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ERROR: type should be string, got "https://doi.org/10.1007/s42399-020-00484-w\nSN Comprehensive Clinical Medicine (2020) 2:2208–2213 MEDICINE MEDICINE To the Editor Undiagnosed food allergy without known reaction to the\navoided food could result in elimination of the suspected food\nfrom a child’s diet [1]. Performing OFC to individual tree nuts\nis time consuming and impractical. Following a negative OFC\nchildren need to regularly include that food in their diet with\nevidence showing this may help to maintain tolerance to that\nfood [2]. The patients in this study are from a retrospective review of\npatients with a negative OFC to mixed tree nut biscuit per-\nformed at Princess Margaret Hospital (PMH), Western\nAustralia between 2016 and 2018. The tree nuts used in the OFC are almond, Brazil nut,\nmacadamia, cashew, pistachio, walnut, pecan, hazel nut, pine\nnut, and coconut. Mixed tree nut biscuit OFC included at least\n2 of the above nuts. The cohort of patients had predominantly negative or low\npositive skin prick test (< 6-mm mean skin prick test weal\ndiameter). Although most of the patients had a negative skin\nprick test (SPT), the challenge was done in hospital as families\nwere anxious or reluctant to introduce the nuts at home. Abstract We studied the introduction rate after a negative challenge to mixed tree nut biscuit. This is a retrospective review of patients who\nunderwent and passed mixed tree nut biscuit challenges performed at Princess Margaret Hospital (PMH) between 2016 and 2018. Follow-up phone calls were made to families to ascertain if the tree nuts included in the tree nut biscuit were still included in the\nchild’s diet 1 to 3 years following negative oral food challenge (OFC). A total of 162 children underwent mixed tree nut biscuit\nchallenge between 2016 and 2018 at Princess Margaret Hospital, Perth, Western Australia. A total of 141 (87%) passed mixed\ntree nut biscuit challenge. Of the 133 children that were contacted (8 children could not be contacted), 104 children still included\nsome or all of the challenge nuts in the child’s diet; with 24 children completely eliminating the challenge nuts (18%), 5 children\neliminated some of the challenge nuts (3.5%). We found a high introduction rate (82%); however, some families may require\nmore support to maintain the tree nuts in the child’s diet following a negative OFC. Keywords Mixed tree nut challenge Following Mixed Tree Nut Biscuit Challenge, Are the Nuts Still\nIncluded in the Diet? Benedicta Itotoh1\n& Ingrid Roche1 & Catherine Power1 Accepted: 24 August 2020\n# The Author(s) 2020\n/ Published online: 7 September 2020 1\nDepartment of Immunology, Perth Children’s Hospital,\nNedlands, Western Australia, Australia Introduction We studied the dietary introduction rate of tree nuts following\na negative OFC. Most of the children avoided tree nuts be-\ncause they were allergic to other foods or sensitized to tree\nnuts with no known clinical reaction. Some were avoiding tree\nnuts because another family member has a nut allergy. The SPT was performed and read as per the published\nguidelines of the Australasian Society of Clinical\nImmunology and Allergy [3]. The SPT size on the day of\nthe challenge was recorded. This article is part of the Topical Collection on Medicine\n* Benedicta Itotoh\nbenedicta.itotoh@health.wa.gov.au\n1\nDepartment of Immunology, Perth Children’s Hospital,\nNedlands, Western Australia, Australia The treating physician decides what nuts were included in\nthe biscuit, and the patient’s family baked and provided the\nmixed tree nut biscuit according to the recipe provided by the\nPMH Immunology Department. The biscuit was then admin-\nistered in a 5-step procedure starting with 1/16, 1/8, 1/4, 1/2,\nand the reminder of the biscuit given at 15-min