Serum calprotectin and joint ultrasound in the definition of disease relapse in non-systemic juvenile idiopathic arthritis: a prospective longitudinal study.

OBJECTIVES: The aim of our study was to investigate the role of serum calprotectin (SC) and muscle-skeletal ultrasound (MSUS) as predictive markers of relapse in patients with juvenile idiopathic arthritis (JIA). METHODS: Sixty non-systemic (ns) JIA patients in clinical remission were recruited to evaluate the risk of disease relapse. SC levels and JIA disease activity were assessed at every visit (3, 6, 12 and 18 months). Joint synovitis, characterised by both synovial effusion (SE) and synovial hyperplasia (SH), was measured by US score (sum of SE, SH, power Doppler and bone erosions) given to each examined joint and US ratio (US score/number of joints examined) at every visit. Associations of SC, US score and US ratio with relapse prevalence was studied longitudinally by using generalised estimating equations model. RESULTS: Thirty-one (51.6%) patients relapsed within 18 months. Patients with higher baseline US scores showed higher risk of relapse at 6 months (OR (95% confidence interval (CI)): 1.96 (1.09-3.52)). Additionally, patients with higher SC values at baseline showed higher risk of relapse at 18 months (1.66 (1.13-2.44)). Patients with higher baseline SC values showed an increased overall odds of relapse up to 18 months of follow-up (1.21 (1.08-1.36)). Furthermore, patients with higher US scores showed an increased overall odds of relapse up to 18 months of follow-up (1.96 (1.56-2.46)). Similarly, patients with higher US ratio showed an increased overall odds of relapse up to 18 months of follow-up (16.62 (7.17-38.54)). CONCLUSIONS: SC was able to identify JIA patients with unstable remission and increased risk of relapse. MSUS represents an interesting additional tool to the clinical evaluation, especially in predicting early relapse.

Molecular Mechanisms of Fetal and Neonatal Lupus: A Narrative Review of an Autoimmune Disease Transferal across the Placenta.

This study, conducted by searching keywords such as "maternal lupus", "neonatal lupus", and "congenital heart block" in databases including PubMed and Scopus, provides a detailed narrative review on fetal and neonatal lupus. Autoantibodies like anti-Ro/SSA and anti-La/SSB may cross the placenta and cause complications in neonates, such as congenital heart block (CHB). Management options involve hydroxychloroquine, which is able to counteract some of the adverse events, although the drug needs to be used carefully because of its impact on the QTc interval. Advanced pacing strategies for neonates with CHB, especially in severe forms like hydrops, are also assessed. This review emphasizes the need for interdisciplinary care by rheumatologists, obstetricians, and pediatricians in order to achieve the best maternal and neonatal health in lupus pregnancies. This multidisciplinary approach seeks to improve the outcomes and management of the disease, decreasing the burden on mothers and their infants.

Drug-Induced Enterocolitis Syndrome in Children.

Drug-Induced Enterocolitis Syndrome (DIES) is a drug-induced hypersensitivity reaction non-IgE mediated involving the gastrointestinal system that occurs 2 to 4 h after drug administration. Antibiotics, specifically amoxicillin or amoxicillin/clavulanate, represent the most frequent drugs involved. Symptoms include nausea, vomiting, abdominal pain, diarrhea, pallor, lethargy, and dehydration, which can be severe and result in hypovolemic shock. The main laboratory finding is neutrophilic leukocytosis. To the best of our knowledge, 12 cases of DIES (9 children-onset and 3 adult-onset cases) were described in the literature. DIES is a rare clinically well-described allergic disease; however, the pathogenetic mechanism is still unclear. It requires to be recognized early and correctly treated by physicians.

The Role of Serum Calprotectin in Defining Disease Outcomes in Non-Systemic Juvenile Idiopathic Arthritis: A Pilot Study.

