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. 2023 Mar 31;96(1):79–82. doi: 10.59249/KGFT1011

A Case Report of Allergic Hypersensitivity to Color Additives in Slurpee® Beverages

David B Weisbrod a,b, Dennis L Caruana c, David Li a, Leo Wan d, Anthony M Szema a,e,f,g,*
PMCID: PMC10052599  PMID: 37009191

Abstract

Introduction: Many commercially available foods and beverages contain color additives to which patients may develop allergic hypersensitivity. Several color additives currently approved for commercial sale in the United States have raised health concerns to a varying degree as testing and evidence of carcinogenicity, genotoxicity, and hypersensitivity has thus far been inadequate. Common uses for color additives include baked goods (eg, cakes, pastries, candy), flavored dairy products such as yogurt, sports-themed drinks (eg, Gatorade® Fruit Punch), and red-dyed Slurpee® beverages. Methods: We present the case of a patient who experienced color additive-related allergic hypersensitivity reactions after consumption of Slurpee® beverages, which may place her at risk when consuming other commercially available beverages and food products containing color additives. Percutaneous skin testing and an oral challenge were administered using three different red color additives (two color additives for skin testing and one color additive for the oral challenge). Results: The specific color additive precipitating her symptoms was not conclusively identified. Review of the literature acknowledges the idea that further research into color additive-related allergy should be conducted as there are many commercially available color additives that can elicit hypersensitivity reactions after consumption. Conclusion: Current research shows that of the red color additives available, Citrus Red, Red No. 3, and Red No. 40 are recognized to elicit such reactions. In order to lessen the burden of color additive-related hypersensitivity in the general population, public education, increased research, and subsequent regulations should be implemented.

Keywords: carmine, Citrus Red, cochineal, Red No. 3, Red No. 40

Introduction

Many commercially available foods and beverages contain color additives to which patients may develop allergic hypersensitivity. Hypersensitivity to food additives may be mediated by two distinct mechanisms: immunologic and non-immunologic. Furthermore, immunologic reactions may arise from allergic reactions (mediated by sensitization of mast cells and release of histamine through an IgE-mediated pathway), cell-mediated immunologic response (non-IgE mediated), or through both IgE and non-IgE mediated pathways. Notably, immunologic activation does not occur in food intolerances, which have varied mechanisms (eg, metabolic, pharmacologic, and/or toxic) [1].

Several color additives currently approved for commercial sale in the United States have raised health concerns to a varying degree as testing and evidence of carcinogenicity, genotoxicity, and hypersensitivity has thus far been inadequate. Of these, three are red color additives—namely, Citrus Red, Red No. 3, and Red No. 40 [2]. Red No. 40, for example, had been shown to accelerate the appearance of immune system tumors in mice in one study but not in another [3]. Although the safety of Red No. 40 in humans remains uncertain, Red No. 40 is the most widely used synthetic coloring and has been documented to cause hypersensitivity reactions [2].

Common uses for Red No. 40 include as a color additive in baked goods (eg, cakes, pastries, candy), flavored dairy products such as yogurt, sports-themed drinks (eg, Gatorade® Fruit Punch), and red-dyed Slurpee® beverages (Figure 1). Gatorade® and Pedialyte® beverage products are often used by athletes to replace fluids and electrolytes lost during performance of strenuous physical activity; however, depending on the product-specific formulation purchased by consumers, these Gatorade® and Pedialyte® products are known to contain color additives, such as Red 40, Blue 1, Yellow 5, and/or Yellow 6. Slurpee® is a brand of frozen slushie beverage marketed by 7-Eleven, Inc. and the Fanta Wild Cherry flavor of Slurpee® is described as follows: “A beverage syrup prepared with high fructose corn syrup, water, citric acid, natural and artificial flavors, quillaia extract, sodium benzoate (to protect taste), yucca extract, and Red 40 [4].”

Figure 1.

