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Haploinsufficiency of A20 (HA20) is an inflammatory disease caused by mutations in the

Background Cystic fibrosis (CF) is one of the most frequent genetic diseases and the median survival of these patients has improved in the last few decades, therefore it becomes necessary to evaluate the long-term complications as renal and cardiovascular risk factors. Aim of the study To evaluate the incidence, the manifestations of renal disease and the possible association with metabolic and endothelial dysfunction markers in the CF population. Materials and methods We performed a cross-sectional, observational study on 226 CF patients. Clinical and laboratory instrumental parameters (metabolic, inflammatory and endothelial dysfunction markers) were evaluated. Results We showed 65 patients with chronic kidney disease (CKD) and 158 patients with a reduced value of forced expiratory volume in 1 s (FEV1), of which 58 patients with a severe reduction of FEV1. Moreover 28 patients had undergone lung transplantation and them had a significant lower estimated Glomerular Filtration Rate (eGFR) with respect to the non-transplanted patients (p Conclusions Our study showed a high prevalence of CKD in CF patients. Moreover we showed an increase of endothelial dysfunction and metabolic indexes in patients with reduced renal function, as SUA, serum triglycerides and LDL, suggesting the need for an early and complete screening of the main metabolic indexes to reduce cardiovascular risk and progression of renal damage, in particular in patients with lung transplant.

Background Pleural effusion in systemic lupus erythematous (SLE) is a common symptom, and recent studies demonstrated that IL-6 has a pivotal role in its pathogenesis. Case presentation We report a case of a 15 years old Caucasian boy with a history of persistent pleural effusion without lung involvement or fever. Microbiological and neoplastic aetiologies were previously excluded. Based on the presence of pleuritis, malar rash, reduction of C3 and C4 levels and positivity of antinuclear antibody (ANA) and anti-double stranded DNA (dsDNA), the diagnosis of juvenile SLE (JSLE) was performed. Treatment with high dose of intravenous glucocorticoids and mycophenolate mofetil was started with partial improvement of pleural effusion. Based on this and on adults SLE cases with serositis previously reported, therapy with intravenous tocilizumab (800 mg every two weeks) was started with prompt recovery of pleural effusion. Conclusion To the best of our knowledge, this is the first case of JSLE pleuritis successfully treated with tocilizumab.

Familial Mediterranean fever (FMF) is characterized by self limited episodes of fever and polyserositis.1 MEFV gene en codes for a protein named Pyrin, which plays a pivotal role in the activation and secretion of IL-1.2 Daily colchicine is highly effective in preventing attacks in this disorder in a dose-related fashion.3 Many definitions of colchicine resistance are available in the literature. The European League Against Rheumatism (EULAR) guidelines defined resistance as one or more attacks per month in compliant patients who had been receiving the maxi mally tolerated dose for at least 6 months.4 A similar definition was confirmed by a recent consensus among experts.5 In the present national multicentric longitudinal study, we analyze the impact of colchicine treatment on disease activity and quality of life in real life in pediatric and adult patients with FMF.

A case of a 7-year-old girl finally diagnosed with Langerhans cell histiocytosis is presented. The differential diagnosis between Langerhans cell histiocytosis and chronic nonbacterial osteomyelitis is discussed.

