Ulcerative Colitis: Thompson R

Summers RW, Elliott DE, Qadir K, Urban JF, Thompson R, Weinstock JV. · Department of Internal Medicine, James A. Clifton Center for Digestive Diseases, University of Iowa Health Care, Iowa City, Iowa, USA. · Am J Gastroenterol. · Pubmed #14499784 No free full text.

Abstract: OBJECTIVES: Inflammatory bowel disease (IBD), especially Crohn's disease (CD), probably results from failure to downregulate a chronic Th1 intestinal inflammatory process. Induction of a Th2 immune response by intestinal helminths diminishes Th1 responsiveness. This study evaluates the safety and effectiveness of helminthic ova in the treatment of active IBD. METHODS: We studied four patients with active CD and three with ulcerative colitis (UC). In an initial treatment and observation period, a single dose of 2500 live Trichuris suis eggs was given orally, and patients were followed every 2 wk for 12 wk. Baseline medications were continued at the same dose throughout the study. Safety was monitored by following the patients' clinical status and laboratory studies at regular intervals. Patients also were monitored regularly using the Crohn's Disease Activity Index, Simple Clinical Colitis Activity Index (SCCAI), and the Inflammatory Bowel Disease Quality of Life Index (IBDQ). To assess safety and efficacy with repetitive doses, two patients with CD and two with UC were given 2500 ova at 3-wk intervals as maintenance treatment using the same evaluation parameters. RESULTS: During the treatment and observation period, all patients improved clinically without any adverse clinical events or laboratory abnormalities. Three of the four patients with CD entered remission according to the Crohn's Disease Activity Index; the fourth patient experienced a clinical response (reduction of 151) but did not achieve remission. Patients with UC experienced a reduction of the Clinical Colitis Activity Index to 57% of baseline. According to the IBD Quality of Life Index, six of seven patients (86%) achieved remission. The benefit derived from the initial dose was temporary. In the maintenance period, multiple doses again caused no adverse effects and sustained clinical improvement in all patients treated every 3 wk for >28 wk. CONCLUSIONS: This open trial demonstrates that it is safe to administer eggs from the porcine whipworm, Trichuris suis, to patients with CD and UC. It also demonstrates improvement in the common clinical indices used to describe disease activity. The benefit was temporary in some patients with a single dose, but it could be prolonged with maintenance therapy every 3 wk. The study suggests that it is possible to downregulate aberrant intestinal inflammation in humans with helminths.

Severs GA, Lawlor TH, Purcell SM, Adler DJ, Thompson R. · Lehigh Valley Hospital-Muhlenberg, Bethlehem, Pennsylvania, USA. · Cutis. · Pubmed #17956013 No free full text.

Abstract: Infliximab is a chimeric immunoglobulin G1kappa monoclonal antibody against tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine that participates in both normal immune function and the pathogenesis of many autoimmune disorders. Treatment with infliximab reduces the biologic activities of TNF-alpha and thus is indicated in the treatment of rheumatoid arthritis, Crohn disease, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and ulcerative colitis. To our knowledge, there have been 13 case reports of new-onset psoriasis, psoriasiform dermatitis, and palmoplantar pustular psoriasis that developed during treatment with infliximab. We report 3 additional cases of biopsy-proven new-onset psoriasis that developed while the patients underwent treatment with infliximab for inflammatory bowel disease. Although the mechanism for the development of psoriasis in these patients is unclear, several possible explanations are proposed. With increasing use of infliximab and other TNF-alpha inhibitors in clinical practice, more cases of similar reactions to these drugs probably will be reported and are necessary to determine the importance of this eruption.

Carvalho RS, Abadom V, Dilworth HP, Thompson R, Oliva-Hemker M, Cuffari C. · Johns Hopkins University School of Medicine, Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Baltimore, MD 21287, USA. · Inflamm Bowel Dis. · Pubmed #16633047 links to  free full text

