Hilary Jericho

Extra-intestinal Manifestations of Celiac Disease: Effectiveness of the Gluten Free Diet

Objective: The aim of the study was to evaluate the effectiveness of the gluten-free diet (GFD) on extraintestinal symptoms in pediatric and adult celiac populations at the University of Chicago. Methods: We conducted a retrospective chart review of the University of Chicago Celiac Center clinic charts from January 2002 to October 2014. Demographics, serologic testing, intestinal biopsies, and extraintestinal symptoms at presentation, 12, 24, and >24 months were recorded. Extraintestinal symptoms included abnormal liver enzymes, arthralgia/arthritis, dermatitis herpetiformis, alopecia, fatigue, headache, anemia, stomatitis, myalgias, psychiatric disorders, rashes, seizures, neuropathy, short stature, delayed puberty, osteoporosis, and infertility. Results: A total of 737 patients with biopsy-confirmed celiac disease or skin biopsy–confirmed dermatitis herpetiformis were included. Patients lost to follow-up, or with insufficient data were excluded leaving 328 patients (157 pediatrics younger than 18 years). For pediatrics, the female to male ratio was 2:1 and the mean age at diagnosis was 8.9 years. For adults, 4:1 and 40.6 years old. Extraintestinal symptom rates were similar in children (60%) and adults (62%). Short stature (33%), fatigue (28%), and headache (20%) were most common in children. Iron deficiency anemia (48%), fatigue (37%), and headache/psychiatric disorders (24%) were common in adults. Children had faster/higher rates of symptom resolution compared with adults. Twenty-eight percent of children with unresolved short stature on a GFD were found to have other comorbidities. Conclusions: Children and adults with celiac disease have similar rates of extraintestinal manifestations. In children short stature, fatigue, and headache were most common, whereas anemia, fatigue, and headache/psychiatric disorders were most common in adults. Children on a strict GFD showed faster and higher rates of symptom resolution as compared to adults. Unresponsive children with short stature must be assessed for comorbidities.

Bile acid pool dynamics in progressive familial intrahepatic cholestasis with partial external bile diversion.

Objectives: Partial external bile diversion (PEBD) is an established therapy for low-&ggr;-glutamyl transferase (GGT) progressive familial intrahepatic cholestasis (PFIC). This study sought to determine whether the dynamics of the cholic acid (CA) and chenodeoxycholic acid (CDCA) pools in subjects with low-GGT-PFIC with successful PEBD were equivalent to those achieved with successful liver transplantation (LTX). Methods: The kinetics of CA and CDCA metabolism were measured by stable isotope dilution in plasma samples in 5 subjects with PEBD, all with intact canalicular bile salt export pump expression and compared with subjects with low-GGT-PFIC with successful LTX. Stomal loss of bile acids was measured in subjects with PEBD. Results: The fractional turnover rate for CA in the PEBD group ranged from 0.5 to 4.2/day (LTX group, range 0.2–0.9/day, P = 0.076) and for CDCA from 0.7 to 4.5/day (LTX group 0.3–0.4/day, P = 0.009). The CA and CDCA pool sizes were equivalent between groups; however, pool composition in PEBD was somewhat more hydrophilic. The CA/CDCA ratio in PEBD ranged from 0.9 to 19.5, whereas in LTX it ranged from 0.5 to 2.6. Synthesis rates computed from isotope dilution correlated well with timed output for both CA (r2 = 0.760, P = 0.024) and CDCA (r2 = 0.690, P = 0.021). Conclusions: PEBD results in bile acid fractional turnover rates greater than LTX, pool sizes equivalent to LTX, and pool composition that is at least as hydrophilic as produced by LTX.

