Facing Pediatric Rheumatic Diseases: The Role of Disease Activity and Parental Emotion Regulation Strategy in Parents' and Children's Psychological Adjustment.

BACKGROUND: Pediatric rheumatic diseases (PRDs) are a group of chronic disorders that start in childhood and are characterized by periodic exacerbations and remissions of symptoms, with limitations in family, school, and social activities. The aim of this study was to detect differences in parents' psychological adjustment and emotion regulation strategies, and parent-reported children's adjustments in families of children with active and inactive PRDs. METHODS: Fifty-four parents (38 mothers and 16 fathers) of children with PRD were recruited from a pediatric unit. Disease activity was evaluated by their pediatric rheumatologist, while parents' depressive and anxiety symptoms, emotion regulation strategies, and children's emotional difficulties and hyperactivity-inattention symptoms were assessed through a web-based survey. RESULTS: Parents of children with active PRDs reported higher levels of their child's emotional difficulties and hyperactivity-inattention symptoms. Linear regression analysis demonstrated that having a child in the active phases of PRD and lower use of cognitive reappraisal lead to higher children's emotional symptoms, while active disease, low use of cognitive reappraisal, and greater expressive suppression were associated with higher hyperactivity-inattention symptoms. Our study highlights that children with PRDs and their parents may be at increased risk for psychological problems, especially during the active disease phase, highlighting the importance of a multidisciplinary approach.

The administration of methotrexate in patients with Still's disease, "real-life" findings from AIDA Network Still Disease Registry.

OBJECTIVES: To describe clinical characteristics of patients with Still's disease treated with methotrexate (MTX) and to assess drug effectiveness evaluating change in disease activity, reduction of inflammatory markers, and glucocorticoid (GC)-sparing effect. METHODS: Patients with Still's disease treated with MTX were assessed among those included in AIDA Network Still Disease Registry. RESULTS: In this registry, 171 patients with Still's disease were treated with MTX (males 43.3%, age 37.1 ± 16.0 years). They were mainly characterised by joint features and fever without a prominent multiorgan involvement. MTX was administered with GCs in 68.4% of patients, with other conventional synthetic DMARDs in 6.4%, and with biologic DMARDs in 25.1%. A significant reduction of the modified systemic score was observed, and 38.6% patients were codified as being in clinical remission at the end of follow-up. The concomitant administration of a biologic DMARD resulted a predictor of the clinical remission. Furthermore, a reduction of inflammatory markers and ferritin levels was observed following the administration of MTX. Additionally, a marked reduction of the dosage of concomitant GCs was identified, while 36.7% discontinued such drugs. Male gender appeared as a predictor of GC discontinuation. MTX was discontinued in 12.3% of patients because of adverse effects, and in 12.3% for lack of efficacy. CONCLUSIONS: Clinical characteristics of patients with Still's disease treated with MTX were described, mainly joint features and fever without a prominent multiorgan involvement. The clinical usefulness of MTX was reported in reducing the disease activity, decreasing the inflammatory markers, and as GC-sparing agent.

A Case of Psoriatic Disease and Hidradenitis Suppurativa in a Child with Chromosome 17q21.31 Microduplication Syndrome.

Psoriatic disease is a chronic, relapsing inflammatory disorder, characterized mostly by cutaneous erythematous scaly plaques sometimes associated with arthritis. Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory disease of the apocrine glands, characterized clinically by painful abscesses, sinus tracts and scars. It typically occurs after puberty, affecting mainly intertriginous areas of the body. There is a strong association between HS and psoriasis since they share the same pathogenic inflammatory pathway. The patient presented: low birthweight, microcephaly, facial dysmorphisms, lumbar hyperlordosis, walking difficulties, global psychomotor developmental delay and learning disabilities. A genetic evaluation revealed a 2.5 Mb de novo microduplication in the 17q21.31 chromosomal region. Dermatological examination revealed HS (Hurley stage II-HS) distributed in the genital area and inguinal folds, psoriatic plaques on the retroauricolar folds, on the elbows bilaterally and on the lateral aspect of the right ankle and psoriatic arthritis. The patient was treated with adalimumab, with a marked improvement of both conditions. To our best knowledge, we report the first case of coexisting Psoriatic Arthritis Disease and Hidradenitis Suppurativa in a child with chromosome 17q21.31 microduplication syndrome. We hypothesize that gene CRHR1 duplication included in the 17q21.31 chromosomal region might be involved in the pathogenesis of both diseases.

Efficacy of Burosumab Every 2 Weeks in an Adult with X-Linked Hypophosphatemia: Should We Learn from Children?

