Multisystem inflammatory syndrome in children: A review.

AIM: To comprehensively review the literature on multisystem inflammatory syndrome in children (MIS-C). METHODS: Narrative review of relevant studies published between April 2020 and January 2024. RESULTS: MIS-C is a SARS-CoV-2-related hyperinflammatory syndrome developing 2-6 weeks after COVID-19 in genetically susceptible individuals. Persisting fever, mucocutaneous manifestations, GI and cardiac involvement, together with lymphopenia and elevated inflammatory and cardiac markers are the main clinical features. It is believed to recognise some pathogenetic and clinical overlap with Kawasaki disease. New case definitions have been proposed after an assessment of the diagnostic performance of existing criteria; epidemiological criterion is however progressively losing its usefulness as the pandemic turns into an endemic and in the areas with the highest rates of COVID-19 vaccination. Current guidelines recommend both intravenous immunoglobulin and glucocorticoids in the first-line immunomodulatory treatment, mainly based on comparative retrospective cohorts; the actual role of biologics remains to be adequately established. Strict follow-up is mandatory, especially for those with severe cardiac involvement, as longitudinal studies evaluate the long-term evolution of cardiac damage. CONCLUSION: In this paper, we review the epidemiological, pathogenetic, clinical and prognostic features of MIS-C, and outline the main questions which still remain unanswered after more than 3 years of research.

Lupus Nephritis in Children: Novel Perspectives.

Childhood-onset systemic lupus erythematosus is an inflammatory and autoimmune condition characterized by heterogeneous multisystem involvement and a chronic course with unpredictable flares. Kidney involvement, commonly called lupus nephritis, mainly presents with immune complex-mediated glomerulonephritis and is more frequent and severe in adults. Despite a considerable improvement in long-term renal prognosis, children and adolescents with lupus nephritis still experience significant morbidity and mortality. Moreover, current literature often lacks pediatric-specific data, leading clinicians to rely exclusively on adult therapeutic approaches. This review aims to describe pediatric lupus nephritis and provide an overview of the novel perspectives on the pathogenetic mechanisms, histopathological classification, therapeutic approach, novel biomarkers, and follow-up targets in children and adolescents with lupus nephritis.

Study Confirms Safety and Effectiveness of Intra-Articular Glucocorticoids for Painful Hip Dislocation in Children and Young Adults with Neurologic Impairment.

BACKGROUND: Hip dislocation is a common source of pain in children with neurologic impairment. When medical interventions fail, orthopedic surgery does not guarantee a definitive result as the displacement may continue postoperatively and a second operation is often required. METHODS: Retrospective analysis of data regarding the safety and effectiveness of an intra-articular corticosteroid injection (IACI) in 11 patients, aged 15 ± 5 years old, collected through a telephonic questionnaire administered to parents. RESULTS: 21 IACIs were performed, a mean number of 1.9 ± 1.5 times for each patient, at a mean age (of the first IACI) of 13.5 ± 5 years. According to the parents, the IACI significantly lowered the number of participants experiencing pain (82% reduction) and using analgesics (60% reduction). There was also a significant improvement in the children's hip mobility (63% reduction in patients experiencing stiffness), decubitus (90% reduction in obligated positioning), behavior (80% reduction in lamenting or crying patients), sleep quality (87.5% reduction in patients awakening every night), and caregivers' quality of life (91% reduction in worried parents). The mean reported duration of the IACIs' benefit was 5.4 ± 2.4 months (range 1-9), with a positive correlation with the number of IACIs (r = 0.48; p-value = 0.04) and a negative correlation with the age at the first injection (r = -0.71; p-value = 0.02). The only reported adverse event was mild local swelling in one child. CONCLUSIONS: the IACI could represent a safe and effective intervention for painful hip dislocation, both before and after surgery, with a long-lasting benefit which seems to increase as multiple IACIs are performed.

Cardiac MRI in midterm follow-up of MISC: a multicenter study.

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.

