Diagnostic relevance of IgE sensitization profiles to eight recombinant Phleum pratense molecules.

BACKGROUND: Grass pollen-related seasonal allergic rhinoconjunctivitis (SARg) is clinically heterogeneous in severity, comorbidities, and response to treatment. The component-resolved diagnostics disclosed also a high heterogeneity at molecular level. Our study aimed at analyzing the characteristics of the IgE sensitization to Phleum pratense molecules and investigating the diagnostic relevance of such molecules in childhood. METHODS: We examined 1120 children (age 4-18 years) with SARg. Standardized questionnaires on atopy were acquired through informatics platform (AllergyCARD™). Skin prick tests were performed with pollen extracts. Serum IgE to airborne allergens and eight P. pratense molecules (rPhl p 1, rPhl p 2, rPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11, rPhl p 12) were tested by ImmunoCAP FEIA. RESULTS: The analysis of IgE responses against eight P. pratense molecules showed 87 profiles. According to the number of molecules recognized by IgE, the more complex profiles were characterized by higher serum total IgE, higher grass-specific serum IgE, and higher number and degree of sensitization to pollens. The most frequent IgE sensitization profile was the monomolecular Phl p 1. Sensitization to Phl p 7 was a reliable biomarker of asthma, whereas Phl p 12 of oral allergy syndrome. Sensitization to Phl p 7 was associated with a higher severity of SARg, and complex profiles were associated with longer disease duration. CONCLUSIONS: In a large pediatric population, the complexity of IgE sensitization profiles against P. pratense molecules is related to high atopic features although useless for predicting the clinical severity. The detection of serum IgE to Phl p 1, Phl p 7, and Phl p 12 can be used as clinical biomarkers of SARg and comorbidities. Further studies in different areas are required to test the impact of different IgE molecular profiles on AIT response.

Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification.

BACKGROUND: Pollen-food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens. METHODS: We examined 1271 Italian children (age 4-18 years) with seasonal allergic rhinoconjunctivitis (SAR). Foods triggering PFS were acquired by questionnaire. Skin prick tests were performed with commercial pollen extracts. IgE to panallergens Phl p 12 (profilin), Bet v 1 (PR-10), and Pru p 3 (nsLTP) were tested by ImmunoCAP FEIA. An unsupervised hierarchical agglomerative clustering method was applied within PFS population. RESULTS: PFS was observed in 300/1271 children (24%). Cluster analysis identified five PFS endotypes linked to panallergen IgE sensitization: (i) cosensitization to ≥2 panallergens ('multi-panallergen PFS'); (ii-iv) sensitization to either profilin, or nsLTP, or PR-10 ('mono-panallergen PFS'); (v) no sensitization to panallergens ('no-panallergen PFS'). These endotypes showed peculiar characteristics: (i) 'multi-panallergen PFS': severe disease with frequent allergic comorbidities and multiple offending foods; (ii) 'profilin PFS': oral allergy syndrome (OAS) triggered by Cucurbitaceae; (iii) 'LTP PFS': living in Southern Italy, OAS triggered by hazelnut and peanut; (iv) 'PR-10 PFS': OAS triggered by Rosaceae; and (v) 'no-panallergen PFS': mild disease and OAS triggered by kiwifruit. CONCLUSIONS: In a Mediterranean country characterized by multiple pollen exposures, PFS is a complex and frequent complication of childhood SAR, with five distinct endotypes marked by peculiar profiles of IgE sensitization to panallergens. Prospective studies in cohorts of patients with PFS are now required to test whether this novel classification may be useful for diagnostic and therapeutic purposes in the clinical practice.

Lack of efficacy of topical furfuryl palmitate in pediatric atopic dermatitis: a randomized double-blind study.