Figure 1

An original photograph depicting examples of foods and beverages containing dye Red 40. (Photograph taken by author DBW on June 14, 2022)

Epidemiologically, the prevalence of color additive-related allergy in adults is estimated to be less than 1% whereas a slightly higher rate is estimated for children (1 to 2%) [5-7]. We describe the case of a patient who presented to an allergy/immunology center for diagnostic evaluation of safety concerns surrounding ingestion of Slurpee® beverages and baked goods containing color additives.

Case Presentation

A 24-year-old female teacher presented to our allergy/immunology center to assess whether ingestion of McCormick® red food coloring would be safe to consume in baked goods or cause hypersensitivity reaction. The patient reported a history of experiencing throat closure within minutes after each of several attempts to ingest the Fanta Wild Cherry flavor of Slurpee® and reported developing a mild facial rash when attempting to consume cupcakes that were dyed red with Wilton® gel-based red food coloring, which contains Red No. 3 and Red No. 40, in addition to Yellow No. 5 and No. 6 [8]. The patient denied experiencing any other symptoms—wheezing, shortness of breath, hypotension—in response to consumption of either Fanta Wild Cherry Flavor of Slurpee® or baked goods made with red color additives.

Notably, throat symptoms did not occur in response to consumption of flavors of Slurpee® other than Fanta Wild Cherry but reliably occurred each time the patient attempted consumption of this Slurpee® flavor. The patient’s past medical history included allergic rhinitis, severe persistent asthma managed with reslizumab (anti-interleukin 5 therapy), and in the past, had positive allergy skin testing to antigens for the following, for which she had been receiving allergy immunotherapy: grass, weed, mold, dust mite, cat, and dog.

Percutaneous skin testing using Duotip-Test® II (Lincoln Diagnostics, Inc., Decatur, IL) was initiated, using two red color additives: Wilton® gel-based red food coloring, to which the patient had a history of developing rash of the face following consumption and McCormick® liquid red food coloring, for which the patient was inquiring whether the product would be safe to consume and had no prior history of allergic hypersensitivity.

The prick method for use of the Duotip-Test® II in percutaneous testing described by Sangsupawanich et al. was used; that is, a drop of color additive was applied to the pair of tines followed by application of the Duotip-Test® II device such that entry of the skin would occur at a 45-degree angle to gently lift the epidermis without causing bleeding [9]. This form of skin testing is regarded as a safe technique to confirm whether one may be allergic to a particular substance that is touched, eaten, or inhaled.

Four skin pricks were made three inches apart on the left forearm after swabbing the skin with alcohol. The four pricks consisted of 1) negative skin test control (glycerin 50%, sodium chloride 0.5%, sodium bicarbonate 0.275%, Jubilant HollisterStier LLC, Spokane, WA); 2) positive skin test control (6mg/mL histamine base, 10 mg/mL histamine dihydrochloride, Jubilant HollisterStier LLC, Spokane, WA); 3) 1 drop of undiluted Wilton® gel-based food coloring; and 1 drop of undiluted McCormick® liquid red food coloring.

The histamine site produced an 8 mm wheal, with a 2 cm flare whereas saline application did not produce a wheal or appreciable flaring. This indicated the patient had, as instructed, not taken antihistamines prior to percutaneous testing. Both color additives utilized did not elicit reaction (ie, negative skin result: no wheals or flaring). Following percutaneous testing, a two-hour oral challenge was offered to definitively rule out hypersensitivity to the food dye to which the patient had no history of allergic response—McCormick® red food coloring. Due to the patient’s reported history of reliably experiencing throat closure in response to ingestion of the Fanta Wild Cherry Slurpee® and history of developing a facial rash in response to consumption of baked goods containing Wilton® gel-based food coloring, the patient was unwilling to undergo oral challenge with either of these products. Given that all consumer products discussed here—Fanta Wild Cherry Slurpee®, Wilton® gel-based food coloring, and McCormick® red food coloring—all contain Red No. 40 as a color additive, oral challenge with only McCormick® red food coloring was determined to be acceptable.