Serum calprotectin (MRP8/14) is currently being studied as a promising biomarker of disease activity and outcome in patients with juvenile idiopathic arthritis (JIA) but the data in the literature are conflicting. The aim of our study was to investigate the potential role of serum calprotectin as biomarker of disease activity and flare/remission in a group of nsJIA patients during a follow-up period of 18 months. In this prospective longitudinal study, two groups of patients with ns-JIA (55 active patients and 56 patients in remission according to Wallace's criteria) and a control group (50 children) were recruited at baseline from January 2020 to September 2021. JIA patients were followed for up to 18 months at four timepoints: 3 months (T1), 6 months (T2), 12 months (T3) and 18 months (T4). At each timepoint, the following were recorded: JADAS27, blood counts, ESR, CRP, albumin, ferritin and serum calprotectin. To illustrate the performance of calprotectin, Kaplan-Meier curves were constructed from baseline to relapse/remission, dichotomizing patients at baseline in positive/negative on the basis progressive calprotectin cut-offs. Associations between baseline factors and relapse were determined using Cox regression models. Multivariate models were constructed to analyze the effect of covariates. Comparing baseline clinical and laboratory data of the three groups (active vs. inactive JIA vs. controls), only serum calprotectin reached statistical significance (active patients vs. inactive (p = 0.0016) and vs. controls (p = 0.0012)). In the inactive group, during the 18 months of follow up, 31 patients (55.3%) had a relapse. Comparing the baseline data of relapsers vs. non-relapsers, serum calprotectin showed higher levels (p = 0.001) in relapsers. In survival analysis, a log rank test showed significant differences of up to 12 ng/mL (p = 0.045). Multivariate Cox regression confirmed that only baseline calprotectin levels were independently associated with disease recurrence. In the active group, in the 12 months of follow-up, 19 patients (38%) entered remission of the disease. In addition, in this group, the only statistical difference at the baseline was the value of MPR8/14 (p = 0.0001). Log rank test showed significant differences up to 10 ng/mL (p = 0.003). In the multivariate Cox regression, serum calprotectin levels at baseline were independently associated with remission. In conclusion, our study would suggest a dual role for calprotectin in predicting future relapse and treatment response in patients with nsJIA, thus influencing therapeutic decisions and management of these patients during follow up.

Coaggregation of Asthma and Type 1 Diabetes in Children: A Narrative Review.

Asthma and type 1 diabetes mellitus (T1DM) are two of the most frequent chronic diseases in children, representing a model of the atopic and autoimmune diseases respectively. These two groups of disorders are mediated by different immunological pathways, T helper (Th)1 for diabetes and Th2 for asthma. For many years, these two groups were thought to be mutually exclusive according to the Th1/Th2 paradigm. In children, the incidence of both diseases is steadily increasing worldwide. In this narrative review, we report the evidence of the potential link between asthma and T1DM in childhood. We discuss which molecular mechanisms could be involved in the link between asthma and T1DM, such as genetic predisposition, cytokine patterns, and environmental influences. Cytokine profile of children with asthma and T1DM shows an activation of both Th1 and Th2 pathways, suggesting a complex genetic-epigenetic interaction. In conclusion, in children, the potential link between asthma and T1DM needs further investigation to improve the diagnostic and therapeutic approach to these patients. The aim of this review is to invite the pediatricians to consider the potential copresence of these two disorders in clinical practice.

C hlamydia trachomatis during pregnancy and childhood asthma-related morbidity: a population-based prospective cohort.

INTRODUCTION: Chlamydia trachomatis is the most commonly reported sexually transmitted disease and although infection during pregnancy is associated with neonatal complications, long-term respiratory consequences are unknown. We aimed to determine whether C. trachomatis infection during pregnancy is associated with asthma-related symptoms across childhood METHODS: This study among 2475 children and their mothers was embedded in a population-based prospective cohort study. Maternal urine samples were tested for C. trachomatis infection during pregnancy. Questionnaires provided information on childhood physician-attended lower respiratory tract infections and wheezing, and current asthma at age 10 years. Lung function was measured by spirometry at age 10 years. RESULTS: The prevalence of C. trachomatis infection during pregnancy was 3.2% (78 out of 2475). C. trachomatis infection during pregnancy was not associated with lower respiratory tract infections until age 6 years, but was associated with a higher odds of wheezing in children until age 10 years (OR 1.50 (95% CI 1.10-2.03)). C. trachomatis infection during pregnancy was associated with an increased odds of asthma (OR 2.29 (95% CI 1.02-5.13)), and with a lower forced expiratory volume in 1 s/forced vital capacity and forced expiratory flow at 75% of forced vital capacity (z-score difference -0.28 (95% CI -0.52- -0.04) and -0.24 (95% CI -0.46- -0.01), respectively) in children at age 10 years. The observed associations were only partly explained by mode of delivery, gestational age at birth or birthweight. CONCLUSIONS: C. trachomatis infection during pregnancy is associated with increased odds of wheezing, asthma and impaired lung function. The causality of the observed associations and potential underlying mechanisms need to be explored.

