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Background: In Europe amoxicillin plus clavulanic acid is the most commonly prescribed antibiotic and sodium benzoate is contained in the suspension formulation as a preservative. Objective: We studied the relevance of sodium benzoate as the culprit agent. In a group of children with a history of adverse reactions to amoxicillin plus clavulanic acid suspension. Study Design: A total of 89 children were enrolled over a period of 3 years (2006 - 2009). Single blind oral provocation tests (OPTs) with amoxicillin plus clavulanic acid, sodium benzoate and placebo were performed. 20 children with recurrent idiopathic urticaria were investigated as a control group. Results: according to personal history: 70% of reactions were late in developing while 23% of reactions were immediate and for 5% of the cases it was not possible to define the timing. 8 children (8/89=9%) resulted positive to the provocation tests with amoxicillin plus clavulanic acid; ten children (10/89=11%) had positive results with sodium benzoate; 3% had a double positivity (i.e. excipient and active drug). The timing of reactions significantly differs between the Amoxicillin plus clavulanic acid and sodium benzoate groups (p=0.002). Conclusion: Sodium benzoate probably acts through a non-immunologic mechanism and care should be given to children allergic to sodium benzoate containing pharmaceutical formulations.

Background Several cases of pine nut allergies and anaphylaxis have been reported in the literature, but only few pine nut allergens have been characterized. The aim of this research is to identify through immunoelectrophoretic techniques the major pine nut allergens in a group of children monosensitized to pine nuts. Methods We studied five children with pine nut allergies and no other sensitization to food except to pine nuts, confirmed by in vivo (prick test, prick-to-prick) and in vitro tests (specific IgE determinations [CAP-FEIA]). The protein profile of pine nuts was analyzed by Sodium Dodecyl sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE). Immunoblotting was performed after incubation of membranes with the sera from the children included in the present study. Results Immunoblotting (SDS-PAGE) demonstrated five similar bands between 6 and 47 kDa in all the subjects studied. Conclusion These bands should be considered the potential allergens for pine nut allergic children.

Background Peach allergy is regarded as one of the most important fresh fruit allergies. Data are available on the state-of-the-art diagnosis, including food challenges, and a component-resolved diagnosis. However, the roles played by different peach allergens with respect to symptom severity are not completely understood. Objective To evaluate the role of serum specific IgE to peach and recombinant allergens in the diagnosis of peach allergies in Italian children. Methods Forty-four children with peach allergy confirmed by a placebo-controlled food challenge were divided into 2 groups based on their symptom severity: patients with mild oral allergy syndrome (OAS) and patients with systemic symptoms (SS). The presence of specific IgE to peach and rPru p 1, rPru p 3, and rPru p 4 was determined. Results The presence of specific IgE to Pru p 4 and Pru p 1 was found significantly more frequently in patients with OAS, whereas specific IgE to Pru p 3 was not found significantly more frequently in patients with SS. Only anti-rPru p 4 IgE levels were significantly higher in patients with OAS, whereas no significant differences were found in anti-rPru p 1 and anti-rPru p 3 IgE levels between patients with OAS compared with patients with SS. Conclusion In Italian children with peach allergies, the presence of specific IgE to Pru p 3 is not associated with SS, and the levels of specific IgE to Pru p 3 do not correlate with the severity of the reactions.

SummaryInherited severe hypoplasminogenaemia is a multisystemic disorder leading to deficient extravascular fibrinolysis. As a clinical consequence wound healing capacity of mucous membranes is markedly impaired leading to ligneous conjunctivitis and several other manifestations. Here we report the molecular genetic and clinical findings on 23 new cases with severe hypoplasminogenaemia. Homozygous or compound-heterozygous mutations in the plasminogen (PLG) gene were found in 16 of 23 patients (70%), three of which were novel mutations reported here for the first time (C166Y, Y264S, IVS10–7T/G). Compared to 79 previously published cases, clinical manifestations of the current group of patients showed higher percentages of ligneous periodontitis, congenital hydrocephalus, and involvement of the female genital tract. In contrast, involvement of the gastrointestinal or urogenital tract was not observed in any of the cases. Patients originated to a large extent (61%) from Turkey and the Middle East, and showed a comparably frequent occurrence of consanguinity of affected families and a greater female to male ratio than was derived from previous reports in the literature. Individual treatment of ligneous conjunctivitis included topical plasminogen or heparin eye drops, topical or systemic fresh frozen plasma, and surgical removal of ligneous pseudomembranes, mostly with modest or transient efficacy. In conclusion, the present study underscores the broad range of clinical manifestations in PLG-deficient patients with a trend to regional differences. Transmission of genetic and clinical data to the recently established Plasminogen Deficiency Registry should help to determine the prevalence of the disease and to develop more efficient treatment strategies.

