Cumin anaphylaxis and allergy to spices in pediatrics: a case report and literature review

Abstract

While spice allergies are rarely documented in children, spices are becoming an increasingly common allergen in pre-packaged foods. Current literature reports contradictory findings regarding the risk of severe reactions in pediatric patients, with some evidence suggesting that small amounts of spices usually used in home-cooked meals may be safe for children. However, allergens, such as spices, are increasingly used in the food industry, coupled with diverse culinary habits and customs, necessitates a re-evaluation of this risk. To the best of our knowledge, this is the first report of cumin anaphylaxis via inhalation in a pediatric patient. Spice allergies should be suspected in patients with allergic manifestations occurring briefly after the consumption or inhalation of multiple different and unrelated foods. Our experience indicates that prick-by-prick tests with spice powders are helpful and should be recommended as part of the diagnostic workup to investigate this peculiar type of food allergy and prevent misdiagnosis of idiopathic anaphylaxis. Limited data concerning the reliability of skin tests with native spices and extracts are available in the literature. Native spices could contain irritant agents leading to false-positive results, but standardized case-control studies are currently lacking. New techniques can be used in the diagnostic process; however, they still need to be validated and integrated into clinical practice. Further investigation is required to quantify the impact of spice allergies on the pediatric population, especially in today’s multiethnic societies.

1 Introduction

The term “spice” refers to any plant-derived product used during cooking for food seasoning to add an aroma (1). Due to the global proliferation of ethnic cuisines, spices have become popular in both individual diets and food industries. Pepper, paprika, garlic, cumin, anise, oregano, and other spices are widely used in cuisine to enhance flavor profiles or serve as food preservatives. Spices are classified based on botanical analogies and taxonomic families (Figure 1) (2).

Similarly, condiments represent ready-to-use sauces, pastes, or mixtures (e.g., ketchup, mustard, soy sauce) added during or after cooking, and some of them also contain spices, rendering ingredient identification sometimes difficult (3).

Allergic signs and symptoms due to spice can be the result of Immunoglobulin E (IgE)- or non-IgE-mediated mechanisms (4). Moreover, severe irritative reactions (mediated by capsaicin) affecting the skin or respiratory tract are difficult to distinguish from immune-mediated reactions (5, 6). Some substances in spices like hot pepper (Piperaceae) and paprika, cayenne or chili (Capsicum annuum) could also increase the permeability of epithelia determining sensitization to proteins from other foods, below a molecular mass of 70 kDa (7). Regarding IgE-mediated spice allergy, no data are available about safe threshold doses, and very low amounts of proteins have been described to cause anaphylaxis (8).

Epidemiological data suggest that spice allergies are relatively rare, accounting for only 2–4% of all food allergies in adults. Adult women appear to be at higher risk, likely due to the use of cosmetics and fragrances. Current literature lacks studies on the prevalence of spice allergies in children. However, consumers constantly and unintentionally ingest undeclared natural flavors or spices, with the risk of severe reactions. Spice labeling is often inaccurate owing to varying national food regulations across countries. Furthermore, spices are frequently secret ingredients in traditional recipes and may cause reactions both upon ingestion and inhalation. In the European Union, Regulation No. 1169/2011 on the provision of food information to consumers has been effective since December 2014. According to Annex V, spices and herbs that constitute less than 2% of a finished product are declared generically as “spices” or “herbs” or “mixtures” thereof. Therefore, unlike mustard, celery, and lupin, which require mandatory declaration, as specified in Annex II, spices and herbs are often not specified in the final food product labeling (9).

In children, anaphylaxis to spices is documented as isolated case reports (Table 1). The European anaphylaxis registry reviewed 1970 cases of anaphylaxis in children (0–17 years) and 4% were linked to spices (curry, poppy, pepper, mustard seed, sunflower seed, and pumpkin seed) (29). In the updated registry, published in 2023, spices are responsible for 32 of 4468 food-induced anaphylaxis cases (0.7%) (30). In a retrospective analysis, Jiang et al. reported spices as the cause of anaphylaxis in 25 of 1501 cases in both children and adults (1.7%) (31). Several additional anaphylactic and systemic reactions to spices in children have been reported worldwide in retrospective studies, based upon clinical data records (32).

In this article, we report the first case of cumin anaphylaxis caused by inhalation in a patient under 18 years of age and performed a narrative review of pediatric spice allergy cases published in the literature.