Introduction: Acute pericarditis is an inflammatory condition causing the occurrence of pericardial effusion. In a third of patients, the disease is recurrent. First line treatment of idiopathic pericarditis consists in non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine; glucocorticoids represent the second line treatment in resistant or intolerant cases. A recent clinical trial has enlightened the effectiveness of anakinra in adults and paediatric patients with colchicine-resistant recurrent pericarditis. Objectives: To describe the clinical characteristics and response to treatment in a cohort of paediatric patients with recurrent pericarditis treated with IL inhibitors. Methods: paediatric patients with recurrent pericarditis followed at 19 Italian centers of paediatric rheumatology or cardiology and treated with IL1 inhibitors were included in the study. Demographic, clinical and response to treatment data were retrospectively collected. Results: 55 patients were included in the study. The mean age at onset of the first episode of pericarditis was 12.53 years. The mean number of relapses of pericarditis before the beginning of treatment with IL1 inhibitors was of 3.4 (range 1 -10). 53 out of 55 patients had previously received treatment with NSAIDS and 44 with colchicine. 44 patients received steroidal treatment: 2 of them displayed a steroidal-resistance and 39 steroidal-dependence with reoccurrence of the symptoms following any attempt to reduce or withdraw this treatment. Anakinra (mean dosage of 1.67 mg/kg/day) was used as first Il-1 inhibitor in 54 of the 55 patients, Canakinumab (150 mg every 4 weeks) in one. 53 out of 54 patients treated with anakinra displayed a complete clinical response to treatment within a mean of 2 days (range 1-7): NSAIDs, glucocorticoids and colchicine were withdraw in 25 out of 26, 31 out of 35 and 15 out of 32 patients respectively. 50 of 54 patients displayed a complete response; among these, three were switched to Canakinumab, 17 patients continued treatment at the same dosage while in 30 patients a reduction of treatment was attempted. 12 patients presented, during anakinra tapering, a disease flare, promptly resolved after an increasing of the dosage. The remaining 18 patients did not present any flare despite the reduction of the drug. Anakinra was withdrawn in 16 patients, with recurrence of the symptoms in 11. 5 patients were treated with Canakinumab: 1 as first anti-IL1 drug, 4 were switched from anakinra (two for poor compliance, one for side effects and one for incomplete control of the disease). 2 out of five patients had a complete control of the diseases, 2 patients discontinued the treatment because of inefficacy and 1 patient required low dose of glucocorticoids to control the disease. At last follow-up 34 patients were on anakinra, 7 on anakinra and colchicine, 2 on canakinumab, 1 on canakinumab plus colchicine and NSAIDs. In 9 patients all treatments were withdrawn for complete control of the disease. Conclusion: This study confirm the effectiveness of IL-1 blockade in paediatric patients with recurrent pericarditis. However most of the patients require prolonged treatment to maintain clinical remission. Moreover, in our cohort of patients the rate of response was higher for anakinra then for canakinumab, suggesting a possible role of IL1α in the pathogenesis of this condition.

Background. Cystic fibrosis (CF) is one of the most frequent genetic diseases. The discovery and implementation of new therapies prolonged the survival of CF patients in the last years. Evaluation of long-term complications could be useful to improve the outcome of these patients. Aim of the Study. To evaluate renal function, metabolic, nutritional, and inflammatory status in CF patients on cystic fibrosis transmembrane regulator (CFTR) modulators therapy as well as lung transplant recipients (LRs) and patients on conservative therapy (control group). Materials and Methods. We performed a prospective, longitudinal study on 69 CF patients. Clinical and laboratory parameters (metabolic and nutritional indices and inflammatory markers) were evaluated in all patients before starting CFTR therapy or transplant (T0) and after 3 years (T1). Results. We enrolled 69 CF patients (42 males). Patients were distributed into three groups. The average age was 35.01 ± 10.57 years for the control group (group 0), 32.47 ± 9.40 years for patients on CFTR modulators therapy (group 1), and 38.93 ± 7.14 years for LRs (group 2). At T1, we showed a significant difference among the three groups in terms of renal function indices: creatinine, eGFR, serum nitrogen as well as serum uric acid, sodium, and potassium ( p < 0.001 , p < 0.001 , p < 0.001 , p < 0.001 , p < 0.001 , and p < 0.001 , respectively), particularly in LRs patients. Significant differences were found in nutritional status parameters among the three groups: total protein, serum albumin, serum fibrinogen, serum transferrin, and white blood cell counts ( p < 0.001 , p = 0.037 , p = 0.04 , p = 0.003 , and p = 0.007 , respectively), particularly in LRs compared with other groups. Moreover, we found significant differences in metabolic profile (HbA1c, p = 0.026 ) and inflammatory status, with a significant difference in C-reactive protein values, neutrophil counts, and neutrophil-lymphocyte ratio (NLR) among the three groups ( p < 0.001 , p = 0.005 , and p = 0.026 , respectively). Conclusions. Our study showed a reduced renal function and poor nutritional status in LRs, along with worse metabolic control. Moreover, we showed a lower inflammatory status in patients on CFTR modulators therapy. Therefore, we suggest early and careful monitoring of renal function, metabolic, and nutritional parameters in CF patients, whether they are on conservative therapy, CFTR modulators therapy, and LRs patients.

