Trends in Childhood Anaphylaxis in Singapore: 2015-2022.

BACKGROUND: There has been limited data regarding the incidence of anaphylaxis in Asia. We aim to describe patterns in patient characteristics, triggers and clinical presentation of childhood anaphylaxis in Singapore. METHODS: This was a retrospective review of emergency electronic medical records of children with anaphylaxis. Patients with the allergy-related diagnoses of anaphylaxis, angioedema, allergy and urticaria based on ICD-9 codes were screened. Cases fulfilling the World Allergy Organization criteria for anaphylaxis were included. RESULTS: A total of 1188 cases of anaphylaxis were identified with a median age of 6.3 years. Extrapolating data from the study sites, from 2015 to 2022, the incidence rate of childhood anaphylaxis emergency visits in Singapore doubled from 18.9 to 38.8 per 100,000 person-years, with an incidence rate ratio (IRR) of 2.06 (95% confidence interval [CI] 1.70-2.49). In 2022, the incidence rate of food anaphylaxis was 30.1 per 100,000 person-years, IRR 2.39 (95% CI 1.90-3.01) and drug anaphylaxis was 4.6 per 100,000 person-years, IRR 1.89 (95% CI 1.11-3.25). The incidence rate in children aged 0-4 years quadrupled during the study period. Common triggers were egg (10.4%), peanut (9.3%), tree nut (8.8%), milk (8%), shellfish (7.8%) and non-steroidal anti-inflammatory drug (4.4%). The majority (88.6%) of patients were treated with intramuscular adrenaline. Total number of allergy-related visits did not increase over time between 2015 and 2019. Rates of severe anaphylaxis, namely anaphylactic shock and admission to high-dependency and intensive care, did not increase over time, with a mean incidence of 1.6, IRR 0.85 (95% CI 0.40-1.83) and 0.7, IRR 1.77 (95% CI 0.54-5.76) per 100,000 person-years, respectively. CONCLUSION: While the number of emergency visits due to childhood anaphylaxis has increased, the number of cases of allergy-related visits, anaphylactic shock and anaphylaxis requiring high-dependency and intensive care did not rise.

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.

Cytokine release syndrome - a unique entity of Augmentin hypersensitivity reaction.

Cytokine release syndrome (CRS) is a type of hypersensitivity reaction which has been previously described with chemotherapy and monoclonal antibodies, but not with antibiotics. We present 2 pediatric cases of Amoxicillin/Clavulanic acid (Augmentin) anaphylaxis resembling CRS. Both our patients presented during the index reaction with symptoms suggestive of an acute systemic inflammatory response mimicking sepsis. Their symptomology was reproducible at drug provocation test as anaphylaxis, but with suboptimal response to intramuscular adrenaline. Their infective workups were unremarkable and illnesses followed a self-limiting course. All these point towards a severe hypersensitivity reaction resembling CRS.

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.

Enzyme replacement therapy desensitization in a child with infantile onset Pompe disease.

BACKGROUND: Enzyme replacement therapy significantly reduces morbidity and mortality in patients with Pompe disease. Development of hypersensitivity reactions to enzyme replacement therapy is common and can adversely affect disease outcomes when treatment is halted or delayed. OBJECTIVE: Our institution reports a case of successful alglucosidase alfa enzyme replacement therapy desensitisation in a 9-year-old girl with infantile onset Pompe disease. METHODS: A desensitisation protocol was tailored to our patient with the help of a multidisciplinary team including the allergist, geneticist, nurses and pharmacists. RESULTS: For our patient, desensitisation was successful using a multi-step three-fold dose escalation protocol. CONCLUSIONS: Desensitisation is possible in individuals with hypersensitivity reactions to enzyme replacement. Desensitisation protocols need to be tailored according to the patient's needs and responses to find a protocol that is safe, effective and simple.

Household environmental microbiota influences early-life eczema development.

Exposure to a diverse microbial environment during pregnancy and early postnatal period is important in determining predisposition towards allergy. However, the effect of environmental microbiota exposure during preconception, pregnancy and postnatal life on development of allergy in the child has not been investigated so far. In the S-PRESTO (Singapore PREconception Study of long Term maternal and child Outcomes) cohort, we collected house dust during all three critical window periods and analysed microbial composition using 16S rRNA gene sequencing. At 6 and 18 months, the child was assessed for eczema by clinicians. In the eczema group, household environmental microbiota was characterized by presence of human-associated bacteria Actinomyces, Anaerococcus, Finegoldia, Micrococcus, Prevotella and Propionibacterium at all time points, suggesting their possible contributions to regulating host immunity and increasing the susceptibility to eczema. In the home environment of the control group, putative protective effect of an environmental microbe Planomicrobium (Planococcaceae family) was observed to be significantly higher than that in the eczema group. Network correlation analysis demonstrated inverse relationships between beneficial Planomicrobium and human-associated bacteria (Actinomyces, Anaerococcus, Finegoldia, Micrococcus, Prevotella and Propionibacterium). Exposure to natural environmental microbiota may be beneficial to modulate shed human-associated microbiota in an indoor environment.

