Karen A. Chachu, MD, PhD

 

Inflammatory bowel disease (IBD) consists of two chronic inflammatory diseases, Crohn’s disease (CD) and ulcerative colitis (UC), as well as a small category of patients (~10%) who have atypical features called IBD-unclassified (IBD-U) or indeterminate colitis. The prevalence of IBD ranges from 0.3% to 0.5% overall in North America and Europe.¹ In North America, the incidences of CD and UC are estimated to be 3.1 to 14.6 per 100,000 person-years and 2.2 to 14.3 cases per 100,000 person-years, respectively; similar rates are seen in Europe.² However, incidences up to 19.2 and 20.2 per 100,000 for UC and CD, respectively, have been reported in Canada.3^,4 The incidences of both UC and CD are increasing over time in Western countries and in rapidly industrializing countries throughout Asia and South America.^5-8

With the increased incidence and advances in the treatment of IBD, many more patients are being treated with corticosteroids, immunomodulators, and biologics. Over time, there has also evolved an understanding of the importance of health maintenance in IBD patients, especially since patients with IBD receive fewer recommended preventive health services than general medical patients even though the use of immunosuppression is an argument for more attention to these issues.⁹ Gastroenterologists may see patients more frequently than their primary care provider (PCP) or PCPs may be unaware of the specific needs of IBD patients. Therefore, it is important that gastroenterologists are knowledgeable about the health maintenance recommendations that can be made to patients and to communicate these to PCPs. Recent society guidelines endorse the importance of this aspect of our practice.¹⁰ The discussion below highlights health maintenance issues that should be fundamental aspects of our IBD practices, however it does not address colon cancer screening and surveillance since these are beyond the scope of this article.
 

Influenza vaccine and pneumococcal vaccine

Influenza A and B outbreaks are commonly seen during the fall and early spring and risk factors for pneumonia and hospitalization include older age, chronic medical conditions, and immunosuppression. The CDC now recommend annual influenza vaccination for all individuals older than six months. For patients on immunosuppression, the vaccine administered should be the inactivated vaccine, as live attenuated vaccines should not be administered to these patients.

Copyright Shawn Rocco

Patients with IBD are also at an increased risk of bacterial pneumonia, the most common etiology of which is pneumococcal pneumonia.¹¹ The Advisory Committee on Immunization Practices (ACIP) recommends that patients on immunosuppression receive a one-time dose of the pneumococcal conjugate vaccine PCV13, followed by a dose of the pneumococcal polysaccharide vaccine PPSV23 one year later (eight weeks at the earliest). A second dose of PPSV23 should be given five years later and a third dose after 65 years of age.

In IBD patients, the influenza and pneumococcal vaccines are both well tolerated without an increased rate of adverse effects over the general population and without an increased risk of IBD flares after vaccination.¹² A common question for patients on biologic therapy is whether the vaccine should be timed at a specific point in the dose cycle. For infliximab, and likely other biologics, the timing does not change the vaccine immunogenicity and patients should be given these vaccines regardless of where they are in the cycle of administration of their biologic.¹³ In addition, there is significant response to influenza and pneumococcal vaccines in patients on combination therapy with immunomodulators and anti-TNFs and concerns about a lack of response to vaccines should not discourage vaccination since benefits are still acquired by patients even if immunogenicity is somewhat decreased.^14,15

Other vaccinations

In addition to the influenza and pneumococcal vaccines, adult and pediatric patients with IBD should follow the ACIP recommendations for tetanus, diphtheria, pertussis (Tdap), Td boosters, hepatitis A, hepatitis B, human papilloma virus (HPV), and meningococcal vaccinations.^16,17

Live vaccines including measles mumps rubella (MMR), varicella, and zoster vaccines are in general contraindicated in immunosuppressed patients on corticosteroids, azathioprine/6-mercaptopurine, methotrexate, anti-TNF, and anti-integrin biologics. An inactive varicella-zoster vaccine will likely be available in the near future and may obviate the need for the live vaccine, which is an important development given the increased risk of zoster in patients with IBD on immunosuppression.¹⁸

Osteoporosis screening

Copyright Shawn Rocco

Both men and women with IBD have an elevated risk of osteoporosis and osteopenia as well as elevated fracture risk.¹⁹ This is related to frequent chronic corticosteroid use, chronic inflammation (high disease activity), women with low BMI, smoking, older age (women > 65, men >70), terminal ileal disease or resection in patients with CD, and proctocolectomy and ileal pouch-anal anastomosis in patients with UC. The recommendations are to obtain baseline bone density evaluation only in patients with risk factors, including young patients since osteopenia can be present at a young age. If If osteopenia is noted, then calcium (1000-1200mg daily) and vitamin D (1000-4000IU daily) supplementation can be associated with improvement in osteopenia.²⁰ If osteoporosis is noted, patients should be referred to rheumatology or endocrinology for evaluation for bisphosphonate therapy which is also associated with improved outcomes.²¹ Bone density testing should be repeated every two years in patients with osteoporosis on treatment and less frequently when there is improvement.²² Given the association of bone metabolism disorders with smoking, this is one more reason to encourage our patients to quit.