intervals if\nchallenge was performed in the outpatient department * Benedicta Itotoh\nbenedicta.itotoh@health.wa.gov.au Materials and Methods To the Editor This article is part of the Topical Collection on Medicine This article is part of the Topical Collection on Medicine * Benedicta Itotoh\nbenedicta.itotoh@health.wa.gov.au SN Compr. Clin. Med. (2020) 2:2208–2213 2209 Table 1\nPossible factors associated with failed introduction following\nnegative OFC to three nuts\nSuccessful\n(eating all nuts\nPartial (eating\nsome nuts)\nUnsuccessful\n(not eating any\nof the nuts)\nTotal\n104\n5\n24\nGender\nMale\n65\n3\n8\nFemale\n39\n2\n16\nAge range\n1 year\n5 months to\n17 years\n7 months\n1 year\n8 months to\n10 years\n4 months\n1 year\n8 months to\n16 years\nSymptoms to\nchallenged nuts\nfollowing\nsuccessful OFC\n0\n1\nHives to hazel\nnut\n1\nRespiratory\nsymptoms Table 1\nPossible factors associated with failed introduction following\nnegative OFC to three nuts Data was obtained from electronic patient records as well\nas patient charts and used in strictly anonymous form, accord-\ning to the code of conduct for medical research approved by\nthe hospital’s Medical Ethical Committee (Child and\nAdolescent Health Service Safety and Quality Committee). Results A total of 162 children underwent mixed tree nut biscuit OFC\nbetween 2016 and 2018 at PMH. A total of 141 passed mixed\ntree nut biscuit challenge (87%). The majority of OFCs were\nconducted in the OPD (70.4%). All 141 patient charts were\nexamined with follow-up phone calls made to families to as-\ncertain if the nuts were still included in the child’s diet 1–\n3 years following the OFC. Eight families could not be\ncontacted. The majority were male (55%). Median age at chal-\nlenge was 8 years and 5 months (range 1 year and 7 months to\n17 years and 7 months). Twenty-seven children were admin-\nistered six nut challenge, 40 underwent 5 nut challenge, 38\nhad 4 nut challenge, 23 had 3 nut challenge, and 13 patients\nhad 2 nut challenge. (OPD) or as a 7-step procedure starting with 1/64, 1/32, 1/16,\n1/8, 1/4, 1/2, and reminder of the biscuit given at 20-min\nintervals if challenge was performed in the day procedure unit\n(DPU). The decision to either perform the challenge in the\nOPD or DPU was determined by the treating physician based\non the clinical risk of allergic reaction. Eight grams of each\nchallenge nut were included in the biscuit. Of the 133 families that were contacted, 104 families still\nincluded some or all of the challenge nuts in the child’s diet. Twenty-four patients completely eliminated the challenge\nnuts (18%) and 5 patients eliminated some of the challenge\nnuts (3.5%). Signed consent for the challenge was obtained from the\nparents prior to the challenge. Patients were recorded as a positive OFC if there were\nobjective signs of an IgE-mediated reaction as follows: angio-\nedema, generalized skin erythema, stridor, cough, wheeze, at\nleast 3 or more noncontact urticaria persisting for 5 min or\nmore, rhinoconjunctivitis, abdominal pain, vomiting, and hy-\npotension [4]. All patients had follow-up phone contact 2–\n4 weeks following the OFC. The patients were termed tolerant\nif they had a negative OFC and were tolerating the nuts at their\n2–4-week follow-up phone calls. Patients that passed the chal-\nlenge were advised to continue eating the nuts included in the\nbiscuit regularly (at least weekly). Discussion Possible factors influencing the introduction of the challenge\nnuts in the diet are shown in Table 1. Other patient character-\nistics with successful, partial, and unsuccessful challenge nut\ndietary introduction are shown in Table 1. There are no statis-\ntically relevant differences between the three groups. Fig. 1 Reasons for eliminating\nnuts from diet Fig. 1 Reasons for eliminating\nnuts from diet 2210 SN