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Q:

Reviewed: February 24, 2020
12/19/2014
I have a 42 year-old male patient who developed ginger allergy with facial angioedema after he has been drinking "ginger" juice for 3 months. He would initially feel scal itchiness, ears flushing, then eyelids and facial angioedema would develop within 30 minutes. I checked CBC, sed rate, C2, C4, ANA, LFTs, all normal. His IgE against ginger also negative. Prick test also negative, but his angioedema was witnessed after he ate ginger. He also recently developed angioedema to curry. My question is, can a person who has negative IgE and skin test to ginger still have true allergy to ginger? Is there any validity to one month antihistamine treatment for this type of acquired food allergy?

A:

Ginger juice is a term used for a variety of drinks that contain multiple ingredients in addition to ginger. It would be helpful to know the specific ingredients in the “ginger” juice your patient was drinking. If his in vitro IgE and prick skin test to ginger is negative, I would be concerned that another ingredient is responsible for his acute symptoms, especially since he is also having symptoms with curry. Curry, which includes curry powder or spice, is also a complex mixture of ingredients with great variability (see Ask The Expert question from archives). The combination of reactions to two complex mixtures would make me suspicious of a common ingredient. I would try to obtain the exact components of the ginger juice and the curry to which he reacted to see if you could identify a common agent.

Spices do show some cross reactivity (see abstracts and references below) but the clinical significance of these findings are difficult to confirm as allergy to spices is rare.

Certainly testing does not have a 100% negative predictive value as foods are modified by digestion and I do not know if you tested with fresh or processed ginger.

I am not aware of a “one month antihistamine treatment” for such allergy. I am not sure if you are referring to antihistamine therapy to suppress symptoms to allow ingestion and the development of tolerance. I would be very skeptical that this would have any value as antihistamine therapy does not usually prevent systemic IgE mediated reactions as mast cells release many factors other than histamine. I believe this treatment approach may place your patient at significant risk.

In summary, allergy can occur with negative skin and in vitro tests due to multiple mechanisms of immunologic response and difficulties in obtaining the most appropriate testing reagent. Allergy does require documentation of an immunologic response, which in your case we have not established. However, the symptoms are highly suggestive and in light of the complex mixtures of substances I suspect there is an allergen responsible. Whether the allergen is ginger or another ingredient should be considered. Your second question addressed a one month antihistamine therapy for acquired food allergy and I am not aware of such a treatment approach.

Van Toorenenbergen, A. W., et al. "Immunoblot analysis of IgE-binding antigens in spices." International Archives of Allergy and Immunology 86.1 (1988): 117-120.
Abstract
The IgE response to coriander and other spices was studied by immunoblotting, after separation of the spice extracts by isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). A major IgE-binding component from coriander had an isoelectric point of pH5. After incubation of SDS-PAGE-separated spice extracts with serum from a patient with an occupational allergy to spices, a closely related pattern of IgE binding to coriander, dill and anise extract was observed. These results suggest that the botanically related spices, coriander, anise and dill, contain common IgE-binding structures.

Wong, HC George. "Allergic contact dermatitis from topical Chinese herbal medicine and generalized urticaria and angioedema."

van Toorenenbergen, Albert W., and Paul H. Dieges. "Immunoglobulin E antibodies against coriander and other spices." Journal of allergy and clinical immunology 76.3 (1985): 477-481.
Abstract
Patient M, working with spices in the food industry, developed asthma on inhalation of dust from spices. Skin prick test results with curry, coriander, and mace were strongly positive. With RAST, specific IgE antibodies against coriander, curry, mace, ginger, and paprika powder could be demonstrated in serum from patient M. It could be demonstrated by RAST inhibition that the IgE-binding components from coriander did not cross-react with the IgE-binding components from ginger and paprika. Leukocytes from a normal donor, after passive sensitization with serum from patient M, released a substantial (?50%) amount of histamine on challenge with extracts of coriander, mace, and curry powder. This study demonstrates that the inhalation of dust from spices can result in an IgE-mediated allergy toward these materials.

Anaphylaxis possibly due to the ingestion of curry
Q: I saw a 44 y.o. man with a convincing history of possible anaphylaxis to curry used in a stir fry dish. He experienced throat tightness, difficulty swallowing, flushing, wheezing, pruitus within minutes of eating which improved with Benadryl. I know that curry contains several ingredients including coriander, cumin, tumeric, fenugreek seeds. What would be the best way to evaluate him? He is interested in determining precisely what caused the reaction if possible. I cannot skin test him to these spices, but do have access to Immunocap testing. Thanks.

A: As you probably understand, the term "curry" does not refer to a single entity. There are many formulations of curry. If you wish to view several of the combinations of ingredients in different formulations. I have copied below lists as the "standard spice blend" of curries found in the West. There are over 25 ingredients listed as possible contents in curry. In addition on that site, you will find eight different preparations using variations of these ingredients.

Therefore, it is important for you to know the exact contents of the curry that your patient ingested. I assume that the contents you have listed constitute the total ingredients in this curry preparation.

Serum-specific IgE tests for these ingredients, if available, would be an excellent way to proceed. However, I do not think you will find all of the ingredients available for testing. For example, I did find a test available for coriander. I also found tests available for curry itself. However, I was unable to locate a test for turmeric or cumin. If indeed, however, you can find tests for each ingredient, you might be able to identify the culprit. It should be kept in mind, however, that these tests simply indicate the presence of IgE antibody against the substance, but whether or not the antibody itself was responsible for the reaction still remains a clinical decision. In other words, sensitivity does not always correlate with clinical reactivity. So, for example, you may find positive tests against more than one antigen, and then you would not be able to identify the cause without an actual oral challenge.

