Patients with inflammatory bowel disease (IBD) frequently turn to their gastroenterologist for their primary care needs, as they have a strong relationship with them and they may be the only physician that they see. It is important that we as internists understand what healthcare our patients need outside the realm of their gastrointestinal tract. A recent study demonstrated that patients with IBD get less primary care screening and maintenance care than non-IBD patients of the same age.1 Since these issues can potentially complicate IBD it is important to at least recognize those issues that deserve attention from a healthcare provider. This review highlights the most common primary healthcare issues that occur in patients at various ages throughout the life cycle.
Patients with inflammatory bowel disease (IBD) often rely on their gastroenterologist for healthcare maintenance. In addition, the gastroenterologist also provides guidance to the patient's primary care physician on a broad range of issues such as vaccinations, osteoporosis screening, and cancer/dysplasia surveillance. Appropriate vaccinations should be administered to patients with IBD, particularly those likely to receive immunosuppression. Live virus vaccines are not appropriate for patients on immunosuppressive therapy, and therefore should be anticipated and given prior to initiating immunosuppression. Screening for osteoporosis is based on a combination of individual risk factors, but a history of prolonged (>3 months) steroid use over 10 mg is reason enough to obtain dual-energy x-ray absorptiometry scanning. Smoking cessation also falls within the realm of the gastroenterologist, as current smoking has a negative impact on Crohn's disease and cessation can be related to exacerbation in ulcerative colitis. Cancer screening includes not only colorectal cancer, but discussion regarding cervical dysplasia, skin cancer, and prostate cancer. Other primary care issues include hypertension and cholesterol monitoring, depression, and ocular health. A comprehensive understanding of all of the issues that can affect a patient with IBD throughout their life cycle is important, as it can impact their natural history, medication decisions, and overall outcomes. (Inflamm Bowel Dis 2009)
Adults with IBD should generally follow the same vaccination schedules as the general population, with some exceptions.2 While the need for vaccination against preventable diseases is increased in the patient with IBD given their chronic illness and immunosuppression, their rate of immunization is quite low. In a study of 169 patients with IBD,3 86% of whom had past or current immunosuppressive medication use, only 45% had tetanus immunization within the last 10 years, 28% received regular flu shots, 9% received pneumococcal vaccination, and 28% had been vaccinated against hepatitis B. The most common reason for nonimmunization with influenza was lack of awareness (49%). As many of these patients see their gastroenterologist more than their internist, it is within our purview to improve vaccination rates in these high-risk patients.
Recommended adult (age 19–26) immunization schedules for 2009 have been published by the Advisory Committee on Immunization Practices (ACIP).4 Below are the major recommendations, although for more detailed information, please read the ACIP guidelines. Vaccines noted with a star (*) are live virus vaccines and should not be given to patients on immunosuppressive therapy, as outlined in the section on live viruses below.
Tetanus, diphtheria, pertussis (Td/Tdap): Adults should received a 1-time dose of Tdap and then Td booster every 10 years.
Human papilloma virus (HPV): 3 doses should be given to females between the ages of 9–26.
IBD: Consideration should be given to older patients who are negative for HPV on Pap smear. Consideration should be given to vaccinating males in the same age range given the increased risk of HPV with immunosuppression and anal cancer with perianal Crohn's disease (CD).
Influenza: 1 dose annually to all patients.
IBD: the intranasal vaccination (LAIV)* is a live virus and is contraindicated in patients on immunosuppressive therapy including corticosteroids, azathioprine/6-mercaptopurine (6MP), methotrexate, and anti-TNF agents.
Pneumococcal: 1 dose between age 19–26 with a second 1-time revaccination after 5 years.
Hepatitis A (HAV): 2 doses.
Many younger patients will have been vaccinated in childhood.
Check blood tests for antibody to HAV.
If never vaccinated, 2-dose vaccination schedule.
If vaccinated, but HAV-negative, then a booster shot is given.
Hepatitis B (HBV): 3 doses.
Many younger patients will have been vaccinated in childhood.
Check blood tests for antibody to HBV and Hepatitis B surface antigen (HBsAG).
If HBsAG is positive, then anti-TNF therapy is contraindicated without concomitant antiviral therapy.
If vaccinated but HBsAb is negative, a booster shot is given.
This is only for adults with anatomic or functional asplenia or terminal complement component deficiencies.