Evolution of SARS-CoV-2 IgG Seroprevalence in Children and Factors Associated with Seroconversion: Results from a Multiple Time-Points Study in Friuli-Venezia Giulia Region, Italy.

Data on the effective burden of the SARS-CoV-2 pandemic in the pediatric population are limited. We aimed at assessing the prevalence of SARS-CoV-2 IgG antibodies in children at three subsequent time-points. The study was conducted between January 2021 and July 2021 among children referring to the Research Institute for Maternal and Child Health "Burlo Garofolo" in Trieste, a referral regional hospital in Friuli Venezia Giulia, Italy. A multivariate analysis was conducted to assess factors independently associated with seroconversion. A total of 594 children were included. Anti-SARS-CoV-2 trimeric Spike protein IgG antibodies were found in 32 (15.4%) children tested in April-May and in 20 (11.8%) in June-July 2021, compared with 24 (11.1%) of those tested in January-February 2021 (p = 0.37, Armitage exact test for trend over time p = 0.76). A subgroup analysis and a multivariate logistic regression analysis were performed considering sociodemographic, clinical, and historical variables. Three categories of children showed statistically significant increased odds of positive anti-SARS-CoV-2 IgG antibodies: children previously positive to a nasopharyngeal swab (AdjOR 15.41, 95%CI 3.44-69.04, p < 0.001), cohabitant with a person with an history of a previous positive nasopharyngeal swab (AdjOR 9.95, 95%CI 5.35-18.52, p < 0.001), and children with a foreign citizenship (AdjOR 2.4, 95%CI 1.05-5.70, p = 0.002). The study suggests that seroprevalence studies may be of limited help in estimating the prevalence of the COVID-19 pandemic in children. Further studies are needed to identify other markers of previous SARS-CoV-2 infection in children, such as CD4+ T cells or memory B-cells.

A Pragmatic Approach to Assessment of Chronic and Recurrent Pain in Children with Severe Neurologic Impairment.

The term "severe neurologic impairment" (SNI) is used to describe a group of disorders of the central nervous system which arise in childhood, resulting in motor impairment, cognitive impairment and medical complexity. As a result, much assistance is required with activities of daily living. Since these patients are often unable to self-report pain, or they may exhibit uncommon behaviors when suffering, pain manifestations may go unrecognized. In this article, the basic principles of how to approach pain in children with SNI are discussed.

Pediatric Adrenal Insufficiency: Challenges and Solutions.

Adrenal insufficiency is an insidious diagnosis that can be initially misdiagnosed as other life-threatening endocrine conditions, as well as sepsis, metabolic disorders, or cardiovascular disease. In newborns, cortisol deficiency causes delayed bile acid synthesis and transport maturation, determining prolonged cholestatic jaundice. Subclinical adrenal insufficiency is a particular challenge for a pediatric endocrinologist, representing the preclinical stage of acute adrenal insufficiency. Although often included in the extensive work-up of an unwell child, a single cortisol value is usually difficult to interpret; therefore, in most cases, a dynamic test is required for diagnosis to assess the hypothalamic-pituitary-adrenal axis. Stimulation tests using corticotropin analogs are recommended as first-line for diagnosis. All patients with adrenal insufficiency need long-term glucocorticoid replacement therapy, and oral hydrocortisone is the first-choice replacement treatment in pediatric. However, children that experience low cortisol concentrations and symptoms of cortisol insufficiency can take advantage using a modified release hydrocortisone formulation. The acute adrenal crisis is a life-threatening condition in all ages, treatment is effective if administered promptly, and it must not be delayed for any reason.

Severe onset of inflammatory myositis in a child: think to paraneoplastic myositis.

