IgG4: not only for allergists.

We describe herein a case of IgG4-related disease with the isolated clinical presentation of malabsorption due to pancreatic failure. Histology of an abdominal lymph node was critical for diagnosis. IgG4-related disease is increasingly recognized as an immunological disorder that can mimic various clinical entities.

Varicella-zoster immunization in pediatric liver transplant recipients: safe and immunogenic.

Varicella can have a severe course in immunosuppressed patients. Although prevention is fundamental, live-attenuated varicella-zoster (VZV) vaccine is not currently recommended in transplant recipients. Our aims were to (1) evaluate VZV immunity in pediatric liver transplant (LT) recipients; (2) immunize (two doses) seronegative patients post-LT; (3) monitor vaccine safety, (4) assess B and T cell vaccine responses. All patients followed at the Swiss National Pediatric LT Center were approached and 77/79 (97.5%) were enrolled (median age 7.8 years). Vaccine safety was monitored by standardized diary cards and phone calls. VZV-specific serology and CD4(+) T cells were assessed before and after immunization. Thirty-nine patients (51.1%) were seronegative including 14 children immunized pre-LT. Thirty-six of 39 seronegative patients were immunized post-LT (median 3.0 years post LT). Local (54.8%) and systemic (64.5%) reactions were mild and transient. The frequency of VZV-specific CD4(+) T cells and antibody titers increased significantly (respectively from 0.085% to 0.16%, p = 0.04 and 21.0 to 1134.5 IU/L, p < 0.001). All children reached seroprotective titers and 31/32 (97%) patients assessed remained seroprotected at follow-up (median 1.7 years). No breakthrough disease was reported during follow-up (median 4.1 years). Thereby, VZV vaccine appears to be safe, immunogenic and provide protection against disease in pediatric LT patients.

Glomerular and tubular function following orthotopic liver transplantation in children treated with tacrolimus.

The aim of this study was to analyze the impact of TAC on medium term (three-yr follow-up) renal function in pediatric liver transplant (OLT) recipients. Glomerular and tubular indices were retrospectively analyzed in 24 consecutive OLT pediatric recipients on TAC. CrCl increased significantly each month post-OLT (p = 0.003), with a trend toward significance between pre-OLT and 36 months (p = 0.17). There was no correlation between CrCl and TAC troughs (p = 0.783). Sixteen percent of patients had CrCl <60 mL/min/1.73 m(2) pre-OLT vs. none at 36 months post-OLT. TRP values were normal throughout the study. UPr/Cr decreased insignificantly over time and correlated significantly with TAC trough levels (p = 0.031). UCa/Cr values normalized by the third-month post-OLT, decreasing significantly over the time (p = 0.000) but did not correlate with TAC troughs. At three months post-OLT, 65.2% of patients needed antihypertensive therapy, and no patients needed more than one antihypertensive treatment after one yr. Despite nephrotoxic side effects in the early postoperative phase, this study shows that 65.5% patients had a normal renal function by three yr post-OLT. Tubular indices correlated with TAC trough levels.

Successful serology-based intervention to increase protection against vaccine-preventable diseases in liver-transplanted children: a 19-yr review of the Swiss national reference center.

As children referred for OLT in Switzerland were not vaccinated optimally, new guidelines were developed and recommended to base catch-up immunization on serum antibody titers against vaccine-preventable diseases, before and after OLT. We measure the results of this serology-based intervention by comparing vaccine coverage and antibody titers in the pre- (1990-2002, P1) and post-intervention (2003-2008, P2) cohorts in a quality control project. Forty-four P1 and 30 P2 children were evaluated. At pre-OLT visit, D, T, SPn, and MMR serologies were checked more frequently in P2 than P1 (p < 0.05). More P2 children were up-to-date for DTaP and MMR (p < 0.05) or had received ≥1 dose of HBV, HAV, SPn, and VZV vaccines (p < 0.05). One yr post-OLT, DT, SPn, MMR, and VZV serologies were more frequently checked (p < 0.05), and antibody titers were higher for DT and HAV (p < 0.05) in P2. Gender, age, or diagnosis did not explain these differences. Among P2 patients, pre- and post-OLT titers for D, T, Hib, HBV, SPn14, and SPn19 were correlated (p < 0.05 for all). Protection against vaccine-preventable diseases of high-risk children like OLT patients can be significantly improved by serology-based intervention for vaccine-preventable diseases.

