Management of tacrolimus‐associated food allergy after liver transplantation

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.     

Increase in de novo food allergies after pediatric liver transplantation: Tacrolimus vs. cyclosporine immunosuppression

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.     

Fish and shellfish allergy in children: Review of a persistent food allergy

The increased consumption of fish and shellfish has resulted in more frequent reports of adverse reactions to seafood, emphasizing the need for more specific diagnosis and treatment of this condition and exploring reasons for the persistence of this allergy. This review discusses interesting and new findings in the area of fish and shellfish allergy. New allergens and important potential cross‐reacting allergens have been identified within the fish family and between shellfish, arachnids, and insects. The diagnostic approach may require prick to‐prick tests using crude extracts of both raw and cooked forms of seafood for screening seafood sensitization before a food challenge or where food challenge is not feasible. Allergen‐specific immunotherapy can be important; mutated less allergenic seafood proteins have been developed for this purpose. The persistence of allergy because of seafood proteins’ resistance after rigorous treatment like cooking and extreme pH is well documented. Additionally, IgE antibodies from individuals with persistent allergy may be directed against different epitopes than those in patients with transient allergy. For a topic as important as this one, new areas of technological developments will likely have a significant impact, to provide more accurate methods of diagnosing useful information to patients about the likely course of their seafood allergy over the course of their childhood and beyond.     

Long-term follow-up of portal hypertension after liver transplantation in children

Abstract:  We aimed to describe the long-term changes in the imaging and clinical features of PHALT in children. A retrospective review was undertaken of consecutive children undergoing their first liver transplant between 1993 and 2003. Details of clinical progress and ultrasound imaging were recorded at one-yr post-transplantation and at last follow-up. Data were extracted on 83 children (median age at transplant 1.7 yr, range one month to 17.5 yr, 44 girls) who underwent 89 transplants. Four of these children died at a mean 5.6 yr (range 3.8–6.9 yr) after transplantation. Of the survivors, follow-up at one yr (n = 83) and at last follow-up (n = 71, median 4.3 yr post-transplant) revealed imaging evidence of splenomegaly in 46% and 44%, ascites in 6% and 4%, and portal systemic collaterals in 12% and 14%, respectively. Gastrointestinal hemorrhage associated with portal hypertension had occurred in no children at one yr and in four (6%) at latest follow-up. Features of portal hypertension on ultrasound scan are common in children before liver transplantation. An important minority of children will suffer clinically significant complications of PHALT during long-term follow-up, caused by both vascular and parenchymal disease.     

Bronchiectasis in children after renal or liver transplantation: a report of five cases

More effective immunosuppressive treatment in children following organ transplantation has significantly improved the survival of the grafts. Therefore, quality of life, long-term prognosis and adverse drug reactions have become more important. One of the main complications of immunosuppressive drugs is infections of the respiratory tract, but irreversible damage to the airways has not been described after renal or liver transplantation. Five children following transplantation of kidney or liver were referred to the Paediatric Pulmonology department because of chronic respiratory complaints. Pulmonary function tests and HRCT scan were performed as routine patient care. Four children with a renal transplant and one with a liver transplant showed chronic bronchitis and moderate to severe airways obstruction. HRCT showed bronchiectasis in all of them. We speculate that the immunosuppressive treatment (in)directly contributes to irreversible airway damage. We recommend including follow-up of lung function in the post-transplantation protocol and considering bronchiectasis in case of respiratory symptoms, to try preventing further damage to the lung.     

Aspergillosis in children after liver transplantation: Single center experience

Aspergillus infection in immunocompromised patients is associated with high morbidity and mortality. We retrospectively reviewed cases of Aspergillosis (A), in a series of 277 children who received LTx between 1990 and 2006. All children were given antifungal prophylaxis after transplantation. Aspergillosis was identified in 10 cases (3.6%) and diagnosis was confirmed when clinical symptoms were associated with identification of Aspergillus sp. or detection of galactomannan antigen. Incidence of Aspergillosis considerably decreased from 6.9% to 0.6% when liposomal amphotericin B was introduced as prophylaxis in high-risk patients. Mean time since LTx to Aspergillosis was 14.5 days. Histologically, Aspergillosis was diagnosed in two cases. Galactomannan antigen was present in two recipients. Aspergillus infection occurs usually within first 30 days after transplantation as a result of a combination of several risk factors. Following risk factors were observed: multiple antibiotic therapy, prolonged intensive care unit stay, poor graft function, retransplantation, relaparotomies, co-infection. Amphotericin B was administered in all cases. Two patients (20%) died because of Aspergillosis Liposomal Amphotericin B prophylaxis in high-risk children decreases the incidence of Aspergillus infection. High index of suspicion and early diagnosis followed by intensive treatment with amphotericin B facilitates achieving mortality rate lower than presented in other reports.     

