Disagreement between guidelines regarding the third step of asthma drug therapy for school-age children.

With the help of a routine clinical case, we highlighted the difference between two of the best asthma guidelines available at the time regarding therapeutic suggestions for the so-called "third step" for school-age asthmatic children. We have analyzed the scientific evidence that each of the two guidelines brings to support their position. Finally, we have motivatedly solved the clinical scenario. However, the question of disagreement between two guidelines remains unresolved. This can lead to unjustified differences in the management of schoolchildren with persistent asthma.

Does delayed urticaria induced by drug allergy exist?

With the help of a routine clinical case about delayed urticaria induced by drug, we have analyzed the scientific societies reports published during the last 5 years on this topic. We highlighted the differences between the EAACI consensus and documents on drug allergy, commenting their positions and some of their definitions on delayed urticaria. However, the question of disagreement between definitions of delayed urticaria can generate confusion. It would be beneficial to have more and "official" clearness about this topic because of its important clinical application to our patients.

Yogurt is tolerated by the majority of children with IgE-mediated cow's milk allergy.

BACKGROUND: Children with IgE-mediated cow's milk allergy (IgE-CMA) with gastrointestinal symptoms tolerate yogurt at 100%. Yogurt tolerance in children with IgE-CMA with urticaria and anaphylaxis was 7%. METHODS: We enrolled children with IgE-CMA with cutaneous, respiratory, gastrointestinal and anaphylactic symptoms. All performed prick by prick (PbP) and oral food challenge (OFC) with yogurt. Some children performed also an OFC with CM mixed with wheat flour and baked, baked liquid CM, parmesan. RESULTS: 34 children were enrolled, 31/34 (91%) with systemic adverse reaction after ingestion of CM (systemic CMA), 3/34 (9%) with isolated contact urticaria (ICU CMA). PbP with yogurt was negative only in one patient. OFC with yogurt was passed (that is, the OFC was negative) by 20/31 (64%) of the children with systemic CMA. 10/11 (91%) of the patients who failed OFC (that is, the OFC was positive) with yogurt were positive to SPT with casein vs. 8/20 (40%) of the patients who passed it (p=0.018). None of the 19 children who passed OFC with yogurt failed all OFC with processed CM forms other than yogurt that tested vs. 4/8 among those who failed OFC with yogurt (p=0.006). The rub test with yogurt was negative in 1/3 (33%) of the patients with ICU CMA. CONCLUSIONS: The results of our study are placed alongside others already present in the literature and concerning other methods of processing CM proteins and help to reduce the dietary restrictions of the majority of children with systemic IgE-CMA.

Cooking influence in tolerance acquisition in egg-induced acute food protein enterocolitis syndrome.

BACKGROUND: Few studies on the age of resolution of Food Protein Induced Enterocolitis Syndrome (FPIES) induced by solid foods are available. In particular, for FPIES induced by egg, the mean age of tolerance acquisition reported in the literature ranges from 42 to 63 months. OBJECTIVE: We have assessed whether the age of tolerance acquisition in acute egg FPIES varies depending on whether the egg is cooked or raw. METHODS: We conducted a retrospective and multicentric study of children with diagnosis of acute egg FPIES seen in 10 Italian allergy units between July 2003 and October 2017. The collected data regarded sex, presence of other allergic diseases, age of onset of symptoms, kind and severity of symptoms, cooking technique of the ingested egg, outcome of the allergy test, age of tolerance acquisition. RESULTS: Sixty-one children with acute egg FPIES were enrolled, 34 (56%) males and 27 (44%) females. Tolerance to cooked egg has been demonstrated by 47/61 (77%) children at a mean age of 30.2 months. For 32 of them, tolerance to raw egg has been demonstrated at a mean age of 43.9 months. No episodes of severe adverse reaction after baked egg ingestion have been recorded. CONCLUSIONS: It is possible to perform an OFC with baked egg, to verify the possible acquisition of tolerance, at about 30 months of life in children with acute egg FPIES.

Predictive value of the number of adverse reaction episodes for the IgE-mediated food allergy diagnosis.

INTRODUCTION AND OBJECTIVES: The reproducibility of the adverse reaction increases the suggestiveness of a history of food allergy. However, the positive predictive value (PPV) of multiple adverse reaction episodes for the diagnosis of IgE-mediated food allergy is not known. This evaluation was the objective of our study. PATIENTS AND METHODS: We retrospectively studied 180 children with a history of non-anaphylactic adverse reactions after the ingestion of a food. All children had the prick test positive for the offending food and performed the oral food challenge (OFC) within 12 months after the last adverse reaction episode (ARE). We have evaluated whether increasing the number of ARE increased the probability that the OFC would be positive (failed). RESULTS: 93 patients (52%) presented one ARE, 49 (27%) presented two ARE, 24 (13%) presented three ARE, 14 (8%) patients presented≥four ARE. The OFC was positive in 94/180 (52%). The outcome of the OFC was found to be positively correlated with the number of ARE (OR=1.56; 95% CI=1.16-2.09; p=0.003). A PPV=100% was observed with a number of ARE≥five. CONCLUSIONS: The number of ARE is an important predictor of the diagnosis of food allergy, although less than we would have imagined. The number of ARE could be used to increase the predictability of the diagnostic tests currently in use, to define clinical prediction rules alternative to OFC and easy to use in clinical practice.