When allergology meets psychiatry: delusional parasitosis (Ekbom's syndrome).

Delusional parasitosis (DP) or Ekbom's syndrome is uncommon psychiatric disorder that may represent a challenge for the allergist. DP is characterized by the fixed belief to be infested with parasites or small living creatures, although there is no medical evidence for this. The management of this condition is difficult, as patients with this paranoid disorder reject psychiatric diagnosis and treatment and often consult many specialists (dermatologists, internists or allergists). The patients may also share the delusional disease with other people living in close emotional relationship. We report herein a delusion of parasitosis simultaneously occurring in two spouses, and discuss the clinical features of the disease.

Prevention of relapse by mesalazine (Pentasa) in pediatric Crohn's disease: a multicenter, double-blind, randomized, placebo-controlled trial.

AIM: This study aimed to test the efficacy of mesalazine in maintaining remission in pediatric Crohn's disease (CD) following successful flare-up treatment. METHODS: In this double-blind, randomized, placebo-controlled trial, 122 patients received either mesalazine 50mg/kg per day (n=60) or placebo (n=62) for one year. Treatment allocation was stratified according to flare-up treatment (nutrition or medication alone). Recruitment was carried out over two periods, as the first period's results showed a trend favoring mesalazine. Relapse was defined as a Harvey-Bradshaw score more than or equal to 5. Time to relapse was analyzed using the Cox model. RESULTS: The one-year relapse rate was 57% (n=29) and 63% (n=35) in the mesalazine and placebo groups, respectively. We demonstrated a twofold lower relapse risk (P<0.02) in patients taking mesalazine in the medication stratum (first recruitment period), and a twofold higher risk in patients taking mesalazine in the nutrition stratum (second recruitment period), compared with the other groups. None of the children's characteristics, which differed across the two recruitment periods, accounted for the between-period variation in mesalazine efficacy. One serious adverse event was reported in each treatment group. CONCLUSION: Overall, mesalazine does not appear to be an effective maintenance treatment in pediatric CD.

Recurring enteric peritonitis associated with non-perforating colon carcinoma.

Peritonitis of enteric origin may occur during treatment with peritoneal dialysis due to visceral perforation or injury or, in the absence of perforation, due to transmural migration of enteric bacteria across the bowel wall into the peritoneal cavity. To the best of our knowledge, peritonitis has not previously been reported associated with carcinomatous colon polyp in the absence of bowel wall perforation. We describe the case of a 31-year-old female who experienced recurring episodes of enteric peritonitis associated with a clinically occult adenocarcinoma of the colon, without having any other known risk factors for peritonitis. A 15 mm carcinomatous polyp was not visible on CT scan but was found at colonoscopy with polypectomy. She proceeded to transverse colectomy; the resected colon showed no evidence of bowel wall perforation. This case demonstrates that a non-perforating carcinomatous polyp of the colon may predispose to enteric peritonitis in the setting of peritoneal dialysis, and it emphasizes the importance of making an aggressive search for underlying pathology, in patients who present with recurring enteric peritonitis or unusual presentations of enteric peritonitis.

[How to deal with gastroesophageal reflux in childhood]. / Le reflux gastro-oesophagien: attitude pratique.

Gastroesophageal reflux is frequent source of consultation at the paediatrician's room, although most GER resolve spontaneously in infancy. In most cases, after a thorough anamnesis and a full physical examination prokinetic and anti-acid medications are started, as well as postural change, without the assistance of a specialist. When reflux is complicated by either oesophagitis, respiratory symptoms, failure to thrive or when the above treatment fail, further investigations need to be undertaken. Their option will depend on the clinical presentation. Rarely GER will lead to surgery.