Myocardial function after autologous bone marrow transplantation in children: a prospective long-term study

Early cardiac complications after autologous bone marrow transplantation (ABMT) were recorded for 49 children with haematological malignancies. There was no procedure-related mortality and only two cases of early post-transplant cardiac complications of clinical relevance, both of which were reversible. For 35 long-time survivors (median follow-up 7 y) serial evaluations before and after ABMT included ECG, chest radiography, echocardiography and equilibrium radionuclide ventriculography (RVG). One patient had frequent supraventricular ectopic beats after ABMT, a finding not previously noted. The mean left ventricular diastolic diameter (LVDD) was 104% of expected before ABMT (95% confidence interval 99-110). During the first year post-transplant LVDD was about 110% of expected, but thereafter normalization occurred. The mean shortening fraction before ABMT was 31% (CI 29-34), compared with the mean value of 34% for healthy children in our laboratory, and it ranged between 29% and 33% during the follow-up period. Mean left ventricular ejection fraction determined by RVG was 65% (CI 61-69) and mean right ventricular ejection fraction was 46% (CI 43-49) before ABMT, and they did not change during follow-up. It is encouraging that these heavily pre-treated children could be autografted without serious cardiac complications or deterioration in myocardial performance in a 5-10-y prospect, but longer follow-up is needed for a final evaluation.     

Renal graft outcome after combined liver and kidney transplantation in children: UCLA and UNOS experience

de la Cerda F, Jimenez WA, Gjertson DW, Venick R, Tsai E, Ettenger R. Renal graft outcome after combined liver and kidney transplantation in children: UCLA and UNOS experience.
Pediatr Transplantation 2010: 14:459–464. © 2010 John Wiley & Sons A/S. Abstract: Although it has been described in adults that renal grafts in the context of CLKT have a lower number of AR episodes and improved renal allograft survival, this has never been examined in pediatrics. We performed a single center retrospective case–control study examining 10 patients aged 10 ± 6 yr with a CLKT that survived the post‐surgery period of six months, and compared outcomes to a group of 20 KO transplants matched for age, era, and immunosuppression. We observed a significant reduction in the incidence of AR episodes in the CLKT group. To evaluate whether or not this experience was reproducible nationally, we performed an analysis of the 1995–2005 UNOS database. As of March 2007, 111 CLKT and 3798 KO transplants were identified from the OPTN/UNOS data. There was a significant improvement in the late kidney graft survival at five yr post‐transplant in the CLKT group. These findings support the concept that liver transplantation is immunologically protective of the kidney allograft in CLKT.     

Food allergy in children suffering from atopic eczema

Whilst the association between eczema and food allergy is well established, the role of dietary manipulation in children with eczema remains controversial. These case histories highlight the differing outcomes that dietary manipulation may have in an infant with early onset, severe eczema and an older child with milder eczema. Management strategies and the evidence to support them are presented, followed by a review of clinical recommendations.     

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??Abdominal pain is a common symptom of food allergy. It may be the main symptom of some diseases of digestive system?? such as infant colic. It may be accompany symptom of some diseases?? such as eosinophilic gastroenteritis?? or it is a manifestation of systemic disease?? such as anaphylaxis. Oral tolerance development?? bacterial intestinal microflora?? intestinal barrier function?? transepithelial transport of food antigens?? eosinophil recruitment in the gastrointestinal tract?? and effect of food allergens on gastrointestinal motility are the contribution to pathophysiology of gastrointestinal food allergy.     

Development of multiple food allergies in children taking tacrolimus after heart and liver transplantation

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.     

Health‐related quality of life after combined liver and kidney transplantation in children

While reduced HRQOL following isolated organ transplantation has been previously reported, there are no data in the context of children following CLKT. Twenty‐three children who underwent CLKT at our institution were included in the study. The indication for CLKT was PH1 in 13 patients and ARPKD in 10 patients. Quantification of HRQOL was facilitated through the use of the PedsQL 4.0 Generic Core Scale. The results of the study were compared to healthy children and published data of children who had undergone LTx or KTx. The CLKT samples' child self‐report showed good HRQOL. No statistically significant difference was found between the patients with PH1 and patients with ARPKD (P=.4). Compared to healthy children, a significant difference in the total scale score, the physical health score, and the school functioning was reported. HRQOL did not differ significantly when compared to patients following isolated LTx or KTx. To improve HRQOL after CLKT, a focus on patients' physical health, educational performances, and overall quality of life is crucial. Thus, coordinated medical care across disciplines and psychological and social support is essential to achieve this goal.     

