tacrolimus and Food-Hypersensitivity

There are increasing reports of atopy/allergy following solid organ transplantation, especially paediatric liver transplantation (LT) with minimal New Zealand (NZ) data. We describe the prevalence of transplant-acquired atopy and allergy (TAA) in NZ paediatric liver transplant recipients, compared to paediatric kidney and adult liver transplants.. TAA focussed health questionnaires were sent to patients selected from the NZ transplant registry (transplanted between January 2003 and December 2017). Demographic and clinical data were also obtained from electronic health records and follow-up phone calls.. A total of 232 patients (62% male) participated (111 adult liver, 82 paediatric liver, 39 paediatric kidney transplant recipients). Tacrolimus was primary immunosuppression for all LT patients; with combined tacrolimus, mycophenolate and corticosteroids for kidney transplants. The number of patients who developed TAA was significantly higher (P < 0.001) in the paediatric LT group (36/82, 44%) compared to adult liver (12/111, 11%) and paediatric kidney transplants (4/39, 10%). Eczema was most common (73%), then IgE-mediated food allergy (FA, 33%), allergic rhinitis (19%) and asthma (17%). Six paediatric LT recipients developed eosinophilic oesophagitis (EoE). Egg was the most common allergen in the IgE-mediated FA group. TAAs were severe enough to warrant a switch from tacrolimus to another agent in seven paediatric LT patients. For paediatric LT patients, female gender and younger age at transplant were risk factors for developing TAA.. TAA is common in paediatric liver transplant recipients, with female gender and younger age at transplant being risk factors identified. This highlights the need for detailed atopic and allergy history to be incorporated in all pre-transplant assessments.

Topics: Adult; Child; Female; Food Hypersensitivity; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Male; Organ Transplantation; Tacrolimus

Allergy and other immune-mediated diseases are more frequently reported in children who have undergone liver transplantation. Furthermore, autoantibodies are also prevalent, suggesting a state of immune dysregulation in these patients. Whether or not these processes occur simultaneously in the same individual has not been studied previously.. A cohort of 43 children who had undergone liver transplantation for nonautoimmune liver disease at median age of 1.3 years was investigated for allergy and autoimmune disease. Sensitization to food and inhalant allergens was assessed, and autoantibodies were measured.. The prevalence of food allergy was 26% and that of respiratory allergy was 23%, whereas 33% and 26% of the subjects were sensitized to food and inhalant allergens, respectively. Autoimmune disease (ie, autoimmune hepatitis) occurred in a single individual (2%), whereas autoantibodies were present in 44% of the children. Food allergy and autoantibodies occurred concomitantly in 19% of the children, which was almost twice the frequency expected by chance (11%, P = 0.04). Respiratory allergy and the presence of autoantibodies were unrelated (12% concurrence versus the expected 10%, P = 0.73). In the logistic regression analysis, autoantibody formation was associated with discontinued immunosuppression and food allergy, with odds ratios of 13 (P = 0.01) and 7.1 (P = 0.03), respectively.. In contrast to respiratory allergy, food allergy and autoantibody formation occurred together in the same children who underwent liver transplantation at a frequency higher than would be expected by chance. This may reflect an underlying immune dysregulation that impairs immune tolerance to both food allergens and autoantigens.

Topics: Adolescent; Allergens; Autoantibodies; Autoantigens; Autoimmune Diseases; Biliary Atresia; Child; Child, Preschool; Cross-Sectional Studies; End Stage Liver Disease; Female; Follow-Up Studies; Food Hypersensitivity; Humans; Immunosuppression Therapy; Infant; Liver Transplantation; Male; Odds Ratio; Postoperative Complications; Prevalence; Tacrolimus

Topics: Bone Marrow Transplantation; Child; Child, Preschool; Female; Food Hypersensitivity; Humans; Immunosuppressive Agents; Male; Odds Ratio; Organ Transplantation; Prevalence; Retrospective Studies; Tacrolimus; Tertiary Care Centers

Topics: Age Factors; Child; Child, Preschool; Cyclosporine; Female; Follow-Up Studies; Food Hypersensitivity; Humans; Immunoglobulin E; Infant; Liver Failure; Liver Transplantation; Male; Prognosis; Sirolimus; Tacrolimus; Time Factors

