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.     

New‐onset post‐transplantation food allergy in children – Is it attributable only to the immunosuppressive protocol?

Abstract:  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.     

Anemia in children after transplantation: etiology and the effect of immunosuppressive therapy on erythropoiesis

Anemia in children after renal transplantation is more common than previously appreciated. Multiple factors appear to play roles in the development of post-transplant anemia, the most common of which is absolute and/or functional iron deficiency anemia. Most experts recommend that iron limited anemias in transplant patients should be diagnosed using the same criteria as for chronic renal failure patients. Serum erythropoietin (EPO) levels are expected to normalize after a successful renal transplantation with a normal kidney function, yet both EPO deficiency and resistance have been reported. While no large controlled trials comparing the effect of different immunosuppressive agents on erythropoiesis after transplantation have been performed, generalized bone marrow suppression attributable to azathioprine (AZA), mycophenolate mofetil (MMF), tacrolimus, antithymocyte preparations has been reported. Pure red cell aplasia (PRCA) occurs rarely after transplantation and is characterized by the selective suppression of erythroid cells in the bone marrow. PRCA has been reported with the use of AZA, MMF, tacrolimus, angiotensin converting enzyme inhibitors (ACEI), but not with cyclosporine (CSA) use. Post-transplant hemolytic uremic syndrome has been reported with orthoclone anti T-cell antibody (OKT3), CSA and tacrolimus therapy. Viral infections including cytomegalovirus, Epstein-Barr virus and human parvovirus B19 have been reported to cause generalized marrow suppression. Management of severe anemia associated with immunosuppressive drugs generally requires lowering the dose, drug substitution or, when possible, discontinuation of the drug. Because this topic has been incompletely studied, our recommendation as to the best immunosuppressive protocol after renal transplantation remains largely dependent on the clinical response of the individual patient.     

Relation between biomarkers and clinical severity in patients with Smith–Lemli–Opitz syndrome

Smith–Lemli–Opitz syndrome (SLOS), a multiple congenital anomaly with severe mental retardation, is caused by decreased activity of 7-dehydrocholesterol reductase. Fifteen Hungarian patients were diagnosed with SLOS on the basis of clinical symptoms, serum cholesterol, 7-dehydrocholesterol, and molecular genetic testing. Their age at the time of diagnosis in mild SLOS (n?=?4, clinical score <20) was 0.5–18 years, cholesterol was 2.37?±?0.8 mmol/L, and 7DHC was 0.38?±?0.14 mmol/L. In the group of typical SLOS (n?=?7, score 20–50), the diagnosis was set up earlier (age of 0.1–7 years); t-cholesterol was 1.47?±?0.7 mmol/L, and 7DHC was 0.53?±?0.20 mmol/L. Patients with severe SLOS (n?=?4, clinical score?>?50) died as newborns and had the lowest t-cholesterol (0.66?±?0.27 mmol/L), and 7DHC was 0.47?±?0.14 mmol/L. Correlation coefficient with clinical severity was 0.74 for initial t-cholesterol and 0.669 for Cho/7DHC. Statistically significant difference was between the initial t-cholesterol of mild and severe SLOS (p?=?0.01), and between the Cho/7DHC ratios of groups (p?=?0.004). In severe SLOS, the percentage of α-lipoprotein was significantly lower than in typical (p?=?0.003) and mild SLOS (p?=?0.004). Although serum albumin, total bilirubin, and hemostasis parameters remained in the reference range during cholesterol supplementation (n?=?10) combined with statin therapy (n?=?9), increase of aspartate aminotransferase and alanine aminotransferase in 50 % of the patients probably refers to a reversible alteration of liver function; therefore, statin therapy was suspended. Conclusion: life expectancy is fundamentally determined by the initial t-cholesterol, but dehydrocholesterol and α-lipoprotein have prognostic value. Accumulation of hepatotoxic DHC may inhibit the synthesis of α-lipoproteins, decreasing the reverse cholesterol transport. During statin therapy, we suggest monitoring of lipid parameters and liver function.     