Background: Recurrent pericarditis affects 15-30% of patients with acute pericarditis. The etiology is poorly understood, with about 80% being idiopathic. Several treatment options are available for recurrences, including NSAIDs, colchicine, glucocorticoids and IL-1 inhibitors (i.e. Anakinra). Standardized guidelines for the management of these patients are still lacking Objectives: To analyze clinical findings and treatment approach in a cohort of pediatric patients with recurrent pericarditis Methods: Patients with at least two episodes of idiopathic pericarditis, followed at two Pediatric Rheumatology centers between 2006 and 2018, were included Results: A total of 42 patients (18 males) were included. Mean age at disease onset was 11.8 years (range 4-17). Chest pain and fever were the presenting symptoms in all patients. In 47% pleural effusion was detected. Laboratory tests showed increased white blood cell count (mean 14.509/mm3), C-reactive protein (mean 18.01 mg/dl) and erythrocyte sedimentation rate (mean 39 mm/h) in all patients. The first episode was variably treated: 18/42 (43%) received NSAIDs alone, 5/42 (11.9%), colchicine alone or associated to NSAIDs and 3/42 patients (7%) received antibiotics alone. 16/42 (38%), not responsive to NSAIDs or colchicine, received glucocorticoides. Patients who received glucocorticoids at the first episode relapsed earlier (median time of 2.1 months range 10 days-5 months), than patients treated with NSAIDs (6.6 months range 10 days -24 months) or with colchicine (5 months range 10 days-5 months) (p Conclusion: Our study confirms the lack of a standardized treatment approach in patients with recurrent pericarditis. Patients treated with glucocorticoid at first episode relapse before than those treated with other drugs. Anakinra is an effective treatment; however, tapering/discontinuation of the drug lead to relapses in several cases. Further experience on larger population is needed to define the best treatment duration and approach to withdrawal of IL-1 inhibitor Disclosure of Interests: Camilla Celani: None declared, Silvia Federici: None declared, Anna Tulone: None declared, Brigitte Bader-Meunier: None declared, Virginia Messia: None declared, Manuela Pardeo: None declared, Claudia Bracaglia: None declared, Pierre Quartier Consultant for: AbbVie, Chugai-Roche, lilly, Novartis, Novimmune, Sanofi, and SOBI, Consultant for: AbbVie, Chugai-Roche, Lilly, Novartis, Novimmune, Sanofi, and SOBI, Speakers bureau: AbbVie, BMS, Chugai-Roche, Novartis, Pfizer, and SOBI, Speakers bureau: AbbVie, BMS, Chugai-Roche, Novartis, Pfizer, and SOBI, Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Antonella Insalaco: None declared

Background Hyperzincaemia and hypercalprotectinemia (HandH) syndrome has been described as a new rare entity characterized by recurrent infections, dermatological involvement, increased inflammatory markers, hepatosplenomegalia and anemia. Little is known about its heterogeneous presentation, pathophysiology and treatment. Objectives To describe three cases with HandH syndrome Methods Serum calprotectin (MRP8/14) was measured according to Buehlmann assay (ELISA) and plasmatic zinc by atomic absorption spectrometry Results Three patients were referred to our centre because an history characterized by recurrent episodes of skin rash, severe oral aphtosis and increased level of serum amyloid A (SAA). Patient 1 presented, since the age of ten years, with recurrent episodes of fever and rash; skin biopsy showed a picture consistent with a lymphocytic lichenoid vasculitis resembling erythema multiforme. Patient 2 presented at birth, with hemolitic anemia and thrombocytopenia. At the age of 5 she was admitted to another hospital due to EBV related hemophagocytic limphohystiocytosis (HLH). At the age of 8, she was first seen at our center because of a persistent desquamant erythematous rash with recurrent abdominal pain and recurrent arthritis. Intestinal biopsy showed small intestine inflammation (erosions in the digiunum). Patient 3 presented with recurrent episodes of fever, rash, two episodes of transient hip synovitis and muscoloskeletal pain. A bone scintigraphy was performed resulting normal. Patients 1 and 2 suffered from recurrent infections (pneumonia, otitis, skin abscesses). Immunological studies revealed in patient 2 a reduction of memory B cells and a reduced response to Toll like receptor 9 agonist. Of note, all the patients presented in their medical history at least one episode of vasculitis: patients 1 and 3 suffered from Schonlein-Henoch’s purpura at the age of 11 and 3 respectively and patient 2 had at the age of 2 years an undefined vasculitis (evaluated elsewhere). Laboratory tests showed in all patients elevated inflammatory markers, zinchemia and serum calprotectin (table) Conclusion We report three patients with high serum levels of calprotectinemia and zinch presenting with a clinical phenotype consistent with previously reported cases. The presence of vasculitis in all of the patients suggest that it may represent the first symptom of this condition. Vasculitis could lead to an increase of serum calprotectin already proposed as a marker of vascular impairment. Moreover, considering the immunological defect detected in one of our patient, we speculate that recurrent infections described in this syndrome may underline an immune-dysregulation process in which the role of zinc metabolism needs to be assessed Disclosure of Interests: Andrea Uva: None declared, Claudia Bracaglia: None declared, Silvia Federici: None declared, Camilla Celani: None declared, Manuela Pardeo: None declared, christoph kessel: None declared, Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Antonella Insalaco: None declared

