MMR

MMR is generally given to children. Adults with an unknown vaccine history should have titers checked. If a patient lacks immunity, the vaccine can be administered as long as there is no plan to start immunosuppressive therapy in the subsequent 6 weeks. It is important to note that MMR can be given safely to household contacts of immunosuppressed patients without fear of adverse effect or virus spread.

Varicella

Varicella vaccine is recommended for immunocompetent children and adults with no prior history of varicella infection. For patients who may be candidates for immunosuppression, a titer should be checked if immune status is unclear. There is no evidence-based data regarding how long to wait after administering the varicella vaccine before safely initiating immunosuppressive therapy. Based on data from the HZV, which contains at least a 10-fold greater titers than the varicella vaccine, waiting at least 4 weeks after varicella or zoster vaccination before initiating immunosuppressive therapy is suggested. Like MMR, vaccination of household contacts of immunosuppressed individuals is not contraindicated for varicella. However, if the vaccinated family member develops a vaccine-related rash, the immunosuppressed patient should avoid contact with the affected individual. If a varicella-naive, immunocompromised patient is exposed to either a vaccine-related rash or to active varicella, prophylactic immunoglobulin is recommended only for the case of exposure to active varicella.

Varicella-Zoster Virus

Herpes zoster, also called shingles, results from reactivation of latent varicella-zoster virus within the dorsal root ganglia. The clinical course among immunocompetent patients is variable, ranging from a unilateral and painful vesicular rash, to debilitating post-herpetic neuralgia. In the general population, about 1 in 3 people develop zoster or a zoster-related diagnosis during their lifetime. The incidence of zoster is greater, and occurs earlier, in transplant patients, HIV-positive patients, and patients with chronic diseases requiring immunosuppression, such as rheumatoid arthritis, lupus, and IBD. In 1 retrospective study, the risk for zoster was greater in those with Crohn disease compared with ulcerative colitis, and in those receiving immunomodulators and corticosteroids compared with those on mesalazine. The HZV licensed in the United States is a live, attenuated strain of varicella zoster virus, and the same strain used in varicella vaccines. Its minimum potency is 14 times the potency of the single antigen varicella vaccine. It is recommended for individuals age 50 years and older to prevent herpes zoster and/or reduce the severity of complications from zoster infection. In 2008, the US Centers for Disease Control (CDC) in conjunction with the Advisory Committee on Immunization Practices (ACIP) recommended that patients on low doses of methotrexate (≤0.4 mg/kg/wk), azathioprine (≤3.0 mg/kg/d), or 6-mercaptopurine (≤1.5 mg/kg/d) for treatment of IBD are not considered sufficiently immunosuppressed to create vaccine safety concerns and should not be contraindications for administration of HZV. The CDC/ACIP workgroup recognized that persons with lower levels of immunosuppression are able to tolerate attenuated varicella-zoster virus–based vaccine such that varicella vaccine is recommended for HIV-infected children without prior immunity to varicella-zoster virus. The workgroup also recognized that even persons with a prior history of varicella (ie, the population for which the HZV would be recommended) are at little or no risk of second episodes of varicella, even when becoming profoundly immunosuppressed, because varicella-zoster virus-specific immunity is well-maintained in those patients. For these reasons, the HZV is recommended for persons taking low levels of immunosuppressive agents.

As with the varicella vaccine, there is no clear data to determine the optimal interval between vaccination and initiation of immunosuppressive therapy. There is a risk of disseminated herpes zoster after initiating immunosuppressive therapy, so windows of 1 to 3 months have been suggested. Household contacts can be immunized, but those who develop a vaccine-related rash should avoid contact with immunocompromised individuals.

Influenza

Influenza is available in both a live, intranasal form and an inactivated, intramuscular form. Regardless of the type or number of immunosuppressive medications a patient is taking, it is important to immunize all IBD patients against influenza, because some have an adequate response to the vaccine, and even a partial response may provide some degree of protection. Although some patients may prefer the intranasal administration, it is important to note that the safety and effectiveness of a live, attenuated influenza vaccine has not been established in groups of patients who are at risk for more complications from influenza. IBD patients should therefore receive the intramuscular inactivated vaccine annually.

