Somatic symptom disorder should be suspected in children with alleged chronic Lyme disease.

We report a case series of seven children admitted to a tertiary level pediatric ward for long-lasting physical symptoms with a previous diagnosis of chronic Lyme disease. In these children, medical history and clinical features were strongly suggestive of a psychopathological disorder, mainly a somatic symptom disorder. What is Known: • There is an increasing number of diagnoses of chronic Lyme disease both in North America and in Europe. Adults receive this diagnosis to explain chronic physical complaints often with negative history and serology. What is New: • Somatic symptom disorder should be suspected in children and adolescents with non-specific symptoms diagnosed with chronic Lyme disease.

Advantage of First-Line Therapeutic Drug Monitoring-Driven Use of Infliximab for Treating Acute Intestinal and Liver GVHD in Children: A Prospective, Single-Center Study.

The high serum concentrations of TNF-α characterize acute graft-versus-host disease (aGVHD), for which infliximab treatment may be beneficial. In 28 pediatric patients, four doses of 10 mg/kg infliximab every seven days were administered after steroid failure (Standard Group, n = 14) or as a first-line therapy (Early Group, n = 14). Population pharmacokinetic analyses and evaluation of serum cytokines were performed. After two months of treatment, complete response in gastrointestinal and liver aGVHD was achieved in 43% and 100% of patients in the Standard and Early groups, respectively. During follow-up, four patients in the Standard Group (but none in the Early Group) experienced an aGVHD recurrence. Viral infections occurred more frequently in the Standard Group after the fifth dose. Infliximab clearance did not differ between groups or according to treatment outcome for each organ involved in aGVHD, whereas serum levels of cytokines significantly differed. Therefore, present findings show that use of first-line, TDM-driven infliximab to treat aGVHD in children may result in better clinical outcomes and tolerability, with a different pattern of cytokines generated according to the moment of beginning of treatment.

Severe Lactic Acidosis Caused by Thiamine Deficiency in a Child with Relapsing Acute Lymphoblastic Leukemia: A Case Report.

Lactic acidosis is characterized by an excessive production of lactic acid or by its impaired clearance. Thiamine deficiency is an uncommon cause of lactic acidosis, especially in countries where malnutrition is rare. We describe the case of a 5-year-old boy who presented with a central nervous system relapse of acute lymphoblastic leukemia. During the chemotherapy regimen, the patient developed drug-induced pancreatitis with paralytic ileus requiring prolonged glucosaline solution infusion. In the following days, severe lactic acidosis (pH 7.0, lactates 253 mg/dL, HCO3- 8 mmol/L) was detected, associated with hypoglycemia (42 mg/dL) and laboratory signs of acute liver injury. Due to the persistent hypoglycemia, the dextrose infusion was gradually increased. Lactates, however, continued to raise, so continuous venovenous hemodiafiltration was started. While lactates initially decreased, 12 h after CVVHDF suspension, they started to raise again. Assuming that it could have been caused by mitochondrial dysfunction due to vitamin deficiency after prolonged fasting and feeding difficulties, parenteral nutrition and thiamine were administered, resulting in a progressive reduction in lactates, with the normalization of pH during the next few hours. In the presence of acute and progressive lactic acidosis in a long-term hospitalized patient, thiamine deficiency should be carefully considered and managed as early as possible.

Pediatric Adrenal Insufficiency: Challenges and Solutions.

Adrenal insufficiency is an insidious diagnosis that can be initially misdiagnosed as other life-threatening endocrine conditions, as well as sepsis, metabolic disorders, or cardiovascular disease. In newborns, cortisol deficiency causes delayed bile acid synthesis and transport maturation, determining prolonged cholestatic jaundice. Subclinical adrenal insufficiency is a particular challenge for a pediatric endocrinologist, representing the preclinical stage of acute adrenal insufficiency. Although often included in the extensive work-up of an unwell child, a single cortisol value is usually difficult to interpret; therefore, in most cases, a dynamic test is required for diagnosis to assess the hypothalamic-pituitary-adrenal axis. Stimulation tests using corticotropin analogs are recommended as first-line for diagnosis. All patients with adrenal insufficiency need long-term glucocorticoid replacement therapy, and oral hydrocortisone is the first-choice replacement treatment in pediatric. However, children that experience low cortisol concentrations and symptoms of cortisol insufficiency can take advantage using a modified release hydrocortisone formulation. The acute adrenal crisis is a life-threatening condition in all ages, treatment is effective if administered promptly, and it must not be delayed for any reason.