 

Skin cancer screening

Multiple studies have demonstrated that immunosuppression, especially with methotrexate and azathioprine/6-mercaptopurine (6MP) is a risk factor for the development of initial and recurrent non-melanoma skin cancer (NMSC) in IBD patients, the data for biologics are less definitive.^23-25 In addition, biologics are associated with increased risk of melanoma in IBD.²⁶ The elevated risk of skin cancer begins in the first year of treatment with thiopurines and may continue after discontinuation. On the basis of this data, screening for melanoma and NMSC is recommended in IBD patients on immunosuppression. Especially for patients on thiopurines it is reasonable for the initial dermatologist visit to occur in the first year of treatment and thereafter with at least annual visits for a full body skin examination. In addition, it is reasonable to recommend regular sunscreen use and protective clothing such as hats.

Cervical cancer screening

A recent meta-analysis shows that women with IBD on immunosuppression have an increased risk of cervical high grade dysplasia and cervical cancer.²⁷ HPV is the major risk factor for cervical cancer and is necessary for its development. The current American College of Gynecology guidelines for women on immunosuppression are to start cervical cancer screening at 21 and annual screening thereafter with Pap and HPV testing.²⁸

Smoking

Smoking has well known associations with poor outcomes in the general population such as increased risk of lung and pancreatic cancers, as well as high risk of cardiovascular disease. In addition, smoking has risks specific to IBD. In CD, smoking is associated with increased disease activity, increased risk of post-operative recurrence, and increased severity of disease.²⁹ Smoking cessation is associated with improved long-term disease outcomes and less risk.³⁰ Making it a point to regularly discuss smoking cessation and partnering with PCPs to offer evidence-based quitting aids may be one of our most significant and beneficial interventions.

Depression and anxiety

Several studies have shown high levels of depression and anxiety in IBD patients and higher levels of depression are associated with increased symptoms, clinical recurrence, poor quality of life and decreased social support.^31-33 A recent systematic review of several studies suggested that antidepressants use in IBD patients benefits their mental health and may improve their clinical course as well.³⁴ As such, screening for depression and anxiety regularly and either offering treatment or referral to psychiatrists and psychologists for further management is recommended.¹⁰

Conclusion

Patients with IBD frequently develop long-term relationships with their gastroenterologists due to their lifelong chronic disease. It is therefore incumbent on us to be attentive to issues related to IBD patients’ preventive care and collaborate with PCPs to coordinate care for our patients since many of these interventions have both short-term and long-term benefits.

Dr. Chachu is assistant professor and gastroenterologist at Duke University, Durham, N.C.

References

1. Kaplan GG, Ng SC. Understanding and Preventing the Global Increase of Inflammatory Bowel Disease. Gastroenterology. 2017;152(2):313-21.e2.

2. Loftus EV, Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology. 2004;126(6):1504-17.

3. Bernstein CN, Wajda A, Svenson LW, et al. The Epidemiology of Inflammatory Bowel Disease in Canada: A Population-Based Study. The American journal of gastroenterology. 2006;101(7):1559-68.

4. Lowe AM, Roy PO, M BP, et al. Epidemiology of Crohn’s disease in Quebec, Canada. Inflammatory bowel diseases. 2009;15(3):429-35.

5. Kappelman MD, Rifas-Shiman SL, Kleinman K, et al. The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2007;5(12):1424-9.

6. Kappelman MD, Moore KR, Allen JK, et al. Recent trends in the prevalence of Crohn’s disease and ulcerative colitis in a commercially insured US population. Digestive diseases and sciences. 2013;58(2):519-25.

7. Ng SC, Kaplan G, Banerjee R, et al. 78 Incidence and Phenotype of Inflammatory Bowel Disease From 13 Countries in Asia-Pacific: Results From the Asia-Pacific Crohn’s and Colitis Epidemiologic Study 2011-2013. Gastroenterology.150(4):S21.

