Juvenile idiopathic arthritis-associated uveitis in the era of biological therapy: how the disease changed in more than 20 years of observation in a tertiary referral center in Rome (Italy).

OBJECTIVES: To describe the ophthalmological characteristics in a Juvenile idiopathic arthritis (JIA) cohort and to evaluate how therapeutic advances have changed the course of the uveitis. METHODS: Analysis of a retrospective cohort study of consecutive JIA pediatric patients including JIA-associated uveitis (JIA-U) and comparison with a previous study in the same uveitis center assessed before the wide-spread of biological therapy. RESULTS: The total of 49 JIA patients were analyzed, of whom 18 JIA-U, compared with a JIA-U past cohort of 66 patients. Systemic corticosteroids were used significantly less in the current JIA-U group (p = 0.008) than in the past one. JIA-U present cohort was on therapy more frequently with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) than the past group (p = 0.039), mostly treated with methotrexate (93.3%). Furthermore, a larger use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) was described in the current JIA-U group (p = 0.005) also associated with csDMARDs (p = 0.003). Adalimumab was used more (72.7%) in the present JIA-U cohort compared to a larger treatment with infliximab (61.5%) in the past (p = 0.005). Higher number of uveitis recurrences was observed in the previous cohort compared to the current one (p = 0.005). Fewer complications were described in this study than in the previous: posterior synechiae (p = 0.007), cataract (p < 0.001), band keratopathy (p < 0.001), and elevated intraocular pressure (IOP) (p = 0.047). CONCLUSION: Current therapies reduced the uveitis recurrences and ocular complications including cataract due also to the lower use of corticosteroids. The new close collaboration with the pediatric rheumatologic center in the same University has contributed to the care improvement and decrease of uveitis complications.

Pediatric urticaria in the Emergency Department: epidemiological characteristics and predictive factors for its persistence in children.

Summary: Introduction. Acute urticaria (AU) in children is a common clinical manifestation responsible for admission to the emergency department (ED). We aimed to analyze the epidemiological characteristics of AU in children and to identify predictors of both severity and progression. Material and methods. We evaluated 314 children admitted to the ED with a diagnosis of AU. We analyzed information concerning its onset, duration, severity, possible triggering factors, and the persistence of symptoms after 1, 3, and 6 months. Results. The most common etiological factors were infections (43.9%); in up to 32.4% of cases, AU was considered as idiopathic. AU was significantly most common in males and pre-school children. At the 6-month follow-up, 9.5% of children presented a persistence of urticaria, mainly those with contact (44.4%) or idiopathic (30.4%) forms. Conclusions. The AU etiology identified by history in the ED may be a significant predictor of persistence after a first attack of AU.

New methods and tools to assess nutritive sucking in new-borns: effect of different feeding bottles on nutritive performance.

Nutritive sucking is a fundamental process assuring the primary infant nourishment in the first months of life. When feeding is impaired for pathological conditions, the growth of the infant may be delayed with a cascade effect on the overall development. While literature studied nutritive sucking development in infants with feeding problems, like in severe premature babies or with low weight at birth, few works assesses to what extent different feeding bottles may influence feeding performance of healthy new-borns. This work proposes a method for functional characterization of feeding bottles based on the most promising and reliable indices used to quantitatively assess feeding skills in clinical applications. Thirty healthy newborns have been fed with two different bottles instrumented with a device for feeding monitoring. Their impact on feeding performance is objectively assessed and discussed. The approach presented here, even if preliminary, paves the way to a new method for functional characterization of feeding bottles. Further studies may allow to confirm our analyses with a higher number of bottles and infants.

Idiopathic intracranial hypertension in a paediatric population: a retrospective observational study on epidemiology, symptoms and treatment.

Idiopathic intracranial hypertension (IIH) is a disorder of unknown origin, which is characterized by elevated intracranial pressure (ICP) without underlying etiological evidence of neurological disease. The purpose of the current study was to evaluate epidemiological features, clinical presentation, diagnostic findings and treatment of sixteen children (7 males and 9 females) with IIH. Medical records of the patients were obtained from the University Paediatric Hospital of Catania, Italy. Clinical features, investigations and treatment approaches were retrieved. The mean age of the sixteen children at onset of symptoms was 9 years (range: 4 to 16 years). Most of the patients were classified as pre-pubertal. Mean BMI was 28.9 kg/m2. In 93.75% of patients headache was the presenting clinical symptom; and in the same percentage papilledema was detected as the accompanied sign during diagnostic flow-chart. The mean lumbar puncture opening pressure (LPOP) was 350 mm H2O. Fifty percent of the cases had normal brain imaging, while 12.5% showed enlarged optic nerve diameter and one patient had an intraocular protrusion of the optic nerve on MRI. Two patients (12.5%) had venous sinus stenosis, and one case showed an abnormal spinal MRI. With regard to therapeutic approaches, 93.75% of the cases were successfully treated with Acetazolamide. None of the patients required surgical procedures, and all neuroimaging findings disappeared after receiving treatment. In the present study we investigated the association of IIH with venous sinus stenosis. We also found ocular ultrasound to be a useful non-invasive alternative method for determining papilledema in paediatric IIH, specifically in an emergency.

