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.

A hydrolysed rice-based formula is tolerated by children with cow's milk allergy: a multi-centre study.

BACKGROUND: Children allergic to cow's milk are fed a soy- or a hydrolysed cow's milk-based substitute. Neither can rule out a sensitization risk. Previous studies have shown that hydrolysed rice is tolerated by animals and children with multiple food hypersensitivities. OBJECTIVE: A prospective clinical assessment of tolerance to a rice-based hydrolysed formula was carried out in children allergic to cow's milk. Patients and methods One hundred children (42 girls and 58 boys, mean age 3.17+/-2.93 years, median 2.20, range 0.18-14.6 years) with a history of immediate reactions to cow's milk and confirmed at double-blind, placebo-controlled food challenge (DBPCFC) when not contraindicated were assessed for clinical tolerance to cow's milk proteins. Their allergy work-up included skin prick tests with whole milk, alpha-lactalbumin (ALA), beta-lactoglobulin (BLG) and total caseins, and specific IgE determinations using CAP technology were performed against whole milk, ALA, BLG and casein. Sensitization to rice and rice-based hydrolysed formula was similarly investigated. Patients' sera were evaluated at immunoblotting for specific IgE to cow's milk proteins, rice and rice-based hydrolysed formula. DBPCFC was carried out with increasing doses of a rice-based hydrolysed formula. RESULTS: All patients were sensitized to cow's milk and/or at least one cow's milk protein fraction. Eighty-seven out of 99 were positive to cow's milk and/or a cow's milk protein fraction at skin prick test. Positive (>0.35 kUA/L) specific IgE determinations were found for cow's milk and/or milk fractions (92/95), rice (21/91) and hydrolysed rice infant formula (4/91). At immunoblotting, sera from 96 children were positive to alpha-casein (n=54), beta-casein (n=38), ALA (n=57), BLG (n=37) and bovine serum albumin (n=61). Similarly, although patients' sera often contained specific IgE against rice proteins at CAP (21/91) and immunoblotting (70/96), only six very weakly positive responses were observed against rice-based hydrolysed formula. All DBPCFC with rice-based hydrolysed formula were negative. CONCLUSIONS: Rice-based hydrolysed formula is a possible alternative not only for children with multiple allergies, but also for children with cow's milk allergy.

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.

Cyclic vomiting syndrome: in vitro nitric oxide and interleukin-6 release by esophageal and gastric mucosa.

Cyclic vomiting syndrome is a disorder characterized by recurrent episodes of nausea and vomiting with complete resolution of symptoms between attacks. Nitric oxide plays a critical role in regulating several components of gastrointestinal mucosal defense and injury. Interleukin-6 has a wide variety of actions in the gastrointestinal apparatus. The purpose of this study was to evaluate the synthesis and release of nitric oxide and interleukin-6 by the esophageal and gastric mucosa in 10 children with cyclic vomiting syndrome, during symptom-free periods, and in 10 controls. The nitric oxide and interleukin-6 release by esophageal mucosa cells obtained from cyclic vomiting patients was quite similar to that in controls, but the release of nitric oxide from gastric mucosa cells of patients was significantly higher than that of controls. Conversely, no interleukin-6 was detectable in gastric mucosa cell supernatants in any of the patients. Further studies are needed to evaluate the relationship between factors triggering cyclic vomiting syndrome and the release of nitric oxide and interleukin-6 by gastric mucosa.

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.

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.

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.

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.

Value of antigliadin antibodies (AGA) in latent coeliac disease (CD).

BACKGROUND: The term latent coeliac disease (CD) is applied to patients who were previously shown to have a normal jejunal mucosa on a free diet. The aim of this study was to determine whether a high AGA value in the serum of patients with coeliac symptoms can also be regarded by itself, without typical mucosal atrophy, as a marker of latent CD, as some authors suggest in relatives of celiac patients. METHODS: We observed 31 patients with suspected CD and pathological values of serum IgA ang IgG AGA. In all we performed intestinal biopsy, assayed antiendomisium antibodies (AEA) in serum, AGA IgA, IgG, and IgM in duodenal jejunal fluid and in some of the lymphocytcs CD3+ gamma/delta+ in the lamina propria of the intestinal mucosa. RESULTS: In this study only pathological values of serum AGA without mucosa atrophy don't seem to be markers of latent CD, but an aspecific allergic response. CONCLUSIONS: As shown by other authors serum AEA, intestinal fluid AGA IgM and lamina propria lymphocytes CD3+ gamma/delta+ seem markers of latent CD.