Vitamin D supplementation during infancy is associated with higher bone mineral mass in prepubertal girls.

The objective of this study was to determine whether vitamin D supplementation of breast-fed infants during the first year of life is associated with greater bone mineral content and/or areal bone mineral density (aBMD) in later childhood. The design was a retrospective cohort study. One hundred and six healthy prepubertal Caucasian girls (median age, 8 yr; range, 7-9 yr) were classified as vitamin D supplemented or unsupplemented during the first year of life on the basis of a questionnaire sent to participating families and their pediatricians. Bone area (square centimeters) and bone mineral content (grams) were determined by dual energy x-ray absorptiometry at six skeletal sites. Vitamin D receptor (VDR) 3'-gene polymorphisms (BsmI) were also determined. The supplemented (n = 91) and unsupplemented (n = 15) groups were similar in terms of season of birth, growth in the first year of life, age, anthropometric parameters, and calcium intake at time of dual energy x-ray absorptiometry. The supplemented group had higher aBMD at the level of radial metaphysis (mean +/- SEM, 0.301+/-0.003 vs. 0.283+/-0.008; P = 0.03), femoral neck (0.638+/-0.007 vs. 0.584+/-0.021; P = 0.01), and femoral trochanter (0.508+/-0.006 vs. 0.474+/-0.016; P = 0.04). At the lumbar spine level aBMD values were similar (0.626+/-0.006 vs. 0.598+/-0.019; P = 0.1). In a multiple regression model taking into account the effects of vitamin D supplementation, height, and VDR genotype on aBMD (dependent variable), femoral neck aBMD remained higher by 0.045 g/cm2 in the supplemented group (P = 0.02). Vitamin D supplementation in infancy was found to be associated with increased aBMD at specific skeletal sites later in childhood in prepubertal Caucasian girls.

Lower femoral neck bone mineral density in prepubertal former preterm girls.

The purpose of this case-control study was to determine bone mineral content and areal bone mineral density at various skeletal sites in former preterm girls, aged 7-9 years, and to compare these data with age-matched term controls. Subjects included 25 white, prepubertal, former preterm girls (gestational age 30.8 +/- 0.3 weeks, birthweight 1461 +/- 56 g [mean +/- SEM]). Controls included 50 healthy, white, prepubertal girls born at term and matched for age (two controls per case). Measurements included anthropometric variables, calcium intake according to a food-frequency questionnaire, bone mineral content (BMC; grams), and areal bone mineral density (aBMD; grams per square centimeter), using dual-energy X-ray absorptiometry (DXA) at six skeletal sites. Thirteen preterm girls and 13 age-matched term controls were reassessed 1 year after the first DXA measurement. The former preterm girls were similar to controls in terms of age and height, but were lighter (24.6 +/- 0.6 vs. 27.0 +/- 0.6 kg, p = 0.02). They also reported a higher median calcium intake (1058 vs. 759 mg/day, p = 0.004). aBMD was lower in former preterms compared with controls at the level of the radial metaphysis (0.283 +/- 0.006 vs. 0.298 +/- 0.004, p = 0.04), femoral neck (0.593 +/- 0.011 vs. 0.638 +/- 0.010, p = 0.007), and total hip (0.596 +/- 0.012 vs. 0.640 +/- 0.010, p = 0.007), but was similar between the two groups at the radial diaphysis (0.437 +/- 0.004 vs. 0.436 +/- 0.004) and femoral diaphysis (1.026 +/- 0.015 vs. 1.030 +/- 0.011). Femoral neck aBMD remained lower compared with controls in the subgroup of preterm girls reassessed after 1 year (0.608 +/- 0.017 vs. 0.672 +/- 0.020, p = 0.02). In random effects models for longitudinal data, taking into account the effects of age, weight, and height on aBMD (dependent variable), femoral neck aBMD remained lower in former preterms (p < 0.001). Prepubertal former preterm girls showed growth recovery, but had lower aBMD at the hip and radial metaphysis than age-matched term controls, despite spontaneously higher calcium intake. Preterm girls had similar aBMD results compared with controls at sites with predominantly cortical bone (radial and femoral diaphysis), which are known to be more sensitive to calcium intake.