Topics: Adolescent; Child; Child, Preschool; Cyclosporine; Female; Food Hypersensitivity; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Infant; Kidney Transplantation; Male; Retrospective Studies; Risk; Tacrolimus

Increasingly, food allergy associated with tacrolimus after pediatric living-donor liver transplantation (LT) has been reported. Tacrolimus prevents the activation of T cells by blocking calcineurin, thus producing an immunosuppressive effect, but tacrolimus induces an imbalance in T-helper type 1 (Th1) and Th2 cells in the food allergy process. This report describes a case of tacrolimus-associated food allergy after pediatric living-donor LT. The patient was a 7-year-old Japanese girl who had undergone living-donor LT at 12 months of age, and whom we first saw in the clinic at age 18 months. She received immunosuppressive therapy by tacrolimus after transplantation. Atopic dermatitis developed in post-transplant month 18. Stridor, facial edema, lip swelling, and skin erythema after consuming tempura udon containing wheat occurred in post-transplant month 39, and she was subsequently diagnosed with anaphylactic shock. Eosinophilic leukocyte and serum immunoglobulin (Ig)E increased, and specific IgE was positive for some food allergens. Pharmacotherapy was therefore changed from tacrolimus to cyclosporine A, after which eosinophilic leukocyte and serum IgE decreased and atopic dermatitis improved.

Topics: Cyclosporine; Enzyme Inhibitors; Female; Food Hypersensitivity; Graft Rejection; Humans; Immunosuppressive Agents; Infant; Liver Cirrhosis; Liver Transplantation; Tacrolimus

Topics: Adult; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cord Blood Stem Cell Transplantation; Cytarabine; Daunorubicin; Drug Therapy, Combination; Egg Hypersensitivity; Etoposide; Female; Food Hypersensitivity; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Humans; Idarubicin; Immunosuppressive Agents; Intestinal Diseases; Leukemia, Myeloid, Acute; Liver Diseases; Male; Middle Aged; Nut Hypersensitivity; Seafood; Tacrolimus; Transplantation Conditioning; Vidarabine

Post-TAFA is an uncommon but serious complication of organ transplantation. This study aimed to compare the incidence of FA in CsA and tacrolimus-treated children following OLT and identify risk factors. The medical charts of all patients who underwent OLT at our institution were reviewed. Between 1985 and 2010, 218 OLTs were performed on 188 pediatric recipients, of which 154 were included in the study. Three patients (3%) of the 102 receiving CsA developed FA, compared with nine (17%) in the 52 tacrolimus-treated patients, the latter exceeding general population reported FA prevalence (RR 5.88; 95% CI: 1.66-20.81). All TAFA cases underwent transplantation before the age of three with an incidence of 29% (9/31) in the tacrolimus-treated children in comparison with 7% (3/41) in the CsA group (RR 3.97; 95% CI: 1.17-13.45). Eosinophilia was present in 81% of children receiving tacrolimus compared with 54% in the CsA group (p = 0.002). We observed a statistically significant increase incidence of FA in tacrolimus-treated children following an OLT and those under the age of three are particularly vulnerable. The underlying process is still unknown and probably multifactorial.

Topics: Age Factors; Child; Child, Preschool; Cyclosporine; Eosinophilia; Female; Food Hypersensitivity; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Incidence; Infant; Liver Failure; Liver Transplantation; Male; Retrospective Studies; Risk Factors; Tacrolimus; Treatment Outcome

We conducted a study to clarify the incidence, clinical course, and risk factors of de novo allergies after liver transplantation. Ninety-three patients who had been followed longer than one yr and who had no previous allergy history were included. Forty-two patients (45.2%) developed de novo allergy. Of them, food allergy developed in 35 (37.6%). Respiratory allergy was observed in three (3.2%), and a patient (1.1%) had drug allergy. Fifty-two (55.9%) of the 93 patients developed eosinophilia. The median age of patients with de novo allergy was 15 months (IR 11.3-20 months). De novo allergy developed five months after liver transplantation (IR 2.3-9.5 months) and lasted for 16 months (IR 8-34.5 months). Younger age at liver transplantation displayed statistically significant differences in development of allergy between allergy and non-allergy groups. Twenty-nine (69.0%) patients improved from allergy during the follow-up period. No patient with de novo gastrointestinal allergy progressed to any respiratory allergy such as asthma. Older age at transplantation, EBV non-risk, and CMV non-risk had statistical significance in allergy improvement. Younger age at transplant predisposes to the development of allergy, while improvement of allergy is achieved more in older age.

