Paola Sabrina Buonuomo

Safety and Efficacy of Etanercept in a Cohort of Patients with Juvenile Idiopathic Arthritis Under 4 Years of Age

Objective. To evaluate safety, tolerability, and efficacy of etanercept in a cohort of patients with juvenile idiopathic arthritis (JIA) under 4 years of age. Methods. Data were collected at every visit during treatment with etanercept in 25 children who began treatment at a mean age of 3 years (range 18–48 months). Safety endpoints included the incidence of any adverse events. Efficacy endpoints included the American College of Rheumatology (ACR) Pediatric 30, 50, and 70 criteria for improvement. Results. Data from 25 patients with JIA treated with etanercept for a mean period of 23 months were analyzed. All patients received concomitant medications: 24 methotrexate, 3 cyclosporin A, and 10 corticosteroids. After the first 6 months of treatment, 15 (71.4%) patients achieved an ACR Pedi30 response and at the last observation 20 (80%) achieved ACR Pedi30. ACR Pedi50 and 70 responses were, respectively, 62% and 43% at 6 months and 72% and 64% at the last followup. Five patients (20%) discontinued etanercept for lack of efficacy. Two (8%) developed adverse events, both primary varicella zoster virus (VZV) infections (both not vaccinated). One was hospitalized because of a necrotizing fasciitis secondary to VZV infection. No cases of tuberculosis, opportunistic infections, or malignancies were reported. Conclusion. In our cohort of patients etanercept proved to be safe and efficacious in the majority of children. The response in toddlers was similar to that in older children. We observed only 1 case of severe infection that required hospitalization and stopped treatment temporarily.

Corneal arcus as first sign of familial hypercholesterolemia

Figure 2. Corneal arcus is separated from the limbus by a thin ring of clear cornea (named “lucid interval of Vogt”). A 4-year-old boy was referred for investigation after his parents noticed the presence of a grayish ring parallel to the limbus of both eyes. His past medical history was unremarkable. His father was affected by familial hypercholesterolemia, which was responsive to statin therapy. The ophthalmologic evaluation described a corneal arcus separated by a 1-mm lucid interval (Figures 1 and 2). Blood exams revealed marked low-density lipoprotein hypercholesterolemia (530 mg/dL), suggesting a diagnosis of familial hypercholesterolemia. Corneal arcus, also named “arcus lipoides” or “arcus corneae,” is a white discoloration of the peripheral cornea near the corneoscleral limbus. There is a thin clear section separating the arcus from the limbus known as the lucid interval of Vogt. Arcus deposits tend to start at 6 and 12 o’clock and fill in until becoming completely circumferential. It develops in association with hyperlipidemia as a result of lipid deposition in the deep corneal stroma and the limbal sclera. Its prevalence increases with age. Corneal arcus should be differentiated from other lipid metabolisms affecting the cornea, such as lecithin-cholesterol acyltransferase deficiency deficiency, “fish eye” disease, or Tangier disease. n

Analysis of readability and quality of web pages addressing both common and uncommon topics in pediatric surgery

INTRODUCTION The quality medical information on Internet is highly variable. The aim of this study is to determine if Web pages addressing four common pediatric surgical topics (CT) and four uncommon pediatric surgical topics (UT) differ significantly in terms of quality and/or characteristics. MATERIALS AND METHODS We performed an Internet search regarding four CT, addressing more frequent clinical conditions with an incidence≤1:1.500 children (inguinal hernia, varicocele, umbilical hernia, and phimosis) and four UT addressing less frequent clinical conditions with an incidence≥1:1.500 children (anorectal malformation, intestinal atresia, gastroschisis, and omphalocele), using a popular search engine (Google). We evaluated readability with the Flesch reading ease (FRE) and the Flesch-Kincaid grade (FKG) and quality of content using the site checker of the HON Code of Conduct (HON code) for each website. RESULTS In this study, 30/40 websites addressing CT versus 33/50 addressing UT responded to our criteria. No differences statistically significant in advertisements between the two groups were found (15 vs. 16%) (p>0.05). No differences were found in terms of time from last update, owner/author type, financial disclosure, accreditation, or advertising. CT had higher quality level according to the HON code (6.54±1.38 vs. 5.05±1.82) (p<0.05). Mean FRE was 47.38±14.27 versus 46.24±14.56, respectively, for CT and UT (p>0.05). The mean FKG was 8.1±1.9 for CT versus 8±1.9 for UT (p>0.05). CONCLUSIONS Websites devoted to pediatric surgical topics have higher readability and quality information for disease diagnosis and natural history. Otherwise, the quality of pediatric surgical information on the Internet is high for CT and UT. A high reading level is required to use these resources.

