[Two Cases of Pseudo-Bartter Syndrome in Childhood: When to Suspect a Rare Onset Pattern of Cystic Fibrosis].

Cystic fibrosis is a multisystem disease with extremely variable onset, symptoms and course. One of the onset modality but also a complication of the disease is the pseudo-Bartter syndrome, characterized by hyponatremia, hypochloremic dehydration and metabolic alkalosis in absence of any renal disease. This syndrome occurs more frequently in the first year of life and has a peak in the summer. In this article, we describe two cases of cystic fibrosis associated with pseudo-Bartter syndrome in childhood. Excluding every possible cause of metabolic alkalosis associated with hyponatremia was crucial for our diagnostic pathway, and the experience gained with the first case helped a lot with the second one.

Fatal Deterioration of a Respiratory Syncytial Virus Infection in an Infant with Abnormal Muscularization of Intra-Acinar Pulmonary Arteries: Autopsy and Histological Findings.

Respiratory syncytial virus (RSV) infection represents a global and noteworthy cause of hospitalization and death in infants of less than 1 year of age. The typical clinical manifestation is bronchiolitis, an inflammatory process of the small airways. The symptoms are usually a brief period of low-grade fever, cough, coryza, breathing difficulties, and reduced feeding. The progression of the disease is difficult to predict, even in previous healthy subjects. Symptoms may also be subtle and underestimated, thus leading to sudden unexpected infant death (SUID). In these cases, RSV infection is discovered at autopsy, either histologically or through real-time reverse transcription polymerase chain reaction (RT-PCR) performed on nasopharyngeal swabs. Herein, we describe a case of RSV infection in a 6-month-old infant with no risk factors, who rapidly deteriorated and unexpectedly died of respiratory insufficiency in a hospital setting. RT-PCR on nasopharyngeal swabs revealed RSV. The autopsy showed diffuse lymphogranulocytic bronchitis and bronchiolitis, and multiple foci of acute pneumonia. Abnormal muscularization of the intra-acinar pulmonary arteries was also observed, which likely contributed to worsening the lung impairment.

Pediatric Recurrent Pericarditis: Appropriateness of the Standard of Care and Response to IL-1 Blockade.

OBJECTIVE: To analyze, in a cohort of pediatric patients with recurrent pericarditis undergoing anti-interleukin (IL)-1 treatment: the agent and dosing used as first-line treatment, the long-term efficacy of IL-1 blockers, the percentage of patients achieving a drug-free remission, and the presence of variables associated with drug-free remission. STUDY DESIGN: Data were collected from patients' charts. The annualized relapse rate (ARR) was used for evaluation of treatment efficacy, and bivariate logistic regression analysis was used for variables associated with drug-free remission. RESULTS: Fifty-eight patients, treated between 2008 and 2018, were included in the study (mean follow-up. 2.6 years). Of the 56 patients treated with first-line drugs, 14 not responsive patients were underdosed. Fifty-seven patients were treated with anakinra: the ARR before and during daily treatment was 3.05 and 0.28, respectively (P < .0001); an increase to 0.83 was observed after the reduction/withdrawal of treatment (P < .0001). The switch from anakinra to canakinumab (5 patients) was associated to an increase of the ARR (0.49 vs 1.46), but without statistical significance (P = .215). At last follow-up, only 9 of the 58 patients had withdrawn all treatments. With the limits of a retrospective study and the heterogeneity between the patients enrolled in the study, a shorter duration of treatment with anakinra was the only variable associated with drug-free remission. CONCLUSIONS: This study shows that most pediatric patients with recurrent pericarditis needing IL-1 blockade received an inadequate treatment with first-line agents. The effectiveness of anakinra is supported by this study, but few patients achieved drug-free remission. The different rate of response to anakinra and canakinumab may suggest a possible role of IL-1α in the pathogenesis of recurrent pericarditis.

Non-coronary cardiac events, younger age, and IVIG unresponsiveness increase the risk for coronary aneurysms in Italian children with Kawasaki disease.