First-year college students, military recruits, and persons traveling to hyperendemic or epidemic areas such as sub-Saharan Africa should be vaccinated.
Measles, Mumps, Rubella (MMR).*
1 or 2 doses between ages 19–49 for adults born in 1957 or after if blood tests do not show immunity to measles, mumps, and rubella.
Female patient planning pregnancy who has no evidence of rubella immunity.
Students in educational institutions.
Live virus vaccine: Contraindicated for patients on biologic therapy.
Varicella* 2 doses.
All adults ages 19 and older without evidence of immunity to varicella or prior vaccination against varicella.
Live virus vaccine: Contraindicated for patients on biologic therapy.
Zoster* 1 dose.
All adults age 60 and greater.
Not recommended for those who have received varicella vaccine.
Zoster vaccine has 14–15 times the inoculum of the varicella, vaccine as more virus is needed to stimulate older patients.
Live virus vaccine: Contraindicated for patients on biologic therapy.
Response to Vaccines
Patients with IBD mount appropriate responses to vaccination, although sometimes at lower levels than the general population. Tetanus toxoid is highly antigenic. A study of 10 patients with inactive CD found normal response to immunization.5
Pediatric patients and young adults given influenza vaccination had appropriate responses in 2 studies6, 7 although the use of infliximab lead to a statistically significant reduced response to vaccination in both studies. There was no exacerbation of disease activity in either study. Melmed et al8 reported that patients with IBD on no immunosuppressive therapy had similar rates of response to pneumococcal vaccination compared to the general population. However, patients on anti-TNF therapy or immunomodulators had a significantly lower response compared to IBD patients not on these medications (P = 0.07) and compared to the general population (P = 0.01).
The rheumatology literature has similar findings, with a generally good response to influenza and pneumococcal vaccination, although this may be reduced with the use of methotrexate and anti-TNF therapy.9, 10
Potential Adverse Events
5-Aminosalicylates (5-ASAs) are commonly used for the treatment of IBD. As these medications act topically and there is limited absorption, serum concentrations should be quite low. However, given the association between salicylates and Reye's syndrome (acute encephalopathy, hepatic dysfunction, microvesicular steatosis), there is a theoretical concern for Reye's syndrome with 5-ASAs.2 However, there are no case reports of this occurring and no formal recommendation to change dosing based on vaccination schedules.
There have been concerns in the rheumatology literature of reactivation of the underlying disease with vaccination.11 At least 1 case report has been noted in IBD as well of a woman with repeated disease flares with influenza vaccination,12 although 2 larger studies in the pediatric population did not find an increase in disease flares with influenza vaccination.6, 7
Live Virus Vaccines
A “live virus” vaccine contains a “living” virus that is able to give and produce immunity, usually without causing illness. A list of common live virus vaccines is provided in Table 1. It is important to note that both typhoid and influenza have both live and attenuated versions of the vaccine. Live polio virus is no longer used in most regions.
|Bacille Calmette-Guerin (BCG)|
|Influenza inhaled (LAIV)|
|Measles, mumps, rubella|
Live virus vaccines should not be given to immunocompromised hosts such as those with malignant neoplasms of the bone marrow or lymphatic system, AIDS, and those on immunosuppressive therapy. The Centers for Disease Control (CDC) have recently updated their recommendations for patients on immunosuppressive therapy receiving Zoster vaccine to the following13:
Contraindicated: Persons on immunosuppressive therapy, including high-dose corticosteroids (>20 mg/day of prednisone or equivalent) lasting 2 or more weeks. Zoster vaccination should be deferred for at least 1 month after discontinuation of such therapy.
Compatible: Short-term corticosteroid therapy (<14 days); low-to-moderate dose (<20 mg/day of prednisone or equivalent); or long-term alternate-day treatment with low to moderate doses of short-acting systemic corticosteroids are not considered sufficiently immunosuppressive to cause concerns for vaccine safety. Persons receiving this dose or schedule can receive zoster vaccine.
Compatible: Therapy with low doses of methotrexate (<0.4 mg/kg/week), azathioprine (<3.0 mg/kg/day), or 6-MP (<1.5 mg/kg/day) for treatment of rheumatoid arthritis, psoriasis, polymyositis, sarcoidosis, IBD, and other conditions are also not considered sufficiently immunosuppressive to create vaccine safety concerns and are not contraindications for administration of zoster vaccine.