Uveitis treatment involves topical corticosteroids along with cycloplegic-mydriatics. Particularly severe cases may require systemic corticosteroids and immunosuppressive drugs. Vernal keratoconjunctivitis (VKC) treatment consists of a brief period of topical corticosteroids and/or cyclosporine. In patients refractory to traditional treatment, the use of 0.1% topical ophtalmic FK- 506 (tacrolimus) ointment has been occasionally reported. This is the first report of the coexistence of uveitis and VKC. The documented response to topical tacrolimus eyedrop of uveitis and VKC is also of interest, in particular since to our knowledge there are no published reports on its clinical use in uveitis.

Background: Little is known about the cause of food-induced anaphylaxis in children or about the factors that might affect its clinical severity. Objective: The aim of this study was to investigate the cause of food-induced anaphylaxis in children in Italy and to identify factors that could influence the appearance of symptoms and the severity of anaphylaxis. Methods: One hundred and sixty-three children with anaphylaxis consecutively attending 29 outpatient allergy clinics throughout Italy were enrolled in this prospective study. Information about past anaphylaxis episodes was collected with a standardized questionnaire. Food sensitization was evaluated by skin-prick test. Results: A clinical history of asthma increased the risk of wheezing [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.1-4.5] and respiratory arrest (OR 6.9; 95% CI 1.4-34.2). A clinical history of chronic/relapsing gastrointestinal symptoms increased the risk of vomiting (OR 2.1; 95% CI 0.9-4.3), hypotension (OR 7.9; 95% CI 1.9-32.0), and bradycardia/cardiac arrest (OR 9.2; 95% CI 0.9-91.3). The severity of present and previous episodes was similar only in patients with mild or moderate anaphylaxis. Peanut and egg were the most frequent causes of severe anaphylaxis. Conclusions: A clinical history of asthma and chronic/relapsing gastrointestinal symptoms (probably linked to food allergy) may predict the development of respiratory and gastrointestinal symptoms and the severity of anaphylaxis. © 2011 John Wiley & Sons A/S.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by severe vomiting, diarrhea, and often failure to thrive in infants. Symptoms typically resolve after the triggering food-derived protein is removed from the diet and recur within few hours after the re-exposure to the causal protein. The diagnosis is based on clinical symptoms and a positive food challenge. In this study, we report a case of FPIES to rice in an 8-month-old boy. We performed a double-blind placebo-controlled food challenge (DBPCFC) to rice and we measured the intracellular T cell expression of interleukin-4 (IL-4); IL-10, and interferon (IFN-) pre-and post-challenge during an acute FPIES reaction and when tolerance to rice had been achieved. For the first time we describe an increase in T cell IL-4 and decrease in IFN- expression after a positive challenge with rice (i.e. rice triggered a FPIES attack) and an increase in T cell IL-10 expression after rice challenge 6 months later after a negative challenge (i.e., the child had acquired tolerance to rice) in an 8 month old with documented FPIES to rice. A Th2 activation associated with high IL-4 levels may contribute to the pathophysiology of the disease. On the other hand, T cell-derived IL-10 may play a role in the acquisition of immunotolerance by regulating the Th1 and Th2 responses.

