Clinical Vignette Abstracts Poster Session I Thursday, November 12, 2009 Cellular/Molecular Biology cv 1 EXTREME PHENOTYPIC DIVERSITY OF TYPE 1 GAUCHER DISEASE IN AFFECTED SIBLING‐PAIR: POSSIBLE ROLE OF SUBSTRATE FLUX Philip B. Stein1, Eduardo Zambrano3, Robert Brown2, Mei Yang1, Diana Beardsley2, Pramod K. Mistry1 1Pediatric GI/Hepatology, Yale New Haven Hospital, New Haven, CT; 2Pediatric Hematology/Oncology, Yale New Haven Hospital, New Haven, CT; 3Pathology, Yale New Haven Hospital, New Haven, CT Type 1 Gaucher disease(GD1) is due to an inherited deficiency of lysosomal glucocerebrosidase (GBA1) leading to systemic build up of its substrate. This inflammation results in a heterogenous phenotype. GD1 exhibits remarkable phenotypic diversity and progression patterns among patients harboring the same GBA1 genotypes as well as among affected sib‐pairs. We report a pair of Hispanic siblings with Neurofibromatosis and GD1. One with symptomatic GD1 in the setting of concurrent T cell lymphoma and another who remains asymptomatic from her GD1. Case Report: A 6 year‐old girl presented with lymphadenopathy, bone pain, and hepatosplenomegaly. A T cell acute lymphoblastic lymphoma diagnosis was established; she received chemotherapy with excellent initial response. In evaluation for the extent of her lymphoma, a bone marrow biopsy revealed large numbers of abnormal histiocytes consistent with Gaucher or pseudo‐Gaucher cells. GD1 was confirmed with low glucosidase activity. Baseline investigations revealed hepatosplenomegaly on MRI and dramatic elevation of GD1 serum biomarkers. The patient was treated with enzyme replacement therapy. There was an impressive reversal of disease manifestations and biomarkers. Concomitantly, a reducation of bone marrow infiltration was seen. The proband's sister was screened and GD1 was confirmed. Both children were found to have the same novel mutation. Evaluation of the sister revealed no hepatosplenomegaly by CT scan or cytopenia on labs. Her biochemical markers have been elevated but stable. Our case report shows the phenotypic diversity of GD1 even among affected siblings with same mutation. This case suggests that flux of substrate glycolipid may be an important determinant of phenotypic diversity in GD1. Our case report emphasizes the need for careful study of GBA1 activity and mutation in patients believed to have pseudo‐Gaucher cells in a variety of diseases. Intestine/Colon/IBD cv 2 PEDIATRIC COLLAGENOUS COLITIS‐ANOTHER CAUSE OF WATERY DIARRHEA IN TODDLERS Laurel Prestridge1, Rosemary Young1, Diane Kocovsky1, Jon Vanderhoof2 1Pediatric Gastroenterology, Boys Town National Research Hospital, Boys Town, NE; 2Pediatric Gastroenterology, Children's Hospital of Boston, Boston, MA Collagenous colitis (CC), a cause of chronic diarrhea in adults is often associated with autoimmune disease. It is rarely reported at less than five years of age. The symptoms of CC in adults include chronic watery diarrhea, abdominal discomfort, weight loss, and fecal incontinence and it is often misdiagnosed as irritable bowel syndrome. The visual appearance of the colonic mucosa is normal and diagnosis requires endoscopic biopsy at multiple levels in the colon due to the patchy nature of the changes. We report 2 cases of CC in otherwise healthy toddlers presenting with watery diarrhea. A 2 ½ year old female developed diarrhea. She had a prior history of cow’s milk intolerance with symptom resolution utilizing a hypoallergenic amino acid formula. The child transitioned to a normal toddler diet at 13 months of age and did well until the age of 30 months at which time she began having frequent loose stools. Toddler diarrhea was suspect but she had no response to carbohydrate restriction. Based on her prior history a trial of dairy restriction resulted in worsening diarrhea. The second child was a male who presented at 15 months of age with watery diarrhea that initally responded to a high fat, low carbohydrate diet however the symptoms returned at age 4. Stool cultures and viral assays on multiple occasions in both children were normal. Neither patient’s family had a history of autoimmune disorders. Upper and lower endoscopies were performed. The intestinal mucosa was visually normal but multiple biopsies demonstrated CC with subepithelial collagen bands in both children. Treatment was initiated with oral budesonide (3mg/day). The female showed a rapid response with resolution of diarrhea within one week. An attempt to wean her from the medication after 6 months resulted in an immediate relapse. Collagenous colitis should be considered in the differential diagnosis of toddlers with watery diarrhea unresponsive to usual dietary management. cv 3 PRESENTATION AND OUTCOMES OF HISTOPLASMOSIS IN PEDIATRIC IBD PATIENTS TREATED WITH ANTI‐TUMOR NECROSIS FACTOR ALPHA THERAPY Jennifer Dotson1, Hayat Mousa1, Dennis Cunningham2, Jonathan Honegger2, Jaggi Preeti2, Wallace Crandall1. 