Topics: Age Factors; Child, Preschool; Drug Hypersensitivity; Eosinophilia; Follow-Up Studies; Food Hypersensitivity; Humans; Hypersensitivity; Immunosuppressive Agents; Incidence; Infant; Liver Failure; Liver Transplantation; Proportional Hazards Models; Respiratory Hypersensitivity; Tacrolimus; Time Factors

Food allergy is increasingly reported after paediatric liver transplantation. The underlying physiopathological mechanism remains incompletely understood. Therefore, we aimed to determine the incidence, clinical presentation, possible risk factors, and prognosis of post-transplant food allergy in children currently followed after liver and renal transplantation. The study population consists of 49 liver and 21 renal transplant patients transplanted between the age of 22 months and 15 years. Data were collected retrospectively from medical records and via a doctor's questionnaire taken from the parents in a monocentric setting. Post-transplant food allergy has developed in 13 liver transplant patients and in none of the renal transplant recipients. Within the liver transplant group, median age at liver transplantation is significantly lower in the food-allergic (10 months) versus non-food-allergic group (3.3 years; p = 0.002). The use of tacrolimus as primary maintenance immunosuppression is associated with food allergy (p = 0.032) and mean donor age is significantly lower in the food-allergic group (p = 0.009). Compared to the renal transplant group, median age at transplantation is significantly lower in the liver patients (p < 0.001). No significant differences are found in primary immunosuppressive regimens between renal and liver transplant patients.. Post-transplant food allergy is an important clinical problem in children after liver transplantation which does not affect renal transplant patients despite similar immunosuppressive regimens. Within the group of liver transplant recipients, tacrolimus use, young age at time of transplant and younger donor age were associated with the development of food allergy.

Topics: Adolescent; Age Factors; Child; Child, Preschool; Female; Food Hypersensitivity; Humans; Immunosuppressive Agents; Incidence; Infant; Infant, Newborn; Kidney Transplantation; Liver Transplantation; Male; Regression Analysis; Retrospective Studies; Risk Factors; Tacrolimus

Topics: Adolescent; Drug Therapy, Combination; Female; Food Hypersensitivity; Humans; Immunoglobulin E; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid; Tacrolimus

Topics: Cord Blood Stem Cell Transplantation; Food Hypersensitivity; Graft vs Host Disease; Humans; Immunosuppressive Agents; Infant; Male; Tacrolimus; Vascular Diseases

Topics: Allergens; Child, Preschool; Cyclosporine; Food Hypersensitivity; Humans; Immunoglobulin E; Immunosuppression Therapy; Immunosuppressive Agents; Infant; Liver Transplantation; Nut Hypersensitivity; Skin Tests; Tacrolimus

Topics: Adrenal Cortex Hormones; Adult; Cyclosporine; Dermatitis, Allergic Contact; Dermatitis, Atopic; Dermatitis, Occupational; Dietary Proteins; Drug Resistance; Facial Dermatoses; Female; Food Hypersensitivity; Hand Dermatoses; Histamine Antagonists; Humans; Immunosuppressive Agents; Methotrexate; Patch Tests; Skin Tests; Tacrolimus

New-onset post-transplantation food allergy has been described mainly after liver transplantation, and its pathogenesis was attributed to the immunomodulatory effects of tacrolimus therapy. The aim of the present study was to evaluate the association of food allergy with solid organ transplantation in our center. The medical records of children who underwent kidney transplantation and children who underwent liver or liver and kidney transplantation from 1986 to 2005 were reviewed. A total of 189 children (124 after kidney transplantation, 65 after liver or liver and kidney transplantation) received tacrolimus as part of the immunosuppressive regimen. New-onset post-transplantation food allergy was documented in four of them: two with liver transplants and two with combined kidney and liver transplants. The absence of new-onset food allergy in the children with isolated kidney transplants is compatible with other reports in the literature. This study supports the concept that the functioning liver itself, and not only tacrolimus immunosuppression, is a main contributor to food allergy in this patient population.