Background: Acute pericarditis is an inflammatory condition causing the occurrence of pericardial effusion. In a third of patients, the disease is recurrent. Most of the cases are idiopathic or occur after a pericardial procedure. First line treatment of idiopathic pericarditis consists in NSAIDs and colchicine; glucocorticoids represent the second line treatment in resistant or intolerant cases. The use of different biologics and immunosoppressant has been reported, with variable responses. A recent clinical trial has enlightened the effectiveness of anakinra in patients with colchicine-resistant recurrent pericarditis. Objectives: To describe the clinical characteristics and response to treatment in a cohort of paediatric patients with recurrent pericarditis treated with IL inhibitors. Methods: Pediatric patients with recurrent pericarditis followed at 19 Italian centers of paediatric rheumatology or cardiology and treated with IL1 inhibitors were included in the study. Demographic, clinical and response to treatment data were retrospectively collected. Results: 55 patients were included in the study. The mean age at onset of the first episode of pericarditis was 12.53 years. The mean number of relapses of pericarditis before the beginning of treatment with IL1 inhibitors was of 3.4. 53 out of 55 patients had previously received treatment with NSAIDS and 44 colchicine. 44 patients received steroidal treatment: 2 of them displayed a steroidal-resistance and 39 steroidal-dependence with reoccurrence of the symptoms following any attempt to reduce or withdraw this treatment. Anakinra (mean dosage of 1.67 mg/kg/day) was used as first Il-1 inhibitor in 54 of the 55 patients, Canakinumab (150 mg every 4 weeks) in one. 53 out of 54 patients treated with anakinra displayed a complete clinical response to treatment within a mean of 2 days: NSAIDs, glucocorticoids and colchicine were withdraw in 25 out of 26, 31 out of 35 and 15 out of 32 patients respectively. 50 of 54 patients displayed a complete response; among these, three were switched to Canakinumab, 17 patients continued treatment at the same dosage while in 30 patients a reduction of treatment was attempted. 12 patients presented, during anakinra tapering, a disease flare, promptly resolved after an increasing of the dosage. The remaining 18 patients did not present any flare despite the reduction of the drug. Anakinra was withdrawn in 16 patients, with recurrence of the symptoms in 11 (9 restarted anakinra, 2 were treated with glucocorticoids and colchicine, with good response). 5 patients were treated with Canakinumab: 1 as first anti-IL1 drug, 4 were switched from anakinra (two for poor compliance, one for side effects and one for incomplete control of the disease). 2 out of five patients had a complete control of the diseases, 2 patients discontinued the treatment because of inefficacy and 1 patient required low dose of glucocorticoids to control the disease. At last follow-up 34 patients were on anakinra, 7 on anakinra and colchicine, 2 on canakinumab, 1 on canakinumab plus colchicine and NSAIDs. In 9 patients all treatments were withdrawn for complete control of the disease. Conclusion: This study confirm the effectiveness of IL-1 blockade in paediatric patients with recurrent pericarditis. However, most of the patients require prolonged treatment to maintain clinical remission. Moreover, in our cohort of patients the rate of response was higher for anakinra then for canakinumab, suggesting a possible role of IL1α in the pathogenesis of this condition. Disclosure of Interests: Roberta Caorsi Consultant for: Novartis, Eli Lilly, Antonella Insalaco: None declared, Chiara Longo: None declared, Giorgia Martini: None declared, Marco Cattalini: None declared, Rita Consolini: None declared, Giovanni Filocamo: None declared, Alessandro Rimini: None declared, Silvia Federici: None declared, Camilla Celani: None declared, Maria Cristina M