A prospective randomly controlled clinical trial on azithromycin therapy for induction treatment of children with nephrotic syndrome

A prospective study was designed to evaluate the efficacy of azithromycin (AZM) when combined with prednisone therapy compared with prednisone therapy alone in children with primary nephrotic syndrome (PNS) undergoing induction treatment. A prospective randomly controlled clinical trial was conducted. Randomization was performed to select the research subjects who were composed of children with PNS and treated with AZM combined with prednisone (the intervention group) and with prednisone alone (the control group). A total of 211 randomly selected patients with PNS received either AZM combined with prednisone (n?=?106) or prednisone alone (n?=?105) for 6 months. At three months in the follow‐up period, 12 patients were lost to follow up (intervention group, 7; control group, 5), and 6 patients had a transient hypocomplementemia (intervention group, 4 ; control group, 2). AZM was administered at a dose of 10 mg/kg q.d (1 dose per day) for three consecutive days. The median duration before remission was 6 days in the intervention group and 9 days in the control group (p?<?0.0001). Relapse rate differed among the groups at 3 months (11.6 vs. 21.4 %, p?=?0.049). No difference in relapse rate was observed between the two groups within 4 to 6 months and at 6 months (p?=?0.168, 0.052). After 4 weeks of treatment, steroid resistance occurred in 1 out of 95 (1.05 %) patients in the intervention group and in 10 out of 98 (10.2 %) patients in the control group (p?=?0.006). After 8 weeks of treatment, no difference was found in steroid resistance between two groups (1/95 vs. 3/98, p?=?0.327). During follow-up at 6 months, no difference was exhibited by the two groups on frequent relapse rates (p?=?0.134). Conclusion: If a course of AZM is added to the glucocorticoid-induced treatment among children with PNS, then the sensitivity of prednisone increases. This increase consequently reduces duration to remission and decreases relapse. However, further studies are necessary to confirm these results.     

An assessment of iron overload in children treated for cancer and nonmalignant hematologic disorders

Our goal was to assess the natural fate of iron overload (IO) following transfusions of packed red blood cells (PRBCs) in children treated for cancer and nonmalignant disorders according to the intensity level of their treatment. Sixty-six children were followed up from February 2010 to March 2013. The transfusion burden was compared between three treatment intensity groups assigned according to the Intensity of Treatment Rating Scale 3.0 (ITR-3). IO was assessed by serial measurements of serum ferritin (SF) (n?=?66) and quantification of tissue iron by magnetic resonance imaging (MRI) (n?=?12). Of the children studied, 36 % (24/66) received moderately intensive treatment (level 2), 21 % (14/66) received very intensive treatment (level 3), and 42 % (28/66) received the most intensive treatment (level 4). The number of PRBC (p?=?0.016), the total transfused volume (p?=?0.026), and transfused volume adjusted to body weight (p?=?0.004) were significantly higher in the level 4 group. By the median follow-up time of 35.5 months (range 8–133), 21–29 % of patients (including level 2 and level 3 children) had SF >1,000 μg/l 1 year after cessation of transfusions. The slowest decrease of SF was observed in the level 4 group. Initial MRI examination demonstrated either mild or moderate IO in the liver and spleen. Repetitive MRI showed significant improvement in relaxation time between the initial and follow-up MRI performances in the liver (5.9 vs. 8.6 ms, p?=?0.03) and the spleen (4.3 vs. 8.8 ms, p?=?0.03). Conclusion: IO diminished over time, but in the level 4 patients, it was detectable for years after cessation of transfusions.     

Epidemiology and outcomes of children with renal failure in the pediatric ward of a tertiary hospital in Cameroon

Background

Pediatric nephrology is challenging in developing countries and data on the burden of kidney disease in children is difficult to estimate due to absence of renal registries. We aimed to describe the epidemiology and outcomes of children with renal failure in Cameroon.

Methods

We retrospectively reviewed 103 medical records of children from 0 to 17 years with renal failure admitted in the Pediatric ward of the Douala General Hospital from 2004 to 2013. Renal failure referred to either acute kidney injury (AKI) or Stage 3–5 chronic kidney disease (CKD). AKI was defined and graded using either the modified RIFLE criteria or the Pediatrics RIFLE criteria, while CKD was graded using the KDIGO criteria. Outcomes of interest were need and access to dialysis and in-hospital mortality. For patients with AKI renal recovery was evaluated at 3 months.