8. Parente JML, Coy CSR, Campelo V, et al. Inflammatory bowel disease in an underdeveloped region of Northeastern Brazil. World Journal of Gastroenterology : WJG. 2015;21(4):1197-206.

9. Selby L, Kane S, Wilson J, et al. Receipt of preventive health services by IBD patients is significantly lower than by primary care patients. Inflammatory bowel diseases. 2008;14(2):253-8.

10. Farraye FA, Melmed GY, Lichtenstein GR, et al. ACG Clinical Guideline: Preventive Care in Inflammatory Bowel Disease. The American journal of gastroenterology. 2017;112(2):241-58.

11. Long MD, Martin C, Sandler RS, et al. Increased risk of pneumonia among patients with inflammatory bowel disease. The American journal of gastroenterology. 2013;108(2):240-8.

12. Rahier JF, Papay P, Salleron J, et al. H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy. Gut. 2011;60(4):456-62.

13. deBruyn J, Fonseca K, Ghosh S, et al. Immunogenicity of Influenza Vaccine for Patients with Inflammatory Bowel Disease on Maintenance Infliximab Therapy: A Randomized Trial. Inflammatory bowel diseases. 2016;22(3):638-47.

14. Brezinschek HP, Hofstaetter T, Leeb BF, et al. Immunization of patients with rheumatoid arthritis with antitumor necrosis factor alpha therapy and methotrexate. Current opinion in rheumatology. 2008;20(3):295-9.

15. Kaine JL, Kivitz AJ, Birbara C, et al. Immune responses following administration of influenza and pneumococcal vaccines to patients with rheumatoid arthritis receiving adalimumab. J Rheumatol. 2007;34(2):272-9.

16. Kim DK, Riley LE, Harriman KH, et al. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older - United States, 2017. MMWR Morbidity and mortality weekly report. 2017;66(5):136-8.

17. Robinson CL, Romero JR, Kempe A, et al. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger - United States, 2017. MMWR Morbidity and mortality weekly report. 2017;66(5):134-5.

18. Cullen G, Baden RP, Cheifetz AS. Varicella zoster virus infection in inflammatory bowel disease. Inflammatory bowel diseases. 2012;18(12):2392-403.

19. Card T, West J, Hubbard R, et al. Hip fractures in patients with inflammatory bowel disease and their relationship to corticosteroid use: a population based cohort study. Gut. 2004;53(2):251-5.

20. Casals-Seoane F, Chaparro M, Mate J, et al. Clinical Course of Bone Metabolism Disorders in Patients with Inflammatory Bowel Disease: A 5-Year Prospective Study. Inflammatory bowel diseases. 2016;22(8):1929-36.

21. Melek J, Sakuraba A. Efficacy and safety of medical therapy for low bone mineral density in patients with inflammatory bowel disease: a meta-analysis and systematic review. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2014;12(1):32-44.e5.

22. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Osteoporosis International. 2014;25(10):2359-81.

23. Peyrin-Biroulet L, Khosrotehrani K, Carrat F, et al. Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease. Gastroenterology. 2011;141(5):1621-28.e1-5.

24. Long MD, Herfarth HH, Pipkin CA, et al. Increased risk for non-melanoma skin cancer in patients with inflammatory bowel disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2010;8(3):268-74.

25. Scott FI, Mamtani R, Brensinger CM, et al. Risk of Nonmelanoma Skin Cancer Associated With the Use of Immunosuppressant and Biologic Agents in Patients With a History of Autoimmune Disease and Nonmelanoma Skin Cancer. JAMA dermatology. 2016;152(2):164-72.

26. Long MD, Martin CF, Pipkin CA, et al. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143(2):390-9.e1.

27. Allegretti JR, Barnes EL, Cameron A. Are patients with inflammatory bowel disease on chronic immunosuppressive therapy at increased risk of cervical high-grade dysplasia/cancer? A meta-analysis. Inflammatory bowel diseases. 2015;21(5):1089-97.

28. Practice Bulletin No. 168: Cervical Cancer Screening and Prevention. Obstetrics and gynecology. 2016;128(4):e111-30.

29. Ryan WR, Allan RN, Yamamoto T, et al. Crohn’s disease patients who quit smoking have a reduced risk of reoperation for recurrence. American journal of surgery. 2004;187(2):219-25.

30. Cosnes J, Beaugerie L, Carbonnel F, et al. Smoking cessation and the course of Crohn’s disease: an intervention study. Gastroenterology. 2001;120(5):1093-9.

31. Fuller-Thomson E, Sulman J. Depression and inflammatory bowel disease: findings from two nationally representative Canadian surveys. Inflammatory bowel diseases. 2006;12(8):697-707.