Compr. Clin. Med. (2020) 2:2208–2213 Table 2\nTree nuts included in biscuit, rate of introduction, and\nelimination from diet\nNuts included in\nmixed tree nut\nbiscuit\nNuts eliminated\nfrom diet following\nOFC\nNuts maintained\nin diet following\nOFC\nAlmond\n97\n21\n77\nBrazil nut\n97\n21\n76\nMacadamia 114\n21\n76\nHazel nut\n66\n13\n53\nPecan\n17\n1\n16\nWalnut\n76\n17\n59\nCashew\n50\n9\n41\nPistachio\n6\n1\n5\nPine nut\n23\n5\n18\nCoconut Table 2\nTree nuts included in biscuit, rate of introduction, and\nelimination from diet The other family describes exacerbation of the child’s asthma\nto all nuts. However, there was no clinical correlation between\nexposure to nuts and exacerbation of asthma with the elimination\nof nuts having no impact on the asthma symptoms. This patient\nwas challenged to almond, Brazil nut, walnut (negative SPT),\nhazel nut (2 × 2 mm SPT), and macadamia nut (1 × 1mm SPT). Of the 5 children whose families partially introduced the\ntree nuts, we note the following: The first child is the same child that excluded hazel nut\nbecause she had hives to hazel nut. She retained almond,\nBrazil, macadamia, and pine nuts in her diet. Two children ate almond only for no defined reason. One\nchild had challenge to almond, Brazil nut, walnut, and\nmacadamia, while the other child had challenge to almond,\nmacadamia, Brazil, hazel, and pine nuts. One child retained 2 of the 4 nuts included in their biscuit\nchallenge (hazel and macadamia nuts) with the remaining nuts\n(brazil and cashew nuts) excluded as this child is reported to\nbe a “fussy eater” by parents. The reasons for the 24 families who completely eliminated\nthe challenge nuts from the child’s diet, in spite of a negative\nOFC, are depicted in Fig. 1. The last child retained 3 of the 5 nuts included in their biscuit\nchallenge (almond, hazel, and macadamia nuts) with the re-\nmaining nuts (brazil and walnut) excluded based on taste. Review of Fig. Fig. 2 SPT prior to OFC Discussion 1 shows 3 children being scared to continue\neating the challenge nuts; 4 children being diagnosed with\nanother nut allergy that was not included in the OFC so the\nfamily choose to avoid all nuts; 1 child being busy with final\nyear of high school; and another child having general poor\nhealth. Average number of tree nuts in challenges was four. Macadamia was the most frequently included tree nut in the\nOFC. Table 2 is a representation of the tree nuts included in\nthe biscuit and tree nuts eliminated or maintained in the diet\nfollowing OFC. Just as macadamia, almond, and Brazil nuts\nwere most likely to be maintained in the diet, they also had\nhigh rates of elimination from diet which may be a reflection\nof the frequency these nuts were included in the OFC. More boys (90%) than girls (83%) had partially or success-\nfully introduced the nuts. Of those that continued to eat the\nnuts, all but 2 families reported there was no reactions to any\nof the nuts. One family reported that the child developed hives\nsecondary to hazel nut exposure. This child had OFC per-\nformed which included almond, hazel nut, Brazil nut,\nmacadamia, and pine nut with the following SPTs: Almond,\nBrazil nut, and macadamia are all negative SPT. Hazel nut\nSPT was 4 × 4 mm. Pine nut SPT was 3 × 3 mm. SPT ranged from negative to 7 × 5 mm prior to the test. SPT was done for all nuts included in the biscuit. Figure 2 is a\nrepresentation of the SPT performed prior to the challenge. Previous reaction to tree nuts included in the biscuit range\nfrom none (sensitized only with no previous exposure) to ob-\njective symptoms as well as nonobjective symptoms. Fig. 2 SPT prior to OFC Fig. 2 SPT prior to OFC 2211 SN Compr. Clin. Med. Discussion (2020) 2:2208–2213 Table 3\nSymptoms to nuts included in biscuits prior to OFC, SPT on day, and outcome on follow-up\nPatients (age and