Italy was the first Western country to be hit by the SARS-CoV-2 epidemic. There is now mounting evidence that a minority of children infected with SARS-CoV2 may experience a severe multisystem ...inflammatory syndrome, called Multisystem inflammatory Syndrome associated with Coronavirus Disease 2019 (MIS-C). To date no universally agreed approach is available for this disease. MAIN BODY: as Italy is now facing a second hity of COVID-19 cases, we fear a recrudescence of MIS-C cases. We have, therefore, decided to prepare a report that will help clinicians to face this novel and challenging disease. We propose a diagnostic algorithm, to help case definition and guide work-up, and a therapeutic approach. MIS-C should be promptly recognized, based on the presence of systemic inflammation and specific organ involvement. Early treatment is crucial, and it will be based on the combined use of corticosteroids, high-dose immunoglobulins and anti-cytokine treatments, depending on the severity of the disease. Ancillary treatments (such as. aspirin and thrombo-profilaxis) will be also discussed.
we propose a document that will help physicians to diagnose and treat MIS-C patients. Given the level of evidence available and the methodology used, this document should not be interpreted as a guideline; the final decision about the optimal management should still be taken by the caring physician, on an individual basis.
Inflammatory Bowel disease (IBD) is a widespread pathological condition with clinical heterogeneity and with different levels of severity. Although IBD usually occurs in young adults, onset in ...childhood and infancy are described in patients within the 10th and second year of age. By genome-wide association studies and meta-analysis, several genetic loci have been identified associated with an increased risk of developing IBD in Western populations with variants that may alter the normal mucosal immunity in the gastrointestinal tract.
The clinical complexity and the heterogeneity of the IBD phenotype probably reflect the presence of genetic heterogeneity where different genes or combinations of them may be involved, together with environmental factors. We hypothesized that patients with early onset IBD could have either more severe genetic variants in genes associated with IBD or multiple variants in different genes. Under the multifactorial diseases is crucial to consider the small contribution of a single variant in all not only to other small variations in the same gene but also in different genes belonging to the same pathway.
We performed direct gene sequencing looking for 94 variations in NOD2, ATG16L1, IL23R, IL10R, IL10 and XIAP genes previously shown as correlated with IBD both in multifactorial and in Mendelian models. All variants identified are known in literature as being associated with IBD except for three variants in the genes NOD2, IL10 and IL10RB that even though present in online databases have never been involved in association studies on IBD patients. Moreover, we coupled genetic variants identification with an accurate “in silico” analysis to verify their predictive impact on the protein structure and function. The in-silico prediction of these variants results as benign therefore even if they exhibit a very low frequency in control population being benign, they cannot be considered pathogenic as monogenic disease but fall within the multifactorial range.
The variants identified in our study partially reflect the association data described in the literature but there are no significant differences with the onset of disease (VEO vs EO-IBD).
•Inflammatory Bowel Disease and Genetic heterogeneity with different severity levels.•Very early onset is associated with more genetic variants.•Genetic variants and in silico analysis to predict the variant impact on the protein.
In this multicenter retrospective study we aimed to evaluate the outcome of cardiac involvement in children affected by multisystem inflammatory syndrome (MIS-C), assessed through cardiac magnetic ...resonance (CMR). Children referring to three Italian tertiary pediatric centers between February 2020 and November 2021 with a diagnosis of MIS-C, who underwent CMR during a follow-up visit, were enrolled. Demographic, clinical, laboratory, treatment, and outcome data were collected. Twenty MIS-C patients (aged 9–17, median 12 years) were included in the study. Heart involvement at onset was testified by hypotension/shock (55%), laboratory evidence of myocardial involvement (100%), reduced LV ejection fraction (EF) on echocardiography (83%), and/or need for inotrope agents (40%); they all presented good clinical, laboratory, and echocardiographic response to treatment. CMR was performed after a median interval of 3 months from discharge. Pericardial effusion and myocardial edema were found in 5% of patients. Mild residual left ventricular (LV) dysfunction was found in 20% of patients, all showing normal echocardiographic LVEF at discharge. Minimal myocardial scars were found in 25% by late gadolinium enhancement (LGE). One patient was evaluated at two consecutive time points, showing partial resolution of a myocardial scar after 7 months from its first finding.
Conclusion
: Despite the severity of heart involvement in the acute MIS-C phase, the mid-term cardiac outcome is good. Direct cardiac tissue viral invasion may be involved in MIS-C pathogenesis.
What is Known:
• Heart involvement is common in MIS-C, but conflicting findings have been shown regarding cardiac outcome when assessed through cardiac MRI.
What is New:
• Midterm cardiac MRI shows mild abnormalities in patients recovered from MIS-C with any grade of severity of cardiac involvement at presentation.