Loss of tolerance for fishes previously tolerated in children with fish food protein induced enterocolitis syndrome.

We describe two case reports presenting some novel information on fish FPIES. Fish FPIES to one fish does not always start at the same time to other fish. Additionally, development of tolerance to the index fish do not necessarily imply tolerance to other reactive fish. This reflects on the best management of children with FPIES fish.

Diagnostic criteria for acute food protein-induced enterocolitis syndrome. Is the work in progress?

Food protein-induced enterocolitis syndrome (FPIES) is a non IgE-mediated gastrointestinal food allergic disorder. Some diagnostic criteria have been published for acute FPIES. Of course, they are not all the same, so the clinician must choose which ones to adopt for his/her clinical practice. We present here a brief review of these criteria and, through two clinical cases, show how the choice of one or the other can change the diagnostic destiny of a child with suspect FPIES.

Is food protein induced enterocolitis syndrome only a non IgE-mediated food allergy?

Food protein induced enterocolitis syndrome (FPIES) is classified as non-IgE-mediated or cell-mediated food allergy, although there is an atypical phenotype so defined for the presence of specific IgEs. All diagnostic criteria for FPIES include the absence of skin or respiratory symptoms of IgE-mediated type. We present four cases that suggest that specific IgEs may have a pathogenic role, resulting in the existence of different FPIES phenotypes. This could be important from a diagnostic and therapeutic point of view.

Ondansetron in acute food protein-induced enterocolitis syndrome, a retrospective case-control study.

BACKGROUND: Therapy for moderate to severe acute food protein-induced enterocolitis syndrome (FPIES) typically consists of intravenous fluids and corticosteroids (traditional therapy). Ondansetron has been suggested as an adjunctive treatment. We aimed to evaluate the efficacy of the parenteral (intravenous or intramuscular) ondansetron vs traditional therapy to resolve the symptoms of acute FPIES. METHODS: Cases of FPIES who had a positive oral food challenge (OFC) were retrospectively examined at two major hospitals over a two-year period (Rome, Italy; and Sydney, Australia). The efficacy of therapy, based on the percentage of cases who stopped vomiting, was compared in cases who received parenteral ondansetron and in cases who received traditional therapy or no pharmacological therapy. RESULTS: A total of 66 patients were included: 37 had parenteral ondansetron, 14 were treated with traditional therapy, and 15 did not receive any pharmacological therapy. Nineteen percentage of children treated with ondansetron continued vomiting after the administration of the therapy vs 93% of children who received traditional therapy (P < 0.05, relative risk = 0.2). Children who received ondansetron or no therapy were less likely to require an admission overnight compared with those who received traditional therapy (P < 0.05). CONCLUSIONS: Parenteral ondansetron is significantly more effective than traditional therapy in resolving acute symptoms of FPIES. The relative risk = 0.2 greatly reduces the bias linked to the lack of randomization. These findings suggest an effective treatment for vomiting in positive FPIES OFCs and allow for more confidence in performing OFCs.

A very unusual case of food allergy, between FPIES and IgE-mediated food allergy.

Food protein induced enterocolitis syndrome (FPIES) is a food-related gastrointestinal hypersensitivity disorder, probably non-IgE-mediated. Over the years, various diagnostic criteria have been proposed to identify FPIES. In the last few years, there was an increased interest from researchers about FPIES's syndrome, that frequently brought to discover new aspects of this disease. We describe an unusual case of FPIES to egg in a 21-months-old child, because of its clinical characteristics that reflect some aspects of IgE-mediated allergy and other of non IgE-mediated allergy. Although we believe that the most correct diagnosis for our case is FPIES, we think also that this is undoubtedly an atypical form. This is in fact, the first description of a patient who simultaneously has both clinical expressions of IgE-mediated FA that of FPIES. Our case highlights the need to review criteria for FPIES diagnosis.

Prevalence of adverse reactions following a passed oral food challenge and factors affecting successful re-introduction of foods. A retrospective study of a cohort of 199 children.

