Use of oral budesonide in the management of protein-losing enteropathy after the Fontan operation.

BACKGROUND: Intestinal inflammation is a component of the pathophysiology of protein-losing enteropathy after the Fontan operation. Oral controlled-release budesonide is 90% metabolized at first pass through the liver, has high enteric anti-inflammatory activity and relatively low systemic effects, and may be an ideal agent for use in treating this disease. METHODS: Budesonide was administered to 9 patients (4 male) with protein-losing enteropathy after the Fontan operation. The median interval between the Fontan operation and diagnosis of protein-losing enteropathy was 4 years (range, 0.1 to 13.3). Prior interventional therapy included pulmonary artery stent (1), fenestration (3), pacemaker placement (3) and Fontan revision (2). Prior medical therapy included oral prednisone (5), heparin (4), sildenafil (2), infliximab (1), and octreotide (1), all without persistent success. The starting daily dose of budesonide was 9 mg for patients 4 years old or older, and 6 mg for patients less than 4 years of age. RESULTS: Mean serum albumin level 3 months before starting budesonide was 1.9 g/dL (range, 1 to 2.4 g/dL). Serum albumin level improved in all patients within 6 months of starting budesonide (mean 2.9 g/dL; range, 2.2 to 3.8 g/dL). Albumin levels of 3 g/dL or more were achieved in 8 of 9 patients within a median of 4.3 months (range, 2 to 25). Side effects included Cushingoid features and osteoporosis (3), infection requiring antibiotic treatment (5), and acne exacerbation (1). Weaning from high initial dose to a lower dose was possible with sustained effect; however, discontinuation of budesonide resulted in recurrence of hypoalbuminemia. CONCLUSIONS: Oral budesonide is an effective therapy for treating protein-losing enteropathy after the Fontan operation. To maintain response, low-dose therapy must be continued.

Alterations in proximal femur geometry in children treated with glucocorticoids for Crohn disease or nephrotic syndrome: impact of the underlying disease.

UNLABELLED: Proximal femur geometry was assessed in children and young adults treated with chronic GCs for CD or SSNS. Subperiosteal width and section modulus were significantly lower in CD and greater in SSNS compared with controls, highlighting the importance of the underlying disease, persistent inflammation, and alterations in lean mass. INTRODUCTION: The impact of glucocorticoid (GC) therapy on bone structure during growth is unknown. Our objective was to characterize proximal femur geometry in children and young adults with Crohn disease (CD) or steroid-sensitive nephrotic syndrome (SSNS) compared with controls and to evaluate the influence of lean mass and GC therapy on bone parameters. MATERIALS AND METHODS: DXA scans of the hip and whole body were obtained in 88 subjects with CD, 65 subjects with SSNS, and 128 controls (4-26 years of age). Hip structural analysis parameters (subperiosteal width, cross-sectional area [CSA], and section modulus in the narrow neck [NN], intertrochanteric region [IT], and femoral shaft [FS]), areal BMD, and whole body lean mass were expressed as Z scores compared with controls. Multivariable linear regression was used to adjust outcomes for group differences in age, sex, race, and height. RESULTS: Mean lean mass Z scores were lower in CD (-0.63, p < 0.001) and greater in SSNS (0.36, p = 0.03) compared with controls. Hip areal BMD Z scores were lower in CD (-0.73, p < 0.001) but not SSNS (-0.02, p > 0.2) compared with controls. In CD, Z scores for subperiosteal width (NN: -1.66, p < 0.001; FS: -0.86, p < 0.001) and section modulus (NN: -0.60, p = 0.003; FS: -0.36, p = 0.03) were significantly lower than controls. In contrast, in SSNS, Z scores were greater for IT subperiosteal width (0.39, p = 0.02), FS CSA (0.47, p = 0.005), and FS section modulus (0.49, p = 0.004). Alterations in section modulus in CD and SSNS were eliminated after adjustment for lean mass. Cumulative GC dose was inversely associated with FS subperiosteal width and section modulus only in CD. CONCLUSIONS: These data show that the effects of GC on proximal femur geometry during growth are influenced by the underlying disease, persistent inflammation, and alterations in lean mass. These data also provide insight into the structural basis of hip fragility in CD.

Eosinophilic esophagitis: a 10-year experience in 381 children.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a disorder characterized by a severe, isolated eosinophilic infiltration of the esophagus unresponsive to aggressive acid blockade but responsive to the removal of dietary antigens. We present information relating to our 10-year experience in children diagnosed with EoE. METHODS: We conducted a retrospective study between January 1, 1994, and January 1, 2004, to evaluate all patients diagnosed with EoE. Clinical symptoms, demographic data, endoscopic findings, and the results of various treatment regimens were collected and evaluated. RESULTS: A total of 381 patients (66% male, age 9.1 +/- 3.1 years) were diagnosed with EoE: 312 presented with symptoms of gastroesophageal reflux; 69 presented with dysphagia. Endoscopically, 68% of patients had a visually abnormal esophagus; 32% had a normal-appearing esophagus despite a severe histologic esophageal eosinophilia. The average number of esophageal eosinophils (per 400 x high power field) proximally and distally were 23.3 +/- 10.5 and 38.7 +/- 13.3, respectively. Corticosteroids significantly improved clinical symptoms and esophageal histology; however, upon their withdrawal, the symptoms and esophageal eosinophilia recurred. Dietary restriction or complete dietary elimination using an amino acid-based formula significantly improved both the clinical symptoms and esophageal histology in 75 and 172 patients, respectively. CONCLUSIONS: Medications such as corticosteroids are effective; however, upon withdrawal, EoE recurs. The removal of dietary antigens significantly improved clinical symptoms and esophageal histology in 98% of patients.