Headache, migraine and obesity: an overview on plausible links.

Headache can represent different disorders with different etiologies; including cardiac, cerebral, vascular, psychiatric, metabolic, neurologic diseases. Recent studies have highlighted that obesity is significantly associated with headache and disability in adults. This rule also applies to children. This review focuses on literature data studying any eventual relationship between headache, migraine and obesity [shown in Body Mass Index (BMI)] in children. Research data have highlighted that there is a relationship between headache physiopathology and central and peripheral mechanisms responsible for food assumption. In this regard, neurotransmitters such as serotonin, and peptides such as orexin and adipocytokines (adiponectin and leptin) seem to play a key role both in food assumption and in headache pathogenesis. These data further emphasize the potential association between headache and BMI. Therefore, those therapeutic strategies aiming to decrease BMI may represent a model of useful treatment to understand whether weight loss reduces the incidence and the severity of headache in obese children. In conclusion, considering the effects of obesity and weight loss on the natural history of headache, important changes are expected in therapeutic management of paediatric headaches.

Efficacy and safety of omalizumab in paediatric age: an update of literature data.

Immunoglobulin E (IgE) was discovered in 1966 and was found responsible for immune defense against helminths, type I hypersensitivity and allergic diseases. IgE mediates allergic responses by binding to Fc receptors (the high affinity Fc-epsilon receptor I and the low affinity Fc-epsilon receptor II or CD23) expressed on tissue mast cells and blood basophils. This binding leads to degranulation and release of pro-inflammatory mediators. Considering the pivotal role of IgE in allergic diseases, antibodies against IgE potentiate an array of new therapeutic strategies and in this regard omalizumab (rhuMAb-E25, Xolair) has been developed as a monoclonal biologic drug to block serum IgEs. Although the use of omalizumab has been studied vigorously in many adult populations with allergic diseases, there are few heterogenous studies on children. There are very few ongoing clinical trials with omalizumab exclusively on children, although some adult studies have concluded pediatric patients as a part of their studies. Nevertheless, in pediatric clinical trials omalizumab has been demonstrated to be effective and safe also in this age group. Herein, the authors present a systematic review of extensive literature data on the use of omalizumab in children and adolescents.

Parasympathetic nervous system involvement in food allergy: description of a paediatric case.

The latest research data emphasize the interaction between the nervous and the immune systems. It has been demonstrated that the central nervous system (CNS) can be involved secondarily due to blood brain barrier (BBB) disruption via pro-inflammatory cytokines released in allergy. More recently it was demonstrated that the parasympathetic nervous system (PNS) could also be equally involved in models of peripheral inflammation such as food allergy; although this last clinical presentation has rarely been described. Herein, the authors report the case of a five-year-old Caucasian female who was admitted to our Pediatric Acute and Emergency Operative Unit for cyclic vomiting. Her vomiting, which was preceded by objective torque vertigo, headache and weakness, had been recurring with constant frequency every two months since she was 3 years old. After a complex diagnostic flow-chart, it was found that this spectrum of neurologic symptoms was due to a food allergy syndrome, which postulates some etiopathogenic hypotheses to explain the relationship between the two mentioned diseases.

Congenital muscular dystrophy and epilepsy: a prospective case series of pediatric patients.

Congenital Muscular Dystrophies (CMDs) can be considered as a heterogeneous group of diseases characterized by marked weakness, generalized hypotonia and joint contractures. They are divided into pure and classical forms, without ocular and cerebral involvement, and complex forms, which are associated with cerebral abnormalities. Seizures have rarely been described in the pure forms while they seem to occur more frequently in complex forms. The aim of our study was to evaluate the incidence of seizure in CMD. Herein, the authors describe 16 cases of congenital muscular dystrophy (CMD) associated with different kinds of epileptic events, in order to study the pathogenic connection between the two clinical manifestations. In all described patients we reviewed the clinical, neurophysiologic, and neuroimaging data to determine any associations with epilepsy. The patients were divided into two groups: 14 cases with merosin positive CMD in one group and 2 patients with Walker Warburg syndrome (WWS) in the second group. In our study we found that in the first group, one benign myoclonic epilepsy (BME), one benign febrile convulsions had occurred. Also in one patient, the EEG revealed a moderately high voltage slow background with diffuse sharp waves reaching 300mV in amplitude with no clinical signs. In the merosin positive CMD patients, the presence of two different epileptic diseases, benign myoclonic epilepsy (BME) in one and febrile convulsion with tonic clinic seizures, may represent a new expression of merosine-positive congenital muscular disease (PCMD) in which the deficiency of an undiscovered muscular protein with a cerebral isoform may be the cause of epileptic events in this group of patients.

