Search

This single-center, observational, retrospective study aimed to evaluate the diagnostic accuracy of pelvic ultrasonographic parameters for detecting central precocious puberty (CPP) in a cohort of female pediatric patients undergoing gonadotropin stimulation tests. The study population consisted of 47 female patients with a suspicion of CPP. Thirty four out of 47 patients (72.34%) were subsequently diagnosed with CPP based on the current laboratory diagnostic criteria (LH peak > 5 IU/L). The ultrasonography results of 39 out of 47 patients (82.97%) were categorized as pubertal, while 31 out of 34 participants (91.17%) in the CPP group exhibited pubertal ultrasonography features. In 13 out of 47 girls (27.65%), a CPP diagnosis was ruled out; however, among these 13 patients, eight exhibited pubertal ultrasonography features suspicious of CPP. We observed a robust concordance between the GnRH test results indicative of pubertal activation and the presence of pubertal pelvic ultrasonographic features in 31 out of 34 children (91.17%). A significant correlation was found between ovarian volume and basal LH and LH/ FSH ratio, and also for basal LH, LH peak, LH/FSH ratio and peak LH/FSH ratio (p = 0.026, p = 0.011, p = 0.031, p = 0.004, respectively). Pelvic ultrasonography had a sensitivity of 91.17% and a specificity of 38.46% in differentiating CPP from premature thelarche.

Background: Complete androgen insensitivity syndrome (CAIS) is a rare disorder of sex development characterized by 46,XY karyotype and testes, yet presenting with a complete female phenotype, which is related to mutations in the androgen receptor (AR) gene. Case presentation: We herein present the case of a 14-year-old adolescent with primary amenorrhea and suspected delayed puberty whose diagnostic journey led to the identification of CAIS through the demonstration of a novel AR variant (c.159_207del). Case-based review: Our report encompasses the complexity of CAIS management, focusing on the risk of malignancy, surveillance options, hormone replacement therapy, timing of an eventual gonadectomy, and the psychosocial impact of such a diagnosis. An algorithm has been formulated for the management of CAIS starting in adolescence, highlighting the conservative approach for those patients unwilling to undergo gonadectomy. Conclusions: Primary amenorrhea and delay in puberty development may provide clues, ultimately leading to a diagnosis of CAIS. This review emphasizes the cruciality of a multidisciplinary approach in managing patients with CAIS, needing for an individualized care to optimize the overall outcome.

Objectives: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome. Study design: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified. Results: Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes. Conclusions: The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities.

Feeding difficulties are constantly present in patients with Crisponi/cold-induced sweating syndrome type 1 (CS/CISS1). The aim of our study was to describe their prevalence and evolution from birth to adult age. We performed an observational study at the Department of Life Sciences and Public Health, Rome. Fourteen patients were included in this study (six M; mean age: 18 years; SD: 10.62 years; median age: 15 years; age range: 6-44 years); six were adults (43%). Data on oral motor abilities from birth were collected. Meal duration, presence of swallowing reflex, dysphagia symptoms, difficulty chewing, and drooling management were assessed. At birth, all patients needed enteral feeding. Introduction of solid food was postponed beyond the age of 18 months in 43% of patients. During childhood and adolescence, mealtime was characterized by increased duration (43%) accompanied by fatigue during chewing (43%), food spillage from the nasal cavities (21%), sialorrhea (86%), and poor/reduced appetite (57%). A mature rotatory chewing skill was never achieved. This report expands the phenotype description of CS/CISS1 and also improves the overall management and prevention of complications in this ultra-rare disease.

Objective: The main aim of this study was to define the best treatment option for multisystem inflammatory syndrome in children (MIS-C) and to analyse the role of anakinra. Methods: This is a multicentre retrospective cohort study. Patients were treated according to the attending physician's decision. The patients were divided into four groups on the basis of the first treatment at time of admittance: (i) IVIG, (ii) IVIG and methylprednisolone (≤2 mg/kg/day), (iii) IVIG with high-dose methylprednisolone (>2 mg/kg/day) and (iv) anakinra with or without IVIG and/or methylprednisolone. Primary outcomes were defined as the presence of at least one of the following features: death, the failure of initial treatment, meaning the need for additional treatment for clinical worsening and cardiac involvement at the end of follow-up. Results: Two hundred thirty-nine patients were recruited. At univariate analysis, persistent heart involvement at discharge was more frequent in those not receiving anakinra as initial treatment (3/21 vs 66/189; P = 0.047). After comparisons between the four treatment regimens, adjusting for the propensity score, we observed that early treatment with anakinra was associated with a lower probability of developing persistent heart disease at the end of follow-up (odds ratio: 0.6; 95% CI: 0.4-1.0). Conclusion: We report that early treatment with anakinra is safe and very effective in patients with severe MIS-C. In addition, our study suggests that early treatment with anakinra is the most favourable option for patients with a higher risk of developing a severe disease outcome.

Introduction: An aberrant immune response involving yet unidentified environmental and genetic factors plays a crucial role in triggering Kawasaki disease (KD). Aims: To assess general and laboratory data at the onset of KD in a single-center cohort of children managed between 2003 and 2023, and retrospectively evaluate any potential relationship with the development of KD-related cardiovascular abnormalities (CVA). Patients and methods: We took into account a total of 65 consecutive children with KD (42 males, median age: 22 months, age range: 2-88 months) followed at the Department of Life Sciences and Public Health in our University; demographic data, clinical signs, and laboratory variables at disease onset, before IVIG infusion, including C-reactive protein, hemoglobin, white blood cell (WBC) count, neutrophil count, platelet count, aminotransferases, natremia, albumin, total bilirubin, and 25-hydroxyvitamin D. Results: Twenty-one children (32.3% of the whole cohort) were found to have echocardiographic evidence of CVA. Univariate analysis showed that diagnosis of KD at <1 year or >5 years was associated with CVA (p=0.001 and p=0.01, respectively); patients with CVA had a longer fever duration, and mostly presented atypical or incomplete presentations. Interestingly, all patients with CVA had lower levels of vitamin D (less than 30 mg/dl, p=0.0001) and both higher WBC and higher neutrophil counts than those without CVA (p=0.0001 and p=0.01, respectively). Moreover, blood levels of albumin were significantly lower in KD patients with CVA compared to those without (11/21, 52% versus 13/44, 30%, p=0.02). Multiple logistic regression with correction for sex showed that serum vitamin D <30 ng/ml, WBC count >20.000/mm3, and age >60 months at KD onset were the only independent factors statistically associated with CVA. Conclusions: Hypovitaminosis D, WBC count over 20.000/mm3, and age above 5 years at KD onset have emerged as independent factors statist