Contraindicated: Persons receiving recombinant human immune mediators and immune modulators, especially the antitumor necrosis factor agents. The safety and efficacy of zoster vaccine administered concurrently with these agents is unknown. If it is not possible to administer zoster vaccine to patients before initiation of therapy, physicians should assess the immune status of the recipient on a case-by-case basis to determine the relevant risks and benefits. Otherwise, vaccination with zoster vaccine should be deferred for at least 1 month after discontinuation of such therapy.
Summary of Recommendations for Vaccination in Patients with IBD
Patients with IBD should generally follow the same vaccination guidelines as the general public, except that patients on anti-TNF should not get live virus vaccines. The best time to vaccinate is when patients are newly diagnosed with IBD and are not on any form of immunosuppression. At this time, vaccination histories should be checked and updated, particularly prior to starting any immunosuppressants. Patients who may require live virus vaccines due to travel or work requirements should be warned prior to starting anti-TNF therapy to update their vaccinations.
Tuberculin Skin Test (TST)
There is an increased risk of tuberculosis (TB) with the use of anti-TNF therapy and patients should be screened prior to initiating biologics—ideally prior to any immunosuppressant. A careful risk history (country of birth, congregate setting [prison, homeless shelter, chronic care facility], substance abuse, healthcare employment) and examination, a purified protein derivative test (TST), and a chest radiograph if TST-positive are the basic screening tools.14 Per the American Thoracic Society (ATS), a positive TST in an immunosuppressed patient (any IBD patient) is 5 mm induration or greater.15 Patients who have had Bacille–Calmette–Guerin (BCG) vaccine may mount a positive TST for up to 10 years from the vaccination. After that point, a positive TST should be considered evidence of exposure or active infection with TB.16
The sensitivity of the TST has been questioned in patients who are immunosuppressed. Mow et al17 reported 82 patients with IBD tested before or during infliximab therapy. None were TST-positive. However, 71% also did not mount a response to the control panel of Candida, tetanus, and/or mumps. Anergy was more likely in those on corticosteroids or immunosuppressants (83% versus 43%). While some have argued for serial TST testing to boost response, this has been associated with an increase in false-positive tests.18, 19 T-cell interferon-γ release assays (TIGRA) testing is more specific for Mycobacterium tuberculosis and is helpful in those with prior BCG vaccination or non-TB mycobacteria.20 Two new tests are currently available: the QuantiFERON–TB Gold test (QFT-G; Cellestis, Valencia, CA) and the T-SPOT-TB (Oxford Immunotec, Abingdon, UK). However, the tests are expensive, logistically challenging (they must be interpreted within 6 hours), and may or may not be more helpful in the immunosuppressed patient.
The CDC/ATS and the British Thoracic Society have no recommendations regarding TST screening after starting anti-TNF therapy. Society guidelines have suggested annual tuberculosis screening, with either TST or TIGRA, in patients on anti-TNF therapy.21 While most patients with TB on anti-TNF therapy appear to have reactivation of latent disease, there are cases of new infection later in therapy.20 However, the efficacy and accuracy of repeat annual testing has not been tested prospectively. It is most important that patients are educated with respect to the symptoms to watch for and that physicians maintain a high degree of vigilance in monitoring for TB infection in their patients with IBD.
Scheduled Laboratory Testing
Patients with IBD should have periodic blood test monitoring: the frequency and type of tests depends on their medication use and comorbid conditions. If the patient is on no medical therapy annual complete blood count (CBC), liver function tests (LFTs) including aminotransferases (AST, ALT), alkaline phosphatase, total bilirubin, and albumin, and a creatinine would be the basic panel. C-reactive protein and sedimentation rate can be helpful in some patients to monitor disease activity and response to therapy.22
Annual fasting glucose, particularly given the steroid use in this population, and lipid profiles should be done as well. At least in the patient with active disease, total and LDL cholesterol will be low,23 but the patient with inactive disease should be screened for the preventable illnesses associated with high lipids. Anemia is common in patients with IBD and is a common cause of fatigue and hair loss.24 A patient with ileal CD should have at least annual vitamin B12 and folate testing. Iron studies should be considered in patients with evidence of anemia or complaints of fatigue or hair loss. Patients should also have annual screening for vitamin D deficiency with serum 25 hydroxyvitamin (OH) D levels. A study of Irish IBD patients found that 50% were vitamin D-deficient in the winter and 19% in the summer.25
Medication-specific recommendations in addition to the basic annual panel and tests above are below. A baseline set of tests (CBC, LFTs, C-reactive protein, sedimentation rate) prior to initiating therapy is helpful to determine medication-associated benefits and abnormalities.
