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PURPOSE The aim of this study was to evaluate the safety and efficacy of tacrolimus 0.1% eye drops in a large population of pediatric patients affected by a severe form of vernal keratoconjunctivitis (VKC) who responded poorly to cyclosporine eye drops. METHODS This is a retrospective study based on standardized clinical charts and data collection of consecutive patients affected by severe VKC who responded poorly to cyclosporine eye drops topical treatment but treated with tacrolimus 0.1% eye drops with a follow-up of 18 months. Four clinical signs were graded for analysis: hyperemia, tarsal papillae, giant papillae, and limbal papillae. The blood tests for kidney and liver function and the tacrolimus level were studied. Visits were scheduled at baseline and at 3, 6, 12, and 18 months. Patients received tacrolimus 0.1% eye drops in both eyes 2 times daily. RESULTS Four hundred thirty-one patients were included. Three hundred twenty-five patients were affected by a seasonal form, whereas the remaining 106 by a perennial form. Statistical analysis on each single score showed a positive relevance (P < 0.001) from baseline to all other visits. No local or systemic complications were recorded. CONCLUSIONS Tacrolimus has been proposed as a treatment for severe forms of VKC. This study has confirmed the safety and efficacy of tacrolimus 0.1% eye drops in a large pediatric population of patients affected by a severe form of VKC who responded poorly to cyclosporine eye drops.

Transplantation-acquired food allergies (TAFA) are frequently reported and considered to be caused by immunosuppressive therapy. The aim of this study was to investigate the allergic and immunologic responses in children who had liver or kidney transplantations.Twelve children receiving liver transplantations and 10 children receiving kidney transplantations were investigated. All children underwent the allergy work-up and in most of them, lymphocyte screening and serum cytokine measurements were also performed.TAFA were found in 7/12 (58%) children with liver transplantations and in none of the 10 children with kidney transplantations. The mean age at transplantation was significantly lower in children who underwent liver transplantations (p0.001). The immunosuppressive therapy administered to children with liver transplantation was tacrolimus in 11 patients and cyclosporine in one patient, while all 10 children with kidney transplantation received tacrolimus plus mycophenolate. The most common antigenic food was egg. The natural killer (NK) cell numbers were significantly higher in liver-transplant children than in kidney-transplant children. No significant differences were found in the serum cytokine levels.This study confirms that liver-transplant children treated with tacrolimus alone have a higher risk of developing TAFA than kidney-transplant children treated with tacrolimus plus mycophenolate. NK cells might be involved in this difference.

Purpose: The aim of the present prospective study was to evaluate the lacrimal fluid concentration of HMGB1 in young patients affected by Vernal Keratoconjunctivitis (VKC) compared to a control gro...

Background The therapeutic strategy for children with cow’s milk allergy (CMA) consists in the elimination of cow’s milk (CM) from their diet. Donkey’s milk (DM) has been reported to be an adequate alternative, mainly to his nutritional similarities with human milk (HM) and excellent palatability. The aim of present prospective study was to evaluate the nutritional impact of DM on the diet of children with CMA in term of children growth. Methods Before the nutritional trial on children and during the study the health and hygiene risks and nutritional and nutraceuticals parameters of DM were monitored. Children with CMA were identified by the execution of in vivo and in vitro tests for CM and subsequent assessment of tolerability of DM with oral food challenge (OFC). Finally, we prescribed DM to a selected group of patients for a period of 6 months during which we monitored the growth of children. A total of 81 children, 70 with IgE mediated cow’s milk protein allergy (IgE-CMPA) and 11 with Food Protein Induced Enterocolitis Syndrome to CM (CM-FPIES), were enrolled. Results Seventy-eight out of 81 patients underwent the OFC with DM and only one patient with IgE-CMPA (1.5 %) reacted. Twenty-two out of 81 patients took part of the nutritional trial. All the 22 patients took and tolerated the DM, moreover DM did not change the normal growth rate of infants. Conclusions In conclusion, DM resulted safe in term of health and hygiene risks and nutritionally adequate: no negative impact on the normal growth rate of children was assessed. Therefore, it may be a suitable alternative for the management of IgE mediated CMA and FPIES, also in the first 6 months of life, if adequately supplemented.

Background: Hazelnut allergy (HA) is one of the more common food allergies (FAs) in Europe with a prevalence of 0.2%. The gold standard for diagnosing FA is oral food challenge (OFC) with the culprit food. Another purpose of OFC is to identify the “threshold level” of food as the dose that elicits symptoms. In this way it is possible to avoid a strict elimination diet and to determine the minimal quantity of the culprit food tolerated by the patient. Objective: The aim of our study was to assess the efficacy and tolerability of hazelnut low-dose OFC (H-LDOFC) in children with HA. Methods: From January 2015 to December 2016, we retrospectively analyzed the charts of patients referred to Allergy Unit of Meyer Children’s Hospital, Florence, Italy for a history of HA. Prick by prick (PbP) and specific serum IgE (s-IgE) to hazelnut were performed. We proposed conducting an H-LDOFC to parents of children with HA. The H-LDOFC was considered completed when a cumulative dose of 2.5 g of hazelnut was reached. We divided the patients who underwent the H-LDOFC into an asymptomatic and a symptomatic group. For statistics we used SPSS for Windows version 16.0 and conducted a t test for comparing the averages, considering a p value of < 0.05 significant. Results: Forty-three out of 70 patients (61.4%) with HA underwent an H-LDOFC. The PbP to hazelnut (mean ± SD) was 7.2 ± 2.9 mm and the s-IgE to hazelnut 25.3 ± 32.5 kU/L. Twenty-eight out of the 43 patients (65.1%) who underwent H-LDOFC reached the cumulative dose of 2.5 g of hazelnut. During the H-LDOFC, 20/43 patients (46.5%) had no reactions and 23/43 patients had a total of 55 reactions: 34 (61.8%) oral allergy syndrome, 8 (14.5%) rash, 6 (10.9%) abdominal pain, 2 (3.6%) urticaria, 2 (3.6%) angioedema, and 3 (5.4%) dyspnea. Atopic dermatitis was found to present the only statistically significant difference (p = 0.002) in patients with symptoms compared to asymptomatic patients during H-LDOFC. Conclusions: To our knowledge, this was the first study to assess the efficacy and tolerability of H-LDOFC in a pediatric population. Our study suggests that in children with HA, H-LDOFC is well accepted and safe because adverse reactions are mild and the majority are represented by localized symptoms (oral allergy syndrome) and efficient, especially in terms of improvement of quality of life. For these reasons it could be more extensively used in the treatment of HA.

