Efficacy of a point-of-care test based on deamidated gliadin peptides for the detection of celiac disease in pediatric patients.

OBJECTIVE: The objective of the study was to assess the effectiveness of a point-of-care test (POCT) based on deamidated gliadin peptides (DGP) compared to the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) criteria diagnosis in the early detection of celiac disease (CD) in pediatric patients. METHODS: One hundred children (≤ 18 years) with suspected CD were selected, including siblings of celiac children that underwent gastroscopy for other gastrointestinal conditions. Patients with severe disease, following a gluten-free diet (GFD), with gastrointestinal bleeding, coagulopathy and infections in the last month were excluded. All children were evaluated with a POCT that detects immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies to DGP and total IgA. The POCT results were compared to CD diagnosis according to current ESPGHAN criteria. This involved the detection of IgA tissue transglutaminase (tTG) antibodies, the results of an intestinal biopsy and genetic testing. RESULTS: The prevalence of CD found in the present study was 48% (95% confidence interval in parenthesis 37.9-58.2%). The results of the POCT were concordant with the CD diagnosis made according to ESPGHAN criteria: 95.8% (85.7-99.4%) sensitivity, 98.1% (89.7-99.7%) specificity, 97.9% (88.7-99.6%) positive predictive value and 96.2% (87.0-99.4%) negative predictive value. Positive and negative likelihood ratios were 49.8 (7.2-347.5) and 0.04 (0.01-0.17), respectively. The POCT showed a 100% diagnostic accuracy in children younger than ten years of age. In total, three discordant results were found. CONCLUSION: Due to the high diagnostic accuracy in the pediatric population, the POCT can be considered as an effective tool for the early diagnosis of CD, especially in patients younger than ten years of age.

Post-transplant lymphoproliferative disorders and other malignancies after pediatric intestinal transplantation: incidence, clinical features and outcome.

PTLDs are a well-recognized and potentially fatal complication after intestinal transplantation. We analyzed the incidence, clinical features, and outcome in a 63 intestinal transplantation series performed in our unit between October 1999 and July 2011. Types of graft included ISB (n = 23), LSB (n = 20), and MV (n = 20). Patients were categorized into three groups of immunosuppression: I (n = 43) received basiliximab, tacrolimus, and steroids; II (n = 11) thymoglobulin and tacrolimus, and III (n = 9) alemtuzumab and tacrolimus. EBV status was serially assessed. All PTLD cases were biopsied to establish histopathological diagnosis. The incidence of PTLD was 14.2% (9/63). Median onset of PTLD after transplant was four months (range: 0.5-28), within first postoperative year in 6 (66.6%) patients. Fever was the most common symptom. Graft removal was needed in four patients (44%). The patient survival rate was 66.6% (6/9). We have not found any association between PTLD and immunosuppression regimen or transplant type. However, there was a statistical association with EBV active infection.

Autoimmune cytopaenia after paediatric intestinal transplantation: a case series.

Autoimmune cytopaenia is a rare, but severe complication after solid organ transplantation. We retrospectively analysed 57 paediatric intestinal transplants performed in 49 patients between 1999 and 2009. Autoimmune cytopaenia was observed in six patients; it appeared after an average of 10 months post-transplant. Warm autoimmune haemolytic anaemia was developed in three patients, cold autoimmune haemolytic anaemia in one and two presented a mixed type. Incidence and causes for haematological cytopaenia such as the following were investigated: immunosuppression, major blood mismatch, viral infection, malignancy, passenger lymphocyte syndrome and lymphoproliferative disorders. Initial treatment included high-dose steroids, intravenous immunoglobulin, plasmapheresis and maintenance of body temperature above 37°C in those with cold autoantibodies. Inclusion of the spleen in multivisceral transplants seems to be an important risk factor. All patients, except one, relapsed after classic therapy, requiring additional treatments. Sirolimus conversion was performed in four patients. One died after infection. The immunosuppressive therapies associated with other concomitant factors, such as viral infections, lymphoproliferative disorders, graft-versus-host disease, passenger lymphocyte syndrome and the inclusion of the spleen as part of multivisceral graft seem to play an important part in the development of autoimmune processes after intestinal transplantation. Therapy is not well established, especially in those resistant to first-line treatment.

The use of sirolimus as a rescue therapy in pediatric intestinal transplant recipients.

To review our experience with SRL as a second-line therapy in our series of 45 SBTx recipients (1997-2009). Retrospective review of five children converted to SRL: 3 M/2 F; median of three yr old (range 20 months-18 yr); rescue indications, adverse events with SRL, resolution of tacrolimus-related side effects, incidence of rejection, PTLD, or GVHD were summarized. Tacrolimus was discontinued (average 13 months after transplant) because of refractory hemolytic anemia in four patients with decreased renal function and because of advanced renal failure and unclear neutropenia in one. PTLD and GVHD had been previously diagnosed in two. Tacrolimus-related side effects disappeared in all five although other immunosuppressants and splenectomy were used simultaneously or later in most of them. Adverse events reported after the conversion were infections (tuberculosis and Pneumocystis carinii in two) and mild hypertriglyceridemia. No rejection, GVHD, or PTLD episode was observed. Four patients are alive with excellent quality of life (median follow-up 18 months). Sirolimus is a safe rescue therapy in SBTx children when tacrolimus is not well tolerated. Renal function and hematologic disorders seem to improve, although other simultaneous strategies could be also involved. Further studies could demonstrate its efficacy as a first-line treatment.

Graft-vs-host disease after small bowel transplantation in children.

PURPOSE: Graft-vs-host disease (GVHD) is a rare complication of transplantation of organs rich in immunocompetent cells. The goal of this study was to report the features of GVHD after small bowel transplantation (SBTx) in children. METHODS: The study involved a retrospective review of patients undergoing SBTx between 1999 and 2009 who had GVHD. RESULTS: Of 46 children receiving 52 intestinal grafts (2 liver-intestine and 3 multivisceral), 5 (10%) developed GVHD. Median age at transplant was 42 (19-204) months. Baseline immunosupression consisted of tacrolimus and steroids supplemented with thymoglobulin (n = 2) or basiliximab (n = 3) for induction. Median time between transplantation and GVHD was 47 (16-333) days. All patients had generalized rash, 2 had diarrhea, and 2 had respiratory symptoms. Other symptoms were glomerulonephritis (n = 1) and conjunctivitis (n = 1). Four developed severe hematologic disorders. The diagnosis was confirmed by skin biopsy in 4 patients and supported by chimerism studies in two. Colonoscopy and opthalmoscopic findings were also suggestive in one. Treatment consisted of steroids and decrease of tacrolimus, with partial response in four. Other immunosuppressants were used in refractory or recurrent cases. Three patients died within 4 months after diagnosis. CONCLUSION: Graft-vs-host disease is a devastating complication of SBTx, with high mortality probably associated with severe immunologic dysregulation.

Chronic rejection with sclerosing peritonitis following pediatric intestinal transplantation.

Intestinal transplantation is considered the usual treatment for patients with permanent intestinal failure when parenteral nutrition has failed. Chronic rejection is a complication difficult to diagnose because of the scarcity and lack of specificity in the symptoms and the characteristics of typical histological findings. We report the case of a four-yr-old patient who received an isolated intestinal transplant. After developing a chronic rejection he presented an intestinal obstruction secondary to a sclerosing peritonitis that required the surgical removal of the graft.