32. Walker EA, Gelfand MD, Gelfand AN, et al. The relationship of current psychiatric disorder to functional disability and distress in patients with inflammatory bowel disease. General hospital psychiatry. 1996;18(4):220-9.

33. Mikocka-Walus A, Pittet V, Rossel J-B, et al. Symptoms of Depression and Anxiety Are Independently Associated With Clinical Recurrence of Inflammatory Bowel Disease. Clinical Gastroenterology and Hepatology.14(6):829-35.e1.

34. Macer BJD, Prady SL, Mikocka-Walus A. Antidepressants in Inflammatory Bowel Disease: A Systematic Review. Inflammatory bowel diseases. 2017;23(4):534-50.

 

Inflammatory bowel disease (IBD) consists of two chronic inflammatory diseases, Crohn’s disease (CD) and ulcerative colitis (UC), as well as a small category of patients (~10%) who have atypical features called IBD-unclassified (IBD-U) or indeterminate colitis. The prevalence of IBD ranges from 0.3% to 0.5% overall in North America and Europe.¹ In North America, the incidences of CD and UC are estimated to be 3.1 to 14.6 per 100,000 person-years and 2.2 to 14.3 cases per 100,000 person-years, respectively; similar rates are seen in Europe.² However, incidences up to 19.2 and 20.2 per 100,000 for UC and CD, respectively, have been reported in Canada.3^,4 The incidences of both UC and CD are increasing over time in Western countries and in rapidly industrializing countries throughout Asia and South America.^5-8

With the increased incidence and advances in the treatment of IBD, many more patients are being treated with corticosteroids, immunomodulators, and biologics. Over time, there has also evolved an understanding of the importance of health maintenance in IBD patients, especially since patients with IBD receive fewer recommended preventive health services than general medical patients even though the use of immunosuppression is an argument for more attention to these issues.⁹ Gastroenterologists may see patients more frequently than their primary care provider (PCP) or PCPs may be unaware of the specific needs of IBD patients. Therefore, it is important that gastroenterologists are knowledgeable about the health maintenance recommendations that can be made to patients and to communicate these to PCPs. Recent society guidelines endorse the importance of this aspect of our practice.¹⁰ The discussion below highlights health maintenance issues that should be fundamental aspects of our IBD practices, however it does not address colon cancer screening and surveillance since these are beyond the scope of this article.
 

Influenza vaccine and pneumococcal vaccine

Influenza A and B outbreaks are commonly seen during the fall and early spring and risk factors for pneumonia and hospitalization include older age, chronic medical conditions, and immunosuppression. The CDC now recommend annual influenza vaccination for all individuals older than six months. For patients on immunosuppression, the vaccine administered should be the inactivated vaccine, as live attenuated vaccines should not be administered to these patients.

Copyright Shawn Rocco

Patients with IBD are also at an increased risk of bacterial pneumonia, the most common etiology of which is pneumococcal pneumonia.¹¹ The Advisory Committee on Immunization Practices (ACIP) recommends that patients on immunosuppression receive a one-time dose of the pneumococcal conjugate vaccine PCV13, followed by a dose of the pneumococcal polysaccharide vaccine PPSV23 one year later (eight weeks at the earliest). A second dose of PPSV23 should be given five years later and a third dose after 65 years of age.

In IBD patients, the influenza and pneumococcal vaccines are both well tolerated without an increased rate of adverse effects over the general population and without an increased risk of IBD flares after vaccination.¹² A common question for patients on biologic therapy is whether the vaccine should be timed at a specific point in the dose cycle. For infliximab, and likely other biologics, the timing does not change the vaccine immunogenicity and patients should be given these vaccines regardless of where they are in the cycle of administration of their biologic.¹³ In addition, there is significant response to influenza and pneumococcal vaccines in patients on combination therapy with immunomodulators and anti-TNFs and concerns about a lack of response to vaccines should not discourage vaccination since benefits are still acquired by patients even if immunogenicity is somewhat decreased.^14,15

Other vaccinations

In addition to the influenza and pneumococcal vaccines, adult and pediatric patients with IBD should follow the ACIP recommendations for tetanus, diphtheria, pertussis (Tdap), Td boosters, hepatitis A, hepatitis B, human papilloma virus (HPV), and meningococcal vaccinations.^16,17