Background Vernal keratoconjunctivitis (VKC) is a chronic sight-threatening ocular disease. Topical cyclosporine A (Cyc) has been widely administered as a steroid-sparing drug, although in about 7–10% of cases, it has been ineffective. The purpose of this study was to evaluate the efficacy of 0.1% topical tacrolimus (Tcr) in patients with severe VKC who failed to respond to 1% Cyc eyedrops. Methods Consecutive patients with severe, Cyc-resistant VKC were enrolled in a double-blind, comparative, crossover (DBCO) trial; all patients were treated with 1% Cyc in one eye and 0.1% Tcr in the other eye for 3 wk. After a washout period of 7 days, patients were instructed to cross over the medications for three additional weeks. Objective ocular score, subjective score, and quality-of-life questionnaires (QoLQ) were collected during the trial. Blood samples were drawn to assess several safety parameters. Results Thirty patients have been enrolled (mean age 9.05 ± 2.12 yr). In each of the two phases of the DBCO trial, a significant improvement in objective and subjective scores was observed in the eyes treated with 0.1% Tcr (p

Background The basophil activation test (BAT), has been proposed as a possible assay for the diagnosis of immediate-type allergy to beta-lactams (BLs). The aim of this study was to assess the utility of BAT in the diagnosis of amoxicillin (AMX) or AMX-clavulanate (AMX-C) IgE-mediated hypersensitivity in children and adults. Material and methods Eighteen children and 21 adults, with clinical history of immediate reactions to AMX or AMX-C, were referred to Anna Meyer Children’s Hospital and San Giovanni di Dio Hospital, respectively. They underwent in vivo tests (skin prick test and intradermal test). Moreover, BAT with AMX or AMX-C was performed within 6 months from the reaction. Results In the pediatric group, the concordance between the skin tests (ST) and BAT results was 83.3%. Upon comparing the symptom grades and ST results to the BAT results, we found that the reaction severity and ST positivity did not correlate with BAT results in children. In the adult group, the concordance between the ST and BAT results was 61.9%. Upon comparing patients with severe reactions and patients with mild reactions in terms of BAT results, we found a BAT sensitivity of 38.5% and a specificity of 100%. When comparing the symptom grades to the BAT results, we found that no patients with mild symptoms had a positive BAT result, whereas 38.5% of patients with severe symptoms had a positive BAT result. Conclusions BAT does not seem to be a useful tool to increase the sensitivity of an allergy work-up to diagnose immediate hypersensitivity to AMX or AMX-C.

Oral immunotherapy (OIT) has been introduced as a new immune-modulating treatment under investigation for food allergies. The aim of our study was to evaluate the success of OIT in a cohort of children with milk allergy. These children underwent OIT in a clinical practice and were followed for up to ten years. The secondary endpoint was to describe the main adverse events during OIT and compare them to those reported in the literature. Eighty-two milk-allergic children started OIT. According to the OIT endpoint reached after one year, all of the children enrolled in the study were divided into four groups: complete desensitization; partial desensitization; step down; and stop groups. Any adverse events that occurred during OIT were also recorded. Of the 82 patients, eight were recruited in the last months of 2010 so they were still ongoing at the end of the study. For that reason, they were excluded from the analysis. The majority (73%) of the 74 children evaluated (51 boys, 23 girls; median age, 7 years; age range, 2–18 years; specific serum IgE for cow’s milk, 36 KUA/L [range, 3–100 KUA/L]; milk SPT wheal diameter, 7 mm [range, 2–15 mm]) reached complete (58.1%) or partial (14.9%) desensitization, 9.4% were subjected to step down. The remaining 17.6% of the children discontinued OIT because of the occurrence of chronic gastroenteric (GE) symptoms (46.1%) or acute asthma (15.3%) following milk intake. In agreement with the literature, we found that chronic GE symptoms was the main reason for OIT discontinuation. OIT represents a valid tool for the treatment of food allergies in children; however, the risk of potential adverse reactions, both IgE- and non-IgE-mediated, should be discussed with parents prior to the initiation of OIT.