Background: A correlation between plasma lipids and timing of pubertal development has been hypothesized, though lipid influence remains unclear in central precocious puberty (CPP). Aim: To assess any possible alterations in the lipid profile and triglyceride glucose index (TyG) in children diagnosed with CPP. Patients and Methods: Retrospective single-center study conducted on children (aged 6.3 ± 2.1 years) evaluated for the suspicion of CPP. Results: Based on the results of the gonadotropin releasing hormone (GnRH) test, considering 5 IU/L as cut-off of for the luteinizing hormone peak, CPP was confirmed in 43 patients (57.3%). Sixteen (37.2%) had a pathologic body mass index (BMI), with 9 (20.9%) being overweight and 7 (16.27%) obese. High total cholesterol was found in 3 patients with CPP (6.97%), high triglycerides were found in 11 patients with CPP (25.58%), high LDL cholesterol was found in 5 patients with CPP (11.62%), low HDL cholesterol was found in 12/43 patients with CPP (27.9%), a pathologic TyG was found in 13/43 patients with CPP (30.23%). No significant association was observed in the lipid profile for patients with or without CPP, except for HDL cholesterol, which was lower in the CPP group (47.1±10.9; p=0.033). However, the association between serum HDL cholesterol and CPP was not confirmed at the multivariate logistic regression analysis adjusted for patients’ sex and age (p=0.1; OR: 1.035; 95%CI: 0.993-1.078). Conclusion: The overall lipid profile of our pediatric patients diagnosed with CPP did not differ from patients having idiopathic precocious thelarche or normal variants of puberty development.

Background: Individuals with hyperinsulinemia may initially not meet any diagnostic criteria for metabolic syndrome, though displaying a higher risk of cardiovascular complications combined with obesity, diabetes, and hypertension. Aim: The main objective of our study was to assess the diagnostic accuracy of various cardiovascular risk indices in hyperinsulinemic children and adolescents; a secondary objective was to estimate the optimal cut-offs of these indices. Patients and methods: This retrospective single-center study was conducted on 139 patients aged 12,1 ± 2,9 years, managed for hyperinsulinism. Results: We found statistically significant differences in homeostasis model assessment of insulin resistance index (HOMA-IR), triglyceride glucose index (TyG), TyG-body mass index, visceral adiposity index, lipid accumulation product index, fatty liver index, and hepatic steatosis index. At the linear logistic regression assessment we found that insulin growth factor-1 (IGF-1), HOMA-IR, and ALT/AST ratio were independently associated with confirmed hyperinsulinism. At the multivariate analysis IGF-1 levels over 203 ng/mL and HOMA-IR higher than 6.2 were respectively associated with a 9- and 18-times higher odds ratio for hyperinsulinism. The other investigated parameters were not significantly related to hyperinsulinism, and could not predict either the presence of hyperinsulinemia or a subsequent cardiovascular risk in our patients. Conclusion: Commonly used indices of cardiovascular risk in adults cannot be considered accurate in confirming hyperinsulinism in children, with the exception of HOMA-IR. Further studies are needed to verify the usefulness of specific cardiovascular risk indices in hyperinsulinemic children and adolescents.

Our study aims to define resting energy expenditure (REE) and describe the main nutritional patterns in a single-center cohort of children with Smith-Magenis syndrome (SMS). REE was calculated using indirect calorimetry. Patients’ metabolic status was assessed by comparing measured REE (mREE) with predictive REE (pREE). Patients also underwent multidisciplinary evaluation, anthropometric measurements and an assessment of average energy intake, using a 3-day food diary, which was reviewed by a specialized dietitian. Twenty-four patients (13 M) were included, the median age was 9 years (IC 95%, 6–14 years), 84% had 17p11.2 deletion, and 16% had RAI1 variants. REE was not reduced in SMS pediatric patients, and the mREE did not difer from the pREE. In patients with RAI1 variants (16%, n=3/24), obesity was more prevalent than those with 17p11.2 deletion (100% vs 38%). Lower proteins intake and higher total energy intake were reported in obese and overweight patients, compared to healthy weight children. No signifcant diference was found between males and females in energy or macronutrient intake. Conclusions: In SMS, the onset of obesity is not explained by REE abnormalities, but dietary factors seem to be crucial. Greater concern should be addressed to patients with RAI1 variants. A better understanding of the molecular mechanisms causing obesity in SMS patients could set the basis for possible future targeted therapies.

Background: Wernicke encephalopathy (WE) is an acute and potentially fatal neuropsychiatric disorder resulting from thiamine deficiency: its etiology and clinical presentation can be heterogeneous and arduously recognized, especially in children and adolescents. Case presentation: An 8-year-old girl arrived to the emergency room with ataxic gait, nystagmus, and mental confusion after a 10-day history of repeated severe vomiting; her recent clinical history was characterized by restricted nutrition due to a choking phobia, which caused substantial weight loss. Brain magnetic resonance imaging revealed a bilaterally increased T2 signal in the medial areas of the thalami and cerebral periaqueductal region. Diagnosis of WE based on clinical and neuroradiological findings was established and confirmed after labwork showing low serum thiamine. Following psychiatric evaluation, the patient was also diagnosed with avoidance-restrictive food intake disorder (ARFID), which required starting cognitive behavioral therapy and introducing aripiprazole. The patient displayed improvement of the radiological findings after one month and complete resolution of her neurological symptoms and signs. Conclusions: Eating disorders like ARFID might forerun acute signs of WE; this possibility should be considered even in pediatric patients, especially when atypical neurological pictures or feeding issues come out.

