Inflammatory Bowel Disease PDF

Inflammatory Bowel Disease Lia Pierson Bruner, MDa,*, Anna Marie White, MD b , Siobhan Proksell, MDc KEYWORDS ! Inflammatory bowel disea...

Inflammatory Bowel Disease Lia Pierson Bruner, MDa,*, Anna Marie White, MD b , Siobhan Proksell, MDc KEYWORDS ! Inflammatory bowel disease ! Crohn disease ! Ulcerative colitis ! Chronic diarrhea ! Immunosuppression KEY POINTS ! Maintain a high degree of suspicion for inflammatory bowel disease (IBD) in patients with characteristic symptoms and consider an appropriate workup through laboratory evalua- tion and endoscopy with biopsy to achieve an early diagnosis. ! Be cognizant of extraintestinal manifestations, which may present before gastrointestinal symptoms. ! Important preventive care in IBD includes colorectal cancer screening, immunizations, and osteoporosis screening. ! Collaboration with gastroenterology is important for both an accurate diagnosis and development of an individualized treatment plan for longitudinal management. INTRODUCTION Inflammatory bowel disease (IBD) consists of a subset of inflammatory diseases involving the small intestine and colon. The primary types are ulcerative colitis (UC) and Crohn disease (CD). These conditions have some overlap in symptoms but repre- sent distinct entities that result from various factors ranging from genetic to environ- mental to immunologic. Although IBD is typically diagnosed and managed by a gastroenterologist, primary care physicians (PCPs) play a pivotal role in longitudinal care encompassing preventive care and symptom management. Most patients with IBD are diagnosed at a young age and require monitoring and guidance for medical management, potential complications, and health maintenance, which should be achieved through collaboration between the PCP and the gastroenterologist. a Augusta University/University of Georgia Medical Partnership, UGA Health Sciences Campus, Russell Hall, Room 235K, 1425 Prince Avenue, Athens, GA 30602, USA; b University of Pitts- burgh School of Medicine, UPMC Shadyside Hospital, North Tower, Room 307, 5230 Centre Avenue, Pittsburgh, PA 15232, USA; c Division of Digestive Health and Liver Disease, University of Miami, Miller School of Medicine, 1120 Northwest 14th Street, CRB, Room 1184, Miami, FL 33136, USA * Corresponding author. E-mail address: [email protected] Prim Care Clin Office Pract 50 (2023) 411–427 https://doi.org/10.1016/j.pop.2023.03.009 primarycare.theclinics.com 0095-4543/23/ª 2023 Elsevier Inc. All rights reserved. A4 5 ( CA 2A / (C CA 2 D A. E4 5 ) 4 A A D 0 CA A E4 CA D / A A CA A A C 4 ) I A D , 4 5 A A5 4 A A D 5 A 412 Bruner et al EPIDEMIOLOGY There are approximately 3 million people with IBD in the United States, with an equal incidence of UC and CD.1 Although most people present with symptoms in their 20s and 30s, IBD can also be diagnosed in the elderly. There are many risk factors for the development of IBD, none of which are guaranteed to lead to its development. Some consensus protective factors and risk factors are shown in Table 1.2,3 PATHOPHYSIOLOGY CD is characterized by intestinal skip lesions with transmural inflammation that can occur anywhere along the gastrointestinal (GI) tract, whereas UC is characterized by continuous superficial inflammation localized to the colon and rectum. Although UC and CD have different intestinal manifestations, underlying pathophysiology is similar and incompletely understood. IBD involves a complex interplay of genetic and environmental factors as they relate to intestinal barrier function, immune response, and microbial dysbiosis. Although no single gene variant appears to be use- ful for diagnosis, more than 200 gene loci, mostly involving innate immunity and epithelial barrier regulation, have been associated with IBD. The marked increase in IBD incidence in industrialized countries and immigrants moving from low-incidence to high-incidence areas suggests that environmental factors also contribute. Differ- ences in intestinal microbiota also seem to affect the disease processes in both pos- itive and negative ways. CLINICAL PRESENTATION Patients with IBD may present with a variety of symptoms that can differ in UC and CD; however, common symptoms include persistent abdominal pain, diarrhea (with or without blood), fatigue, and weight loss (Table 2).4,5 Symptoms do not necessarily correlate with disease activity. Extraintestinal manifestations (EIM) are relatively common and are similar for UC and CD. EIM can include aphthous stomatitis, iritis, episcleritis, uveitis, arthritis, cardiovascular diseases (CVDs), thromboembolism, er- ythema nodosum, pyoderma gangrenosum, sacroiliitis, primary