INTRODUCTION: Atopic dermatitis is a common disease in children. It is usually treated with topical steroids and/or calcineurin inhibitors in association with emollients but topical antioxidants have been recently introduced as a therapeutic option for children. The aim of this study was to evaluate the efficacy and tolerability of furfuryl palmitate, a new antioxidant molecule, in a multicenter, randomized, double-blind, vehicle-controlled study. PATIENTS AND METHODS: Children with atopic dermatitis were randomized into 2 groups treated for 2 weeks. One group of children (n = 60) was treated with a basic emollient cream and the other (n = 57) was treated with the same cream enriched with furfuryl palmitate. RESULTS: In both groups, there was a significant reduction (P < .001) in atopic dermatitis-measured using the SCORAD index-after 14 days. The reduction in the per-protocol analysis was higher for the basic cream. Treatment success was defined as a reduction of 20% or more in the SCORAD index from baseline to day 14. Patients who used treatment not permitted by the protocol were also considered treatment failures. The intention-to-treat analysis showed 70% positive results for the basic treatment and 29% for the treatment containing furfuryl palmitate (P < .0001) with a number needed to treat of 2.4 (95% confidence interval, 1.6-4.6). The emollient cream without furfuryl palmitate was observed to be more efficacious by pediatricians and parents, and no differences were reported between the 2 products in terms of tolerability. CONCLUSIONS: Both products proved to be efficacious in treating atopic dermatitis in children, but the emollient cream not containing furfuryl palmitate showed better clinical efficacy.

Food allergy and infantile autism.

The etiopathogenesis of infantile autism is still unknown. Recently some authors have suggested that food peptides might be able to determine toxic effects at the level of the central nervous system by interacting with neurotransmitters. In fact a worsening of neurological symptoms has been reported in autistic patients after the consumption of milk and wheat. The aim of the present study has been to verify the efficacy of a cow's milk free diet (or other foods which gave a positive result after a skin test) in 36 autistic patients. We also looked for immunological signs of food allergy in autistic patients on a free choice diet. We noticed a marked improvement in the behavioural symptoms of patients after a period of 8 weeks on an elimination diet and we found high levels of IgA antigen specific antibodies for casein, lactalbumin and beta-lactoglobulin and IgG and IgM for casein. The levels of these antibodies were significantly higher than those of a control group which consisted of 20 healthy children. Our results lead us to hypothesise a relationship between food allergy and infantile autism as has already been suggested for other disturbances of the central nervous system.

The use of antileukotrienes in paediatrics.

Allergic diseases include a variety of different illnesses (rhinitis, conjunctivitis, asthma, urticaria, dermatitis) whose physiological and pathological basis is the release of chemical mediators such as histamine, PAF (platelet activating factor), metabolites of arachidonic acid and chemotactic factors from mastocytes, basophils and eosinophils. The numerous drugs used for allergy treatment now include the new pharmacological category of cysteinyl leukotriene antagonists. The cysteinyl leukotrienes (LTC4, LTD4 and LTE4) are chemical mediators of the inflammation involved in the pathogenesis of asthma, the biological effects of which are bronchial constriction and an increase in both mucus secretion and vascular permeability. Recent studies carried out above all on adult patients suggest that antileukotrienes can play an important part not only in the acute phase but also in controlling the chronic development of bronchial asthma. Antileukotrienes have also been successfully used by some authors to control atopic dermatitis and urticaria. Though further controlled testing will be required, these applications broaden the possible range of treatments for allergic disease in all its many aspects.

Clinical and therapeutic aspects of sinusitis in children with bronchial asthma.

Eighty children between 4 and 14 years of age suffering from bronchial asthma were investigated. Fifty-five of them showed clinical and radiological findings of sinusitis. Of these, 13 patients with purulent postnasal drip were treated with ampicillin, phenylephrine and triprolidine (therapy A) and for the other 42 ampicillin was replaced by beclomethasone (therapy B). Thirty-four of 55 children showed improvement in sinus X-rays; 20 children had a considerable decrease in the severity of asthma and many symptoms cleared up after the therapy for sinusitis (P less than 0.001). In conclusion, owing to the high prevalence of sinusitis in children with bronchial asthma, all asthmatic children should be investigated to check for a sinus disease.

[Reappearance of alopecia areata in a coeliac patient during an unintentional challenge with gluten]. / Ricomparsa di alopecia areata in una paziente celiaca durante un challenge involontario con glutine.

