Fibrosing Colonopathy Presenting in a Patient with Cystinosis.

Fibrosing colonopathy is a unique pathology characterized by long segment stricture, usually of the ileocecal region. Historically, it is most commonly described in patients with cystic fibrosis (CF). Fibrosing colonopathy is felt to be secondary to excessive doses of exogenous lipase medication. This condition is rarely seen in the last decade. In this case presentation, fibrosing colonopathy was identified in a patient with the lysosomal storage disorder of cystinosis. Fibrosing colonopathy has not previously been described in patients with cystinosis. The patient was found to have fibrosing colonopathy after perforation of the colon during a colonoscopy for bloody diarrhea. This case report aims to draw attention to a noteworthy case of fibrosing colonopathy in a patient who does not have cystic fibrosis, but rather cystinosis.

Racial/ethnic differences in spontaneous HCV clearance in HIV infected and uninfected women.

BACKGROUND/AIMS: Among individuals without human immunodeficiency virus (HIV), African Americans have lower spontaneous clearance of hepatitis C virus (HCV) than Caucasians, and women have higher clearance than men. Few studies report racial/ethnic differences in acute HCV in HIV infected, or Hispanic women. We examined racial/ethnic differences in spontaneous HCV clearance in a population of HCV mono- and co-infected women. METHODS: We conducted a cross sectional study of HCV seropositive women (897 HIV infected and 168 HIV uninfected) followed in the US multicenter, NIH-funded Women's Interagency HIV Study (WIHS), to determine the association of race/ethnicity with spontaneous HCV clearance, as defined by undetectable HCV RNA at study entry. RESULTS: Among HIV and HCV seropositive women, 18.7 % were HCV RNA negative, 60.9 % were African American, 19.3 % Hispanic and 17.7 % Caucasian. HIV infected African American women were less likely to spontaneously clear HCV than Hispanic (OR 0.59, 95 % CI 0.38-0.93, p = 0.022) or Caucasian women (OR 0.57, 95 % CI 0.36-0.93, p = 0.023). Among HIV uninfected women, African Americans had less HCV clearance than Hispanics (OR 0.18, 95 % CI 0.07-0.48, p = 0.001) or Caucasians (OR 0.26, 95 % CI 0.09-0.79, p = 0.017). There were no significant differences in HCV clearance between Hispanics and Caucasians, among either HIV infected (OR 0.97, 95 % CI 0.57-1.66, p = 0.91) or uninfected (OR 1.45, 95 % CI 0.56-3.8, p = 0.45) women. CONCLUSIONS: African Americans were less likely to spontaneously clear HCV than Hispanics or Caucasians, regardless of HIV status. No significant differences in spontaneous HCV clearance were observed between Caucasian and Hispanic women. Future studies incorporating IL28B genotype may further explain these observed racial/ethnic differences in spontaneous HCV clearance.

Cytokine profiles in peripheral blood of children and adults with Crohn disease.

BACKGROUND: Increasing evidence suggests that cytokine dysregulation in T-helper 1 and T-helper 2 (TH1/TH2) subsets contributes to the pathogenesis of Crohn disease (CD). The present pilot study examines the hypothesis that cytokine profiles differ between pediatric and adult patients with CD. METHODS: Production of TH1 cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) and of TH2 cytokines interleukin-4 (IL-4) and IL-6 was analyzed in peripheral blood of patients with CD and healthy controls (n=20) using flow cytometry after in vitro stimulation. RESULTS: In both pediatric and adult subjects, frequencies of TNF-α CD4+ T cells were higher in patients with CD than in controls (P=0.009 and P=0.047, respectively). Percentages of cells expressing IL-4 were slightly increased (P=0.036), whereas those for IFN-γ were decreased (P=0.009) in pediatric patients with CD compared with controls. As expected, the overall production of TH1 cytokines was higher in adults compared with pediatric subjects. When memory CD4+CD45RO+ T cells were considered, lower IFN-γ expression was observed in pediatric subjects with CD compared with controls (P=0.009), matching the trend seen in the general CD4+ T cell population. The percentage of CD4+CD45RO+ T cells was increased in adult patients with CD compared with pediatric patients with CD (P=0.016). CONCLUSIONS: The present study describes a peripheral blood TH1/TH2 cytokine imbalance in CD and suggests different immunological mechanisms in children and adults for disease pathogenesis.