sclerosing cholangi- tis (PSC), and gallstones. These conditions can occur before IBD is diagnosed, so PCPs need to be able to recognize these conditions (Fig. 1) and should have a high index of suspicion for IBD in patients with these conditions who have, or go on to develop, GI symptoms. Many EIM, other than PSC, ankylosing spondylitis, and uveitis, parallel the clinical course of IBD, giving a window into intestinal disease activity.6 Table 1 Protective factors and risk factors in inflammatory bowel disease Protective Factors Risk Factors Ulcerative colitis2 ! Appendectomy before disease ! Smoking cessation development ! Transition from plant-based to ! Plant-based diet processed diet Crohn disease3 ! Breastfeeding ! Smoking ! Statin medications ! Antibiotics in childhood ! Mediterranean diet ! Aspirin and NSAID use ! Oral contraceptive use ! Low-fiber, highly processed diet A4 5 ( CA 2A / (C CA 2 D A. E4 5 ) 4 A A D 0 CA A E4 CA D / A A CA A A C 4 ) I A D , 4 5 A A5 4 A A D 5 A  Inflammatory Bowel Disease 413 Table 2 Clinical presentation of inflammatory bowel disease History Physical Examination Ulcerative ! Abdominal pain ! Tenesmus ! Abdominal tenderness to colitis4 ! Bloody diarrhea ! Weight loss palpation (with or without ! Fatigue ! Acute abdomen (guarding, mucus) rebound tenderness), abdominal distension, and fever may suggest toxic megacolon, a surgical emergency Crohn ! Varies by disease ! Nausea and vomiting ! Abdominal tenderness to disease5 site/extent ! Weight loss palpation ! Abdominal pain ! Fatigue ! Palpable mass may suggest ! Diarrhea abscess (with or without ! Fecaluria and pneumaturia blood) suggest fistula ! Perianal disease DIAGNOSIS The diagnosis of IBD is based on the overall presentation and diagnostic features found during workup, including endoscopic evaluation with biopsy. Initial workup should include a basic laboratory evaluation as well as stool studies to rule out infec- tion and to assess for inflammation (fecal calprotectin; sensitivity 93%, specificity 96%)7 (Table 3). If there is a high suspicion for IBD, consider adding laboratory tests Fig. 1. Extraintestinal manifestations of IBD that PCPs should recognize. (From Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 35, Fig. 69. (Aphthous Stomatitis), and Kühbacher T, Schreiber S. Chapter 9: Approach to the Patient with Inflammatory Bowel Disease. In: Faigel, DO, Cave, DR, eds. 1st ed. Saunders Elsevier; 2008:91-103. (Erythema Nodosum), and Schwartz MH: Textbook of physical diagnosis: his- tory and examination, ed 6, Philadelphia, 2009, Saunders. (Iritis); and Courtesy Misha Rose- nbach, MD (Pyoderma Gangrenosum).) A4 5 ( CA 2A / (C CA 2 D A. E4 5 ) 4 A A D 0 CA A E4 CA D / A A CA A A C 4 ) I A D , 4 5 A A5 4 A A D 5 A 414 Bruner et al Table 3 Initial primary care workup for possible inflammatory bowel disease Stool Studies Laboratory Studies Laboratory Studies to Consider Stool PCR (or culture) Complete blood count Iron panel Clostridioides difficile Complete metabolic Vitamin B12 (may be included in panel stool PCR panel) Ova and parasites C-reactive protein Quantiferon gold (tuberculosis screen) Fecal calprotectin Hepatitis B (surface antigen, core antibody, and possibly surface antibody depending on vaccination status. Note that this is different from an acute hepatitis panel.) as needed before starting immunosuppressive therapy, including tuberculosis and hepatitis B testing. Notably, genetic testing and antibody panels are not indicated when making an IBD diagnosis. Given the relatively young age at presentation, the need for endoscopic evaluation, and risks of radiation exposure, computed tomogra- phy is usually avoided unless there is concern for an acute abdomen, in which case emergent surgical consultation and imaging may be necessary. If symptoms persist and there is suspicion for IBD, the patient should be referred to gastroenterology to ensure prompt indentification and treatment, thus reducing potential complications. TREATMENT In the past decade an expansive armamentarium of biologic and small-molecule ther- apies has become available to induce and maintain remission in IBD. The general clas- ses of treatment as well as their potential adverse effects and necessary monitoring are listed in Table 4. After an initial diagnosis, anti-inflammatory medication, such as prednisone, may be used as a bridge to steroid-sparing maintenance therapy in consultation with gastro- enterology. Surgical intervention may also be necessary depending on the severity and complications of IBD, including strictures and fistulas. This can range from a total colectomy to a segmental resection of the