Background: Pyogenic sterile arthritis, pyoderma and acne (PAPA) syndrome is an autosomal dominant inflammatory disorder caused by mutations in the PSTPIP1 gene primarily affecting joints and skin. The E250K mutation cause the hyperzincaemia/hypercalprotectinemia syndrome termed PSTPIP1-associated-related proteinemia inflammatory (PAMI) syndrome in which a bone marrow involvement is reported Objectives: To describe the clinical presentation of 7 PAPA patients followed at a single pediatric rheumatology center Methods: For each patient clinical and laboratory data were collected from medical charts. PSTPIP1 was sequenced through Sanger Sequencing or targeted resequencing using a customized panel, and analyzed with the NextSeq® platform (Illumina) Results: We describe 7 patients from 4 unrelated families with the E250K mutation in a mother and 2 siblings, the A230T variant in a father and his son and the R405C and D266N respectively in the last 2 unrelated patients. Disease onset occurred within the 7th year of life in all patients. Patients 3 and 4 (table) presented since the 1st year of life recurrent episodes of fever without any cutaneous or articular symptoms. In both patients inflammatory markers were elevated during fever episodes, but persistently negative during wellbeing not requiring any therapy. The variants described in these patients were not previously reported. However their pathogenic role is supported by the detection of markedly high serum calprotectin levels (>10.000 microg/ml). The predominant feature of patients 1 and 2 was articular involvement with recurrent episodes of arthritis associated to acne. Patient 1 was initially treated with prednisone with good clinical response but relapse of arthritis at discontinuation followed by the development of a sterile muscle abscess. An anti-TNF drug was started in both patients with complete clinical response. Patient 5 reported severe acne and psoriasis, and recurrent episodes of sterile arthritis. She presented a persistent elevation of acute phase reactants with severe anemia and leukopenia not resolving after splenectomy. His son (pts 6) presented with recurrent episodes of sterile arthritis, hepato-splenomegaly, anemia and neutropenia. Zinc and calprotectin serum levels resulted respectively 728 micromol/l and 2600 microg/ml. IL-1 inhibition determined a complete normalization of inflammatory parameters with no effects on anemia and neutropenia. In patient 6 zinchemia decreased to almost normal value after 4 months of therapy. Patient 7 presented at the age of 4 years a sterile lymphnode abscess. She also presented with splenomegaly and neutropenia with persistent elevation of acute phase reactants. Anakinra was proposed but not administered for poor compliance Conclusion: The clinical picture of patients carrying PSTPIP1 mutation may be heterogeneous. In our cohort TNF-inhibitors were successfully used in PAPA patients preventing new arthritis episodes and resolving cutaneous manifestation where present. In 2 patients the clinical picture was mild not requiring continuous treatment. One PAMI patient had a good response to IL-1 inhibition, which however, had no effect on hematological manifestations Disclosure of Interests: : Silvia Federici: None declared, Camilla Celani: None declared, Virginia Messia: None declared, Giulia Marucci: None declared, christoph kessel: None declared, Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Antonella Insalaco: None declared