Body-composition alterations consistent with cachexia in children and young adults with Crohn disease.

BACKGROUND: Crohn disease (CD) in children is associated with low body mass index (BMI), poor growth, and delayed maturation; alterations in lean and fat mass, however, are poorly characterized. OBJECTIVE: The objective was to quantify lean and fat mass in children and young adults with CD and in healthy control subjects, relative to height and pubertal maturation. DESIGN: This cross-sectional study assessed whole-body lean and fat mass by using dual-energy X-ray absorptiometry in 104 subjects with CD and in 233 healthy control subjects aged 4-25 y. Linear regression was used to determine the effect of CD on body composition and to generate sex-specific SD scores (z scores) for lean and fat mass relative to height. RESULTS: Subjects with CD had lower height-for-age and BMI-for-age z scores (P < 0.001 for both) than did control subjects. CD was associated with significant deficits in lean mass after adjustment for height, age, race, and Tanner stage (P = 0.003); deficits in fat mass were not observed. The mean (+/-SD) lean mass-for-height and fat mass-for-height z scores in the subjects with CD were -0.61 +/- 0.92 and -0.04 +/- 0.86, respectively. Within the control group, fat mass-for-height was positively correlated with lean mass-for height (r = 0.41, P < 0.0001); this association was absent in the subjects with CD. CONCLUSIONS: Children and young adults with CD had significant deficits in lean mass but preserved fat mass, which is consistent with cachexia. Further research is needed to identify physical activity, nutritional, and antiinflammatory interventions to improve body composition in persons with CD.

Whole body BMC in pediatric Crohn disease: independent effects of altered growth, maturation, and body composition.

UNLABELLED: Whole body BMC was assessed in 104 children and young adults with CD and 233 healthy controls. CD was associated with significant deficits in BMC and lean mass, relative to height. Adjustment for lean mass eliminated the bone deficit in CD. Steroid exposure was associated with short stature but not bone deficits relative to height. INTRODUCTION: Children with Crohn disease (CD) have multiple risk factors for impaired bone accrual. The confounding effects of poor growth and delayed maturation limit the interpretation of prior studies of bone health in CD. The objective of this study was to assess BMC relative to growth, body composition, and maturation in CD compared with controls. MATERIALS AND METHODS: Whole body BMC and lean mass were assessed by DXA in 104 CD subjects and 233 healthy controls, 4-26 years of age. Multivariable linear regression models were developed to sequentially adjust for differences in skeletal size, pubertal maturation, and muscle mass. BMC-for-height z scores were derived to determine CD-specific covariates associated with bone deficits. RESULTS: Subjects with CD had significantly lower height z score, body mass index z score, and lean mass relative to height compared with controls (all p < 0.0001). After adjustment for group differences in age, height, and race, the ratio of BMC in CD relative to controls was significantly reduced in males (0.86; 95% CI, 0.83, 0.94) and females (0.91; 95% CI, 0.85, 0.98) with CD. Adjustment for pubertal maturation did not alter the estimate; however, addition of lean mass to the model eliminated the bone deficit. Steroid exposure was associated with short stature but not bone deficits. CONCLUSION: This study shows the importance of considering differences in body size and composition when interpreting DXA data in children with chronic inflammatory conditions and shows an association between deficits in muscle mass and bone in pediatric CD.

Self-assessment of sexual maturity status in children with Crohn's disease.

OBJECTIVE: To evaluate the validity of self-assessment of sexual maturity status (SMS) in children with Crohn's disease (CD), a pediatric chronic disease that often affects growth and development. STUDY DESIGN: Self-assessment of SMS in 100 children (34 girls) ages 8 to 18 years with CD from the Children's Hospital of Philadelphia was compared with an independent assessment by one well trained pediatrician, using drawings and written descriptions of Tanner stages of breast, genital, and pubic hair development. RESULTS: Overall, subjects with CD (age, 14.3 +/- 2.8 years) had delayed growth status based on height-for-age (HAZ) and weight-for-age Z scores (WAZ). Boys were more growth delayed (HAZ, -0.90 +/- 1.1; WAZ, -0.75 +/- 1.3) than girls (HAZ, -0.45 +/- 1.3; WAZ, -0.20 +/- 1.1). Kappa coefficients (kappa) showed excellent agreement between child and physician assessment of SMS, ranging from kappa = 0.74 to 0.85, depending on sex and SMS component, corresponding to a 79% to 88% agreement. When not in agreement, children tended to overestimate their SMS. Boys who overestimated (n = 8) had significantly higher weight and BMI status than boys who assessed accurately. CONCLUSIONS: Self-assessment of SMS was a reliable and valid method in children with CD and is useful in screening for maturational delay in children with chronic disease.