The aim of this paper is to provide an alternative and more efficient screening test for allergy with respect to traditional UNICAP and prick skin tests, which are commercially available nowadays. The proposed test is aimed at monitoring the interaction of the IgE protein with the allergen in an allergic subject. The idea relies on the fact that the interaction between the IgE and the corresponding allergen happens through binding mechanisms between the IgE and the allergen structure, changing the ionic content of the serum. This latter can be monitored by impedance measurements and confirmed by reactive oxygen species (ROS) evaluation in leukocyte subpopulations. Therefore, in this paper we propose a novel system for the detection of allergies based on impedance measurements and confirmed by ROS measurements. This type of measurement approach has never been presented in the literature for this purpose. A measurement protocol has been developed to guarantee reproducibility and repeatability of the assay. This paper describes both the instrument—specifically designed for impedance evaluation—and the measurement protocols for both methodologies, defining univocally, in this way, the overall measurement technique.

Allergic reactions associated to the use of macrolides are uncommon; in particular only two cases of anaphylaxis with erithromycin and clarithromycin have been reported to date. The aim of this study was to investigate macrolide-induced anaphylaxis. Between December 2007 and December 2011, 136 consecutive children were referred to the Allergy Unit of A. Meyer Children's Hospital because of a past history of reactions to macrolides. Allergy work-ups were carried out according to the European Network for Drug Allergy protocol. Anaphylaxis was diagnosed according to the clinical criteria proposed by Sampson et al. and graded according to Brown SGA et al. Sixty-six out of 136 patients completed the allergologic work-up and among them we investigated three cases of anaphylaxis due to azithromycin which included one child with anaphylaxis to both clarithromycin and azithromycin. In two of the children with anaphylaxis, the diagnosis was only confirmed with the skin prick test, the third was positive to the Intradermal Test. The azithromycin allergy shows a surprisingly high sensitivity to the in-vivo tests. Moreover, this study shows that cross-reactivity may occur between different macrolidic molecules; it has even been suggested that macrolide allergies are unlikely to be class allergies.

Hormones may play a role in the pathophysiology of vernal keratoconjunctivitis (VKC). An increased incidence of thyroid autoantibodies was recently observed in VKC, although there were no data on thyroid function. Two hundred and eighty-eight patients (202 males, 86 females; range 5.5 to 16.9 years) with VKC were evaluated and compared with 188 normal age- and sex-matched subjects. In all subjects, serum concentrations of free T4, TSH, thyroperoxidase, thyroglobulin, and TSHr autoantibodies were evaluated. In VKC, the family history of thyroid diseases showed no significant differences compared to the controls (9.4 versus 8.6%), whereas the family history of autoimmune diseases was significantly higher (13.2% versus 6.3%;P<0.05). Subclinical hypothyroidism was diagnosed in 6.6% (versus 1.6% of the controls;P<0.05) and overt hypothyroidism in 0.7% (versus 0.0% of the controls;P=NS). Finally, 5.2% of patients were positive for thyroid autoantibodies, which were significantly higher with respect to the controls (0.5%,P<0.05). In the patients positive for thyroid autoantibodies, 80% showed a sonography pattern that suggested autoimmune thyroiditis. Thyroid function and autoimmunity abnormalities are frequently present in children with VKC. Children with VKC should be screened for thyroid function and evaluated for thyroid autoimmunity.

Hypersensitivity reactions to tramadol are rare and the drug is commonly considered safe. Here, we report the first case of anaphylaxis to tramadol in a child. We point out the difficulty in reaching a confident diagnosis when testing opioid alkaloid drugs with histamine-releasing properties. Additionally, we showed the importance of a well-performed allergy work-up, especially when testing drugs with low experience and when standardized concentrations have not been tested. Moreover, this case provides insight into the possibility of severe reactions, and even anaphylaxis, to tramadol.

We describe the case of a child affected by milk-protein induced enterocolitis, in which oral challenge with corn was performed without symptoms after a negative specific Atopy Patch Test. Food protein-induced enterocolitis syndrome (FPIES) is an uncommon nonIgE-mediated gastrointestinal food hypersensitivity of infancy, characterized by severe vomiting and diarrhea arising within 1 to 3 hours after ingestion of the causative food. Little is known about the pathophysiology of FPIES. The absence of food-specific IgE as demonstrated by negative skin prick tests suggests that the disease is not caused by an early onset IgE-mediated reaction. Atopy Patch Test has been described as sensitive and predictive in this syndrome. The hypothesis on the immunological pathogenesis has been discussed on the basis of literature data.

Non-steroidal anti-inflammatory drugs are suspected to cause drug hypersensitivity very frequently in paediatric patients. In this article, we describe the first case of anaphylaxis to flurbiprofen in a child and provide insight into the possibility of severe reactions and even anaphylaxis to over-the-counter flurbiprofen. Finally, the importance of a rigorous allergy work-up in reaching a confident diagnosis and providing the patient with a safe alternative is shown.