Growth hormone excess in children with neurofibromatosis type-1 and optic glioma

In children with neurofibromatosis type 1 (NF1) and optic pathways glioma (OPG), growth hormone (GH) excess has been rarely reported and mainly associated to central precocious puberty. The aim of our study is to evaluate the prevalence of GH excess, the association with central precocious puberty, the relation with tumor site and the evolution over time in a large cohort of children with NF1 and OPG. Sixty‐four NF1 children with OPG were evaluated. Patients with stature and/or height velocity >2 SD for age were studied for GH secretion. Seven out of 64 children (10.9%) with NF1 and optic pathways glioma showed GH excess, isolated in 5 cases and associated to central precocious puberty in 2. All the children with GH excess had a tumor involving the chiasma. Children with GH excess underwent medical treatment with lanreotide and a minimum clinical/biochemical follow up of 2 years is reported. The present study demonstrates that GH excess should be considered as a relative frequent endocrine manifestation in NF1 patients, similarly to central precocious puberty. Therefore, these patients should undergo frequent accurate auxologic evaluations. On the other hand, an increase in height velocity in children with NF1, even despite normal ophthalmological exams, can suggest the presence of OPG and therefore represents an indication to perform brain MRI.

Lipid profiles in a large cohort of Italian children with Down syndrome

OBJECTIVES Results of epidemiological studies of lipid profiles in individuals with Down Syndrome (DS) in different settings showed discordant results but laboratory norms for this population has been lacking. The aim of our study is to evaluate lipid profiles in a large population of Italian children with DS. METHODS Lipid profiles of 357 patients with diagnosis of DS were recorded. RESULTS Multiple linear regression was employed to estimate models for each lipid fraction as a function of sex and age in patients with DS. CONCLUSIONS The main contribution of this paper is to provide data about lipid profile on a large cohort of people with Down syndrome. Long-term surveillance will be crucial to establish if this specific lipid profile may translate into increased morbidity and mortality from cardiovascular diseases (CVD).

Incidental finding of severe hypertriglyceridemia in children. Role of multiple rare variants in genes affecting plasma triglyceride

BACKGROUND The incidental finding of severe hypertriglyceridemia (HyperTG) in a child may suggest the diagnosis of familial chylomicronemia syndrome (FCS), a recessive disorder of the intravascular hydrolysis of triglyceride (TG)-rich lipoproteins. FCS may be due to pathogenic variants in lipoprotein lipase (LPL), as well as in other proteins, such as apolipoprotein C-II and apolipoprotein A-V (activators of LPL), GPIHBP1 (the molecular platform required for LPL activity on endothelial surface) and LMF1 (a factor required for intracellular formation of active LPL). OBJECTIVE Molecular characterization of 5 subjects in whom HyperTG was an incidental finding during infancy/childhood. METHODS We performed the parallel sequencing of 20 plasma TG-related genes. RESULTS Three children with severe HyperTG were found to be compound heterozygous for rare pathogenic LPL variants (2 nonsense, 3 missense, and 1 splicing variant). Another child was found to be homozygous for a nonsense variant of APOA5, which was also found in homozygous state in his father with longstanding HyperTG. The fifth patient with a less severe HyperTG was found to be heterozygous for a frameshift variant in LIPC resulting in a truncated Hepatic Lipase. In addition, 1 of the patients with LPL deficiency and the patient with APOA-V deficiency were also heterozygous carriers of a pathogenic variant in LIPC and LPL gene, respectively, whereas the patient with LIPC variant was also a carrier of a rare APOB missense variant. CONCLUSIONS Targeted parallel sequencing of TG-related genes is recommended to define the molecular defect in children presenting with an incidental finding of HyperTG.