gender)\nSymptoms to nuts in biscuits\nprior to OFC\nNuts included in biscuits\nSPT to nuts on the\nday of OFC\nOutcome on follow-up\nMale\n8 years 6 months\nUpper respiratory symptoms\nAlmond, pine nut, macadamia\nNegative to all\nAll nuts maintained in diet\nMale\n2 years 10 months\nGeneralized rash\nAlmond, Brazil nut, cashew\nNegative to all\nAll nuts maintained in diet\nFemale 12 years 1 month\nThroat tightness\nAlmond, hazel nut, Brazil nut,\ncashew, macadamia\nNegative to all\nNone of the nuts maintained\nin diet, no reason given\nFemale 13 years 6 months\nUrticaria to products labeled\nmay contain traces\nAlmond, Brazil nut, walnut,\nMacadamia\nAlmond (3 × 4 mm)\nBrazil nut (2 × 4 mm)\nwalnut negative\nMacadamia(3 × 3 mm)\nAll nuts maintained in diet\nFemale 3 years 2 months\nFacial rash, itchy tongue\nAlmond, Brazil nut, cashew,\nwalnut, macadamia\nNegative to all\nAll nuts maintained in diet\nMale\n13 years 10 months\nFacial erythema to pine nuts\nBrazil nut, pine nut, macadamia\nBrazil nut 4 × 5 mm\nMacadamia 2 × 3 mm\nPine nut negative\nAll nuts maintained in diet 3\nSymptoms to nuts included in biscuits prior to OFC, SPT on day, and outcome on follow-up Of all the 139 who had negative OFC, 6 describe symp-\ntoms to the challenge nuts prior to the challenge. Characteristics of this group are reflected in Table 3. Our study reveals that there is a high success rate of passing\nthe mixed tree nut OFC with the majority of families continu-\ning to eat the nuts. Recurrence of tree nut allergy following\nOFC has not been reported to date. The presence of asthma, eczema, allergic rhinitis, and other\nfood allergies was determined in out-patient clinic consulta-\ntion before the OFC. This information is detailed in Table 4. It will be interesting to follow up children that failed the\nintroduction of the challenge nuts to note if immunologic tol-\nerance is maintained. Most of the patients that passed the challenge had multiple\nfood allergies. There were 256 cases of documented single or\nmultiple food allergies. Conclusion There are some limitations to our study. It is a retrospective\nstudy which relied on the documentation of the treating physi-\ncian. We also note the majority of patients had negative or low\npositive SPT which is not representative of patients with true tree\nnut allergy. The families prepared the tree nut biscuit as per our\nguidelines though this is not standardized with all tested tree nuts. Our data show that open mixed tree nut OFC is useful in\nexcluding multiple tree nut allergies in children with low sus-\npicion of clinical allergy. Some families will require more\nsupport to maintain the challenge nuts in the child’s diet fol-\nlowing a negative OFC. Table 4\nPatient characteristics for successful, partially successful, and\nunsuccessful introduction of tree nuts\nSuccessful\nPartially successful\nUnsuccessful\nEczema\n25\n1\n7\nAsthma\n25\n0\n5\nAllergic rhinitis\n21\n1\n4\nOther tree nut allergy\n50\n3\n5\nPeanut allergy\n53\n3\n8\nOther food allergy\n111\n2\n21 Table 4\nPatient characteristics for successful, partially successful, and\nunsuccessful introduction of tree nuts Authors’ Contribution Authors 1, 2, and 3 contributed to the conception\nand design of the work and acquisition, analysis, and interpretation of\ndata and also contributed to drafting the work and revising it critically for\nimportant intellectual content as well as final approval of the version to be\npublished. All authors agree to be accountable for all aspects of the work\nin ensuring that questions related to the accuracy or integrity of any part of\nthe work are appropriately investigated and resolved. Discussion Of these 64 are allergic to peanuts, 58\nallergic to other tree nuts not included in the OFC, 47 allergic\nto egg, 18 allergic to cow’s milk, and 69 allergic to other