Purpose To evaluate the prevalence of keratoconus (KC) and other corneal abnormalities by means of videokeratography and tomography in a large series of patients affected by vernal keratoconjunctivitis (VKC). Design Cross-sectional study. Methods Setting: Single-center children's hospital. Study Population: A total of 651 consecutive patients with VKC and a control group of 500 were prospectively recruited between May 1, 2012 and September 30, 2013, with a minimum follow-up of 12 months. Observation Procedure: All patients were evaluated by means of a Scheimpflug camera combined with a Placido corneal topographer. Keratoconus, suspected keratoconus, or its absence were determined in each patient. The corneal symmetry index of front (SI f ) and back curvature (SI b ), shape indices, and thicknesses were compared between the 2 groups. Main Outcome Measures: Prevalence of keratoconus and corneal indices modifications. Results Five out of 651 patients (0.77%) demonstrated topographic signs of KC. Two of them were bilateral. All patients were older than 7 years of age, and the mean age was 11.54 years. Four other patients (0.61%) were classified as KC suspects by the screening program. Of 304 patients older than 11 years (mean age 14.4 years), 4 (1.32%) were found to have KCN, and 4 (1.32%) were KC suspects. The corneal indices of patients in the VKC group were extremely similar to those in the control group. ( P > .05). Conclusions The prevalence of KC in our patient population, compared with previous reports in the literature, is much lower. The similar corneal indices in both groups suggest the absence of permanent corneal deformation due to VKC.

The aim of this work is to provide an alternative and more efficient screening test in order to monitor the interaction of the IgE protein once in contact with the allergen in an allergic subject. The idea relies on the fact that the interaction between the IgE and the corresponding allergen happens through a bonding mechanism. According to this interaction it is possible that some of ionic bond or electrostatic interaction will happen between the IgE and the allergen structure changing the ionic content of the medium. This latter can be monitored through impedenzimetric measurements. Therefore in this paper we propose a novel system for the detection of allergies based on impedenzimetry This type of measurement instrument has never been presented in the literature for this purpose. Moreover a measurement protocol has been defined to make the measurements reproducible and repeatable over time. The following description addresses both the instrument and the measurement protocol identified for this purpose, defining univocally, in this way, the overall measurement technique.

Although amoxicillin-clavulanic acid (AMX/CLV) can be associated with hypersensitivity reactions, ranging from minor and self-limiting to anaphylaxis, this is the first reported case of a reproducible maculopapular exathema (MPE) with drug fever occurring after a single therapeutic dose, not associated with drug reaction with eosinophilia and systemic symptoms (DRESS). This case presented with delayed onset skin hypersensitivity reactions and fever that were finally associated with increased neutrophil counts plus high C-reactive protein (CRP) levels. The patient was a 14-year-old Caucasian girl with a history of AMX/CLV-associated reactions. In 2012, during an Epstein Barr virus infection, she had an MPE during AMX/CLV therapy. In February 2014, she was given AMX/CLV for a febrile bacterial infection and noted another itchy MPE 12 hours after the first dose. She stopped the drug, and in May 2014, she was referred to the Allergy Unit of Anna Meyer Children’s Hospital for evaluation. Skin tests were performed according to the European Network for Drug Allergy recommendations in the following sequence: (a) skin prick testing (SPT) with 20 mg/mL AMX and AMX/ CLV; and (b) an intradermal (ID) testing with 1/100 and 1/10 dilutions of the full-strength (200 mg/mL) AMX and AMX/CLV concentration at 20to 30-minute intervals. Positive and negative controls for SPT and ID were obtained using histamine (ALK-Abello, Milan, Italy: 10 and 1 mg/mL) and normal saline. A positive skin test result was when the SPT wheal was greater than 3 mm and was accompanied by erythema with a negative saline control result or when the ID was greater than 3 mm from the initial wheal or an increase in the diameter of the initial wheal was associated with a flare and a negative saline control result within 15 minutes. ID tests were also read after 24-72 hours for delayed T-cell-mediated reactions. Specific IgE to amoxicillin, ampicillin, and penicillin G and V were measured (Immunocap RAST, Uppsala, Sweden) and were all negative. Because all of the skin and in vitro tests were negative, an open challenge drug provocation test (DPT) to AMX/CLV using 1/ 10, 2/10, and then 7/10 of the therapeutic dose every 30 minutes (50/mg/kg/day in 2 doses) was administered following the current guidelines. She had no acute reactions, and after 2 hours of observation, she was discharged. After 3 hours from the last dose, she was vomiting and had a fever (39.4 C), headache, and generalized erythema. After 8 hours, she had diarrhea and difficulty sleeping. She was transported to the emergency department of Anna Meyer Children’s Hospital where her vital signs, complete blood count, and CRP levels were found to be within the normal range. She was discharged with the suspicion of a concurrent viral infection. In October 2014, the ID tests with AMX/CLAV were again negative. The DPT with AMX/CLV was repeated with the same graded challenge protocol, and after 3 hours, she again noted vomiting and had a fever, headache, and an itchy MPE. Later she had difficulty sleeping and diarrhea. The next day, she was admitted to the Anna Meyer Children’s Hospital Allergy Unit, where her blood was drawn and the following results were observed: 12.3 mg/mL CRP (normal value < 0.50 mg/dL); white blood cells count (WBC) of 14,950 mmc; neutrophils 90%; and liver function and a erythrocyte sedimentation rate within the normal ranges. After 2 days, the MPE was reduced and the girl no longer had a fever (Figure 1). After a month, a lymphocyte transformation test (LTT), induction of hapten-specific short-term T-cell lines, and cytokine production measurements were performed (see this article’s Online Repository at www.jaci-inpractice.org). The LTT was strongly positive to both AMX and AMX/CLV (Figure 2, A), and the T-cell lines that were specific for AMX and AMX/CLV could be induced. The LTT positivity and induction of the hapten-specific T-cell lines were also confirmed 6 months apart from the reaction (data not shown). A flow cytometric analysis showed high percentages of TNF-a producing T-cell blasts (Figure 2, B). No significant production of CXCL8, IL-6, or IL-17 could be found (data not shown). Drug fever is a rare event occurring in only approximately 3%-5% of adverse drug reactions. In 18%-29% of patients who

