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Recently I had a 33 yo female with a history of birch pollen allergy come in after 2 episodes of anaphylaxis after salads. Both salads were store bought but contained several different ingredients including nuts (which she consumes regularly.) Because there was no obvious trigger by history and skin testing to food extracts in the office, she brought in the salads for fresh food testing. Surprisingly, she had large positive tests (measuring up to 13/50) to several varieties of lettuce including red leaf, romaine and arugula. She had negative tests to nuts. Despite her positive skin tests to the lettuces, I am hesitant to diagnose her with an anaphylactic reaction to lettuce simply because I have not seen this before and that it seems like there is little protein in lettuce that could cause such a severe reaction. (She needed epinephrine on both reactions.) Is lettuce a likely cause for anaphylaxis in this case? Should I just feel comfortable in calling it lettuce allergy given the positive skin tests or should I keep looking for another cause? (of note, baseline tryptase not elevated)


I congratulate on “going the extra mile” to define your patient’s problem. It was not clear from the question but I suspect you made the lettuce testing reagents from the salad components. If so, did you test any controls (yourself or staff) to see if false positive or irritant reactions occur? This is always important with “in house” made testing materials. Did you obtain a specific-IgE blood test to confirm the skin test (available from ThermoFisher, code f215)?

There are cases of lettuce associated anaphylaxis with specific-IgE identified for lipid transfer protein (Lac s 1), 9 kDa, which is associated with cross-reactivity with other lipid transfer protein-containing foods (7). Between 4 and 14 protein bands have been described in varietals of lettuce and many of these show some recognition by human IgE. (1,3, 4-6) There may be some cross reactivity between lettuce allergens and peach, cherry, carrot, sycamore pollen and Asteraceae (compositae) among others. Much of this cross-reactivity is likely related to the lipid transfer protein. Carrot and lettuce share many allergens but carrot seems to have greater allergenicity (2). Pollen food syndrome has been described as would be expected with the lipid transfer protein content (1-5,7-8,12, 23-24) Mugwort and ragweed are in the same family (Asteraceae) but cross reactivity has not been consistently confirmed.

In summary, lettuce anaphylaxis is not common but is well described. I would conclude that your patient has this type of sensitivity. I would confirm with in vitro specific-IgE. False positive allergy tests are reported as with all foods but the history is convincing. Pollen food syndrome, particularly with peach or cherry, would support a lipid transfer protein sensitivity. Carrot allergy is also a concern and you may wish to test for this since carrot may be a more potent source of similar allergens. You may also want to test for sycamore pollen sensitivity as this has been associated with more severe lettuce reactions. The varietals of lettuce likely contain similar allergens therefore all lettuce varietals should be avoided.

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

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

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