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.

Predictivity of clinical efficacy of sublingual immunotherapy (SLIT) based on sensitisation pattern to molecular allergens in children with allergic rhinoconjunctivitis.

BACKGROUND: The diagnostic and therapeutic approach to grass pollen allergy is now possible by detecting specific IgE (sIgE) to its allergenic components. AIM: To evaluate the correlation between the sensitisation to different molecular Phleum pratense (Phl p) allergens and clinical efficacy of SLIT. METHODS: The pilot study included 36 patients affected by allergic rhinoconjunctivitis, all treated with SLIT actively. We performed serum analysis of sIgE to Phl p 1, 2, 4, 5, 6, 7, 11 and 12. The Average Rhinoconjunctivitis Total Symptom Score (ARTSS) and the Average Combined Score (ACS) were evaluated before and after one year of immunotherapy. RESULTS: Three different groups of sensitisation were defined based on the range of IgE reactivity to Phleum pratense allergens at baseline: group I (sIgE reactive to 1-3 allergens); group II (sIgE reactive to 4-5 allergens); and group III (sIgE reactive to 6-8 allergens). At T0 ACS was 1.79±0.18 in group I; 1.81±0.23 in group II; and 1.95±0.34 in group III. At T1 ACS was 0.85±0.55 in group I; 1.01±0.31 in group II; and 1.44±0.39 in group III. At T1 there was a significant improvement of ARTSS and ACS for group I (p=0.001). CONCLUSIONS: Sublingual immunotherapy with a grass pollen is efficacious irrespective of the patients' baseline sensitisation to either single or multiple grass pollen molecular allergens. We found that patients with few sensitisations have a greater improvement in combined symptom and medication score. SLIT improves the clinical course of allergic patients although new sensitisations may appear.

The growth of Streptococcus mutans in different milks for infant feeding.

After birth various bacterial species, mainly streptococci, colonize the oral cavity and are frequently isolated from carious lesions in children. Previous studies suggest that an earlier colonization of a child's mouth by cariogenic organisms might be related to a higher risk of caries. The aim of this study is to assess the influence of different milks for infant feeding on the growth of Streptococcus mutans (SM) colonies. Three human milk samples from three different mothers and five infant formulas were tested. To prepare the bacterial inoculum, SM was grown in Brain Heart Infusion broth for 18 hours at 37°C in microaerophilic atmosphere. The growth of SM was determined immediately after the inoculation of milks (T0) and after 24 hours (T24) of incubation. After 24 hours of incubation (ΔT= CFUs/ml at T24 – CFUs/ml at T0) the bacterial growth changes were different among milks. Among the complementary milks tested, ΔT of formulas supplemented with Lactobacillus reuteri and with Bifidobacterium lactis was lower than those of non-supplemented formula. In conclusion, on the basis of the reduced SM growth in milks supplemented with probiotics, we may speculate that these formulas have a preventive effect on the development of caries in children.

Risk factors affecting quality of life in a group of Italian children with asthma.

The measure of Quality of Life (QoL) has become one of the most important criteria used to assess the impact of chronic illness, such as asthma, on the patient’s daily life, in adults and children alike. The objective of our open observational study was to measure the QoL and analyze several factors that potentially affect QoL, such as symptoms and functional respiratory parameters, in a cohort of children with asthma. One hundred and twenty-seven children with asthma, 6 to 14 years of age, living in the city of Rome, were enrolled as outpatients. They were subjected to Skin Prick Tests (SPT), underwent spirometry and filled out the Pediatric Asthma Quality of Life Questionnaire (PAQLQ). One hundred and eleven children were diagnosed with intermittent asthma, 12 (10%) with mild asthma, and four with moderate persistent asthma. Ninety-six children had a positive SPT. The mean total score of QoL, obtained from the questionnaire, was 5.4 (∓1.2 SD). Two QoL groups were created. Children with total QoL score <5.5 were included in the “Lower QoL” score group while children with total QoL score ≥ 5.5 were included in the “Higher QoL” score group. Children in the Higher group and their mothers had a higher mean age, suffered from fewer asthma exacerbations during the year preceding the study, and showed a higher mean value of forced expiratory volume (FEV1) compared to the children in the Lower category. Using Logistic regression we identified the main factors that may affect QoL as FEV1, symptoms in the previous year and mother’s age. QoL is correlated with the frequency of asthma exacerbations and FEV1 values. Furthermore, our research shows that a significant impairment of QoL may also occur in patients with normal lung function, pointing out the importance of evaluating QoL in all children with asthma.

Serum resistin levels in children with primary snoring.

