Food allergy and tacrolimus.

Abstract

To the Editor: We congratulate Lacaille et al. for their interesting report of life-threatening food allergy in a child who had a severe allergic reaction to food while receiving tacrolimus (FK506) therapy after liver transplantation (1). In their report, they speculated that tacrolimus induces an imbalance between Th1 and Th2 leukocyte subsets, or in interferon-γ and interleukin-4 production, with a loss of control of the synthesis of immunoglobulin (Ig) E antibodies. We also have encountered two children with atopic backgrounds who displayed an allergic reaction to food after liver transplantation. Case 1 involved a 2.5-year-old girl who underwent living-related transplantation of a graft from her mother for ornithine transcarbamoylase deficiency (OTCD). She had atopic dermatitis before transplantation. The primary immunosuppressants used were tacrolimus and prednisolone. Two years and 5 months after transplantation (at the age of 5.9 years), edema appeared around her mouth and extended to the whole face while she was eating baked horse mackerel. Total levels of IgE were elevated (189.4 IU/ml; normal level for her age, <140 IU/ml) as were levels of specific IgE antibodies against horse mackerel, rainbow trout, cod, sea bass, and eel. The dose of tacrolimus was tapered after 6 months, while similar allergic reactions occurred three times. Fish meat was excluded from her diet, and there was no subsequent episode of allergic reaction. Case 2 involved a 3-year-old girl who underwent auxiliary partial orthotopic living-related transplantation of a graft from her father for OTCD (2,3). Her mother had asthma. The primary immunosuppressants used were tacrolimus and prednisolone. Doses of these were tapered 3 months after transplantation. While she was eating steamed cod, she vomited, and edema appeared around her mouth and extended to the whole face. The edema disappeared after treatment with high-dose steroids. Total levels of IgE were elevated (1046.2 IU/ml) as were levels of specific IgE antibodies against cod, tuna, salmon, mackerel, horse mackerel, sardine, herring, rainbow trout, sea bass, and flatfish. The dose of tacrolimus was tapered and prednisolone was discontinued after 12 months (at the age of 4 years), and similar allergic reactions occurred five times. Fish meat was excluded from her diet, and there was no subsequent episode of allergic reaction. We measured the plasma concentrations of interleukin-4 and interferon-γ in both children at two time points: before transplantation and at the time a high serum level of IgE was detected (case 1, 1450 IU/ml; case 2, 189.4 IU/ml) after the allergic reaction had occurred. The results showed modest increase in both cases (3-4 pg/ml compared with less than 2 pg/ml before transplant), with no significant change in interferon-γ. These changes in serum cytokines provide little insight into the single-cell response, and are not much help. In addition to the report by Lacaille et al., Kawamura et al. (4) encountered a patient, who experienced extremely high serum levels of IgE during immunosuppressive therapy with tacrolimus. They investigated IL-4 gene expression during tacrolimus therapy and found that levels of expression were low when the trough level of tacrolimus was high, and expression was reduced at higher serum levels of IgE and tacrolimus were higher. We cannot investigate the sources of interleukin-4 and IgE. Because both patients had an allergic background, the association of fish allergy with tacrolimus is uncertain. In Japan, the major (>90%) food allergens are eggs, milk, soybeans, rice, wheat, and buckwheat (5). Fish allergy is very rare. There are a few reports (1) of food allergy after transplantation with cyclosporin and tacrolimus immunosuppression. Further studies will be required to determine the relationship between food allergy and tacrolimus. Ayano Inui Haruki Komatsu Tomoo Fujisawa Hiroshi Matsumoto Yoshihiro Miyagawa Department of Pediatrics; National Defense Medical College; Saitama, Japan