Aminosalicylates: annual creatinine.
Overall, the risk of renal insufficiency with the use of aminosalicylates is minimal.26
Corticosteroids: 25-OH Vitamin D, metabolic panel, and glucose.27
A thiopurine methyl transferase (TPMT) should be checked prior to initiation of therapy.
Weekly CBC with differential for the first 4 weeks, at least every 3 months thereafter (our practice is monthly for 6 months and then every 2–3 months).
Periodic liver function tests at least every 3 months.
Periodic CBC and liver function tests.
Our practice is every 2 weeks for 1 month, every month for 6 months, and then at least every 3 months.
Biologic therapy (infliximab, adalimumab, certolizumab pegol, natalizumab).27
Prior to initiating therapy: hepatitis A, B, and C. If no evidence of prior exposure to A or B, vaccinate.
Active hepatitis B infection is a relative contraindication to anti-TNF therapy. Patients should be on appropriate antiretrovirals prior to initiating anti-TNF therapy.
On maintenance therapy.27
As anti-TNF therapy has rarely been associated with bone marrow suppression and liver function test abnormalities, these laboratory tests should be periodically monitored every 3–6 months.
Colonoscopy has many roles in the management of patients with IBD. It is useful to determine the extent and severity of disease, to determine the efficacy of therapy (mucosal healing), to look for postoperative recurrence, and to survey for colorectal cancer. For complete guidelines on the appropriate surveillance for colorectal cancer, please refer to the IBD journal consensus statement.28
Aside from the known cardiac, pulmonary, and oncologic risks associated with smoking, it has a negative effect on patients with CD as well. A recent survey of 675 IBD patients found that active smoking is a risk factor for CD and passive smoking is detrimental for the prognosis of CD. Among patients with ulcerative colitis (UC), however, active smoking shows beneficial effects.29 Smoking may reduce response to medications, increase risk of postoperative recurrence, and shorten the duration of remission in patients with CD.30
As stopping smoking may improve the course of CD, among other benefits, it should be strongly advocated by the gastroenterologists caring for these patients. One drug that may be useful in this setting and have triple benefits is bupropion. Not only is it an effective antismoking agent, it helps in the management of depression (which many patients with IBD suffer from) and case reports suggest it is effective for the treatment of CD as well.31
Osteoporosis, a chronic and progressive bone disease characterized by low bone mass, microarchitectural deterioration of bone, and consequent increased bone fragility and fracture risk is a major public health concern.32 Fractures associated with osteoporosis are a principal cause of both morbidity and mortality and have significant associated costs. Therefore, the prevention and treatment of this disease are of paramount importance.
Over the last decade, osteoporosis has increasingly been recognized as a significant medical problem in patients with IBD as well. IBD patients have markedly reduced bone mineral densities (BMD). As BMD decreases, the risk of associated fractures increases.33 Several population-based studies, however, have shown only a modest increase in osteoporotic fractures in patients with CD.34, 35 Furthermore, some patients with IBD have a normal bone mineral density but still incur fragility fractures. Other variables such as increased disease activity and concomitant cytokine release likely also play a role.
Dual-energy x-ray absorptiometry scanning (DXA) is the gold standard for diagnosing osteopenia and osteoporosis.36 Currently, osteoporosis is diagnosed on the basis of a low bone mineral density ≥2.5 standard deviations below the average bone density in gender-matched young adults (T-score less than −2.5) or when patients sustain a fragility fracture (a fall from standing height or less). Osteopenia is a less advanced state of low BMD (T-score of −1 to −2.5). For every 10% drop in bone mineral density, the risk of fracture risk increases 2–3 times.37, 38 Pertinent risk factors for osteoporosis in IBD patients include: low bone mineral density, age, drug exposure including glucocorticoids (usually exceeding 7.5 mg of prednisolone daily), cyclosporine A, and methotrexate, vitamin D deficiency, malabsorption, poor nutritional status including low calcium intake, sedentary life style, below normal body weight, current smoking, personal history of adult fracture, excess alcohol or caffeine consumption, and history of repeated falls or increased risk of falling.