BACKGROUND: After a passed oral food challenge (OFC), regular and normal food consumption is attended. The main objective of this study is to assess the safety of tested food dietary re-introduction after a passed OFC. PATIENTS AND METHODS: In 2014, a telephone survey was submitted to patients who passed OFC and those who failed it only presenting with contact urticaria (we consider these OFC as passed), between 2009 and 2013. Questionnaire items included demographic data, food allergy details, food consumption after the OFC was performed, recurring symptoms and life style changes. RESULTS: 249 OFC questionnaires were collected from 199 children, 228 OFC were passed, 21 were failed exclusively due to contact urticaria. The most tested food was cows' milk. In 71% of cases target food was re-introduced in patients diet in normal amounts. We found children >2 years introduced less frequently tested food than infants. In 2% of cases adverse reactions to offending food were reported, but severe reactions never occurred. DISCUSSION: The majority of children of this study ate target food regularly and their family's quality of life improved. In our study, adverse reactions frequency in patients who passed OFC was very low and never serious. We highlight the importance of re-assessing proper food consumption in every patient who passed OFC.

Matrix effect on baked milk tolerance in children with IgE cow milk allergy.

BACKGROUND: Children with IgE-mediated cow's milk allergy (IgE-CMA) often tolerate baked milk within a wheat matrix. In our study we evaluated the impact of wheat matrix and of little standardised cooking procedures on tolerance of baked milk. We also tested tolerance versus parmigiano reggiano (PR) and whey-based partially hydrolysed formula (pHF). METHODS: Forty-eight children with IgE-CMA were enrolled. They underwent prick-by-prick (PbP) and open oral food challenge (OFC) with baked cow's milk (CM), both within a wheat matrix (an Italian cake named ciambellone) and without (in a liquid form), with PR and with pHF. After a passed OFC, children continued to eat the food tolerated. In particular, after passed OFC with ciambellone, children were allowed to eat any food containing CM within a wheat matrix, with the only condition that it was baked at 180°C for at least 30min. Three months after, parents were asked to answer a survey. RESULTS: 81% of children tolerated ciambellone, 56% liquid baked CM, 78% PR and 82% pHF. Negative predictive value of PbP performed with tested foods was 100%. No IgE-mediated adverse reactions were detected at follow-up carried out by the survey. CONCLUSIONS: Wheat matrix effect on tolerance of baked milk was relevant in slightly less than half of cases. If our results are confirmed by larger studies, a negative PbP will allow patients to eat processed CM without undergoing OFC. Moreover, in order to guarantee tolerance towards baked milk, strict standardised cooking procedures do not seem to be necessary.

Effect of multiple honey doses on non-specific acute cough in children. An open randomised study and literature review.

BACKGROUND: Honey is recommended for non-specific acute paediatric cough by the Australian guidelines. Current available randomised clinical trials evaluated the effects of a single evening dose of honey, but multiple doses outcomes have never been studied. OBJECTIVES: To evaluate the effects of wildflower honey, given for three subsequent evenings, on non-specific acute paediatric cough, compared to dextromethorphan (DM) and levodropropizine (LDP), which are the most prescribed over-the-counter (OTC) antitussives in Italy. METHODS: 134 children suffering from non-specific acute cough were randomised to receive for three subsequent evenings a mixture of milk (90ml) and wildflower honey (10ml) or a dose of DM or LDP adjusted for the specific age. The effectiveness was evaluated by a cough questionnaire answered by parents. Primary end-point efficacy was therapeutic success. The latter was defined as a decrease in cough questionnaire score greater than 50% after treatment compared with baseline values. RESULTS: Three children were excluded from the study, as their parents did not complete the questionnaire. Therapeutic success was achieved by 80% in the honey and milk group and 87% in OTC medication group (p=0.25). CONCLUSIONS: Milk and honey mixture seems to be at least as effective as DM or LDP in non-specific acute cough in children. These results are in line with previous studies, which reported the health effects of honey on paediatric cough, even if placebo effect cannot be totally excluded.

Risk of adverse IgE-mediate reaction at the first egg ingestion in children with atopic dermatitis. Results of a case-control study.

BACKGROUND: Studies have reported that children with atopic dermatitis (AD) have a high risk of adverse reactions at first egg ingestion. METHODS: We enrolled 79 children with AD retrospectively and 45 children without AD (control group) prospectively, who had never eaten egg. All children underwent skin prick tests (SPT) with commercial extracts and prick by prick with natural food (raw and boiled egg). Oral food challenge (OFC) was performed in SPT positive patients. RESULTS: Sixty-six percent (52/79) of AD group and 11% (5/45) of Control group had at least one positive SPT (p<0.001), Relative Risk (RR)=5.9 and Odds Ratio=15.4. Of the 46/52 sensitised children in the AD group, 36 children ate egg for the first time in hospital during an OFC and 10 children ate egg at home because of their parents' choice, with 19/46 (41%) resulting in allergic reactions to raw and/or boiled egg. Four/five sensitised children in the control group underwent OFC and three of them (75%) showed an allergic reaction to raw, but not boiled egg. Thirty percent (14/46) of AD group had a systemic reaction vs. 25% (1/4) of Control group. CONCLUSION: A child with AD has a RR of sensitisation to egg six times higher than a child without AD, before the first known ingestion. We propose to test sensitisation to egg in every child with AD who has never eaten egg, and to perform OFC in those with positive SPT in hospital setting.