Inpatient Care during the COVID-19 Pandemic: A Survey of Italian Physicians.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern. OBJECTIVE: We explored the clinical management of inpatients with COVID-19 in Italy. METHODS: A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed. RESULTS: A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%. CONCLUSIONS: In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available.

Influence of inhaled corticosteroids on pubertal growth and final height in asthmatic children.

BACKGROUND: Controversial data exist on the possibility that inhaled corticosteroids (ICs) affect growth in children with mild-to-moderate asthma. We assessed whether ICs affect growth and final height (FH) in asthmatic children compared to controls. METHODS: A retrospective study was conducted on 113 asthmatic children compared with 66 control children. Asthmatic children presented with mild-to-moderate asthma and had exclusive ICs. Anthropometric data of four specific time-points were collected for both groups (pre-puberty, onset and late puberty, and FH) and converted to standard deviation scores (SDS). Growth trajectories were assessed as follows: (i) in puberty, using peak height velocity (PHV) and pubertal height gain SDS (PHG-SDS); (ii) until FH achievement, using FH-SDS and FH gain SDS (FHG-SDS). Repeated measurement analysis was performed across longitudinal study visits. A general linear model (GLM) was performed in asthmatic group evaluating the effect of corticosteroid type, treatment duration, and cumulative dose on FH corrected for multiple variables. RESULTS: At pre-puberty, height and weight SDS were similar between the groups (p > 0.05). Height SDS progressively declined over the study period in asthmatic patients from pre-puberty to FH (p-trend < 0.05), whereas it did not change over time in controls (p-trend > 0.05), in both boys and girls. Asthmatic children had exclusive ICs [budesonide (n = 36) vs. fluticasone (n = 43) vs. mometasone (n = 34)] for a mean period of 6.25 ± 1.20 years and a mean cumulative dose of 560.07 ± 76.02 mg. They showed decreased PHG-SDS and lower PHV compared to controls (all p < 0.05). FH-SDS and FHG-SDS were significantly reduced in asthmatic group compared to controls. FH in asthmatic patients was 2.5 ± 2.89 cm lower in boys and 2.0 ± 2.03 cm lower in girls than controls. The GLM showed that FH achievement was dependent on the type of ICs, duration of the treatment, and cumulative dose (p < 0.05). CONCLUSIONS: ICs affect pubertal growth determining reduced final height in asthmatic children compared to controls, in a dose- and duration-dependent manner.

Vitamin D supplementation modulates the immune system and improves atopic dermatitis in children.

BACKGROUND: Vitamin D seems to influence the evolution of atopic dermatitis (AD) in children. METHODS: We tested the vitamin D serum levels of 39 children with AD (AD group t0) and of 20 nonallergic healthy controls (C group). AD severity was evaluated using the AD scoring system (SCORAD index). Cytokine serum levels (IL-2, IL-4, IL-6, IFN-γ, TNF-α) and atopy biomarkers were also measured. The patients were then treated with vitamin D oral supplementation of 1,000 IU/day (25 mg/day) for 3 months. We then reevaluated the vitamin D serum levels, AD severity and cytokine serum levels in all of the treated children (AD group t1). RESULTS: The cross-sectional analysis on patients affected by AD (AD group t0) showed that the initial levels of all the tested cytokines except for TNF-α were higher than those of the healthy control group (C group), falling outside the normal range. After 3 months of supplementation the patients had significantly increased vitamin D levels (from 22.97 ± 8.03 to 29.41 ± 10.73 ng/ml; p = 0.01). A concomitant significant reduction of both the SCORAD index (46.13 ± 15.68 at the first visit vs. 22.57 ± 15.28 at the second visit; p < 0.001) and of all the altered cytokines (IL-2, IL-4, IL-6, IFN-γ) was also found. CONCLUSIONS: This study showed vitamin D supplementation to be an effective treatment in reducing AD severity in children through normalization of the Th1 and Th2 interleukin serum pattern.