Live vaccines including measles mumps rubella (MMR), varicella, and zoster vaccines are in general contraindicated in immunosuppressed patients on corticosteroids, azathioprine/6-mercaptopurine, methotrexate, anti-TNF, and anti-integrin biologics. An inactive varicella-zoster vaccine will likely be available in the near future and may obviate the need for the live vaccine, which is an important development given the increased risk of zoster in patients with IBD on immunosuppression.¹⁸

Osteoporosis screening

Copyright Shawn Rocco

Both men and women with IBD have an elevated risk of osteoporosis and osteopenia as well as elevated fracture risk.¹⁹ This is related to frequent chronic corticosteroid use, chronic inflammation (high disease activity), women with low BMI, smoking, older age (women > 65, men >70), terminal ileal disease or resection in patients with CD, and proctocolectomy and ileal pouch-anal anastomosis in patients with UC. The recommendations are to obtain baseline bone density evaluation only in patients with risk factors, including young patients since osteopenia can be present at a young age. If If osteopenia is noted, then calcium (1000-1200mg daily) and vitamin D (1000-4000IU daily) supplementation can be associated with improvement in osteopenia.²⁰ If osteoporosis is noted, patients should be referred to rheumatology or endocrinology for evaluation for bisphosphonate therapy which is also associated with improved outcomes.²¹ Bone density testing should be repeated every two years in patients with osteoporosis on treatment and less frequently when there is improvement.²² Given the association of bone metabolism disorders with smoking, this is one more reason to encourage our patients to quit.

 

Skin cancer screening

Multiple studies have demonstrated that immunosuppression, especially with methotrexate and azathioprine/6-mercaptopurine (6MP) is a risk factor for the development of initial and recurrent non-melanoma skin cancer (NMSC) in IBD patients, the data for biologics are less definitive.^23-25 In addition, biologics are associated with increased risk of melanoma in IBD.²⁶ The elevated risk of skin cancer begins in the first year of treatment with thiopurines and may continue after discontinuation. On the basis of this data, screening for melanoma and NMSC is recommended in IBD patients on immunosuppression. Especially for patients on thiopurines it is reasonable for the initial dermatologist visit to occur in the first year of treatment and thereafter with at least annual visits for a full body skin examination. In addition, it is reasonable to recommend regular sunscreen use and protective clothing such as hats.

Cervical cancer screening

A recent meta-analysis shows that women with IBD on immunosuppression have an increased risk of cervical high grade dysplasia and cervical cancer.²⁷ HPV is the major risk factor for cervical cancer and is necessary for its development. The current American College of Gynecology guidelines for women on immunosuppression are to start cervical cancer screening at 21 and annual screening thereafter with Pap and HPV testing.²⁸

Smoking

Smoking has well known associations with poor outcomes in the general population such as increased risk of lung and pancreatic cancers, as well as high risk of cardiovascular disease. In addition, smoking has risks specific to IBD. In CD, smoking is associated with increased disease activity, increased risk of post-operative recurrence, and increased severity of disease.²⁹ Smoking cessation is associated with improved long-term disease outcomes and less risk.³⁰ Making it a point to regularly discuss smoking cessation and partnering with PCPs to offer evidence-based quitting aids may be one of our most significant and beneficial interventions.

Depression and anxiety

Several studies have shown high levels of depression and anxiety in IBD patients and higher levels of depression are associated with increased symptoms, clinical recurrence, poor quality of life and decreased social support.^31-33 A recent systematic review of several studies suggested that antidepressants use in IBD patients benefits their mental health and may improve their clinical course as well.³⁴ As such, screening for depression and anxiety regularly and either offering treatment or referral to psychiatrists and psychologists for further management is recommended.¹⁰

Conclusion

Patients with IBD frequently develop long-term relationships with their gastroenterologists due to their lifelong chronic disease. It is therefore incumbent on us to be attentive to issues related to IBD patients’ preventive care and collaborate with PCPs to coordinate care for our patients since many of these interventions have both short-term and long-term benefits.

Dr. Chachu is assistant professor and gastroenterologist at Duke University, Durham, N.C.

References

1. Kaplan GG, Ng SC. Understanding and Preventing the Global Increase of Inflammatory Bowel Disease. Gastroenterology. 2017;152(2):313-21.e2.

2. Loftus EV, Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology. 2004;126(6):1504-17.

3. Bernstein CN, Wajda A, Svenson LW, et al. The Epidemiology of Inflammatory Bowel Disease in Canada: A Population-Based Study. The American journal of gastroenterology. 2006;101(7):1559-68.

4. Lowe AM, Roy PO, M BP, et al. Epidemiology of Crohn’s disease in Quebec, Canada. Inflammatory bowel diseases. 2009;15(3):429-35.