Neurogenic pulmonary edema and variations of hemodynamic volumetric parameters in children following head trauma.

BACKGROUND: Currently there is no clear evidence of how changes in hemodynamic parameters are involved in the onset of neurogenic pulmonary edema. Aim of the study has been to correlate the principal variations of the intracranial pressure and volumetric hemodynamic parameters with the variations of extravascular lung water following severe head trauma in children. METHODS: We studied 28 children, 16 males and 12 females, mean ± SD age 71±29 months (range 24-130 months), admitted for traumatic head injury with Glasgow Coma scale ≤8. All patients received volumetric hemodynamic, and intracranial pressure monitoring following initial resuscitation and every four hours thereafter or whenever a hemodynamic deterioration was suspected. All readings were divided in 2 groups: with intracranial pressure (ICP) >15 mmHg or ≤15 mmHg. RESULTS: During the cumulative in hospital stay a total 508 sets of measurements were done. In the group with ICP >15 mmHg vs. that with ICP ≤15 mmHg we observed increased Extravascular Lung Water Index (EVLWi) (11.05±2.28 vs. 6.96±0.87 P<0.0001) and pulmonary permeability (8.50±1.19 vs. 5.08±0.90, P<0.0001), and decreased systemic vascular resistances, (1,451±371 vs. 1,602±447 P<0.0001) cerebral perfusion (48.87±18.67 vs. 69.72±11.36 P<0.0001) and PaO2/FiO2 ratio (349±122 vs. 490±96 P<0.0001). There was a significant correlation between EVLWi and pulmonary permeability (R2=0.83, P<0.0001). Fluid overload and cardiac functional index did not change significantly. CONCLUSION: The increased EVLWi observed in children following severe head trauma seems mainly related with pulmonary vascular permeability which is significantly increased when ICP is >15 mmHg.

Pregnancy in a methylmalonic acidemia patient with kidney transplantation: a case report.

Presently pregnancy is no more exceptional in women with metabolic diseases. However, it still poses significant medical problems both before and after childbirth. The challenge is even greater if the mother has undergone organ transplantation, because of her metabolic disease. We report on a case of pregnancy in a patient 29-year-old with methylmalonic acidemia cblA type (OMIM 251100) who received a renal transplantation at the age of 17 for end-stage renal disease (ESRD) caused by her primary disease. During pregnancy neither metabolic crises nor renal function changes were observed in the mother, with the only exception of a mild increase of her systemic blood pressure. To the fetus pregnancy was uneventful and during the first 30 months after birth the baby's neuropsychomotor development was normal and there were no episodes of metabolic derangement. This is evidence that methylmalonicacidemia cblA, even when treated with renal transplantation for inherent ESRD, is no contraindication to pregnancy. It is even possible that a functioning transplanted kidney contributes to improve metabolic parameters.

Comparison of times of intervention during pediatric CPR maneuvers using ABC and CAB sequences: a randomized trial.

BACKGROUND: The proposed introduction of the CAB (circulation, airway, breathing) sequence for cardiopulmonary resuscitation has raised some perplexity within the pediatric community. We designed a randomized trial intended to verify if and how much timing of intervention in pediatric cardiopulmonary resuscitation is affected by the use of the CAB vs. the ABC (airway, breathing, circulation) sequence. PATIENTS AND METHODS: 340 volunteers, paired into 170 two-person teams, performed 2-rescuer healthcare provider BLS with both a CAB and ABC sequence. Their performances were audio-video recorded and times of intervention in the two scenarios, cardiac and respiratory arrest, were monitored. RESULTS: The CAB sequence compared to ABC prompts quicker recognition of respiratory (CAB vs. ABC=17.48 ± 2.19 vs. 19.17 ± 2.38s; p<0.05) or cardiac arrest (CAB vs. ABC=17.48 ± 2.19 vs. 41.67 ± 4.95; p<0.05) and faster start of ventilatory maneuvers (CAB vs. ABC=19.13 ± 1.47s vs. 22.66 ± 3.07; p<0.05) or chest compressions (CAB vs. ABC=19.27 ± 2.64 vs. 43.40 ± 5.036; p<0.05). CONCLUSIONS: Compared to ABC the CAB sequence prompts shorter time of intervention both in diagnosing respiratory or cardiac arrest and in starting ventilation or chest compression. However, this does not necessarily entail prompter resumption of spontaneous circulation and significant reduction of neurological sequelae, an issue that requires further studies.

Kidney transplantation in a girl with methylmalonic acidemia and end stage renal failure.