Acute rhinosinusitis (ARS) is one of the most common reasons for physician visits and for significant school absenteeism, although precise data on its prevalence and incidence are still lacking. RS is defined as acute if there are symptoms lasting

Vernal Keratoconjunctivitis (VKC) is a severe chronic bilateral inflammation of the ocular surface characterized by seasonal exacerbations. Long-term prognosis is generally good; however, 6% develop sequelae responsible for permanent visual impairment. Corneal involvement is almost always present, consisting of punctate keratitis, shield ulcers (3–11%) and late corneal neovascularization. In recent years, topical cyclosporine A preparations at 2% in oil or at 1% in polyvinyl alcohol, have been successfully proposed for long term VKC treatments. It has been previously proven that medical treatment is not always sufficient, especially when it is employed to treat shield ulcer plaques. In such conditions, surgery may be effective for avoiding long term complications such as amblyopia, strabismus, infections and corneal perforation. In this paper, we show the efficacy of surgical debridement by means of simple scraping associated with topical cyclosporine treatment for the management of vernal shield ulcers complicated with plaques.

Vernal keratoconjunctivitis (VKC) is a chronic and potentially sight-threatening disease. Topical corticosteroids (Cs) seem to be the only effective treatment for this condition, although severe side effects may occur owing to their prolonged use. More recently, cyclosporine (Cyc) eye drops have been reported as a valid alternative, but so far such treatment has only been successfully experimented for a short time and in small numbers of patients. The aim of our study is to evaluate the long term safety and efficacy of topical cyclosporine eye drops in children suffering from VKC. Over a period of 7 years we followed a large group of children suffering from severe VKC. They were selected to start cyclosporine eye drop treatment, because of the prompt relapse of their disease as soon as they stopped topical corticosteroids administration. All patients were followed-up in an ambulatory care assessment. A total of 156 children with VKC were treated with topical cyclosporine eye drops over a period ranging from two to seven years [mean time 3.8 +/- 1.09 years] during the seasonal relapse [range 9-66 months; mean time 24.7+/-10.4 months]. Two formulations, at 1% and 2% (82% and 18%, respectively) concentrations, of cyclosporine eye drops were made. The dosage administered was one drop in each eye from two to four times a day, depending on the severity of the disease and the season. The ocular objective scores were determined and compared every year, at the beginning and at the end of each treatment period. Blood samples were collected once a year in order to check both kidney and liver functions, as well as cyclosporine serum levels. We enrolled 156 patients (mean age 8.31+/-2.79 years; 116 males and 40 females) who were followed-up over a period of 7 years [156 (100%) children during the first and the second year; 138 (88.5%) patients until the third year; 90 (57.7%) until the fourth year; 32 (20.5%) until the fifth year; 10 (6.4%) until the sixth year and 2 (1.3%) until the seventh year]. The ocular objective scores significantly improved (p less than 0.001) over the years when comparing them at the beginning and the end of each seasonal treatment period, except for the last year. Over the treatment period, non-significant changes were recorded in terms of kidney and liver enzymatic activities and also in terms of cyclosporine serum levels. Cyclosporine eye drops, either at 1% or 2% concentrations, resulted safe and effective for long-term treatment of VKC in 156 children. The lack of significance of the score results during the seventh year can be explained by the small number of subjects treated for such a long period. A systematic ocular examination and both liver and kidney functional investigations allowed us to exclude the possibility of local or systemic side effects due to cyclosporine. If either transient or long-lasting, the occurrence of burning was referred by some of the patients treated, but none of them required to discontinue the drug. In conclusion, this is the first study showing that topical cyclosporine is easily handled even by children, with safe and effective results even when it is used over a long period of time. Our findings, though encouraging, need to be confirmed by further studies.

Mori F, Pucci N, Rossi ME, de Martino M, Azzari C, Novembre E. Oral desensitization to milk: how to choose the starting dose! Pediatr Allergy Immunol 2010: 21: e450–e453. © 2009 John Wiley & Sons A/S A renewed interest in oral desensitization as treatment for food allergy has been observed in the last few years. We studied a novel method based on the end point skin prick test procedure to establish the starting dose for oral desensitization in a group of 30 children higly allergic to milk. The results (in terms of reactions to the first dose administered) were compared with a group of 20 children allergic to milk as well. Such control group started to swallow the same dose of 0.015 mg/ml of milk. None reacted to the first dose when administered according to the end point skin prick test. On the other side, ten out of 20 children (50%) from the control group showed mild allergic reactions to the first dose of milk. In conclusion the end point skin prick test procedure results safe and easy to be performed in each single child in order to find out the starting dose for oral desensitization to milk, also by taking into account the individual variability.