5. Kappelman MD, Rifas-Shiman SL, Kleinman K, et al. The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2007;5(12):1424-9.

6. Kappelman MD, Moore KR, Allen JK, et al. Recent trends in the prevalence of Crohn’s disease and ulcerative colitis in a commercially insured US population. Digestive diseases and sciences. 2013;58(2):519-25.

7. Ng SC, Kaplan G, Banerjee R, et al. 78 Incidence and Phenotype of Inflammatory Bowel Disease From 13 Countries in Asia-Pacific: Results From the Asia-Pacific Crohn’s and Colitis Epidemiologic Study 2011-2013. Gastroenterology.150(4):S21.

8. Parente JML, Coy CSR, Campelo V, et al. Inflammatory bowel disease in an underdeveloped region of Northeastern Brazil. World Journal of Gastroenterology : WJG. 2015;21(4):1197-206.

9. Selby L, Kane S, Wilson J, et al. Receipt of preventive health services by IBD patients is significantly lower than by primary care patients. Inflammatory bowel diseases. 2008;14(2):253-8.

10. Farraye FA, Melmed GY, Lichtenstein GR, et al. ACG Clinical Guideline: Preventive Care in Inflammatory Bowel Disease. The American journal of gastroenterology. 2017;112(2):241-58.

11. Long MD, Martin C, Sandler RS, et al. Increased risk of pneumonia among patients with inflammatory bowel disease. The American journal of gastroenterology. 2013;108(2):240-8.

12. Rahier JF, Papay P, Salleron J, et al. H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy. Gut. 2011;60(4):456-62.

13. deBruyn J, Fonseca K, Ghosh S, et al. Immunogenicity of Influenza Vaccine for Patients with Inflammatory Bowel Disease on Maintenance Infliximab Therapy: A Randomized Trial. Inflammatory bowel diseases. 2016;22(3):638-47.

14. Brezinschek HP, Hofstaetter T, Leeb BF, et al. Immunization of patients with rheumatoid arthritis with antitumor necrosis factor alpha therapy and methotrexate. Current opinion in rheumatology. 2008;20(3):295-9.

15. Kaine JL, Kivitz AJ, Birbara C, et al. Immune responses following administration of influenza and pneumococcal vaccines to patients with rheumatoid arthritis receiving adalimumab. J Rheumatol. 2007;34(2):272-9.

16. Kim DK, Riley LE, Harriman KH, et al. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older - United States, 2017. MMWR Morbidity and mortality weekly report. 2017;66(5):136-8.

17. Robinson CL, Romero JR, Kempe A, et al. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger - United States, 2017. MMWR Morbidity and mortality weekly report. 2017;66(5):134-5.

18. Cullen G, Baden RP, Cheifetz AS. Varicella zoster virus infection in inflammatory bowel disease. Inflammatory bowel diseases. 2012;18(12):2392-403.

19. Card T, West J, Hubbard R, et al. Hip fractures in patients with inflammatory bowel disease and their relationship to corticosteroid use: a population based cohort study. Gut. 2004;53(2):251-5.

20. Casals-Seoane F, Chaparro M, Mate J, et al. Clinical Course of Bone Metabolism Disorders in Patients with Inflammatory Bowel Disease: A 5-Year Prospective Study. Inflammatory bowel diseases. 2016;22(8):1929-36.

21. Melek J, Sakuraba A. Efficacy and safety of medical therapy for low bone mineral density in patients with inflammatory bowel disease: a meta-analysis and systematic review. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2014;12(1):32-44.e5.

22. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Osteoporosis International. 2014;25(10):2359-81.

23. Peyrin-Biroulet L, Khosrotehrani K, Carrat F, et al. Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease. Gastroenterology. 2011;141(5):1621-28.e1-5.

24. Long MD, Herfarth HH, Pipkin CA, et al. Increased risk for non-melanoma skin cancer in patients with inflammatory bowel disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2010;8(3):268-74.

25. Scott FI, Mamtani R, Brensinger CM, et al. Risk of Nonmelanoma Skin Cancer Associated With the Use of Immunosuppressant and Biologic Agents in Patients With a History of Autoimmune Disease and Nonmelanoma Skin Cancer. JAMA dermatology. 2016;152(2):164-72.

26. Long MD, Martin CF, Pipkin CA, et al. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143(2):390-9.e1.

27. Allegretti JR, Barnes EL, Cameron A. Are patients with inflammatory bowel disease on chronic immunosuppressive therapy at increased risk of cervical high-grade dysplasia/cancer? A meta-analysis. Inflammatory bowel diseases. 2015;21(5):1089-97.