Little data is available on long-term renal impairment in survivors from childhood sarcoma. We investigated the prevalence of renal impairment and hypertension after very long-term follow-up in survivors who reached adulthood after treatment for childhood sarcoma.A cross-sectional single center study was performed. Outcomes included estimating glomerular filtration rate (eGFR), albuminuria, glycosuria, serum phosphate and magnesium, tubular reabsorption phosphate (TRP), chronic kidney disease (CKD) according to the "Kidney Disease: Improving Global Outcomes" (KDIGO) guidelines and blood pressure (BP).Out of 87 5-year sarcoma survivors, 30 adults (10F/20M, median age at diagnosis 9 years, median age at investigation 26 years, median follow-up 16 years, mean 19 years) were identified. Renal impairment was detected in four cases (13.3%); three of these fulfilled the criteria for CKD. Among the adult survivors, a subgroup of 15 cases (50%) had received ifosfamide without confounding factors such as a diagnosis of genito-urinary rhabdomyosarcoma or administration of other potentially nephrotoxic chemotherapy (platinum-based drugs or methotrexate); no renal dysfunction was detected in this subgroup. In the whole cohort of sarcoma survivors, hypertension was diagnosed in four cases (13.3%); BP was significantly correlated with body mass index [p .014].In our series of adult survivors treated for a diagnosis of sarcoma in their childhood, the prevalence of CKD was 10%. We found survivors treated with ifosfamide as the only nephrotoxic agent did not present glomerular or tubular toxicity at long term follow-up, but further studies including a larger number of cases are required to confirm it.

To investigate the role of some variables, including allergy and autoimmunity, in the pathogenesis of vernal keratoconjunctivitis (VKC). The VKC is a chronic and often severe form of bilateral keratoconjunctivitis. Usually, it begins during the first decade and disappears during the end of the second decade of life.26 patients with VKC were selected. The diagnosis was performed by the ophthalmologist through a score based on ocular signs and subjective symptoms before and after administration of 1% cyclosporine A (Cy) eyedrops. Each variable was graded: 0 = absent; 1 = mild; 2 = moderate; 3 = severe. Patients with a total score ≥7 were included in the study. Blood samples were collected at the initial time for the determination of autoimmunity by total IgE and antinuclear antibodies (ANA). A Skin Prick Test (SPT) was performed on each patient to common inhalants and food allergens.53.8% of the children resulted atopic. The most important allergens were house dust mites and grasses. 46.1% of the patients showed total IgE100 UI/ml and 30.8% had ANA positivity at the first determination. The photophobia occurred in 42.3% of children, most frequently with respect to other symptoms like secretion or tearing (30.8%), foreign body sensation (15.4%), itching and conjunctival hyperemia (11.5%).Fortunately all children improved their symptoms after Cy eyedrop therapy. Moreover, there was an elevated percentage (30.8%) of children with ANA positivity compared with the values in the general pediatric population. Despite the fact that it is a non-specific autoantibody, its high presence in a population of children with VKC may have an important role in clarifying etiopathogenesis and chronic inflammation.

The pathogenesis of rhinosinusitis (RS) is related to inflammation, caused by infections in the acute form of the disease but also by other agents in the chronic forms. Cytology allows to evaluate the defensive components, such as hair cells and muciparous cells, while the presence in the nasal mucosa of eosinophils, mast cells, bacteria and/or fungal hyphae, or spores indicates the nasal pathology. The anatomic and physiologic characteristics of the otorhinosinusal system account for the frequent concomitant involvement of the different components. The pivotal pathophysiologic sites are the ostiomeatal complex, the spheno-ethmoidal recess, and the Eustachian tube. The latter is the link with acute otitis media (AOM), which is the most common disease in infants and children and has major medical, social, and economic effects. Moreover, because of the strict relationship between upper and lower airways, nasal sinus disease may contribute to asthma and sinusitis may be considered as an independent factor associated with frequent severe asthma exacerbations. Concerning the role of allergy, the available data do not permit to attribute a central role to atopy in sinusitis and thus allergy testing should not be a routine procedure, while an allergologic evaluation may be indicated in children with OM, especially when they have concomitant rhinitis.

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.

OBJECTIVE: Allergic rhinitis (AR) is a disease with high and increasing prevalence. The management of AR includes allergen avoidance, anti-allergic drugs, and allergen specific immunotherapy (AIT), but only the latter works on the causes of allergy and, due to its mechanisms of action, modifies the natural history of the disease. Sublingual immunotherapy (SLIT) was proposed in the 1990s as an option to traditional, subcutaneous immunotherapy. MATERIAL AND METHODS: We reviewed all the available controlled trials on the efficacy and safety of SLIT. RESULTS AND CONCLUSION: Thus far, more than 60 trials, globally evaluated in 6 meta-analyses, showed that SLIT is an effective and safe treatment for AR. However, it must be noted that to expect clinical efficacy in the current practice SLIT has to be performed following the indications from controlled trials, that is, sufficiently high doses to be regularly administered for at least 3 consecutive years.