X-linked hypophosphatemia is a genetic condition that leads to fibroblast-growth-factor 23 (FGF23) increase, causing phosphate renal wasting. Since 2018, burosumab, an anti-FGF23 antibody, has been used for this disease with different dosage in children and adults. We report the case of burosumab administration every 2 weeks, as usually done in children. We retrospectively evaluated parathormone (PTH), alkaline phosphatase, serum phosphate, tubular reabsorption of phosphate (TRP), and 25OH vitamin D every 2 weeks in a 29-year-old man with nephrocalcinosis and tertiary hyperparathyroidism who did not respond to standard treatment with burosumab nor to maximum dosage and was treated with burosumab 90 mg every 2 weeks. His serum phosphate and TRP increased with this regimen compared with 4 weeks frequency (respectively 1.74 ± 0.26 mg/dL vs. 2.3 ± 0.19 mg/dL [p 0.0004] and 71.3% ± 4.8% vs. 83.9% ± 7.9% [p 0.01]) with decrease in PTH (183 ± 24.7 pg/mL vs. 109 ± 12.2 pg/mL [p 0.04]). Burosumab may be a good choice in adult patients with X-linked hypophosphatemia; new data are needed regarding the increase in dosage and/or frequency of administration as usually done in children, to achieve disease control.

Post-Infectious Acute Cerebellar Ataxia Treatment, a Case Report and Review of Literature.

BACKGROUND: infectious mononucleosis is very common during childhood and neurological manifestations are extremely rare. However, when they occur, an appropriate treatment must be undertaken to reduce morbidity and mortality as well as to ensure appropriate management. METHODS: we describe the clinical and neurological records of a female patient with post-EBV acute cerebellar ataxia, whose symptoms rapidly resolved with intravenous immunoglobulin therapy. Afterwards, we compared our results with published data. RESULTS: we reported the case of an adolescent female with a 5-day history of sudden asthenia, vomiting, dizziness, and dehydration, with a positive monospot test and hypertransaminasemia. In the following days, she developed acute ataxia, drowsiness, vertigo, and nystagmus with a positive EBV IgM titer, confirming acute infectious mononucleosis. The patient was clinically diagnosed with EBV-associated acute cerebellitis. A brain MRI showed no acute changes and a CT scan showed hepatosplenomegaly. She started therapy with acyclovir and dexamethasone. After a few days, because of her condition's deterioration, she received intravenous immunoglobulin and demonstrated a good clinical response. CONCLUSIONS: although there are no consensus guidelines for the treatment of post-infectious acute cerebellar ataxia, early intervention with intravenous immunoglobulin might prevent adverse outcomes, especially in cases that do not respond to high-dose steroid therapy.

Point-of-Care Thoracic Ultrasound in Children: New Advances in Pediatric Emergency Setting.

Point-of-care thoracic ultrasound at the patient's bedside has increased significantly recently, especially in pediatric settings. Its low cost, rapidity, simplicity, and repeatability make it a practical examination to guide diagnosis and treatment choices, especially in pediatric emergency departments. The fields of application of this innovative imaging method are many and include primarily the study of lungs but also that of the heart, diaphragm, and vessels. This manuscript aims to describe the most important evidence for using thoracic ultrasound in the pediatric emergency setting.

Preliminary data revealing efficacy of Streptococcus salivarius K12 (SSK12) in Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome: A multicenter study from the AIDA Network PFAPA syndrome registry.

Objective: To evaluate the potential role of Streptococcus salivarius K12 (SSK12) in controlling febrile flares in patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Further aims were to assess the impact of SSK12 on (i) flare duration, (ii) variation in the degree of the highest body temperature during flares, (iii) steroid-sparing effect, and (iv) change of PFAPA accompanying symptoms before and after SSK12 introduction. Patients and methods: The medical charts from 85 pediatric patients with PFAPA syndrome (49 males and 36 females) enrolled in the AIDA registry and treated with SSK12 for a median period of 6.00 ± 7.00 months in the period between September 2017 and May 2022 were examined. Children recruited had a median time of disease duration of 19.00 ± 28.00 months. Results: The number of febrile flares significantly decreased comparing the 12 months before [median (IQR), 13.00 (6.00)] and after SSK12 initiation [median (IQR), 5.50 (8.00), p < 0.001]. The duration of fever was significantly reduced from 4.00 (2.00) days to 2.00 (2.00) days [p < 0.001]. Similarly, the highest temperature in°C was found significantly lower in the last follow-up assessment [median (IQR), 39.00 (1.00)] compared to the period prior to SSK12 start [median (IQR), 40.00 (1.00), p < 0.001]. Steroid load (mg/year) of betamethasone (or any equivalent steroid) significantly decreased between 12 months before treatment with SSK12 [median (IQR), 5.00 (8.00) mg/year] and the last follow-up visit [median (IQR), 2.00 (4.00) mg/year, p < 0.001]. The number of patients experiencing symptoms including pharyngitis/tonsillitis (p < 0.001), oral aphthae (p < 0.001) and cervical lymphadenopathy (p < 0.001) significantly decreased following SSK12. Conclusion: SSK12 prophylaxis given for at least 6.00 months was found to reduce febrile flares of PFAPA syndrome: in particular, it halved the total number per year of fever flares, shortened the duration of the single febrile episode, lowered body temperature by 1°C in the febrile flare, provided a steroid-sparing effect, and significantly reduced the accompanying symptoms related to the syndrome.