Primary Snoring (PS) has been positioned at the milder end of the Sleep-Disordered Breathing severity continuum characterized by snoring and it is usually underestimated. PS is defined as snoring without apnea, frequent arousals, or gas exchange abnormalities and recent studies demonstrated that children with PS have increased blood pressure and reduced arterial distensibility. The association between adipokines and SDB has been recently investigated, though most of the studies were focused on OSAS where intermittent hypoxia characterizing the disease may lead to an inflammatory cascade and to the release of several adipokines, contributing to oxidative stress. Resistin, initially described s an adipokine increasing insulin resistance, has been recently identified as a novel important member of the cytokine family involved in the regulation of inflammation. The aim of our study was to investigate circulating resistin levels in normal weight children with PS. Sixty-five children of normal weight aged between 4 and 14 years of age were selected for habitual snoring. Children with positive polysomnography were excluded from the study. Serum resistin levels were detected in all children with PS. Thirty-three healthy non-snorer children with similar age, sex and BMI were selected as a control group. A significantly higher level of resistin was observed in patients with PS compared to the control group (4.67±1.91 ng/ml vs 3.98±1.58 ng/ml; p<0.01). Patients with inconclusive pulse oximetry showed significantly higher resistin levels than those with negative recordings recordings (5.29±1.91 ng/ml vs 4.20±1.93 ng/ml; p<0.008). Moreover, there was a significant increasing trend between sieric adipokine level and the frequency of snoring (p<0.006). Our results suggest that systemic inflammation and oxidative stress may also play a significant role in the pathophysiology of PS.

Improvement of a rapid screening test for chronic granulomatous disease.

Diagnosis of CGD is made by demonstrating absent or markedly reduced oxidase activity in stimulated neutrophils. The screening test proposed is based upon the naked eye evaluation of the reduction of NBT on a solid surface. It seems to be a useful tool for rapid and inexpensive detection of CGD patients, especially for large-scale screening purposes. The test was carried out on forty-five subjects: two males affected by CGD, three female carriers and forty healthy donors. The test confirmed the results obtained with flow cytometric and NBT assays.

Habitual snoring in children with previous allergic sensitization.

Previous studies have reported a high prevalence of allergy in children with Habitual Snoring (HS), but the relationship between allergy in the early years of life and the subsequent development of this Sleep Disordered Breathing (SDB) is yet to be elucidated. The purpose of the present study was to determine the role of early, under 36 months of age, allergic sensitization to food (with or without sensitization to airborne allergens) in determining the development of HS 8-10 years after. One hundred and forty-eight children (10-14 years, mean age 12 years) with a history of food allergy were selected. Under the age of 36 months, atopic status was assessed by skin prick test for a panel of airborne and food allergens. Questionnaires filled in by parents were used to collect information on children's snoring and associated symptoms. HS was defined as snoring three or more times per week. At 1-3 years of age 54 children were positive to food allergens alone, and 94 were positive also to airborne allergens. After 8-10 years of life, when patients were aged between 10 and 14 years, habitual snoring was reported in 37 children. Furthermore, among the 54 children under three years of age sensitized only to food, 8 became HS while of the 94 children sensitized to both food and inhalants allergens 29 developed HS. The difference between those two groups was statistically significant (p=0.04). We reported a significant risk of developing HS in children with early allergic sensitization. Specifically this risk was higher when food allergy was associated with inhalant allergy. The onset of upper airway inflammation due to allergic triggers in subjects under three years of age may be related to the subsequent development of SDB after 8-10 years.

The evaluation of adenoid hypertrophy and obstruction grading based on rhinomanometry after nasal decongestant test in children.