Background Lymphatic malformations are vascular developmental anomalies varying from local superficial masses to diffuse infiltrating lesions, resulting in disfigurement. Patients’ outcomes range from spontaneous regression to severe sequelae notwithstanding appropriate treatment. The current classification guides, in part, clinicians through the decision-making process, prognosis prediction and choice of therapeutic strategies. Even though the understanding of molecular basis of the disease has been recently improved, a standardized management algorithm has not been reached yet. Results Here, we report our experience on five children with different lymphatic anomalies of the head and neck region treated by applying a multidisciplinary approach reaching a consensus among specialists on problem-solving and setting priorities. Conclusions Although restitutio ad integrum was rarely achieved and the burden of care is challenging for patients, caregivers and healthcare providers, this study demonstrates how the referral to expert centres can significantly improve outcomes by alleviating parental stress and ameliorating patients’ quality of life. A flow-chart is proposed to guide the multidisciplinary care of children with LMs and to encourage multidisciplinary collaborative initiatives to implement dedicated patients’ pathways.

This single-center, observational, retrospective study aimed to evaluate the diagnostic accuracy of pelvic ultrasonographic parameters for detecting central precocious puberty (CPP) in a cohort of female pediatric patients undergoing gonadotropin stimulation tests. The study population consisted of 47 female patients with a suspicion of CPP. Thirty four out of 47 patients (72.34%) were subsequently diagnosed with CPP based on the current laboratory diagnostic criteria (LH peak > 5 IU/L). The ultrasonography results of 39 out of 47 patients (82.97%) were categorized as pubertal, while 31 out of 34 participants (91.17%) in the CPP group exhibited pubertal ultrasonography features. In 13 out of 47 girls (27.65%), a CPP diagnosis was ruled out; however, among these 13 patients, eight exhibited pubertal ultrasonography features suspicious of CPP. We observed a robust concordance between the GnRH test results indicative of pubertal activation and the presence of pubertal pelvic ultrasonographic features in 31 out of 34 children (91.17%). A significant correlation was found between ovarian volume and basal LH and LH/ FSH ratio, and also for basal LH, LH peak, LH/FSH ratio and peak LH/FSH ratio (p = 0.026, p = 0.011, p = 0.031, p = 0.004, respectively). Pelvic ultrasonography had a sensitivity of 91.17% and a specificity of 38.46% in differentiating CPP from premature thelarche.

Background: Artificial intelligence (AI) has become a popular tool for clinical and research use in the medical field. The aim of this study was to evaluate the accuracy and reliability of a generative AI tool on pediatric familial Mediterranean fever (FMF). Methods: Fifteen questions repeated thrice on pediatric FMF were prompted to the popular generative AI tool Microsoft Copilot with Chat-GPT 4.0. Nine pediatric rheumatology experts rated response accuracy with a blinded mechanism using a Likert-like scale with values from 1 to 5. Results: Median values for overall responses at the initial assessment ranged from 2.00 to 5.00. During the second assessment, median values spanned from 2.00 to 4.00, while for the third assessment, they ranged from 3.00 to 4.00. Intra-rater variability showed poor to moderate agreement (intraclass correlation coefficient range: -0.151 to 0.534). A diminishing level of agreement among experts over time was documented, as highlighted by Krippendorff's alpha coefficient values, ranging from 0.136 (at the first response) to 0.132 (at the second response) to 0.089 (at the third response). Lastly, experts displayed varying levels of trust in AI pre- and post-survey. Conclusions: AI has promising implications in pediatric rheumatology, including early diagnosis and management optimization, but challenges persist due to uncertain information reliability and the lack of expert validation. Our survey revealed considerable inaccuracies and incompleteness in AI-generated responses regarding FMF, with poor intra- and extra-rater reliability. Human validation remains crucial in managing AI-generated medical information.

Background and objective: IgA vasculitis (IgAV), a predominantly pediatric leukocytoclastic disease, has an unpredictable, though largely benign, evolution. The aim of this study was to retrospectively investigate any potential clinical or laboratory predictors of gastrointestinal involvement in a single-center cohort of children with IgAV. Patients and methods: A total of 195 children with a history of IgAV, regularly followed-up for an average period of 1 ± 2.6 years via outpatients clinics of the pediatric rheumatology unit in our University, were assessed, analyzing their clinical and laboratory variables in relationship with their disease evolution and outcome. Results: Univariate analysis showed that a higher neutrophil granulocyte count and lower lymphocyte count (expressed as a percentage of the total white blood cells) were significantly associated with the presence of gastrointestinal involvement at the first examination (65.2 ± 13% versus 58.8 ± 12%, p = 0.02, and 26.4 ± 11% versus 32.1 ± 11%, p = 0.02, respectively). A positive pharyngeal swab for Streptococcus pyogenes, a deficiency of 25-hydroxyvitamin D, a persistence of purpuric rash for more than 1 month, and purpuric lesions in the genital area were also associated with gastrointestinal involvement (p = 0.0001, p = 0.0001, p = 0.007 and p = 0.001, respectively). However, multiple logistic regressions with correction for the patients’ sex and age showed that lower 25-hydroxyvitamin D levels, persistent rash, and genital lesions were independently and significantly associated with signs of gastrointestinal involvement. We then performed a secondary analysis (both univariate and multivariate) to investigate whether vitamin D deficiency was associated with other IgAV manifestations: we found that only 25-hydroxyvitamin D deficiency remained significantly associated with gastrointestinal involvement in IgAV. Conclusions: Patients with IgAV and vitamin D deficiency might be more prone to developing gastr

Objectives: Limited information is available on the clinical features, treatment modalities and outcomes of the juvenile idiopathic arthritis (JIA) categories of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA). This study was aimed to describe the characteristics of Italian children with ERA and JPsA and to compare them with those of patients with the other categories of JIA. Methods: Patients were part of a multinational sample included in a study aimed to investigate the prevalence of disease categories, treatment approaches, and disease status in patients from across different geographical areas (EPOCA Study). All patients underwent a retrospective assessment, based on the review of clinical chart, and a cross-sectional evaluation, which included assessment of physician- and parent-reported outcomes and laboratory tests, and recording of ongoing therapies. Results: Of the 9081 children with JIA enrolled in the EPOCA Study, 1300 were recruited at 18 paediatric rheumatology centres in Italy. 45 (3.5%) had ERA and 49 (3.8%) had JPsA. Several remarkable differences in demographic features and frequency of articular and extra-articular manifestations, disease damage, impairment in physical function and health-related quality of life, school-related problems, comorbidities, and ongoing treatments were observed between ERA and JPsA and the other JIA categories. Conclusions: We described the characteristics of Italian children with ERA and JPsA and highlighted their peculiarities and their differences from the other JIA subsets. These data provide useful insights for future revisions of JIA classification and a benchmarking against which the features from other cohorts may be compared.