Simple febrile seizures: new cut off for the duration of the crises.

BACKGROUND: Our study aimed to identify a new cut-off for febrile seizure (FS) with a good prognosis, thereby replacing the 15 min described in the standard definition of simple febrile seizure (SFS). METHODS: Our study was a retrospective observational study (from January 2018 to December 2018) on children admitted to the Pediatric emergency room of the Santobono-Pausilipon Hospital, Naples, Italy, Pediatric Unit of Latina, Rome, Italy, and Policlinico-Vittorio-Emanuele University Hospital, Catania, Italy, for fever, which developed SFS during the hospitalization. All included patients had their seizures classified as SFS according to the international criteria for epilepsy. We assumed a duration cut-off, and we analyzed the EEG results, neurological follow-up at 12 months, and the recurrence of the febrile seizures the following year. Then, with another calculation, we identify an optimal cut-off of 6 min. Finally, we divided the population into two groups: children with seizures having a duration greater than or less than 6 min. RESULTS: We found that the population with FS with a duration greater than 6 min presented EEG alteration at follow-up visits, neurological disorders, and a recurrence of FS during the following year. CONCLUSIONS: We suggest to introduce a new cut-off for the duration of FS that better represents the benign nature of a simple febrile event.

Emergency Department Admissions of Children with Chest Pain before and during COVID-19 Pandemic.

OBJECTIVES: We compared the number of accesses, causes, and instrumental evaluations of chest pain in children between the pre-COVID-19 era and the COVID-19 period and analyzed the assessment performed in children with chest pain, highlighting unnecessary examinations. METHODS: We enrolled children with chest pain admitted to our emergency department between January 2019 and May 2021. We collected demographic and clinical characteristics and findings on physical examinations, laboratory tests, and diagnostic evaluations. Then, we compared the number of accesses, causes, and instrumental assessments of chest pain between the pre-COVID-19 era and the COVID-19 era. RESULTS: A total of 111 patients enrolled (mean age: 119.8 ± 40.48 months; 62 males). The most frequent cause of chest pain was idiopathic (58.55%); we showed a cardiac origin in 4.5% of the cases. Troponin determination was performed in 107 patients, and the value was high only in one case; chest X-rays in 55 cases and echocardiograms in 25 cases showed pathological findings, respectively, in 10 and 5 cases. Chest pain accesses increased during the COVID-19 era (p < 0.0001), with no differences in the causes of chest pain between the two periods. CONCLUSIONS: The increase in accesses for chest pain during the COVID-19 pandemic confirms that this symptom generates anxiety among parents. Furthermore, our findings demonstrate that the evaluation of chest pain is still extensive, and new chest pain assessment protocols in the pediatric age group are needed.

Urea/Creatinine Ratio's Correlation with Creatine Kinase Normalization in Pediatric COVID-19 Patients with Myositis: Evaluating Prognostic and Predictive Value.