OBJECTIVES: Adenoid hypertrophy (AH) is a very common problem in children. Nasal Fiberoptic Endoscopy (NFE) represents the gold standard method to diagnose AH. Rhinomanometry represents a valid diagnostic support. The aim of our study was to analyze the grade of nasal obstruction caused by AH, in a group of children, with rhinomanometry standard and after ND test versus NFE. PATIENTS AND METHODS: Two hundred and eighty-four of 300 collaborative children, diagnosed as chronic oral breathers, were enrolled. All children underwent a complete physical examination, anterior active rhinomanometry and a second rhinomanometry after the administration of the nasal decongestant (ND) xylometazoline. All children were evaluated using Nasal Fiberoptic Endoscopy (NFE). RESULTS: At rhinomanometry nasal obstrucion was found of grade 1 in 102 (35.9%) children, of grade 2 in 41 (14.4%), of grade 3 in 52 (18.3%), of grade 4 in 37 (13%) and of grade 5 in 52 (18.3%). Those patients were tested also with rhinomanometry after ND: grade 1 in 108 (38%) children, grade 2 in 52 (18.3%), grade 3 in 56 (19.7%), grade 4 in 23 (8.1%) and grade 5 in 45 (15.8%). At NFE: 83 (29.2%) patients presented a grade 0, 73 (28.7%) a grade 1, 51 (17.9%), 34 (11.9%) a grade 3 and 43 (15.1%) a grade 4. Comparing the grade of nasal obstruction in NFE and in RM after ND we found a great correlation for grade 1 and grade 5 (respectively 84.3% and 79,1%, p < 0.001) and low correlation for the others grades of obstruction. When compared to NFE, rhinomanometry test after ND had 81.1% sensitivity and 84.3% specificity. Operating Characteristic (ROC) curves were derived using data related to rhinomanometry vs NFE, and to Rhinomanometry after ND vs NFE. CONCLUSIONS: Rhinomanometry after ND, compared to rmhinomanometry, is more specific and useful to evaluate nasal obstruction due to AH in children. RM after ND is a great tool to assess the severity of nasal obstruction. In fact, the minimum and maximum degrees of obstruction to the RM after ND correlate significantly (p < 0.01) with those of NFE.

Serum levels of IL-17 in patients with vernal keratoconjunctivitis: a preliminary report.

BACKGROUND AND AIM: Vernal Keratoconjunctivitis (VKC) is a chronic and often severe form of bilateral tarsal and/or bulbar conjunctivitis. The purpose of the present study is to measure the Interleukin-17 (IL-17) serum levels in children with VKC evaluating the role of the systemic inflammation in patients affected by VKC. PATIENTS AND METHODS: Fifteen patients were enrolled with VKC aged between 6 and 10 years of life. Serum were obtained from the peripheral blood samples collected from all the children included in the study to evaluate serum level of IL-17. RESULTS: Serum levels of IL-17 were significantly higher in patients with VKC than in healthy controls (10.3 ± 9.36 pg/ml vs. 3.3 ± 6.20 pg/ml respectively; p < 0.04). CONCLUSIONS: The presence of a significantly higher level of IL-17 in patients with VKC suggests a possible role of this cytokine in the pathogenesis of VKC. Further studies on larger samples of patients are warranted to confirm These findings in order to identify new possible therapeutic targets.

Efficacy of sublingual specific immunotherapy on allergic asthma and rhinitis in children's real life.

BACKGROUND: Sublingual-specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies. AIM: We performed a case-control study to evaluate the effect of SLIT in children with allergic asthma and rhinitis. PATIENTS AND METHODS: The study plan included 140 patients (age 6-14 yr, 43% girls and 57% boys) presenting allergic rhinitis and/or asthma, 70 treated with SLIT actively for three years and 70 controls never treated with specific immunotherapy (only symptomatic drugs). Rhinitis Symptom Score (RSS), Asthma Symptom Score (ASS) and Medication Score (MS) were evaluated at beginning and during the 3 years of immunotherapy. results: There was a significant improvement of RSS (mean ± SD) in the SLIT group: baseline 5.31 ± 2.01, third year 1.38 ± 1.06 (p < 0.0001 vs baseline). CONTROL GROUP: baseline 5.00 ± 1.08, third year 4.68 ± 1.152 (P » NS). ASS (mean ± SD) in the SLIT group: baseline 4.09 ± 2.21, third year 1.23 ± 1.4 (p < 0.0001 vs baseline). CONTROL GROUP: baseline 4.04 ± 2.46, third year 3.62 ± 2.26 (p » NS). MS (mean ± SD) in the SLIT group: baseline 3.30 ± 1.4, third year 0.88 ± 1.26 (p < 0.0001 vs baseline). CONTROL GROUP: baseline 3.19 ± 1.23, third year 3.39 ± 1.12 (p » NS). There are no statistically significant differences among monosensitized/polysensitized patients and at different age ranges. None of the patients included reported severe systemic reactions or anaphylaxis. CONCLUSIONS: During the treatment, the active group showed sustained reductions in mean asthma and rhinitis symptom scores when compared with controls to confirm the efficacy and safety of sublingual immunotherapy.

Vernal keratoconjunctivitis: atopy and autoimmunity.