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.

Adolescent with facial swelling.

BackgroundA previously well 15-year-old girl presented with a 2-month history of facial swelling that progressively worsened to involve the neck. There was associated dyspnoea, orthopnoea, headache and throat discomfort. Two weeks before presentation, the patient had an episode of fever for 5 days. On examination, vital signs were within normal limits. Swelling, plethora and venous distension of the face and neck were apparent (figure 1).

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.

A Case of Serious Adverse Reaction Following Rabies Vaccination.

Introduction. Rabies is one of the most deadly infectious disease. We present a challenging case of an adverse reaction following rabies vaccine in a child. Case Summary. A 10-year-old girl was bitten by a stray dog in Bali and was prescribed rabies post-exposure prophylaxis. She developed breathlessness, abdominal cramps, and lips and eyes swelling 30 minutes after the second dose of rabies vaccine. The subsequent vaccine was successfully administered as a graded challenge with premedication. The final dose was administered in entirety under close observation. She developed transient hypotension 30 minutes later, which spontaneously resolved. Conclusion. There were multiple challenges in the care of this pediatric patient who was potentially exposed to rabies and experienced systemic adverse events during the course of post-exposure prophylaxis. A thorough clinical assessment should be made to weigh benefits versus risks of proceeding with rabies vaccination, bearing in mind that the disease is deadly.

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.

Anaphylaxis to cow's milk formula containing short-chain galacto-oligosaccharide.

BACKGROUND: On the basis of the proven prebiotic effects of oligosaccharides in cow's milk formula (CMF) in infants, CMFs are supplemented with oligosaccharides. OBJECTIVE: We present a series of 5 cases of cow's milk-tolerant but atopic patients with a history of respiratory allergies. All had anaphylaxis after the ingestion of CMF supplemented with short-chain galacto-oligosaccharide (scGOS). The allergen trigger was investigated. METHODS: Clinical histories were collated. Skin prick tests (SPTs) and basophil activation tests (BATs) were carried out with the eliciting CMF that triggered anaphylaxis, with or without supplemented prebiotics (scGOS) and with scGOS fractions containing oligosaccharides of different chain lengths. RESULTS: The median age of presentation was 6 years (range, 5-38 years). Anaphylaxis occurred within 30 minutes of the first known exposure to CMF supplemented with prebiotics in all patients. Only 1 patient was subjected to oral challenge, which resulted in an anaphylactic reaction. All patients demonstrated IgE sensitization through SPTs and BATs to scGOS and fractions of scGOS containing 3 sugar units or greater but not to cow's milk or long-chain fructo-oligosaccharide. Eight child control subjects tolerant to regular ingestion of scGOS-supplemented CMF and 1 adult volunteer were found to have negative results to scGOS through SPTs and BATs. In addition, in vitro BATs with donor basophils sensitized with sera from 2 of the 3 reported cases showed reactions to scGOS. The scGOS-induced basophil activation was inhibited in the presence of wortmannin, a phosphatidylinositol 3-kinase inhibitor. CONCLUSIONS: This study describes an unusual form of IgE-mediated anaphylaxis triggered by low-molecular-weight oligosaccharides in scGOS. The primary sensitizer for this phenomenon requires further investigation.

Allergic rhinitis and non-allergic rhinitis in children in the tropics: prevalence and risk associations.

BACKGROUND: The age-related comparative prevalence of allergic rhinitis (AR) and non-allergic rhinitis (NAR) in children is poorly defined. We aimed to characterize AR and NAR in children. METHODS: This study enrolled children with chronic rhinitis who presented to a tertiary paediatric center for a diagnostic skin prick test (SPT). Parents completed a medical history questionnaire for their child, including disease activity for asthma and rhinitis. Sociodemographic data was obtained and all participants underwent a common inhalant SPT panel. A positive SPT indicated AR. RESULTS: From March 2001 to March 2009, 6,660 children (64% male) were enrolled (aged 6 months to 19 years, mean 7.82 years). Only 3.7% (249) of the children were <2 years old, and almost 30% of these had AR. Most children with AR (73%) presented after age 6. Males were more likely to have AR (vs. NAR) (OR 1.5; CI 1.39-1.77). Antihistamine and salbutamol use did not differ between children with AR and NAR. Children with AR were more likely to require adjunct therapy with inhaled corticosteroids (51.2% vs. 43.2%, P < 0.001), have drug hypersensitivity (especially antipyretic drugs) (2.5% vs. 1.3%, P = 0.384) or an asthma admission (9.1% vs. 6.0%, P < 0.001). CONCLUSIONS: AR is more common in male children, is relatively rare below the age of 2 years, and accounts for two-thirds of all childhood chronic rhinitis and 73.3% of all chronic rhinitis in school-aged children (≥6 years old). Children with AR have more severe rhinitis symptoms and more often suffer from asthma-related events and admissions.