Monosegmental liver transplantation from an adult to an infant.

A shortage of small pediatric organ donors has led to the development of reduced size liver transplantation in children. However, the discrepancy between donor and recipient weight can limit the use of this procedure despite transplantation of the left lobe only. Monosegmental liver transplantation using segment III only was recently described. We report here the case of an 11 month old, 6.9 kg boy who received another monosegmental graft (segment II) from a 78 kg donor on an urgent basis. Because of the lack of parenchymal landmarks between segments II and III, sterile methylene blue solution was injected into the portal vein of segment III: parenchyma of this segment colored immediately and was resected accordingly. Three and a half years later, the growth, development, and nutrition of this child were normal. This procedure seems to be helpful when the left lobe of the graft is obviously too large.

Taurine improves the absorption of a fat meal in patients with cystic fibrosis.

The effect of taurine supplementation on the absorption of a fat meal was evaluated in patients with cystic fibrosis. In a cross-over design study, five patients with cystic fibrosis (12.1 +/- 2.6 years of age) and three control subjects received either placebo or taurine (30 mg/kg/d) for two 1-week periods, a month apart, followed by a fat meal test. Blood samples were drawn 0, 1, 2, 3, 5, 8 hours after the meal. Four patients with cystic fibrosis and severe steatorrhea despite appropriate enzyme therapy showed a significant (P less than .05) improvement in the absorption of triglycerides, total fatty acids, and linoleic acid while receiving taurine supplements. Three control subjects and one child with cystic fibrosis and mild steatorrhea receiving enzyme therapy did not experience such an effect. The difference in triglyceride absorption, when calculated as the area under the curve, receiving and not receiving taurine was significantly (P less than .05) correlated with the degree of steatorrhea. Furthermore, in contrast to control subjects, the fatty acid composition of chylomicrons in these four study patients showed important discrepancies with that of the fat meal and was corrected, in part, by taurine supplementation. These results suggest that taurine supplementation could be a useful adjunct in the management of patients with cystic fibrosis with ongoing fat malabsorption and essential fatty acid deficiency.

Craniofacial anomalies and malformations in respiratory chain deficiency.

We report on facial anomalies including round face, high forehead, flat philtrum, apparently low-set ears, and short neck in 4 unrelated patients with mitochondrial respiratory enzyme deficiency. Pre- and postnatal growth retardation with microcephaly, brachydactyly, and hypoplasia of distal and middle phalanges was present in all 4 cases. The diagnosis of respiratory chain deficiency was confirmed by enzymatic and molecular studies. The combination of facial anomalies, prenatal growth failure, and malformations is suggestive of antenatal expression of the disease, and raises the question of the part that respiratory chain deficiencies play in human malformations.

Body composition analysis by dual-energy x-ray absorptiometry in adults with cystic fibrosis.

Assessment of nutritional status is important in cystic fibrosis (CF). We performed body composition analysis by dual-energy x-ray absorptiometry (DXA) in 12 adults with CF, 7 of them with malnutrition as defined by percentage of ideal body weight (IBW) lower than 90. The DXA allowed for determination of bone body mass (BBM), lean body mass (LBM), and fat body mass (FBM). A deficit in BBM and LBM was found to be present in all seven patients with malnutrition when compared with a group of young normal adults. By contrast, deficit in FBM was inconstant. Deficits in bone and lean were associated with each other. They did not depend on the severity of steatorrhea, but were highly correlated to ventilatory impairment. In conclusion, DXA provides new and potentially useful information on the nutritional status of these patients. In addition, it confirms the close association of malnutrition and lung disease in CF.

Total parenteral nutrition-associated cholestasis in rats: comparison of different amino acid mixtures.