Carbohydrate Tolerance Threshold for Unannounced Snacks in Children and Adolescents With Type 1 Diabetes Using an Advanced Hybrid Closed-Loop System.

OBJECTIVE: To find a carbohydrate (CHO) tolerance threshold for unannounced snacks to avoid the 2 h increase in glycemia (difference between pre- and postmeal blood glucose [ΔBG]) ≥50 mg/dL in advanced hybrid closed-loop (a-HCL) users. RESEARCH DESIGN AND METHODS: Fourteen children and adolescents with type 1 diabetes (7 females; mean age [± SD] 14.5 ± 3.6 years), users of the Medtronic MiniMed 780G, participated in the study. For 12 days, they did not perform insulin bolus before breakfasts, with defined different quantities and types of CHO, with or without fats, performing blood glucose (BG) before and 2 h after the meal. RESULTS: A cutoff of 19.8 g of total CHO was found to determine a ΔBG of 50 mg/dL. BG never exceeded 250 mg/dL. Mean time in range was ≥70% in the 2 h following each snack. CONCLUSIONS: Unannounced snacks of up to 20 g of CHO can avoid ΔBG ≥50 mg/dL in MiniMed 780G users, although unannounced meals of up to 30 g of CHO are safe.

Population Pharmacokinetics of Intravenous Acyclovir in Oncologic Pediatric Patients.

Background: Acyclovir represents the first-line prophylaxis and therapy for herpes virus infections. However, its pharmacokinetics in children exposes them to the risk of ineffective or toxic concentrations. The study was aimed at investigating the population pharmacokinetics (POP/PK) of intravenous (IV) acyclovir in oncologic children. Methods: Patients (age, 8.6 ± 5.0 years, 73 males and 47 females) received IV acyclovir for prophylaxis (n = 94) and therapy (n = 26) under a therapeutic drug monitoring (i.e., minimum and maximal plasma concentrations, >0.5 and <25 mg/L, respectively). Plasma concentrations were fitted by nonlinear mixed effect modeling and a simulation of dosing regimens was performed. Findings were stratified according to an estimated glomerular filtration rate (eGFR) threshold of 250 ml/min/1.73 m2. Results: The final 1-compartment POP/PK model showed that eGFR had a significant effect on drug clearance, while allometric body weight influenced both clearance and volume of distribution. The population clearance (14.0 ± 5.5 L/h) was consistent across occasions. Simulation of standard 1-h IV infusion showed that a 10-mg/kg dose every 6 h achieved target concentrations in children with normal eGFR (i.e., ≤250 ml/min/1.73 m2). Increased eGFR values required higher doses that led to an augmented risk of toxic peak concentrations. On the contrary, simulated prolonged (i.e., 2 and 3-h) or continuous IV infusions at lower doses increased the probability of target attainment while reducing the risk of toxicities. Conclusion: Due to the variable pharmacokinetics of acyclovir, standard dosing regimens may not be effective in some patients. Prospective trials should confirm the therapeutic advantage of prolonged and continuous IV infusions.

WHO standards-based tools to measure service providers' and service users' views on the quality of hospital child care: development and validation in Italy.