An excellent place to look for the availability of tests to the various ingredients that you find in his preparation is the website of the Phadia ImmunoCap. If you will Google "Phadia ImmunoCap," it will pull up the site, and then one need only click on "allergens" to pull up the various allergens available. Then click on "food of plant origin" to see those which might be included in curry.

Again, these tests would only detect serum-specific IgE against these ingredients, and would not necessarily establish a cause and effect relationship between the particular ingredients to which specific IgE is present and the reaction.

It also might help you to be acquainted with some of the literature regarding anaphylaxis to curry powder. One of the earlier references in this regard describes a patient with anaphylaxis to curry powder (1).

I have also copied below an abstract of a case report from the Journal of Allergy and Clinical Immunology regarding an allergic reaction to curry. The approach to this patient may give you further suggestions as to how you might proceed.

In addition, skin tests to spices actually can be performed. There are several references describing this procedure. For your interest, I have copied below an abstract from one of these articles (Moneret-Vautrin DA, et al.). The article itself contains the methods by which the skin tests were done.

In summary:
Curry can contain multiple ingredients and it is important, if you do proceed with an evaluation, to make sure that you evaluate all of the ingredients in the curry ingested by your patient. There are two ways to evaluate immediate hypersensitivity reactions to the ingredients in curry. A serum-specific IgE assay is certainly an excellent way to do this, but tests for all of the ingredients may not be available. You could also consider, as described in the abstract copied below (and other publications as well), skin testing to the individual ingredients. Regardless, a positive test, as you know, indicates only sensitivity, and does not necessarily document a cause and effect relationship between the tested allergen and the event.

Thank you again for your inquiry and we hope this response is helpful to you.

CURRY POWDER:
Ingredients
In the West, the standard spice blend contains cardamom, turmeric, fenugreek, cumin and chillies, while various others can be included, such as ginger, cloves, nutmeg, coriander, mustard, garlic, fennel, and black pepper, to name a few."
Introduction: Allergic symptoms caused by spices are infrequent and usually mild. Anaphylaxis to curry powder is a rare case of spice allergy. To our knowledge, this is the first case confirmed anaphylaxis to curry powder in child in Korea.
Methods and results: A 15-years-old boy visited in our hospital. He complained that when he ate curry and rice in two months ago, he developed immediate palatal itching, generalized urticaria, headache and dyspnea. His chest radiographs are normal findings. He had no history of asthma but methacholine provocation challenge test revealed positive finding (PC20 3.62mg/ml). Skin prick tests revealed positive findings to asparagus, house dust mite (Dp, Df), flower pollens (aster, chrysanthemum, golden rod), weed pollens (mugwort, ragweed, dandelion, short ragweed). Specific IgE to Dp, Df, soy bean was positive (6.52, 31.2, 1.91 U/ml) and his total IgE was 1207 U/ml (CAP system). After informed consent, we performed oral provocation test to confirmed relationship between his symptoms and curry powder. He ate curry powder 20g with only water and we measured his PEFR per 10 minutes. After 30 minutes, he developed profused sweating and dyspnea. When we treated with epinephrine and bonchodilator, his symptoms improved. He developed same symptoms after 2 hours later and his symptoms well controlled by same medication.
Conclusion: This is the first case confirmed anaphylaxis to curry powder in child in Korea

The Journal of Allergy and Clinical Immunology
Volume 113, Issue 2, Supplement , Page S317, February 2004
Abstract
Allerg Immunol (Paris). 2002 Apr;34(4):135-40.
Food allergy and IgE sensitization caused by spices: CICBAA data (based on 589 cases of food allergy).
Moneret-Vautrin DA, Morisset M, Lemerdy P, Croizier A, Kanny G.
Service de Médecine Interne, Immunologie Clinique et Allergologie-Hôpital Central 29, avenue de Lattre de Tassigny, 54035 Nancy.
Abstract
Background: Spices originate in various botanical families: Apiaceae, Lamiaceae, Lauraceae, Leguminosae, Liliaceae, Myristicaceae, Myrtaceae, Piperaceae, Solanaceae, Zingiberaceae....
Methodology: Prick-tests to native spices have been carried out in patients suspected of food allergies to spices. The CICBAA data bank includes 589 cases of food allergies, a part of which has benefited from investigations for spices. Data about the rate of sensitization and food allergy are available.
Results: Frequent sensitization to Apiaceae is observed: coriander, caraway, fennel, celery: 32% of prick-tests in children, 23% of prick-tests in adults. Sensitization to Liliaceae: garlic, onion, chive, is observed in 4.6% of prick-tests in children, 7.7% of prick-tests in adults. Rare cases of sensitization to paprika and saffron are recorded. Prick-tests to nutmeg, ginger and clove are currently negative. 10 food allergies related to the mugwort-celery-spices syndrome are reported: coriander: 1, caraway: 2, fennel: 3, garlic: 3, onion: 1. Food allergy to spices is unfrequent: 2% of the totality of food allergies. However, only adults are allergic to spices and allergy to spices accounts for 6.4% of food allergies in adults. Tiny amount of proteins are usually ingested. Patients at risk of spice allergy are young adults sensitized to mugwort and birch allergens, sharing cross-sensitization with various food vegetal allergens. The clinical suspicion raises from frequent post-prandial systemic reactions. Other allergens of vegetal origin have to be cleared. Diagnosis can be established by DBPCFC using powdered spices in capsules. PMID: 12078423 [PubMed - indexed for MEDLINE]

Reference:
1. Ohmuma N, et al. Anaphylaxis to curry powder. Allergy 1998 (April); 53(4):452-454.

Sincerely,
Phil Lieberman, M.D.

I hope this information is of help to you and your patient.

All my best.
Dennis K. Ledford, MD, FAAAAI

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