Validation and modification of simplified diagnostic criteria for autoimmune hepatitis in children.

BACKGROUND & AIMS: Criteria for the diagnosis of autoimmune hepatitis (AIH) were formalized in 1993 and revised in 1999. Simplified criteria were developed in 2008 for adults only. We aimed to establish clinically useful diagnostic criteria for AIH in children by validating the 2008 criteria in a pediatric cohort. METHODS: Baseline data were available in 37 and 31 AIH and 40 and 26 non-AIH subjects to calculate 1999 and 2008 criteria, respectively. Sensitivity and specificity of the simplified criteria were calculated using 1999 criteria as the standard for subjects with available data for both criteria. RESULTS: The 1999 standard designated 29 of 31 subjects (94%) as definite AIH and 2 of 31 subjects (6%) as probable AIH. The simplified criteria identified 25 of 31 subjects (81%) as definite AIH, 2 of 31 subjects (6%) as probable AIH. Only 1 of 5 patients with AIH who presented with fulminant hepatic failure (FHF) was identified by the simplified criteria as having AIH. The 2008 diagnostic criteria had a sensitivity of 87% and a specificity of 89% (area under the receiver operating characteristic curve, 0.98). After removing data from patients with FHF from the analysis, the sensitivity increased to 100%. Modifying the 2008 diagnostic criteria to include either level of globulin or immunoglobulin G resulted in a similar sensitivity (92%) and specificity (95%) values (area under the receiver operating characteristic curve, 0.99). CONCLUSIONS: The 2008 criteria diagnose AIH in children with high levels of sensitivity and specificity, and are easier to use in the clinic. Diagnosis of AIH in patients who present in FHF requires the 1999 criteria. Levels of globulin and immunoglobulin G can be used interchangeably in the simplified diagnostic criteria.

Solitary rectal ulcer syndrome in children and adolescents.

OBJECTIVES: The aim of this study was to describe the presenting symptoms, endoscopic and histologic findings, and clinical courses of pediatric patients diagnosed with solitary rectal ulcer syndrome (SRUS). METHODS: We describe 15 cases of SRUS diagnosed at our institution during a 13-year period. Cases were identified by review of a pathology database and chart review and confirmed by review of biopsies. Data were collected by retrospective chart review. RESULTS: Presenting symptoms were consistent but nonspecific, most commonly including blood in stools, diarrhea alternating with constipation, and abdominal/perianal pain. Fourteen of 15 patients had normal hemoglobin/hematocrit, erythrocyte sedimentation rate, and albumin at diagnosis. Endoscopic findings, all limited to the distal rectum, ranged from erythema to ulceration and polypoid lesions. Histology revealed characteristic findings. Stool softeners and mesalamine suppositories improved symptoms, but relapse was common. CONCLUSIONS: SRUS in children presents with nonspecific symptoms and endoscopic findings. Clinical suspicion is required, and diagnosis requires histologic confirmation. Response to present treatments is variable.

Management of portal hypertension in children.

Management of portal hypertension in children has evolved over the past several decades. Portal hypertension can result from intrahepatic or extrahepatic causes. Management should be tailored to the child based on the etiology of the portal hypertension and on the functionality of the liver. The most serious complication of portal hypertension is gastroesophageal variceal bleeding, which has a mortality of up to 30%. Initial treatment of bleeding focuses on stabilizing the patient. Further treatment measures may include endoscopic, medical, or surgical interventions as appropriate for the child, depending on the cause of the portal hypertension. ß-Blockers have not been proven to effectively prevent primary or secondary variceal bleeding in children. Sclerotherapy and variceal band ligation can be used to stop active bleeding and can prevent bleeding from occurring. Transjugular intrahepatic portosystemic shunts and surgical shunts may be reserved for those who are not candidates for transplant or have refractory bleeding despite medical or endoscopic treatment.