Borderline cognitive level in a family with Bazex-Dupré-Christol syndrome

Bazex‐Dupré‐Christol syndrome (BDCS) [OMIM 301845] is an X‐linked dominant disorder of the hair follicle characterized by multiple basal cell carcinomas, follicular atrophoderma, congenital hypotrichosis, and hypohidrosis. Additional features include multiple milia, trichoepitheliomas, and axillary hidradenitis suppurativa as well as a variety of other symptoms. Some patients with a diagnosis of BDCS have had poor school performance. But no other associated psychopathological disorders have been described in the literature. We describe the neuropsychological characteristics and the co‐occurring psychopathological disorders in an Italian family (brother and sister, and their mother) affected by BDCS. The BDCS phenotype in this family was characterized by hypotrichosis, atrophoderma follicularis, milia, and trichoepitheliomas. No basal cell carcinomas were documented. At neuropsychological assessment the three affected family members all had a borderline cognitive level. Other identified psychopathological disorders included attention deficit hyperactivity disorder, executive deficits, academic difficulties, deficits in lexical skills, and internalizing problems. The presence of cognitive impairment in the three family members affected by BDCS suggests that cognitive impairment may be associated with the syndrome. It may be useful to assess neuropsychological performance in patients with BDCS to identify possible associated neuropsychological disorders.

Question 2: Should steroids be used in the treatment of septic arthritis?

You are the paediatric registrar on duty when a 12-year-old boy is admitted to your ward with a strong suspicion of septic arthritis of the left knee. He plays soccer at competitive level; the boy and his parents are concerned about the long-term consequences for his playing. While you are waiting for the result of the white count of the synovial fluid to confirm the diagnosis and promptly start antibiotic therapy, you remember a recent discussion about the use of steroids in infectious disease, and so you decide to review the literature and analyse whether the use of steroids as an adjuvant therapy could improve the prognosis of your patient. ### Structured clinical question In children with septic arthritis (population) does steroid therapy in addition to antibiotic therapy (intervention) reduce the duration of symptoms and late sequelae (outcome) compared with the antibiotic treatment only (comparison)? Medline through PubMed and The Cochrane library from start until November 2013 were searched. Keywords used were septic arthritis and steroid, dexamethasone and glucocorticoid limited to humans. Two double-blind randomised placebo-controlled studies were found and included in this analysis (see table 1). Through bibliography analysis, two additional studies based …

Persistent neck pain in a girl: Klippel-Feil syndrome

A 4-year-old girl was referred for recurrent neck pain. On examination, she was noted to have a short neck with very limited range of motion and a low-set posterior hairline. Suspecting Klippel-Feil Syndrome (KFS), X-rays (figure 1A and B) and CT (figure 1C and D) with three-dimensional reconstruction (see online supplementary video 1) were performed and a complex malformation of the cervical spine and craniocervical junction was detected. …

Thricho-rhino-phalangeal syndrome and severe osteoporosis: A rare association or a feature? An effective therapeutic approach with biphosphonates

Trichorhinophalangeal syndrome (TRPS) is a rare, autosomal dominant malformation syndrome characterized by hair, craniofacial and skeletal abnormalities, skin laxity, deformation of phalanges and anomalies of pelvis, femurs, and tibias. Three subtypes have been described: TRPS I, caused by mutations in TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. We present the case of a 7‐year‐old boy, affected by TRPS with a severe osteoporosis and several spontaneous bone fractures, an association described only once in the literature, successfully treated with biphosphonates. Bone mineral density (BMD) at dual‐energy X‐ray Absorptiometry (DXA) was of 0.331 g/cm2 at lumbar spine with. He had four spontaneous femoral fractures in a year, and for this reason he was been operated for positioning intramedullary osteosynthesis and orthopedic supports. Due to the severity of the clinical and radiological pattern it was established, after approval of the Ethical Committee, to begin off‐label therapy with infusions of neridronate at a dose of 2 mg/kg IV every 3 months. The treatment was, in this patient, effective both in terms of clinical (absence of new fractures) and mineralomethric (+45% BMD ath the lumbar level). We therefore suggest that treatment with biphosponates can be taken in account as a possible therapeutic option in case of bone fragility in patients with TRPSI.