Inflammatory Bowel Disease Cause-specific Mortality: A Primer for Clinicians

Background:Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) is perceived to harbor significant morbidity but limited excess mortality, thought to be driven by colon cancer, compared with the general population. Recent studies suggest mortality rates seem higher than previously understood, and there are emerging threats to mortality. Clinicians must be up to date and able to clearly convey the causes of mortality to arm individual patients with information to meaningfully participate in decisions regarding IBD treatment and maintenance of health. Methods:A MEDLINE search was conducted to capture all relevant articles. Keyword search included: “inflammatory bowel disease,” “Crohn's disease,” “ulcerative colitis,” and “mortality.” Results:CD and UC have slightly different causes of mortality; however, malignancy and colorectal cancer–associated mortality remains controversial in IBD. CD mortality seems to be driven by gastrointestinal disease, infection, and respiratory diseases. UC mortality was primarily attributable to gastrointestinal disease and infection. Clostridium difficile infection is an emerging cause of mortality in IBD. UC and CD patients have a marked increase in risk of thromboembolic disease. With advances in medical and surgical interventions, the exploration of treatment-associated mortality must continue to be evaluated. Conclusions:Clinicians should be aware that conventional causes of death such as malignancy do not seem to be as significant a burden as originally perceived. However, emerging threats such as infection including C. difficile are noteworthy. Although CD and UC share similar causes of death, there seems to be some differences in cause-specific mortality.

[1]  I. Kohane,et al.  Mortality and extraintestinal cancers in patients with primary sclerosing cholangitis and inflammatory bowel disease. , 2014, Journal of Crohn's & colitis.

[2]  Siddhant Yadav,et al.  Inflammatory bowel disease is associated with an increased risk of melanoma: a systematic review and meta-analysis. , 2014, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[3]  Subrata Ghosh,et al.  Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies. , 2013, Gastroenterology.

[4]  A. Ananthakrishnan,et al.  Genetic risk factors for Clostridium difficile infection in ulcerative colitis , 2013, Alimentary pharmacology & therapeutics.

[5]  W. Bemelman,et al.  Ten Years of Infliximab for Crohn’s Disease: Outcome in 469 Patients from 2 Tertiary Referral Centers , 2013, Inflammatory bowel diseases.

[6]  M. Cottone,et al.  Systematic review: macrophage activation syndrome in inflammatory bowel disease , 2013, Alimentary pharmacology & therapeutics.

[7]  K. Schmiegelow,et al.  Use of azathioprine and the risk of cancer in inflammatory bowel disease. , 2013, American journal of epidemiology.

[8]  E. Horváth-Puhó,et al.  Five-Year Mortality in Colorectal Cancer Patients with Ulcerative Colitis or Crohn's Disease: A Nationwide Population-based Cohort Study , 2013, Inflammatory bowel diseases.

[9]  T. Tenhave,et al.  Crohn’s Disease and Ulcerative Colitis Are Associated With Elevated Standardized Mortality Ratios: A Meta-Analysis , 2013, Inflammatory bowel diseases.

[10]  A. Ananthakrishnan,et al.  Infection-related hospitalizations are associated with increased mortality in patients with inflammatory bowel diseases. , 2013, Journal of Crohn's & colitis.

[11]  M. Frisch,et al.  Trends in overall and cause-specific mortality among patients with inflammatory bowel disease from 1982 to 2010. , 2013, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[12]  D. Solomon,et al.  Tumor necrosis factor α inhibitor therapy and cancer risk in chronic immune-mediated diseases. , 2013, Arthritis and rheumatism.

[13]  J. Brewer,et al.  Thiopurines and risk of nonmelanoma skin cancer in inflammatory bowel disease. , 2013, JAMA dermatology.

[14]  F. Carrat,et al.  Risk of Melanoma in Patients Who Receive Thiopurines for Inflammatory Bowel Disease Is Not Increased , 2012, The American Journal of Gastroenterology.

[15]  W. Sandborn,et al.  Serious Infection and Mortality in Patients With Crohn's Disease: More Than 5 Years of Follow-Up in the TREAT™ Registry , 2012, The American Journal of Gastroenterology.

[16]  B. V. Pedersen,et al.  Decreasing risk of colorectal cancer in patients with inflammatory bowel disease over 30 years. , 2012, Gastroenterology.

[17]  Christopher F. Martin,et al.  Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. , 2012, Gastroenterology.

[18]  T. Jess Need for improved societal effort to keep inflammatory bowel disease patients in the labour market? , 2012, Gut.

[19]  H. Huhtala,et al.  Mortality in ulcerative colitis and Crohn's disease. A population-based study in Finland. , 2012, Journal of Crohn's & colitis.