It has been suggested that the quantity of amino acids perfused is a pathogenetic factor in total parenteral nutrition (TPN)-associated hepatotoxicity. However, the effect of the qualitative pattern of amino acid solutions has not been studied. Rats on parenteral nutrition for 5 days received 10.2 g of dextrose and 3.4 g of amino acids daily. Bile flow (microliter/min/g liver protein) after administration of Vamin was 16.2 +/- 0.8, which was similar to that in controls given chow and dextrose iv, but it was significantly higher (p less than 0.001) than those on Travasol (12.3 +/- 0.8). The decrease in bile flow was not related to the large concentrations of alanine and glycine present in Travasol. However, the addition to Travasol of serine present only in Vamin increased bile flow significantly. Bile acid secretion rate, biliary lipid constituents, calcium, sodium, and glucose showed little change. In contrast, alpha-amino nitrogen was increased (p less than 0.05) in Vamin-perfused animals. Steatosis was noted in only a few animals in the Travasol group, and was not associated with an increase in the triglycerides content of the liver. Glycogen and protein content of the livers did not differ. The data show that the composition of amino acid solutions may be a determinant of TPN-induced cholestasis and suggest that the presence of methyl donor amino acids may have a protective effect.

Postoperative chylothorax in children: differences between vascular and traumatic origin.

Twenty-four children with postoperative chylothorax were encountered among 1,264 consecutive thoracic operations over a 7-year period and form the basis of this study. Chylothorax was caused by direct lesion to the thoracic duct or lymphatic vessels in 17 patients and was associated with superior vena cava (SVC) obstruction in seven. Of the latter, five had bilateral chylothorax. Chylothoraces secondary to venous hypertension and thrombosis have a longer interval between operation and diagnosis compared with direct trauma as well as a longer duration and larger volume of chylous drainage. Treatment was entirely nonoperative in 16 patients and operative in 8. Nonoperative treatment consisted of pleural needle aspiration or suction drainage in association with a medium chain triglyceride (MCT) diet (n = 11) or total parenteral nutrition (TPN) after failure of MCT (n = 5). Direct operation on the thoracic duct was performed in 5 patients, four had pleurodesis, and 2 had pleuroperitoneal shunts inserted. All patients were cured of their chylothorax and there were no deaths. Patients with major vein thrombosis were the most difficult to treat. On the basis of this experience, we suggest a step-by-step approach: (1) insertion of chest tube after 3 to 4 pleural punctures; (2) 1-week trial of MCT diet, with intravenous support to correct protein losses; (3) TPN if chylothorax increases or persists with large volumes; (4) Doppler echocardiography or phlebography to rule out obstruction of major thoracic veins; and (5) insertion of TPN line in inferior vena cava in case of such obstruction; and (6) direct surgical approach to the thoracic duct after 4 weeks of unsuccessful nonoperative treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of severe underlying pathology and hypovolemic shock on the development of acute pancreatitis in children.

Acute pancreatitis in children is a little known and poorly defined disease, and thus rarely considered in the diagnosis of pediatric abdominal pain. In the past 14 years, the authors treated 21 children who had acute pancreatitis. Trauma was the cause of the disease in 29% of the patients. One third (33%) had hypovolemic shock-related pancreatitis (mostly after either cardiopulmonary bypass or severe gastrointestinal bleeding). Furthermore, a major proportion (38%) had severe underlying organic disease. The clinical presentation was unremarkable; most patients (83%) had abdominal pain, especially in the epigastrium, and vomiting was the only other clinical sign exhibited by more than 50%. The Glasgow score (a severity grading system based on eight laboratory values and calculated within the first 48 hours after admission) had good specificity but poor sensitivity. Amylasemia had no predictive value. More than half our patients (57%) had complications, mainly pseudocysts (24%) and relapse (14%), and about one quarter (24%) had severe pancreatitis. There were two deaths (10%), and all surviving children (90%) eventually were symptom-free. Treatment was conservative in the majority of cases; eight patients (38%) required surgery. Hypovolemic shock and a severe underlying pathology were identified as risk factors for the occurrence of severe pancreatitis (P < .005) or death (P < .001), but not for the development of complications.

