Dr Marco H.K. Ho
Specialist in Paediatric Immunology and Infectious Diseases
President, Hong Kong Institute of Allergy
- What are the trends in childhood allergy and adverse food reactions over the past decade?
- Have there been changes in the prevalence and severity of allergies in relation to the HKIA’s recommendations for allergy prevention?
- What is the latest science in the treatment/prevention of allergies?
- Do you see potential for the use of oral immunotherapies?
- What are some noteworthy cases of allergies in children you have encountered during your practice?
- What are your tips for healthcare professionals for the prevention of allergies?
MH: Dr. Marco Ho
R: What are the trends in childhood allergy and adverse food reactions over the past decade?
MH: Our team in 2012 published the results of a Hong Kong-wide food allergy survey in children aged 14 and below.1 7,393 participants were sampled between 2005 and 2006 with 352 respondents disclosing adverse food reactions (4.8%).1 Allergies to shellfish (37.8%), chicken egg (14.5%), dairy (10.8%), peanuts (8.5%) and fruit (8.5%) were the most frequently reported.1 This was the first population-based study on food allergies in Hong Kong children,1 and no investigations of a similar nature have since been conducted.
However, when we looked at hospitalisations for anaphylaxis among children in Hong Kong, we discovered a marked increase over the last decade for both total anaphylaxis (incidence rate ratio [IRR] 1.09, p<0.001) and food-related anaphylaxis (IRR 1.16 p<0.001), and this was most pronounced in children under 15 years.2 Food, rather than medicines, had also become the predominant cause for anaphylaxis and the most common triggers were peanuts, seafood (fish and crustaceans), eggs, dairy, tree nuts, and seeds.2 It is interesting that peanuts have become the most common food trigger for anaphylaxis (as seafood was the leading cause previously),3 suggesting a possible increase in peanut allergies in Hong Kong.2
“The last decade saw a marked increase both total anaphylaxis and food-related anaphylaxis [in Hong Kong]…and this was most pronounced in children under 15 years”
R: Have there been changes in the prevalence and severity of allergies in relation to the HKIA’s recommendations for allergy prevention?
MH: The HKIA’s (Hong Kong Institute of Allergy) recommendations to prevent allergies in children include avoiding food restriction during pregnancy and lactation; and breastfeeding during the first 6 months of life.4 While this guideline was published in 2016, I have not yet seen any significant decreases in the prevalence and severity of allergies in children – perhaps more work needs to be done to identify families with children at higher risk of developing allergies and to steer physicians towards focusing on the active prevention, rather than treatment, of allergies.
The HKIA also suggests the use of hydrolysed formula milk in high-risk infants if exclusive breastfeeding is not feasible,4 however, the American Academy of Pediatrics (AAP) recently withdrew their recommendation for using hydrolysed formula milk to prevent allergic disease in high-risk infants,5 citing the results of a 2016 meta-analysis that found inconsistent evidence to support its use.5,6 This decision by the AAP is controversial as the benefits of hydrolysed formula milk may have been ‘diluted’ due to the large number of studies in the meta-analysis, and in addition, most infants in the meta-analysis exclusively received formula milk from birth, which may not be representative of real-world feeding.6 In any case, both the HKIA and ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology and Nutrition) support the use of hydrolysed formula milk for reducing allergies in certain high-risk infants,4,7 and I believe this is a viable intervention that should still be considered if breastfeeding is not feasible.
R: What is the latest science in the treatment/prevention of allergies?
MH: A recent trial of particular interest is the 2018 PALISADE study on the use of AR101 – an investigational, peanut-derived oral immunotherapy to increase the tolerance of peanut protein for people with peanut allergies.8 The phase 3 study randomized 551 participants aged 4–55 years with a clinical history of peanut allergies to receive either AR101, given in gradual doses from 3–300 mg, or a placebo.8 The investigators found that AR101 was particularly effective at increasing the tolerance of peanuts for younger patients: at the end of the approximate 12-month trial period, 67.2% (250/372) of participants aged 4–17 years who received AR101 were able to tolerate at least 600 mg of peanut protein – roughly two peanut kernels – without any noteworthy allergic symptoms, compared with only 4% (5/124) of participants who received placebo (p<0.001).8 In addition, when participants were challenged with peanut protein at the end of the study, 10% of 4–17-year-olds who received AR101 required rescue adrenaline, compared with 53% in the placebo group.8 No life-threatening adverse events were reported during the study, and the frequency and severity for the side effects that did occur were considered acceptable.8
“AR101 is an investigational, peanut-derived oral immunotherapy to increase the tolerance of peanut protein for people with peanut allergies… [and is] particularly effective at increasing the tolerance of peanuts for younger patients.”
R: Do you see potential for the use of oral immunotherapies?
MH: There are currently no FDA-approved treatments for peanut allergy,8 and while I see potential for the use of oral immunotherapies, such as AR101, there are still limitations to its utility: AR101 only slightly increases tolerance to peanut protein and provides a ‘safety net’ of protection against accidental exposure to peanuts, rather than allowing patients to consume peanuts in large amounts. In addition, the protective effect of AR101 only persists if individuals are on continuous treatment. Whether the community embraces AR101 will depend on the patient’s goals – some may not wish to subject themselves to long-term treatment merely to protect against accidental peanut consumption, instead, I foresee that AR101 will be most beneficial for higher risk individuals who are prone to anaphylaxis or severe allergic symptoms upon peanut exposure.