[20]  L. Peyrin-Biroulet,et al.  Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies. , 2012, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[21]  P. Rutgeerts,et al.  A Pooled Analysis of Infections, Malignancy, and Mortality in Infliximab- and Immunomodulator-Treated Adult Patients With Inflammatory Bowel Disease , 2012, The American Journal of Gastroenterology.

[22]  R. Erichsen,et al.  Thirty-day mortality after elective and emergency total colectomy in Danish patients with inflammatory bowel disease: a population-based nationwide cohort study , 2012, BMJ Open.

[23]  Subrata Ghosh,et al.  Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. , 2012, Gastroenterology.

[24]  J. Hugot,et al.  Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease. , 2011, Gastroenterology.

[25]  Harminder Singh,et al.  Increased risk of nonmelanoma skin cancers among individuals with inflammatory bowel disease. , 2011, Gastroenterology.

[26]  G. Kaplan,et al.  Postoperative complications and mortality following colectomy for ulcerative colitis. , 2011, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[27]  J. Val Old-age inflammatory bowel disease onset: A different problem? , 2011 .

[28]  M. V. van Oijen,et al.  Risk of nonmelanoma skin cancer in patients with inflammatory bowel disease who use thiopurines is not increased. , 2011, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[29]  G. Nguyen,et al.  Venous Thromboembolism in Inflammatory Bowel Disease: An Epidemiological Review , 2011, The American Journal of Gastroenterology.

[30]  I. Roifman,et al.  Chronic inflammatory diseases and cardiovascular risk: a systematic review. , 2011, The Canadian journal of cardiology.

[31]  D. Rampton,et al.  Systematic review: Clostridium difficile and inflammatory bowel disease , 2011, Alimentary pharmacology & therapeutics.

[32]  U. Navaneethan,et al.  Impact of Clostridium difficile infection in patients with ulcerative colitis. , 2011, Journal of Crohn's & colitis.

[33]  C. Trenor,et al.  Thrombosis and inflammatory bowel disease: A call for improved awareness and prevention , 2011, Inflammatory bowel diseases.

[34]  J. D. del Val,et al.  Old-age inflammatory bowel disease onset: a different problem? , 2011, World journal of gastroenterology.

[35]  H. Tilg,et al.  Inflammatory bowel disease is a risk factor for recurrent venous thromboembolism. , 2010, Gastroenterology.

[36]  P. Dagnelie,et al.  Mortality in inflammatory bowel disease in the Netherlands 1991–2002: Results of a population‐based study: The IBD South‐Limburg cohort† , 2010, Inflammatory bowel diseases.

[37]  H. Ikeuchi,et al.  Surgery for ulcerative colitis in 1,000 patients , 2010, International Journal of Colorectal Disease.

[38]  E. Cabré,et al.  Infliximab safety profile and long‐term applicability in inflammatory bowel disease: 9‐year experience in clinical practice , 2010, Alimentary pharmacology & therapeutics.

[39]  C. Porter,et al.  Increased risk for non-melanoma skin cancer in patients with inflammatory bowel disease. , 2010, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[40]  G. Nguyen,et al.  Increased Prevalence of and Associated Mortality With Methicillin-Resistant Staphylococcus aureus Among Hospitalized IBD Patients , 2010, The American Journal of Gastroenterology.

[41]  P. Munkholm,et al.  Overall and cause‐specific mortality in Crohn's disease: A meta‐analysis of population‐based studies , 2009, Inflammatory bowel diseases.

[42]  E. Loftus,et al.  Safety profile of IBD therapeutics: infectious risks. , 2009, Gastroenterology clinics of North America.

[43]  W. Sandborn,et al.  Adalimumab safety in global clinical trials of patients with Crohn's disease , 2009, Inflammatory bowel diseases.

[44]  A. Ananthakrishnan,et al.  Treatment of Ulcerative Colitis in the Elderly , 2009, Digestive Diseases.

[45]  C. Ha,et al.  Risk of Arterial Thrombotic Events in Inflammatory Bowel Disease , 2009, The American Journal of Gastroenterology.

[46]  S. Steele,et al.  National Trends and Outcomes for the Surgical Therapy of Ileocolonic Crohn’s Disease: A Population-Based Analysis of Laparoscopic vs. Open Approaches , 2009, Journal of Gastrointestinal Surgery.

[47]  N. Harpaz,et al.  Severity of Inflammation as a Predictor of Colectomy in Patients With Chronic Ulcerative Colitis , 2009, Diseases of the colon and rectum.

[48]  Y. Panis,et al.  Impact of Complex Crohn's Disease on the Outcome of Laparoscopic Ileocecal Resection: A Comparative Clinical Study in 124 Patients , 2009, Diseases of the colon and rectum.