Topics: Adolescent; Child; Child, Preschool; Female; Food Hypersensitivity; Humans; Immunosuppressive Agents; Infant; Kidney Transplantation; Liver; Liver Transplantation; Male; Postoperative Complications; Retrospective Studies; Tacrolimus

Angioedema and chronic diarrhea in patients taking immunosuppressants are not always because of side effects and could be a new onset of food allergy. Our aim is to discuss the pathogenesis and treatment of the post-transplant development of food allergies. The first patient was receiving tacrolimus subsequent to heart transplantation and developed angioedema after consumption of dairy products at 12 months after transplantation. He was found to be allergic to multiple foods by both RAST and ImmunoCAP tests. The second patient with argininosuccinic aciduria, post-liver transplant, also received tacrolimus and developed chronic non-mucoid/bloody diarrhea at seven months following transplantation. ImmunoCAP test was positive only for egg white and peanuts. Biopsy showed eosinophilic infiltration of the mucosa from the stomach to the rectum. Elimination diets in both patients resolved the symptoms. These cases suggest a direct relationship between tacrolimus and development of food allergy.

Topics: Angioedema; Child, Preschool; Food Hypersensitivity; Heart Transplantation; Humans; Immunoglobulin E; Immunosuppressive Agents; Liver Transplantation; Male; Skin Tests; Tacrolimus; Time Factors

We report three pediatric liver transplant recipients receiving tacrolimus immunosuppression presented with vomiting, heme-positive stools and failure to thrive, who had subtotal villous atrophy in their histology because of food protein sensitivity. Case findings and current literature of the casual relationship between tacrolimus and food allergies briefly reviewed.

Topics: Cadaver; Child; Child, Preschool; Duodenitis; Endoscopy; Female; Food Hypersensitivity; Humans; Immunosuppressive Agents; Infant; Liver Transplantation; Male; Tacrolimus; Treatment Outcome

Topics: Child; Food Hypersensitivity; Gastritis; Humans; Immunosuppressive Agents; Intestinal Mucosa; Liver Transplantation; T-Lymphocytes; Tacrolimus

De novo development of food allergy is an infrequent but potentially serious complication of transplantation. An increased prevalence of food allergy noted specifically in children receiving tacrolimus immunosuppression supports the hypothesis that selective suppression of Th1 lymphocytes by the IL-2 inhibitor immunosuppressants CsA, and the more potent drug, tacrolimus , promotes Th2 lymphocytes and an allergic immune response. This study was undertaken to characterize the IgE-mediated immune response, in CsA and tacrolimus-treated, post-OLT children. Thirty children and adolescents aged 1.9-21 yr, mean: 10.6 yr, (6.4 yr post-tx.) were studied. Immunosuppression-CsA: 10 patients, tacrolimus; 20 patients. Blood eosinophils, total IgE levels and specific IgE antibodies (Immulite 2000 Allergy; Diagnostic Products Corp., Los Angeles, CA, USA) to a panel of food and inhaled allergens were measured and correlated with clinical symptoms of allergy. Eosinophilia (>500/mm(3)) range: 599-3125, mean: 1294, was present in 10/20 of patients treated with tacrolimus and 1/10 treated with CsA. IgE levels were elevated in eight of these 10 tacrolimus-treated patients and in two CsA patients ; five were <3 yr of age and IgE levels ranged from 54 to 111 IU/mL (mean: 83), normal for age <45 IU/mL and five were > or =9 yr and IgE levels ranged from 134 to 1606 IU/mL (mean: 557), normal for age <87 IU/mL. Specific IgE levels to a wide panel of food allergens were positive in five tacrolimus-treated patients and to both food and inhaled allergens in three patients (two tacrolimus-treated, one CsA). Four children (tacrolimus-treated) had symptoms of food allergy . None had a family history of allergy. Eosinophilia is present in up to 50% of children and adolescents receiving tacrolimus immunosuppression. The majority of these patients also have elevated levels of total and specific (mainly to food allergens) IgE antibodies. Most patients are asymptomatic and do not manifest food allergy or asthma.