BACKGROUND: Vernal Keratoconjunctivitis (VKC) is a rare chronic ocular inflammatory disease and it mainly affects boys in the first decade of life. Although it is a self-limiting disease, patients may present many phases characterized by an exacerbation of inflammatory symptoms with a consequent decline of the quality of life. PURPOSE: define the clinical and immunological profile of patients affected by VKC and investigate their familiar history of autoimmune disorders and their autoimmunity pattern. PATIENTS AND METHODS: 28 children were enrolled (20 males, 71%) aged between 4 and 14 years of life affected by VKC. Family history of allergic and immunological diseases was collected for each patient. In particular, it was asked whether some components of their families were affected by Hashimoto's thyroiditis, type I diabetes, psoriasis or rheumatoid arthritis and Systemic Lupus Erythematosus (SLE). All VKC children underwent a serological evaluation of anti-nuclear antibodies (ANA). RESULTS: A family history of immunological disorders was found in 46% of patients, 28% of Hashimoto's thyroiditis, 14% of type I diabetes, 14% of psoriasis, and 1 of Systemic Lupus Erythematosus. Furthermore, 35% of patients was ANA positive and they corresponded to patients with a higher ocular score and with the most important clinical symptoms. CONCLUSIONS: the detection of ANA positivity and of a familiar history of autoimmune disorders in a high percentage of children with VKC may help us to better understand the association of this ocular inflammatory disease with systemic autoimmune disorders and atopic condition.

Food allergy and the development of asthma symptoms.

Allergies are multifactorial diseases the onset of which depends also on genetic and environmental factors in early life. Thus, environmental factors can affect the immune response and modify lung development, thereby leading to asthma. The role of the factors used to date to predict asthma development is modest, and clinical criteria should always be considered in association with familiarity for atopy. The aim of this study is to evaluate the risk of asthma in a population with positive skin prick test (SPT) (which is a reliable marker of atopy) to food allergens, regardless of clinical manifestations in the early years of life. The cohort of children enrolled in our study who had a positive SPT to food in the first three years of life had a prevalence of asthma after 7-14 years, double that of the general pediatric population. This prevalence increased significantly in patients with SPT positivity for food and inhalant allergens. We identified a correlation between the sensitization profile in children under the age of 36 months and the development of asthma during a period of 7-14 years. This study confirms that early sensitization is an important risk factor for the development of asthma, particularly in association with sensitization to inhalants, and that the persistence of food sensitization in school-age children and adolescents is associated to more severe asthma.

Transient hypogammaglobulinemia of infancy: intravenous immunoglobulin as first line therapy.

IVIG (Intravenous immunoglobulin) have significantly improved the prognosis and the quality of life of immunodeficient patients and are routinely used as substitutive therapy. Transient hypogammaglobulinemia of infancy (THI) is a primary humoral immunodeficiency characterized by a transient IgG defect, but is not considered as a disease that justifies substitutive treatment and thus the use of IVIG as an alternative to antibiotic prophylaxis remains controversial also in symptomatic children. We treated 13 THI children severely symptomatic with IVIG (400mg/kg/every 3 weeks ) for a limited period (2 or 3 months) and followed them for 1 to 3 years. During the follow-up, the frequency of overall infections decreased approximately tenfold (from 0.39 to 0.047 infection/month per child) and no severe infections were reported. Although this study lacks untreated controls, the results suggest that the observed clinical improvement is correlated to IVIG therapy. Furthermore, our study suggests that the infused IVIG have no long-term effect on endogenous IgG production and do not lengthen the immunodeficiency condition since all children produced a normal amount of specific IgG in response to vaccination carried out 5 months after the end of infusions. In conclusion, our results suggest that IVIG may stop the vicious circle of infection-immunodeficiency and should be considered as a first line therapy in highly symptomatic THI children.

Risk factors for upper airway diseases.

Upper respiratory infection is the most common reason for seeking medical care for children. Recurrent viral respiratory infections and subsequent complications are a burden for children, their families and society. It has been estimated that at least 6 percent of children younger than 6 yr of age presents recurrent respiratory infections, as consequence of an increased exposure to infectious agents during the first years of life, when immune functions are still immature. Pediatricians must identify risk factors predisposing to upper respiratory tract infections and plan specific preventive strategies, ie avoidance of precocious day-care attendance and secondary smoke. Vaccination against influenza and pneumococcal diseases should always be recommended.

An infant with diaphragmatic eventration and respiratory distress.

The authors report a rare case of partial diaphragmatic eventration in a 4-month-old infant with recurrent wheezing and low serum IgA values. Because of persistent respiratory symptoms after therapy with inhaled short-acting beta2 agonists and inhaled nebulized corticosteroids, surgery was undertaken to correct the defect. Despite surgery, the clinical symptoms did not improve. Consequently, gatroesophagel reflux was considered and the diagnosis was confirmed with pH-metry, after which the infant was started on a protonic pump inhibitor therapy (PPI), achieving clinical improvement. Our experience suggests that in infants with congenital diaphragmatic eventration who present with respiratory distress gastro-oesophageal reflux should be suspected, and PPI therapy should be started before planning surgery.