Results

Median age was 84 months (1QR:15–144) with 62.1% males. Frequent clinical symptoms were asthenia, anorexia, 68.8% of participants had anuria. AKI accounted for 84.5% (n?=?87) and CKD for 15.5% (n?=?16). Chronic glomerulonephritis (9/16) and urologic malformations (7/16) were the causes of CKD and 81.3% were at stage 5. In the AKI subgroup, 86.2% were in stage F, with acute tubular necrosis (n?=?50) and pre-renal AKI (n?=?31) being the most frequent mechanisms. Sepsis, severe malaria, hypovolemia and herbal concoction were the main etiologies. Eight of 14 (57%) patients with CKD, and 27 of 40 (67.5%) with AKI who required dialysis, accessed it. In-hospital mortality was 50.7% for AKI and 50% for CKD. Of the 25 patients in the AKI group with available data at 3 months, renal recovery was complete in 22, partial in one and 2 were dialysis dependent. Factors associated to mortality were young age (p?=?0.001), presence of a coma (p?=?0.021), use of herbal concoction (p?=?0.024) and acute pulmonary edema (p?=?0.011).

Conclusion

Renal failure is severe and carries a high mortality in hospitalized children in Cameroon. Limited access to dialysis and lack of specialized paediatric nephrology services may explain this dismal picture.

     

Tacrolimus-associated eosinophilic gastroenterocolitis in pediatric liver transplant recipients: role of potential food allergies in pathogenesis

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.     

儿童肾移植临床免疫抑制用药探讨

目的　探讨儿童肾移植免疫抑制治疗特点。方法　回顾性分析 31例儿童肾移植患者(男 18例,女 13例)的临床资料。根据起始免疫抑制方案不同,分为 3组:A组(环孢素A+硫唑嘌呤+泼尼松)7例;B组(环孢素A+霉酚酸酯 +泼尼松)17例;C组 (他克莫司 +霉酚酸酯 +泼尼松)7例。统计 3组免疫抑制药物调整及维持剂量、移植肾功能变化和术后并发症。结果　1年人 /肾存活率为100% /96.8%,3年人 /肾生存率为94.4% /88.9%。三组各观察点肌酐实测值差异无显著性意义 (P<0.05)。他克莫司组药物副作用小且能保持良好的肾功能。泼尼松调整幅度大、维持量小,与其他组差异有显著性意义(P<0.01)。结论　肾移植是儿童终末期肾病的有效治疗措施。遵循儿童个体差异的免疫抑制治疗是移植后预防排斥的重点。他克莫司、霉酚酸酯、泼尼松三联抗排斥治疗是儿童肾移植理想的免疫抑制治疗方案。     

Tacrolimus immunosuppression - an association with asymptomatic eosinophilia and elevated total and specific IgE levels

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.     

Superior Mesenteric Arterial Flow Pattern is Associated with Major Adverse Events in Adults with Fontan Circulation

Factors contributing to the failure of Fontan circulation in adults are poorly understood. Reduced superior mesenteric arterial (SMA) flow has been identified in pediatric Fontan patients with protein-losing enteropathy. SMA flow has not been profiled in an adult Fontan population and its association with adverse events is unknown. We aimed to examine associations between SMA flow patterns and adverse events in adult Fontan patients. We performed a retrospective review of adult Fontan patients who underwent echocardiograms between 2008 and 2014. SMA Doppler data included peak systolic and end-diastolic velocity and velocity time integral (VTI). Systolic/diastolic (S/D) ratio and resistive index were calculated. The relationship between SMA flow parameters and major adverse events (death or transplantation) was examined using proportional hazard Cox regression analyses. Kaplan–Meyer analysis was conducted to construct survival curve of patients with and without adverse events. 91 post-Fontan adult patients (76 % systemic left ventricle, 20 % atriopulmonary Fontan, mean age 27.9 years) were analyzed. Adverse events occurred in nine patients (death = 4, transplant = 5). When compared with the non-event group, the event group had increased end-diastolic velocity [hazard ratio (HR) 1.5, 95 % confidence interval (CI) 1.1–1.8; p = 0.002], increased systolic VTI (HR 1.5, 95 % CI 1.1–2.2, p = 0.02), increased diastolic VTI (HR 1.7, 95 % CI 1.2–2.4, p = 0.004), decreased S/D velocity ratio (HR 0.32, 95 % CI 0.14–0.71, p = 0.006), decreased S/D VTI ratio (HR 0.76, 95 % CI 0.61–0.97, p = 0.02), and decreased resistive index (HR 0.29, 95 % CI 0.14–0.60, p = 0.0007). Increased end-diastolic velocity and VTI in mesenteric arterial flow, with lower systolic/diastolic ratio and resistive index, were associated with death and need for heart transplant in adult Fontan patients. The mesenteric hyperemic flow was also associated with clinical signs of portal venous outflow obstruction, suggesting the presence of vasodilatory state in end-stage adult Fontan circulation.     