Practice guidelines for the diagnosis and management of osteoporosis in IBD were published by the American Gastroenterology Association (AGA) and American College of Gastroenterology (ACG) in 2003. The recommendations by each organization were virtually the same and stated that bone mineral density with DXA scanning be assessed only in a select group of patients with IBD. Screening was suggested in postmenopausal women or men over the age of 50, in patients with prolonged corticosteroid use (greater than 3 consecutive months or recurrent courses), patients with a personal history of a low trauma fracture, or patients with hypogonadism.39, 40
Ultimately, osteoporosis is a preventable disorder. Although treatment of the disease is beyond the scope of this review, there are a few safe and inexpensive interventions that may be used in high-risk groups. The first are lifestyle modifications such as smoking cessation, regular weight-bearing exercise, minimizing alcohol and caffeine consumption, as well as discontinuing medications that affect perception and balance (e.g., benzodiazepines, tricyclics, antipsychotics, and antihistamines). Finally, adequate calcium (1200 mg per day in postmenopausal women) and vitamin D (400–800 IU per day) intake have been shown to be effective in fracture prevention.41, 42
Glucocorticoid use is the most common variable associated with decreased BMD in IBD patients. The greatest bone loss occurs in the first 6 months of the initial course of corticosteroids.43 Therefore, the greatest intervention in patients with IBD is to minimize the use of glucocorticoids, when possible, and to use steroid-sparing agents such as azathioprine and anti-TNF medications, if applicable.
BLOOD PRESSURE SCREENING
Hypertension affects ≈50 million individuals in the United States and about 1 billion people worldwide. As the US population ages, the prevalence of hypertension will likely increase.
The Seventh Report of the Joint National Committee on the prevention, detection, evaluation and treatment of high blood pressure (JNC 7) defines hypertension as ≥140/90 mmHg or ≥130/80 mmHg for patients with diabetes or chronic kidney disease. Individuals with a systolic blood pressure of 120–139 mmHg or a diastolic blood pressure of 80–89 mmHg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent cardiovascular disease.
The IBD population is at increased risk for secondary hypertension primarily due to some of the medications used in treating the disease, with corticosteroids and cyclosporine being the most notable. A select number of patients may need treatment during and after prednisone or cyclosporine therapy but most hypertension resolves with removal of the causative agent.44–46
When treating hypertension, the first approach in treatment is lifestyle modification. Major lifestyle modifications shown to lower blood pressure include weight reduction in those individuals who are overweight or obese,47 adoption of the Dietary Approaches to Stop Hypertension (DASH) eating plan,48 and reduction of dietary sodium,49, 50 increase in physical activity,51, 52 and moderation of alcohol consumption.53 If antihypertensives are needed, JNC 7's recommendation is to start with a thiazide agent.54 Other agents that tend to be well tolerated in the IBD population are the calcium-channel blockers. This has the added benefit of slowing demineralization of bone in osteoporotic patients which, as mentioned above, can be a significant problem in IBD patients. Ultimately, if the hypertension is caused by corticosteroid or cyclosporine administration, discontinuation of the offending agent should be attempted.
Psychosocial factors play an important role in IBD. The psychological well-being of patients is often affected given the disease's chronic relapsing nature, the use of immunosuppressive agents, and the medication side effects.55, 56 The presence of a psychological disorder in IBD is associated with poor health-related quality of life57, 58 and self-perceived functional disability59 irrespective of symptom severity. Moreover, data suggest that depressed patients are less compliant60 and pursue greater healthcare utilization.61
Rates of depression in IBD range from 15%–35%.59, 62 In a population-based study, Walker et al63 reported that the lifetime risk for major depressive disorder was more than twice as high in the IBD sample, occurring in more than a quarter of those with IBD. In addition, for those patients with a history of depression the onset was well before the diagnosis of IBD. This is important for clinicians to know, given that patients are likely at risk even on the initial gastroenterologic evaluation. Therefore, one must be vigilant in screening IBD patients for depression and implementing appropriate medical treatment.