Background: Among aneuploidies compatible with life, trisomy 22 mosaicism is extremely rare, and only about 25 postnatal and 18 prenatal cases have been described in the literature so far. The condition is mainly characterized by facial and body asymmetry, cardiac heart defects, facial dysmorphisms, growth failure, delayed puberty, and variable degrees of neurodevelopmental delay. Problem: The scattered information regarding the condition and the dearth of data on its natural history and developmental outcomes restrict genetic counseling, particularly in prenatal settings. Moreover, a prompt diagnosis is frequently delayed by the negative selection of trisomic cells in blood, with mosaicism percentage varying among tissues, which often entails the need for further testing. Purpose/topic: The aim of our work is to provide assistance in prenatal and postnatal genetic counseling by systematically delineating the current knowledge of the condition. This entails defining the prenatal and postnatal characteristics of the condition and presenting novel data from three cases, both prenatally and postnatally. Additionally, we report the developmental outcomes observed in two new patients.

Introduction: Fetal alcohol syndrome (FAS) is associated with a positive maternal history of drinking during pregnancy and the presence of characteristic dysmorphic features due to alcohol teratogenic effect. No evidence is yet available regarding the use of growth hormone (GH) for children with FAS for whom GH deficiency has not been confirmed. Case Presentation: We have highlighted an improvement in auxological parameters of a child with FAS and normal GH stimulation tests, using a GH dosage similar to that used in idiopathic GH deficit, without side effects. Conclusion: GH therapy in children with FAS may lead to an improvement in growth rate and an increase in final height, although, this condition is not included in the specific recommendations for use of GH. Prolonged follow-up and prospective studies are needed to evaluate long-term efficacy and monitor any possible onset of side effects.

Introduction: Vascular events account for a considerable burden of morbidity and mortality in Behçet syndrome (BS). Thrombosis occurs in 1.8–21 % pediatric BS patients, even if the real prevalence is still largely unknown. Objectives: To report clinical features and outcomes of pediatric BS patients with thrombosis and to compare the demographic and clinical characteristics of BS patients with and without thrombosis. Methods: Retrospective data collection of BS patients with thrombosis (T+) included in the EUROFEVER registry. BS patients without thrombosis (T-), belonging to the same rheumatology units, were matched in a 2:1 ratio. Results: 37 T+ were compared to 74 T- patients. At onset, ICBD criteria fulfillment was higher in the T- group (p = 0.015). Caucasian patients were more often T-, Turkish patients were more frequent in T+ group (p = 0.002). At onset, pustulosis was most frequently observed in the T- (p < 0.001) as well as gastrointestinal symptoms (p < 0.001) and ocular involvement (p = 0.022). Neurological symptoms were more often described in T+ (p = 0.034). As for T+, thrombosis was reported at BS presentation in 8/37 (21.6 %). For the T + e patients who developed thrombosis later, oral aphthosis (p = 0.003), genital aphthosis (p = 0.014) were more frequently observed at BS onset, while pustulosis (p = 0.005) and fever (p = 0.043) coexisted with thrombosis. Thrombosis was mainly venous (26/37,70.3 %), involving the cerebral sinuses (21/37, 56.8 %). After thrombosis, 35/37 (94.6 %) T+ patients received an immunomodulatory treatment compared with 16/29 (55.2 %) pre-thrombosis. A recurrence was reported in 6/31(19.4 %). Conclusion: Thrombosis was reported at BS presentation in one fifth of cases. Pustolosis and fever were more frequently concomitant to thrombosis. Sinus veins were the most frequent site.

Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still’s disease patients and Behçet’s disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet’s disease patients and 497 Still’s disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still’s disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet’s disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (b1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (b1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (b1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (b1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (b1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (b1 = 2.089, 95% CI. 0.7- 3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

Achondroplasia (ACH), the most common form of skeletal dysplasia, is characterized by severe disproportionate short stature, rhizomelia, exaggerated lumbar lordosis, brachydactyly, macrocephaly with frontal bossing and midface hypoplasia. Ligamentous laxity has been reported as a striking feature of ACH, but its prevalence and characteristics have not been systematically evaluated yet. There is growing evidence that ligamentous laxity can be associated with chronic musculoskeletal problems and may affect motor development leading to abnormal developmental trajectories. This study aimed to assess the prevalence of ligamentous laxity in children with ACH through standardized tools, the Beighton scale and its modified version for preschool-age children. A total of 33 children (mean age 6.4 ± 3.2 years; age range 1–12.5 years) diagnosed with ACH by the demonstration of a pathogenic variant in the FGFR3 gene and 33 age- and sex-matched healthy controls were included in the study. Both ligamentous laxity assessment and neurological examinations were performed; medical history was also collected from caregivers. Children with ACH showed a 2 times higher risk of ligamentous laxity than the group without skeletal dysplasia (OR = 2.2; 95% CI = 1.0 to 4.7), with 55% of children meeting the diagnostic criteria for hypermo bility. No significant difference in ligamentous laxity was observed between males and females. Joint involvement analysis revealed characteristic patterns, with knee hypermobility observed in 67% of patients, while rare was elbow hypermobility. Longitudinal assessments indicated a decreasing trend in ligamentous laxity scores over time, suggesting a potential decrease in hypermobility issues during adulthood. The findings of this study provide valuable insights into the prevalence and characteristics of ligamentous laxity in ACH. Implementation of standardized ligamentous laxity assessments might guide patients’ follow-up and facilitate early interventions, h

Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy affecting children, being marked by chronic inflammation which mostly impacts on both skin and skeletal muscles; diagnostic criteria of JDM include an unforeseeable mixture of clinical features, while treatment modalities commonly require corticosteroids or immunosuppressant agents. Although the pathogenesis of JDM is not completely understood, several infectious triggers have been linked to its priming via anecdotal reports related to children. Pediatric cases of recent-onset JDM have been temporally associated to an infectious disease by the power of increased titers of circulating antibodies to a putative infectious agent, including parasites, and/or detectable viral RNA or bacterial DNA. With this narrative review we offer an update about JDM association with a host of infections, namely parvovirus B19, Epstein-Barr virus, Coxsackie virus, human immune deficiency virus, severe acute respiratory syndrome coronavirus 2, Mycoplasma pneumoniae and Toxoplasma gondii, as resulting from the medical literature. Few are the evidence-proved results addressing JDM as an unambiguous post-infectious disorder and available data specifically related to children are poor, highlighting the need of further research into the exploration between environmental cut-out factors and JDM.

Kawasaki disease (KD) is an acute vasculitis with an intrinsic risk of severe involvement of coronary arteries. The worldwide spread of KD and the importance of early diagnosis for preventing cardiovascular complications have ascertained the need for updating guidelines for prompt disease recognition and treatment efficacy assessment. All KD patients who comply with the definition of classic or atypical disease should be treated with intravenous immunoglobulin (IVIG) soon after diagnosis. The objective of our narrative review was to analyze the medical literature about case reports with atypical KD in relation to diagnosis and potential identification of predictors of nonresponsiveness to IVIG. Our analysis has shown that the seminal challenge in KD management is the timeliness of diagnosis, although both extreme variability and transience of clinical manifestations make this goal difficult. A non-negligible percentage of patients, especially in the first 6 months of life, might have atypical manifestations of KD, whose painstaking differential diagnosis may be tricky. Many attempts to develop universal scoring systems and detect children at higher risk of IVIG resistance have been rather unsuccessful. Additionally, KD may show different evolutions according to unraveled demographic, genetic, or epigenetic factors. Further research is needed to elucidate all open questions about KD and clarify the long-term outcome of its potential complications.

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±7.00 months was found to reduce febrile flares of PFAPA syndrome: in particular, it halved the total number per year of fever flares, shortened the

Achondroplasia is an autosomal dominant genetic disease representing the most common form of human skeletal dysplasia: almost all individuals with achondroplasia have identifiable mutations in the fibroblast growth factor receptor type 3 (FGFR3) gene. The cardinal features of this condition and its inheritance have been well-established, but the occurrence of feeding and nutritional complications has received little prominence. In infancy, the presence of floppiness and neurological injury due to foramen magnum stenosis may impair the feeding function of a newborn with achondroplasia. Along with growth, the optimal development of feeding skills may be affected by variable interactions between midface hypoplasia, sleep apnea disturbance, and structural anomalies. Anterior open bite, prognathic mandible, retrognathic maxilla, and relative macroglossia may adversely impact masticatory and respiratory functions. Independence during mealtimes in achondroplasia is usually achieved later than peers. Early supervision of nutritional intake should proceed into adolescence and adulthood because of the increased risk of obesity and respiratory problems and their resulting sequelae. Due to the multisystem involvement, oral motor dysfunction, nutrition, and gastrointestinal issues require special attention and personalized management to facilitate optimal outcomes, especially because of the novel therapeutic options in achondroplasia, which could alter the progression of this rare disease.

Feeding, eating and deglutition difficulties are key concerns in patients with cardiofaciocutaneous syndrome (CFCS). This study intends to quantify the development of feeding skills from birth to adulthood in patients with CFCS. Twenty-seven patients (eight males; mean age: 16.7 ± 8.3 years; median age: 15 years, age range: 1.5–38 years) with molecularly confirmed clinical diagnosis of CFCS were prospectively recruited from the Rare Disease Unit, Paediatrics Department, Fondazione Policlinico Agostino Gemelli-IRCCS, Rome, Italy, over a one-year period. Pathogenic variants along with key information regarding oro-motor features were collected. Sialorrhea was quantified using the Drooling Quotient 5. Feeding abilities were screened using the Italian version of the Montreal Children’s Hospital Feeding Scale (I-MCH-FS). The oral sensory processing section of the Sensory Profile completed the assessment. Mild-to-profuse drooling was experienced by 25% of patients, and food taste selectivity was a constant during infancy (65%), with persistence even beyond adolescence. Nineteen percent of participants with long-term enteral feeding dependency had BRAF, KRAS and MAP2K1 mutations. These findings document that mealtime challenges in CFCS do not remain restricted only to the paediatric age, and that supportive care until adulthood plays a key role.

The aim of this study was to evaluate a potential correlation between results of the oral glucose tolerance test (OGTT) and the auxological/metabolic parameters in a cohort of overweight patients assessed for suspicion of hyperinsulinism. We analyzed 206 patients, comparing those with insulin peak below (nonhyperinsulinemic) and over 100 uIU/mL (hyperinsulinemic) at the OGTT. We found a significant difference in weight (p = 0.037), body mass index (BMI, p < 0.001) and BMI standard deviations (SD, p < 0.001), waist circumference (p = 0.001), hip circumference (p = 0.001), and waist-to-height ratio (WHtR, p = 0.016) between the two groups. Analyzing the median insulin value during OGTT in the whole population, a weakly positive correlation emerged with weight SD (p < 0.001; rho = 0.292) and a moderate positive correlation with BMI SD (p < 0.001; rho = 0.323). We also found a weakly positive correlation with waist circumference (p = 0.001; rho = 0.214), hip circumference (p = 0.001; rho = 0.217), and WHTR (p = 0.016; rho = 0.209) and a moderate positive correlation with the HOMA index (p < 0.001; rho = 0.683). The median insulin value correlates with high triglyceride (p < 0.001; rho = 0.266) and triiodothyronine values (p = 0.003; rho = 0.193) and with low HDL values (p < 0.001; rho= 0.272). In clinical practice the interpretation of laboratory and anthropometric parameters could predict the level of insulin, highlighting also a possible underlying diagnosis of insulin resistance and/or hyperinsulinemia without performing an OGTT.

