IgE-mediated fish allergy in Singaporean children.

BACKGROUND: Fish is one of the common causes of food allergy and there is limited literature about fish allergy in Singapore. OBJECTIVE: We aimed to describe the demographics, clinical features, and natural history of children with IgE-mediated fish allergy. METHODS: A retrospective review was conducted for children diagnosed with fish allergy in a tertiary pediatric hospital in Singapore between 2015 and 2020. RESULTS: The diagnosis of fish allergy was made in 108 patients based on a convincing history of IgE-mediated allergic reaction and a positive skin prick test. The median age at first reaction was 12 months (range 6-168) with most reacting on first ingestion (62.0%). The most common fish causing reactions were threadfin (48.1%), salmon (33.3%) and cod (31.5%). Majority presented with cutaneous symptoms (97.2%). Anaphylaxis occurred in 6.5%. Five were mono-sensitized (4.6%), 77 were oligo-sensitized (71.3%) and 26 were polysensitized (24.1%). Most can tolerate another species of fish (75.9%), most commonly salmon (37.0%), tuna (24.1%) and cod (22.2%). Median duration of follow up was 24 months (range 0-176). Twenty-eight out of 108 children (25.9%) acquired natural tolerance to index fish at a median age of 60 months (range 18-159). CONCLUSIONS: Most children with fish allergy can tolerate at least one other species of fish and resolution of fish allergy is possible. Thus, it is important to follow-up with an allergist to evaluate which fish species can be included in their diet to avoid unnecessary dietary restrictions.

Clinical, histopathological features and efficacy of elimination diet and proton-pump inhibitor therapy in achieving histological remission in Asian children with eosinophilic gastritis.

AIM: Paediatric eosinophilic gastritis (EG) is a rare disorder and existing literature on diagnostic criteria and management remains lacking. We aim to describe the clinical spectrum and assess the efficacy of dietary elimination and proton-pump inhibitor (PPI) therapy, with particular emphasis on histologic remission in children with primary EG. METHODS: We performed a retrospective study of patients aged 0-18 years diagnosed with EG at a single centre in Singapore from 2013 to 2021. EG was diagnosed based on histological criteria of infiltration of >30 eosinophils per high-power film (HPF) in >5 separate HPFs from gastric biopsies, in the absence of other causes. First-line treatment consisted of PPI therapy and empiric 1-6 food elimination diet (FED). Outcomes measured were clinical, endoscopic and histological remission (defined as eosinophil count <20/HPF in gastric biopsies). RESULTS: Twenty-one (66.7% females) patients were included with median age at diagnosis of 15 months (range:3-192). Majority presented with vomiting (76.2%) and gastrointestinal bleeding (71.4%). Twenty patients were initiated on FED+PPI and 16 had post-treatment biopsies. Clinical, endoscopic and histologic remissions were achieved in 94.7%, 81.3% and 68.8% respectively following FED+PPI. Histologic remission was significantly associated with younger age (9 vs. 132 months; P = 0.026). Four patients who did not respond to FED+PPI were started on oral viscous budesonide, of whom one achieved histological remission and two had clinical improvement. CONCLUSIONS: FED+PPI is effective as first-line treatment in achieving histological remission in paediatric EG particularly in younger patients. Topical corticosteroids can be considered for those who have failed FED+PPI therapy.

An Evaluation of the Mechanisms of Galacto-Oligosaccharide (GOS)-Induced IgE Cross-Linking on Basophils in GOS Allergy.

The prebiotics, galacto-oligosaccharides (GOS), are small carbohydrate molecules with 1-7 galactose units linked to glucose and have been shown to trigger IgE-mediated anaphylaxis in some cases following ingestion. It is still an unresolved question of how GOS cross-links IgE on basophils. In this study, we examined whether human galectins, a class of lectins that bind specifically to ß-galactoside carbohydrates, are involved in GOS-induced basophil activation. Basophil activation test to GOS and control allergen, Blomia tropicalis (Blo t) extract were performed in the presence or absence of four sugar-based galectin inhibitors (lactose, thiodigalactoside [TDG], TD139, and GB1107) and one peptide-based inhibitor, G3-C12. Results showed that TD139, GB1107, and G3-C12 did not display a specific inhibitory effect on GOS-induced basophil activation as compared to control allergen. An inhibitory effect of lactose and TDG on GOS-induced basophil activation was observed and varied between subjects with up to 100% inhibition at low doses of GOS. The results of competitive ELISA suggest that the inhibitory effects of high dose lactose and TDG on the basophil activation is likely due to the cross-reactivity of GOS-specific IgE to lactose and TDG. Basophil activation is performed using purified basophils suggested that cell surface receptors on other blood cells were not required to induce basophil activation. In conclusion, our results suggest that GOS, a low molecular weight sugar, is able to cross-link IgE independently.