foods\n(wheat, other legumes, sesame, sea food, and kiwi fruit). To further improve rates of introduction of the tree nuts\nfollowing negative OFC, we should encourage families to\nmaintain the nuts in the child’s diet. Contact between families\nand the Immunology Department should be streamlined to\nallow contemporaneous contact at the time of a possible reac-\ntion to the challenge nuts. Previous study by Van Der Valk et al. looked at introduc-\ntion of cashew nut following a negative OFC at 6 months with\na successful introduction rate of 43.3% [5]. Our study found a\ncombined total of successful and partial introduction rate of\n82% for all challenge nuts. Compliance with Ethical Standards Conflict of Interest\nThe authors declare that they have no conflict of\ninterest. 2212 SN Compr. Clin. Med. (2020) 2:2208–2213 patient records as well as patient charts and used in strictly anonymous\nform. Verbal consent was obtained from the parent prior to commencing\nthe phone interview. Ethical Approval\nData was obtained from electronic patient records as\nwell as patient charts and used in strictly anonymous form, according to\nthe code of conduct for medical research approved by the hospital’s\nMedical Ethical Committee (Child and Adolescent Health Service\nSafety and Quality Committee). patient records as well as patient charts and used in strictly anonymous\nform. Verbal consent was obtained from the parent prior to commencing\nthe phone interview. Appendix Informed Consent\nSigned consent for the challenge was obtained from\nthe parents prior to the challenge. In accordance with the hospital’s guide-\nlines for use of patient’s records, data was obtained from electronic Recipe for mixed tree nut biscuit. 1.\nDiagnosing and managing food allergy in children Holloway,\nEdward; Fox, Adam, Fitzsimons, Roisin. Practitioner; London Vol.\n255, Iss. 1741. 2213 SN Compr. Clin. Med. (2020) 2:2208–2213 Open Access This article is licensed under a Creative Commons\nAttribution 4.0 International License, which permits use, sharing, adap-\ntation, distribution and reproduction in any medium or format, as long as\nyou give appropriate credit to the original author(s) and the source, pro-\nvide a link to the Creative Commons licence, and indicate if changes were\nmade. The images or other third party material in this article are included\nin the article's Creative Commons licence, unless indicated otherwise in a\ncredit line to the material. If material is not included in the article's\nCreative Commons licence and your intended use is not permitted by\nstatutory regulation or exceeds the permitted use, you will need to obtain\npermission directly from the copyright holder. To view a copy of this\nlicence, visit http://creativecommons.org/licenses/by/4.0/. 2. Fleischer DM, Conover-Walker MK, Christie L, Burks AW, Wood\nRA. The natural progression of peanut allergy: resolution and the\npossibility of recurrence. J Allergy Clin Immunol St Louis. 2003;112(1):183–9. https://doi.org/10.1067/mai.2003.1517. 3. Australasian Society of Clinical Immunology and Allergy. Skin\nPrick Testing Working Party. Skin Prick testing for the diagnosis\nof allergic disease. Updated 2020. Available at https://\nwww.allergy.org.au/ASCIA_HP_SPT_Guide_2020 4. Thalayasingam M, Noble V, Franzmann A, O’Sullivan M. Outcome\nof mixed nut biscuit challenge in low risk patients who are on tree nut\nexclusion diet. Paediatr Allergy Immunol. 2015. https://doi.org/10. 1111/pai.12437. 5. van der Valk JPM, van Wijk RG, Dubois AEJ, de Groot H, de Jong\nNW. Failure of introduction of cashew nut after a negative oral food\nchallenge test in children. Paediatr Allergy Immunol. 2016. https://\ndoi.org/10.1111/PAI.12591. References Publisher’s Note\nSpringer Nature remains neutral with regard to juris-\ndictional claims in published maps and institutional affiliations."