Skin prick tests (SPT) with latex extracts are commonly used in the diagnostic approach of natural rubber latex (NRL) allergy. Non-ammoniated latex extracts are commonly utilized for this purpose. There is only one commercially available ammoniated latex extract for both diagnostic and therapeutic purposes. To our knowledge, no direct clinical comparisons have been made so far comparing sensitivity and specificity of different latex extracts in patients with clinically confirmed latex allergy. The objective of this study was to evaluate sensitivity and specificity of non-ammoniated or ammoniated SPT of latex extracts in children with a clinical history suggestive of NRL allergy. Forty-two subjects (age 4-15 yr), referred to our Allergy Clinic Center, with suspected clinical signs of NRL allergy were evaluated. Patients were selected according to the following inclusion criteria: pediatric patients of age above 4 yr with a suspected clinical history of urticaria, rhinoconjunctivitis and/or asthma due to sensitization to NRL. A definitive NRL allergy diagnosis was made on the identification of latex-specific IgE (>0.7 kU/l), positive glove use test and a highly indicative clinical history. NRL allergy was confirmed in 26 (62%) subjects. SPT for latex were performed with three different SPT solutions containing non-ammoniated NRL extracts (product A: Lofarma SpA, Milan, Italy and product B: Stallergenes, Milan, Italy) or an ammoniated extract (product C: ALK-Abello, Madrid, Spain). A positive result was considered as the appearance of a wheal with a diameter >3 mm. In patients with confirmed NRL allergy, wheal mean (s.d.) diameters were 7.3 (2.1) with product C, and 5.7 (2.3) and 4.4 (1.8) with products B and A respectively (p = 0.004 C vs. B and A). Mean wheal diameters were significantly higher for product C in comparison with product B and A (p < 0.04). Sensitivity according to the different products tested was 65% (product A); 81% (product B) and 96% (product C) (p = 0.0084; C vs. A). No difference between the three products was observed regarding diagnostic specificity (94%, 88% and 94%, product A, B and C, respectively). Our study shows that diagnostic sensitivity of different latex extract for SPT could differ. In this particular clinical setting (i.e., children with NRL allergy) ammoniated latex extract shows a higher sensitivity in comparison with non-ammoniated products. This aspect should be considered in the diagnostic approach in subjects with suspected NRL allergy. In children with clinical confirmed latex allergy, sensitivity and specificity of different commercially available skin prick test could vary. Ammoniated latex extract has shown a higher sensibility in comparison with non-ammoniated products.

The upper eyelashes in vernal keratoconjunctivitis (VKC) patients have been reported to be longer than in healthy age- and gender-matched subjects. Eyelash length positively correlated to the severity of the disease and negatively to the employment of cyclosporine eye drops, suggesting that specific humoral factors could be involved in both ocular inflammation and elongation of the eyelashes. The aim of the present study is to evaluate a possible relationship between eyelash length and the duration of topical cyclosporine treatment. The length of the upper eyelashes of 34 VKC patients never treated with topical cyclosporine (Cyc-NT) was matched with that of 58 VKC patients treated with cyclosporine (Cyc-T). The latter group was divided into three subgroups, depending on the duration of therapy: 1–6 months (group 1; 21 subjects), 7–12 months (group 2; 19 subjects), >12 months (group 3; 19 subjects). Cyc-NT patients' eyelashes were significantly longer than those of VKC patients treated for 1–6 months (group 1). No significant difference was found between Cyc-NT and Cyc-T patients in group 2 and group 3. The differences between Cyc-T patients and group 1 and 2, group 2 and 3, and group 1 and 3 were not statistically significant. The eyelash shortening observed seems directly related to the rapid improvement of ocular symptoms induced by the treatment. A receptor down-regulation by mediators of ocular inflammation may explain this data, although different cytokines, hormones or other humoral mediators could be expressed on the ocular surface at different stages of the disease, mainly in periods of rapid change of the clinical course.

The diagnosis of latex allergy is made on clinical history, but a confirmatory skin prick test (SPT) or a serological assay based on a commercial latex extract is always recommendable. Different raw materials can be used in the preparation of commercial latex extracts. Such extracts can consequently show both different qualitative profiles and a different diagnostic potential. Therefore, the selection of a proper latex extract is essential for in vitro and in vivo diagnosis of latex allergy. In the present study three different latex extracts, prepared from different raw materials (ammoniated -AL-, serum -SL-, or rubber particles -RPE- latex), are compared by in vitro techniques using sera from twenty patients with latex allergy. SDS-PAGE technique was used to compare the antigenic profile of the three latex extracts. Subsequently, their allergenic profiles were evaluated by immunoblotting technique using the individual sera from the twenty latex allergic patients. The diagnostic potential of the three latex extracts was also evaluated using direct Radio-Allergo-Sorbent Test (RAST) as well as skin prick tests (SPTs). In order to establish the more appropriate latex extract in a perspective of in vivo diagnosis of latex sensitization, the same latex extracts were subsequently compared by an in vivo SPT involving ten of the above subjects. The SDS-PAGE profiles of the three latex extracts examined were quite different. SL extract showed numerous bands comprised between 10–100 kDa. RPE extract was characterized by two intense bands at 14 and 20 kDa while AL extract showed the poorer antigenic composition. Analogously, immunoblotting analysis evidenced a different profile in relation to both different patients and extracts. For only two out of the twenty sera, direct RAST results showed a same positive class in relation to the different latex extracts used. SPT with SL extract showed, in respect to the other extracts (AL, RPE), a significantly higher wheal. This study showed that SL extract is able to express the best in vitro and in vivo diagnostic potential. Thus, its use should be preferred for the diagnosis of patients affected by latex allergy.

Although reversible H2 receptor antagonists are usually well tolerated, there are few reports on anaphylactic reactions triggered by ranitidine. Here we report the first case of anaphylaxis to ranitidine in a child. This was an IgE-mediated event occurring in a patient who had never used ranitidine before.

