Food Allergen Sensitisation Patterns in Omani Patients with Allergic Manifestations

Objectives
This study aimed to evaluate the relationship between food allergen sensitisation patterns and allergic manifestations in Omani patients and highlight the importance of specific immunoglobulin E (IgE) testing.


Methods
This retrospective study included all patients referred due to allergic manifestations to the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, from November 2012 to November 2016. Specific IgE blood testing was performed to determine sensitisation to common foods known to cause allergic reactions.


Results
A total of 164 patients were referred to SQUH over the study period, with 35.4% presenting with one allergic manifestation, 48.8% with 2-3 and 15.9% presenting with more than three manifestations. There was a family history of allergies in 70.7% of patients. Eosinophil counts and total and specific IgE levels were elevated in 18.9%, 54.9% and 73.2% of patients, respectively. Patients demonstrated sensitisation to cow milk (47.6%), wheat (41.5%), chicken eggs (34.8%), mixed tree nuts (34.1%), lentils (33.5%), peanuts (32.9%), soy (32.3%), shrimp (23.2%) and fish (15.2%). Overall, 19.5% were sensitised to a single allergen, 14% were sensitised to 2-3 and 39.6% were sensitised to more than three allergens. Almost one-third (29.3%) of patients suffered from food-induced anaphylaxis, of which 85.4% were prescribed self-injectable adrenaline.


Conclusion
To the best of the authors' knowledge, this study is the first to describe food allergen sensitisation patterns among Omani patients with allergic manifestations. In conjunction with clinical symptoms, the correct interpretation of specific IgE levels is important to diagnose food allergies and make safe decisions about reintroducing foods.

A llergic diseases constitute a group of hypersensitivity disorders resulting in clinical symptoms involving different organs, such as the skin (i.e.urticaria and angioedema), respiratory system (i.e.coughing, wheezing and breathing difficulties), gastrointestinal system (i.e.vomiting, diarrhoea and abdominal pain) and cardiovascular system (i.e.flushing, tachycardia and syncope). 1The most severe form of allergic reaction is anaphylaxis, which can be life-threatening. 2The underlying mechanism of immediate or type I hypersensitivity is primarily due to the formation of specific immunoglobulin E (IgE) molecules against a particular allergen, usually a peptide or protein.Upon subsequent exposure, the crosslinking of IgE receptors on mast cells triggers the activation and release of mediators responsible for the symptoms, primarily histamine, leukotrienes, prostaglandins and tryptase. 3,4ood is a common cause of allergic symptoms, although the exact prevalence of food allergies varies in different countries due to differences in dietary habits.Generally, studies in developed countries report food allergy rates of 8% and 4% among children and adults, respectively. 5,6Common trigger foods include cow milk, eggs, soy, wheat, fish, seafood, peanuts and tree nuts among children and fish, seafood, peanuts and tree nuts among adults. 7,8For most patients, the diagnosis is made based on clinical symptoms; however, an in vivo skin prick test may be necessary.More recently, diagnoses have been achieved by measuring in vitro levels of IgEspecific antibodies in the blood sera. 4,9oth in vivo-and in vitro-specific IgE testing are very sensitive, with high false-positive rates; however, both forms of testing have an excellent negative predictive value, which helps in excluding allergies, especially in doubtful cases. 9Parents or physicians often suspect food after an allergic manifestation and patients are advised to avoid foods that are considered allergenic prior to a proper evaluation by a specialist.Double-blind placebo-controlled food challenges are the gold-standard diagnostic tool for food allergies and are usually used in research centres; however, such testing is timeconsuming and often requires special precautions. 10,11o the best of the authors' knowledge, local food allergen sensitisation patterns have not been previously studied in Oman.As such, this study aimed to evaluate the relationship between food allergen sensitisation patterns and allergic manifestations in Omani patients.In addition, the importance of specific IgE testing is highlighted.

