Wheat is the most popular grain worldwide. Flour and bran are used in the production of many food products, such as bread, breakfast cereals, and pasta. Being a binding agent, wheat is added to desserts, cream, and ice cream. Starch is used for coating pills and roasted coffee grains, as well as in a variety of pharmaceuticals, cosmetics, and chemical industries [1, 2].

Its use is so widespread that people suffering from gluten-related disorders face difficulty avoiding it [2]. Wheat allergy, as a sIgE- mediated reaction, is a complex disease due to the many allergenic components in wheat [3, 4]. These patients tend to have severe reactions compared to reactions from other kinds of food, such as eggs and cow milk [5].

Hypersensitivity IgE-mediated reactions to wheat can be due to either ingestion or inhalation (food allergy or respiratory allergy) [6]. Wheat can also cause contact allergy when using cosmetics that contain hydrolyzed wheat protein [7, 8]. Allergic conjunctivitis can be caused by various allergens, such as mixed pollens, house dust, mites, hay dust, feather, and animal dander [9]. The natural history of IgE-mediated WA has been infrequently reported and studied [10]. However, little information is available about the relationship between wheat and allergic conjunctivitis. The diagnosis of the condition can be tricky because wheat is present in so many different foods. Therefore, a high index of suspicion is required [11].

Accordingly, the aim of the present study is to investigate the prevalence of wheat allergy among patients with resistant AC, when to suspect it, how to confirm the diagnosis, and the relationship between wheat allergy and the severity of the AC.

Patients’ demographics and baseline characteristics are shown in Table 1.

Fig. (1). Skin prick test results interpretation: P: Positive control; N: Negative control: Wheat wheal; blue circle.

Wheat allergy is an allergic reaction that is mainly induced by eating food products that contain wheat. Diagnosis can be challenging because wheat is present in many different foods [11]. Little information is available about the relationship between wheat allergy and allergic conjunctivitis.

Although wheat allergy is rare, it is one of the most widespread food allergies. The patterns and prevalence of food allergy are highly variable in different parts of the world, which is attributed to a complex interplay of environmental, genetic, and epigenetic factors [13]. Prevalence of wheat allergy, in general, was found to be 0.21% in one study [14] and ranged from 0.2-1.3% in other studies [15, 16].

Our study revealed an incidence of 10% of wheat allergy among patients with resistant AC. Wheat allergy is considered resistant as the triggering allergen is present in many products; therefore, it is difficult for the patient to correlate between exposure to a certain product and the development of symptoms. Moreover, symptoms will not resolve except after the stoppage of exposure to the triggering allergen.

Regarding the age difference in the study, patients in WSG had a significantly younger age than WTG. This is consistent with previous reports that young age groups have a higher prevalence of wheat allergies compared to adults because their immune and digestive systems have not yet matured, and this age group is more likely to develop this type of allergy if wheat is introduced after 6 months of birth [11, 17].

Furthermore, the study reported a higher frequency of female gender in WSG than in WTG (though insignificant). It was reported previously that female dominance is a significant factor in terms of food allergy [18].

The study revealed a positive family history of allergy in 100% of WSG vs. 67% of WTG. A positive family history of allergy was reported to be an important risk factor for wheat allergy, and these patients tend to have a high atopic potential [19].

Fig. (2). An example case of a patient with allergic conjunctivitis sensitized to wheat flour. Same patient one month after avoiding wheat-containing food and replacing wheat flour with corn flour.

The protocol for treating AC in our institutions is to start with short-term steroid eye drops to control acute symptoms, then continue on maintenance therapy with any steroid-sparing agents. If symptoms are persistent or the frequency of steroid-containing eye drops increases, AC is considered resistant, indicating the presence of a triggering allergen highly probable. The patient is then referred to a total serum IgE level assessment as a screening test for IgE-mediated allergy; if high levels are found, then the patient is referred to allergy clinics for allergen identification by SPT and specific IgE level.

The study revealed significantly higher total IgE levels in WSG than in WTG. Allergy sensitization mediated by IgE is the basis of allergic diseases, and elevated total IgE is frequently included as a diagnostic criterion for allergic diseases. Total IgE levels are not elevated only in allergic disorders but also in parasitic diseases and in a specific immune deficiency termed hyper IgE syndrome; both were excluded in this study. Low total IgE indicates a low probability of specific IgE sensitization [20]. Skin prick testing is an essential procedure to confirm sensitization in IgE-mediated allergy in subjects with rhinoconjunctivitis, urticaria, atopic eczema, asthma, anaphylaxis, and drug and food allergy [21]. Specific IgE is integral to the pathogenesis of allergic disorders, and it is crucial to detect the causal allergens in AC to prevent and treat the disease [22].

The study revealed that both SPT and S IgE were +ve for wheat flour allergen in 50% of wheat-sensitive patients. Positive S IgE but –ve SPT results were found in 30% of WSG, whereas +ve SPT and –ve sIgE results were detected in 20% of WSG.

This disagreement between the results of SPT and S IgE levels could explain that the immune response is different in the blood and the skin. Schoos et al. [23] showed substantial discordance between SPT and specific IgE results, suggesting that the two testing methods complement each other and cannot be used interchangeably; if only one type of testing is performed, a substantial number of allergic sensitizations may be missed [24].

The study revealed the presence of a significantly higher frequency of multiorgan allergy in WSG (100%) vs. 20% in WTG. Allergic multiorgan disease triggered by wheat flour allergen in the form of rhinoconjunctivitis and asthma was previously reported. Symptoms developed in the form of watery eyes, itching, sneezing, nasal stuffiness and rhinorrhea [25]. Another study reported a combination of allergic rhinoconjunctivitis, asthma and urticarial from wheat flour sensitization. This sensitization tends to disappear with age [26].

Recognition of such a form of allergy is very important because the improvement of symptoms will be significantly noticeable if the patient refrains from being exposed to foods containing wheat flour (Fig. 2), replacing wheat flour with corn flour and managing the condition by allergen immunotherapy.

From this study, we concluded that if AC is IgE mediated, resistant, and in a severe form with symptoms in a young patient having a positive family history of atopy and multiorgan allergy, wheat-mediated AC is highly probable. Further studies are necessary in order to conclude a causal association between wheat flour sensitization and AC.