Mustard
Summary
Mustard is the most important spice crop available globally, that belongs to the family Brassicaceae. Mainly, three species of this family are used in food industry: white (Sinapsis alba), brown (Brassica juncea) or black (Brassica nigra) mustard. Mustard is widely used in Indian, French, German and Irish cuisines, as well as for medicinal purposes. This plant is native to Asia, especially China, but has now spread throughout Asia, Japan, Africa and Europe. The prevalence of mustard allergy is common in Europe, where the consumption is comparatively higher, particularly in France.
Oral ingestion of mustard can lead to allergic reactions, such as oral allergy syndrome and anaphylaxis, allergic rhinitis, asthma and atopic dermatitis. Four of the proteins from white mustard, named, Sin a 1, Sin a 2, Sin a 3 and Sin a 4, and only one protein from brown mustard, Bra j 1, have been identified as having allergenic potential.
Cross reactivity between mustard and mugwort pollens is widely reported as the mugwort-mustard allergy. Besides mugwort, it also shows cross reactivity with nuts, legumes, corn, peach (Rosaceae fruits), cabbage, cauliflower and broccoli (Brassicaceae vegetables).
Epidemiology
Worldwide distribution
The prevalence rates of mustard allergy appear to vary worldwide due to different eating habits. It is commonly found in Europe, where the consumption is comparatively higher than the rest of the world, particularly in France, accounting for 1-7% of food allergy being estimated through various studies. It is considered the fourth most common food allergen in France.
In a prospective study conducted in France on 544 hypersensitive children, 9% reported mustard food allergy. In another French prospective study conducted on 30 subjects sensitized to mustard, allergic reactions were reported in 23.3% of subjects in double-blind or single-blind oral food challenge. Mustard was the cause of food allergy in 4% of children with atopic dermatitis, based on a study conducted in France.
Mustard is also increasingly being used in Spanish cuisine, however, only a few case reports of contact dermatitis, urticaria, and anaphylaxis have been reported. No extensive prevalence studies have been published so far. In a study conducted on 49 patients mono-sensitized to lipid-transfer proteins (LTP) in Italy, 4% of patients were found to be sensitive to mustard.
Furthermore, mustard is also widely used in India, however, limited data is available regarding its allergy. In a prospective study conducted in India on 78 allergic rhinitis patients, mustard showed positive SPT in 78.2% of the patients. Another study conducted in India reported 11 food-allergic patients showing elevated specific IgE to mustard (n=138).
Although the prevalence of mustard allergy in Canada is less known, its severity is reported to be high, with reports of serious reactions like anaphylaxis, after consuming a small quantity of mustard.
Risk factors
Allergy to mugwort could pose a risk of mustard allergy, due to the high prevalence of mugwort-mustard allergy syndrome. Also, patients allergic to mustard should avoid all the other members of the Brassicaceae family.
Pediatric issues
According to a prospective study performed on 35 children with positive SPT to mustard, allergy to mustard was found to begin early in life, however, its clinical symptoms in children were not as severe as in adults. The most common clinical symptom found was atopic dermatitis, while severe allergic reactions like anaphylaxis were not seen in children.
Route Of Exposure
Main
Oral ingestion of mustard through food items is the primary route of exposure to allergy.
Secondary
Inhalation could be the secondary route of allergen exposure. This was demonstrated by a study conducted on 35 atopic hypersensitive patients to mustard, where respiratory tract symptoms were found to precede onset of food allergy in 29 patients, indicating primary sensitization through inhalant or respiratory route.
Clinical Relevance
Oral allergy symptoms and Anaphylaxis
Oral allergy syndrome (47.4%) was found to be the most frequent symptom in a prospective study conducted on 38 mustard-hypersensitive patients, followed by urticaria or angioedema in 42.1% and systemic anaphylaxis in 10.5%, with one incidence of mustard-dependent exercise-induced anaphylaxis.