Topics: Adolescent; Adult; Child; Child, Preschool; Cyclosporine; Eosinophilia; Female; Food Hypersensitivity; Humans; Immunoglobulin E; Immunosuppressive Agents; Infant; Liver Function Tests; Liver Transplantation; Male; Tacrolimus

Tacrolimus is a macrolide agent that is now the primary immunosuppressant used in prevention of graft rejection in transplant recipients. It has been found to be superior to cyclosporine (CSA) for rescue therapy as well as for earlier weaning of steroids. Both tacrolimus and CSA share similar toxicity profiles; however, their gastrointestinal side effects have received little attention. We report three cases of eosinophilic colitis in liver transplant recipients, maintained on tacrolimus as immunosuppressive medication post-liver transplantation. These patients also had high serum immunoglobulin (Ig)E levels, eosinophilia and IgE-positive radioallergosorbent test for milk proteins. The colitis appeared to be mediated by food allergies. Each patient had symptomatic improvement following reduced immunosuppression and an appropriately restricted diet. We conclude that tacrolimus may play a role in the initiation of food allergies, leading to eosinophilic colitis. More studies are needed in a controlled setting to identify the prevalence of similar findings among other pediatric liver transplant recipients.

Topics: Child; Colitis; Eosinophilia; Food Hypersensitivity; Humans; Immunoglobulin E; Immunosuppressive Agents; Infant; Liver Transplantation; Male; Tacrolimus

Roughly one third of children with atopic dermatitis (AD) have IgE-mediated food allergy. Most parents and pediatricians assume foods also cause the eczema, a focus that diverts proper skin therapy and has negative outcomes including nutritional deficiency, costly referrals, and unnecessary testing. This project investigates the relationship between food allergy and AD, both before and after treatment in an established AD population. During an open trial of topical tacrolimus we observed a decrease in parental food allergy concern during good control of their child's eczema. We tested this observation by follow-up interviews and a questionnaire study to compare parental estimates of food allergy concerns after therapy with concerns before beginning the trial. Study subjects were children 11 years old and younger with AD and suspicion of food allergy. AD and food allergy parameters, pre- and post-treatment, were retrospectively assessed by a questionnaire given to the parents.. Twenty-three patients were enrolled: 16 had positive food allergy tests (7 RAST and/or 10 skin prick tests) and 30% had a definite history of immediate IgE reactions to foods. Ninety-five percent of parents felt that food allergy exacerbated their child's AD. Treatment durations were 3 to 45 months. Parental concern of food allergy decreased significantly from 7.7 to 4.0 on a 10 point scale (P < .001). Additionally, estimated food reactions decreased by approximately 80% during 1- and 6-month periods (P = .001).. In this selected university-based childhood AD population, nearly all parents were convinced their child had food allergy and further that the food contributed to the AD. The level of concern about food reactions was significantly decreased and the number of food reactions declined during effective topical therapy. This preliminary assessment of parental perceptions suggests that successful, stable therapy of AD reduces perceived food reactions and allays parental concerns about food allergy. Such therapy may encourage parents to refocus on direct skin care as the primary effort in AD therapy. We conclude that the effect of successful AD treatment on food allergy and food allergy concern are of interest and worthy of further study.

Topics: Child; Child, Preschool; Dermatitis, Atopic; Female; Food Hypersensitivity; Humans; Immunosuppressive Agents; Male; Retrospective Studies; Tacrolimus

Topics: Administration, Cutaneous; Child; Dermatitis, Atopic; Female; Food Hypersensitivity; Humans; Immunosuppressive Agents; Tacrolimus

Topical treatment with tacrolimus may be complicated by ingestion-related flushing caused by consuming small amounts of alcohol, a reaction that can be mistaken for food allergy.. To increase awareness of a drug interaction with alcohol that can mimic food allergy.. We describe 3 patients who used topical tacrolimus, 2 with an atopic history and 1 without, who presented with a flushing reaction after ingesting alcohol.. Cessation of topical tacrolimus use resolves the alcohol-related skin reaction.. A careful history, including consideration of alcohol use, should be obtained in patients who use topical tacrolimus and present with new skin complaints, because these factors may be evidence of an avoidable drug interaction and not worsening of atopic disease or a food allergy.