"Probiotics Usage in Childhood Helicobacter pylori Infection": chapter 51 of the volume "Probiotics,prebiotics,and synbiotics . Bioactive foods in health promotion" . Probiotics may represent a novel approach to the management of H. pylori infection. Although the majority of the studies in children have reported estimated odds ratios greater than 1.0, implying an estimated benefit for the addition of probiotics to triple H. pylori eradication therapy, only few reached statistical significance. Moreover, the very few trials performed in children on the effect of probiotics alone suggest only a temporary inhibition of H. pylori that disappears once the administration of the inhibiting factors is interrupted. Nonetheless, the majority of these studies were based on the relatively small samples, and therefore, they may lack the statistical power necessary to detect an important effect of the probiotics. Finally, in most studies, the effect of probiotic treatment on H. pylori infection in children has been estimated indirectly by 13C-UBT. Probiotic treatment seems to be able to reduce H. pylori therapy-associated side effects and indirectly may help to improve the eradication rate. However, its beneficial effects appear to be strain-specific. We conclude that standardized multicenter, placebo-controlled studies in larger series of children are needed to confirm benefits of probiotics in the management of H. pylori infection in children, including its effect on the severity of H. pylori gastritis. Additional work is necessary to determine the strain, dose and administration to be used. Long-term studies are also needed in children to prove whether the persistent-suppressive effect of probiotics on H. pylori and its associated gastritis could prevent diseases such as gastric cancer or peptic ulcer.

Background Vernal keratoconjunctivitis (VKC) is a chronic disease affecting conjunctiva even though the immunopathogenetic mechanisms underlying this inflammation are unclear. The aim of our study is to investigate serum levels of HMGB1 and circulating sRAGE in children affected by VKC before and after treatment with cyclosporine A (CsA) eye drops and in a group of healthy children. Methods Twenty-four children affected by VKC aged between 5 and 12 yrs of life were enrolled at the Department of Pediatrics, Division of Allergy and Immunology, ‘Sapienza’ University of Rome. Twenty-four healthy children without atopy, ocular, and systemic disease, cross-matched for sex and age to patients affected by VKC, represented the controls. All children affected by VKC were treated with CsA 1% eye drops for 4 wks, and blood samples were collected before and 2 wks after the end of treatment while the controls underwent to a single blood sample at the time of enrollment. Results Serum basal levels of HMGB1 and sRAGE were higher in children with VKC when compared with controls while, in patients affected by VKC, no difference was detected between atopic and non-atopic, and between ANA-positive and ANA-negative children. A significant reduction in serum HMGB1 and sRAGE levels was detected after the therapy while CsA serum levels were negative. Conclusions Our study gives a support to the definition of VKC as a systemic inflammation in which HMGB1 and its soluble receptors could play a role.

We describe the case of a 10-year-old girl with a history of severe persistent asthma and exercise-induced-asthma, controlled using an appropriate treatment with inhaled corticosteroid-long-acting beta-2 adrenergic agonists (ICS+LABA) and leukotriene receptor antagonists. She was healthy until the age of 8 years, when she presented two episodes of radiologically diagnosed pneumonia. After that, she began to present persistent cough, also nocturnal, stridor, dyspnea and respiratory distress and she was sent by pediatrician to our hospital. She performed a global spirometry which shows an obstructive and restrictive phenotype (FEV1: 75,3% and MEF50: 57,6%), without a significantly dilatation after inhaled salbutamol (400 mcg). She underwent to a systemic therapy with oral corticosteroid, with not benefit. She had no fever neither upper respiratory tract infections. We excluded gastro-esophageal reflux disease, cystic fibrosis, mycoplasma and chlamydia pneumonia. Cardiological examination was negative. During hospitalization, she spontaneously expectorated a thick fibrinous mucoid formation. A chest X-ray and a computed tomography (CT) scan showed atelectasis of both lung, widespread hyperlucency, and occlusion of the right main bronchus, compatible with a diagnosis of plastic bronchitis. Plastic bronchitis is a rare disease characterized by the formation of large gelatinous or rigid branching airway casts. The prevalence and etiology of plastic bronchitis are still unknown and the symptoms may also overlap with those of other diseases such as severe asthma, in the severe mucus plugging sometimes seen in allergic bronchopulmonary aspergillosis (ABPA) or in middle lobe syndrome. In the pathogenesis of the disease the inflammation is usually present and initiates cast formation. Treatment includes bronchodilators, inhaled and oral corticosteroids, mucolytics, airway clearance therapy and antibiotics. Other therapies can include inhaled heparin, urokinase, tissue plasminogen activator (TPA), dornase alfa and oral macrolide antibiotics as mucoregulatory therapy 2.