Coronavirus disease 2019 (COVID-19) has been chiefly linked with substantial respiratory complications. However, emerging studies have brought attention to the occurrence of severe muscle inflammation (myositis) related to COVID-19, potentially leading to multi-organ failure and increased mortality. Myositis is generally characterized by heightened serum creatine kinase (CK) levels. Acute myositis is characterized by an infiltration of viruses into calf muscle fibers, which may cause a subsequent inflammatory response leading to calf muscle pain. Symptomatic and supportive management, along with explanation and reassurance, is all that is required in managing this condition. While the association between myositis and severe outcomes has been recognized in adults, it remains less understood in the pediatric population. The current retrospective study, conducted at Policlinico San Marco University Hospital in Catania, aimed to analyze clinical and laboratory factors associated with myositis in pediatric patients with SARS-CoV-2 infection. Between January 2022 and January 2023, ten pediatric patients diagnosed with myositis and SARS-CoV-2 infection were evaluated. The study highlighted clinical manifestations such as fever, calf muscle pain, and abnormal gait. Lab results showed elevated CK levels among other findings. All patients underwent treatment, with the majority recovering without complications. A notable correlation was observed between CK levels, blood urea nitrogen (BUN), and the urea/creatinine ratio (UCR). The study also discusses potential pathophysiological mechanisms behind SARS-CoV-2's impact on skeletal muscles, emphasizing an indirect inflammatory response. Our findings underscore that while myositis in children with SARS-CoV-2 infection appears to follow a benign and self-limiting trajectory, it is crucial to monitor specific markers for early intervention and management. Further research is warranted to elucidate the underlying mechanisms and improve clinical outcomes.

Smell and Taste in Children with Covid-19.

Objectives: To assess the frequency of loss of smell and taste in children during Covid-19 infection and their prevalence along with other symptoms, as well as the recovery of chemosensory function once healed. Methods: To evaluate symptoms during infection, we adapted the Scandinavian adaptation of the Multi-Clinic Smell and Taste Questionnaire and the modified Monel-Jefferson questionnaire. For smell analysis we used Odor Identification (OI) and two variants of the Odor Discrimination (OD) test, and we compared the results with those of a control group. Results: We enrolled nine patients in our experimental group and nine in our control group. Fever was the most frequent symptom (55% of cases), followed by anosmia and ageusia (44% of cases), muscle pain and asthenia (22% of cases) and diarrhea, abdominal pain, cough, and headache (11% of cases). In 11% of cases, olfactory symptoms were the only manifestation of the disease. There was no statistically significant difference in OI test and OD tests between the two groups (Children healed from Covid-19 and Control Group). Conclusion: Loss of smell and taste are the second most common symptoms of pediatric Covid-19, and they should always be tested because they can be the only manifestations of infection. Olfactory function in Covid-19 children decreases with increasing age and improves with the passage of time after illness.

Febrile infection-related Epilepsy Syndrome (FIRES): a severe encephalopathy with status epilepticus. Literature review and presentation of two new cases.

FIRES is defined as a disorder that requires a prior febrile infection starting between 2 weeks and 24 h before the onset of the refractory status epilepticus with or without fever at the onset of status epilepticus. The patients, previously normal, present in the acute phase recurrent seizures and status epilepticus followed by a severe course with usually persistent seizures and residual cognitive impairment. Boundary with "new onset refractory status epilepticus (NORSE) has not clearly established. Pathogenetic hypothesis includes inflammatory or autoimmune mechanism with a possible genetic predisposition for an immune response dysfunction.Various types of treatment have been proposed for the treatment of the acute phase of the disorder to block the rapid seizures evolution to status epilepticus and to treat status epilepticus itself. Prognosis is usually severe both for control of the seizures and for cognitive involvement.FIRES is an uncommon but severe disorder which must be carefully considered in the differential diagnosis with other epileptic encephalopathy.

Development and implementation of the AIDA International Registry for patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis syndrome.

Objective: Aim of this paper is to illustrate the methodology, design, and development of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to patients with the Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Methods: This is a physician-driven, non-population- and electronic-based registry proposed to gather real-world demographics, clinical, laboratory, instrumental and socioeconomic data from PFAPA patients. Data recruitment is realized through the on-line Research Electronic Data Capture (REDCap) tool. This registry is thought to collect standardized information for clinical research leading to solid real-life evidence. The international scope and the flexibility of the registry will facilitate the realization of cutting-edge study projects through the constant updating of variables and the possible merging and transfer of data between current and future PFAPA registries. Results: A total of 112 centers have already been involved from 23 countries and 4 continents starting from August 24th, 2021, to April 6th, 2022. In total 56/112 have already obtained the formal approval from their local Ethics Committees. The platform counts 321 users (113 principal investigators, 203 site investigators, two lead investigators, and three data managers). The registry collects retrospective and prospective data using 3,856 fields organized into 25 instruments, including PFAPA patient's demographics, medical histories, symptoms, triggers/risk factors, therapies, and impact on the healthcare systems. Conclusions: The development of the AIDA International Registry for PFAPA patients will enable the on-line collection of standardized data prompting real-life studies through the connection of worldwide groups of physicians and researchers. This project can be found on https://clinicaltrials.gov NCT05200715.