Lung function assessment in children with Long-Covid syndrome.

INTRODUCTION: A significant percentage of patients who survived the Coronavirus Infection Disease 2019 (COVID-19) showed persistent general and respiratory symptoms even months after recovery. This condition, called Post-Acute Sequelae of COVID-19 or Long-Covid syndrome (LCS), has been described also in children with positive history for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Little is known about the pathophysiologic mechanisms underlying this syndrome. The aim of this study was to investigate any difference between children with LCS and asymptomatic peers with previous COVID-19 in terms of lung function and lung ultrasound (LUS) patterns. Secondly, we tested associations between lung function abnormalities and LUS findings with Long-Covid. METHODS: We carried out a prospective, descriptive, observational study including 58 children aged 5-17 years: 28 with LCS compared to 30 asymptomatic children with previous COVID-19. We collected demographic data, history of asthma, allergy or smoke exposure, and acute COVID-19 symptoms. After a median period of 4.5 months (1%-95% range 2-21) since the infection, lung function was assessed by spirometry, body plethysmography, diffusion lung capacity for carbon monoxide (DLCO). Airways inflammation was investigated by fractional exhaled nitric oxide (FeNO). LUS was performed independently by two experienced clinicians. RESULTS: We found that children with LCS were older than controls (mean (SD) 12 (4.1) vs. 9.7 (2.6); p = .04). Children with LCS complained more frequently fatigue (46.4%), cough (17.9%), exercise intolerance (14.3%) and dyspnea (14.3%). Lung function was normal and similar between the two groups. The frequency of LUS abnormalities was similar between the two groups (43.3% children with LCS vs. 56.7% controls; p = .436). Children with LCS showed lower FeNO values (log difference -0.30 (CI 95% -0.50, -0.10)), but no association of LCS with a lower lung function and abnormal LUS findings was found. CONCLUSIONS: LCS seems to be more frequent in older age children. Lung functional and structural abnormalities were not different between children with LCS and asymptomatic subjects with previous COVID-19. In addition, children with LCS showed lower FeNO values than controls, suggesting its potential role as a marker in LCS. However, further and larger studies are needed to confirm our findings.

Potential Predictors of Long COVID in Italian Children: A Cross-Sectional Survey.

BACKGROUND: Identifying predictive factors of long COVID syndrome (LCS) is essential to preventing and managing this condition. We investigated the prevalence, symptoms, and risk factors of LCS in a cohort of Italian children and adolescents. METHODS: We carried out a cross-sectional survey on demographic characteristics and clinical data related to COVID-19 phase and LCS in a cohort of children and adolescents, sending a questionnaire by using the PEDIATOTEM platform. RESULTS: The prevalence of LCS was 25% (99/396). The most frequent symptoms of LCS included nasal congestion, diarrhea, headache, and fatigue. We found no association between demographic data (gender, age, and ethnicity) and LCS. Additionally, we showed that patients with concurrent allergic rhinitis, atopic dermatitis, respiratory disease, gastrointestinal disease, and rheumatologic disease had a higher risk of LCS than patients without those comorbidities. Patients experiencing fatigue, muscle, and abdominal pain in COVID-19 showed a higher risk of LCS than patients complaining of other symptoms. We found no association between vaccination and LCS. CONCLUSIONS: Specific comorbidities or symptoms during acute illness were identified as being risk factors for LCS. Understanding which are the risk factors for LCS could yield a clearer picture of its pathogenesis.

Associations of C reactive protein to albumin ratio, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio with disease activity in patients with juvenile idiopathic arthritis.

