Predicting relapse in Crohn’s disease: a biopsychosocial model

Background: Crohn’s disease (CD) is a chronic relapsing inflammatory bowel disorder. Both biological and psychosocial factors may modulate the illness experience. Aim: The aim of this study was to identify clinical, biological and psychosocial parameters as predictors of clinical relapse in quiescent CD. Methods: Patients in medically induced remission were followed prospectively for 1 year, or less if they relapsed. Disease characteristics were determined at baseline. Serum cytokines, anti-Saccharomyces cerevisiae antibodies, C-reactive protein (CRP), erythrocyte sedimentation rate and intestinal permeability were measured every 3 months. Psychological distress, perceived stress, minor life stressors and coping strategies were measured monthly. A time-dependent multivariate Cox regression model determined predictors of time to relapse. Results: 101 patients (60 females, 41 males) were recruited. Fourteen withdrew and 37 relapsed. CRP (HR = 1.5 per 10 mg/l, 95% CI 1.1 to 1.9, p = 0.007), fistulising disease (HR = 3.2, 95% CI, 1.1 to 9.4, p = 0.04), colitis (HR = 3.5 95% CI 1.2 to 9.9, p = 0.02) and the interaction between perceived stress and avoidance coping (HR = 7.0 per 5 unit increase for both scales, 95% CI 2.3 to 21.8, p = 0.003) were predictors of earlier relapse. Conclusions: In quiescent CD, a higher CRP, fistulising disease behaviour and disease confined to the colon were independent predictors of relapse. Moreover, patients under conditions of low stress and who scored low on avoidance coping (ie, did not engage in social diversion or distraction) were least likely to relapse. This study supports a biopsychosocial model of CD exacerbation.

[1]  J. Mawdsley,et al.  RECENT ADVANCES IN BASIC SCIENCE PSYCHOLOGICAL STRESS IN IBD: NEW INSIGHTS INTO PATHOGENIC AND THERAPEUTIC IMPLICATIONS , 2005 .

[2]  S. Kreiner,et al.  Alimentary tract andpancreas Prognosis inCrohn's disease -based onresults froma regional patient group fromthecounty ofCopenhagen , 1985 .

[3]  R. Sylvester,et al.  Identifying patients with a high risk of relapse in quiescent Crohn's disease. The GETAID Group. The Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives. , 1995, Gut.

[4]  A. Prada,et al.  Controlled trial of oral 5‐aminosalicylic acid for the prevention of early relapse in Crohn's disease , 1997, Alimentary pharmacology & therapeutics.

[5]  C. Fernández-Rodríguez,et al.  A stress management programme for Crohn's disease. , 2004, Behaviour research and therapy.

[6]  Paul Bennett,et al.  Psychological factors and inflammatory bowel disease: A review of a decade of literature , 2001 .

[7]  G. Corrao,et al.  Intestinal permeability test as a predictor of clinical course in Crohn's disease , 1999, American Journal of Gastroenterology.

[8]  M. Samsom,et al.  Serotonin synthesis and uptake in symptomatic patients with Crohn's disease in remission. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[9]  J. Wright,et al.  Predictors of acute relapse of Crohn's disease , 1987, Digestive Diseases and Sciences.

[10]  C. Mittermaier,et al.  Impact of Depressive Mood on Relapse in Patients With Inflammatory Bowel Disease: A Prospective 18-Month Follow-Up Study , 2004, Psychosomatic medicine.

[11]  Michael Weiner,et al.  Moderating Effects of Coping on the Relationship Between Stress and the Development of New Brain Lesions in Multiple Sclerosis , 2002, Psychosomatic medicine.

[12]  J. Schölmerich,et al.  The role of the sympathetic nervous system in intestinal inflammation , 2006, Gut.

[13]  S. Folkman,et al.  The impact of daily stress on health and mood: psychological and social resources as mediators. , 1988, Journal of personality and social psychology.

[14]  T. Kamarck,et al.  A global measure of perceived stress. , 1983, Journal of health and social behavior.

[15]  D. Drossman,et al.  Biopsychosocial issues in irritable bowel syndrome. , 2005, Journal of clinical gastroenterology.

[16]  J. Pollard,et al.  A review of stress-relapse interactions in multiple sclerosis: important features and stress-mediating and -moderating variables , 2005, Multiple sclerosis.

[17]  E. Loftus Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. , 2004, Gastroenterology.

[18]  M. Sans,et al.  Inflammatory bowel disease: the role of environmental factors. , 2004, Autoimmunity reviews.

[19]  G. L. Engel The need for a new medical model: a challenge for biomedicine , 1977 .

[20]  J. Belaiche,et al.  Soluble interleukin-2 receptor in Crohn's disease. Assessment of disease activity and prediction of relapse. , 1995, Digestive diseases and sciences.

[21]  A. Forbes,et al.  Functional symptoms in inflammatory bowel disease and their potential influence in misclassification of clinical status , 2005, Alimentary pharmacology & therapeutics.

[22]  I. Bjarnason,et al.  Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. , 2000, Gastroenterology.

[23]  J. Andrews,et al.  Antidepressants and inflammatory bowel disease: a systematic review , 2006, Clinical practice and epidemiology in mental health : CP & EMH.

[24]  Impaired Synthesis or Cellular Storage of Norepinephrine, Dopamine, and 5-Hydroxytryptamine in Human Inflammatory Bowel Disease , 2004, Digestive Diseases and Sciences.