A patient with coeliac disease presenting alopecia areas as the only symptom is described. Alopecia disappeared completely after a few months of strict gluten free diet and reappeared after an unintentional prolonged introduction of gluten. After a severe gluten free diet, a new and persistent hair growth in the alopecia areas was observed. The possibility a direct relationship in some cases, between coeliac disease and alopecia areata is confirmed.

Association between insulin dependent diabetes mellitus and coeliac disease. A study on 175 diabetes patients.

BACKGROUND: The association between diabetes mellitus and coeliac disease has been known for many years. In a random group of 175 insulin dependent diabetes mellitus patients of varying ages the following tests have been carried out: serum antigliadin antibodies (AGA) of IgA and IgG class, antireticulin antibodies (ARA) and antiendomisyum antibodies (AEA), both of IgA class. MATERIALS AND METHODS: The patients, 85 males and 90 females, had ages ranging from 1 yr to 30 yrs (102 in paediatric age--mainly between 6 and 14 years--and 73 adults). Patients with pathological values for AEA and/or ARA underwent an intestinal biopsy. RESULTS: Out of 175 patients studied, 21 had pathological values for AEA with or without pathological values for ARA and AGA, and 2 patients had only pathological values for ARA. 23 patients (21 with pathological values for AEA with or without ARA and AGA, 2 only for ARA ) underwent intestinal biopsy, all patients with pathological values for AEA had villous atrophy. The prevalence of coeliac disease among IDDM patients was 8.8% (95% CI 3.3 to 14.3) for the children and 16.4% (95% CI 7.9 to 24.9) for the adults. In patients with mucous atrophy, ARA, AGA IgA and IgG were pathological in 85%, 71% and 61% respectively. Symptoms and insulin requirements in all patients affected by coeliac disease before and after one year on a gluten free diet were also evaluated. The patients had clinical features with prevalently one or only few atypical symptoms which disappeared on a gluten free diet. Insulin requirements after one year on a gluten free diet appeared unchanged in coeliac patients. CONCLUSIONS: The need to screen all diabetic patients for coeliac disease is underlined.

Partial idiopathic epilepsy: recovery after allergen-free diet.

The hypothesis that certain foods or allergens might bring about convulsions has been suggested repeatedly in the literature over the last century. Some clinical studies have highlighted an unusually high prevalence of allergic disorders in patients with epilepsy. This paper reports the consistent disappearance of partial idiopathic epilepsy symptoms in a nine-year-old patient as a result of diet free of cow's milk protein. This case appears to confirm the possible role of food allergy in certain types of epilepsy in patients of pediatric age.

[Paucity of interlobular bile ducts in twins and maternal abuse of psychopharmaceuticals during pregnancy]. / Paucità delle vie biliari interlobulari in due gemelli ed assunzione materna di psicofarmaci in gravidanza.

We report the case of twins with intrahepatic cholestasis in "paucity of interlobular bile ducts". Both the children presented an associated cardiac defect even if dissimilar and a transient tubulopathy. Despite the presence of these alterations we suppose that these cases can be included among the group of rare nonsyndromic paucity of interlobular bile ducts. The different extent of the pathology in the two patients suggest a toxic etiology which could have struck more severely the twin who were less protected by the utero-placental barrier. In the literature reports we found some cases of extrahepatic biliary atresia related with maternal amphetamine addiction, but no cases of intrahepatic atresia. As during pregnancy the mother had abused of a number of drugs and in particular of amphetamine, we suppose that the amphetamine addiction can account for the hepatic pathology.

[Osteomyelitis and arthritis caused by Streptococcus group B in a 40-day-old boy]. / Osteomielite ed artrite causate da streptococco di gruppo B in un bambino di 40 giorni di vita.

Group B streptococci (GBS) have gained much attention in recent years as a cause of serious infection in the newborn. Traditionally two clinical syndromes have been defined as "early onset", with fulminant septicemia, pneumonia and meningitis, and "late onset", with a mild meningitis. More recently some previously unrecognized clinical presentations of GBS disease have been documented. These include asymptomatic bacteremia, septic arthritis, osteomyelitis, ethmoiditis with orbital cellulitis, pneumoniae with empyema, conjunctivitis. The literature to date reports 30 instances of osteomyelitis due to GBS. This report describes a forty days infant with a group B streptococcal osteomyelitis of the proximal humerus. Has been also emphasized the increased frequency and the benign clinical course of streptococcal osteomyelitis in the neonate.