The oral challenge was administered during the patient’s next visit to the allergy/immunology center with the McCormick® red coloring. Using a food scale, 50 grams of red-colored icing were measured. Two hours after ingesting red-colored icing, our patient did not exhibit any symptoms (eg, throat closure, development of a facial rash) previously reported after completion of both tests with the red dye utilized. Moreover, she denied experiencing difficulty swallowing, shortness of breath, pruritis, or paresthesias following ingestion of the red-colored icing.

Discussion

In 2004, the United States Congress passed the Food Allergen Labeling and Consumer Protection Act [10], which identified eight foods as major food allergens: milk, eggs, fish, shellfish, tree nuts, peanuts, wheat, and soybeans. This law was followed in 2021 with the Food Allergy Safety, Treatment, Education, and Research Act [11], further expanding the definition of major food allergen and declaring that the Department of Health and Human Services must report on certain information related to food allergy research and data collection activities. However, not all color additives require identification on food labels other than FD&C Yellow 5.

Color additives made from cochineal extract and carmine (natural red dye) are derived from insects and are allergenic substances that must be declared on the label of all food and cosmetic products. Carmine has also been implicated in urticaria, angioedema, recurrent intermittent episodes of generalized dermatitis, asthma, and anaphylaxis [12]. Red color additives, such as Red No. 2 and 40, are derived from Dactylopius coccus, an insect that grows on the prickly pear cactus; are produced from the aqueous-alcohol extract of the dried, gravid female insect; and consist of 10% carminic acid plus the residual insect body [12].

In a similar fashion, sulfites, such as sodium bisulfite, are a preservative that may trigger asthma in sensitive individuals and must be declared on the label if there is at least 10 parts per million present. Color additives and preservatives such as these can be found in many commercially sold products that were mentioned previously: yogurt, cupcakes, shakes, smoothies, and slushies.

Symptoms of food allergies can range from mild to severe and typically begin within a few minutes to a few hours after ingestion or inhalation of the allergen. These symptoms include tingling of the mouth, hives, itching, eczema, angioedema, constriction of the airways, and a severe drop in blood pressure. Certain individuals may have allergic hypersensitivity reactions to colored additives because color additives are widely found in beverages, desserts, processed vegetables, and even makeup. In mild cases, this may cause itching or rash, but in severe cases, throat closure may occur.

Diagnosis of food allergies can be a daunting task because most standard methods are unable to differentiate sensitization from clinical allergy. Sensitization is different; symptoms may not develop despite being exposed to a potential allergen. Whereas those who are clinically allergic must also be sensitive as they have developed symptoms. Overdiagnosis and unnecessary avoidance of suspected allergens can occur if testing is misinterpreted due to the limited accuracy of testing modalities such as skin prick testing.

Testing for IgE antibodies to certain protein components in foods is one of the many newer diagnostic techniques being employed to improve the accuracy of the food allergy diagnostic workup [13]. Additionally, some laboratories are able to perform serum testing for IgE to carmine; however, a physician supervised oral food challenge remains the only definitive method of confirming a allergy to foods and food additives, and serum IgE testing for carmine would not have altered our recommendations for this patient [14]. Oral challenge develops a direct cause and effect relationship between a potential allergen and a rapid onset of symptoms elicited after exposure.

Patients with allergy to color additive(s) require an interdisciplinary approach to care. The patient whose case is presented herein reported successful prevention of symptom exacerbations when red-dyed foods are avoided, thereby rendering dietary changes other than avoidance of consumer products containing red color additives unnecessary.

Conclusion

Current research shows that of the red color additives available, Citrus Red, Red No. 3, and Red No. 40 are recognized to elicit such reactions. Percutaneous testing followed by oral challenge may be considered as part of the diagnostic evaluation of patients with suspected allergic hypersensitivity to color additives in food and beverage products. In order to lessen the burden of color additive-related hypersensitivity in the general population, public education, increased research, and subsequent regulations should be implemented.

Author Contributions

DBW serves as the article guarantor, performed the data collection/analysis, and wrote the manuscript. Authors DLC, DL, and LW were integral in the design of the case report as well as reviewing and editing the manuscript. Author AMS is the supervising physician, mentor, and the conceiver of the case report.

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