Background—Central precocious puberty (CPP) is characterized by clinical, biochemical, and ra-diological features similar to those of normal puberty, but CPP occurs before the age of eight in girls and before the age of nine in boys, subsequently leading to a reduction in the final body height in adulthood due to premature fusion of growth plates. The diagnosis of CPP is confirmed with a gonadotropin-releasing hormone (GnRH) stimulation test, which can lead to different interpreta-tions because the diagnostic peak levels of luteinizing hormone (LH) can vary. Patients and methods—This was a single-center, retrospective observational study investigating the possible correlation between gonadotropin peaks on the GnRH test and auxological, metabolic, and radi-ological parameters of patients evaluated for CPP. We collected and analyzed data from the medical records of children with suspected CPP over a period from January 2019 to July 2022 who underwent a GnRH test at the Fondazione Policlinico Universitario Agostino Gemelli in Rome, It-aly. Results—Our correlation analysis revealed no statistically significant differences in any aux-ological and radiological parameters. Among laboratory parameters, baseline levels of LH, folli-cle-stimulating hormone, sex hormone-binding globulin, and 17-beta estradiol were higher in children with a definitive diagnosis of CPP than in those with a negative GnRH test. In particular, the levels of LH at baseline and after the GnRH test were statistically significant in the group of CPP patients, consistent with the interpretation of the test. In the multivariate analysis, using a cut-off value of 4.1 IU/L, LH peaks showed both very high sensitivity (94%) and very high speci-ficity (95%); all other variables showed high specificity (90%) but unsatisfactory sensitivity. Con-clusion—Basal hormone dosages and, especially, basal levels of LH should be considered

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.

Background: Despite the recent advances in the field of autoinflammatory diseases, most patients with recurrent fever episodes do not have any defined diagnosis. The present study aims at describing a cohort of patients suffering from apparently unexplained recurrent fever, in whom non-radiographic axial spondylarthritis (SpA) represented the unique diagnosis identified after a complete clinical and radiologic assessment. Materials and methods: Patients' data were obtained from the international registry on Undifferentiated Systemic AutoInflammatory Diseases (USAIDs) developed by the AutoInflammatory Disease Alliance (AIDA) network. Results: A total of 54 patients with recurrent fever episodes were also affected by non-radiographic axial SpA according to the international classification criteria. SpA was diagnosed after the start of fever episodes in all cases; the mean age at the diagnosis of axial SpA was 39.9 ± 14.8 years with a diagnostic delay of 9.3 years. The highest body temperature reached during flares was 42°C, with a mean temperature of 38.8 ± 1.1°C. The most frequent manifestations associated to fever were: arthralgia in 33 (61.1%) cases, myalgia in 24 (44.4%) cases, arthritis in 22 (40.7%) cases, headache in 15 (27.8%) cases, diarrhea in 14 (25.9%) cases, abdominal pain in 13 (24.1%) cases, and skin rash in 12 (22.1%) cases. Twenty-four (44.4%) patients have taken daily or on-demand non-steroidal anti-inflammatory drugs (NSAIDs) and 31 (57.4%) patients have been treated with daily or on demand oral glucocorticoids. Colchicine was used in 28 (51.8%) patients, while other conventional disease modifying anti-rheumatic drugs (cDMARDs) were employed in 28 (51.8%) patients. Forty (74.1%) patients underwent anti-tumor necrosis factor (TNF) agents and 11 (20.4%) were treated with interleukin (IL)-1 inhibitors. The response to TNF inhibitors on recurrent fever episodes appeared more effective than that observed with anti-IL-1 agents; colchicine and other cDMARD

Background: Smith-Magenis syndrome (SMS) is caused by either interstitial deletions in the 17p11.2 region or pathogenic variants in the RAI1 gene and is marked by a distinct set of physical, developmental, neurological, and behavioral features. Hypercholesterolemia has been described in SMS, and obesity is also commonly found. Aim: To describe and characterize the metabolic phenotype of a cohort of SMS patients with an age range of 2.9–32.4 years and to evaluate any correlations between their body mass index and serum lipids, glycated hemoglobin (HbA1c), and basal insulin levels. Results: Seven/thirty-five patients had high values of both total cholesterol and low-density lipoprotein cholesterol; 3/35 had high values of triglycerides; none of the patients with RAI1 variants presented dyslipidemia. No patients had abnormal fasting glucose levels. Three/thirty-five patients had HbA1c in the prediabetes range. Ten/twenty-two patients with 17p11.2 deletion and 2/3 with RAI1 variants had increased insulin basal levels. Three/twenty-three patients with the 17p11.2 deletion had prediabetes. Conclusion: Our investigation suggests that SMS ‘deleted’ patients may show a dyslipidemic pattern, while SMS ‘mutated’ patients are more likely to develop early-onset obesity along with hyperinsulinism.

CTNNB1 syndrome is an autosomal-dominant neurodevelopmental disorder featuring developmental delay; intellectual disability; behavioral disturbances; movement disorders; visual defects; and subtle facial features caused by de novo loss-of-function variants in the CTNNB1 gene. Due to paucity of data, this study intends to describe feeding issues and oral-motor dyspraxia in an unselected cohort of 10 patients with a confirmed molecular diagnosis. Pathogenic variants along with key information regarding oral-motor features were collected. Sialorrhea was quantified using the Drooling Quotient 5. Feeding abilities were screened using the Italian version of the Montreal Children’s Hospital Feeding Scale (I-MCH-FS). Mild-to-severe coordination difficulties in single or in a sequence of movements involving the endo-oral and peri-oral muscles were noticed across the entire cohort. Mild-to-profuse drooling was a commonly complained-about issue by 30% of parents. The mean total I-MCH-FS t-score equivalent was 43.1 ± 7.5. These findings contribute to the understanding of the CTNNB1 syndrome highlighting the oral motor phenotype, and correlating specific gene variants with clinical characteristics.

Most autoinflammatory diseases have a pediatric onset heralded by fever and stereotyped inflammatory symptoms: the zenith of such flares is marked by manifold phenotypes, explaining why diagnosis of these disorders may go unnoticed until adulthood. This editorial shows the complexity of autoinflammation in children and its protean presentations.

