Low-Dose Oral Food Challenge with Hazelnut: Efficacy and Tolerability in Children.

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.

Anaphylaxis to Over-the-Counter Flurbiprofen in a Child.

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.

Tacrolimus vs. cyclosporine eyedrops in severe cyclosporine-resistant vernal keratoconjunctivitis: A randomized, comparative, double-blind, crossover study.

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 < 0.001). Likewise, the quality of life significantly improved despite only half the eyes being successfully treated. Serum creatinine and blood parameters were constantly within the normal range, and both blood Cyc and Tcr concentrations remained below the lowest detectable levels. CONCLUSIONS: Topical Tcr is very effective and safe in the short term for patients suffering from severe VKC resistant to topical Cyc.

A kwashiorkor case due to the use of an exclusive rice milk diet to treat atopic dermatitis.

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.

Anaphylaxis to Intravenous Ranitidine in a Child.

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.

Anaphylaxis to Intravenous Tramadol in a Child.

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.

Children monosensitized to pine nuts have similar patterns of sensitization.

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.

Management of acute rhinosinusitis.

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 <12 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.

Correlation of anti-Pru p 3 IgE levels with severity of peach allergy reactions in 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.

Risk factors for severe pediatric food anaphylaxis in Italy.

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.

Long-Term Safety and Efficacy of Tacrolimus 0.1% in Severe Pediatric Vernal Keratoconjunctivitis.

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.

Oral desensitization to milk: how to choose the starting dose!

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 highly 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.

Increased Lacrimal Fluid Level of HMGB1 in Vernal Keratoconjunctivitis.

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 group of healthy subjects of same age. Methods: Tear fluids was collected in a group of VKC patients and compared to a control group of healthy subjects. HMGB1 concentration was measured using the HMGB1 ELISA II test both in VCK and control subjects. Results: The mean concentration of HMGB1 in tear fluids of 45 VKC patients was 0,977 ± 0,72 ng/ml whereas in the control group was 0,24 ± 0,25 ng/ml and the difference was statistically significant (p = 0,000106) Conclusion: The concentration of HMGB1 in VCK patients was found to be significantly increased, suggesting a possible role of this protein in the inflammatory mechanism of VKC.

Donkey's Milk in the Management of Children with Cow's Milk protein allergy: nutritional and hygienic aspects.

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.

Sensitivity and specificity of different skin prick tests with latex extracts in pediatric patients with suspected natural rubber latex allergy--a cohort study.

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-Abellò, 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.