Systemic acute rhinosinusitis therapy consists mostly of antibiotic treatment because pathogens play a major role. Amoxicillin is the drug of choice for treatment of acute rhinosinusitis, with second- and third- generation cephalosporins, azythromycin, clarithromycin, and telithromycin as possible options, especially in the case of allergy to amoxicillin. If the clinical course suggests that an anaerobic pathogen is more likely, clindamycin or metronidazole can be considered in combination with a broad-spectrum drug. In antimicrobial treatment of chronic sinusitis there is no consensus on treatment length, organism coverage, or which antibiotics are most effective because the bacteriology is variable with polymicrobial anaerobic and aerobic organisms present. Adjuvant therapies need to be proven by additional studies. Chronic rhinosinusitis is heterogeneous and treatment should vary according to the causative factor involved. Short courses of systemic steroids have been found very useful to decrease mucosal swelling and inflammation in chronic rhinosinusitis. However, no randomized controlled studies have been performed to validate their efficacy in children. A variety of other agents are used in the treatment of chronic rhinosinusitis including antihistamines, decongestants, and leukotriene modifiers. To date, there is no good evidence from randomized controlled studies to support the use of any of these agents in the treatment of this disease in either children or adults.

L’adrenalina ha uno stretto indice terapeutico. La sua somministrazione puo dare effetti collaterali come ansieta, agitazione, cefalea, vertigini, palpitazioni, pallore e tremori, per dosi terapeutiche, a qualsiasi eta, e per qualsiasi via di somministrazione, anche per inalazione [1]. Tali effetti appaiono strettamente dose-dipendenti e in uno studio randomizzato in doppio cieco a gruppi paralleli eseguito in bambini di 5–8 anni si e dimostrato che pallore, ansieta e tremori e un caso un aumento del QTc si verificavano per dosi di adrenalina utili ad ottenere un consistente rialzo pressorio, cioe pari a 0,01–0,014 mg/kg [2]. Quelli trattati con un dosaggio inferiore, pari a 0,008–0,009 mg/kg avevano minori e piu transitori effetti collaterali, ma non raggiungevano un significativo rialzo pressorio. Molto raramente si puo arrivare ad aritmie ventricolari, angina, infarto miocardio, edema polmonare, improvviso brusco aumento della pressione sanguigna ed emorragia endocranica [3, 4]. Queste manifestazioni sono state segnalate soprattutto in caso di sovradosaggio e per somministrazione endovenosa. Pertanto, per la maggiore frequenza di effetti collaterali, la via endovenosa viene consigliata solo dopo che ripetute somministrazioni intramuscolari non si sono dimostrate efficaci e sotto controllo con ECG [5].

L’anafilassi e la piu grave delle reazioni allergiche, e un bambino che ha subito un episodio di anafilassi e a rischio di nuovi episodi [1]. La principale strategia nella gestione del bambino a rischio di anafilassi e innanzi tutto la prevenzione degli episodi futuri. Un corretto programma di prevenzione dell’anafilassi puo essere articolato solo per i casi che hanno gia presentato un pregresso analogo episodio, pertanto l’identificazione del fattore causale e lo strumento piu importante per ridurre i rischi di una recidiva.

Fornire dei dati epidemiologici sull’anafilassi e complicato per diversi motivi: in primo luogo, non esiste una definizione di anafilassi universalmente accettata e, poiche nel tempo sono state proposte diverse definizioni, i dati epidemiologici disponibili in letteratura variano ovviamente anche sulla base della definizione adottata. I risultati degli studi sono, inoltre, diversi a seconda della popolazione utilizzata. Infine, gli studi piu spesso sono stati eseguiti su popolazione selezionata, perche arruolata in un Ospedale, in un Pronto Soccorso o presso ambulatori specialistici o di pediatria generale.

In accordo con quanto raccomandato dall’American Academy of Allergy Asthma and Immunology, si suggerisce di inviare ad una consulenza allergologica ogni bambino affetto da un episodio di anafilassi, sospetta o conclamata, per un approfondito inquadramento diagnostico e terapeutico [1]. Questo sia perche l’anafilassi e un evento potenzialmente grave e mortale, sia per evitare una ingiustificata prescrizione di un farmaco (l’adrenalina autoiniettabile) costoso e non del tutto privo di effetti collaterali.

Il farmaco di elezione per la terapia dell’anafilassi e l’adrenalina che, rispetto agli altri, si fa preferire per efficacia e rapidita d’azione. E infatti in grado di contrastare tutti i piu importanti segni e i sintomi dell’anafilassi: riduce la vasocostrizione periferica e l’edema, induce broncodilatazione, ha un effetto isotropo e cronotropo positivo sul miocardio e infine sopprime l’ulteriore rilascio di mediatori.