A literature search was performed using PubMed, MEDLINE, and EMBASE databases to identify articles concerning spice allergy and anaphylaxis in the pediatric population. Articles published between January 1989 and March 2024 were selected. The search strategy included the terms “spices” and “herbs” combined with “food allergy,” “spice allergy,” “IgE-mediated allergy,” and “anaphylaxis,” along with pediatric-related keywords (“child,” “pediatric,” and “adolescent”). Case reports, case series, retrospective studies, and prevalence studies were included in this analysis. Articles describing allergic reactions following spice ingestion or inhalation were considered.

We also described a case report of anaphylaxis upon the inhalation of cumin spices in a pediatric patient. Information was retrieved from the patients’ electronic medical records. Informed consent was obtained from the patient’s parents for the publication of this case report.

2 Case description

A 17-year-old girl of Moroccan origin living in Tuscany was admitted to the Meyer Children’s Hospital IRCCS Allergy Unit for asthma, allergic rhinitis, and IgE-mediated food allergy.

Previous skin prick tests (SPT) were positive for kiwi, house dust mites, dog and cat dander, grass pollen, eggs, cod, strawberries, walnuts, and latex. Nonetheless, she tolerated all ingested foods except kiwis and was prescribed a kiwi-free diet.

She regularly used inhaled corticosteroid-formoterol therapy and reported poor control of respiratory signs and symptoms, with at least one acute asthma attack per month. The patient’s family history was negative for atopy.

The girl had never touched or ingested cumin in the past; she had consumed and tolerated all other spices, including turmeric, saffron, cardamom, and coriander. Since the age of three, the girl had experienced multiple reactions characterized by itching, rhinitis, and sneezing associated with face flushing after cumin inhalation; all reactions occurred while meals were prepared by her mother.

At the age of 17, the girl was in the kitchen while her mother was cooking eggs with cumin, and she immediately showed shortness of breath associated with rhinitis, generalized itching, flushing, and eye and lip angioedema. She did not report any physical exercise, medication, or food consumption before cumin exposure. The girl was administered a single oral dose of levocetirizine (10 mg) and betamethasone (4 mg) at home immediately after the onset of clinical manifestations.

She then presented to the hospital emergency department (ED), where she appeared in good clinical condition but with mild dyspnea, generalized itching, lip edema, and bilateral wheezing with an oxygen saturation of 93%. Other vital signs were normal.

The reaction was treated in the ED with a single dose of intramuscular epinephrine (0.01 mg/kg/dose, maximum 0.5 mg), intravenous chlorphenamine (0.25 mg/kg/dose), hydrocortisone (10 mg/kg/dose), and saline solution infusion at the hospital, with complete signs and symptom remission within 3–4 hours. Blood tests showed normal blood counts, biochemical profiles, and C-reactive protein levels; tryptase was not tested, probably due to the clear anaphylactic symptoms in the ED.

After 1 month, she was re-evaluated at the Allergy Unit outpatient clinic and a prick-by-prick (PbP) test was performed using cumin powder obtained from the trituration of dried seeds; the patient showed a strong positive response (wheal = 9 mm). The positive and negative controls for the test were a histamine (10 mg/ml; Lofarma, Milan, Italy) and normal saline SPT, respectively.

The patient was advised to avoid ingesting cumin and kiwi and to always carry an epinephrine autoinjector after training for proper use.

Given the risk of anaphylaxis, an oral challenge with cumin was not performed.

The patient’s clinical history is summarized in Figure 2.

3 Discussion

In the literature, a wide spectrum of reactions to spices is described (33), mainly caused by food ingestion, predominantly documented in adults and sometimes associated with occupational exposure. Indeed, spice allergy is largely considered an occupational disease affecting the adult population (4), several case reports of anaphylaxis are documented in adults (10–14, 16–21, 34). In industrial settings, food workers may develop contact dermatitis or occupational asthma following inhalation of dust with garlic, onion, and chili pepper (35).

However, data on anaphylactic episodes following spice inhalation are limited. Chiu et al. reported an anaphylactic episode in a 40-year-old woman with a history of seasonal and perennial allergic rhinitis due to inhalation of food cooked with dill. Interestingly, in the past she complained of systemic symptoms after ingestion of this spice, and after repeated exposures, even by inhalation (12).

Although several foods can elicit anaphylaxis due to inhalation (36, 37), only one pediatric case report of anaphylaxis due to spice inhalation has been described: a 6-year-old girl with urticaria and respiratory symptoms after inhalation of powdered American ginseng (28). Our article reports the first case of anaphylaxis caused by cumin inhalation in a patient aged less than 18 years.