[49]  I. Roifman,et al.  Evidence of endothelial dysfunction in patients with inflammatory bowel disease. , 2009, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[50]  T. Concannon,et al.  Epidemiology of Clostridium difficile Colitis in Hospitalized Patients with Inflammatory Bowel Diseases , 2009, Diseases of the colon and rectum.

[51]  A. Ananthakrishnan,et al.  Inflammatory bowel disease in the elderly is associated with worse outcomes: A national study of hospitalizations , 2008, Inflammatory bowel diseases.

[52]  Justina J. Sam,et al.  Rising Prevalence of Venous Thromboembolism and Its Impact on Mortality Among Hospitalized Inflammatory Bowel Disease Patients , 2008, The American Journal of Gastroenterology.

[53]  F. Klebl,et al.  Intraabdominal septic complications following bowel resection for Crohn’s disease: detrimental influence on long-term outcome , 2008, International Journal of Colorectal Disease.

[54]  G. Kaplan,et al.  A National Survey of the Prevalence and Impact of Clostridium difficile Infection Among Hospitalized Inflammatory Bowel Disease Patients , 2008, The American Journal of Gastroenterology.

[55]  G. Meijer,et al.  Retrospective analysis of old-age colitis in the Dutch inflammatory bowel disease population. , 2008, World journal of gastroenterology.

[56]  Beata Wojtczak,et al.  Analysis of results of surgical treatment in Crohn's disease. , 2008, Hepato-gastroenterology.

[57]  P. Hermanek,et al.  Die Chirurgie des Morbus Crohn: Klinische Studie an 155 Patienten mit Darmresektionen , 2008 .

[58]  G. Kaplan,et al.  Impact of hospital volume on postoperative morbidity and mortality following a colectomy for ulcerative colitis. , 2008, Gastroenterology.

[59]  C. Bernstein,et al.  The incidence of arterial thromboembolic diseases in inflammatory bowel disease: a population-based study. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[60]  P. Munkholm,et al.  Changes in Clinical Characteristics, Course, and Prognosis of Inflammatory Bowel Disease during the Last 5 Decades: A Population‐Based Study from Copenhagen, Denmark , 2007, Inflammatory bowel diseases.

[61]  T. Sørensen,et al.  Overall and Cause-Specific Mortality in Ulcerative Colitis: Meta-analysis of Population-Based Inception Cohort Studies , 2007, The American Journal of Gastroenterology.

[62]  R. Sandler,et al.  Inflammatory Bowel Disease Is Not a Risk Factor for Cardiovascular Disease Mortality: Results from a Systematic Review and Meta-Analysis , 2007, The American Journal of Gastroenterology.

[63]  K. Abrams,et al.  Meta‐analysis: mortality in Crohn’s disease , 2007, Alimentary pharmacology & therapeutics.

[64]  K. Abrams,et al.  Long‐term prognosis in Crohn's disease: an epidemiological study of patients diagnosed more than 20 years ago in Cardiff , 2007, Alimentary pharmacology & therapeutics.

[65]  H. Sørensen,et al.  Survival After Colorectal Cancer in Patients with Crohn's Disease: A Nationwide Population-Based Danish Follow-Up Study , 2007, The American Journal of Gastroenterology.

[66]  L. Melton,et al.  Survival and cause specific mortality in patients with inflammatory bowel disease: a long term outcome study in Olmsted County, Minnesota, 1940–2004 , 2006, Gut.

[67]  W. Sandborn,et al.  Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry. , 2006, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[68]  L. Nyström,et al.  Excess mortality in incident cases of diabetes mellitus aged 15 to 34 years at diagnosis: a population-based study (DISS) in Sweden , 2006, Diabetologia.

[69]  L. Nyström,et al.  Excess mortality in incident cases of diabetes mellitus aged 15 to 34 years at diagnosis: a population-based study (DISS) in Sweden , 2006, Diabetologia.

[70]  J. Si,et al.  Clinical presentation of inflammatory bowel disease: a hospital based retrospective study of 379 patients in eastern China. , 2005, Chinese medical journal.

[71]  E. Loftus Management of extraintestinal manifestations and other complications of inflammatory bowel disease , 2004, Current gastroenterology reports.

[72]  D. Palli,et al.  Divergent patterns of total and cancer mortality in ulcerative colitis and Crohn’s disease patients: the Florence IBD study 1978–2001 , 2004, Gut.

[73]  V. Binder Epidemiology of IBD during the twentieth century: an integrated view. , 2004, Best practice & research. Clinical gastroenterology.

[74]  W. Sandborn,et al.  Venous Thromboembolism in Inflammatory Bowel Disease , 2004, American Journal of Gastroenterology.

[75]  P. Munkholm,et al.  Survival and cause-specific mortality in ulcerative colitis: follow-up of a population-based cohort in Copenhagen County. , 2003, Gastroenterology.