Annual ophthalmologic screening is recommended. Patients on corticosteroid use may develop glaucoma27 and also have temporary vision changes while on the medication. Any patient complaining of eye pain or vision changes should be referred for evaluation immediately, as some complications may lead to permanent vision loss. IBD patients may also have subclinical extraintestinal manifestations involving the eye. One study of 60 patients with IBD found ophthalmologic manifestations in 26/60 (43%) of patients. These included conjunctivitis, episcleritis, retinal vasculitis, and optic neuritis.64
CANCER AND DYSPLASIA
Cervical cancer was once 1 of the most common causes of cancer deaths in US women. However, the mortality rate decreased by over 70% between the years of 1955–1992 largely because of mass screening with the Papanicolaou (Pap) smear.65
Human papilloma virus, acquired through sexual transmission, is the most important risk factor for cervical neoplasia. Host factors such as age, nutritional status, immune function, and smoking are thought to modulate the incorporation of the viral DNA into the host cells. Women with IBD, often requiring immunosuppressive therapy for management, have been shown to have a higher prevalence of abnormal Pap smears than age-matched controls.66, 67 More recent data, available only in abstract form, suggest that young female smokers with IBD on immunomodulatory therapy are a particularly susceptible population.
Currently, the American College of Obstetrics and Gynecology (ACOG) recommends annual screening for cervical dysplasia in women under the age of 30. Women 30 years of age and older who have had 3 normal consecutive Pap smears are then assessed every 2–3 years. For patients who are immunocompromised, including HIV-infected women and those who have undergone transplantation, screening should be performed twice in the first year after diagnosis and then annually subsequently. Given the above data, young female smokers on immunosuppressive therapy with IBD should be recognized as a vulnerable population.
The HPV vaccine (Gardasil, Merck) is indicated for the prevention of cervical dysplasia caused by HPV high-risk types 16 and 18, as well as 6 and 11 which are associated with genital warts. It is recommended for females ages 9 to 26 prior to the initiation of sexual activity, as well as for those who have already engaged in intercourse. The CDC also recommend the administration of the vaccine to women with a history of HPV infection or an abnormal Pap smear. However, the data do not indicate that the vaccine will have a therapeutic effect on an existing cervical lesion. Women with IBD on immunosuppressants should be considered candidates for the vaccine regardless of sexual activity. Screening for cervical intraepithelial neoplasia (CIN) and cancer should continue in both vaccinated and unvaccinated women according to the aforementioned guidelines.
Anal and cervical squamous cell carcinomas share much in common. They have similar histopathology and behavior as well as epidemiologic risk factors and both have an etiologic link to high-risk strains of human papillomavirus (HPV 16, 18).68–70
Although anal carcinoma is less common than cervical cancer, the US incidence of squamous cell cancers of the anus (SCCA) has increased by about 96% in men and about 39% in women in the past 20–30 years.71–73 The prognosis of SCCA varies widely according to the extent. With local disease, the 5-year survival is 78% versus 56% for regional disease and 18% with distant disease.74
Anal Pap smears are available but current guidelines for their use do not exist and, therefore, they are not used routinely. However, some practitioners screen high-risk patients, such as those with HIV-infection or men having sex with men (MSM), routinely. Information about the incidence of SCCA in IBD is limited.
Further investigation is needed to assess the validity of anal Pap smear screening and the utility of screening in the IBD population. Certainly, this is an important area and practitioners' increased awareness of anal dysplasia is clearly important to identify early disease.
Breast cancer is the most common malignancy in US women and is the second leading cause of death among American women.74 This is especially germane to CD, where evidence suggests that first-degree relatives of CD patients, specifically mothers, may have a 2-fold higher frequency rate of breast cancer compared with controls.75 In addition, the recent study by Sogaard et al76 suggests that CD patients with breast cancer are not treated as aggressively as controls, and their survival, when treated with chemotherapy, is worse than in patients without IBD.