OBJECTIVES: Kawasaki disease (KD) is the most frequent cause of acquired heart disease in children in high-income countries because of coronary artery involvement. Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors. METHODS: Multicenter retrospective and prospective study including 372 consecutive children (58% boys; mean age 34.3 ± 30.3 months, Caucasian 85%) was diagnosed with KD. We divided the cohort into 2 groups according to the presence of coronary anomalies (CAA) and aneurysms. We compared the groups and studied the risk factors for CAA and for aneurysms, the most severe lesions. RESULTS: Children with CAA were 91/372 (24.46%, aneurysms 20/372, 5.37%). Children with CAA were more likely to have a longer duration of fever (p < 0.001), later day of treatment (p < 0.001), to be IVIG non-responders and late treated (p < 0.001), while age, clinical presentation, and seasonality were not different. They also had significantly higher WBC and neutrophils, lower lymphocytes, Hb and Na during the acute stage, and slower resolution of inflammation. Age, IVIG unresponsiveness, and presence of non-coronary cardiac findings were independent risk factors for CAA and for aneurysms, while neutrophils just for CAA. Age under 6 months was a risk factor for the aneurysm. Aneurysms occurred more frequently in the first quartile of the age of KD onset (under 14 months). CONCLUSION: Very young children with non-coronary cardiac findings are at increased risk for a more severe form of KD with aneurysms. These children could benefit from adjunctive therapy beside IVIG, especially if they have higher markers of inflammation, particularly neutrophils. Key points • Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors. • Risk factors for coronary involvement have been extensively studied in the Asian population, and others have been validated in cohorts with mixed ethnicities. • In our predominantly Caucasian population, non-coronary cardiac findings, age younger than 6 months, and IVIG unresponsiveness are independent risk factors for a more severe form of KD with aneurysms.

[Acro-ischemic injuries in children-adolescents during CoViD-19 pandemic: from lifestyle changes due to lockdown to interferone.] / Le lesioni acro-ischemiche nei bambini-adolescenti in tempi di CoViD-19: dal micro-ambiente da clausura all'interferone.

At the end of March 2020, just over a month after the first ascertained case of CoViD-19 infection in Italy, the first reports of acute lesions of acro-ischemia appeared, especially in pre-adolescents and adolescents. These manifestations have been called in the course of these months in various ways, from "acro-ischemia acuta", "erythema pernio", "chilblains", up to characterize them more recently as "CoViD Toes". Clinical manifestations do not usually associate with other typical symptoms of Covid-19 and do not find a classical and defined serological antibody response (IgG and IgM). From a clinical point of view it is a localized and self-resolving problem of an interesting and relatively new pathogenetic model of disease in relation to a viral agent. Future studies must make us understand if there is in this specific condition a low viral load is not detectable by current methods and if this explains the inability to produce an adequate immune response for CoViD-19. It is important to determine whether the interferon immune response in some subjects can be the cause of both the low viremia and the endothelial damage so localized in the acral-site, as happens in other models of diseases (chilblain-lupus like). On the contrary, some authors believe that the acral lesions are attributable to chilblains caused by a series of favourable environmental conditions due to forced enclosure. We report the descriptive experience of 14 cases of acro-ischemia in children and adolescents observed in the territorial area of Ravenna and Rimini. The cases were subjected to the nasopharyngeal swab and to the search for antibodies with ELISA method for CoViD-19 both with negative results.

[Atypical Kawasaki disease with acute cholestasis and early coronary involvement at onset in an adolescent]. / Malattia di Kawasaki atipica esordita con colestasi acuta ed interessamento coronarico precoce in un adolescente.

Kawasaki disease is an acute febrile illness of childhood that affects usually children younger than 5 years of age. The diagnosis is based on typical clinical features. Atypical or incomplete forms of Kawasaki disease can be observed in almost 20% of patients and at onset is a clinical challenge leading to diagnostic and therapeutic delays with higher risk of coronary abnormalities. We report the case of a 13-year-old boy who presented with febrile cholestasis, abdominal pain and early coronary anomalies that was diagnosed with Kawasaki disease. Atypical findings of our case at onset were the age, the clinical presentation and the timing of appearance of coronary anomalies. A high index of suspicion of Kawasaki disease should be maintained in patients presenting with febrile cholestatic jaundice.

Inability of Asian risk scoring systems to predict intravenous immunoglobulin resistance and coronary lesions in Kawasaki disease in an Italian cohort.

Since resistance to intravenous immunoglobulin (IVIG) is associated with coronary lesions (CALs) in Kawasaki disease (KD), it is crucial to identify patients at risk to protect them from coronary involvement. The available risk scores to predict IVIG resistance were developed in Asian populations in whom their effectiveness has been proven, but data on non-Asian children are limited. The aim of this study is to evaluate the ability of the Kobayashi, Egami, and Formosa risk scores to predict IVIG resistance and CALs in Italian patients with KD. A multicenter retrospective analysis involving children with KD diagnosed between 2000 and 2015 was carried out: 257 patients were enrolled (57.9% boys, 89.9% Caucasian); 43 patients were IVIG resistant (16.7%). The scores have low sensitivity and specificity in predicting IVIG resistance: respectively, KS 64% and 62.5%, ES 41.4% and 77.4%, and FS 70.8% and 44.9%. The predictive value of the 3 scores for predicting CALs was also poor.Conclusion: Kobayashi, Egami, and Formosa Scores are ineffective in predicting IVIG resistance and coronary involvement in a predominantly Caucasian cohort. A specific score system for mostly Caucasian children with KD is needed enable the early identification of those at risk for CALs who could benefit from intensified treatment. What is Known: • There are several risk scores developed in the Asian population to early identify patients with KD at risk for immunoglobulin-resistance and thus for coronary lesions. • Data are scarce on their effectiveness in non-Asian children. What is New: • We present a comprehensive analysis of the ability of 3 Asian risk scores in a cohort of mostly Caucasian children to predict immunoglobulin resistance and coronary involvement. • Low sensitivity and specificity of the Asian scores for immunoglobulin-resistance and coronary lesions suggest the need for criteria specific for different ethnicities.