Cross-Sectional Survey on BNT162b2 mRNA COVID-19 Vaccine Serious Adverse Events in Children 5 to 11 Years of Age: A Monocentric Experience.

OBJECTIVE: Our aim was to evaluate the safety of COVID-19 vaccine in children resident in the Latina Local Health Authority. METHODS: We conducted a telephone survey among children aged 5-11 years receiving BNT162b2 mRNA COVID-19 vaccine between December 15 and 21. The main outcomes included the presence of allergic reactions or anaphylaxis, adverse events after 24-48 h, 7 and 20 days of taking the first and second doses of medications, and documented SARS-CoV-2 infection after vaccination. The information obtained was automatically linked to a spreadsheet and analyzed. RESULTS: 569 children were enrolled. The mean age was 114 ± 4.24 months; there were 251 males in the study. The vaccine showed a favorable safety profile; no anaphylaxis or serious adverse events were reported. The most common symptoms both after the first and second dose were injection site reactions, asthenia, and headache. Injection site reactions were more frequent after the first dose (p = 0.01), while systemic symptoms were more frequent after the second dose (p = 0.022). These symptoms were more frequent in patients with comorbidities (p = 0.0159). CONCLUSION: Our findings confirm the safety of COVID-19 vaccine in children younger 11 years and could be useful to promote its diffusion in pediatric ages in order to achieve "herd immunity" and prevent the virus's circulation.

Comparing parental distress and children's difficulties between parents of children with rheumatic diseases and parents of healthy children in families facing the COVID-19 pandemic.

The COVID-19 pandemic could be a threat for the health status of children with a chronic condition. The present study aimed to explore parents' and children's psychological adjustment during the current pandemic, pursuing a triple objective: to compare the psychological adjustment of parents of children with pediatric rheumatic diseases (PRDs) and parents of healthy children; to analyze children's psychological symptoms (emotional problems and hyperactivity) before and during the COVID-19 pandemic, and with or without a PRDs diagnosis; to explore the associations of children's emotional problems and hyperactivity with parents' psychological adjustment, parent-child interactions and belonging or not to families with PRDs. This cross-sectional study involved 56 parents of children with PRDs and 53 parents of healthy children. Self-report questionnaires about parents' depression, anxiety, parenting stress, and children's emotional symptoms and hyperactivity-inattention were administered. No differences were detected on psychological adjustment between parents of children with PRDs and parents of healthy children. Parents of children with PRDs reported statistically significant higher levels of children's emotional problems and hyperactivity before the pandemic, compared to parents of healthy children; during COVID-19 pandemic, emotional symptoms increased for both groups, while hyperactivity-inattention symptoms increased only in the group of healthy children. Children's emotional difficulties were associated with higher levels of parental anxiety, worse parent-child interaction and having PRDs; children's hyperactivity symptoms were related to parent-child difficult interaction and higher levels of parental depression. Findings suggest the importance to target the children in relation to their parents, when approaching the psychological aspects of PRDs.

Evaluation of Renal Function and Scars in Children With Primary Vesicoureteral Reflux.

OBJECTIVE: To evaluate growth, glomerular and tubular function, renal damage, scars in children affected by primary VUR. METHODS: We retrospectively evaluated the clinical records of our Unit from January 2006 to September 2020. For each patient we evaluated growth, laboratoristic and scintigraphic glomerular and tubular function, renal damage and collective system urodynamics at baseline and at the last visit. RESULTS: We enrolled 41 patients affected by primary VUR and treated with continuous antibiotic prophylaxis. Glomerular function and urodynamics did not change over time. EFNa directly correlated with weight (r 0.44 P .004) and TRP inversely correlated with severity of reflux (r -0.32, P .04). Female sex was associated to nephrolithiasis (OR 17.0, P .02) and proteinuria (at T0 OR 5.8 P .03 at T1 OR 5.8, P .03). Daily proteinuria increased with age (r 0.66, P <.0001 at T0 and r 0.44 P .004 at T1) while protein-to-creatinine ratio decreased. Renal scars at T0 inversely correlated with glomerular and tubular function at T1 but they did not correlate with severity or laterality of reflux. CONCLUSION: Even if renal function remains stable through years, it is critical to identify the subjects with significant congenital renal damage.

Adenomesenteritis following SARS-CoV-2 Vaccination in Children: A Case Report and Review of The Literature.

At present, the vaccine authorized in children aged 5 years and older is the BNT162b2 messenger RNA COVID-19 vaccine. Unlike adults, there is limited data available in the pediatric age describing adverse events after vaccine. We report a case of adenomesenteritis in a young girl following the first dose of vaccine.