Tetanus and Diphtheria

Tetanus and diphtheria is recommended every 10 years, with the tetanus, diphtheria, and acellular pertussis given at least once during this period. Any patient with an unclear vaccine history should receive the primary series of tetanus vaccines, which consists of 3 doses. After the initial series, all patients should receive the booster every 10 years. Two studies looking at immune response to the booster have found conflicting results in IBD patients—one suggested impaired humoral response to the booster in IBD, whereas the other found normal antitetanus antibody levels. Despite this inconsistency, it is recommended to administer tetanus and diphtheria vaccine to the standard vaccine schedule in all IBD patients.

HPV

HPV is recommended for all females beginning at age 11 or 12 and extending to age 26 years old, including those with a history of genital warts, abnormal Papanicolaou test (Pap), or positive HPV DNA test. In October 2011, the CDC’s ACIP voted to expand recommendations to include vaccinating adolescent males age 11 to 12, with catch up doses for males aged 13 to 21 years in an effort to expand protection to more men and women, citing low rates of vaccination among women as the motivation for altering the original recommendations, and attempting to minimize any stigma associated with receiving the vaccine. The new recommendation, however, will not become official until voted on by the CDC and published in their Morbidity and Mortality Weekly Report . Female patients with IBD on immunosuppressive agents are at increased risk of cervical dysplasia, and as a result the administration of HPV vaccine should be a priority in this group.

Pneumococcal Vaccine

Pneumococcal vaccine is recommended for all IBD patients, regardless of age or immunosuppressive regimen. A 1-time revaccination is recommended after 5 years in patients ages 65 and older and in individuals on immunosuppressive agents. Although it is preferable to administer the vaccine before beginning immunomodulator and/or biologic therapy, even those patients already on immunosuppressants may have some degree of protection.

Hepatitis B

Hepatitis B has been implicated in case reports of fatal liver failure after the initiation of biologic therapy. As such, it is now recommended to check hepatitis B serology before starting anti-TNF therapy. In patients who lack immunity, doses should be administered at 0, 2, and 4 to 6 months; postvaccine titers should be checked 1 month after the last dose to ensure an adequate response. Patients on immunosuppressive therapy may not achieve an adequate postvaccine titer, although younger patients seem to have a higher rate of response. Subsequent studies have examined both readministration of the 3-vaccine series using twice the standard dose, or subsequent administration of the combined hepatitis A and B vaccine with similar results: Both seem to be effective in increasing postvaccine titers to adequate levels.

Meningococcal Vaccine

Meningococcal vaccine is recommended for adults who are asplenic or have complement deficiencies, college students living in dormitories, military recruits, and individuals traveling to endemic areas for meningococcal disease. Because many IBD patients are young and otherwise healthy, it is important to remember to vaccinate for meningococcus if appropriate.

Cervical Cancer Screening

There is a higher prevalence of abnormal Pap smears in women with IBD, and this is associated with treatment with immunomodulators. In 1 study comparing 40 IBD patients who underwent routine cervical cancer screening with a total of 134 Pap smears, the incidence of abnormal Pap in a woman with IBD was 42.5% versus 7% among age-, race-, and parity-matched controls. The authors also noted a significant increase in higher risk cervical cytology in the IBD group, and more abnormalities in Pap smears performed more than 6 months after exposure to an immunosuppressant (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.2–4.1; P = .021). All abnormal tests were associated with either HPV serotype 16 or 18, so it is important to document a current Pap smear to assess for cervical cytology and HPV infection before, or soon after, initiating immunosuppressive therapy. The HPV vaccine is given in 3 doses over a 6-month period, and is indicated for prevention of disease caused by HPV types 16 and 18, which is associated with 70% of cervical cancers, as well as types 6 and, 11 which are associated with genital warts. As above, women with IBD on immunosuppressive agents should be considered for the vaccine, and all women on immunomodulator therapy should undergo annual Pap testing as recommended by the American College of Obstetrics and Gynecology’s guidelines. In some situations, women with HPV and dysplasia may require discontinuation of their immunomodulators.