Bronchopulmonary dysplasia and neurodevelopmental outcome in extremely preterm neonates

We tested the hypothesis that the use of supplemental oxygen (sO₂) at discharge from the NICU in extremely preterm neonates is associated with a greater risk of neurodevelopmental impairment (NDI) at 18 months corrected gestational age (CGA) than the risk of NDI of those neonates discharged in room air. Four hundred twenty-four charts were retrospectively reviewed from infants born at <27 weeks and transferred to Nationwide Children’s Hospital from December 1, 2004 to June 14, 2010. Use of sO₂ was evaluated on day of life (dol) 28, at 36 weeks post-menstrual age (PMA), and at discharge. Logistic regression was used to identify postnatal risk factors associated with sO₂ at discharge and NDI. At dol 28, 96 % of surviving patients received sO₂, and therefore had bronchopulmonary dysplasia (BPD) by definition from a National Institutes of Child Health and Human Development workshop. At 36 weeks PMA, 89 % continued on sO₂ (moderate/severe BPD), and at discharge, 74 % continued on sO₂. When factors associated with NDI were examined, the need for mechanical ventilation ≥28 days (adjOR?=?3.21, p?=?0.01), grade III–IV intraventricular hemorrhage (IVH) (adjOR?=?4.61, p?<?0.01), and discharge at >43 weeks PMA (adjOR?=?2.12, p?=?0.04) were the strongest predictors of NDI at 18 months CGA. There was no difference in Bayley Scales of Infant Development, third edition composite scores between patients with no/mild BPD and patients with moderate/severe BPD (cognitive p?=?0.60, communication p?=?0.53, motor p?=?0.19) or those scores between patients on and off oxygen at discharge (cognitive p?=?0.58, communication p?=?0.70, motor p?=?0.62). Conclusions: The need for sO₂ at discharge is not associated with an increased risk of NDI in these patients. The strongest predictors of poor neurodevelopmental outcome in this population were prolonged positive pressure support, grade III–IV IVH, and discharge at >43 weeks PMA.     

Anorexia nervosa in a pediatric renal transplant recipient and its reversal with cyclosporine

We report a 16‐yr‐old female who developed AN within a month after renal transplantation and its resolution after switching from tacrolimus to cyclosporine. Her initial maintenance immunosuppressive regimen after renal transplantation consisted of tacrolimus, mycophenolate, and steroid. She had 7 kg weight loss within the first month of transplant with subsequent 10, 12, 17, and 19 kg loss after three, five, seven, and nine months of transplant, respectively. Besides weight loss and disturbances in body image, the patient developed alopecia, bradycardia, and persistent secondary amenorrhea. Upon switching to cyclosporine from tacrolimus nine months after transplant, she started regaining weight with 5 kg gain within two months and 10 kg after four months. She restarted her menstrual cycle, alopecia and bradycardia resolved, and her body image disturbance improved. Here, we describe a very unusual neuropsychiatric side effect of tacrolimus and its resolution with another calcineurin inhibitor, cyclosporine, in an adolescent renal transplant recipient.     