Given the above findings, screening for breast cancer in IBD patients is of paramount importance. The American Cancer Society guidelines from 2003 recommend that the average-risk woman have a clinical breast examination (CBE) every 3 years and counseling to raise awareness of breast cancer symptoms beginning at the age of 20 followed by annual mammography and CBE beginning at the age of 40. Monthly breast self-examination is no longer recommended but women should be informed of its potential benefits, limitations, and harms (including false-positives).77
Women at high risk should have an annual MRI and mammogram. This includes women with a known BRCA mutation, who are untested but have a first-degree relative with a BRCA mutation, and patients who, on breast cancer risk-estimation models, have an estimated lifetime risk of greater than 20%. Other indications for MRI screening include: women who have been treated with radiation to chest between ages 10–30 years or who are mutation carriers or first-degree relatives of other high-risk genetic syndromes such as Li Fraumeni syndrome, Cowden syndrome, or Bannayan–Riley–Ruvalcaba syndrome. There is no specific upper age limit at which screening mammography should be discontinued. As long as the patient is in good health and can undergo breast cancer treatment, she should be screened.78
An estimated 1 in 6 men in the US will receive the diagnosis of prostate cancer in his lifetime and over 27,000 men in the US died of prostate cancer in 2006.71 However, prostate cancer is a clinically variable disease. A significant proportion of cases detected through screening will never cause symptoms during a patient's lifetime. As such, many patients may not benefit from screening and may, in fact, be harmed by early cancer detection and treatment. Therefore, screening for prostate cancer remains controversial. The US Preventive Services Task Force states that the evidence for prostate cancer screening is insufficient to assess the balance of benefits and harms for men younger than age 75. The Task Force does not recommend screening in men over the age of 75 because the potential risks outweigh the benefits (Class D recommendation).79
The American Cancer Society (ACS) guidelines for prostate cancer screening emphasize the importance of shared decision-making on testing between the physician and patient. The Society recommends that prostate-specific antigen (PSA) and digital rectal exam (DRE) should be offered yearly beginning at the age of 50 to patients who have a life expectancy of at least 10 years. Before a decision about screening is made, a discussion about the potential benefits and risks associated with testing should take place. Men at high risk, including men of sub-Saharan African descent and those with a first-degree relative diagnosed with prostate cancer at less than 65 years of age, should begin screening at age 45. Those with an even greater risk, with more than 1 first-degree relative with an early prostate cancer, can begin screening at age 40. If the PSA is less than 1.0 ng/mL, then no additional screening is needed until age 45. If the PSA is between 1 ng/mL and 2.5 ng/mL, then annual testing is recommended. If the PSA is 2.5 ng/mL or greater, then further evaluation with biopsy should be considered.77
The preponderance of evidence of the risk of skin cancer and immunosuppression has largely been reported in the transplant literature. Nonmelanoma skin cancers (NMSC) account for over 90% of all skin cancers posttransplantation.80–82 Squamous cell carcinoma, the most common skin cancer in transplant patients, occurs 65 to 250 times more frequently than in the general population,81–83 whereas the incidence of basal cell cancer is only 10 times higher in transplant patients.82
The incidence of NMSC increases significantly with the duration of immunosuppression. In Dutch recipients, for example, the skin cancer incidence rises from 0.2% at 1 year to 41% long-term.84 Moreover, in some series the addition of cyclosporin to azathioprine and prednisolone increases the risk of NMSC by 3-fold,85 but did not have an effect in other series.81, 86
The increased risk of melanoma with immunosuppression has been reported in some81, 87–90 but not all studies.83 In Australia, a 2-fold increase was observed in renal transplant patients relative to the nontransplant population85 and a 3-fold increase was seen in methotrexate-exposed rheumatoid arthritis patients as compared to the general population.91 However, both fair complexion and UV radiation are thought to be additional risk factors92 and, therefore, the rates in Australia may be higher secondary to greater sun exposure.
Data on skin cancer rates in IBD are sparse and conflicting. Ekbom et al,93 in a Swedish population-based study, demonstrated an increased risk of squamous cell cancer in CD but not in UC patients. However, in a population-based study from Denmark there was a trend of increased occurrence of skin cancers but the differences were not statistically significant.94
Given the paucity of evidence, routine skin cancer surveillance is not currently recommended in patients with IBD on immunosuppression, but increased awareness of possible lesions is of paramount importance for early detection and treatment.
The role of the gastroenterologist is to achieve and maintain remission and monitor for adverse events in a patient with IBD. However, given the young age of many of these patients, the multiple potential comorbidities, and the frequent role of the gastroenterologist as the principal physician managing their care, a working knowledge of the special healthcare needs of this population is vital. The Addendum Table provides a checklist of key health maintenance issues for the patient with IBD.