IgE-mediated cow's milk protein allergy in Singaporean children.

BACKGROUND: Cow's milk protein allergy (CMA) is the second most common food allergy in Singapore. However, there is limited data on local paediatric CMA. OBJECTIVE: We aimed to describe the demographics, clinical characteristics, natural history and diagnostic performance of skin prick test (SPT) and cow's milk-specific immunoglobulin E (CM-IgE) in Singaporean children diagnosed with IgE-mediated CMA. METHODS: A retrospective review of medical records was conducted for children with an SPT performed to cow's milk between 2011 and 2016. RESULTS: There were 355 patients included, 313 cow's milk allergic and 42 cow's milk tolerant. The median age of reaction was 6 months (IQR 4-8). The most common allergic presentation was cutaneous reactions, followed by gastrointestinal reactions. Six patients (1.9%) reported anaphylaxis at initial presentation and 16 children (5.1%) experienced anaphylaxis to cow's milk at least once in their lifetime. Most of the CMA patients (81.8%) acquired natural tolerance by 6 years old. SPT to cow's milk of ≥ 7 mm and CM-IgE of ≥ 13 kU/L showed good discriminative abilities in predicting a failed oral food challenge (OFC) outcome. CONCLUSIONS: CMA is a food allergy which commonly presents during infancy, and parents need to be aware of the likelihood of severe allergic reactions, including anaphylaxis. Prognosis for CMA is generally favourable. Future prospective cohort studies are required to better understand the natural history and better define the diagnostic cut-off values for allergy testing in our population.

Outcome of drug provocation testing in children with suspected beta-lactam hypersensitivity.

BACKGROUND: Suspicion of beta-lactam (BL) hypersensitivity is often based on parental report. Evaluation is important as incorrect labelling has clinical consequence. OBJECTIVE: To describe the outcomes of drug provocation test (DPT) in children with suspected hypersensitivity. METHODS: A retrospective study of patients who completed BL DPT from 1 August 2016 to 31 December 2017 at a paediatric allergy centre in Singapore. Suspected hypersensitivity reactions were classified as immediate (onset ≤1 hour) or delayed (onset > 1 hour). Patients with immediate reactions underwent skin prick test (SPT) followed by DPT if SPT was negative. Patients with delayed reactions underwent DPT directly. RESULTS: We identified 120 children who reported 121 suspected hypersensitivity reactions. The median age at reaction was 2.0 years (interquartile range [IQR], 1.0-5.0 years) and the median age at DPT was 7.4 years (IQR, 4.2-11.1 years). The timing of suspected hypersensitivity reaction was immediate in 21% (25 of 121), delayed in 66% (80 of 121), and uncertain in 13% (16 of 121). Commonly implicated drugs were amoxicillin in 45% (54 of 121), amoxicillin-clavulanate in 37% (45 of 121), and cephalexin in 8% (10 of 121). Commonly reported symptoms were maculopapular rash 44% (53 of 121), urticaria 34% (41 of 121), and angioedema 22% (27 of 121). All SPTs (n = 26) were negative. There were 118 diagnostic DPTs to index drug and 3 DPTs to alternative drug. A negative challenge result was obtained in 93% (110 of 118) of diagnostic DPTs: 92% (96 of 104) and 100% (14 of 14) of DPTs to penicillin group and cephalosporins respectively. All challenge reactions were mild. CONCLUSION: Our study supports the opinion that prior skin tests may not be necessary for children who report nonsevere reactions and directly performing diagnostic DPT is a safe approach in the evaluation of suspected childhood BL hypersensitivity.

Perioperative anaphylaxis: A five-year review in a tertiary paediatric hospital.