Methylmalonic acidemia (MMA) is an inborn error of organic acid metabolism that occurs in infancy with hypotonia, vomiting, dehydration, lethargy and failure to thrive and is biochemically characterized by metabolic ketoacidosis, hyperammonemia and sometimes hyperglycinemia. It results from deficiency of methylmalonyl-CoA mutase activity due to a defect in the mutase apoenzyme or to deficient function of one of the enzymes required for metabolism of its cofactor vitamin B12. Tubulointerstitial nephritis with progressive impairment of renal function is one of the most frequent long-term complications. We describe a case of a 17-year-old girl with methylmalonic acidemia unresponsive to vitamin B12 therapy. The clinical symptoms appeared at 4 months of life. She progressed into end stage renal disease and in January 1996 she started on hemodialytic treatment. In November 1996 we performed a kidney transplant. At present, urinary excretion of methylmalonic acid is normal and the renal function of the transplanted kidney is normal without any rejection episodes. We think that a kidney transplant could be a good therapeutic choice for the metabolic alterations in MMA with end stage renal disease. Indeed it would seem that the small methylmalonyl-CoA mutase activity present in the transplanted kidney could be sufficient to ensure normal metabolism of organic acids. Otherwise, the therapeutic goal can be achieved with a protein-restricted diet.

Peritoneal dialysis in an infant with type 1 diabetes and hyperosmolar coma.

Hyperosmolar coma which is characterized by severe hyperglycemia in absence of chetosis is very rare in pediatric age with only 11 cases reported in the literature. The outcome of the condition is usually poor with mental retardation being the most common event. Here a case of hyperosmolar coma is described in a female of three months of age who was treated with peritoneal dialysis 11 hours after admittance to hospital. This female patient has been receiving insulin from three months of age and today at the age of 10 years she leads a normal life despite being on insulin therapy. A very low level of C-peptide (<0.3 ng/ml) clearly confirms she is affected by Type 1 diabetes. To our knowledge this is the first case report of hyperosmolar coma in a neonate with Type 1 diabetes who survived this condition without late neurological consequences.

Bilateral mandibular cysts associated with cyclosporine use: a case report.

Cyclosporin A (CsA) is used in the treatment of patients undergoing renal transplantation. There are a number of side effects associated with its use. In particular, the gingival overgrowth represents the most important in the oral cavity. The authors present a case of bilateral mandibular cysts in an 8-year-old boy, treated with CsA after renal transplantation. The genesis of the mandibular cysts might be associated with the combined use of CsA and a calcium channel blocker post-transplantation. CsA-induced gingival overgrowth might contribute to cysts by two mechanisms: interference with control mechanisms that regulate the reabsorption of gingival stromal tissue, allowing progressive dental eruption, and an increase in the gingival connective tissue components. Gingival hypertrophy might mechanically obstruct the eruption of the developing tooth.

Red blood cell membrane lipid peroxidation and resistance to erythropoietin therapy in hemodialysis patients.

BACKGROUND: Chronic hemolysis, inadequate production of erythropoietin (EPO) or an impaired response of erythroid stem cells to EPO are the main factors of anemia in end-stage renal disease (ESRD) patients. Oxidative damage of red blood cell (RBC) membrane is a well-established cause of chronic hemolysis in hemodialysis (HD) patients. Administration of high-dose recombinant human EPO (rHuEPO) fails to correct anemia in 5 to 10% HD patients although all established factors of resistance to rHuEPO therapy have been previously ruled out or corrected. PATIENTS AND METHODS: We investigated the degree of RBC membrane oxidative damage in 9 HD patients who failed to respond to maximal rHuEPO administration (more than 200 UI/Kg weekly for 4 months consecutively, group A), compared to 10 patients who showed a good response to standard rHuEPO therapy (group B) and to 10 patients who needed no treatment (group C). RBC malondialdehyde (MDA) was assumed as the index of oxidative stress in erythrocyte membrane. RESULTS: No significant difference in erythrocyte MCV and MCHC, iron status, parathyroid function, aluminum and dialysis-related blood loss was observed between patients of group A, B and C. RBC MDA, reticulocyte count, plasma-free hemoglobin (fhb) and serum lactate dehydrogenase (LDH) were significantly higher while plasma haptoglobin was significantly lower in patients of group A compared to patients of groups B and C. Moreover, a significant inverse relationship was observed between RBC MDA and either plasma hemoglobin, RBC count and hematocrit when all patients were evaluated together. CONCLUSION: In conclusion, increased oxidative damage of RBC membrane is often detectable in HD patients who fail to respond to rHuEPO administration even in the absence of all established factors of resistance to EPO. Peripheral response to rHuEPO may be normal in these patients and persistent anemia may be related to enhanced hemolysis due to oxidative stress. Oxidative damage itself may therefore be considered a factor of resistance to EPO.