During COVID-19 outbreak, a large number of children with severe inflammatory disease has been reported. This condition, named Pediatric Multi-inflammatory Syndrome temporally associated with ...COVID-19 (PIMS-TS) or Multisystem Inflammatory Syndrome associated with Coronavirus Disease 2019 (MIS-C), shares some clinical features with Kawasaki disease and is frequently complicated by myocarditis or shock. It has been suggested that MIS-C belongs to the group of cytokine storm syndromes triggered by SARS-CoV-2 infection. So far, intravenous immunoglobulin (IVIG) and systemic glucocorticoids are the most common therapeutic approaches reported in this group of patients. However, the use of anakinra in patients with severe forms of COVID-19 is showing promising results. Here we reported two patients with multisystem inflammatory syndrome complicated with shock. Both the patients presented a poor response to IVIG and systemic glucocorticoids and received anakinra. Treatment with IL-1 receptor antagonist showed a rapid improvement of clinical conditions and biochemical analysis in both patients and demonstrated a good safety profile. Thus, we look forward for future controlled clinical trials with the aim to demonstrate the effectiveness of anakinra in patients with MIS-C and established precise criteria for its use.
The role of musculoskeletal ultrasound in JIA is still controversial, although there is growing evidence on its utility, especially in the diagnosis of tenosynovitis.
We presented a retrospective ...cross-sectional study of a group of patients with JIA with ankle swelling followed in a Pediatric Rheumatology Service of a tertiary-level pediatric hospital in Northern Italy during the follow-up period between January 1st 2003 and December 31st 2019. Preliminary results have been presented at the EULAR Congress 2021. We enrolled only patients who underwent msk-US, and we identified those with a clinical and sonographic diagnosis of tenosynovitis. For each patient, we collected data on demographics, clinical characteristics, and therapeutic strategies during the follow-up.
On December 31st 2019, 56 swollen ankles of 48 patients were assessed with msk-US. Twenty-two ankles showed sonographic signs of joint synovitis, sixteen ankles presented signs of both joint synovitis and tenosynovitis, and fourteen ankles presented sonographic signs of tenosynovitis only. Overall, tenosynovitis was detected on 27 (56%) out of 48 children with at least a swollen ankle. In 13 patients out of 27 with tenosynovitis (48%), there was no joint synovitis of ankle or foot. Twenty-five patients with tenosynovitis (92%) achieved clinical and radiological remission: seven patients achieved remission of tenosynovitis with methotrexate only, and fifteen patients with biological drugs alone or in combination therapy.
We observed that more than half of the patients with ankle swelling presented a tenosynovitis, and about 50% of them did not show sonographic signs of an active joint synovitis. Among patients with tenosynovitis, biological therapy alone or in association with DMARDs showed effectiveness in inducing disease remission.
There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). ...The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities.
The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups.
One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data.
Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.
To estimate the incidence and describe the spectrum of inflammatory and autoimmune diseases linked to SARS-CoV-2 infection and COVID-19 vaccination in children from two neighbouring south central ...European countries.
We performed a multi-centre prospective cohort study of children under 18 years diagnosed with inflammatory/autoimmune diseases linked to SARS-CoV-2 infection or COVID-19 vaccination, who were admitted to the paediatric tertiary care hospitals in Slovenia and Friuli Venezia Giulia, Italy, from January 1, 2020, to December 31, 2021. Disease incidence was calculated based on laboratory-confirmed cases only.
Inflammatory and autoimmune diseases linked to SARS-CoV-2 were diagnosed in 192 children (127 laboratory-confirmed), of whom 112 had multisystem inflammatory syndrome (MIS-C), followed by vasculitis, neurological and cardiac diseases. Calculated risk of MIS-C was 1 in 860 children after SARS-CoV-2 infection and cumulative incidence of MIS-C was 18.3/100,000 of all children. Fifteen children had severe COVID-19. Two patients with MIS-C and a patient with myositis presented after COVID-19 vaccination. All 3 had at presentation also a serologically proven recent SARS-CoV-2 infection. After MIS-C, nine patients were vaccinated against COVID-19 and 25 patients had a SARS-CoV-2 reinfection, without recurrence of MIS-C.
Autoimmune diseases following SARS-CoV-2 infection in children were 8.5 times as common as severe COVID-19. MIS-C was the most common manifestation and its incidence in this predominantly white population was higher than previously reported. MIS-C does not seem to recur after SARS-CoV-2 reinfection or COVID-19 vaccination. Autoimmune diseases were much more common after SARS-CoV-2 infection than after COVID-19 vaccination.
Swollen Ankle with a Hole: Brodie Abscess Bossini, Benedetta; Da Lozzo, Prisca; Conversano, Ester ...
The Journal of pediatrics,
September 2021, 2021-09-00, Volume:
236
Journal Article