Celiac Disease Symptom Resolution: Effectiveness of the Gluten Free Diet

Objective: The aim of the study was to evaluate the efficacy of the gluten-free diet (GFD) on gastrointestinal (GI) and extra-intestinal (EI) symptom resolution and identify predictors for persistence of symptoms in all celiac patients at the University of Chicago. Methods: We conducted a retrospective chart review from 2002 to 2015. GI symptoms included abdominal pain, bloating, constipation, diarrhea, failure to thrive/weight loss, nausea, reflux, and vomiting. EI symptoms included abnormal liver enzymes, arthralgia/arthritis, dermatitis herpetiformis, alopecia, fatigue, headache, anemia, stomatitis, myalgia, psychiatric disorders, rashes, seizures, neuropathy, short stature, delayed puberty, osteoporosis, and infertility. Results: A total of 554 patients (227 children) with celiac disease (CeD) were included. Abdominal pain, diarrhea and failure to thrive were the most common GI symptoms in children whereas diarrhea, bloating, and abdominal pain were most common in adults. Short stature, fatigue, and headache were the most common EI symptoms in children whereas iron deficiency anemia, fatigue, and headache/psychiatric disorders were most common in adults. Children had significantly higher rates of EI and GI symptom resolution as compared to adults, with greater rates of improvements in GI versus EI symptoms at more than 24 months. Long duration of symptoms, female sex, and non-adherence to a GFD were the most important significant predictors of failure to clinically improve. Conclusions: On a strict GFD, children report greater rates of both GI and EI symptom resolution as compared to adults with greater rates of improvement in GI over EI symptoms. Early recognition of CeD and close attention to diet adherence may help in symptom resolution.

Celiac Disease and Wheat Intolerance Syndrome: A Critical Update and Reappraisal.

ABSTRACT Since the first description of celiac disease (CeD) by Samuel Gee in 1888 and the later “miraculous discovery” that bread was responsible for this condition following World War II in Europe, there has been an exponential growth of knowledge regarding CeD. Just when we thought that we knew everything there was to know about it, the disease is, however, offering new challenges, with its presentation having significantly morphed over the years from cases of overt gastrointestinal symptoms, malnutrition, and atrophic villi on duodenal biopsies to that of largely extraintestinal, subtle, or mild symptoms. Along with these changes, unexpectedly a new parallel entity appeared a few years ago and is gaining ground: the so-called nonceliac gluten sensitivity, an improper name because it should actually be referred to as wheat intolerance syndrome given that the role of gluten in all such cases is far from demonstrated and the implication of an immune involvement suggested by the term “sensitivity” is still unfounded. Lastly, wheat can be an offender also through an immunoglobulin E-mediated allergy, whose presence must also be evaluated and ruled out in selected cases. The practicing physician is therefore now challenged with the task of discerning which patients need to be assessed for one or the other of these disorders, and how. This review aims at providing an updated, critical reassessment of these 2 entities.

Successful treatment with rituximab of an epstein-barr virus-associated leiomyosarcoma occurring after liver transplantation

E pstein-Barr virus (EBV)–associated smooth muscle tumors (SMTs) have increasingly been recognized in children (1), typically following solid organ and stem cell transplantation, chemotherapy for malignancies, and in immunosuppressed states such as acquired immunodeficiency syndrome (1–3). We report a case of successful treatment of an EBV-associated SMT with rituximab, in a 2.5-year-old girl, 15 months following liver transplantation for biliary cirrhosis. To the best of our knowledge, this is the first report of rituximab used in the treatment of EBV-associated SMT. The patient was born full term following an uneventful pregnancy and delivery. She was diagnosed as having cryptogenic cirrhosis at 7 months of age and rapidly progressed to end-stage liver disease. She underwent an orthotopic liver transplant without complications and received a whole organ from a deceased male donor. Her initial immunosuppressive regimen included cyclosporine, 10 mg kg 1 dose 1 twice daily, prednisone, 0.3 mg/kg daily, and azathioprine, 1 mg/kg daily. One month posttransplant, she developed steroid-resistant acute cellular rejection, which was treated with an 8-day course of thymoglobulin, 1.5 mg/kg daily, methylprednisolone, 10 mg/kg daily for 4 days, and her calcineurin inhibitor was switched to tacrolimus, 0.2 mg kg 1 dose 1 twice daily, and adjusted to maintain goal levels between 10 and 12 ng/dL. Given her episode of steroid-resistant acute rejection, she was maintained at this goal until 12 months posttransplant, at which time her goal levels decreased to 8 and 10 ng/dL. Her antimetabolite was continued. Thirteen months posttransplant, she developed elevated aminotransferases with a markedly elevated EBV level, as detected

Extra-Intestinal Manifestation of Celiac Disease in Children

The aim of this literature review is to discuss the extra-intestinal manifestations of celiac disease within the pediatric celiac population.