Severe skin reactions such as urticaria and angioedema have also been reported due to the ingestion of mustard, in forms like sauce or dips. Furthermore, it is considered as one of the most common spices that causes IgE-induced severe anaphylaxis. Certain case reports exist, showing mustard-induced skin allergies, that may manifest as contact dermatitis, eczema, pruritic lesions, urticaria or angioedema. This may be due to the presence of a volatile agent in mustard oil, known as allyl isothiocyanate, responsible for the particular pungent odor.
The clinical manifestations of mustard allergy, observed in a study conducted on 49 mustard-allergic children in France, included skin reactions (urticaria, angioedema) in 21 patients (42.8%), gastrointestinal reactions in 1 patient (2%) and conjunctivitis in 2 patients (4%). The oral allergy syndrome and anaphylaxis were also reported in 2% of children. In another prospective study conducted on 29 mustard-allergic patients in Spain, skin reactions like angioedema and general urticaria were reported in 55.2% and 34.5% patients, respectively. Furthermore, 17.2% of patients reported gastric symptoms, 27.6% reported oral allergy syndrome, 37.9% reported respiratory symptoms, like dyspnea, 13.8% reported conjunctivitis and 48% of patients reported anaphylaxis.
Mustard-induced anaphylaxis has been reported for the last 20 years. Several cases have been identified in France, Spain, Germany and the USA, where anaphylactic reactions to mustard have been reported after ingestion of food-containing mustard. In a study conducted in France, mustard was the cause of anaphylactic reactions in 3% of patients with severe reactions to food (n=60).
Allergic rhinitis
In a prospective study conducted on 29 mustard-allergic individuals in Spain, allergic rhinitis was reported in 10.3% of patients. In another prospective study involving 35 atopic patients with mustard hypersensitivity in Spain, allergic rhinitis was reported in 33 patients (94.2%).
Asthma
In a prospective study conducted in France, the prevalence of asthma was reported to be 4% in mustard-allergic children (2 out of 49 children). In another prospective study involving 35 atopic mustard-hypersensitive patients in Spain, 22 patients reported bronchial asthma (62.8%).
Atopic Dermatitis
Atopic dermatitis was found to be commonly reported in patients with mustard allergy. In a prospective study conducted in France, the prevalence of atopic dermatitis was reported to be 42.8% in mustard-allergic children (21 out of 49 children). In a prospective study involving 35 atopic mustard-hypersensitive patients in Spain, atopic dermatitis as well as respiratory symptoms were observed in 4 patients (11.4%).
Two case studies (case 1: female aged 48 years and case 2: male aged 25 years) with allergic contact dermatitis were identified (India and China), with reports of positive patch test to mustard.
Cross-Reactivity
Cross-reactivity between aeroallergens, like pollens and mustard, is widely reported. Association between mustard and mugwort (Artemisia vulgaris) pollen was found to be significant (p<0.001) in studies conducted on patients with mustard hypersensitivity.
The mugwort-mustard allergy is a term coined to describe this association of mugwort pollinosis, with food allergy from the Brassicaceae family members like white and Indian mustard, and others such as cabbage, broccoli and cauliflower. The cross-reactive allergen components, responsible, are not yet confirmed, but possible ones include LTPs (Art v 3, Sin a 3), profilins (Art v 4, Sin a 4) and Art v 60 kDa.
Mustard as a hidden allergen is found to have potential cross-reactivity with allergens of nuts, legumes, corn and Rosaceae fruits, especially peach. In a prospective study conducted on 38 Spanish mustard-allergic patients, all were found sensitized to other members of the Brassicaceae family (cabbage, cauliflower and broccoli), while 97.4% were sensitized to nuts (excluding almond and peanut), 94.7% to legumes, 78.9% to corn and 89.5% to Rosaceae fruits, suggesting cross-reactivity among them. Additionally, cross-sensitization was observed to be significant (Pearson correlation=0.006) among mustard and peach, in an observational cohort study involving 35 peach-allergic patients.
A review suggested that no clinical cross-reactivity at either inhalation or food allergy level exists between rapeseed and mustard, although cross-sensitization may be present. However, Sin a 1 showed marked cross-reactivity with rapeseed allergen Bn III at IgE antibody level. Furthermore, 2S albumin from sunflower seed was found to be cross-reactive with 2S albumin of mustard.