Severe anaphylaxis to sheep's milk cheese in a child desensitized to cow's milk through specific oral tolerance induction.

Specific oral tolerance induction to food (SOTI) is a new promising treatmentfor persistent IgE-mediatedfood allergy. Our paper reports a case of a 5-year-old girl with cow's milk allergy, who developed severe anaphylaxis after the ingestion of a croissant containing sheep's milk ricotta cheese, even though she had been previously desensitized to cow's milk through SOTI. The sheep's milk specific allergen causing the severe allergic reaction (a derivative of alpha-casein of 54,1kDa) was identified by SDS-PAGE and immunoblotting. We conclude that SOTI is a species-specific procedure and the induced tolerance to cow's milk doesn't necessarily provide protection against milk of other mammals. Therefore, children desensitized to cow's milk through SOTI should strictly avoid the intake of milk of other mammals, until tolerance to those kinds of milk is documented by an oral food challenge.

Can food protein induced enterocolitis syndrome shift to immediate gastrointestinal hypersensitivity? A report of two cases.

Food protein induced enterocolitis syndrome (FPIES) is a food-related non-IgE-mediated gastrointestinal hypersensitivity disorder. Atypical FPIES is characterized by the presence of specific IgE for the causative food. The guidelines suggested for diagnostic oral food challenge in pediatric patients affected by suspected FPIES are different from the ones for children with IgE-mediated food allergy. We describe two cases of atypical FPIES that turned into IgE-mediated gastrointestinal anaphylaxis. Our experience suggests to adapt OFC according to the outcome of specific IgE for the causative food When causative food-related IgE werepositive, we suggest to follow the guidelines for IgE mediated food allergy.

Oral desensitization in egg acute food protein-induced enterocolitis syndrome.

OBJECTIVE: Strict avoidance of trigger food is the primary management of food protein-induced enterocolitis syndrome (FPIES). No published data are available on active induction of tolerance with oral desensitization (OD) in FPIES. CASE REPORT: We carried out an OD in a 9 and a half years old boy with persistent acute egg FPIES. OD was performed with increasing doses of raw egg every week, starting with an initial dose of 0.2 ml. The boy presented mild and transient gastrointestinal adverse reactions when the 4 ml dose was reached. He could tolerate a whole raw egg in less than 14 months. CONCLUSIONS: Even though randomized controlled clinical trials on patients including various phenotypes of FPIES are needed, our experience is encouraging about the possible efficacy and safety of OD in this food allergy.

Specific oral tolerance induction for food. A systematic review.

BACKGROUND: Specific oral tolerance induction (SOTI) is a new therapeutic approach in the treatment of persistent food allergy. OBJECTIVE: The purpose of this article is to systematically review the literature in order to identify, appraise, and synthesize the evidence about SOTI efficacy and safety. METHODS: A comprehensive search for citations was conducted on May 2, 2009 using MEDLINE via PubMed. Randomized controlled trials (RCTs) including subjects of any age were considered. All these studies were assessed, discussed in details and evaluatedfor quality by authors in a standardized independent way. RESULTS: 15 clinical trials were found. Of these, six trials met the inclusion criteria: three were open label RCT, three were double blind placebo controlled RCT. Two were conducted using sublingual immunotherapy, four using oral desensitization. Overall, the methodological quality of the studies was sufficient. The mean Jadad score of the studies was 3.33 (range = 2-5). Main characteristics and results of the studies were showed and discussed. CONCLUSIONS: SOTI seems to be a possible approach to accelerate the development of tolerance in children affected by food allergy. However, other studies are needed to clarify which is the best treatment and protocol to follow in order to reduce the adverse events and to increase the percentage of success, before thinking that SOTI might be part of the clinical practice.

Clinical evaluation and treatment of acute asthma exacerbations in children.

This update on treatment of asthma exacerbations in children is the result of an Italian Pediatric Society Task-force, made up of a panel of experts working in 2007-2008. The aim is to give clear indications on the use of the drugs most employed in children, grading the quality of evidence and the strength of recommendations. Suggestions on their limits due to unlicensed and off-label use are reported. The level of evidence and the strength of recommendations for different therapeutic approaches demonstrate that frequently the use of drugs in children is extrapolated from the experience in adults and that more studies are required to endorse the correct use of different drugs in asthmatic children.