[25]  M. Singer,et al.  Predictors of disease-related concerns and other aspects of health-related quality of life in outpatients with inflammatory bowel disease , 2004, European journal of gastroenterology & hepatology.

[26]  F Kern,et al.  Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. , 1976, Gastroenterology.

[27]  I. Arnott,et al.  Abnormal Intestinal Permeability Predicts Relapse in Inactive Crohn Disease , 2000, Scandinavian journal of gastroenterology.

[28]  R. Modigliani,et al.  A simple biological score for predicting low risk of short‐term relapse in Crohn's disease , 2006, Inflammatory bowel diseases.

[29]  C. Prantera,et al.  Oral 5-aminosalicylic acid (Asacol) in the maintenance treatment of Crohn's disease , 1992 .

[30]  M. Portella,et al.  Life Events and Inflammatory Bowel Disease Relapse: A Prospective Study of Patients Enrolled in Remission , 2006, The American Journal of Gastroenterology.

[31]  H. Kessler,et al.  Psychotherapy with chronic inflammatory bowel disease patients: A Review , 2006, Inflammatory bowel diseases.

[32]  Sheldon Cohen,et al.  Keynote presentation at the eight international congress of behavioral medicine Mainz, Germany August 25–28, 2004 , 2005, International journal of behavioral medicine.

[33]  J. Berlin,et al.  Risk factors for early postoperative recurrence of Crohn's disease. , 1998, Gastroenterology.

[34]  Izabela Sorić,et al.  Coping Inventory for Stressful Situations (CISS) , 2002 .

[35]  A. Petrie,et al.  Serum levels of C‐reactive protein in Crohn's disease and ulcerative colitis , 1982, European journal of clinical investigation.

[36]  Sheldon Cohen Perceived stress in a probability sample of the United States , 1988 .

[37]  J. Lennard-jones,et al.  Classification of inflammatory bowel disease. , 1989, Scandinavian journal of gastroenterology. Supplement.

[38]  R. Lazarus,et al.  Comparison of two modes of stress measurement: Daily hassles and uplifts versus major life events , 1981, Journal of Behavioral Medicine.

[39]  Ronald C. Kessler,et al.  Strategies for measuring stress in studies of psychiatric and physical disorders. , 1995 .

[40]  Stuart Oskamp,et al.  The social psychology of health , 1990 .

[41]  J. Meddings Barrier Dysfunction and Crohn's Disease , 2000, Annals of the New York Academy of Sciences.

[42]  Samir A. Shah,et al.  Psychosocial determinants of relapse in ulcerative colitis: a longitudinal study , 2003, American Journal of Gastroenterology.

[43]  N. Endler,et al.  Stress, anxiety and coping: The multidimensional interaction model. , 1997 .

[44]  A. Cohen,et al.  Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis. , 2001, Gastroenterology.

[45]  G. Bouma,et al.  The immunological and genetic basis of inflammatory bowel disease , 2003, Nature Reviews Immunology.

[46]  R. Maunder Evidence that Stress Contributes to Inflammatory Bowel Disease: Evaluation, Synthesis, and Future Directions , 2005, Inflammatory bowel diseases.

[47]  J. Belaiche,et al.  A high serum concentration of interleukin‐6 is predictive of relapse in quiescent Crohn's disease , 1997, European journal of gastroenterology & hepatology.

[48]  J. Moskowitz,et al.  Coping: pitfalls and promise. , 2004, Annual review of psychology.

[49]  Karina W Davidson,et al.  The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology. , 2005, Journal of the American College of Cardiology.

[50]  P. Munkholm,et al.  Disease activity courses in a regional cohort of Crohn's disease patients. , 1995, Scandinavian journal of gastroenterology.

[51]  J. Belaiche,et al.  Frequently relapsing Crohn's disease is characterized by persistent elevation in interleukin-6 and soluble interleukin-2 receptor serum levels during remission , 2000, International Journal of Colorectal Disease.

[52]  J. Kennedy,et al.  A SmaI PCR-RFLP in the 5' noncoding region of the human D4 dopamine receptor gene (DRD4). , 1994, Human heredity.

[53]  P. Rutgeerts,et al.  The role of C-reactive protein as an inflammatory marker in gastrointestinal diseases , 2005, Nature Clinical Practice Gastroenterology &Hepatology.

[54]  J. Kiecolt-Glaser,et al.  Stress-induced immune dysfunction: implications for health , 2005, Nature Reviews Immunology.

[55]  R. Clouse,et al.  Do life events or depression exacerbate inflammatory bowel disease? A prospective study. , 1991, Annals of internal medicine.

[56]  J. Jørgensen, P. J. Ranløv, P. J. Bjerrum, H. Diem Is an Increased Intestinal Permeability a Valid Predictor of Relapse in Crohn Disease? , 2001 .

[57]  N. Endler,et al.  Coping with Health Problems: Developing a Reliable and Valid Multidimensional Measure. , 1998 .

[58]  J. von Wietersheim,et al.  [The significance of recurrence-inducing events for patients with chronic inflammatory bowel diseases. Results of a prospective longitudinal study over three years]. , 1994, Psychotherapie, Psychosomatik, medizinische Psychologie.

[59]  R. Hilsden,et al.  Intestinal permeability changes in response to acetylsalicylic acid in relatives of patients with Crohn's disease. , 1996, Gastroenterology.

[60]  S. Fais,et al.  The clinical significance of serum C reactive protein levels in Crohn's disease. Results of a prospective longitudinal study. , 1988, Journal of clinical gastroenterology.