[76]  P. Munkholm Review article: the incidence and prevalence of colorectal cancer in inflammatory bowel disease , 2003, Alimentary pharmacology & therapeutics.

[77]  F. Carbonnel,et al.  Long-Term Evolution of Disease Behavior of Crohn's Disease , 2002, Inflammatory bowel diseases.

[78]  D. Maki,et al.  The Commonality of Risk Factors for Nosocomial Colonization and Infection with Antimicrobial-Resistant Staphylococcus aureus, Enterococcus, Gram-Negative Bacilli, Clostridium difficile, and Candida , 2002, Annals of Internal Medicine.

[79]  C. Kelly,et al.  Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[80]  B. Armstrong,et al.  The epidemiology of UV induced skin cancer. , 2001, Journal of photochemistry and photobiology. B, Biology.

[81]  I. Grimm,et al.  Inflammatory bowel disease in the elderly. , 2001, Gastroenterology clinics of North America.

[82]  H. Freeman Colorectal cancer complicating Crohn's disease. , 2001, Canadian journal of gastroenterology = Journal canadien de gastroenterologie.

[83]  C. Bernstein,et al.  The Incidence of Deep Venous Thrombosis and Pulmonary Embolism among Patients with Inflammatory Bowel Disease: A Population-based Cohort Study , 2001, Thrombosis and Haemostasis.

[84]  C. Bernstein Neoplastic and other complications of inflammatory bowel disease , 2000, Current gastroenterology reports.

[85]  A. Zinsmeister,et al.  Ulcerative colitis in Olmsted County, Minnesota, 1940–1993: incidence, prevalence, and survival , 2000, Gut.

[86]  A. Zinsmeister,et al.  Erratum: Crohn's disease in Olmsted County, Minnesota, 1940-1993: Incidence, prevalence, and survival (Gastroenterology (1998) 114 (1161- 1168)) , 1999 .

[87]  A. Zinsmeister,et al.  Crohn's disease in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival. , 1998, Gastroenterology.

[88]  D. Palli,et al.  General and cancer specific mortality of a population based cohort of patients with inflammatory bowel disease: the Florence study , 1998, Gut.

[89]  P. Munkholm,et al.  Inflammatory bowel diseases with onset in childhood. Clinical features, morbidity, and mortality in a regional cohort. , 1997, Scandinavian journal of gastroenterology.

[90]  P. Prior,et al.  Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis. , 1994, Gut.

[91]  D. Sachar,et al.  Cancer in Crohn's disease: dispelling the myths. , 1994, Gut.

[92]  M. Webberley,et al.  Thromboembolism in inflammatory bowel disease: role of platelets. , 1993, Gut.

[93]  P. Munkholm,et al.  Colorectal cancer risk and mortality in patients with ulcerative colitis. , 1992, Gastroenterology.

[94]  D. Sachar,et al.  Malignant melanoma in inflammatory bowel disease. , 1992, The American journal of gastroenterology.

[95]  G. Whelan Ulcerative colitis--what is the risk of developing colorectal cancer? , 1991, Australian and New Zealand journal of medicine.

[96]  Robert H. Collins,et al.  Colon cancer, dysplasia, and surveillance in patients with ulcerative colitis. A critical review. , 1987, The New England journal of medicine.

[97]  R. Beart,et al.  Vascular complications of inflammatory bowel disease. , 1986, Mayo Clinic proceedings.

[98]  L. Brandt,et al.  Clinical characteristics and natural history of colitis in the elderly. , 1982, The American journal of gastroenterology.

[99]  N. Carr,et al.  Inflammatory bowel disease in the older patient , 1982, The British journal of surgery.

[100]  P. Hermanek,et al.  [Surgery of Crohn's disease: a study of 155 patients after intestinal resection (author's transl)]. , 1981, Deutsche medizinische Wochenschrift.

[101]  D. Sackett,et al.  Cancer risk in ulcerative colitis: scientific requirements for the study of prognosis. , 1980, Gastroenterology.

[102]  V. Rusch,et al.  Crohn's disease in the older patient. , 1980, Surgery, gynecology & obstetrics.

[103]  P. Prior Malignancy in crohn's disease. , 1972, British journal of preventive & social medicine.

[104]  Wantz Ge,et al.  Ulcerative colitis in the elderly patient. , 1968 .

[105]  A. Diethelm,et al.  Ulcerative colitis in the elderly patient. , 1968, Surgery, gynecology & obstetrics.

[106]  R. Gage,et al.  Life histories of patients with chronic ulcerative colitis: a review of 2,000 cases. , 1968, Gastroenterology.

[107]  Sloan Wp,et al.  Life histories of patients with chronic ulcerative colitis: a review of 2,000 cases. , 1950 .

[108]  B. Crohn,et al.  The sigmoidoscopic picture of chronic ulcerative colitis (non-specific) , 1925 .