28. Practice Bulletin No. 168: Cervical Cancer Screening and Prevention. Obstetrics and gynecology. 2016;128(4):e111-30.

29. Ryan WR, Allan RN, Yamamoto T, et al. Crohn’s disease patients who quit smoking have a reduced risk of reoperation for recurrence. American journal of surgery. 2004;187(2):219-25.

30. Cosnes J, Beaugerie L, Carbonnel F, et al. Smoking cessation and the course of Crohn’s disease: an intervention study. Gastroenterology. 2001;120(5):1093-9.

31. Fuller-Thomson E, Sulman J. Depression and inflammatory bowel disease: findings from two nationally representative Canadian surveys. Inflammatory bowel diseases. 2006;12(8):697-707.

32. Walker EA, Gelfand MD, Gelfand AN, et al. The relationship of current psychiatric disorder to functional disability and distress in patients with inflammatory bowel disease. General hospital psychiatry. 1996;18(4):220-9.

33. Mikocka-Walus A, Pittet V, Rossel J-B, et al. Symptoms of Depression and Anxiety Are Independently Associated With Clinical Recurrence of Inflammatory Bowel Disease. Clinical Gastroenterology and Hepatology.14(6):829-35.e1.

34. Macer BJD, Prady SL, Mikocka-Walus A. Antidepressants in Inflammatory Bowel Disease: A Systematic Review. Inflammatory bowel diseases. 2017;23(4):534-50.

 

Inflammatory bowel disease (IBD) consists of two chronic inflammatory diseases, Crohn’s disease (CD) and ulcerative colitis (UC), as well as a small category of patients (~10%) who have atypical features called IBD-unclassified (IBD-U) or indeterminate colitis. The prevalence of IBD ranges from 0.3% to 0.5% overall in North America and Europe.¹ In North America, the incidences of CD and UC are estimated to be 3.1 to 14.6 per 100,000 person-years and 2.2 to 14.3 cases per 100,000 person-years, respectively; similar rates are seen in Europe.² However, incidences up to 19.2 and 20.2 per 100,000 for UC and CD, respectively, have been reported in Canada.3^,4 The incidences of both UC and CD are increasing over time in Western countries and in rapidly industrializing countries throughout Asia and South America.^5-8

With the increased incidence and advances in the treatment of IBD, many more patients are being treated with corticosteroids, immunomodulators, and biologics. Over time, there has also evolved an understanding of the importance of health maintenance in IBD patients, especially since patients with IBD receive fewer recommended preventive health services than general medical patients even though the use of immunosuppression is an argument for more attention to these issues.⁹ Gastroenterologists may see patients more frequently than their primary care provider (PCP) or PCPs may be unaware of the specific needs of IBD patients. Therefore, it is important that gastroenterologists are knowledgeable about the health maintenance recommendations that can be made to patients and to communicate these to PCPs. Recent society guidelines endorse the importance of this aspect of our practice.¹⁰ The discussion below highlights health maintenance issues that should be fundamental aspects of our IBD practices, however it does not address colon cancer screening and surveillance since these are beyond the scope of this article.
 

Influenza vaccine and pneumococcal vaccine

Influenza A and B outbreaks are commonly seen during the fall and early spring and risk factors for pneumonia and hospitalization include older age, chronic medical conditions, and immunosuppression. The CDC now recommend annual influenza vaccination for all individuals older than six months. For patients on immunosuppression, the vaccine administered should be the inactivated vaccine, as live attenuated vaccines should not be administered to these patients.

Copyright Shawn Rocco

Patients with IBD are also at an increased risk of bacterial pneumonia, the most common etiology of which is pneumococcal pneumonia.¹¹ The Advisory Committee on Immunization Practices (ACIP) recommends that patients on immunosuppression receive a one-time dose of the pneumococcal conjugate vaccine PCV13, followed by a dose of the pneumococcal polysaccharide vaccine PPSV23 one year later (eight weeks at the earliest). A second dose of PPSV23 should be given five years later and a third dose after 65 years of age.

