The authors describe two cases in which a wrong diagnosis of allergy has negatively affected the normal health behaviour of the children and their families.

Unfortunately, physical abuse in children is a frequent condition. Paediatricians need to be aware and to know what signs are more frequently associated with this condition. Bruising, bone fractures, burns, retinal haemorrhages, subdural haematomas are associated with the presence of physical abuse and they should be searched for in front of suspected history. This article describes the clinical signs mostly associated with physical abuse in children and describes what features make these clinical signs highly suggestive of physical abuse. The images and figures will help the reader to contextualize the text.

The aim of this study was to evaluate the interaction between gastrointestinal (GI) disorders, sleep problems, and challenging behaviors in children with a diagnosis of Autism Spectrum Disorder (ASD) and their effect on parental stress. The secondary objective was to assess the frequency and type of GI and feeding disorders in a sample of children with ASD through a multidisciplinary assessment and, finally, to investigate families' perceptions and satisfaction with the proposed multidisciplinary approach. All children underwent a comprehensive gastroenterological and neuropsychiatric evaluation supported by standardized questionnaires. Pediatric gastroenterologists, specifically trained in Applied Behavior Analysis (ABA), provided advice for parent-delivered behavioral intervention for food selectivity. Thirty-six children with an autism diagnosis (29 males, age 4.5 +/-2.2 years, mean +/- SD) were enrolled. A positive correlation between sleep problems and aggressive behavior was found, and this association was stronger in children experiencing more problematic mealtime behaviors (b = 0.788, p = 0.014). Sleep difficulties were associated with stereotyped behaviors and parent-perceived stress. Parents interviewed about the gastroenterology visit perceived this multidisciplinary approach as helpful in addressing food selectivity. This study shows that sleep and mealtime issues can have a synergistic negative impact on ASD symptoms. A multidisciplinary approach and an integrated assessment of GI, feeding problems, and sleep disorders could be helpful in diagnosing comorbidities and to provide targeted advice to parents.

An 8-year-old boy presenting with a long-standing cranial bumps was eventually diagnosed with bone fibrodysplasia. The clinical features of this condition and its possible association with McCune-Albright syndrome are discussed.

RASopathies and mTORopathies are groups of genetic syndromes associated with increased activation of the RAS-MAPK or the PI3K-AKT-mTOR pathway, resulting in altered cell proliferation during embryonic and postnatal development. The RAS-MAPK and the PI3K-AKT-mTOR pathways are connected to each other and play a crucial role in adaptive immunity. However, with the exception of Activated PI3K delta syndrome (APDS), immune function has not been deeply studied in these disorders. We collected clinical and immunophenotypic data of a cohort of patients with RASopathies and mTORopathies. Overall, we enrolled 47 patients (22 females, 25 males, age 2–40 years): 33 with neurofibromatosis type 1, 11 Noonan syndrome and 3 Bannayan-Riley-Ruvalcaba syndrome. 8 patients reported a history of invasive infections requiring hospitalization and intravenous antibiotic therapy. Only 3 patients reported a history of unusual, difficult-to-treat or deep-seated infection. Adenotonsillectomy was performed in 11 patients (24%). However, in most cases (83%) patients' parents did not perceive their child as more prone to infections than their peers. Lymphocyte subpopulations were analyzed in 37 of the 47 patients (16 female, 21 males, age 1–40 years). Among the studied lymphocyte subsets, the only consistent alteration regarded an increased percentage of immature B cells (recent bone marrow emigrants) in 34 out of 37 (91,9%) patients, and an increased percentage of double negative T cells in 9 patients. In conclusion, although borderline immune abnormalities were present in a significant proportion of subjects and adenotonsillectomy was performed more frequently than expected for the general population, no major immune disturbance was found in this cohort of patients.