1Gastroenterology, Nationwide Children's Hospital, Columbus, OH; 2Infectious Disease, Nationwide Children's Hospital, Columbus, OH Objectives: Tumor necrosis factor alpha (TNFα) antagonists are commonly used to treat inflammatory bowel disease (IBD). Unfortunately, these agents may predispose patients to serious infections, including endemic fungal infections such as histoplasmosis. Limited data exist on the presentation, appropriate treatment, and outcomes of histoplasmosis in patients receiving anti‐TNFα therapy. We sought to describe cases of histoplasmosis in the setting of pediatric patients with IBD who received anti‐TNFα therapy, and to review the available literature on presentation, treatment, outcomes, and continuation of TNFα antagonists. Methods: We surveyed local pediatric gastroenterology and infectious diseases physicians to identify IBD patients who developed histoplasmosis while on anti‐TNFα therapy in the past 5 years. Chart reviews were conducted and cases were reviewed with their primary gastroenterologist and infectious diseases specialists. The existing medical literature was reviewed. Results: Three patients were identified. They presented with symptoms of fever, sweats, malaise, weight loss, headaches, cough, dyspnea, and chest pain within 2‐12 months of initiating therapy. In each case, immunosuppressive medications were held, and antifungal therapy was given. Anti‐TNFα therapy was resumed in 1 patient together with prolonged antifungal prophylaxis. All patients recovered from the infection and none had recurrence of active disease. On literature review, few pediatric cases were identified and none discussed restarting anti‐TNFα therapy. Discussion: We described 3 cases of patients treated with anti‐TNFα therapy who developed histoplasmosis, including 1 patient who resumed treatment with anti‐TNFα therapy in addition to antifungal prophylaxis. If anti‐TNFα therapy is resumed, close monitoring for symptoms of recurrence and screening (urine histoplasma antigen levels) for activation of disease are strongly recommended. cv 4 DISSEMINATED HISTOPLASMA CAPSULATUM AND PNEUMOCYSTIS CARINII PNEUMONIA IN A CHILD WITH CROHN’S DISEASE RECEIVING INFLIXIMAB Sonia Michail, Ryan Simon, Wright State Boonshoft School of Medicine, Dayton, OH Tumor necrosis factor alpha (TNF‐alpha) plays a crucial role in the cellular inflammatory response and regulates the body’s ability to effectively contain a number of opportunistic infections. Anti‐ TNF‐alpha therapy has been increasingly used in children with inflammatory bowel disease. Several reports of adult patents with tuberculosis, histoplasma, and pneumocystis have been associated with infliximab therapy. Many of these infections can become disseminated and carry a high risk of mortality. We report an eight year‐old child with disseminated histoplasma capsulatum and pneumocystis carinii pneumonia who had received infliximab as monotherapy for managing his Crohn’s disease. This child was diagnosed at age 2. He developed an idiosyncratic response with severe bloody diarrhea requring hospitalization with 5‐ASA preparations. The use of 6‐mercaptopurine was associated with drug‐induced hepatitis. He received infliximab for 15 months before he developed intermittent fevers, cough, and hepatosplenomegaly. CT scan of his lungs showed large hilar adenopathy and a reticulo‐nodular pattern of the lung parenchyma. Biopsies of the hilar lymph nodes showed pneumocystis and lymph node tissue cultures grew histoplasma capsulatum. He had elevated serum titers for histoplasma and positive urine histoplasma antigens. He was placed on trimethoprim‐sulfamethoxazole and itraconazole therapy with good response and resolution of radiographic changes in the lungs and mediastinum within 4 weeks of therapy. This report highlights the importance of monitoring pediatric patients for potential infectious complications related to therapy with anti‐ TNF‐alpha. It is important to consider rare causes of opportunistic infections as more children are placed on biologic therapies. Histoplasma infections are especially important in endemic areas such as the Midwest where this patient resides. cv 5 ACUTE PANCREATITIS IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE(IBD):IDIOPATHIC OR MEDICATION‐INDUCED? Aakash Goyal, Shailender Madani, Namir Al‐Ansari, Suhasini Macha, Mohammad El‐Baba Pediatric Gastroenterology, Children's Hospital of Michigan, Detroit, MI BACKGROUND: Patients with IBD are at increased risk for acute pancreatitis (AP). The association of AP and IBD is described in adults and causes are biliary lithiasis, medications, duodenal