Liver transplantation in children: past, present and future.

The tremendous progress accomplished during the last twenty years in liver transplantation has permitted the treatment of infants and children who can now benefit from a new organ before an and stage liver disease. The main indications in paediatrics are congenital biliary obstructions, metabolic disorders leading to cirrhosis and fulminant hepatitis. Nevertheless, in the future, other treatments for metabolic and viral diseases will be possible. The shortage of paediatric donors has been partially alleviated by the method of reduced liver, however the general shortage of organs has led to the use of split livers and living-related donors. Overall survival in children can be expected above 80%. In Geneva, 15 paediatric patients were transplanted, 3 twice, over a 6-year period with a survival rate of 86%. The indications were the same as in other centers. Acute rejection was often noted, but easily treated, mainly by steroid bolus. 13 patients have been followed up for more than 1 year and have had satisfactory growth and normal liver function tests. Whenever a liver transplantation is performed, paediatricians have hopes and fears; hope of an improvement of growth and neuro-psychological developments and fears of side effects of immunosuppressive drugs, such as renal function impairment or lymphoproliferative syndrome. The future in the field of liver transplantation will require new methods, with the aim of decreasing the necessity of whole organ transplantation. This includes alternative treatments for metabolic disorders, transplantation of isolated hepatocytes, possibly after gene therapy, and the use of an artificial liver. Some of this future is already present.

The addition of lipids increases the total parenteral nutrition-associated cholestasis in the rat.

Cholestasis is one of the most frequent complications of Total Parenteral Nutrition (TPN). Among the components of TPN, amino acids (AA) and dextrose are considered responsible in terms of quantity. The aim of this study was to determine whether IV lipids have a protective effect on the liver lesions induced by TPN, as well as on the bile flow in rats. Two groups of 6 animals, 6 receiving TPN containing AA and dextrose (Group A-D) and 6 receiving AA, dextrose and lipids (Group A-D-L) were studied. Both groups received the same amount of AA (3.4 g/day) and the same amount of energy (50 kcal/day). The TPN lasted 3 days, after which blood samples were obtained for liver function tests and the bile flow was determined gravimetrically, subsequently the liver was removed for histological analysis. A significant weight loss (p < 0.01) was observed in both groups (Group A-D: -13 +/- 4 g; Group A-D-L: -16 +/- 2g). The bile flow was significantly lowered in A-D-L at 10.14 +/- 1.27 microliters/minute when compared to Group A-D (15.61 +/- 1.31 microliters/minute). The Aspartate Amino Transferase (AST) plasma level was elevated at 188 +/- 20 UI in Group A-D and at 185 +/- 33 UI in Group A-D-L. Gamma-Glutamyl-Transferase (gamma-GT) plasma level was in the normal range in both groups. In conclusion, this study indicates that TPN-associated cholestasis is significantly increased by lipid addition. However, the hepatocellular necrosis seems unchanged.

Splenic cysts in pediatric patients--a report on 8 cases and review of the literature.

8 cases of splenic cysts are reported: treatment was surgical in 4 large cysts (greater than 5 cm, 3 epidermoids and 1 pseudocyst), and non-operative in 4 small cysts (less than 5 cm, 3 post-traumatic pseudocysts and 1 congenital cyst, probably epidermoid). Follow-up was over a period of 3 months to 7 years. 3 among the 4 post-traumatic pseudocysts were followed up by ultrasound until resolution (3 months to 3 years), and 1 large pseudocyst was operated on due to rupture following benign trauma. 3 large cysts were epidermoid in origin, 1 was electively operated, and 2 were discovered and operated on because of complications (rupture, infection). Only one total splenectomy was performed; surgery preserved the spleen in all other cases; but 1 epidermoid cyst presents now with a recurrence. Based on this experience, we suggest frozen section of the cyst wall during surgery, to decide the type of partial splenectomy to be performed: total cystectomy or marsupialization.