Although the use of glucocorticoids (GC) is well established, the therapeutic response to these agents often shows important interindividual differences, in particular among young patients with inflammatory bowel diseases (IBD). Currently, GC resistance or dependence cannot be predicted by clinical or laboratory findings. The aim of this study was to investigate the association of gender and age with GC efficacy and with the expression of Glucocorticoid-Induced Leucine Zipper (GILZ). One hundred thirty patients (mean age at enrolment 12.6 years, 53 Crohn's disease, 70 males) were enrolled in this retrospective study. IBD patients with active disease despite prednisone at a daily dose of up to 2 mg/kg over a period of 4 weeks were defined as steroid resistant. Patients who initially responded but relapsed upon dose reduction were considered steroid-dependent. Total RNA was extracted from biopsies of 14 patients (9 males) and the levels of GILZ mRNA were evaluated by real-time PCR. Association between clinical response to prednisone and the considered demographic variables was evaluated using logistic regression models. After 4 weeks of treatment, 112 patients were responders to prednisone and 18 were resistant; at this time-point, resistant patients were older than responders (p=0.032). After 12 weeks, 42, 71 and 12 patients were sensitive, dependent and resistant respectively; at this time-point, females were more prone than males to develop prednisone dependence vs a good response (p=0.028) while age had no effect. Age was associated with response both at 4 and 12 weeks in the subgroups of females: resistant patients were older than sensitive ones at 4 weeks (p=0.02). Likewise, at 12 weeks of therapy, dependent patients resulted older than sensitive ones (p=0.05). No association of age with prednisone response was found in males. In a subgroup of 14 patients (5 females), GILZ mRNA expression in intestinal biopsies was higher in males (p=0.0031). Patients with unfavorable response (7) presented lower GILZ expression at disease onset in comparison to the responder group (p=0.017). Older females with IBD have a higher incidence of prednisone unfavorable response and reduced intestinal expression of the GC pharmacodynamic marker GILZ.

Although the effectiveness of probiotics has only been proven in specific conditions, their use in children is massively widespread because of their perception as harmless products. Recent evidence raises concerns about probiotics' safety, especially but not only in the paediatric population due to severe opportunistic infections after their use. This review aimed at summarising available case reports on invasive infections related to probiotics' use in children. For this purpose, we assessed three electronic databases to identify papers describing paediatric patients with documented probiotic-derived invasive infections, with no language restrictions. A total of 49 case reports from 1995 to June 2021 were identified. The infections were caused by Lactobacillus spp. (35%), Saccharomyces spp. (29%), Bifidobacterium spp. (31%), Bacillus clausii (4%), and Escherichia coli (2%). Most (80%) patients were younger than 2 years old and sepsis was the most observed condition (69.4%). All the patients except one had at least one condition facilitating the development of invasive infection, with prematurity (55%) and intravenous catheter use (51%) being the most frequent. Three (6%) children died. Given the large use of probiotics, further studies aiming at evaluating the real incidence of probiotic-associated systemic infections are warranted.

A 9-year-old boy was evaluated for a malformation of his right forearm present from birth (Figure 1). e Type 1 neurofibromatosis was confirmed by genetic testing.

