Lucrezia Sarti

Side effects and their impact on the success of milk oral immunotherapy (OIT) in children

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.

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.

Drug fever after a single dose of amoxicillin-clavulanic acid

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

Anaphylaxis to the amoxicillin skin prick test: utility of the basophil activation test in diagnosis

Anaphylaxis in response to a skin prick test (SPT) with the culprit Currently, it is not possible to calculate the specificity because a DPT drug rarely occurs in patients with a suspected drug allergy.1 The diagnosis of b-lactam hypersensitivity is usually based on the patient’s clinical history, positive skin test results, or specific IgE antibody measurements. The basophil activation test (BAT) should be performed in cases in which the diagnosis of a drug allergy is highly suspected but is not supported by the results of skin testing or in vitro IgE measurements are not available.2,3 We report the case of a 77-year-old woman with a medical history of itchy erythema while taking oral amoxicillin who was referred to the Allergy Unit of San Giovanni di Dio Hospital. The patient was receiving ramipril and lansoprazole therapy for high blood pressure and gastroesophageal reflux respectively since 60 years of age. A SPT with amoxicillin was performed at a concentration of 20 mg/mL. The allergy workup was conducted according to the European Network for Drug Allergy recommendations.4 Basophilic cells were selected from the lymphocyte population using antiCCR3 according to the method of Ebo2 (Flow-CAST High Sense; Buhlmann Laboratorie AG, Shonenbuch, Switzerland). At least 300 basophils were assessed in each assay. The up-regulation of the activation marker CD63 and CD203c was calculated as the percentage of the CD63and CD203c-positive cells. A positive result required the percentage of activated basophils after incubation with the allergen to exceed 5%. In addition, the percentage of basophils activated after allergen stimulation should be at least double the percentage of spontaneously activated basophils (stimulation index, 2). The result of the SPT with amoxicillin was highly positive with pseudopods. Shortly after the SPT, the patient developed profuse sweating and became unconscious. The patient was given epinephrine at 0.01 mg/kg intramuscularly, and the injection was repeated 5 minutes later because of persistent hypotension (blood pressure, 70/40 mm Hg). The patient’s tryptase level was 17 mg/mL (basal level, 5 mg/mL) 3 hours later. The patient was discharged 4 hours later. The patient had positive penicillin V, ampicillin, and amoxicillin serum specific IgE. Two months later the BAT was performed with amoxicillin, clavulanic acid, minor determinant mixture, penicilloyl-polylysine, and cefuroxime. The results were positive to amoxicillin, clavulanic acid, and minor determinant mixture. The results were negative to penicilloyl-polylysine and cefuroxime. A SPTand intradermal testwith cefuroxime (20mg/mL) were performed and produced negative results. On the basis of these results, we performed an oral drug provocation test (DPT) with cefuroxime, and the patient tolerated the drug. The BAT was repeated 1month laterwith cefuroxime, and the resultwas positive. Skin testing remains the most important method to confirm b-lactams allergy; the sensitivity of skin testing is up to 70%.

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.

T-cell activation in two cases of Stevens-Johnson syndrome after receiving amoxicillin-clavulanic acid

could all be correctly classified in the predictive tree (unpublished data). Our study was conducted in a single centre, which could be considered as a selection bias. However, the repartition of proven food allergy in our patients was close to other French data.14 Because our sample was rather small (126 patients), the risk factor assessment was limited and some risk factors found in other studies were not confirmed in our cohort. Another limitation of our study concerns the diagnosis of bronchospasm during OFC. In 10 cases (6.8%), spirometry was not performed during the OFC, the reaction needing to be treated in emergency. The diagnosis of bronchospasm was then made based on the symptoms presented by the patients. Finally, it should be underlined that we evaluated the appearance of bronchospasm during OFC, which is different from what people experience in “real life,” when consumed doses and cofactors could change the thresholds, symptoms, and the conditions of reactivity. In conclusion, we found that almost onethird of our foodallergic patients develop foodinduced bronchospasm, with a high risk of peanut allergy. These results should be confirmed by other studies, but suggest that the management of foodallergic patients must take into account the risk of bronchospasm, even in nonasthmatic patients, especially if suffering from peanut allergy.

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.