[Lyme disease in central Italy. Description of a case of a 3-year-old girl]. / La malattia di Lyme nell'Italia centrale. Descrizione di un caso in una bambina di 3 anni.

The Authors describe a case of Lyme disease in a 3 year old child who lives in the center of Italy, in the Rome area. In this report it has been underlined the presence of Lyme disease also in central Italy and the importance of early diagnosis and therapy in order to prevent severe complications.

Niikawa-Kuroki (Kabuki) syndrome in two siblings.

The Niikawa-Kuroki (Kabuki make-up) syndrome is a recognizable pattern of malformation consisting of mental retardation, dysmorphic cranio-facial features, bone and joint anomalies, postnatal growth deficiency and susceptibility to infections. Two male siblings, 8 and 5 years of age, displaying characteristic clinical and radiological manifestations of this syndrome as well as their father, who displays only some of the facial features, are presented.

Intradermal skin tests with Dermatophagoides pteronyssinus in asthmatic children: correlation with specific IgE and bronchial provocation tests.

The purpose of the present study was to compare the results of the skin tests, the specific IgE levels and bronchial provocation tests in a group of sensitive asthmatic children with a Dermatophagoides pteronyssinus extract standardized by the RAST inhibition method. Skin tests showed a positive 'end point' in twelve children of 0.5 U/ml antigen; in eleven 5 U/ml; seven of 50 U/ml; six of 500 U/ml. Specific IgE was present in thirty-three children (92%). A close relationship between positive skin tests and serum IgE levels was found. Bronchial provocation tests were positive in twenty-eight children (78%): eight children with both positive RAST and positive skin tests had negative bronchial provocation tests.

Association of HLA-DQ7 antigen with cow milk protein allergy in Italian children.

In this study we investigated the HLA association with cow milk allergy. Thirty-seven Italian children with cow milk allergy and 35 randomly selected age-matched healthy children as control group were included in the study. DNA typing was performed by restriction fragment length polymorphism (RFLP) technique. We show the first statistically significant positive association between the expression of the HLA-DQ7 antigen and cow milk allergy. Several immunological tests (skin prick test, RIA, radioallergosorbent test (RAST) and ELISA) were performed to evaluate the humoral immune responses of DQ7 positive and DQ7 negative allergic patients. Our results show that among the DQ7 positive patients the majority presented a high humoral response. Furthermore, the in vitro proliferative response of patients to the beta-lactoglobulin antigen was performed to evaluate their cell-mediated immune response. We observed that the number of the nonresponders was higher in the DQ7 positive patients when compared to the DQ7 negative patients. Our data indicate an association of HLA-DQ7 antigen with cow milk protein allergy and that the DQ7 positive patients had a prevalence of humoral rather than cellular responses.

[Blocking antibodies after specific hyposensitization therapy in asthmatic children (author's transl)]. / Valutazione degli anticorpi bloccanti in bambini asmatici trattati con terapia iposensibilizzante specifica.

The Maunsell-test for the evaluation in vivo of a rise in blocking antibodies after specific hyposensitization therapy was perfomed in 27 children with asthma and/or graminaceous rhinitis. The Authors have found a good correlation between blocking antibodies level and clinical improvement.

Allergy and childhood epilepsy: a close relationship?

OBJECTIVES: The possibility that certain foods or allergens may induce convulsions has already been reported in the literature. None of the relevant studies has, however, shown a close correlation between allergy and epilepsy, most reports being anecdotal and open to various causal hypotheses. The case-control study reported here was undertaken to test the hypothesis that epilepsy is linked to allergy. MATERIAL AND METHODS: Seventy-two epileptic children and a group of 202 controls in the same age bracket were investigated for allergy together with their immediate families. RESULTS: The study revealed significantly higher rates of eczema in the mothers and rhinitis in the siblings of the patients studied as well as generally higher incidence of allergic pathologies in both of these groups with respect to the relevant controls. A significantly higher incidence of allergy to cow's milk and asthma was also documented in the epileptic children with respect to the control group. Prick tests gave a significantly higher rate of positive results for cow's milk proteins in the cases examined with respect to the controls. The total serum IgE of a random sample of cases and controls showed no difference in mean values. CONCLUSION: The study appears to bear out the hypothesis of a higher incidence of allergy in the children with epilepsy and their immediate families than in the controls and their families.