A 12-year-old boy presented with a 1-year history of painful swelling of the left ankle. The pain was recurrent, exacerbated by mechanical loading, occasionally nocturnal, and responsive to nonsteroidal anti-inflammatory drugs. The patient was afebrile. Physical examination revealed a tender, nonfluctuating swelling of the left distal tibia, without flare or erythema; the range of motion was painfully limited. Inflammatory markers and complete blood count were normal. Tuberculin skin test resulted negative. Plain radiographs showed a longitudinal lytic lesion extending across the growth plate of the left distal tibial metaphysis, highly suggestive of Brodie abscess (Figure). Magnetic resonance images confirmed the finding. The patient underwent surgical curettage and received 10 days of intravenous oxacillin plus clindamycin followed by a 3-week course of oral amoxicillin-clavulanate. Methicillin-sensitive Staphylococcus aureus was isolated from the cultures. Histology confirmed the diagnosis of chronic osteomyelitis. Brodie abscess is a form of chronic pyogenic osteomyelitis consisting of a central suppuration area encapsulated by sclerotic tissue.1Van der Naald N. DPJ Smeeing Houwert R.M. Hietbrink F. Govaert G.A.M. van der Velde D. Brodie's abscess: a systematic review of reported cases.J Bone Jt Infect. 2019; 4: 33-39Crossref PubMed Scopus (17) Google Scholar,2Auh J.S. Binns H.J. Katz B.Z. Retrospective assessment of subacute or chronic osteomyelitis in children and young adults.Clin Pediatr (Phila). 2004; 43: 549-555Crossref PubMed Scopus (36) Google Scholar The most affected sites are the metaphysis of long bones, commonly the tibia and femur. In adolescents, a history of minor trauma without a fracture or open wound is typical. Brodie abscess is an insidious clinical diagnosis; it may present with localized tenderness, recurrent pain, or swelling of the affected site. Because the infection is well-circumscribed, inflammatory markers may be normal and systemic symptoms are usually lacking.1Van der Naald N. DPJ Smeeing Houwert R.M. Hietbrink F. Govaert G.A.M. van der Velde D. Brodie's abscess: a systematic review of reported cases.J Bone Jt Infect. 2019; 4: 33-39Crossref PubMed Scopus (17) Google Scholar, 2Auh J.S. Binns H.J. Katz B.Z. Retrospective assessment of subacute or chronic osteomyelitis in children and young adults.Clin Pediatr (Phila). 2004; 43: 549-555Crossref PubMed Scopus (36) Google Scholar, 3Foster C.E. Taylor M. Schallert E.K. Rosenfeld S. King K.Y. Brodie abscess in children: a 10-year single institution retrospective review.Pediatr Infect Dis J. 2019; 38: e32-e34Crossref PubMed Scopus (5) Google Scholar Instead, the radiologic appearance of Brodie abscess is so characteristic that diagnosis can be straightforward, ruling out other focal conditions.4Gould C.F. Ly J.Q. Lattin Jr., G.E. Beall D.P. Sutcliffe III, J.B. Bone tumor mimics: avoiding misdiagnosis.Curr Probl Diagn Radiol. 2007; 36: 124-141Crossref PubMed Scopus (68) Google Scholar,5Agrawal P. Sobti A. A Brodie's abscess of femoral neck mimicking osteoid osteoma: diagnostic approach and management strategy.Ethiop J Health Sci. 2016; 26: 81-84Crossref PubMed Google Scholar Plain radiographs typically show an area of bone destruction with regular margins and sinuous shape surrounded by sclerosis; in contrast, bone tumours rarely present with sinuous margins. Moreover, growth plate involvement secondary to abscess casting is highly suggestive of Brodie abscess, making the other diagnosis unlikely.1Van der Naald N. DPJ Smeeing Houwert R.M. Hietbrink F. Govaert G.A.M. van der Velde D. Brodie's abscess: a systematic review of reported cases.J Bone Jt Infect. 2019; 4: 33-39Crossref PubMed Scopus (17) Google Scholar,3Foster C.E. Taylor M. Schallert E.K. Rosenfeld S. King K.Y. Brodie abscess in children: a 10-year single institution retrospective review.Pediatr Infect Dis J. 2019; 38: e32-e34Crossref PubMed Scopus (5) Google Scholar,6Jennin F. Bousson V. Parlier C. Jomaah N. Khanine V. Laredo J.D. Bony sequestrum: a radiologic review.Skeletal Radiol. 2011; 40: 963-975Crossref PubMed Scopus (41) Google Scholar Surgical debridement is needed to eradicate chronic osteomyelitis, allowing drainage cultures and histologic examination. Empiric antibiotic treatment should be targeted against S. aureus, the most common pathogen found in Brodie abscess.1Van der Naald N. DPJ Smeeing Houwert R.M. Hietbrink F. Govaert G.A.M. van der Velde D. Brodie's abscess: a systematic review of reported cases.J Bone Jt Infect. 2019; 4: 33-39Crossref PubMed Scopus (17) Google Scholar

Congenital hyperinsulinism (CHI) is the most common cause of severe persistent hypoglycemia in infants with an estimated incidence of 1 in 50 000 live births.1 Treatment of CHI includes medical, surgical, or combined therapies: oral diazoxide is the first-line medication, often ineffective due to inactivating mutations in the genes encoding the ATP-sensitive potassium channel. Second-line agents include the use of parenterally administered somatostatin analogs such as octreotide. Newer options such as continuous subcutaneous octreotide infusion and long-acting somatostatin analogs may not be feasible and safe for the use during the first weeks of life; therefore, conventional therapy with multidose daily octreotide injections is often required with a considerable physical and emotional impact on the quality of life of newborns and their caregivers. Furthermore, parents are usually in constant fear of hypoglycemia, since irreversible brain damage and permanent developmental issues may result, with consequent constant monitoring of blood glucose.2 This report describes a diazoxide-unresponsive patient with a focal form of CHI due to a novel mutation in ABCC8 successfully treated with octreotide by a subcutaneous injection port and a continuous glucose monitoring system (CGMS) to simplify glycemic control.

Hereditary fructose intolerance is an autosomal recessive disorder of fructose metabolism caused by catalytic deficiency of aldolase B enzyme [1].