Although several cases of severe hypoalbuminemia resulting from rice milk have been described in the past, today the use of rice milk without nutritional counseling to treat eczema is still a continuing, poor practice. We describe a kwashiorkor case in an infant with severe eczema exclusively fed with rice milk. It is well documented that rice milk is not a sufficient protein source. Moreover, only a small portion of eczema is triggered by food allergy. In conclusion this case raises the importance of managing dietary changes facing food allergies with responsibility for specialized consensus among pediatricians, nutritionists, endocrinologists and allergists all of them specialist professionals.

Gleich's syndrome is characterized by recurrent localized angioedema, hypereosinophilia, elevated levels of IgM, rapid weight gain, itchy urticaria and fever. Little is known about the pathogenesis of this disease. Increased serum levels for IL5, IL6 and C5a have been reported before and during clinical exacerbations. In order to better understand the role of the T cells in Gleich's syndrome we analyzed the intracellular cytokine expression in CD3+ cells of a patient affected by the disease. As hypereosinophilia was documented, we asked whether IL-4 and IL-5 levels were increased, and the intracytoplasmatic expression of these Th2-cytokines was determined. The percentage of T lymphocytes (CD3-gated cells) of both CD8− and CD8+ phenotype expressing different cytokines showed an unusually high percentage of Th2-related cytokine (IL-4, IL-5 and IL-13) expressing T lymphocytes. The two new variants (myeloproliferative and lymphoproliferative) seem to account for hypereosinophilia in patients with hypereosinophilic syndrome (HES). In the lymphroliferative variant, the presence of a clonal CD3-CD4+ Th2 like lymphocyte secreting IL-4 and IL-5 in peripheral blood, may explain the hypereosinophilia and the hyper-IgE. In our study we show that the patient had a lymphoproliferative variant and her T cell had a Th2 type phenotype. Moreover, we suggest that Th2 lymphocytes may play a role in the pathogenesis of Gleich's syndrome. Further studies are needed to evaluate the possibility that a polyclonal aspecific activation of Th2 type cells can lead to hypereosinophilia, IgE production and the other manifestations typical of Gleich's syndrome.

Background A predominance of Th2 response has been suggested in vernal keratoconjunctivitis (VKC), and a high prevalence of IgE-sensitized (IgE-S) patients has been reported (positive skin prick test or serum-specific-IgE). Palpebral and bulbar VKC are considered to be expressions of the same disease and only occasional racial and histopathological differences are described between the two forms. Tear levels of eosinophil cationic proteins have been correlated with the severity of ocular symptoms; however, there is no published study that demonstrates the presence of serum markers of disease activity. Objective This study was performed to evaluate the prevalence of IgE-sensitization in palpebral, bulbar and mixed VKC and to determine possible useful markers of disease activity in peripheral circulation. Methods A total of 110 white VKC patients (mean age 8.3 years, range 3.2–18 years) were evaluated for ocular score in the active phase of the disease. Skin prick tests and serum-specific IgE for common allergens, serum-total IgE, peripheral blood eosinophil counts (PBECs) and serum eosinophil cationic protein (s-ECP) were determined. Fifteen age-matched non-IgE-S control children underwent the same determinations. Results s-ECP, PBECs and s-total IgE were significantly higher in IgE-S than in non-IgE-S VKC patients and in non-IgE-S VKC patients than in controls. A lower prevalence of IgE-S patients was found in bulbar vs. tarsal (P = 0. 050) or mixed forms (P = 0.002). The score of giant papillae was strongly correlated with s-ECP levels (P

Corticosteroids have been the only effective topically administered treatment for severe vernal keratoconjunctivitis (VKC), but their prolonged use is often associated with complications. Topical cyclosporine therapy has been used in the past decade, but few controlled trials have been conducted, and conflicting results have been reported.This study sought to evaluate the efficacy and safety of ocular administration of cyclosporine in VKC.Twenty-four children with severe VKC were treated with cyclosporine 2% eyedrops. The treatment began in spring and lasted 4 months. One eye was treated with cyclosporine (Cs-eye); the fellow eye received the vehicle as placebo (Pl-Cs-eye) during the first 2 weeks in a double-blind, placebo-controlled trial and thereafter was treated with cyclosporine (open trial). Patients were instructed to protect their eyes against sunlight. Ocular symptoms and signs were scored at entry and at 2 weeks, 4 weeks, and 4 months after the beginning of treatment. All children underwent biochemical and immunologic evaluations.Compared with baseline, scores for ocular signs and symptoms at 2 weeks decreased significantly in the Cs-eyes (P0.001), and signs improved in the Pl-Cs-eyes (P = 0.001). A significant difference was noted between Cs-eyes and Pl-Cs-eyes at 2 weeks for both subjective (P0.005) and objective (P0.001) scores. At 4 weeks, scores for signs (P0.001) and symptoms (P = 0.01) were reduced in the Pl-Cs-eyes, with no further improvement in the Cs-eyes. At 4 months, clinical scores had declined further, and serum eosinophil cationic protein levels were significantly lower than at entry (P = 0.009). Most patients reported mild burning sensation and tearing after administration of cyclosporine. Four patients (17%) required an additional brief period of topical corticosteroid therapy.Cyclosporine eyedrops were effective and safe for treating severe VKC, without causing major side effects. Most of the therapeutic effect was achieved after 2 weeks. The initial therapeutic effect was maintained during the next 3 months, with a further slow decrease in the symptoms.