INTRODUCTION: Recent works in the scientific literature reported the role of C reactive protein to albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as biomarkers of disease activity in rheumatic diseases. OBJECTIVES: To investigate the role of CAR, PLR and NLR as potential markers of disease activity in children with non-systemic JIA (nsJIA) and their correlation with the risk of persistent disease activity of flare during follow up. METHODS: Our prospective, cross-sectional study involved 130 nsJIA patients (74 with active disease and 56 with inactive disease according to Wallace criteria) and 62 healthy controls. Demographic, clinical and laboratory data were collected at baseline (T0) and at 3 (T1), 6 (T2), 12 (T3) and 18 months (T4) during follow up. Disease activity was evaluated through Juvenile Arthritis Disease Activity Score (JADAS-27). RESULTS: At baseline, CRP and CAR were higher in patients than in controls (p = 0.046), while no differences were found for NLR and PLR. However, there was no positive correlation between CAR, NLR, PLR and JADAS-27 in JIA patients. To better investigate the role of CAR, NLR and PLR as markers of disease activity, we used a generalized estimating equation (GEE) model, applied to all patients either with or without active disease. According to this analysis, CAR and NLR baseline levels were predictive of higher risk of disease activity at 6 months follow up (p < 0.001). CONCLUSIONS: CAR and NLR could indicate persistent disease activity in patients with JIA. Their predictive value could be increased by their combined use and by the observation of their trend during follow up, since increasing CAR values over time could predict a disease flare in the brief time.

Neuropsychological Symptoms and Quality of Life during the COVID-19 Pandemic in Children: A Survey in a Pediatric Population in the Abruzzo Region, Italy.

BACKGROUND: The SARS-CoV-2 pandemic has significantly affected the pediatric population. Long-term sequelae (Long COVID-19) may particularly involve the central nervous system, with possible effects on psychological well-being and quality of life (QoL), aspects that were already influenced by the restrictive measures and general social impact of the pandemic. METHODS: We conducted a cross-sectional survey that aims at investigating the neuropsychological effects and the QoL impairment of SARS-CoV-2 on a cohort of children and adolescents in the Abruzzo region (Italy). A questionnaire was submitted to caregivers with the help of the PEDIATOTEM platform. A control group of healthy subjects was also included to distinguish between the effects of infection from the general influence of the pandemic. RESULTS: A total of 569 subjects responded: 396 COVID-19 patients (99 of whom had Long COVID-19) and 111 controls. After the pandemic, when compared with the COVID-19 group, the controls reported significantly increased appetite, sleeping habits, and time spent remotely with friends and a reduction in physical activity and time spent in person with friends. A significant higher rate of controls asked for psychological/medical support for emotional problems. On the other hand, the Long COVID-19 group showed more fatigue and emotional instability with respect to non-Long-COVID-19 subjects. No differences in QoL results (EuroQOL) were found between the COVID-19 patients and controls, while the Long-COVID-19 subgroup showed significantly higher rates of pain/discomfort and mood instability, as confirmed by the analysis of variation of responses from the pre-COVID-19 to the post-COVID-19 period. CONCLUSIONS: Among COVID-19 patients, neuropsychological and QoL impairment was more evident in the Long COVID-19 subgroup, although emotional and relational issues were also reported by uninfected patients, with a growing request for specialist support as a possible consequence of social restriction.

New Indications of Biological Drugs in Allergic and Immunological Disorders: Beyond Asthma, Urticaria, and Atopic Dermatitis.

Asthma, chronic urticaria, and atopic dermatitis are some of the most numerous allergic diseases affecting children. Recent advances in the understanding of their specific intracellular molecular pathways have led to the approval of monoclonal antibodies targeting definite inflammatory molecules in order to control symptoms and improve quality of life. Less is known about other allergic and immunologic disorders such as rhinosinusitis with nasal polyps, eosinophilic esophagitis, anaphylaxis, and food allergy undergoing allergen immunotherapy. The increasing evidence of the molecular mechanisms underlying their pathogeneses made it possible to find in children new indications for known biological drugs, such as omalizumab and dupilumab, and to develop other ones even more specific. Promising results were recently obtained, although few are currently approved in the pediatric population. In this review, we aim to provide the latest evidence about the role, safety, and efficacy of biologic agents to treat allergic and immunologic diseases in children.

Case report: Increased troponin level in 125 children during COVID-19.