Making a diagnosis of perioperative anaphylaxis and identifying culprit drugs are diagnostic challenges. The aim of this study is to describe the perioperative presentation of anaphylaxis and results of patients who underwent allergy evaluation. This is a retrospective review of perioperative anaphylaxis of severity Grade 2 and above based on the Australian and New Zealand Anaesthetic Allergy Group criteria from 2015 to 2019 in a tertiary paediatric hospital. Data collected were demographics, clinical features, investigations and management. Of the 35,361 cases of paediatric anaesthesia, there were 15 cases of perioperative anaphylaxis, giving an incidence of four in 10,000. The median age was seven years (interquartile range four-15 years) with a male predominance of 86.7% (13/15). The severity of anaphylaxis was Grade 2 in 33.3% (5/15) and Grade 3 in 66.7% (10/15). The commonest presenting feature was hypotension (13/15, 86.7%) while the earliest symptom was respiratory change (9/15, 60.0%). Dynamic tryptase was raised in 75% (6/8) of the patients with adequate tryptase samples. Eight patients (53.3%) completed allergy testing, of whom five patients (62.5%) had IgE-mediated anaphylaxis with skin test positive to cefazolin (n = 3), atracurium (n = 1) and rocuronium (n = 1). Three patients (25.0%) had non-IgE-mediated reactions with negative skin tests. Although only half the patients completed allergy evaluation, a culprit drug could be identified in 62.5%, with antibiotics being the commonest. This emphasises the need for appropriate evaluation in cases of suspected perioperative anaphylaxis.

A 5-year retrospective review of children with peanut allergy in the largest paediatric hospital in Singapore.

BACKGROUND: The prevalence of peanut allergy (PA) among children has increased significantly over the past decade. Even though the prevalence of PA in Singapore is considered low, peanut is the top trigger for food-induced anaphylaxis in Singaporean children. OBJECTIVE: To describe the demographic characteristics and clinical features of children with PA. METHODS: This is a 5-year retrospective review of children diagnosed with PA based on clinical history coupled with a positive skin prick test to peanut or positive oral food challenge results. RESULTS: There were 269 patients (53.9% males) with a clinical diagnosis of PA. The median age at first allergic presentation for the PA group was 24 months old, with interquartile range of 13-39 months. The most common form of peanut introduced was roasted peanut. The rate of peanut anaphylaxis was 7.1%. Concomitant tree nut sensitization was found in 32.3% of this cohort, predominantly to cashew nut. Majority of them have a personal history of atopy - 75.8% with eczema, 63.6% with allergic rhinitis, and 19.7% with asthma. CONCLUSION: This is the first large review of peanut-allergic children in Singapore. Prospective population-based studies are needed to establish the true prevalence and risk factors associated with the development of this potentially life-threatening condition.

Goat's milk anaphylaxis in a cow's milk tolerant child.

Goat's milk (GM) allergy commonly occurs together with cow's milk (CM) allergy due to cross-reactivity between highly homologous proteins. We present an unusual case of GM anaphylaxis in a CM tolerant child.

Predictive value of peanut skin prick test, specific IgE in peanut-sensitized children in Singapore.

BACKGROUND: The predictive decision points for both peanut skin prick test (SPT) wheal size and serum IgE concentrations, in peanut-sensitized children, have not been evaluated in Singapore. OBJECTIVE: We aim to derive clinically useful predictive decision points to be used for risk stratification of oral food challenge (OFC) in peanut-sensitized patients. METHODS: Patients with a positive SPT to peanut, performed during a 4-year period between 2012 and 2016, were included in a retrospective chart review. The patients were assessed for their peanut allergy status based on a convincing clinical history. Their first SPT and serum IgE results done at presentation to our centre were used. RESULTS: There were 269 patients with a clinical diagnosis of peanut allergy based on recent immediate reaction to peanut and 59 patients whom were tolerating peanuts regularly. There were 251 patients sensitized to peanut, without prior known peanut exposure. A wheal size of ≥8 mm and a peanut-specific IgE of ≥6 kU/L each provided for a 95% positive predictive value of clinical reaction to peanuts; the larger the wheal size on SPT, the higher the probability. CONCLUSION: The cutoff values derived in this study can help clinicians in the risk assessment of OFC in peanut-sensitized patients. Prospective studies using OFCs for the diagnosis of peanut allergy are needed to confirm the diagnostic performance of these tests in predicting OFC outcomes.

The Epidemiology of Food Allergy in the Global Context.

There is a lack of high-quality evidence based on the gold standard of oral food challenges to determine food allergy prevalence. Nevertheless, studies using surrogate measures of food allergy, such as health service utilization and clinical history, together with allergen-specific immunoglobulin E (sIgE), provide compelling data that the prevalence of food allergy is increasing in both Western and developing countries. In Western countries, challenge-diagnosed food allergy has been reported to be as high as 10%, with the greatest prevalence noted among younger children. There is also growing evidence of increasing prevalence in developing countries, with rates of challenge-diagnosed food allergy in China and Africa reported to be similar to that in Western countries. An interesting observation is that children of East Asian or African descent born in a Western environment are at higher risk of food allergy compared to Caucasian children; this intriguing finding emphasizes the importance of genome-environment interactions and forecasts future increases in food allergy in Asia and Africa as economic growth continues in these regions. While cow's milk and egg allergy are two of the most common food allergies in most countries, diverse patterns of food allergy can be observed in individual geographic regions determined by each country's feeding patterns. More robust studies investigating food allergy prevalence, particularly in Asia and the developing world, are necessary to understand the extent of the food allergy problem and identify preventive strategies to cope with the potential increase in these regions.