R: What are some noteworthy cases of allergies in children you have encountered during your practice?
MH: While the most common triggers of food allergies among children in Hong Kong are shellfish, eggs, dairy products, peanuts and fruit;1 after many years of practice I’ve come to realise that any food item can potentially cause a reaction. Notable examples specific to this part of the world include lotus seed allergies, rendering children unable to enjoy mooncakes and other traditional Hong Kong desserts. I’ve also encountered allergies to bird nests, pandan leaves, and buckwheat – which is a seed rather than a grain and is the main ingredient of the soba noodle.
“Dust mites, which thrive in warm and humid environments like Hong Kong, share a similar tropomyosin structure with shellfish…individuals who become allergic to dust mites can then develop an adverse reaction to shellfish.”
Shellfish allergies in Hong Kong are interesting because many cases appear to be secondary to dust mite allergies. The causative allergen in shellfish appears to be tropomyosin, a protein involved in muscle contraction for invertebrates.9,10 Dust mites, which thrive in warm and humid environments like Hong Kong,9 share a similar tropomyosin structure with shellfish, which can result in cross-reactivity where individuals who become allergic to dust mites can then develop an adverse reaction to shellfish.9–11 Oral allergy syndrome (or pollen-food allergy syndrome), which is more frequently seen in the West, occurs via a similar mechanism: individuals with tree and grass allergies cross-react to allergens in fruits and nuts such as apples, bananas and hazelnuts.9,12 Patients with oral allergy syndrome often present with itchy mouth and throat, or swelling of the lips, mouth and tongue.12
R: What are your tips for healthcare professionals for the prevention of allergies?
MH: Healthcare professionals can recommend the ‘Healthy Meal Planning Guide’ published by the Department of Health; the booklet is a useful and practical resource to guide parents on weaning children aged 6–24 months onto semi-solid and solid foods.14 While there is no specific mention of preventing allergies, the booklet contains numerous recipes that incorporate potentially allergenic foods, such as steamed eggs or cooked peanuts in soup,14 which can be used to introduce potentially allergenic foods to help build tolerance.
The prevention of secondary food allergies in children is often overlooked in Hong Kong: food allergies can arise when parents restrict foods in children with an existing allergic condition, such as eczema, potentially leading to IgE-mediated reactions once the previously tolerated foods are re-introduced.15 While food elimination diets may help a certain subset of patients,16,17 healthcare professionals need to ensure that patients principally follow an eczema-friendly skin care plan with adequate amounts of emollients and topical steroids, and that any deliberate elimination diets are scrutinized by healthcare professionals to mitigate the development of late-onset and often life-long food allergies.15,16
The past decade has seen an increase in the number of hospitalisations due to food-related anaphylaxis in Hong Kong children, with peanuts, seafood, eggs, dairy, tree nuts, and seeds as the most common triggers. Healthcare professionals can refer parents to the Department of Health’s ‘Healthy Meal Planning Guide’ – a resource containing numerous recipes that can introduce potentially allergenic foods and help build tolerance in infants transitioning to semi-solid and solid foods. Healthcare providers should also be vigilant of food-restricting diets in patients with allergic conditions (ie, eczema), as these can lead to potentially life-long secondary food allergies.
Latest developments in the field of allergy prevention include a peanut-derived oral immunotherapy called AR101. In phase 3 trials, the therapy was able to increase the tolerance of peanuts in individuals with a history of peanut allergies, compared to placebo. While still in development, AR101 may prove useful for higher risk individuals who are prone to anaphylaxis or severe allergic symptoms upon accidental peanut exposure.
- Ho MHK, et al. Asian Pacific J Allergy Immunol 2012;30:275–284.
- Wang Y, et al. J Allergy Clin Immunol Pract 2018;6:1050–1052.
- Smit DV, et al. J Emerg Med 20015; 28:381–388.
- Chan AWM, et al. Hong Kong Med J 2016;22:279–285.
- Greer FR, et al. Pediatrics 2019;143:183–191.
- Boyle RJ, et al. BMJ 2016;doi:10.1136/bmj.i974.
- Vandenplas Y, et al. J Pediatr Gastroenterol Nutr 2014;58:549–552.
- Vickery BP, et al. N Engl J Med 2018;379:1991–2001.
- Wong L, et al. Allergy Asthma Immunol Res 2016;8:101–106.
- Ayuso R, et al. Int Arch Allergy Immunol 2002;129:38–48.
- Santos ABR, et al. J Allergy Clin Immunol 1999;104:329–337.
- Webber CM, et al. Ann Allergy, Asthma Immunol 2010;104:101–108.
- Department of Health - Hong Kong SAR Government. 7-Day Healthy Meal Planning Guide for 6 to 24 month old children (2017).
- Nachshon L, et al. J Allergy Clin Immunol 2014;AB212:Abstract 723.
- Katta R, et al. J Clin Aesthet Dermatol 2014:7:30–36.
- Lever R, et al. Pediatr Allergy Immunol 1998;doi:10.1111/j.1399–3038.1998.tb00294.x.