Background Vernal Keratoconjunctivitis (VKC) is an allergic conjunctivitis, often not easily diagnosed and properly treated. The disease is very debilitating for patients, may be complicated by corneal lesions and can evolve to keratoconus. Purpose The exponential increase in VKC patients led us to start a close collaboration between pharmacists and allergists, ophthalmologists, and chemists. The goal was to address and solve problems caused by the lack of adequate knowledge of VKC, in order to find a diagnostic-therapeutic course, improve patient compliance and provide high-quality products as an alternative to conventional treatments. Material and methods After discussions with allergists and ophthalmologists, pharmacists formulated 3 different kinds of eye drops as treatment: ciclosporin 1% and tacrolimus 0.1%, both in methylcellulose 0.15%, and ciclosporin 2% in sunflower oil. The stability of such formulations was demonstrated by using liquid chromatography coupled to a triple quadrupole mass spectrometer. The pharmacist now prepares a weekly supply of eye drops, after allergists pass on the number of children who will undergo eye examinations. Then, the pharmacist proceeds, after allergist confirmation, to arrange for eye drops to be sent directly to patients’ homes in the whole country. Results The LC/MS/MS and sterility analysis results allowed the pharmacist to declare that formulations in methylcellulose 0.15% and in sunflower oil were safe for up to 45 days. Such formulations were chosen considering also patient compliance. Indeed, one of the results of the team collaboration has been the development of the formulation in sunflower oil, which can be stored at room temperature; thus leading to huge advantages in terms of patient compliance. Conclusion The preparation of a galenical formulation of such quality has contributed to the efficacy of the treatment. Moreover, the sharing of information between medical doctors, pharmacists and nurses has led to personalised assistance that is highly responsive to health needs. Reference Leonardi A. Prog Retin Eye Res 2002;21(3):319–39 No conflict of interest.

Natural rubber latex (NRL) allergy remains an important allergic disease triggering urticaria, asthma, angioedema and anaphylaxis. Specific immunotherapy can help to solve problems related to NRL allergy. So far, no controlled clinical trials have been performed in children suffering from NRL allergy.To evaluate the safety and efficacy of sublingual immunotherapy (SLIT) with a commercial NRL extract in children with NRL allergy.Randomized, double-blind, placebo-controlled, 12-month trial.Twenty-six children (aged 4-15 years) with NRL allergy, who had cutaneous and/or respiratory symptoms, including oral allergy syndrome to fruits containing cross-reactive allergens, were recruited. Twelve children were randomized to SLIT with a commercial NRL extract and eight to placebo (3:2). An additional six children with NRL allergy served as untreated controls.A glove use test was utilized to monitor skin and systemic symptoms triggered by NRL exposure at baseline and 3, 6, 9 and 12 months later. Oral allergy symptoms were also monitored.No side effects related to treatments were observed in any patient. A significant improvement of symptom score in treated patients in comparison with baseline values was observed at 3 months (p = 0.01) and consolidated after 1 year of treatment (p = 0.0005). In comparison with placebo, significant improvements were observed starting at 9 months from study start (p = 0.015) and at 12 months (p = 0.005). The number of foods triggering oral allergy symptoms increased in placebo and control subjects, but not in active treated patients (p = 0.05).Latex SLIT was safe and efficacious in paediatric patients with NRL allergy.

An association was found between Anisakis simplex (As) and Dermatophagoides pteronyssinus (Dp) sensitization. One recent study shows a cross-reactivity between As and Dp and tropomyosin (tr) is suspected as being one of the proteins responsible of this cross-reaction. The aim of our study was: 1) to confirm the cross-reactivity between Dp and As; 2) to determine the importance of tr in this cross reaction. SDS-PAGE analysis of Dp and As (metabolic and somatic) extracts was carried out. Then an IgE immunoblotting test using serum from a patient who had specific IgE only to Dp and As and immunoblotting inhibition experiments using Dp extract and tr as inhibitors were performed. We found that patient's serum reacted: 1) against larval As antigens with a molecular weight (mw) of 25 kilodalton (kD) and a mw > 100 kD, 2) against various metabolic As antigens with a mw > 100 kD, a mw ranging approximately from 35 to 50 kD, and a mw around 20 kD, and 3) against Dp proteins with mw between 35 and 55 kD. Preincubation of patient's serum with Dp extract caused the disappearance of reactivity against antigens with a mw > 100 kD in both larval and metabolic As extracts and against proteins with mw ranging approximately from 35 to 50 kD in the metabolic As extract. Preincubation of patient's serum with As extract caused the disappearance of reactivity against antigens with mw between 35 and 55 kD in the Dp extract. Pre-incubation of patient's serum with tr did not induce any change in the immunoblotting profile. The results show that 1) cross-reactive components between Dp and As are some proteins with a mw ranging approximately from 35 to 50 kD and with a mw > 100 kD, and 2) tr is not involved in cross-reactivity between As and Dp.

