Anaphylaxis in a pectin- and cashew nut-allergic child caused by a citrus bath

概要

Infants and children with severe eczema and/or egg allergy have a higher risk of tree nut allergies,1 among which, it is well known that cashew nut cross-react with pistachio nut.2 A recent study reported an allergic association between cashew nut and pectin or citrus fruits.3 Here, we report a case that had type-1 al- lergy to cashew nut and pectin who developed severe anaphylaxis after a citrus bath. A 7-year-old boy presented to an emergency room complaining of generalized wheals and dyspnea after 5e10 min of bathing with Japanese citrus (yuzu) bath additives (Fig. 1a, b). Pediatricians diagnosed anaphylaxis and administered an intramuscular injection of epinephrine. Then, he was referred to a dermatology clinic to determine the culprit allergens. He had a complication of atopic dermatitis and a history of anaphylaxis caused by cashew nuts. His symptom of atopic dermatitis was moderate disease (score 3) according to investigator's global assessment. His parents had eaten cashew nuts at home and also made homemade seasonings with yuzu. He also experienced itchy oral discomfort when he drank a pectin-containing fermented milk product. Because cross-sensitization among cashew nut, pectin, and citrus fruits had been reported,3 we suspected the transdermal allergic reaction to yuzu bath additives. We per- formed a skin prick test that revealed strong reactions to cashew nuts, pistachios, yuzu endocarp, ingredients in the bath additives, pectin from citrus (from Nacalai Tesque, Kyoto, Japan), and a pectin-containing fermented milk product (from Yakult Honsha, Tokyo, Japan) (Fig. 1c). He had high allergen-specific IgE levels for cashew nut component Ana o 3 (19.6 UA/mL) and crude cashew nut (9.62 UA/mL) by ImmunoCAP® test, although his non-specific IgE was 144 IU/mL.

To confirm anaphylaxis had been caused through IgE-mediated reaction, we performed a basophil-activation test4 by using the Allergenicity Kit (Beckman Coulter, Fullerton, CA, USA) for the quantification of basophil CD203c expression. As expected, the in- cubation of his blood, but not that of a healthy subject, with yuzu additives, pectin, or cashew nuts increased the number of CD203chigh basophils in vitro (Supplementary Fig. 1).

To assess the culprit allergen in citrus, we performed a Western blot (WB) assay and found a band specific for the endocarp of yuzu reacting with the patient's IgE, but not the exocarp or flesh of the fruit (Supplementary Fig. 2, area within dotted line). Because pectin is mainly contained in the endocarp of citrus fruit, this result is consistent with pectin allergy. Furthermore, the bands found in the WB assay in dotted line were smeared, suggesting the allergen comprises a mixture of various molecular weights. In addition, to assess potential cross-reactivity among yuzu, cashew nuts, and pectin, we performed an inhibition test using an enzyme-linked immunosorbent assay (ELISA). The patient had specific IgE to cashew nut, but this reactivity was inhibited by the addition of cashew nuts and pectin (Fig. 2a). The reactivity was reduced to almost zero when inhibited by cashew nuts, whereas pectin blocked 25 % of the reactivity. Of note, our case had specific IgE to the endocarp of yuzu, bath additives containing yuzu extracts, and pectin (Fig. 2b). Interestingly, the IgE reactivity to cashew nuts was completely inhibited by the addition of cashew nuts themselves, whereas it was partially inhibited by the addition of pectin. Also, we showed that IgE reactions to the endocarp of yuzu were completely inhibited by pectin and cashew nuts.

Pectin is a structural heteropolysaccharide found in the cell walls of vegetables and fruits such as citrus, apple, and sugar beet pulp.5 Pectin is often added to fermented dairy drinks because of its stabilizing effect.6 Ra€sa€nen et al., reported the first case study of cross-reactivity between pectin and cashew nut allergy in 1998.7 Ferdman reported a possible association among pectin, cashew nut, and pistachio.3 In general, allergy to cashew nut usu- ally cross-reacts with pistachio.2 Our study revealed that allergens in yuzu or pectin partially cross-reacted with cashew nut. We hy- pothesized that the main allergen of cashew nut, Ana o 3 (14 kDa), does not cross-react with yuzu or pectin because of the difference in their molecular weights. We assume that another allergen of 50e80 kDa (by WB assay) has cross-reactivity with cashew nut, yuzu, and pectin. Of note, specific IgE in previously reported Japa- nese cases of Citrus unshiu allergy bound to a 50e70 kDa frag- ment.8 The reported allergen component in cashew nut is Ana o 19, with a molecular weight of approximately 50 kDa; however, we have no data to prove cross-reactivity between Ana o 1 and cit- rus allergens. In a study of patients allergic to cashew nut, WB assay showed strong IgE binding to Ana o 1 in three patients and weak binding in seven patients.9 This suggests that a small number of patients with cashew nut allergy might also be allergic to yuzu and pectin.

We present a case of anaphylaxis, caused by yuzu bath additives. Taking a citrus bath is a Japanese health practice in winter. Howev- er, we do not recommend these baths for people with an allergy to pectin, cashew nut, or pistachio. Our patient also complained of itchy oral discomfort when he drank a fermented dairy product, because it contained pectin. Therefore, pectin-containing bever- ages might also be a risk for people with an allergy to pectin, cashew nut, or pistachio. To the best of our knowledge, this is the first study to report anaphylaxis induced by yuzu bath additives, probably due to transdermal contact to allergens. After the patient was advised to avoid allergens as discussed above, he developed no additional allergic reactions.

In conclusion, we showed partial cross-reactivity between cashew nut and pectin or yuzu, although our data are limited because this is a case report. Furthermore, we did not perform ab- sorption spectrochemical analyses to prove the culprit allergen was Ana o 1, because the smear-like bands obtained on WB were rela- tively weak. We assume that a small number of patients with cashew nut allergy are also allergic to yuzu or pectin. Such patients should avoid contact with pectin including drinking, inhalation, or contact by bathing.

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