Helicobacter pylori seropositivity in children with atopic dermatitis as sole manifestation of food allergy.

A positive association between Helicobacter pylori antibodies and food allergy presenting with gastrointestinal symptoms has recently been reported. A subset of a H. pylori strain possesses an antigen, CagA, as a virulence factor. Anti-H. pylori and anti-CagA IgG titre have been determined in children with atopic dermatitis (AD) as the sole clinical manifestation of food allergy. In this study, thirty patients with AD as the sole clinical manifestation of food allergy were examined (group A). For comparative purposes, 30 patients affected by food allergy with gastrointestinal symptoms (group B) and 30 affected by atopic asthma (group C) were studied. Anti-H. pylori and anti-CagA immunoglobulin G (IgG) were determined in all individuals by means of the enzyme-linked immunosorbent assay. The anti-H. pylori IgG titre was significantly higher in group A and group B vs. group C (p < 0.05); no significant difference was detected between group A and group B (p > 0.05). No significant difference in anti-CagA titre was found between the groups. These data demonstrate a positive association between H. pylori antibodies and AD as the sole manifestation of food allergy. Further investigations are needed to evaluate the cause-effect relationship between H. pylori seropositivity and AD.

Cyclic vomiting syndrome and food allergy/intolerance in seven children: a possible association.

UNLABELLED: Cyclic vomiting syndrome (CVS) is characterized by repeated unpredictable, explosive and unexplained bouts of vomiting. The episodes have a rapid onset, persist over a number of hours or days, and are separated by symptom-free intervals. Despite the recent interest in this disorder, its aetiology, pathogenesis and even its target organ remain unknown. The purpose of this study is to investigate the role played by food allergy in CVS. The report concerns eight children (five male, three female), mean age 8 years (3-13 years), suffering from CVS for 2 years at least. The diagnosis of CVS was based on characteristic history, normal physical examination and negative laboratory, radiographic, neurological and endoscopic studies. Despite the absence of clinical signs typical of food allergy, skin prick tests were positive in six of the eight patients (75%). Specific IgE were present in 4/8 (50%) of the patients. Skin tests and specific IgE were positive for cow's milk proteins, egg white and soya. IgE levels were higher than the mean + 2SD in 5/8 (63%) of the patients. A double blind placebo controlled food challenge (DBPCFC) was carried out on seven of the eight patients who displayed clinical improvement after an elimination diet for cow's milk (and other foodstuffs indicated by positive skin tests). The DBPCFC was positive in all seven children. Clinical follow-up revealed a state of well-being over the 6 months of observation. CONCLUSION: It appears reasonable to suggest that food allergy plays a role in cyclic vomiting syndrome.

Partial cryptogenetic epilepsy and food allergy/intolerance. A causal or a chance relationship? Reflections on three clinical cases.

The possibility that certain foods or allergens may induce convulsions has already been reported in the literature. None of these studies has, however, shown a close correlation between food allergy and epilepsy, most reports being anecdotal and open to various aetiological hypotheses. The present report concerns 3 children with cryptogenetic partial epilepsy, diagnosed by means of electroencephalography, with behavioural disorders (hyperactivity, sleep disorders and writing difficulties). In these patients, instead of using anticonvulsive agents, treatment was based upon a cows milk-free diet, working on the hypothesis that there could be a casual relationship between intolerance to this food item and the epileptic symptoms. An improvement was observed in the children's behaviour and moreover, the electroencephalographic anomalies disappeared. Upon double blind oral provocation tests, these patients did not present an immediate reaction, but only after a few days. starting the controlled diet again led, in all cases, to disappearance of the electroencephalogram. In conclusion, it would appear feasible to hypothesize the role of food intolerance in the onset of convulsive crises, even if limited to certain types of epilepsy such as the cryptogenetic partial form.