Objective. Vernal keratoconjunctivitis (VKC) is a chronic conjunctivitis that affects children mainly in temperate areas, with exacerbations in spring and summer. Eyelashes provide natural protection for the eyes from sunshine, wind, and foreign bodies. These factors induce a worsening of signs and symptoms in VKC, whereas mechanical protection of the eyes produces relief. The aim of this study was to evaluate eyelash length in a large series of VKC patients and in age- and gender-matched healthy subjects. Methods. Upper eyelash length was measured in 93 VKC patients (mean age: 8.7 years; range: 4–18 years) with a digital caliper. History, clinical form, type of presentation, degree of severity, and drug therapy were evaluated. Skin tests and serum-specific immunoglobulin E for common allergens, serum-total immunoglobulin E, peripheral blood eosinophil counts, and serum eosinophil cationic protein were determined. Two age- and gender-matched control subjects for each VKC patient underwent the same eyelash measurement. Results. The upper eyelashes were significantly longer in VKC patients than in control subjects (mean ± SD: 8.9 ± 1.17 mm vs 7.9 ± 1.07 mm). In healthy subjects, a negative correlation was found between eyelash length and age. With multivariate analysis, unlike control subjects, the eyelash length in VKC patients did not correlate with age, was positively correlated with the degree of severity of VKC, and was negatively correlated with the use of topical cyclosporine. Conclusions. Patients with VKC had longer eyelashes than healthy matched subjects. The ocular inflammation, by unknown chemical mediators, was likely responsible for the excessive eyelash growth. The finding may represent a defensive mechanism against physical agents that might have a crucial role in the etiopathogenesis of this disease.

Background: Atopic dermatitis (AD) affects infants, children, and adults with a wide degree of severity; several scoring systems have been used in trials and clinical practice. Infants and young children have a typical distribution of the lesions, but a correlation among skin surface involvement, intensity and subjective symptoms has not been reported in age groups. Aims of the study: To evaluate the clinical features of AD in infants and young children, by using the SCORAD index. A simplified scoring method for clinical practice is also discussed. Methods: The SCORAD index was assessed in 63 infants and young children with AD [mean age (±SD) 17.5 ± 11.15 months]; the single parameters of the index were evaluated, and compared with each other. Serum eosinophil cationic protein (s-ECP) and urinary eosinophil protein X (u-EPX) levels were determined and correlated with the SCORAD index. Results: The presence of erythema, edema/papulation, and oozing/crust was significantly high in these patients. A strong positive correlation resulted among the three SCORAD index parameters (extent-intensity: P

INTRODUCTION: Vernal keratoconjunctivitis (VKC) is a chronic conjunctivitis that mainly affects children living in temperate areas. The notable difference between genders and VKC’s resolution with puberty have persistently suggested a role of hormonal factors in VKC development. OBJECTIVE: To describe six cases of males with VKC and growth hormone deficiency (GHD) reported as a long-term follow-up during rhGH treatment. METHODS: Six consecutive male patients (median age at GHD diagnosis 9.7, range 7.9 to 13.1 years) with VKC, were recruited from July 2005 to July 2013 at the Paediatric Endocrinology Unit of Anna Meyer Children’s Hospital in Florence, Italy. In these patients, anthropometric data were collected periodically. In three of these patients, data were collected to near-adult or adult height. RESULTS: Familial history was uneventful for all patients. The target height was normal, ranging from 0.65 standard deviation scores (SDS) to 2.01 SDS. The patients showed a normal birth-weight (from −1.21 to 1.35 SDS) and birth-length (from −0.93 to 1.21 SDS). At GHD diagnosis, all of the patients exhibited demonstrated important growth retardation (from −2.05 to −2.78 SDS). Plasmatic concentrations of IGF-1 and IGFBP-3 were low (from −1.85 to −3 SDS and from −1.81 to −2.76 SDS, respectively). GH stimulation tests showed classic GHD symptoms in all of the patients. Pubertal onset was normal. All of the patients treated with rhGH responded well to rhGH treatment. Adult height, evaluated in three patients, was in accordance with their target height. CONCLUSIONS: To our current knowledge, we have described for the first time six patients affected by VKC with GH deficiency, in some of whom we performed a long-term follow-up to adult height. Further studies will be needed to establish whether GHD may be a common feature of VKC patients. Nevertheless, it appears to be useful to carefully follow statural growth of VKC patients, while the possibility of a GH deficiency must to be taken into account in the presence of growth failure.