Sensitization to foods from the Rosaceae family and pollens may be attributed to Sin a 3 and Sin a 4. A study revealed that 11S globulins from tree nuts, such as pistachio, almond, hazelnut and walnut shared IgG epitopes with Sin a 2 and reduced its IgE binding ability. A similar effect was not observed with peanut. Further, no cross-reactivity was observed between Sin a 1 and proteins of the Brassicaceae family, with similar genetic homology.
Sequence similarity of mustard LTP Sin a 3 is reported to be 65% with LTP from cabbage (Bra o 3) and 50-55% with LTP from peach (Pru p 3), apple (Mal d 3), cherry (Pru a v 3) and hazelnut (Cor a 8), as well as with pathogenesis-related PR-10 protein (Fra a 3). Moreover, the sequence similarity of mustard profilin Sin a 4 has been shown to be around 80% with profilin from melon (Cuc m 2) and peach (Pru p 4), and also some similarity with profilins from chenopod (Che a 2) and birch (Bet v 2).
References
- Khan IU, Dubey W, Gupta V. Taxonomial Aspect and Brief Description of Mustard Plant: A Review. Universal Journal of Pharmacy. 2015;4(1):20-4.
- Morisset M, Moneret-Vautrin DA, Maadi F, Frémont S, Guénard L, Croizier A, et al. Prospective study of mustard allergy: first study with double-blind placebo-controlled food challenge trials (24 cases). Allergy. 2003;58(4):295-9.
- Saini PK, Mathur B, Kumar B, Yadav RK, Pandey S. A Classical Review on Mustard. International Journal of Chemical Science. 2018;2(3):29-32.
- Sharma A, Verma AK, Gupta RK, Neelabh, Dwivedi PD. A Comprehensive Review on Mustard-Induced Allergy and Implications for Human Health. Clin Rev Allergy Immunol. 2019;57(1):39-54.
- L'Hocine L, Pitre M, Achouri A. Detection and identification of allergens from Canadian mustard varieties of Sinapis alba and Brassica juncea. Biomolecules. 2019;9(9):489.
- Madhusoodan KJ, Hrideek TK, Kuruvilla KM, Thomas J. Mustard - Cultivation Practices. Indian Journal of Arecanut, spices and medicinal plants. 2004;5(4):157-61.
- Palle-Reisch M, Cichna-Markl M, Hochegger R. Development and validation of a duplex real-time PCR assay for the simultaneous detection of three mustard species (Sinapis alba, Brassica nigra and Brassica juncea) in food. Food Chem. 2014;153:66-73.
- Sinapsis alba; Brassica juncea; Brassica nigra [Internet]. CAB International. 2019 [cited Nov 17, 2020].
- Angelina A, Sirvent S, Palladino C, Vereda A, Cuesta-Herranz J, Eiwegger T, et al. The lipid interaction capacity of Sin a 2 and Ara h 1, major mustard and peanut allergens of the cupin superfamily, endorses allergenicity. Allergy. 2016;71(9):1284-94.
- European Food Safety Authority PoDPNaA. Opinion of the Scientific Panel on Dietetic products, nutrition and allergies [NDA] on a request from the Commission relating to the evaluation of allergenic foods for labelling purposes. EFSA Journal. 2004;2(3):32.
- Rancé F, Kanny G, Dutau G, Moneret-Vautrin DA. Food hypersensitivity in children: clinical aspects and distribution of allergens. Pediatr Allergy Immunol. 1999;10(1):33-8.
- Mailhol C, Giordano-Labadie F, Lauwers-Cances V, Ammoury A, Paul C, Rance F. Point prevalence and risk factors for food allergy in a cohort of 386 children with atopic dermatitis attending a multidisciplinary dermatology/paediatric allergy clinic. Eur J Dermatol. 2014;24(1):63-9.
- Caballero T, San-Martín MS, Padial MA, Contreras J, Cabañas R, Barranco P, et al. Clinical characteristics of patients with mustard hypersensitivity. Ann Allergy Asthma Immunol. 2002;89(2):166-71.
