[Chronic nonbacterial osteomyelitis: description of three pediatric cases.] / Osteomielite cronica non-batterica: descrizione di tre casi pediatrici.

Chronic recurrent multifocal osteomyelitis (CRMO) or also called chronic non-bacterial osteomyelitis (CNO) is the most common autoinflammatory bone disease. It is characterized by the presence of symptomatic and non-symptomatic bone lesions, mono or multifocal. The main sites involved are the metaphyses of the long bones, the bones of the pelvis, the vertebrae, the clavicle, the mandible. Local symptoms include pain, swelling, and warmth in the absence or presence of fever. The inflammatory process can involve the skin (palmoplantar pustulosis or acne) and the intestine. Diagnosis is complex and uses imaging techniques (X-ray, total-body MRI, scintigraphy) as well as common laboratory tests aimed at identifying an inflammatory state. In doubtful cases, especially in the monofocal forms, it is mandatory to perform a biopsy examination to rule out malignancy. The differential diagnosis includes neoplastic diseases, chronic infections, metabolic diseases, traumatic outcomes. Treatment is not standardized and involves the use of non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, sulfasalazine, methotrexate, TNF inhibitors and bisphosphonates based on the experience of the individual centers. We report the experience of our Center (Operative Unit of Pediatrics S. Anna Hospital in Ferrara) with the description of 3 clinical cases, diagnosed from 2016 to 2018, treated with bisphosphonates with good clinical response and remission in two of them, while one patient had an adverse reaction to pamidronate and was subsequently successfully treated with methotrexate.

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.

Infrared thermography in children: a reliable tool for differential diagnosis of peripheral microvascular dysfunction and Raynaud's phenomenon?

BACKGROUND: Infrared Thermography (IRT) has been used for over 30 years in the assessment of Raynaud Phenomenon (RP) and other peripheral microvascular dysfunctions in adults but, to date, very little experience is available on its use in children for this purpose. The first aim of the study was to assess reproducibility of thermographic examination after cold exposure by comparing inter-observer agreement in thermal imaging interpretation. The secondary aim was to evaluate whether IRT is reliable to diagnose and differentiate peripheral circulation disturbances in children. METHODS: Children with clinical diagnosis of primary Raynaud's phenomenon (PRP), secondary RP (SRP), acrocyanosis (AC) and age-matched controls underwent sequential measurements of skin temperature at distal interphalangeal (DIP) and metacarpophalangeal (MCP) joints with IRT at baseline and for 10 min after cold challenge test. Intraclass correlation coefficient (ICC) was calculated for inter-rater reliability in IRT interpretation, then temperature variations at MCP and DIP joints and the distal-dorsal difference (DDD) were analysed. RESULTS: Fourteen PRP, 16 SRP, 14 AC and 15 controls entered the study. ICC showed excellent agreement (> 0.93) for DIPs and MCPs in 192 measures for each subject. Patients with PRP, SRP and acrocyanosis showed significantly slower recovery at MCPs (p < 0.05) and at DIPs (p < 0.001) than controls. At baseline, higher temperature at DIPs and lower at MCPs was observed in PRP compared with SRP with significantly lower DDD (p < 0.001). Differently from AC, both PRP and SRP showed gain of temperature at DIPs and less at MCPs after cold challenge. PRP but not SRP patients returned to DIPs basal temperature by the end of re-warming time. Analysis of DDD confirmed that controls and PRP, SRP and AC patients significantly differed in fingers recovery pattern (p < 0.05). CONCLUSION: IRT appears reliable and reproducible in identifying children with peripheral microvascular disturbances. Our results show that IRT examination pointed out that PRP, SRP and AC patients present significant differences in basal extremities temperature and in re-warming pattern after cold challenge therefore IRT can be suggested as an objective tool for diagnosis and monitoring of disease.

Extreme thrombocytosis in systemic juvenile idiopathic arthritis. A case report.

BACKGROUND: Systemic onset juvenile idiopathic arthritis (SoJIA) is a rare inflammatory disorder characterized by remitting fevers, evanescent rash, generalized lymphadenopathy, hepatomegaly/splenomegaly, and/or serositis. CASE PRESENTATION: Here we report the case of a 5 years-old girl with SoJIA complicated by severe thrombocytosis. Treatment with the Interleukin-1ß (IL-1ß) receptor antagonist Anakinra caused a fast reduction of blood platelets and of the associated systemic inflammatory response. Measurement of IL-1ß, IL-6 and Tpo plasma levels at different time points confirmed the etiopathogenetic role of IL-1ß in causing the thrombocytosis, while Tpo did not appear to be involved and this explains the excellent response to treatment with Anakinra. CONCLUSION: The excellent response to treatment with the IL-1ß receptor antagonist, suggests a key pathogenic role of IL-1ß in thrombocytosis as well as in the associated systemic symptoms of inflammation.

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.

Papillary thyroid cancer in thalassaemia.