Methods
This retrospective study included all patients referred to the allergy clinic of the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, between November 2012 and November 2016.For each patient, a routine history was taken and a physical examination was conducted.A diagnosis of an allergic manifestation was made based on clinical symptoms of anaphylaxis, acute or chronic urticaria/angioedema, eczema/dermatitis, angioedema without urticaria, asthma, rhinitis or vomiting/ diarrhoea.
As part of their diagnostic work-up, patients underwent blood investigations to determine their eosinophil count and total and specific IgE levels for common food triggers (i.e.cow milk, chicken eggs, fish, soy, wheat, shrimp, peanuts, lentils and mixed tree nuts).Total and specific IgE levels were measured using the Immuno-CAP ® Phadia ® 100 immunoassay analyser (Thermo Fisher Scientific, Waltham, Massachusetts, USA), as per the manufacturer's instructions.Assays were calibrated to the 75/502 IgE standard of the World Health Organization. 12Reference cut-off values were established at <165 and <0.35 kIU/L for normal total and specific IgE levels, respectively.Eosinophil counts of >0.8 × 10 9 /L were considered raised.The coefficient of variation between runs was <10%.
Allergic symptoms were correlated with any obvious food triggers based on information received from the patients or their parents/caregivers.In addition, the patients were questioned regarding the consumption of other common allergenic food triggers.Other information, such as demographic characteristics, a family history of allergies and age at the onset of symptoms, was retrieved from the patients' electronic medical records.Patients with allergic manifestations who had ingested common food triggers and reported no symptoms or signs of sensitisation on exposure to those foods were not tested and were excluded from the study.
All patients were given medical advice based on available clinical information at post-investigation follow-up visits.Symptomatic treatment was provided in cases of dermatitis, asthma, rhinitis or chronic urticaria.In cases of anaphylaxis, patients were prescribed self-injectable adrenaline and trained on its use. 13,14nalysis of the data was performed using the Statistical Package for the Social Sciences (SPSS), Version 20.0 (IBM Corp., Armonk, New York, USA).Frequencies and percentages were calculated using simple functions.Statistical differences were measured using Pearson's Chi-squared test.Differences were considered significant at P <0.05.
This study was approved by the Medical Research & Ethics Committee of the College of Medicine & Health Sciences, Sultan Qaboos University (MREC #1648).

Results
A total of 164 new patients were referred to SQUH during the study period because of suspected food allergies.Of these, 53 (32.3%) were female and 111 (67.7%) were male.At referral, 92.5% of patients were <18 years old, with a mean age at presentation of 5.8 years old (range: one month-53 years).The mean age at onset of symptoms was 3.3 years old (range: one week-48 years).The mean interval between onset of symptoms and diagnosis was 30.5 months.Allergies presented as a single manifestation in 58 patients (35.4%), while 2-3 manifestations were present in 80 patients (48.8%) and more than three manifestations occurred in 26 patients (15.9%).There was a family history of allergies in 116 patients (70.7%).
Table 1 illustrates the frequency of sensitisation to common food triggers according to allergic manifestation.Normal total IgE levels were observed in 67 patients (40.9%), of which 35 (52.2%) had positive specific IgE levels.Overall, 21.3% of patients had positive specific IgE levels and normal total IgE levels.Sensitisation to a single allergen was present in 19.5% of patients, sensitisation to 2-3 allergens in 14% and sensitisation to more than three allergens in 39.6%.The remaining 26.8% were not sensitive to any allergens.Figure 1 presents monosensitisation and polysensitisation rates according to allergic manifestation.