Introduction: Increase in cardiac biomarkers during Coronavirus disease 2019 (COVID-19) was frequent regardless of the presence of myocarditis and multisystem inflammatory syndrome in children (MIS-C). Several studies described MIS-C, but few papers evaluated cardiac manifestations in children with SARS-CoV-2 infection without MIS-C and investigated the role of troponin in absence of electrocardiogram (ECG) and echocardiographic alterations. The aim of this case series is to describe the cardiac manifestations during COVID-19 in children, trying to explain the meaning of laboratory findings during COVID-19, especially of increased troponin. Materials and methods: We conducted a retrospective case series of children aged <18 years admitted at the Department of Pediatrics, University of Chieti, for SARS-CoV-2 infection between 1st March 2020 and 31th July 2022. All patients with documented SARS-CoV-2 infection underwent a laboratory evaluation at admission. Children with increased troponin I and/or BNP underwent electrocardiographic and echocardiographic exams. Results: 125 children were admitted for SARS-CoV-2 infection to our Department of Pediatrics, of whom 17 (13.6% of cases) with different patterns of cardiac involvement. Specifically, 5 subjects (4.0% of admitted children) were diagnosed as MIS-C and 12 children (9.6%) manifested a cardiac involvement in terms of increased troponin with or without ECG and echocardiography anomalies. Troponin, C-reactive protein, procalcitonin and BNP values resulted higher in patients with MIS-C compared to patients without MIS-C. Furthermore, patients with MIS-C had higher neutrophils and lower lymphocytes compared to patients without MIS-C. ECG abnormalities were found in 4/5 patients with MIS-C and in 2/12 patients without MIS-C. Echocardiographic anomalies were found in all patients with MIS-C, especially in terms of valve regurgitation and ejection fraction reduction and in 2/12 patients without MIS-C, especially in terms of pericardial effusion. Despite high troponin levels, children presented a favorable clinical evolution. Conclusion: The increase in troponin level in children with COVID-19 could also be due to respiratory causes or a massive inflammatory state. In our case series, patients with increased troponin associated to COVID-19 presented a favorable clinical course with clinical and laboratory remission almost always within 7 days.

The Role of Nasal Cytology and Serum Atopic Biomarkers in Paediatric Rhinitis.

A Nasal Provocation Test allows the differentiation of allergic and non-allergic rhinitis, but it is difficult and expensive. Therefore, nasal cytology is taking hold as an alternative. We carried out a cross-sectional study, including 29 patients with persistent rhinitis according to ARIA definition and negative skin prick tests. Nasal symptoms were scored from 0 to 5 using a visual analogue scale, and patients underwent blood tests to investigate blood cell count (particularly eosinophilia and basophilia), to analyze serum total and specific IgE and eosinophil cationic protein (ECP), and to perform nasal cytology. We performed a univariate logistical analysis to evaluate the association between total serum IgE, serum eosinophilia, basophils, and ECP and the presence of eosinophils in the nasal mucosa, and a multivariate logistic model in order to weight the single variable on the presence of eosinophils to level of the nasal mucosa. A statistically significant association between serum total IgE levels and the severity of nasal eosinophilic inflammation was found (confidence interval C.I. 1.08-4.65, odds ratio OR 2.24, p value 0.03). For this reason, we imagine a therapeutic trial with nasal steroids and oral antihistamines in patients with suspected LAR and increased total IgE levels, reserving nasal cytology and NPT to non-responders to the first-line therapy.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Myth or Reality? The State of the Art on a Controversial Disease.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) syndrome is one of the most controversial diseases in pediatric rheumatology. Despite first being described more than 25 years ago as the sudden and rapid onset of obsessive-compulsive disorder (OCD) and/or tic disorder symptoms as complications of a Group A beta-hemolytic Streptococcus (GAS) infection, precise epidemiological data are still lacking, and there are no strong recommendations for its treatment. Recent advances in the comprehension of PANDAS pathophysiology are largely attributable to animal model studies and the understanding of the roles of Ca++/calmodulin-dependent protein kinase (CaM kinase) II, disrupted dopamine release in the basal ganglia, and striatal cholinergic interneurons. The diagnosis of PANDAS should be made after an exclusion process and should include prepubescent children with a sudden onset of OCD and/or a tic disorder, with a relapsing/remitting disease course, a clear temporal association between GAS infection and onset or exacerbation of symptoms, and the association with other neurological abnormalities such as motoric hyperactivity and choreiform movements. Antibiotic medications are the primary therapeutic modality. Nonetheless, there is a paucity of randomized studies and validated data, resulting in a scarcity of solid recommendations.