Thyroid cancer is the most frequent endocrine neoplasm in the general population. Its incidence is 5-10/100,000 per year, with an annual death rate of 0.2-1.2/100,000 in men and 0.4-2.8/100,000 in women. In thalassaemia patients the frequency of this disease is unknown. In this paper we describe five cases of papillary thyroid cancer in thalassaemia patients followed at the Day Hospital for Thalassaemia and Haemoglobinopathies, in Ferrara, Italy. We consider the possible key role of iron as a carcinogenic agent and we also discuss the practical implications of our clinical observations.

Epidemiology of rotavirus-associated hospital admissions in the province of Ferrara, Italy.

OVERVIEW: Hospital discharge forms with specific codes for rotavirus gastroenteritis in children 0 to 14 years of age were reviewed in the period 2003-2005 in the province of Ferrara. RESULTS: A total of 4,238 children were admitted to the pediatric departments; 151 patients were diagnosed with rotavirus gastroenteritis. The average annual rate of hospitalization for rotavirus gastroenteritis was 1.54/1,000 children <14 years of age and 2.9/1,000 children <5 years of age. Most hospitalizations (72%) involved children aged <60 months. The average length of hospital stay was about 5 days. Considering the Emilia Romagna regional reimbursement codes referable to rotavirus disease, the estimated costs of our 151 cases range from 214,033 euros to 341,832 euros. CONCLUSIONS: The results of this study contribute to the awareness of rotavirus epidemiology in Italy and underline the potential impact of rotavirus vaccination in our province.

Exaggerated TSH response to TRH ("sub-biochemical" hypothyroidism) in prepubertal and adolescent thalassaemic patients with iron overload: prevalence and 20-year natural history.

The severity of thyroid dysfunction in patients with beta-thalassaemia major is variable in different series. An exaggerated thyrotropin response to thyrotropin-releasing-hormone (TRH) has been found in 1 out of 5 beta-thalassaemia major patients. Because it is not well known how many of these patients will develop overt or subclinical hypothyroidism, we reviewed retrospectively the thyroid status (thyroid hormones, TBG, TG basal and TSH peak after TRH test) of 24 children and adolescents with beta-thalassemia major (mean age 12.1+/-3.9 years) on periodic transfusion therapy, regularly followed in our Centre during the last 20 years. As controls we studied 30 normal subjects aged 13.4+/-2.5 years. In our group of 24 thalassaemics an exaggerated TSH response to TRH test was found in 8 (33.3%), 3 of whom developed subclinical or overt hypothyroidism from 3 to 11 years later. TSH peak values correlated directly with ferritin levels, ALT, and compliance index to chelation therapy. Our data suggest that an exaggerated TSH response to TRH test is frequent in beta-thalassemia major, and may evolve into subclinical or overt hypothyroidism as we found in 37.5% of our patients with sub-biochemical hypothyroidism.

Cardiomyopathy and pericardial effusion in a 7 year-old boy with beta-thalassaemia major, severe primary hypothyroidism and hypoparathyroidism due to iron overload.

The primary cause of cardiac dysfunction in thalassemia is believed to be myocardial iron overload. Besides iron, other factors may play a role in the impairment of myocardial contractility, including prolonged heart tissue hypoxia, pericardial involvement, arrhythmias, endocrine complications and vitamin D deficiency. We present the case of a 7 year-old boy with ?-thalassaemia major and cardiac dysfunction, pericardial effusion and associated endocrinopathies. His serum thyrotropin (TSH) level was increased, and total and free thyroxine (FT4) were low. In addition, biochemical results and serum PTH level were compatible with a diagnosis of hypoparathyroidism. Other laboratory findings were not consistent with rheumatic heart disease, viral myocarditis or autoimmune disease. The child was treated with digoxin, diuretics, oral calcium, vitamin D, L-thyroxine (25 microg daily, which was later gradually increased) and subcutaneous iron chelation therapy (45 mg/kg, six days/week). The patient was discharged from our Unit after 7 days and within 3 months he had appreciable myocardial improvement and disappearance of the pericardial effusion.

Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome.

The SLC12A3 gene encodes the thiazide-sensitive Na-Cl co-transporter (NCCT) expressed in the apical membrane of the distal convoluted tubule of the kidney. Inactivating mutations of this gene are responsible for Gitelman syndrome (GS), a disorder inherited as an autosomal recessive trait. We searched for SLC12A3 gene mutations in 21 Italian patients with the clinical and biochemical features of GS (hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and the absence of nephrocalcinosis). All coding regions with their intron-exon boundaries were analyzed using PCR and SSCP techniques followed by sequencing analysis. We identified 21 different mutations evenly distributed throughout the gene without any mutation hot-spot. Fifteen are novel variants, including 12 missense mutations, one deletion, one deletion-insertion and one splice site mutation: R158Q, T163M, W172R, G316V, G374V, G463E, A464T, S615W, V677M, R852S, R958G, C985Y, 2114-2120delACCAAGT, 2144-2158delGCCTTCTACTCGGATinsTG, and 531-2A>G.