Although anaphylaxis is considered a life-threatening event, there is a lack of information on the clinical characteristics at presentation, both in adults and in children.To describe in a nonselected population the clinical characteristics and the treatments of acute anaphylaxis triggered by different agents.This is a retrospective review of the clinical features of 113 episodes of acute anaphylaxis resulting in admission to a university hospital. Initially, the 107 patients visited the emergency room and were then admitted to the hospital.Most anaphylactic events (63%) occurred at home. The most frequent symptoms involved the respiratory system (78%) and the skin (90%). Drugs, especially nonsteroidal anti-inflammatory drugs and antibiotics, were the most frequent cause of anaphylaxis in adults (49%). Patients with drug-induced anaphylaxis were older and more often had cardiovascular symptoms (hypotension and tachycardia) (P = 0.0064). Hymenoptera venom was the second most frequent cause of anaphylaxis (29%). Most of the patients with hymenoptera venom anaphylaxis were male (80%) and more frequently they had no history of atopy (P = 0.012). In food-induced anaphylaxis, the cardiovascular system was less likely to be involved (P0.05) (39%). Seafood seems to be frequently involved in food-induced anaphylaxis in our area. Specific immunotherapy-induced anaphylaxis occurred more often in younger patients (P = 0.032). Epinephrine seems to be underused in Italy (only 15% of patients received it), especially for respiratory symptoms.Anaphylaxis triggered by different agents may have different clinical presentations and may occur in different types of patients. In Italy, the inadequate use of epinephrine for anaphylaxis treatment needs to be publicized to both physicians and the general population.

IT is well known that allergy plays a pathogenic role in the development of atopic dermatitis (AD) (1). However, approximately 20% of AD patients suffer from a skin disease that clinically resembles the skin lesions and the distribution pattern of AD, but is not associated with atopic status. This kind of ‘‘intrinsic’’ AD (iAD) seems to differ from the classical or ‘‘extrinsic’’ form (eAD) both in the T-cell cytokine production and in the immunohistology (2, 3), but no data are available about its natural history. In this study, we investigated the persistence of AD and the development of respiratory allergic diseases in a group of children seen at the ages of 2 and 11 years according to the skin prick test (SPT) reactivity to allergens at those ages. The parents of 111 children with AD evaluated at our allergy unit in 1989–90 were asked for re-evaluation of the children about 9 years later. Seventy percent of the children (77/111) underwent clinical history, and SPTs to food (egg white, wheat, milk, tomato, codfish, and soy [Lofarma, Milan, Italy]) and inhalant allergens (dust mite, cat, dog, Alternaria, grass pollen, Parietaria, mugwort, olive pollen, and Cupressus sempervires [Lofarma]). AD was diagnosed according to Hanifin & Rajka (4). The presence of asthma and SPT reactivity was studied as previously described (5, 6). According to the SPT results, we defined the following groups: 1) ‘‘early atopic’’, i.e., those children who were already SPT positive at age 2 and were still SPT positive at age 11 2) ‘‘late-onset atopic’’, i.e., those who were negative at age 2 but became SPT positive by the age of 11 3) ‘‘nonatopic’’, i.e., those who were SPT negative at the ages of both 2 and 11. We considered patients SPT negative at age 2 as having iAD. The data were analyzed by the statistical program SPSS 6.0 for Windows with the chi-square and chi-square for trend tests. A two-sided type 1 error lower than 0.05 was considered statistically significant. Seventy-seven AD patients, with a mean age (uSE) of 24.1u2.28 months at the first evaluation, and 132u3.24 months at the second evaluation, were identified. At diagnosis, all of them had AD (77/77), 22% (17/77) had asthma, and 64% (49/77) had at least one positive SPT. At 11 years of age, 46% of them had AD (36/77), 43% (33/77) had asthma, and 84% had (65/77) at least one positive SPT. Forty-nine out of the 77 (64%) studied children had early atopy, 16/77 (21%) had late-onset atopy, and 12/77 (15%) were nonatopic. None of the nonatopic children developed asthma by age 11 (0/12), compared with the 25% (4/16) and the 59% (29/49) of the late-onset and early atopic children, respectively (chi square for trend, P,0.0002). AD was still present by age 11 in 67% (8/12) of nonatopic AD as compared with 44% (7/16) and 43% (21/49) of the late-onset and early atopic children (Fig. 1). Altogether, the 28 AD children ALLERGY 2001: 56 :452^463 . COPYRIGHT G MUNKSGAARD 2001 . ISSN 0105-4538 . ALL RIGHTS RESERVED . CONTRIBUTIONS TO THIS SECTION WILL NOT UNDERGO PEER REVIEW, BUT WILL BE REVIEWED BY THE ASSOCIATE EDITORS .