PFAPA syndrome belongs to the family of autoinflammatory disorders, and its pathophysiology remains mysterious; it is probably related to oligo or polygenic mechanisms and recurs over a variable length of time in combination with clinical signs relating to the oral cavity and cervical lymph nodes. Pharyngitis and cervical adenitis are distinctive manifestations of PFAPA syndrome, which is largely underdiagnosed among the non-hereditary causes of pediatric fevers and is sometimes confused with other hereditary periodic fevers, primary or acquired immunodeficiency disorders, and cyclic neutropenia. Unfortunately, options for successfully managing the disease and stopping the recurrence of fevers are limited. Interventions focused on innate immunity cells might enhance their response and convey possible benefits for these children; how the microbiome interacts with peculiar genotypes to influence PFAPA expression is an open question, and the acquisition of metagenomic data will create opportunities to examine the evolutionary tuning of the microbiome to the host and shed light on the manifold human–microbiome partnership.

The clinical features of achondroplasia can cause acute self-limited pain that can evolve into chronic pain. Pain causes a low quality of life, in terms of physical, emotional, social, and school functioning in both adult and children with achondroplasia. We conducted a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement to describe prevalence, assessment tools, causes and management strategies of pain in this rare disease. We found that shoulder and knee pain is typically referred during infancy, while knee pain is generally referred around 5–6 years of age. The prevalence of general pain in adolescence can be as high as 90%. Chronic pain in the achondroplasia population increases with age, with up to 70% of adults reporting general pain and back pain. Recognizing the multiple determinants of acute and chronic pain in patients with achondroplasia may enable physicians to better understand and manage this burden, particularly with the advent of new drugs that may modify some of the striking features of achondroplasia.

Introduction: This paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet’s disease (BD). Methods: The project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry. Results: Respondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet’s Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0–30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1–50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range – 1.8–4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p < 0.001), the presence of any major organ involvement (p < 0.031), the presence of gastro-intestinal (p < 0.001), neurological (p = 0.012) and musculoskeletal (p = 0.022) symptoms, recurrent fever (p = 0.002), and headache (p < 0.001) were associated to a higher number of accesses to the healthcare system. Multiple linear regression showed that the BDQoL score could significantly predict the global socioeconomic impact of BD (F = 14.519, OR 1.162 [CI 0.557–1.766], p < 0.001). Discussion: Preliminary results from the AID

This report suggests that SHOC2-mutated patients may display autoimmune phenomena, though triggers leading to the development of a clinically overt autoimmune disease remain obscure. Unfortunately, there is yet no clear consensus as to whether the association with autoimmune thyroiditis, pancreatitis or cytopenia in SHOC2 mutations is coincidental.

The clinical features of achondroplasia can cause acute self-limited pain that can develop into chronic pain. Pain causes a low quality of life, in terms of physical, emotional, social, and school functioning in both adult and children with achondroplasia. We conducted a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement to describe prevalence, assessment tools, causes and management strategies of pain in this rare disease. We found that shoulder and knee pain is typically referred during infancy, while knee pain is generally referred around 5-6 years of age. The prevalence of general pain in adolescence can be as high as 90%. Chronic pain in the achondroplasia population increases with age, with up to 70% of adults reporting general pain and back pain. Recognizing the multiple determinants of acute and chronic pain in patients with achondroplasia may enable physicians to better understand and manage this burden, particularly with the advent of new drugs that may modify some of the known features of achondroplasia.

The paper discusses relevant issues related to GnRH test for diagnosing central precocious puberty

Neuropsychiatric symptoms combined with oral pigmentation and undetermined fever are presented as revealing hints of autoimmune Addison’s disease.

The authors regret < for the oversight to mention that this work has been done on behalf of the Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO) >. The authors would like to apologise for any inconvenience caused. ____________________________ DOI of original article: < 10.1016/j.semarthrit.2022.151957>

The use of a simplified GnRH test with a single dose of LH assessed 30 minutes after GnRH agonist represents a valid alternative to the traditional test required for establishing the diagnosis of central precocious puberty. Although cost optimization and higher facilities for children are important issues, further confirmatory studies with larger populations of children suspected to have central precocious puberty will help confirming the effectiveness of this strategy.

Background: The Montreal Children's Hospital Feeding Scale (MCH-FS) allows paediatricians and other health care professionals to identify feeding difficulties among children. Aim: To translate and adapt the MCH-FS into Italian, and to evaluate the validity and reliability of this Italian version of the Montreal Children's Hospital Feeding Scale (I-MCH-FS). Methods & procedures: A total of 150 children with special healthcare needs were admitted to the Rare Disease Unit of the Paediatrics Department at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy, between March 2021 and March 2022 (74 males; mean age = 3.85 ± 1.96 years; median age = 4 years; age range = 6 months-6 years and 11 months) and 150 healthy participants (83 males; mean age = 3.5 ± 1.98 years; median age = 3 years; age range = 6 months-6 years and 11 months) were included in the study, which was approved by the local ethics committee. The original version of the MCH-FS was translated and cross-cultural adapted through five stages: (1) initial translation, (2) synthesis of the translations, (3) back translation, (4) expert committee and (5) test of the prefinal version. Test-retest reliability and internal consistency were assessed using Pearson r, Spearman r and Cronbach's alpha, respectively. Construct validity was established by comparing data obtained from patients with those of healthy participants using the Mann-Whitney U-test. Outcomes & results: A Pearson r of 0.98, a Spearman r of 0.95 and Cronbach's alpha value of 0.86 were obtained. In the clinical group, 40.6% children were classified as having feeding disorders (n = 61), while in the normative group 4.7% were diagnosed with feeding problems (n = 7). Mean total score of the clinical group was significatively different from the normative's. Conclusions & implications: The I-MCH-FS is a valid and reliable one-page, quick screening tool used to identify feeding disorders among children with special needs i

To date, the feeding and oral-motor abilities of patients with CHARGE syndrome (CS) have not been longitudinally assessed. This study aims to investigate the level of these abilities at different ages and evaluate how they evolve during growth. We retrospectively analysed oral-motor features of 16 patients with molecularly confirmed CS (age range 4-21 years old; mean 11 years; SD 6 years; median 10 years). Nearly 100% of CS new-borns had weak sucking at birth, and half of them demonstrated poor coordination between breathing and swallowing. Over time, the percentages of children with tube feeding dependence (60% at birth) faced a slow but steady decrease (from 33% at 6 months, 25% at 12 months, to 13% at school age) in tandem with the decreasing risk of aspiration. The ability of eating foods requiring chewing was achieved at school age, after the acquisition of an adequate oral sensory processing. A mature chewing pattern with a variety of food textures was not achieved by more than half of patients, including those requiring artificial enteral nutrition. Most patients started prolonged oral-motor treatments with speech language therapists in early childhood. Conclusions: Although feeding and swallowing disorders are constant features in CS patients, a slow and gradual development of feeding abilities occurs in most cases. Rehabilitation plays a key role in overcoming structural and functional difficulties and attaining appropriate eating skills.