In IBD patients, the influenza and pneumococcal vaccines are both well tolerated without an increased rate of adverse effects over the general population and without an increased risk of IBD flares after vaccination.¹² A common question for patients on biologic therapy is whether the vaccine should be timed at a specific point in the dose cycle. For infliximab, and likely other biologics, the timing does not change the vaccine immunogenicity and patients should be given these vaccines regardless of where they are in the cycle of administration of their biologic.¹³ In addition, there is significant response to influenza and pneumococcal vaccines in patients on combination therapy with immunomodulators and anti-TNFs and concerns about a lack of response to vaccines should not discourage vaccination since benefits are still acquired by patients even if immunogenicity is somewhat decreased.^14,15

Other vaccinations

In addition to the influenza and pneumococcal vaccines, adult and pediatric patients with IBD should follow the ACIP recommendations for tetanus, diphtheria, pertussis (Tdap), Td boosters, hepatitis A, hepatitis B, human papilloma virus (HPV), and meningococcal vaccinations.^16,17

Live vaccines including measles mumps rubella (MMR), varicella, and zoster vaccines are in general contraindicated in immunosuppressed patients on corticosteroids, azathioprine/6-mercaptopurine, methotrexate, anti-TNF, and anti-integrin biologics. An inactive varicella-zoster vaccine will likely be available in the near future and may obviate the need for the live vaccine, which is an important development given the increased risk of zoster in patients with IBD on immunosuppression.¹⁸

Osteoporosis screening

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Both men and women with IBD have an elevated risk of osteoporosis and osteopenia as well as elevated fracture risk.¹⁹ This is related to frequent chronic corticosteroid use, chronic inflammation (high disease activity), women with low BMI, smoking, older age (women > 65, men >70), terminal ileal disease or resection in patients with CD, and proctocolectomy and ileal pouch-anal anastomosis in patients with UC. The recommendations are to obtain baseline bone density evaluation only in patients with risk factors, including young patients since osteopenia can be present at a young age. If If osteopenia is noted, then calcium (1000-1200mg daily) and vitamin D (1000-4000IU daily) supplementation can be associated with improvement in osteopenia.²⁰ If osteoporosis is noted, patients should be referred to rheumatology or endocrinology for evaluation for bisphosphonate therapy which is also associated with improved outcomes.²¹ Bone density testing should be repeated every two years in patients with osteoporosis on treatment and less frequently when there is improvement.²² Given the association of bone metabolism disorders with smoking, this is one more reason to encourage our patients to quit.

 

Skin cancer screening

Multiple studies have demonstrated that immunosuppression, especially with methotrexate and azathioprine/6-mercaptopurine (6MP) is a risk factor for the development of initial and recurrent non-melanoma skin cancer (NMSC) in IBD patients, the data for biologics are less definitive.^23-25 In addition, biologics are associated with increased risk of melanoma in IBD.²⁶ The elevated risk of skin cancer begins in the first year of treatment with thiopurines and may continue after discontinuation. On the basis of this data, screening for melanoma and NMSC is recommended in IBD patients on immunosuppression. Especially for patients on thiopurines it is reasonable for the initial dermatologist visit to occur in the first year of treatment and thereafter with at least annual visits for a full body skin examination. In addition, it is reasonable to recommend regular sunscreen use and protective clothing such as hats.

Cervical cancer screening

A recent meta-analysis shows that women with IBD on immunosuppression have an increased risk of cervical high grade dysplasia and cervical cancer.²⁷ HPV is the major risk factor for cervical cancer and is necessary for its development. The current American College of Gynecology guidelines for women on immunosuppression are to start cervical cancer screening at 21 and annual screening thereafter with Pap and HPV testing.²⁸

Smoking

Smoking has well known associations with poor outcomes in the general population such as increased risk of lung and pancreatic cancers, as well as high risk of cardiovascular disease. In addition, smoking has risks specific to IBD. In CD, smoking is associated with increased disease activity, increased risk of post-operative recurrence, and increased severity of disease.²⁹ Smoking cessation is associated with improved long-term disease outcomes and less risk.³⁰ Making it a point to regularly discuss smoking cessation and partnering with PCPs to offer evidence-based quitting aids may be one of our most significant and beneficial interventions.

Depression and anxiety

Several studies have shown high levels of depression and anxiety in IBD patients and higher levels of depression are associated with increased symptoms, clinical recurrence, poor quality of life and decreased social support.^31-33 A recent systematic review of several studies suggested that antidepressants use in IBD patients benefits their mental health and may improve their clinical course as well.³⁴ As such, screening for depression and anxiety regularly and either offering treatment or referral to psychiatrists and psychologists for further management is recommended.¹⁰

Conclusion

Patients with IBD frequently develop long-term relationships with their gastroenterologists due to their lifelong chronic disease. It is therefore incumbent on us to be attentive to issues related to IBD patients’ preventive care and collaborate with PCPs to coordinate care for our patients since many of these interventions have both short-term and long-term benefits.

Dr. Chachu is assistant professor and gastroenterologist at Duke University, Durham, N.C.

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