Background: Allergic or pseudo-allergic reactions to macrolides antibiotics are relatively uncommon (0.4-3% of treatments). The allergological work-up for the diagnosis of macrolides hypersensitivity is undefined. Methods: In our study we analyzed 95 children with history of macrolides reactions. Skin tests were performed according to EAACI guidelines by prick tests (PT) followed by intradermal test (ID) with the culprit drug. Oral Double Blind Provocation Tests (ODBPT) were performed in order to exclude or confirm a real state of drug hypersensitivity and to check the cross-reactivity. Results: 46 females and 49 males (mean age 6.2 years) described a total of 102 reactions to macrolides (28 immediate and 70 late). The most frequently involved drug was clarithromycin (69.6%). It mainly provoked mucocutaneous eruptions. All the children with suspected clarithromycin allergy underwent the ODBPT, but the diagnosis was confirmed in the 6.25% of cases and they all tolerated an alternative macrolidic drug. Azythromycin resulted less frequently involved (19,6%) but it caused the more severe reactions. The two patients (50% of those with history of immediate reactions) with anaphylaxis to azythromycin had positive skin tests with the culprit drug, however they both tolerated clarithromycin. Conclusion: Clarithromycin even being the most common cause of allergic reactions, it usually provokes mild cutaneous flares and a real state of hypersensitivity is rarely proven. On the contrary, azythromycin rarely resulted as cause of drug reactions but when it occurs these are severe. At last even in case of anaphylaxis allergy to macrolides seems not to be a class allergy.

There are no data concerning the significance of allergen specific nasal challenge to latex (ASNCL) in the pediatric population and the effect of mometasone furoate nasal spray [(MFNS), topic corticosteroid exerting a potent anti-inflammatory activity] in children with latex allergic rhinitis. The aims of this study are: to investigate the clinical and immune pathological effects of ASNCL in children with latex allergy; to study the effects of MFNS pre-medication on the clinical and immune pathological effects of ASNCL in children with latex allergy. Thirteen children [6 male and 7 female, mean (SD) age 9.6 (2.9) years] with latex allergy and seven children [3 male and 4 female, mean (SD) age 9.9 (3.8) years] without latex allergy underwent ASNCL. Nasal symptoms were recorded, nasal lavage fluid was collected to measure tryptase, eosinophil cationic protein (ECP), interleukin-5, interferon-γ levels, and spirometric test was performed for each patient without or with pre-medication with MFNS. ASNCL induced a clinical allergic response and increased tryptase levels only in children with latex allergy. No serious adverse events occurred after ASNCL. MFNS pre-medication reduced both tryptase and ECP levels only in children with latex allergy. ASNCL is a simple, reliable and useful tool to make or confirm the diagnosis of nasal symptoms due to latex; it allows us to study both clinical symptoms and local immunological changes. MFNS pre-medication before an ASNCL may prevent some immunological responses induced by ASNCL without clinical allergic modifications.