New-onset diabetes mellitus presenting with diabetic ketoacidosis after pediatric liver transplantation

Abstract:  The development of NODM is a common metabolic complication after liver transplantation. Presentation of post-liver transplant diabetes mellitus with DKA is rare especially among pediatric patients. We reported three pediatric patients who presented with DKA after liver transplantation. The underlying diseases leading to transplantation were cryptogenic liver cirrhosis, Wilson disease, and congenital hepatic fibrosis. None of the three patients had a history of diabetes prior to transplantation and all of them were cases of NODM after transplantation. All three patients presented with severe hyperglycemia, significant ketosis, and metabolic acidosis of variable severity. All of them received tacrolimus as one of the immunosuppressant agents. The patients received a liver transplant from a DD. The patients were treated with intravenous insulin injection (0.1 U/kg/h) and recovered from DKA, but one case expired in the intensive care unit because of bacterial sepsis after recovery from DKA. Our experience suggests that PTDM may result in ketoacidosis, and we emphasize the importance of paying more attention to glucose metabolism and risk of diabetes mellitus in patients with immunosuppressive therapy, especially tacrolimus.     

Does the pediatric end-stage liver disease score or hepatic artery resistance index predict outcome after liver transplantation for biliary atresia?

The pediatric end-stage liver disease score (PELD) was devised and validated as a tool for predicting mortality and morbidity in children with chronic liver disease waiting for a liver transplant (LT). It has become a useful guide for prioritizing organ allocation in the United States. The hepatic artery resistance index (HARI) also predicts waiting list mortality in children with biliary atresia. Does the PELD score or HARI predict outcome after LT for biliary atresia? Twenty consecutive children who underwent LT for biliary atresia between 2001 and 2005 were reviewed. Their PELD score was calculated periodically between listing and transplantation and HARI was measured at listing. Outcome variables were operative blood transfusion requirements, ICU stay and postoperative stay. Median age at LT was 8 (2–204) months. After allowing for the type of graft, the PELD score and the change in PELD score between listing and LT (ΔPELD) showed no significant correlation with blood transfusion requirements, but both the PELD score at listing and ΔPELD showed a trend toward a statistically significant positive correlation with overall hospital stay. Pre-transplant HARI showed a statistically significant positive correlation with the PELD score at listing (r = 0.46, p = 0.05) but did not correlate significantly with hospital stay. In this relatively small but homogeneous group of children undergoing LT for biliary atresia, PELD, and ΔPELD scores showed a trend toward a statistically significant positive correlation with overall hospital stay. However, neither PELD scores nor the pre-transplant HARI showed a definite correlation with outcome. Post-transplant complications are probably more important factors determining ICU and hospital stay in children currently transplanted for biliary atresia.     

Effect of Multisensory Stimulation on Neuromotor Development in Preterm Infants

Objective

To investigate the effect of Auditory, Tactile, Visual and Vestibular stimulus (ATVV) on neuromotor development in preterm infants.

Methods

Fifty preterm infants born at 28–36 wk with a birth weight ranging from 1,000–2,000 g were recruited for the study. They were block randomized into a control group (n?=?25) and study group (n?=?25). New Ballard score was used for the baseline measurement of neuromaturity in both groups. In neonatal intensive care unit (NICU), the study group received multisensory stimulation for 12 min per session, 5 sessions per wk along with routine NICU care either from 33 wk corrected gestational age for infants born at 28–32 wk or from 48 h of birth for infants born at 33–36 wk until discharge from the hospital. The control group received the routine NICU care. At term age the preterm infants were assessed using Infant Neurological International Battery (INFANIB) and the groups were compared using independent t test.

Results

The multisensory stimulated infants showed higher neuromotor score (p?=?0.001) compared to the control group. The french angle components of INFANIB including heel to ear (p?=?0.016) and popliteal angle (p?=?0.001) were statistically significant between the groups.

Conclusions

Multisensory stimulation appears to have a beneficial effect on the tonal maturation in preterm infants. However, further studies are warranted to investigate the long-term effects of multisensory stimulation on neurodevelopmental outcome in preterm infants.     

Impact of pediatric intestinal transplantation on intestinal failure in Japan: findings based on the Japanese intestinal transplant registry

Introduction

We assessed the impact of intestinal transplantation on Japanese pediatric patients with intestinal failure with data from the Japanese intestinal transplant registry.

Methods

Standardized forms were sent to all known intestinal transplantation programs, requesting information on transplants performed between 1996 and June 30, 2012. Patients younger than 18 years were analyzed. Patient and graft survival estimates were obtained using the Kaplan–Meier method.