Topics: Adult; Dermatitis, Atopic; Ethanol; Exanthema; Female; Food Hypersensitivity; Humans; Immunosuppressive Agents; Male; Tacrolimus

Occurrences of allergic reactions induced by various foods have been reported in pediatric liver graft recipients receiving tacrolimus immunosuppression. We describe herein a female infant, who was admitted to our hospital with life-threatening angioedema because of banana hypersensitivity, 8 months after orthotopic liver transplantation. Food allergies should be screened in all tacrolimus-immunosuppressed pediatric liver recipients who show suggestive clinical symptoms. Banana must be added to allergen batteries during etiologic investigations. Cyclosporine represents an option for drug conversion to prevent organ rejection.

Topics: Biliary Atresia; Cyclosporine; Female; Food Hypersensitivity; Humans; Immunoglobulin E; Immunosuppressive Agents; Infant; Liver Transplantation; Musa; Tacrolimus; Tomography, X-Ray Computed; Trachea; Treatment Outcome

The authors report on their experience with food-induced angioedema in tacrolimus-immunosuppressed pediatric liver recipients.. Among 121 children treated with tacrolimus after liver transplantation, those who presented with angioedema are reported.. Twelve children (10%) experienced angioedema related to food allergy while on tacrolimus. Mean ages at transplantation and angioedema were 1.3 years and 3.75 years, respectively. Angioedema occurred within a mean of 28 months from onset of tacrolimus. Eleven children experienced two or more angioedema attacks without consequences. One child presented with anaphylactic shock that caused postischemic cerebral damage. Besides eviction of food allergens, eight children were switched from tacrolimus to cyclosporine, whereas tacrolimus dosage was decreased in four. Reintroduction of food allergens was successfully performed only in those who were switched to cyclosporine.. A causal relationship between tacrolimus and the occurrence of food-induced angioedema is suggested. The switch from tacrolimus to cyclosporine should be considered.

Topics: Angioedema; Child, Preschool; Female; Food Hypersensitivity; Humans; Immunosuppressive Agents; Infant; Liver Transplantation; Male; Tacrolimus

Topics: Food Hypersensitivity; Humans; Immunosuppressive Agents; Infant; Liver Transplantation; Tacrolimus

Topics: Angioedema; Child; Food Hypersensitivity; Humans; Immunosuppressive Agents; Liver Transplantation; Postoperative Complications; Tacrolimus

Cyclosporine A (CsA) and tacrolimus (Tac), both calcineurin inhibitors, have been used extensively for immunosuppressive therapy in pediatric liver transplant recipients. They share a similar mechanism of action, the inhibition of cytokine gene transcription primarily interleukin-2 (IL-2) in T lymphocytes. Despite the strong immunosuppressive property, there are several reports of food allergy in pediatric transplant recipients under Tac immunosuppression, but not CsA. In this paper we report on 3 of 50 pediatric liver transplant recipients diagnosed with food allergy and asthma while receiving systemic Tac/CsA immunosuppression and the discuss the role of calcineurin inhibitors in this situation.

Topics: Adolescent; Asthma; Child; Child, Preschool; Cyclosporine; Drug Therapy, Combination; Food Hypersensitivity; Humans; Immunosuppressive Agents; Liver Transplantation; Retrospective Studies; Tacrolimus

Topics: Adolescent; Child; Child, Preschool; Food Hypersensitivity; Humans; Immunosuppressive Agents; Organ Transplantation; Tacrolimus

Topics: Allergens; Animals; Child, Preschool; Female; Fishes; Food Hypersensitivity; Humans; Immunosuppressive Agents; Tacrolimus