Among spices, cumin (Cuminum cyminum L.) belongs to the Apiaceae (Umbelliferae) family and its yellowish-brown seeds are valued for their aroma and warm taste in cuisine as well as for pharmaceutical applications (38). Being the second most used spice in the world, cumin rarely triggers allergic reactions, although isolated cases of anaphylaxis are reported in adults (11).

Generally, the most allergenic spices in children belong to the Apiaceae family, which includes also coriander, fennel, celery, chervil and dill, and the Liliaceae family, including garlic, onion, chives, shallot and saffron (5).

As reported by Cercle d’Investigations Cliniques et Biologiques en Allergologie Alimentaire, a French society for food allergy research, real sensitization to spices in children suspected of food allergy could be more common than we thought. In a study that included 589 cases of food allergy, 26/81 (32%) of children showed a positive prick test for Apiaceae. Notably, of the children tested for cumin, 20% were prick test-positive, while sensitization to Liliaceae (e.g. garlic, onion, and chive) was only 4.6%. Despite the high sensitization rate in children, no case of pediatric allergy to spice has been confirmed in this case series (39).

Severe allergic reactions to spices have been described in the pediatric population in several case reports, as well as mild-to-moderate reactions (Table 2).

For instance, an anaphylactic reaction after eating venison prepared with a marinade containing various spices, unveiled allergy to black and cayenne pepper in a 17-month-old child (25). Moreover, two cases of anaphylaxis after the ingestion of curry and pastes containing fenugreek have been described in children. Joseph et al. reported a case of fenugreek anaphylaxis in a 14-year-old boy who developed hives, chest tightness, abdominal pain, and vomiting after eating a spread made of fenugreek, lemon, garlic, and cilantro (26). Ju Suk et al. reported a curry allergy in a 15-year-old boy who presented with immediate palatal itching, generalized urticaria, headache, and dyspnea after eating aromatized rice with curry, confirmed by oral food challenge (24). Che et al. also reported the case of a 14-year-old male who developed anaphylaxis (pruritus, chest heaviness, urticaria and wheezing) after eating curry made with fenugreek (27). The same article reports anaphylaxis to sumac in a 14-year-old female shortly after eating a salad containing za’atar, a mixture of sumac, sesame, dried thyme and salt, typical of Lebanese cuisine (27). Other authors reported a case of an 8-year-old boy who experienced anaphylaxis after consuming a chamomile-tea infusion (40). Among the less severe reactions, a breastfed 9-month-old baby who accidentally ingested homemade garlic sauce for the first time started coughing and exhibited generalized erythema, most likely because the mother’s milk acted as the primary sensitizer. Positive PbP tests with the same sauce were demonstrated in the infant (41).

However, spice allergy may be difficult to hypothesize and investigate, even more so in children (53).

First, the diagnostic workup is often challenging because of a history of ingestion of a mixture, raising the possibility of multiple putative allergens. Indeed, some composite products (food and beverages) can contain spices and herbs that are not included in the ingredient list owing to their small quantity. For example, coriander used as a natural flavoring in beer has been linked to anaphylaxis in a case report, and it was not declared in label; this may represent a problem in adolescent-adult age (54). On the contrary, herbs and spices are often used in phytotherapy in infant products, and mustard and lupin could be found in pre-packaged foods for toddlers until the Legislation was changed (55). Moreover, due to allergen similarity, hidden allergens could be masked in spice: undeclared peanut and almond in a taco spice were subsequently found in cumin, as contaminants (56).

Our patient recognized cumin as causative of the reaction by herself; despite this, we underline the importance of a detailed medical history that evaluates all ingredients and ethnic habits, highlighting the role of the prick test with spice powder, as in our case, to avoid the improper diagnosis of idiopathic anaphylaxis and the risk of future reactions. Furthermore, the identification of spice allergies could be very difficult because of the widely varying laws governing food labeling; spices may not be described in detail in both traditional recipes and ready-made meals.

Second, the diagnostic process for spice allergies can be difficult. Muhlemann et al. demonstrated that prick tests with native spices and spice extracts produced comparable results, whereas s-IgE testing was negative in more than half of the cases (57). In other studies, the sensitivity of the prick test using extracts changed considerably; Niinimaki et al. reported a higher rate of positivity when skin tests were performed with extracts containing a 5% concentration of spice (weight to volume) (58, 59). Better standardization of the method is necessary to minimize false-positive results using native species for the PbP test, which is considered a potential irritant capacity for some of them. Some studies emphasized the role of native prick tests with herbs and spices in the diagnostic workup of pediatric patients with pollinosis, encouraging larger clinical studies to investigate the clinical impact of herb sensitization in children (60).