Cashew nut allergy in Singaporean children.

BACKGROUND: There has been an increasing trend of nut allergies in Singapore. OBJECTIVE: The aim of this study was to review the clinical characteristics of children with cashew nut allergy. METHODS: A retrospective analysis was conducted in a tertiary paediatric referral centre in Singapore from 2008 to 2015. A total of 99 subjects with positive specific IgE (≥0.35 IU/L) to cashew nut were identified. Clinical features including demographics, clinical reaction to cashew nut, associations with other nuts and test specific measurements were recorded. RESULTS: The results showed that cutaneous symptoms (71.2%) were the most common allergic manifestations. Anaphylaxis occurred in 3.8% of children. In addition, all cashew nut allergic subjects were cross-reactive (either sensitized or allergic) to pistachio. Cross-reactivity rate with peanuts was 53.8%. There was a strong prevalence of atopy among cashew nut allergic subjects. CONCLUSION: In conclusion, cashew nut allergy is a significant tree nut allergy in Singapore.

Debates in Allergy Medicine: Oral immunotherapy shortens the duration of milk and egg allergy - the con argument.

Oral immunotherapy (OIT) has been shown to be effective for inducing desensitization in children with cow's milk and egg allergy. In contrast, there is limited evidence that OIT can induce tolerance or sustained unresponsiveness in food allergic patients. Sustained unresponsiveness, determined by a food challenge following a period of secondary avoidance, has been suggested to reflect a more enduring state of tolerance and is pertinent when considering the ability of OIT to shorten the duration of food allergy. While it has been shown that children who tolerate baked forms of egg and milk are more likely to develop tolerance compared to those who are allergic to baked forms of these foods, there is no convincing evidence that OIT using modified allergen in baked foods can hasten resolution of cow's milk and egg allergy. Instead, it is likely that baked milk and baked egg tolerant children represent a sub-phenotype of milk and egg allergy that is more likely to resolve spontaneously over time.

An unusual case of infant seizures with anaphylaxis to wheat.

Wheat allergy is one of the commonest food allergies in childhood and it typically presents with IgE mediated reactions, including anaphylaxis. Seizures are not typically reported to be a direct manifestation of anaphylaxis, though it can occur secondary to hypoxia following significant haemodynamic compromise. We describe a case of a previously well infant, who presented with anaphylactic shock to wheat and responded well to the initial management, but subsequently developed a cluster of brief generalised tonic clonic seizures without any ongoing haemodynamic instability. The tryptase level that was performed at 4-5 hours post reaction was raised at 49.1 µg/L. Skin prick test to wheat, wheat specific IgE, the omega-5 gliadin IgE were positive. Extensive work-up was performed to look for an underlying cause of seizures and all returned negative. To our knowledge, this is the first case report describing an unusual presentation of multiple seizures in a young infant, in association with an anaphylactic episode. In the absence of any other seizure provoking factor and underlying cause, we believe the association is more likely causative than coincidental.

Cause and Clinical Presentation of Anaphylaxis in Singapore: From Infancy to Old Age.

BACKGROUND: The study objective was to compare age-related differences in the cause and clinical presentation of anaphylaxis. METHODS: We conducted a prospective study of patients visiting the emergency department for anaphylaxis. Data were collected from 3 emergency departments from 1 April 2014 to 31 December 2015. Patient electronic records with the diagnoses of allergy, angioedema, urticaria, and anaphylaxis (ICD-9 codes 9953, 9951, 7080, 9950, 7089) were screened and cases fulfilling World Allergy Organisation criteria for anaphylaxis were included. RESULTS: A total of 426 cases of anaphylaxis were identified with a median age of 23 years (range 3 months to 88 years and 9 months). The causes of anaphylaxis were food (n = 236, 55%), drugs (n = 85, 20%), idiopathic (n = 64, 15%), and insect bites or stings (n = 28, 7%). The most common food was shellfish (n = 58, 14%) and the most common drugs were non-steroidal anti-inflammatory drugs (n = 26, 6%). There were more cases of food anaphylaxis in children than in adults (72 vs. 42%, p < 0.001) and more cases of drug anaphylaxis in adults than in children (28 vs. 10%, p < 0.001). Compared to patients of other ages, infants and young children had more gastrointestinal symptoms (adjusted odds ratio [aOR] 2.1, 95% CI 1.1-3.9), while schoolchildren and adolescents had more respiratory symptoms (aOR 2.7, 95% CI 1.4-5.2). Adults had more cardiovascular symptoms (aOR 2.9, 95% CI 1.8-4.6) and hypotension (aOR 3.7, 95% CI 2.1-6.8) compared to children. However, 42% of the infants lacked blood pressure measurements. CONCLUSIONS: Knowledge of age-related variation in the cause and clinical presentation of anaphylaxis aids in diagnosis and acute management.