OBJECTIVES: Evidence showed that, even in high-income countries, children and adolescents may not receive high quality of care (QOC). We describe the development and initial validation, in Italy, of two WHO standards-based questionnaires to conduct an assessment of QOC for children and young adolescents at inpatient level, based on the provider and user perspectives. DESIGN: Multiphase, mixed-methods study. SETTING, PARTICIPANTS AND METHODS: The two questionnaires were developed in four phases equally conducted for each tool. Phase 1 which included the prioritisation of the WHO Quality Measures according to predefined criteria and the development of the draft questionnaires. In phase 2 content face validation of the draft questionnaires was assessed among both experts and end-users. In phase 3 the optimised questionnaires were field tested to assess acceptability, perceived utility and comprehensiveness (N=163 end-users). In phase 4 intrarater reliability and internal consistency were evaluated (N=170 and N=301 end-users, respectively). RESULTS: The final questionnaires included 150 WHO Quality Measures. Observed face validity was excellent (kappa value of 1). The field test resulted in response rates of 98% and 76% for service users and health providers, respectively. Among respondents, 96.9% service users and 90.4% providers rated the questionnaires as useful, and 86.9% and 93.9%, respectively rated them as comprehensive. Intrarater reliability was good, with Cohen's kappa values exceeding 0.70. Cronbach alpha values ranged from 0.83 to 0.95, indicating excellent internal consistency. CONCLUSIONS: Study findings suggest these tools developed have good content and face validity, high acceptability and perceived utility, and good intrarater reliability and internal consistency, and therefore could be used in health facilities in Italy and similar contexts. Priority areas for future research include how tools measuring paediatric QOC can be more effectively used to help health professionals provide the best possible care.

Direct drug provocation test for the diagnosis of self-reported, mild and immediate drug hypersensitivity reaction in children and adolescents: our real-life experience.

BACKGROUND: Approximately 10% of the parents report suspected drug hypersensitivity reactions to at least one drug in their children, but most of these reactions are not confirmed after an adequate diagnostic work-up. The diagnosis of drugs hypersensitivity is frequently laborious and based on anamnesis, skin tests, serum specific IgE research and drug provocation test. Nevertheless, drug provocation test is necessary to confirm or definitively exclude the diagnosis of allergy. Aims of our study were to evaluate the real incidence of drug hypersensitivity in a large pediatric population and the validity of a short diagnostic algorithm. METHODS: One hundred nine patients with a history of self-reported, immediate and mild drug hypersensitivity reactions to ß-lactam antibiotics, macrolides and non-steroidal anti-inflammatory drugs underwent drug provocation test without prior skin or blood tests. After one-year, a telephone questionnaire was conducted in order to evaluate patient's use of the tested drug and any reactions. RESULTS: Only 7 of the 109 patients (6.4%) resulted positive to drug provocation test. No severe reactions were reported. After the challenge, 64 patients took the culprit drug again within one year and only two reported a drug reaction. CONCLUSIONS: Drug hypersensitivity is highly overestimated. Our results prompt the opportunity to directly perform the challenge for those children with self-reported, mild and immediate drug hypersensitivity reaction.

FPIES in exclusively breastfed infants: two case reports and review of the literature.

BACKGROUND: Food Protein-Induced Enterocolitis Syndrome (FPIES) is a non IgE-mediated food allergy that generally affects children in the first year of life. Usually symptoms break out when formula milk or solid foods are introduced for the first time but they might also appear in exclusively breastfed infants, since the trigger elements, especially cow's milk proteins, can be conveyed by maternal milk as well. FPIES in exclusively breastfed babies is a very rare clinical condition and only few cases have been reported in the medical literature. CASE PRESENTATION: We describe two cases of FPIES in exclusively breastfed babies. The first one is a two-month-old infant with a brief history of vomit and diarrhea that presented to the Emergency Department in septic-like conditions. The main laboratory finding was a significant increase in methemoglobin (13%). Clinically, we noted that, when breastfeeding was suspended, diarrhea drastically improved, and vice versa when maternal milk was reintroduced. An amino acid-based formula allowed a complete normalization of the symptoms. The second one is a three-month-old infant admitted for a 3 days history of persistent vomit and diarrhea. Blood tests showed a raised level of methemoglobin (7%). An esophagogastroduodenoscopy was performed and biopsies showed an eosinophilic infiltration of the duodenal mucosa. A maternal exclusion diet and an amino acid-based formula allowed a rapid regularization of the bowel function. CONCLUSIONS: We searched all the cases of FPIES in exclusively breastfed babies reported in the medical literature, identifying eight patients, with an average age of 3 months (range 15 days - 6 months). The majority of the cases were initially diagnosed as gastroenteritis or sepsis, five cases were characterized by an acute on chronic scenario and cow's milk was the most frequently involved food. Methemoglobin was never tested. An oral food challenge test was performed in two patients. FPIES in exclusively breastfed infants is a rare condition that, in the presence of compatible history and symptoms, should be considered also in exclusively breastfed babies. The evaluation of methemoglobin can simplify the diagnostic process.