In conclusion, studies have focused on the sensitivity and specificity of skin tests (both with native spices and extracts) with variable results, and blood tests for spices are missing. Most studies are on a small sample, mostly in adults without a documented history of spice allergy. Moreover, experts consider that there are currently limited data regarding the reliability of skin tests and s-IgE; therefore, when the suspicion of spice allergy is strong, despite negative test results, a double-blind placebo-controlled food challenge with powdered spices entrapped in capsules should be performed (45). Notably, although several studies addressing skin tests and in vitro assays date back more than two decades, these limitations persist. Modern, standardized diagnostic tools for spice allergies in children may be available, but they are not yet validated or widely used. One example is the use of multiplex tests, which represent a promising diagnostic frontier, offering simultaneous testing for multiple spices (e.g., anise, cumin seeds, oregano, paprika, and parsley). Unfortunately, multiplex tests, as well as the basophil activation test, were not available for our case report at the time of writing.

Third, sensitization to spices could also happen after primary sensitization by inhalation of pollen and following a cross-reaction, especially with birch or wormwood (such as in celery-mugwort-spice syndrome) (61–63). Wagner et al. recently demonstrated a stronger correlation in children than adults, even a two-to-four-fold higher, between prick test positivity for Lamiaceae or Apiaceae and pollinosis (birch, mugwort or grass pollen), although spice allergy symptoms in the sample have not been studied (60). In his study, pediatric patients with pollinosis responded 16–18 times more often to skin tests with herbs of Apiaceae family and 28 times more often to lemon balm (Lamiaceae family) than patients without pollinosis.

In these patients, inhalation of allergenic proteins could be the main mechanism of sensitization, since Bet v 1 homologues and profilins in Apiaceae and Solanaceae families are labile to high temperature and sensitive to gastric digestion, and determine cross-reactions between spices and vegetables within the same family, such as celery, carrot, and many popular spices, such as cumin, anise, and fennel.

Indeed, cross-reactions are more frequent among spices from the same phylogenetic tree (2, 4). Most of the reactions to anise, dill, coriander, and cumin are caused by allergenic determinants which belong to the family of Bet v 1 and profilin homologues like in cumin (Cum c 1 and Cum c 2), fennel (Foe v 1 and Foe v 2), coriander (Cor s 1 and Cor s 2) and anise (Pim a 1 and Pim a 2) (64), but also to other allergens like the defensin like protein 1 in celery (Api g 7) (61). Moreover, in 2020, Slowianek et al. identified new allergens in anise and caraway, respectively glyceraldehydes-3-phosphate dehydrogenase and elongation factor α, together with other cumin IgE-binding proteins with variable molecular mass (of 54, 42, 38, 31, and 20 kDa) (65).

Concerning the extent and type of processing, spice allergens in food may be degraded, but enhancement of the IgE-binding capability is sometimes possible (2). In hot spice paprika, high temperature destroys Bet v 1 homologues, but an osmotin named Protein P23 was demonstrated to be heat-resistant (66). Jensen-Jarolim et al. proved that dried Apiaceae spices still contain intact Bet v 1 and profilin homologues (64). In Apiaceae and Solanaceae families, cross-reactive carbohydrate determinants are also expressed, which are more resistant to food processing, including grinding and roasting (2, 64).

Moreover, due to the presence of seed-storage proteins (such as mustard, sesame, peanut, Brazil nut, and walnut), other spice types may also cause cross-reactions with different foods. The 7S-vicilin and 11S-legumin allergens revealed considerable homologies to peanut Ara h 1 and Ara h 3, respectively, explaining clinical cross-reactivity between peanut and fenugreek (67). Being fenugreek part of the Leguminosae family, allergic patients can be cross reactive to other legumes, like fava beans and lentils (68).

The current perception of plant-based foods and food-flavoring agents as innocuous and the increasing use of ethnic and creative cuisines in the pediatric population may affect the future prevalence of this rare entity (69). Therefore, spice variability warrants further molecular research to identify all allergic determinants, assess the reliability of the prick test considering the different irritant capacities of the spice, and highlight the need for a registry of pediatric spice allergy cases to better understand its potential clinical impact. Clinical history should always guide subsequent investigations, and spice allergies in children may be difficult to suspect unless careful anamnestic investigation is performed. Multiplex tests may further aid in identifying such cross-reactivity and profiling individual risk to the patient. Finally, follow-up clinical studies in pediatric populations are needed to understand the long-term prognosis of spice allergies.

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