Dose-dependent anaphylaxis to orange juice without detectable specific immunoglobulin E.

Immediate allergic reactions to orange are rare and immunoglobulin (Ig) E–mediated [1]. We report the case of a 28-year-old man with anaphylaxis induced by fresh orange juice. The reaction was dose-dependent and could only be confi rmed by challenge test, because specifi c IgE to orange was undetectable by skin prick test (SPT) and CAP immunoassay. The patient had experienced identical anaphylactic reactions on 2 occasions within 20 minutes after consumption of 300 mL of fresh orange juice. The symptoms were feeling of heat, fl ushing, itching on the palms and head, rhinitis, and generalized urticaria. His history was remarkable in that he had no symptoms when he ate 2 oranges or drank 300 mL of a commercial orange juice product. The patient was not suffering from allergic disease (asthma, rhinitis, atopic dermatitis) and had negative SPT results to aeroallergens and common food allergens. Surprisingly, SPT results with commercial extract and fresh juice of all citrus family members (orange, lemon, mandarin, and grapefruit) were also negative, as was an intradermal test with fi ltered orange juice. Specifi c IgE to orange, lemon, mandarin, rPru p 3 (lipid transfer protein) and profi lin was not identifi ed by CAP immunoassay (Phadia, Uppsala, Sweden). A challenge test was performed with fresh orange juice administered at increasing doses (50, 100, 150, 200, 300 mL) every 30 minutes. Within 20 minutes of drinking 150 mL of fresh orange juice the patient experienced an anaphylactic reaction with generalized urticaria similar to that reported in his history. The same reaction also appeared after 30 minutes with 150 mL of lemon, mandarin, and grapefruit juice. An oral challenge test with 2 commercial orange juice products was positive at 600 mL and 800 mL, respectively. A provocation test with fresh orange juice boiled for 2 minutes induced a mild anaphylactic reaction at 500 mL, thus demonstrating that the offending allergen is heat-labile but not completely inactivated by boiling. Allergic reactions to orange are rare, and manifestations range from oral allergy syndrome to mainly IgE-mediated anaphylaxis [2,3]. The case we report is unique because a dosedependent anaphylactic reaction to orange juice occurred with no detectable specifi c IgE to orange. In our case, a carefully performed open challenge test with fresh orange juice proved to be the only reliable procedure for the diagnosis to be established. Our patient experienced anaphylactic reactions whenever he consumed more than 150 mL of fresh orange juice. The provocation test indicated that the offending allergen exists in all other fresh citrus fruit juices. This fi nding is consistent with the results of other immunodetection studies with allergens [4,5]. We showed that the culprit allergen in our study was at least partly heat-labile, because the patient reacted only after consuming a large amount (500 mL) of boiled orange juice. This allergen does not belong to any of the 3 recently identifi ed major orange allergens–profi lin (Cit s 2), germin-like protein (Cit s 1), and lipid transfer protein (Cit s 3)–because these were all found to be heat-resistant [1-3]. The culprit allergen is likely to be uncovered after proteolytic degradation of certain unknown orange proteins (pro-allergen) during digestion. This is a reasonable explanation why specific IgE to orange allergen was undetectable in this patient. A similar mechanism has been proposed for anaphylaxis to sesame seed in patients with a negative SPT result [6]. Moreover, extremely low sensitivity to orange in this case–the patient tolerated 100 mL of fresh orange juice–-could affect the diagnostic sensitivity of SPT. We can infer that anaphylaxis to orange juice occurs as a dose-dependent reaction with no detectable specifi c IgE to orange. A challenge test in this case was the only reliable diagnostic technique that was more sensitive than SPT with fresh juice. The culprit allergen was partly heat-labile and found to exist in all other citrus fruits.