- Asero R, Mistrello G, Roncarolo D, Amato S. Detection of some safe plant-derived foods for LTP-allergic patients. Int Arch Allergy Immunol. 2007;144(1):57-63.
- Tripathi DM, Kumar S, Gupta A, N. M. A Prospective Study of Mustard Allergy in Allergic Rhinitis Cases. Bombay Hospital Journal. 2001;43(2):4.
- Kumar R, Kumari D, Srivastava P, Khare V, Fakhr H, Arora N, et al. Identification of IgE-mediated food allergy and allergens in older children and adults with asthma and allergic rhinitis. Indian J Chest Dis Allied Sci. 2010;52(4):217-24.
- Marambe HK, McIntosh TC, Cheng B, Wanasundara JPD. Quantification of major 2S allergen protein of yellow mustard using anti-Sin a 1 epitope antibody. Food Control. 2014;44:233-41.
- Figueroa J, Blanco C, Dumpiérrez AG, Almeida L, Ortega N, Castillo R, et al. Mustard allergy confirmed by double-blind placebo-controlled food challenges: clinical features and cross-reactivity with mugwort pollen and plant-derived foods. Allergy. 2005;60(1):48-55.
- Pałgan K, Żbikowska-Gotz M, Bartuzi Z. Dangerous anaphylactic reaction to mustard. Arch Med Sci. 2018;14(2):477-9.
- Worm M, Grünhagen J, Dölle S. [Food-induced anaphylaxis - data from the anaphylaxis registry]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2016;59(7):836-40.
- Andre F, Andre C, Colin L, Cacaraci F, Cavagna S. Role of new allergens and of allergens consumption in the increased incidence of food sensitizations in France. Toxicology. 1994;93(1):77-83.
- Allergen Nomenclature "Sinapsis alba - All Allergen" and "Brassica juncea - All Allergen" [Internet]. WHO/IUIS Allergen Nomenclature Sub-Committee. 2019 [cited Nov 17, 2020]. Available from: http://www.allergen.org/search.php?Species=Sinapis%20alba; http://www.allergen.org/search.php?Species=Brassica%20juncea.
- Vereda A, Sirvent S, Villalba M, Rodríguez R, Cuesta-Herranz J, Palomares O. Improvement of mustard (Sinapis alba) allergy diagnosis and management by linking clinical features and component-resolved approaches. J Allergy Clin Immunol. 2011;127(5):1304-7.
- Hummel M, Wigger T, Brockmeyer J. Characterization of mustard 2S albumin allergens by bottom-up, middle-down, and top-down proteomics: a consensus set of isoforms of Sin a 1. J Proteome Res. 2015;14(3):1547-56.
- Verhoeckx KCM, Vissers YM, Baumert JL, Faludi R, Feys M, Flanagan S, et al. Food processing and allergenicity. Food Chem Toxicol. 2015;80:223-40.
- Popescu FD. Cross-reactivity between aeroallergens and food allergens. World J Methodol. 2015;5(2):31-50.
- Sugita Y, Makino T, Mizawa M, Shimizu T. Mugwort-Mustard Allergy Syndrome due to Broccoli Consumption. Case Rep Dermatol Med. 2016;2016:8413767.
- Fiocchi A, Dahdah L, Riccardi C, Mazzina O, Fierro V. Preacutionary labelling of cross-reactive foods: The case of rapeseed. Asthma Res Pract. 2016;2:13.
- Skypala IJ. Food-Induced Anaphylaxis: Role of Hidden Allergens and Cofactors. Front Immunol. 2019;10:673.
- Skypala IJ, Cecchi L, Shamji MH, Scala E, Till S. Lipid Transfer Protein allergy in the United Kingdom: Characterization and comparison with a matched Italian cohort. Allergy. 2019;74(7):1340-51.
- Sirvent S, Akotenou M, Cuesta-Herranz J, Vereda A, Rodríguez R, Villalba M, et al. The 11S globulin Sin a 2 from yellow mustard seeds shows IgE cross-reactivity with homologous counterparts from tree nuts and peanut. Clin Transl Allergy. 2012;2(1):23.