Background The drug provocation test (DPT) is the gold standard to rule out drug hypersensitivity. There are standardized DPT protocols to diagnose immediate reactions to drugs, but not for nonimmediate reactions. Objective The aim of this study was to show the sensitivity and specificity of an allergy work-up that included a 5-day DPT in children with histories of nonimmediate reactions to amoxicillin through focusing on a pediatric population with histories of immediate and nonimmediate reactions to amoxicillin. Methods Two hundred consecutive patients with histories of amoxicillin reactions referred to the Allergy Unit of Anna Meyer Children's Hospital for suspected drug allergy from 2008 to 2011 underwent in vivo tests with the culprit drug according to European Academy of Allergy and Clinical Immunology guidelines. Moreover, most of those children, regardless of the skin tests results, were challenged with amoxicillin for a total of 5 days. Results In 4 years, 200 patients were evaluated for a history of drug hypersensitivity to amoxicillin. The majority of patients (76%) had a history of mild nonimmediate reactions. All 200 patients underwent skin tests, and 9 of 200 tested positive. A total of 177 DPTs were performed with amoxicillin for 5 days in each child. Diagnosis of amoxicillin allergy was confirmed by a DPT in 17 patients (9.6%); 14/17 had history of nonimmediate reactions; 4/14 (26.6%) reacted on day 5. Conclusion According to our results, a long-term DPT protocol increases the sensitivity of the allergy work-up, and it should be recommended for patients with a history of amoxicillin nonimmediate reaction.

Neonatal short bowel syndrome (SBS) follows early intestinal resections that may expose the children to increased intestinal contact with undigested food proteins and to the risk of food allergy. We report three consecutive cases of cow's milk allergy (CMA) in SBS infants. We reviewed three cases of CMA developed in 37 children with neonatal SBS followed up in the last 10 years. The setting of the survey was the Gastroenterology-Hepatology and Nutrition Unit of the Pediatric Hospital ‘Bambino Gesu’ in Rome. The diagnosis of CMA was based on the oral food challenge and was supported by the results of the skin prick tests (SPT) and/or the specific immunoglobulin (Ig) E. Two patients had persistent liquid stools and periodic episodes of vomiting when they were fed with an intact milk protein-based formula, that disappeared with extensively hydrolyzed formula and amino-acid-based formulae, respectively. The third patient developed maculo-papular rash, flushing and angioedema, when he was introduced a regular formula. The challenge-confirmed CMA in all patients. Positive specific IgE for milk proteins was documented in all the three patients. Two out of the three patients had positive familial history for allergy and positive SPT. Our findings suggest that the SBS patients require a careful clinical monitoring of the tolerance for the cow’s milk proteins, because CMA could be more frequent than expected. A prospective regular assessment for the potential cow milk sensitization by SPT and specific IgE may clarify the nature of the association and support the clinical surveillance. Multicenter studies are required to better evaluate this comorbidity.

Background Clarithromycin is one of the most frequently prescribed oral macrolidic antibiotics in the pediatric population. Suspected adverse reactions to clarithromycin have been frequently described by parents of children examined in pediatric allergy units, but there is a lack of reliable methods available in detecting the presence of specific IgE antibodies. Objective To investigate the prevalence of a clarithromycin allergy in children seen in a pediatric allergy unit using standardized skin tests and oral provocation tests (OPTs). Methods Sixty-four children were referred with a history of a clarithromycin-associated adverse drug reaction. All these children underwent skin tests and OPTs. The nonirritating intradermal skin test concentration for clarithromycin was determined in a control group of 18 children who had tolerated clarithromycin in the previous month. Results The threshold nonirritating intradermal concentration was established at the 10:2 dilution (0.5 mg/mL). Nine of the 64 children had an immediately positive intradermal response to the 10:2 dilution and only 1 child to the 10:3 dilution (0.05 mg/mL). None had positive skin prick test results or delayed skin responses to intradermal tests. Four of 64 children (6%) with previously described adverse reactions due to clarithromycin intake had a positive OPT reaction. When we correlated the intradermal skin test results to the OPT results, intradermal test sensitivity and specificity were 75% and 90%, respectively. Conclusion Intradermal tests seem to be useful in allergologic workup in children with suspected clarithromycin hypersensitivity and may help reduce the need for OPTs.

Long-term efficacy of surgical removal of pseudomembranes in a child with ligneous conjunctivitis treated with plasminogen eyedrops

Acute rhinosinusitis (ARS) is one of the most common reasons for physician visits and for significant school absenteeism, although precise data on its prevalence and incidence are still lacking. RS is defined as acute if there are symptoms lasting12 wk with complete resolution. Superinfection by bacteria following a viral infection is the most important mechanism of ARS. Diagnosis of ARS should be made on clinical grounds alone. Typically, acute bacterial RS is self-limited and goes through spontaneous recovery within 4 wk. Recognizing the occurrence of bacterial superinfections of the sinuses during a common viral respiratory infection is fundamental to making the decision to start an appropriate antibiotic treatment. Topical treatments such as saline irrigation, nasal decongestants, steroids, antihistamines, and fungicides are all in widespread pediatric use, but analyzing the literature gives poor evidence of efficacy, except for topical steroids. RS is a multifactorial condition that poses a diagnostic and management challenge to infectivologist and ear-nose-throat specialists as well as to pediatricians.