Skip to main content

Two cases of transplant-acquired food allergy who developed resensitization after a negative oral food challenge

Abstract

Background

Cases of food allergy after hematopoietic stem cell and solid organ transplantation in previously nonallergic transplant recipients were reported as transplant-acquired food allergy (TAFA), but information about its long-term outcome is still limited. A phenomenon where patients reacquire food allergy by resuming daily consumption after a negative oral food challenge has not yet been reported.

Case presentation

We report two cases of TAFA after liver transplantation and cord blood transplantation. In each case, the threshold of daily consumption to cause allergic symptoms decreased when a negative oral food challenge was obtained.

Conclusions

Our cases show an importance of gastrointestinal tract as a route of food sensitization because thresholds that caused allergic reactions decreased during their resuming process. We need to be careful with possible resensitization once a negative substantial dose was confirmed.

Background

A common mechanism of food allergy (FA) is the breakdown of immunologic and clinical tolerance to an ingested food, but its detailed mechanism is still unclear [1]. Cases of FA after hematopoietic stem cell and solid organ transplantation in previously nonallergic transplant recipients were reported as transplant-acquired food allergy (TAFA) [2], but information about its long-term outcome is still limited [3,4,5,6]. A phenomenon where patients reacquire FA by resuming daily consumption after a negative oral food challenge (OFC) has not yet been reported. Because the mechanisms of TAFA may help understand general FA, unique cases of TAFA with long-term outcomes should be accumulated. Here, we report two cases of TAFA after liver transplantation and cord blood transplantation (CBT). In each case, the threshold of daily consumption to cause allergic symptoms decreased when a negative OFC was obtained.

Case presentation

Case 1

A 1-year-and-10-month-old boy who was diagnosed with Alagille syndrome received a live-donor liver transplant from his nonallergic father. His food allergy was diagnosed by immunoglobulin E (IgE) associated immediate symptoms related to food ingestion, such as vomiting with wheat, and vomiting and systemic urticaria with soybean (Table 1). No allergic history except for the food allergy had been reported at the transplantation. His transplantation was uneventful, and tacrolimus has been used as a preventive agent for rejection. Egg allergy, which is the most common food allergy in this age group in Japan, was suspected because he experienced allergic reactions to wheat and soybean; he also had sensitization to hen’s egg white (EW) (Table 1). As he had avoided to eat hen’s egg completely, initial consumption of EW was planned in our hospital when he was 2 years and 5 months old. Consequently, the OFC was negative with 15 g of boiled EW, and he was initiated on daily consumption of boiled EW by adding stepwise doses (1 g every 3 days). The consecutive daily consumption was unremarkable until he encountered systemic urticaria with 26 g of boiled EW about 1 month after the negative OFC. His systemic urticaria was reproducible with lower doses of boiled EW for a few days without contamination of wheat and soybean, and respiratory symptoms including wheezing from consuming 9 g of boiled EW finally gave him up to continue eating. High titers of EW-specific IgE were accompanied by allergic reactions, and the titers gradually decreased with the complete elimination of hen’s egg consumption (Table 1). Regarding wheat and soybean, daily consumption without any concern has been accomplished in his natural course of food allergy.

Table 1 Series of food-specific IgE in Case 1

Case 2

A 51-year-old male without any history of allergic disease was diagnosed with anaplastic large cell lymphoma (ALCL), and he received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy as an induction regimen. Although salvage-intensive treatment, including a CBT, was required for CHOP-refractory ALCL, the CBT had achieved a complete response. Unfortunately, despite the prophylactic use of tacrolimus, grade 3 intestinal graft-versus-host disease (GVHD) characterized by vomiting and watery diarrhea (> 1500 mL per day) was diagnosed based on histological GVHD findings 2 months after. Refractory diarrhea forced him to consume ingredient nutrition with small amounts of snacks. GVHD therapy using systemic steroids and mesenchymal stem cell therapy was effective.

Six months after the CBT, he was finally allowed to consume solid food. On the next day, he unexpectedly experienced fever, frequent vomiting, diarrhea, and refractory hypotension with unknown mechanism that required continuous noradrenaline injection. Many kinds of food antigen could be contaminated in the solid foods because no attention had been paid for his possible food allergy. But Baumkuchen, that is a desert containing egg, milk, and wheat, and yogurt were critical to cause immediate severe hypotension in the episode. Blood examination revealed that he was sensitized to multiple antigens (Table 2), including hen’s egg, milk, and wheat. After the diagnosis of FA, he never experienced allergic reactions by avoiding these diets. OFC was conducted after 1 year and 9 months of the CBT, and his negative allergic status was proven through the boiled egg challenge with one whole egg. Daily consumption of one whole egg was started without any allergic symptoms, but it finally caused vomiting and watery diarrhea on the seventh day. The symptoms were reproducible with the next boiled egg challenge with one whole egg after 1 week of the first episode, and resensitization to EW supported his allergic reaction to it (Table 2). Although specific IgE assays (i.e., MAST and CAP assay) were used for the assessment, because MAST assay is useful for screening and CAP assay is quantitative for management of diagnosed food allergy, his sensitization was obvious in the same assay [8]. Limited information related to food allergy of the donor was available in a CBT setting.

Table 2 Series of food-specific IgE in Case 2

Discussion and conclusions

Although these cases had different backgrounds in terms of age and type of organ or hematopoietic transplantation, both gave up consuming an allergen, which was proven to be negative in the OFC. In Case 1, a gradual decrease in thresholds that caused allergic reactions was observed within a month of resuming hen’s egg intake. This might not be a case of TAFA because he never consumed it when the liver transplant was done. Further discussion is needed to diagnose TAFA for such cases. Ovomucoid-specific IgE was reported as a useful marker of symptomatic egg allergy [7]. Although pre transplant clinical response was unclear in this case, it might be a clinical related marker of TAFA because the enhancement was obvious with daily consumption of boiled egg. Case 2 was a rare case of TAFA after CBT, and only 16 cases were summarized in a recent case report [6]. TAFA is transient in most pediatric cases after CBT, but less is known in adult cases. We need to be careful with possible resensitization once a negative substantial dose was confirmed in an OFC.