Osteoporosis

IBD patients have an increased risk of developing osteoporosis and osteopenia. In 1 study of 2035 IBD patients, bone density was performed in 317 patients with osteopenia identified in 48% and osteoporosis in 26%. Further studies have demonstrated that the typical incidence of osteoporosis in IBD has generally been in the range of 10% to 15%. It is thought that low bone density in IBD is multifactorial, resulting from vitamin D malabsorption, glucocorticoid use, and the direct effects of systemic inflammation on bone. General risk factors for osteopenia and osteoporosis include age over 60 years, family history, lifestyle and dietary habits, low body mass index, obstetric history, severity of intestinal inflammation, and use of corticosteroids, with the American Gastroenterological Association (AGA) guidelines noting age and glucocorticoid use as the strongest risk factors, so every effort should be made to limit exposure to corticosteroids.

Universal testing of bone density is recommended with 1 or more of the following risk factors: age older than 60, low body mass index, smoking, postmenopausal women, steroid treatment for at least 3 months, repeated courses of steroids, and a history of fractures. In 2003, both the AGA and the American College of Gastroenterology issued guidelines that recommended screening all IBD patients meeting 1 of 5 criteria: Postmenopausal state, ongoing corticosteroid treatment, cumulative prior use of corticosteroids exceeding 3 months, history of low-trauma fractures, and age over 60 years.

The gold standard for assessing fracture risk is via dual x-ray absorptiometry (DEXA), and results of DEXA scan can be used to guide therapy. Osteopenia is defined as a T -score of −1 to −2.5 on DEXA, and osteoporosis is a T -score below −2.5.

For patients with a T score above −1, recommendations are preventative, and should include calcium and vitamin D supplementation, exercise, smoking cessation, limiting alcohol use, and minimizing corticosteroid use. Patients with osteopenia should also implement these measures, and consider repeat the DEXA in 2 years. Bisphosphonates are recommended for known osteoporosis ( T -score < −2.5), history of atraumatic fracture, or failure to withdraw from corticosteroids after 3 months. Finally, if an IBD patient is found to be osteoporotic or sustains a low-trauma fracture, screening for secondary causes of low bone density, such as celiac disease, hypogonadism, and vitamin D deficiency, should be performed.

Colorectal Cancer Screening

Patients with long-standing ulcerative colitis are at an increased risk for developing dysplasia and colorectal carcinoma. According to AGA guidelines, all patients, regardless of extent of disease, should undergo a screening colonoscopy a maximum of 8 years after onset of symptoms, with biopsies taken throughout the entire colon to assess the microscopic extent of inflammation. Patients with ulcerative proctitis or proctosigmoiditis are not at increased for IBD-related cancer, and thus may be screened according to average risk recommendations. Patients with extensive or left-sided colitis should begin surveillance 1 to 2 years after initial screening colonoscopy. Crohn disease patients with colitis involving at least one third of the colon should also have these surveillance guidelines applied.

The optimal surveillance intervals have not been clearly defined. After 2 examinations without evidence of dysplasia or cancer, surveillance intervals can be extended to every 1 to 3 years. Although there has been concern that after 20 years of disease, the risk of colorectal cancer increases and perhaps surveillance intervals should be reduced again to every 1 to 2 years, recent data actually suggest that this is not necessary. Surveillance intervals can be continued at 1 to 3 years, but should be determined on an individual basis depending on an individual’s risk factors. Factors that should prompt more frequent examinations include first-degree relatives with colorectal cancer, ongoing inflammation (either endoscopically or histologically), and anatomic abnormalities such as foreshortened colon, strictures, or multiple inflammatory pseudopolyps. Patients with primary sclerosing cholangitis are at increased risk for developing colorectal cancer, and should undergo surveillance at the time of diagnosis and annually thereafter.