Abstract: BACKGROUND: Indeterminate colitis (IC) is a subgroup of inflammatory bowel disease (IBD) that cannot be characterized as either ulcerative colitis (UC) or Crohn's disease (CD). Our aims are to determine the prevalence of IC in our pediatric patient population and to describe its clinical presentation, natural history,and disease distribution. METHODS: We performed a retrospective database analysis of all children diagnosed with IBD at the Johns Hopkins Children's IBD Center between 1996 and 2001. Patient demographics, including age, sex, and age at disease onset, were tallied. Disease distribution was identified on the basis of a review of all endoscopic, colonoscopic, histopathological, and radiological records. All of the patients were followed up clinically to determine the extent of disease progression on the basis of the initial diagnosis of IC. RESULTS: Among 250 children registered in the database, 127 (50.8%) had a diagnosis of CD, 49 (19.6%) had UC, and 74(29.6%) had IC. Patients with IC had a significantly younger mean +/- SEM age (9.53 +/- 4.8 years) at diagnosis compared with patients with CD (12.4 +/- 3.8 years; P < 0.001) but not compared with patients with UC (7.41 +/- 3.5 years). Among the patients with IC, 59 (79.7%) had a pancolitis at diagnosis, and the remaining 15 had left-sided disease that progressed to a pancolitis within a mean of 6 years. Twenty-five patients (33.7%) with an initial diagnosis of IC were reclassified to either CD or UC after a median follow-up of 1.9 years (range 0.6-4.5 years). Forty-nine patients (66.2%) maintained their diagnosis of IC after a mean follow-up of 7 years (SEM 2.5 years). CONCLUSIONS: IC is a distinct pediatric subgroup of IBD with a prevalence that is higher than that observed in adults. Children with IC have an early age of disease onset and a disease that rapidly progresses to pancolitis. Longitudinal studies are needed to determine the clinical implications of this pediatric IBD subgroup.

Whittall T, Wang Y, Kelly CG, Thompson R, Sanderson J, Lomer M, Soon SY, Bergmeier LA, Singh M, Lehner T. · Mucosal Immunology Unit and Dept. of Oral Immunology, Guy's, King's and St Thomas' Medical and Dental Schools, Guy's Hospital, London SE1 9RT, UK. · Clin Exp Immunol. · Pubmed #16487255 links to  free full text

Abstract: Summaryand interleukin (IL)-12 by dendritic cells (DC) from patients with Crohn's disease. TNF-alpha concentration was increased significantly when DC from Crohn's disease were stimulated with HSP70 or CD40L and this was associated with signalling by the extracellular signal regulated kinase (ERK) 1/2 and p38 mitogen activated protein (MAP) kinase pathway. IL-12 production was also increased when DC were stimulated with HSP70. Cells eluted from inflamed intestinal mucosa from Crohn's disease, stimulated with HSP70, CD40L or lipopolysaccharide produced significantly greater TNF-alpha and IL-12 concentrations than cells from uninflamed mucosa. Significant inhibition of TNF-alpha production was demonstrated when DC from peripheral blood mononuclear cells or cells eluted from intestinal mucosa of Crohn's disease were treated with either the HSP70 inhibitory peptide (aa 457-496) or peptides derived from CD40 and CD40L. These inhibitory peptides target the CD40-CD40L and the emerging CD40-HSP70 co-stimulatory pathway. Our findings offer a novel strategy to prevent excessive production of TNF-alpha in Crohn's disease.

Darbari A, Sena L, Argani P, Oliva-Hemker JM, Thompson R, Cuffari C. · Department of Pediatrics, The Johns Hopkins University, Baltimore, MD 21287, USA. · Inflamm Bowel Dis. · Pubmed #15168803 No free full text.

Abstract: BACKGROUND: Recent advances in gadolinium-enhanced magnetic resonance imaging (G-MRI) have been developed to enhance the resolution of the intestinal mucosa and facilitate the differentiation of ulcerative colitis (UC) from Crohn's disease (CD). The objective of this study is to apply this technology in Pediatrics. METHODS: A G-MRI was performed on 58 consecutive children with suspected IBD between 1999 and 2002 using intravenous gadolinium, fat suppression, and respiration-suspended sequences to enhance the resolution of the intestinal wall. The sensitivity and specificity in diagnosing either UC or CD was determined by comparing the G-MRI to the established histologic diagnosis. RESULTS: G-MRI confirmed the diagnosis of either CD (21) or UC (7) with a sensitivity and specificity of 96% and 92%, respectively. Among the 21 patients with CD, 14 showed proximal small bowel involvement by G-MRI. In total, 17 patients were diagnosed with indeterminate colitis (IC) based on histologic criteria alone, and among these patients, G-MRI had a significantly lower non-classification rate (P < 0.02). In comparison, endoscopy was less sensitive (57%), but more specific (100%) than either histology or G-MRI in diagnosing IBD. G-MRI also showed a strong concordance with computed tomography in diagnosing CD (P = 0.001). CONCLUSION: G-MRI is a both a sensitive and specific radiologic tool in diagnosing pediatric IBD. In patients with CD, G-MRI may be useful in identifying proximal small bowel involvement. Longitudinal follow-up studies are needed in those patients diagnosed with IC to determine the predictive value of G-MRI testing.