Patients with Noonan syndrome typically have a target height <2 standard deviations compared to the general population, and half of the affected adults remain permanently below the 3rd centile for height, though their short stature might result from a multifactorial etiology, not-yet fully understood. The secretion of growth hormone (GH) following the classic GH stimulation tests is often normal, with baseline insulin-like growth factor-1 (IGF-1) levels at the lower normal limits, but patients with Noonan syndrome have also a possible moderate response to GH therapy, leading to a final increased height and substantial improvement in growth rate. Aim of this review was to evaluate both safety and efficacy of GH therapy in children and adolescents with Noonan syndrome, also evaluating as a secondary aim the possible correlations between the underlying genetic mutations and GH responses.

Severe gastrointestinal symptoms are one of the main reasons for switching from conventional artificial tube feeding to blenderized tube feeding (BTF). This study aimed to describe and quantify the impact of BTF on gastrointestinal symptoms in children and adults. We analyzed four databases (PubMed, Scopus, Cochrane Library, and Google Scholar). The review was performed following the PRISMA extension for Scoping Reviews checklist. The methodological quality of articles was assessed following the NIH quality assessment tools. The initial search yielded 535 articles and, after removing duplicates and off-topic articles, 12 met the inclusion criteria. All included papers unanimously converged in defining an improvement of gastrointestinal symptoms during blenderized feeding: the eight studies involving pediatric cohorts report a decrease from 30 to over 50% in gagging and retching after commencing BTF. Similar rates are reported for constipation and diarrhea improvement in most critically ill adults. Experimental studies and particularly randomized controlled trials are needed to develop robust evidence on the effectiveness of BTF in gastrointestinal symptom improvement with prolonged follow-up and adequate medical monitoring.

This study aims to describe musculoskeletal manifestations (MSM) in children with Behçet’s syndrome (BS), their association with other disease manifestations, response to therapy, and long-term prognosis. Data were retrieved from the AIDA Network Behçet’s Syndrome Registry. Out of a total of 141 patients with juvenile BS, 37 had MSM at disease onset (26.2%). The median age at onset was 10.0 years (IQR 7.7). The median follow-up duration was 21.8 years (IQR 23.3). Recurrent oral (100%) and genital ulcers (67.6%) and pseudofolliculitis (56.8%) were the most common symptoms associated with MSM. At disease onset, 31 subjects had arthritis (83.8%), 33 arthralgia (89.2%), and 14 myalgia (37.8%). Arthritis was monoarticular in 9/31 cases (29%), oligoarticular in 10 (32.3%), polyarticular in 5 (16.1%), axial in 7 (22.6%). Over time, arthritis became chronic-recurrent in 67.7% of cases and 7/31 patients had joint erosions (22.6%). The median Behçet's Syndrome Overall Damage Index was 0 (range 0–4). Colchicine was inefcacious for MSM in 4/14 cases (28.6%), independently from the type of MSM (p=0.46) or the concomitant therapy (p=0.30 for cDMARDs, p=1.00 for glucocorticoids); cDMARDs and bDMARDs were inefcacious for MSM in 6/19 (31.4%) and 5/12 (41.7%) cases. The presence of myalgia was associated with bDMARDs inefcacy (p=0.014). To conclude, MSM in children with BS are frequently associated with recurrent ulcers and pseudofolliculitis. Arthritis is mostly mono- or oligoarticular, but sacroiliitis is not unusual. Prognosis of this subset of BS is overall favorable, though the presence of myalgia negatively afects response to biologic therapies.

Objective: IgA vasculitis (IgAV) (formerly Henoch-Schonlein ̈ Purpura, HSP) rarely causes severe skin lesions in children. The purpose of the research was to determine whether severe skin manifestations were associated with a more severe disease course. Methods: Severe cutaneous manifestations were defined as presence of hemorrhagic vesicles, bullae, ulcerations and/or necroses. Data were collected retrospectively from 12 international tertiary university medical centers. Results: A total of 64 patients with the most severe skin changes in IgAV/HSP and median (Q1, Q3) age of 8.08 (5.08, 11.92) years at the disease onset were compared with 596 IgAV/HSP patients without these manfiestations and median (Q1, Q3) age of 6.33 (4.50, 8.92) years. The patients with severe cutaneous manifestations were older in comparison to other patients with IgAV/HSP (p<0.001), they developed nephritis more frequently (40.6% vs. 20.6%, p = 0.001) with worse outcome of renal disease (p = 0.001). This group of patients also had higher frequencies of severe gastrointestinal complications like hematochezia, massive bleeding and/or intussusception (29.3% vs. 14.8%, p<0.001). D-dimer concentrations were significantly higher in these patients (4.60 mg/L vs. 2.72 mg/L, p = 0.003) and they had more frequent need for treatment with systemic glucocorticoids (84.4% vs. 37.2%, p<0.001) in comparison with the control group. Further multivariate analysis showed that severe cutaneous changes were associated with higher risk of developing nephritis [OR=3.1 (95%CI 1.04–9.21), p = 0.042] and severe gastrointestinal complications [OR=3.65 (95%CI 1.08–12.37), p = 0.038]. Conclusion: Patients with IgAV/HSP and severe skin manifestations had a more severe clinical course and more frequently required glucocorticoids compared to classic IgAV/HSP patients.