BACKGROUND: Juvenile idiopathic inflammatory myopathies (JIIMs) are a group of heterogenous, acquired, autoimmune disorders that affect the muscle. While the association between IIMs and malignancy has been widely reported in adults, cancer-associated myositis (CAM) is rare in children, so that routine malignancy screening is not generally performed. This report shows a case of severe CAM in a child. CASE PRESENTATION: An 11-years-old girl presented with worsening dyspnea after a 3-weeks history of progressive proximal weakness, myalgia, dysphagia, and weight loss. Her past history was remarkable for a type I Arnold-Chiari malformation associated with an anterior sacral meningocele. Physical examination showed severe hypotony and hypotrophy. Pulse oximetry and blood test showed a type II respiratory failure (SpO2 88%, pCO2 68 mmHg) and increased muscle enzyme levels (CPK 8479 U/L, AST 715 U/L, ALT 383 U/L, LDH 1795 U/L). The patient needed invasive mechanical ventilation. Inflammatory myositis was considered and treatment with intravenous methylprednisolone (30 mg/Kg/day for 3 days followed by 2 mg/Kg/day) and IVIG (1 g/kg/day for 2 days) was started. Muscle biopsy showed endomysial and perimysial necrosis and inflammation. The presence of serum anti-TIF1-γ antibody positivity led to a malignancy screening. Whole-body MRI showed a mature teratoma underneath sacral meningocele and both lesions were surgically removed. Given the histological and clinical severity of the myopathy, mycophenolate (500 mg twice a day) and rituximab (360 mg/m2, 4 weekly infusions) were added. Due to extreme muscular wasting, severe malnutrition and intolerance to enteral feeding the patient needed a transient tracheostomy and parenteral nutrition, followed by physiotherapy, speech therapy and nocturnal non-invasive ventilation. A complete remission was achieved 3 months after. CONCLUSIONS: Among cancer-associated autoantibodies (CAAs) in adult patients, anti-TIF1-γ carries the highest risk of CAM, which recognizes with a high likelihood a paraneoplastic pathogenesis. In children, anti-TIF1-γ antibody has been associated with severe cutaneous disease, lipodystrophy, and chronic disease course, but not with CAM, which is overall rare in younger patients. Severe onset of a JIIM, especially if anti-TIF1-γ antibody positive, should prompt suspect of a CAM and lead to a screening for malignancy.

Prevalence of SARS-CoV-2 infection in Italian pediatric population: a regional seroepidemiological study.

BACKGROUND: Data on the effective burden of the SARS-CoV-2 pandemic in pediatric population are very limited, mostly because of the higher rate of asymptomatic or paucisymptomatic cases among children. Updated data on COVID-19 prevalence are needed for their relevance in public health and for infection control policies. In this single-centre cross-sectional study we aimed to assess prevalence of SARS-CoV-2 infection through IgG antibodies detection in an Italian pediatric cohort. METHODS: The study was conducted in January 2021 among both inpatients and outpatients referring to Research Institute for Maternal and Child Health "Burlo Garofolo" in Trieste, Friuli Venezia-Giulia, Italy, who needed for blood test for any reason. Collected samples were sent to Italian National Institute of Health for analysis through chemiluminescent immunoassay (CLIA). RESULTS: One hundred sixty-nine patients were included in the study, with a median age of 10.5 ± 4.1 years, an equal distribution for sex (49.7% female patients), and a 55.6% prevalence of comorbidities. Prevalence of anti-SARS-CoV-2 trimeric Spike protein IgG antibodies was 9.5% (n = 16), with a medium titre of 482.3 ± 387.1 BAU/mL. Having an infected cohabitant strongly correlated with IgG positivity (OR 23.83, 95% CI 7.19-78.98, p < 0.0001), while a cohabitant healthcare worker wasn't associated with a higher risk (OR 1.53, 95% CI 0.4-5.86, p 0.46). All of the 5 patients who had previously tested positive to a nasopharyngeal swab belonged to the IgG positive group, with a 3-month interval from the infection at most. CONCLUSION: We assessed a 9.5% SARS-CoV-2 seroprevalence in a pediatric cohort from Friuli Venezia-Giulia region in January 2021, showing a substantial increase after the second peak of the pandemic occurred starting from October 2020, compared to 1% prevalence observed by National Institute of Statistics (ISTAT) in July 2020.