Some mechanisms of TAFA are proposed in clinical and animal studies [2]. A passive transfer of donor immune cells is the most frequently proposed mechanism. Allergen-specific IgE, allergen-specific lymphocytes, liver-resident dendritic cells, and sinusoidal endothelial cells were reported as sources of immune cells. Other possible mechanisms are the action of tacrolimus [9] and immature gastrointestinal and immune system [10]. Tacrolimus promotes Th2 responses to induce IgE secretion from B cells and increases intestinal permeability [9]. Our cases of TAFA are surprising because they were sensitized by an ingested food for a relatively limited period. Although the mechanism of sensitization has been recently focused on epicutaneous route [11], these cases encouraged us to refocus on the role of the gastrointestinal tract.

We experienced two cases of TAFA. Because thresholds that caused allergic reactions decreased during their resuming process, the cases show an importance of gastrointestinal tract as a route of food sensitization. Unique cases should still be accumulated to clarify the detailed mechanism of TAFA; this might shed light on the origin of FA.

Availability of data and materials

Not applicable.

Abbreviations

ALCL:

Anaplastic large cell lymphoma

CAP:

Capsulated hydrophilic carrier polymer

CBT:

Cord blood transplantation

EW:

Egg white

FA:

Food allergy

GVHD:

Graft-versus-host disease

Ig:

Immunoglobulin

LC:

Lumi count

MAST:

Multiple antigen simultaneous test

OFC:

Oral food challenge

TAFA:

Transplant-acquired food allergy

References

  1. Sicherer SH, Sampson HA. Food allergy: a review and update on epidemiology, pathogenesis, diagnosis, prevention, and management. J Allergy Clin Immunol. 2018;141:41–58.

    Article  CAS  PubMed  Google Scholar 

  2. Hosakoppal SS, Bryce PJ. Transplant-acquired food allergy: current perspectives. J Asthma Allergy. 2017;10:307–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Legendre C, Caillat-Zucman S, Samuel D, Morelon S, Bismuth H, Bach JF, et al. Transfer of symptomatic peanut allergy to the recipient of a combined liver-and-kidney transplant. N Engl J Med. 1997;337:822–4.

    Article  CAS  PubMed  Google Scholar 

  4. Frischmeyer-Guerrerio PA, Wisniewski J, Wood RA, Nowak-Wegrzyn A. Manifestations and long-term outcome of food allergy in children after solid organ transplantation. J Allergy Clin Immunol. 2008;122:1031-3.e1.

    Article  PubMed  Google Scholar 

  5. Mavroudi A, Xinias I, Deligiannidis A, Parapanissiou E, Imvrios G. Long term outcome of acquired food allergy in pediatric liver recipients: a single center experience. Pediatr Rep. 2011;4:6.

    Article  Google Scholar 

  6. Kawahara A, Nakanishi T, Goto M, Akao K, Katsuragi T, Tsukada J. Post-transplant food anaphylaxis in an adult cord blood transplant recipient (Ms. No. IJHM-D-20–01037R1). Int J Hematol. 2021;114:292–6.

    Article  PubMed  Google Scholar 

  7. Ando H, Moverare R, Kondo Y, Tsuge I, Tanaka A, Borres M, et al. Utility of ovomucoid-specific IgE concentrations in predicting symptomatic egg allergy. J Allergy Clin Immunol. 2008;122:583–8.

    Article  CAS  PubMed  Google Scholar 

  8. Wolthers OD, Staberg M. The usefulness of the multiple allergen simultaneous test-chemiluminescent as compared to the Phadia Immunocap IgE test panel system in children and adolescents. Recent Pat Inflamm Allergy Drug Discov. 2013;7:96–9.

    Article  CAS  PubMed  Google Scholar 

  9. Wasuwanich P, Batsis I, Thawillarp S, Alford MK, Mogul D, Wood RA, et al. Post-transplant gastrointestinal disorders and lymphoproliferative disorder in pediatric liver transplant recipients on tacrolimus. Transpl Immunol. 2021;68:101438.

    Article  CAS  PubMed  Google Scholar 

  10. Prescott SL, Macaubas C, Holt BJ, Smallacombe TB, Loh R, Sly PD, et al. Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile. J Immunol. 1998;160:4730–7.

    Article  CAS  PubMed  Google Scholar 

  11. Brough HA, Nadeau KC, Sindher SB, Alkotob SS, Chan S, Bahnson HT, et al. Epicutaneous sensitization in the development of food allergy: what is the evidence and how can this be prevented? Allergy. 2020;75:2185–205.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

No funding.

Author information

Authors and Affiliations

Authors

Contributions

AN and TN constructed the idea for the manuscript. TN, KO, TS, and SK take responsibility for patient follow-up. AN, TN, KO, TS, SK, SI, and SS contributed to the interpretation of the data. SK, SI, and SS critically reviewed the manuscript. SI and SS provided final approval for manuscript publication. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Takayasu Nomura.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the parents of case 1 and the patient of case 2 for the publication of this case report.

Competing interests

The authors have no competing interests to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nakaoka, A., Nomura, T., Ozeki, K. et al. Two cases of transplant-acquired food allergy who developed resensitization after a negative oral food challenge. Allergy Asthma Clin Immunol 19, 24 (2023). https://doi.org/10.1186/s13223-023-00784-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13223-023-00784-5

Keywords