Gastrointestinal presentation of Kawasaki disease: A red flag for severe disease?

BACKGROUND: Kawasaki disease (KD) is a febrile systemic vasculitis of unknown etiology and the main cause of acquired heart disease among children in the developed world. To date, abdominal involvement at presentation is not recognized as a risk factor for a more severe form of the disease. OBJECTIVE: To evaluate whether presenting abdominal manifestations identify a group at major risk for Intravenous immunoglobulin (IVIG)-resistance and coronary lesions. METHODS: Retrospective study of KD patients diagnosed between 2000 and 2015 in 13 pediatric units in Italy. Patients were divided into 2 groups according to the presence or absence of abdominal manifestations at onset. We compared their demographic and clinical data, IVIG-responsiveness, coronary ectasia/aneurysms, laboratory findings from the acute and subacute phases. RESULTS: 302 patients (181 boys) were enrolled: 106 patients with, and 196 patients without presenting abdominal features. Seasonality was different between the groups (p = 0.034). Patients with abdominal manifestations were younger (p = 0.006) and more frequently underwent delayed treatment (p = 0.014). In the acute phase, patients with abdominal presentation had higher platelet counts (PLT) (p = 0.042) and lower albuminemia (p = 0.009), while, in the subacute phase, they had higher white blood cell counts (WBC) and PLT (p = 0.002 and p < 0.005, respectively) and lower red blood cell counts (RBC) and hemoglobin (Hb) (p = 0.031 and p 0.009). Moreover, the above mentioned group was more likely to be IVIG-resistant (p < 0.005) and have coronary aneurysms (p = 0.007). In the multivariate analysis, presenting abdominal manifestations, age younger than 6 months, IVIG- resistance, delayed treatment and albumin concentration in the acute phase were independent risk factors for coronary aneurysms (respectively p<0.005, <0.005, = 0.005 and 0.009). CONCLUSIONS: This is the first multicenter report demonstrating that presenting gastrointestinal features in KD identify patients at higher risk for IVIG-resistance and for the development of coronary aneurysms in a predominantly Caucasian population. CLINICAL TRIAL REGISTRATION: 8/20014/O/OssN.

"Cyrano nose" associated with hepatic hemangiomas successfully treated with propranolol.

Hemangioma of the nasal tip is commonly described as "Cyrano nose" and his treatment is extremely difficult because of its location and possible severe aesthetic complications like definitive nasal deformation. We describe a patient who presented at two months of age with a "Cyrano nose" associated with multiple hepatic and cutaneous hemangiomas, which completely resolved after therapy with propranolol. Treatment was well tolerated and aesthetic result was excellent.

Long-term clinical significance of thyroid autoimmunity in children with celiac disease.

OBJECTIVE: To evaluate the long-term outcome of thyroid function and autoimmunity in a large series of children with celiac disease. STUDY DESIGN: This longitudinal, retrospective study (duration of follow-up, 8.9 +/- 4.0 years) was conducted at the Pediatric Department, University of Bologna, Italy. One hundred thirty-five consecutive patients diagnosed between June 1990 and December 2004 and followed on a gluten-free diet were examined. Inclusion criteria were good dietary compliance and duration of follow-up for at least 3 years. RESULTS: Of 101 patients who never showed positive antithyroid titers during the follow-up, 86 remained euthyroid; 15 showed high thyroid-stimulating hormone values at diagnosis that normalized in 11 cases after 12 to 18 months of gluten withdrawal. Of 31 patients with persistently positive antibody titers, 23 (74%) remained consistently euthyroid during the follow-up and 8 (26%) had a subclinical hypothyroidism. The prevalence of cases with positive antibodies was similar in children with growth retardation or gastroenterological symptoms at diagnosis and different durations of gluten exposure. CONCLUSIONS: The presence of antithyroid antibodies in children with celiac disease has a low predictive value for the development of thyroid hypofunction during the indicated surveillance period. Longer follow-up is needed.