With respect to obtaining surveillance biopsies throughout the colon, there are no prospective studies looking at the optimal number of specimens to obtain. One study has recommended a minimum of 33 biopsies be taken in patients with pancolitis. Chromoendoscopy has been shown to have higher sensitivity for detecting dysplasia than traditional white light endoscopy, so an alternative to 33 random biopsies is for targeted biopsies to be performed by endoscopists skilled in this technique. In general, it is ideal to perform surveillance while disease is in remission; however, surveillance should not be put off if the disease continues to be active.

The British Society of Gastroenterology (BSG) guidelines are similar, but warrant discussion because they address several additional points. The BSG guidelines recommend screening beginning at 10 years after onset of colonic symptoms. Surveillance is then recommended in either 1-, 3-, or 5-year intervals, depending on extent of disease and individual risk factors (primary sclerosing cholangitis or family history prompts more frequent screening). British guidelines favor chromoendoscopy with targeted biopsies, but if this technique is unavailable random biopsies throughout the colon are reasonable. Finally, like the American guidelines, the BSG recommends that if a dysplastic polyp is detected within an area of inflammation and can be removed entirely, it is not necessary to recommend colectomy.

Skin Cancer Screening

Nonmelanoma skin cancers (NMSC) are among the most common malignancies in the United States, and include both squamous cell and basal cell carcinoma. Previous data suggested that there are over 1,000,000 new cases of NMSC per year, although new data estimate as many as 3.5 million cases per year. There is an increased incidence of NMSC in patients after solid organ transplantation on immunosuppressive agents. Several epidemiologic studies have documented an increase in NMSC cases in IBD patients. In 1 study from the United States, persistent use of thiopurines (>365 days) was associated with an increased risk of NMSC (OR, 4.27; 95% CI, 3.08–5.92). In patients on anti-TNF agents, the OR was 2.18 (95% CI, 1.07–4.46). The combined use of thiopurines and anti-TNF agents was associated with an even higher risk (OR, 6.75; 95% CI, 2.74–16.65).

There are no specific IBD guidelines for prevention of NMSC, but IBD patients should follow recommendations for the general population, which include sun protection strategies. It should be noted that the United States Preventative Services Task Force (USPSTF) concluded that there was insufficient evidence to recommend universal screening for skin cancer by primary care clinicians or self-examination. Although there are no IBD guidelines for the secondary prevention of skin cancer by performing annual skin examinations, the case can be made that IBD patients on immunomodulators or biologics warrant regular (annual) examinations.

Smoking Cessation

All IBD patients should be encouraged to stop smoking. Smoking cessation is a crucial aspect in the management of Crohn patients that is often overlooked. Individuals who smoke have an increased prevalence of Crohn disease. Crohn disease patients who are smokers have more severe ileal disease, more frequent flares, and an increased need for steroids and immunomodulators, as well as higher rates of surgery. Smoking cessation is associated with a decreased risk of relapses and decreased need for steroids and immunomodulators. The negative effects of smoking are dose dependent, so even a partial decrease in the number of cigarettes smoked daily is beneficial in improving the course of Crohn disease.

Depression Screening

Depression is a common problem that may affect as many as 15% to 35% of individuals with IBD. In 1 population-based study, the lifetime risk for major depressive disorder was more than twice as high in the IBD cohort, occurring in more than one quarter of those with IBD. Predisposing factors for the development of depression include the chronic relapsing nature of the disease, as well as some of the medications used as treatment. The American College of Preventive Medicine (ACPM) and the USPSTF recommend screening in all clinical practices that have systems in place to assure accurate diagnosis, effective treatment, and follow-up of depression. The ACPM also cites several studies that have concluded effective screening can be performed with just 2 brief questions :

• 1
  

  Over the past month, have you felt down, depressed, or hopeless?

  
  
• 2
  

  Over the past month, have you felt little interest or pleasure in doing things?