Adrenal insufficiency during physiological stress in children after kidney or liver transplantation

The aim of this study was to assess the prevalence and risk factors of AI in pediatric recipients of kidney or liver transplantation admitted because of a physiological stress episode and to identify patients that might be at risk of adrenal crises by clinical and laboratory parameters at admission. Adrenal function was prospectively evaluated by a standard (250 μg) adrenocorticotropin test in 48 recipients. Data on clinical and laboratory parameters were collected. AI was diagnosed in 11 patients: 10/32 (31.3%) children on long-term steroid treatment and 1/16 (6.25%) untreated. The only risk factor for AI was corticosteroids cumulative dose of >0.15 mg/kg/day during the last six months (p = 0.02, OR 6.67; 95% CI: 0.97-45.79). No correlation was found between clinical or laboratory signs of adrenal crisis on admission and the presence of AI. None of the patients with AI who did not receive stress dose (n = 8) developed adrenal crisis. AI is relatively common in children receiving prolonged corticosteroid treatment after kidney or liver transplantation. Clinical parameters on admission could not reliably identify patients with AI. Universal administration of a stress dose during physiological stress might not be required. However, at this point, the only method to identify patients that will benefit from a stress dose is through the ACTH test.     

Increase in de novo allergies after paediatric liver transplantation: the Brisbane experience

Noble C, Peake J, Lewindon PJ. Increase in de novo allergies after paediatric liver transplantation: The Brisbane experience.
Pediatr Transplantation 2011: 15: 451–454. © 2011 John Wiley & Sons A/S. Abstract: Pediatric liver transplantation is a successful procedure with 10‐yr survival rate of 70%; following transplantation, the emphasis on promoting good quality of life is important. The increasing prevalence of allergic disorders in the general population and an increase in food allergy following solid organ transplantation are described in patients, especially in children, but the contribution to morbidity post‐OLT has not been addressed. Objectives: Identifying the incidence de novo allergies post‐OLT performed by QLTS over 11 yr. Methods: Comprehensive medical record review of OLT recipients during study period. Results: From 1st July 1998 to 1st August 2009, 78 children received 85 cadaveric OLT; 60 children survived. Allergic disease was documented in 24/60 (40%) survivors. De novo food allergies were diagnosed in 12/60 (20%) ( Table 2 ), 9/12 occurred in children who were infants at time of transplant. Ten of 12 had severe allergies, six anaphylactic; 6/60 (10%) carry an EpiPen. Only 31/60 (51%) diagnosed are followed in Queensland, suggesting severe allergic disease in our cohort is an underestimate. Conclusion: Serious allergic disease post‐OLT is clinically important, especially in infants at time of transplant, and should be targeted for specialist allergist referral and risk management.

Table 2. Allergic diseases reported in pre‐ and post‐OLT

Long-term outcome after liver transplantation in children

Children (defined as under 18 yr of age) account for approximately 12.5% of all liver transplants in the United States. Even though the annual number of liver transplantation procedures remains relatively constant, the population of long-term survivors of liver transplantation has grown. Presently, the population of long-term survivors of liver transplantation is 10-fold greater then the number of transplantations carried out each year. For long-term survivors of liver transplantation, the goal is to maintain graft function and wellness while decreasing the morbidity associated with long-term immunosuppression. The primary diagnosis leading to liver transplantation in children do not recur in the allograft. Consequently, many of the complications of liver transplantation, both early and long term, relate to the need for immunosuppression. Children may be at increased risk to develop significant end-organ damage as a result of increased serum lipid levels, elevated blood pressure, altered glucose metabolism, decreased renal function, cancer, and diminished bone accretion that occur as a result of immunosuppressive therapy or complications of therapy. As survival rates have increased, health care providers have begun to assess health-related quality of life. We will review our current knowledge of long-term outcome following pediatric liver transplantation in children.     

Cognitive abilities,behaviour and quality of life in children after liver transplantation

Kaller T, Boeck A, Sander K, Richterich A, Burdelski M, Ganschow R, Schulz KH. Cognitive abilities, behaviour and quality of life in children after liver transplantation.
Pediatr Transplantation 2010: 14:496–503. © 2010 John Wiley & Sons A/S. Abstract: Aims: We investigated interrelations between cognitive abilities, behavioural problems, quality of life and disease‐related variables of children after LTX. Methods: Our sample consisted of 25 children. They were 8.5/2.8 (M/SD) years old and had received the transplant 5.5/3.1 years previously. For assessment we used well‐established instruments. Results: Liver transplanted children scored below the population mean on the cognitive as well as on the behavioural instrument and showed scores below average in the scales Self‐esteem, Friends and Total Score regarding QoL. Behavioural problems were associated with poorer cognitive performance (r=?0.38 to ?0.63). QoL regarding physical well‐being was correlated with sequential processing (r=0.41). Lower sequential processing scores were associated with lower QoL. Also between behavioural parameters and QoL correlations could be determined. Children with more behavioural problems experienced lower QoL (r=?0.40 to r=?0.76). Age at onset of disease showed correlations with behavioural and QoL parameters (r=?0.49 resp. r=0.44). Cognitive functioning was associated with medical complications (r=?0.44). Conclusions: High interrelations between cognitive functioning, behavioural deficits and QoL were obtained. Especially noticeable are correlations between sequential processing and internalized behavioural functions as both are associated with left lateralized brain functioning. This relationship could indicate differential effects on brain development during the preoperative phase.