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.define the clinical and immunological profile of patients affected by VKC and investigate their familiar history of autoimmune disorders and their autoimmunity pattern.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).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.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.

Background Allergy represents a risk factor at the base of sleep-disordered breathing in pediatric age. Among allergic diseases, the atopy is characterized by a tendency to be “hyperallergic.” Sleep-disordered breathing is also known in orthodontics as correlated with the morphology of craniofacial complex. The aim of this study was to investigate the relation between atopy and sleep-disordered breathing (oral breathers with habitual snoring), comparing atopic children with sleep-disordered breathing (test group) with nonatopic ones with sleep-disordered breathing (control group), in the prevalence of dento-skeletal alterations and other risk factors that trigger sleep-disordered breathing, such as adenotonsillar hypertrophy, turbinate hypertrophy, obesity, and alteration of oxygen arterial saturation. Methods In a group of 110 subjects with sleep-disordered breathing (6 to 12 years old), we grouped the subjects into atopic (test group, 60 subjects) and nonatopic (control group, 50 subjects) children and compared the data on the following: skin allergic tests, rhinoscopy, rhinomanometry, night home pulsoxymetry, body mass index, and dento-facial alterations. Results Even if our results suggest that atopy is not a direct risk factor for sleep-disordered breathing, the importance of a physiologic nasal respiration in the pathogenesis of sleep-disordered breathing seems to be demonstrated in our study by the higher prevalence of hypertrophy in the adenotonsillar lymphatic tissue, odontostomatological alterations, alterations of the oxygen saturation to pulsoxymetry, and higher prevalence of obesity observed in our children with sleep-disordered breathing, in percentages higher than that of the general pediatric population previously observed in the literature. Conclusions The importance of a physiologic nasal respiration in the pathogenesis of sleep-disordered breathing is demonstrated in our study.

Nasal respiratory obstruction is a very common otolaryngologic problem, often caused by adenoid hypertrophy (AH). 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 diagnostic value of rhinomanometry after nasal decongestant (ND) test for the evaluation of adenoid hypertrophy in children.Seventy-one of 97 collaborative children, aged 6-12 years, affected by upper airways obstructive symptoms and diagnosed as 'chronic oral breathers' by a standardized questionnaire were included in the study. The first evaluation included a complete physical examination, anterior rhinoscopy and anterior active rhinomanometry. Patients with a positive rhinomanometry underwent a second rhinomanometry after the administration of the nasal decongestant (ND) xylometazoline. All children were evaluated using nasal fiberoptic endoscopy (NFE).At rhinomanometry a normal nasal airflow was found in 19 (26.8%) of children while nasal obstruction was underlined in 52 (73.2%). These patients were tested also with rhinomanometry after ND which confirmed the presence of nasal obstruction in 29 (55.7%) of patients. All patients included in the study underwent a NFE: 34 (47.8%) of them presented severe AH with an occlusion75% of the choanal opening (grade ≥ 3) and 37 (52.2%) presented no or a mild form of AH (grade3). When compared to NFE, rhinomanometry test after ND had 82.7% sensitivity and 82.6% specificity. Positive predictive value and negative predictive value were 85.7% and 79.2%, respectively. Two receiver operating characteristic (ROC) curves were derived using data related to rhinomanometry vs NFE, and to rhinomanometry after ND vs NFE.Rhinomanometry after ND, compared to rhinomanometry, is more specific and useful to evaluate nasal obstruction due to AH in children, and it may be helpful to avoid unnecessary surgical procedures in children with temporary nasal obstruction.

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 fortyeight 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 (36.5%) children were positive to food allergens alone, and 94 (63.5%) 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 (25%) children. Furthermore, among the 54 children under three years of age sensitized only to food, 8 (14.8%) became HS while of the 94 children sensitized to both food and inhalants allergens 29 (30.9%) 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.