illness, and viral infections mainly cause it. Clinical and laboratory alterations usually normalize rapidly; generally, the only ...medical intervention required is supportive (hydration and analgesic medication). The low awareness about BACM often led to delayed diagnosis and unneeded ancillary investigations. This study aims to better characterize the clinical and laboratory features of BACM to improve the diagnostic process and inpatient and outpatient management. We conducted a retrospective study selecting all children admitted to Meyer’s Children’s Hospital-IRCCS (Florence, Italy) with a diagnosis of BACM over the last 5 years, both those visited at Emergency Department (ED) and those admitted to the Pediatric Unit. Clinical, laboratory, and instrumental data were collected from electronic clinical records and analyzed. Overall, sixty-five patients were enrolled; 49 children were visited and discharged directly from ED, whereas 16 were admitted in the Pediatric or Neurologic Wards. The median age was 6.56 years (IQR 4.9–9.1). Male gender (66.1%) and Caucasian ethnicity (70%) were prevalent. Most patients were admitted during winter, and a second peak was found in autumn. All patients had bilateral calf pain, most of them (87.7%) associated with asthenia and refuse to walk (93.8%). Prodromal symptoms were fever (75.3%), cough (32.3%), coryza (26.1%), sore throat (26.1%), and vomiting (15.3%). The median value of CPK was 1827 U/L (IQR 915.5–2462) at peak. CPK median time to normalization was 7 days (IQR 7–8.5) from the nadir. Influenza B was the virus most frequently BACM associated, followed by Influenza A; a novel association with Sars-CoV-2 has been detected. Two patients had pathogenic variants at the Next Generation Sequencing myopathies panel.
Conclusion
: School-aged children admitted to the hospital with walking difficulty and myalgia, generally after an upper respiratory tract infection with a moderate CPK elevation, should remind at first of BACM. Rapid complaint resolution and biochemical markers normalization will prevent unnecessary tests and inappropriate therapies.
What is Known:
•
BACM is a self-limited syndrome associated with acute infections. Influenza A and B viruses are the main etiological agents, but BACM may be related to many other microorganisms like Parainfluenza virus, Epstein-Barr virus, Cytomegalovirus, Human herpesvirus 6, Respiratory syncytial virus, Coxsackieviruses, Mycoplasma pneumoniae, Streptococcus pyogenes, Legionella, and Salmonella spp.
•
Clinical and laboratory alterations usually normalize rapidly; generally, the only medical intervention required is supportive (hydration, analgesic medication). Evolution in rhabdomyolysis and kidney damage is possible but rarely reported.
What is New:
•
Sars-CoV-2 could be an emerging possible cause of BACM. During and after the Sars-CoV-2 outbreak, virus infection seasonality has changed, and so has BACM seasonality.
•
Screening tests for muscular and metabolic disorders are recommended in recurrent myositis and/or cases with marked CPK elevation (≥ 5000 U/L).
We aimed to describe otogenic lateral sinovenous thrombosis (OLST), a rare, potentially life-threatening complication of otomastoiditis.
Children diagnosed with OLST in a tertiary-care Hospital from ...2014 to 2019 was retrospectively selected. Clinical and radiological features, timing of diagnosis, treatment and outcome are reported.
Seven children (5 males) were studied. Fever and neurological symptoms (headache, lethargy, diplopia, dizziness and papilledema) were always present. Otalgia and/or otorrhea were found in 6 children; none had signs of mastoiditis. Diagnosis was reached after 7 days (median) from clinical onset. Brain CT-scan was performed in 5 children being diagnostic for 3. Venography-MRI detected OLST and mastoiditis in all cases without parenchymal lesions. Treatment was based on intravenous rehydration, antibiotic and low-molecular weight heparin; acetazolamide was added in 3 children. Mastoidectomy and ventriculoperitoneal-shunting were selectively performed. Patients were discharged after 26 days (median). Follow-up neuroimaging showed sinus recanalization after a median time of 6 months.
A multidisciplinary approach is needed to optimize diagnostic-therapeutic protocols of pediatric OLST.
The multisystem inflammatory syndrome in children (MIS-C) is a severe clinical entity affecting the coagulative system; although thromboembolic events (TEs) are not common, most patients receive ...anticoagulation. We retrospectively assessed patients below 18 years admitted with MIS-C at Meyer Children's Hospital (Florence, Italy). Data on baseline clinical and laboratory presentation, treatment, and outcome, including differences between patients with and without thrombotic prophylaxis, were analyzed. Thirty-two children 1 to 15 years were included. Seventeen patients (53.1%) required intensive care admission, 2 (8.7%) had obesity, 7 (30.4%) a central venous catheter, and 14 (43.8%) an impaired cardiac function. Twelve patients (37.5%) received prophylactic anticoagulation: they had more frequent cardiac involvement (91.7 vs. 50%, P =0.02) and higher ferritin levels (median 1240 vs. 501.5 ng/mL, P <0.001). No differences were found in median d -dimers between the 2 groups. Twenty-one patients (65.6%) had d -dimers >5×upper limit of normal but the indication for anticoagulation was not driven by d -dimers. No patient had hemorrhagic events and only 1 patient (3.1%) had a superficial thrombotic event (under thromboprophylaxis). Our series and the available literature data on MIS-C and thromboembolic events suggest that TEs are a rare complication of MIS-C that is frequently associated with high d -dimer values. However, also in MIS-C, the well-established risk factors of pediatric TEs (ie, older age, central venous catheter, obesity, and cancer) should guide thromboembolic risk assessment.
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