Adjuvant Therapies in Food Immunotherapy.

Finding an effective curative treatment for food allergy is a research priority. Although oral immunotherapy (OIT) is effective at inducing desensitization, the temporary nature of this effect and high rates of adverse reactions have highlighted a need for novel strategies to improve tolerance induction and safety. One such strategy is the use of an adjuvant together with food immunotherapy to either suppress allergic reactions and/or modulate the underlying allergic immune response. In particular, the use of bacterial adjuvants seems to be a promising means of enhancing OIT-induced sustained unresponsiveness and warrants further investigation.

Absence of esophageal eosinophilia in a toddler with severe eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a clinicopathologic disease characterised by esophageal dysfunction and eosinophil-predominant inflammation. Diagnosing EoE in children is particularly challenging as they tend to present with nonspecific symptoms and their mucosal specimens may have less than the threshold number of eosinophils. Reluctance to subject children to multiple endoscopic procedures and anesthesia often results in treatment with a proton pump inhibitor (PPI) first to evaluate clinical response. This approach presents a problem as a diagnosis of EoE may be missed. Here we present a case of a child with severe EoE whose initial biopsy did not show esophageal eosinophilia but progressed on to advance dis ease despite clinical response to PPI therapy.

Pilot study of the use of Yin Qiao San in children with conventional antipyretic hypersensitivity.

BACKGROUND: Children with a diagnosis of cross-reactive hypersensitivity to both paracetamol and nonsteroidal anti-inflammatory drugs are limited in their choice of antipyretics. OBJECTIVE: The aim of this pilot study is to evaluate the feasibility of using a Chinese proprietary medicine, Yin Qiao San (YQS), for fever relief. METHODS: A single centre, open label, prospective clinical trial exploring the tolerability and feasibility of using YQS for fever relief in children who are unable to use conventional antipyretic medications. Children between 1-18 years of age with hypersensitivity to multiple antipyretics were recruited. Eligible participants underwent an oral provocation test with YQS. Children who passed the oral provocation test were instructed to take a prescribed dose of YQS when the temperature was >38.0℃ and continued till the fever settled. Time taken for fever resolution and any adverse events were collected. RESULTS: A total of 21 children, mean age 10.7 years, had a diagnosis of paracetamol and ibuprofen hypersensitivity. All except one patient successfully tolerated an oral challenge of YQS. Of the 88 doses of YQS taken for fever over 38.0℃, 16 (18%) had documented temperature reduction 2 hours after ingestion and 30 (34%) had documented temperature reduction 4 hours after ingestion. There were 2 reports of urticaria after YQS use which were attributed to flare of recurrent spontaneous urticaria during the illness. None of the patients developed symptoms of circulatory compromise or respiratory distress. CONCLUSION: YQS is generally well tolerated in patients with paracetamol and ibuprofen hypersensitivity.

Tolerance to etoricoxib in children with nonsteroidal anti-inflammatory drug hypersensitivity.

BACKGROUND: Cyclooxygenase-2 (COX-2) inhibitors have been found to be safe alternatives in adults with cross-intolerant hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs). However they are usually not prescribed in children and there is little information about their tolerance in the pediatric age group. OBJECTIVE: This study aims to evaluate the tolerance to etoricoxib in children with hypersensitivity to multiple antipyretics. METHODS: A retrospective case series of children diagnosed with hypersensitivity reactions to NSAIDs and/or paracetamol who underwent a drug provocation test (DPT) with etoricoxib. Information on atopy, family history of allergic diseases, and medication usage was collected. Outcomes of the DPTs and tolerance to etoricoxib were also evaluated. RESULTS: A total of 24 children, mean age 13.5 years, had a diagnosis of cross-intolerant hypersensitivity to NSAIDs and/or paracetamol. All except one patient successfully tolerated an oral challenge with etoricoxib. Of those who passed the DPT, the majority continued to use etoricoxib with no problems. It was found to be moderately effective in reducing fever and pain. CONCLUSION: Etoricoxib can be used as a safe alternative in older children with hypersensitivity to multiple antipyretics.