Hyperimmunoglobulinaemia in Babinga Pygmies is present from infancy.

Pygmies, a population characterized by short stature, have high immunoglobulin (Ig) concentrations. In this study, we evaluated Ig levels in Cameroons Babinga Pygmies from infancy to adulthood and the effects of a national health program on these Ig levels. We found that IgG and IgM levels were outside the normal range for Italians of the same age and were comparable to those measured in Babinga Pygmies living in the same region by Siccardi in 1975. In conclusion, the hypergammaglobulinaemia of Babinga Pygmies is already present in infants and is not affected by sanitation improvements, suggesting that it could be partly genetically-determined.

The future of sublingual immunotherapy.

Sublingual immunotherapy (SLIT) is currently the most prescribed form of allergen immunotherapy in many European countries. Its use has been accepted in the international consensus publications, and recently also the scepticism of USA scientists is attenuated. Still, this treatment may be improved, and the possible developments consist of modification of the materials, use of adjuvants and use of recombinant allergens. Moreover, new applications of SLIT, such as food allergy, seem promising. Concerning materials, the future form of SLIT is likely to be represented by tablets, which were already tested for efficacy and safety with grass pollen extracts, and are likely to increase the convenience for the patient by the use of no-updosing schedule. Adjuvants fitting with the characteristics of SLIT seem to be CpG oligodeoxynucleotides (CpG), able to interact with the Toll-like receptor 9 (TLR9) whose activation induces a Th1-like pattern of cytokine release, combination of 1,25-dihydroxyvitamin D3 plus dexamethasone (VitD3-Dex), and Lactobacillus plantarum. The approach with recombinant allergens, named component-resolved diagnosis, offers the possibility to tailor immunotherapy, which was found to be effective in two randomized trials of subcutaneous SIT (16-17), while studies with SLIT are not yet available. Regarding food allergy, an important controlled study demonstrated that SLIT with hazelnut is able to increase patients tolerance over possible reactions from inadvertent assumption of the culprit food, and warrants for further trials with other foods.

Clinical evaluation and treatment of acute asthma exacerbations in children.

This update on treatment of asthma exacerbations in children is the result of an Italian Pediatric Society Task-force, made up of a panel of experts working in 2007-2008. The aim is to give clear indications on the use of the drugs most employed in children, grading the quality of evidence and the strength of recommendations. Suggestions on their limits due to unlicensed and off-label use are reported. The level of evidence and the strength of recommendations for different therapeutic approaches demonstrate that frequently the use of drugs in children is extrapolated from the experience in adults and that more studies are required to endorse the correct use of different drugs in asthmatic children.

Oral breathing and dental malocclusions.

AIM: Aim of the present study was to evaluate existing correlations between oral breathing and dental malocclusions. METHODS: The study was conducted on a paediatric group of 71 oral breathers selected at the Allergology and Paediatric Immunology Department of Umberto I General Hospital, University of Rome "La Sapienza" (Italy). The children were selected based on inclusion/exclusion criteria. Children aged 6 to 12 years with no history of craniofacial malformations or orthodontic treatment were included. The results were compared with a control group composed of 71 patient aged 6 to 12 years with nasal breathing. After their medical history was recorded, all patients underwent orthodontic/otolaryngological clinical examinations. The following diagnostic procedures were then performed: latero-lateral projection teleradiography, orthopantomogram, dental impressions, anterior rhinomanometry before and after administering a local vasoconstrictor, nocturnal home pulse oximetry (NHPO) recording, spirometry test, skin prick test, study cast evaluation and cephalometric analysis following Tweed's principles. The intraoral examination assessed: dental class type, overbite, overjet, midlines, crossbite, and presence of parafunctional oral habits such as atypical swallowing, labial incompetence, finger sucking and sucking of the inner lip. Evaluation of the study casts involved arch perimeter and transpalatal width assessment, and space analysis. RESULTS: The results showed a strong correlation between oral breathing and malocclusions, which manifests itself with both dentoskeletal and functional alterations, leading to a dysfunctional malocclusive pattern. CONCLUSION: According to the authors' results, dysfunctional malocclusive pattern makes it clear that the association between oral breathing and dental malocclusions represents a self-perpetuating vicious circle in which it is difficult to establish if the primary alteration is respiratory or maxillofacial. Regardless, the problem needs to be addressed and solved through the close interaction of the paediatrician, otorhinolaryngologist, allergologist and orthodontist.