Eosinophil cationic protein (ECP) and eosinophil protein X (EPX) or eosinophil-derived neurotoxin (EDN) are released by eosinophil granulocytes in allergic diseases. Serum ECP (s-ECP) levels have been correlated with disease activity in atopic dermatitis (AD) in adults and young patients, and high urinary EPX (u-EPX) levels in asthmatic patients seem to reflect active disease. A relationship between AD severity and u-EPX concentration in young children has not been previously studied.This study was performed to evaluate whether the severity of AD in infants and young children was correlated with s-ECP and u-EPX levels.Fifty-four infants and children (mean age, 17.7 months; range, 4-48 months) with AD and without other allergic conditions were evaluated. The severity of AD was measured by using the SCORAD index. S-ECP, serum total IgE, serum-specific IgE for common allergens, and peripheral blood eosinophil counts (PBECs) were determined. In forty-two children u-EPX was also measured. Seven age-matched control patients underwent the same determinations.S-ECP and u-EPX were significantly higher in children with AD than in control children (mean, 23.9 vs 3.5 microg/dL [P.001] and 57.7 vs 6.0 microg/mmol creatinine [P.001]). A significant correlation was found between SCORAD and s-ECP (P =.002), u-EPX (P =.01), and PBECs (P =.01) and between symptom index and uEPX (P =.0004). PBECs were strongly correlated to s-ECP and u-EPX (P.0001). However, 5 patients with moderate and severe AD (11.9%) showed low levels of s-ECP, u-EPX, and PBECs.S-ECP and u-EPX were useful markers of AD activity in infants and young children. When taken together, the two determinations could give more information about the clinical course of the illness. Some patients seemed to have clinical exacerbations without an involvement of eosinophils and their products.

Background Little is known about the frequency of and the features associated with recurrent anaphylaxis in pediatric populations. During 1994 to 1996, we enrolled 76 children affected by anaphylaxis in a prospective study to analyze their clinical and allergic features. Objective To undertake a follow-up study of these children to ascertain how many experienced a recurrence of anaphylaxis. Methods After a mean interval of 7 years, a pediatric allergist conducted a telephone interview of patients who had been enrolled in our 1994-1996 study. Results A telephone interview was successfully completed in 46 (61%) of the 76 patients who had been enrolled in our 1994-1996 study. Of these 46 patients, 14 (30%) had experienced a recurrence of anaphylaxis. Children with atopic dermatitis either during 1994 to 1996 (64% vs 34%; P = .04) or at the time of the current study (43% vs 16%; P = .03) and those with urticaria-angioedema at the time of the current study (93% vs 31%; P = .0002) were found to be at a significantly higher risk for recurrent anaphylaxis. Furthermore, those children who were sensitive to at least 1 food allergen during 1994 to 1996 were more likely to have experienced a recurrence of anaphylaxis (93% vs 56%; P Conclusions This study suggests that patients may have a greater risk of recurrence of anaphylaxis if they have atopic dermatitis, urticaria-angioedema, or at least 1 positive result of skin prick tests to food allergens.

Oral tolerance has been related to generation of T regulatory cells (Treg) or clonal anergy/deletion, respectively by administering low and high doses of fed antigens. CD4+CD25+ regulatory T cell clones can be induced by the antigen in Peyers patches of animal models. We selected ten subjects (mean age: 89.4 +/- 36.21 months; group A) with severe cows milk allergy. They underwent oral desensitization (OD) according to the current protocols. In six months they reached a tolerance of 50 ml of cows milk. CD4+CD25+Foxp3+ T(reg) blood levels were measured at the beginning of OD (A) and after 6 months (A), but almost the same values were obtained: A = 0.36 +/- 0.11 percent; A prime= 0.59 +/- 0.15 percent. These results were compared with a control group (C) of non-atopic children. Naturally outgrowing cows milk allergy can be related to high blood levels of CD4+CD25+Foxp3+ T(reg), as previously reported in children. On the other hand, a forced oral desensitization through a progressive intake of the antigenic food seems not to be related to an enhancement of CD4+CD25+Foxp3+ T(reg) levels in peripheral blood, making the role of long-lasting systemic immunologic changes unlikely.