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.

Fever: a novelty among the symptoms accompanying migraine attacks in children.

Our casistic of 1787 children with headache, is made up of 943 males (53%) and 844 females (47%) aged 3-14 years. 1724 had primary headache. To make a precise diagnosis of primary headache, all the children have been subjected to a rigorous anamnesis, physical and diagnostic examination (blood, urine test, head x-rays-scans, sight test with cat's eyes). Symptoms that frequently accompany headache are: phono-photophobia, (47%), pallor (43%) nausea (41%) vomit (31%) intolerance to movement (40%) and fever (9%). We especially focused on fever which presented together with migraine in 156 (9%) of the 1724 subjects examined. Headache is an important syndrome and frequent in early childhood. Actually the hypothesis used to explain the etiopathogenetic mechanism is based on a disregulation of the neurotransmitters like serotonin, catecholamine and the prostaglandins.

[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.

Positive association between Helicobacter pylori infection and food allergy in children.

BACKGROUND: In children Helicobacter pylori has been involved as a pathogenetic factor in gastritis and duodenal ulcer and as a cofactor in protein-losing enteropathy, chronic diarrhoea, short stature, and gastritis lymphoproliferative disease. A subset of an H. pylori strain possesses an antigen, CagA, as a virulence factor. In the present study we determined anti-H. pylori IgG and anti-CagA IgG titres in children with food allergy. METHODS: Ninety paediatric patients were studied: 30 with food allergy, 30 with atopic asthma, and 30 with inflammatory bowel disease. Anti-H. pylori IgG and anti-CagA IgG were determined in all children by means of a commercial enzyme immunoassay (ELISA). RESULTS: The anti-H. pylori IgG titre was significantly higher in allergic patients than in the other two groups. The anti-CagA IgG titre did not differ significantly between the patients. CONCLUSIONS: These findings show a positive association between H. pylori infection and food allergy in children. We hypothesize that virulence factors other than CagA may be involved in the pathogenesis of H. pylori infection in paediatric patients with food allergy.

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.

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.

[Risk factors associated with the phenomenon of long-term care in psychiatry. A case-control study conducted in the Servizio di Igiene Mentale of Cassentino (Arezzo)]. / Fattori di rischio associati al fenomeno della lungoassistenza in psichiatria. Uno studio caso-controllo condotto nel Servizio di Igiene Mentale del Casentino (Arezzo).

OBJECTIVE: This work has been carried out to identify any factor associated with the long-term treatment through the analysis of all the data concerning the sociodemographic, psychosocial, anamnestic and clinical variables existing before the disease. MATERIAL AND METHOD: The research, carried out by the Mental Health Service in Bibbiena (U.S.A. 21) is a retrospective "case-control" study using a sample of 140 patients (70 "cases" and 70 "controls") that had the first contact with the psychiatric service in the period 1973-1989. We have defined l'cases" those patients who have been treated by the Service on a continuing basis for at least 5 years without an interruption more than three months. The "controls" were patients selected at random from the same population of "cases", resident in the same districts (catchment area of Casentino), but treated for a period shorter than 5 years. "Cases" and "controls" were in pairs on the ground of sex, age (range +/-5 years) and year of admittance to the service. A doctor of the postgraduate school of psychiatry was aware of "case" or "control" state, collected all informations using a questionnaire filled in according to medical records, psychiatric admission registers and information received by the psychiatric service staff. RESULTS: The study suggests that significance risk factors for long-term patients are:--diagnosis of schizophrenia. --a history of past suicide attempts and assaultive behavior.