Discussion
Food allergies represent a management challenge for the affected patient, their parents and/or caregivers and the healthcare provider.However, a thorough patient history, physical examination and diagnostic testing can help in managing the condition and minimising the risk of complications.After diagnosis, food allergies should be treated with strict avoidance of the identified allergenic foods.Patients and/or their parents or caregivers should be educated about possible allergen sources, taught to check the labels of processed foods and cautioned to be careful about eating in restaurants to minimise the risk of cross-contamination and accidental exposure.
In cases of anaphylaxis, patients should be prescribed self-injectable adrenaline and trained on its use in case of accidental exposure. 13,14[17][18] To the best of the authors' knowledge, this study is the first to describe food allergen sensitisation patterns in Omani patients with allergic manifestations.The true prevalence of food allergies in Oman is unknown; however, recent data indicate that the prevalence of allergic manifestations such as asthma, rhinitis and eczema in schoolchildren is increasing. 19,20Moreover, given changing sociodemographic patterns and dietary habits in the Gulf region, it is expected that allergies will continue to have a significant impact on the national healthcare system. 21In the current study, the majority of patients had atopic manifestations and most had a family history of allergies and elevated total IgE levels; these factors may explain the high rate of positive specific IgE reactions to common food triggers.3][24] However, the mean period of time between onset of symptoms and diagnosis was approximately two years, indicating that there is a need to enhance awareness of food allergies and promote early referral services in Oman.
Varying rates of monosensitisation and polysensitisation have been reported in the international literature depending on the baseline characteristics of the studied population. 25In the present study, the rate of monosensitisation (positive specific IgE levels to one allergen) was 19.5%, with 14% of patients positive for 2-3 allergens.Polysensitisation (i.e. a reaction to more than three allergens) was seen in 39.6% of patients, manifesting mostly as atopic dermatitis.However, not all positive sensitising allergens are responsible for clinical symptoms.In such cases, the predictive value of specific IgE levels is useful in conjunction with clinical symptoms to confirm an allergy diagnosis.In addition, specific IgE testing can help allergists to determine the correct time to reintroduce certain allergenic foods.
0][31] The role of specific IgE to food allergens has been well established in acute urticaria/angioedema, anaphylaxis, atopic dermatitis and, to some extent, gastrointestinal allergies such as eosinophilic oesophagitis; however, its role in respiratory allergic manifestations such as asthma and rhinitis is probably marginal. 32,33While patients with clinical allergic manifestations do have positive specific IgE results to food allergens, they may also have other manifestations or allergies which might account for the results.In the presence of normal total IgE levels, certain patients may also display positive specific IgE reactions to certain foods, as was the case for 21.3% of patients in the current study.This finding may be accompanied by clinical allergic manifestations; for example, 14.6% of anaphylactic patients had normal total IgE levels, yet high specific IgE levels.This finding emphasises the importance of searching for specific allergens in the presence of normal total IgE levels and consistent allergic manifestations.
Prior to commencing school, most children outgrow food allergies such as those to cow milk, chicken eggs and wheat. 34,35In fact, parents may sometimes continue feeding common food triggers to allergic children if the resulting reaction is mild or not anaphylactic.A double-blind oral food challenge is considered the gold standard for diagnosing food allergies; however, such an approach may not necessarily be applied to all patients as it is time-consuming and logistically difficult to safely perform. 10,11,327][38] Recent evidence, however, does not support restriction of these foods beyond four months of age. 39

Conclusion
This study determined sensitisation rates to common food triggers by measuring specific IgE levels in Omani patients with different clinical allergic manifestations.The results were in line with previous research in other populations.Further studies would be helpful for healthcare policy makers, especially with regards to reducing allergy-related mortality rates due to food-induced anaphylaxis and other causes.Preventative measures would help to minimise comorbidities and reduce the economic burden of allergies on the Omani healthcare system.c o n f l i c t o f i n t e r e s t The authors declare no conflicts of interest.

f u n d i n g
No funding was received for this study.

Table 1 :
Frequency of raised eosinophil counts and total immunoglobulin E levels and sensitisation to common food triggers among Omani patients according to allergic manifestation (N = 164) EC = eosinophil count; IgE = immunoglobulin E. *Significant at P <0.05 according to a Pearson's Chi-squared test.Food Allergen Sensitisation Patterns in Omani Patients with Allergic Manifestations e486 | SQU Medical Journal, November 2018, Volume 18, Issue 4