Results

Of the 14 intestinal transplants, 4 were deceased and 10 were living donor transplants. The primary indications were: short gut syndrome (n = 7), intestinal functional disorder (n = 6), and re-transplantation (n = 1). The overall 1- and 5-year patient survival rates were 77 and 57 %, respectively. In transplants performed after 2006 (n = 6), the one-year patient survival rate was 83 %, and the 5-year survival rate was 83 %. Graft one- and 5-year survival rates were 83 and 83 %, respectively. The living-related transplant survival rate was 80 % at 1 year and 68 % at 2 years, compared to 67 and 67 % for cadaveric transplant recipients. There were no statistically significant differences in patient (p = 0.88) and graft (p = 0.76) survival rates between living donor and cadaveric transplant recipients. All current survivors discontinued PN.

Conclusion

Intestinal transplantation has become an effective therapy for patients with intestinal failure who cannot tolerate PN.     

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.     

An objective measure to identify pediatric liver transplant recipients at risk for late allograft rejection related to non-adherence

Non-adherence to a prescribed immunosuppressive regimen increases risk for late allograft rejection (LAR). We implemented a protocol for immunosuppression management which decreased variation in calcineurin inhibitor blood levels in pediatric liver transplant recipients by controlling for confounders such as physician practice variability. We hypothesized that patients with increased variation in tacrolimus blood levels despite implementation of the immunosuppression management protocol were at increased risk for LAR. We conducted a single center retrospective cohort study of 101 pediatric liver transplant recipients who were at least one year post liver transplantation and receiving tacrolimus for immunosuppression. The primary outcome variable was biopsy proven allograft rejection. Primary candidate predictor variables were the standard deviation (SD) of tacrolimus blood levels (a marker of drug level variability), mean tacrolimus blood level, age, and insurance type. SD of tacrolimus blood levels was determined for each patient from a minimum of four outpatient levels during the study period. Unadjusted and adjusted logistic regression models were used to determine the prognostic value of candidate predictors. The median and interquartile range of the SD of tacrolimus blood levels was 1.6 (1.1, 2.1). Eleven episodes of LAR occurred during the study period. Ten of the 11 episodes occurred in patients with tacrolimus blood level SD > 2. Insurance type, mean tacrolimus blood level and SD of tacrolimus blood levels were significantly related to LAR in the unadjusted analyses (p<0.05). A multivariable model including age, insurance type, mean and SD of tacrolimus blood levels was significantly associated with LAR (validated C-statistic = 0.88, p = 0.012). The adjusted odds of rejection for a one unit increase in the SD of tacrolimus blood level was 3.49 (95% CI 1.31 to 9.29). Effects of age and insurance status on LAR did not provide independent prognostic value after controlling for SD. Variation in tacrolimus blood levels is associated with an increased risk of LAR in pediatric liver transplant recipients. Despite standardized management of tacrolimus levels to control for confounders, some patients were found to have significant variability of tacrolimus blood levels. This may be due to non-adherence and amenable to targeted psychosocial and behavioral interventions to prevent LAR.     

Presentation of atopic disease in a large cohort of pediatric liver transplant recipients

Atopic disease occurs in solid organ transplant recipients with an increasingly recognized frequency. The time course for the development of these atopic diseases in liver transplantation has not been described. The objective was to characterize the atopic manifestations of children receiving chronic immunosuppression after orthotopic liver transplantation (OLT). Chart review and follow-up questionnaire were utilized for 176 OLT pediatric recipients at a single institution for manifestations of allergic disease. Atopic disease was present in 25 (14.2%) patients. Median age at transplant was 16 months with a median follow-up of 63 months. Food allergy and non-food related atopic symptoms presented at a median of 11.5 (IQR, 6-28) and 19 (IQR, 5-41) months post-transplantation, respectively. The median age at transplant of the non-atopic children was 72 months, higher than patients with atopy (p < 0.001). Food allergy and atopic skin disease symptoms were present in 40% and 56% of cases, respectively. Asthma, allergic rhinitis, or both were found in 66% of cases. The onset of symptoms of food allergy and eczema (median, 12 months post-transplantation) preceded symptoms of allergic rhinitis and asthma. (median of 27 and 30 months post-transplantation, respectively). Atopy occurs in ～14% of pediatric liver transplant recipients, with manifestations including food allergy, eczema, allergic rhinitis, and asthma.