bowel. COMPLICATIONS Potential complications of UC include disease recurrence, toxic megacolon, fulminant colitis, perforation, dysplasia, and colorectal cancer. Given the transmural nature of inflammation in CD, additional complications can include stricture, fistula, abscess, and luminal malignancy. In addition, patients with IBD can develop nutritional defi- ciency, iron deficiency, and vitamin B12 deficiency as a result of disease activity and/or surgical interventions. Both PCPs and gastroenterology should monitor pa- tients for these long-term complications of IBD. Interestingly, clinical symptoms of UC activity correlate poorly with endoscopic evidence of disease severity, so periodic endoscopy is important to prevent undertreatment.8 PREGNANCY Women with IBD can have safe and healthy pregnancies with remission being a goal. Mesalamines, azathioprine, tumor necrosis factor (TNF)-a inhibitors, anti-integrin antibodies, and interleukin-12/23 antagonists do not seem to increase risk of A4 5 ( CA 2A / (C CA 2 D A. E4 5 ) 4 A A D 0 CA A E4 CA D / A A CA A A C 4 ) I A D , 4 5 A A5 4 A A D 5 A  Table 4 Inflammatory bowel disease medications Laboratory Monitoring Potential Adverse Medication Class Medications (Route) Mechanism of Action Pretreatment Testing Parameters Effects ) A4 Aminosalicylates Mesalamine (oral) Anti-inflammatory CBC CBC 4 ! Acute interstitial CMP CMP (especially renal nephritis 5 function) ! Mesalamine A hypersensitivity ( (paradoxical reaction to A D treatment) A CA A A C ! Agranulocytosis CA 2A with sulfasalazine 4 (rare) ) Immunomodulators Azathioprine/6- Purine metabolism CBC CBC ! Nausea mercaptopurine antagonist CMP CMP / ! Flulike symptoms (oral) TPMT level Thiopurine (fever, joint pain, 0 A D 5 A I Consider NUDT15 genotyping metabolites swelling, rash) (C CA ! Elevated liver function tests A A D ! Low white blood count , 4 ! Pancreatitis (rare, usually occurs early CA 2 D A in treatment) E4 CA D 5 A Methotrexate (oral or Dihydrofolate CBC ! Nausea SQ) reductase inhibitor CMP ! Elevated liver function tests / A A5 4 A. E4 5 (continued on next page) Inflammatory Bowel Disease 415  416 Table 4 (continued ) Laboratory ) A4 Bruner et al Monitoring Potential Adverse 4 Medication Class Medications (Route) Mechanism of Action Pretreatment Testing Parameters Effects 5 Biologics Infliximab (IV) TNF-a inhibitors ! Quantiferon ! HBcAb CBC ! URI A Adalimumab (IV) Goldc ! CBC CMP ! Other infections ( Golimumab (IV) ! HBsAbd ! CMP (some serious) Certolizumab (IV) ! HBsAg ! Psoriasis (atypical A D pattern) A CA A A C ! Hepatotoxicity CA 2A 4 ! Fatigue Ustekinumab (IV, then IL-12/IL-23 antagonist ! Quantiferon ! HBcAb CBC ! URI SQ) IL-23 antagonist Goldc CMP ) ! CBC ! Other infections Risankizumab (IV, ! HBsAbd ! CMP ! PRES with / then SQ) ! HBsAg ustekinumab (very rare) 0 A D 5 A I Vedolizumab (IV; SQ a4 b7 integrin ! Quantiferon ! HBcAb CBC ! Nasopharyngitis (C CA to be approved in antagonist Goldc ! CBC CMP ! Hepatotoxicity the near future) ! HBsAbd ! CMP ! PML (one reported A A D ! HBsAg case in patient with other risk factors) , 4 Natalizumabb (IV) a4 b1 integrin ! Quantiferon ! HBcAb CBC ! JCV infection antagonist Goldc CBC CMP CA 2 D A E4 CA D ! ! Other infections 5 A ! HBsAbd ! CMP JCV Ab ! Hepatotoxicity ! HBsAg ! JCV Ab Tofacitiniba (oral) JAK 1,3 inhibitor ! Quantiferon ! HBcAb Lipid panel (4–8 wk ! Infection Goldc Lipid Panel after initiation, / A A5 4 A. E4 5 ! ! Increased lipid ! HBsAbd ! CBC then periodically) levels (not shown to ! HBsAg ! CMP CBC have clinical CMP significance thus far)  ! Herpes zoster (at higher doses) Upadacitiniba (oral) JAK 3 inhibitor ! Quantiferon ! HBcAb Lipid panel (12 wk ! Infection Goldc ! Lipid panel after initiation, ! URI ! HBsAbd ! CBC then periodically) ! Acne ) ! HBsAg ! CMP CBC ! Increased lipid A4 CMP levels 4 5 ! Hepatotoxicity Ozanimoda,b (oral) S1P receptor ! Quantiferon ! Baseline EKG CBC ! Infection A modulator (blocks Goldc ! Ophthalmic CMP ! URI ( lymphocyte ability ! HBsAbd examination ! Hepatoxicity to emerge from ! HBsAg ! FEV1/FVC if Rare: A D lymph nodes) clinically A CA A A C ! HBcAb ! Bradycardia ! CBC indicated ! Macular edema CA 2A 4 ! CMP ! Decline in respiratory function ) Abbreviations: CBC, complete blood count; CMP, complete metabolic panel; EKG, electrocardiogram; FEV1/FVC, forced expiratory volume in 1 second/forced vital / capacity; HBcAb, hepatitis B core antibody; HBsAg, hepatitis B surface antigen; IV, intravenous; JAK, Janus kinase; JCV Ab, John Cunningham virus antibody; PML, progressive multifocal leukoencephalopathy; PRES, posterior reversible encephalopathy syndrome; S1P, sphingosine 1 phosphate; SQ, subcutaneous; TPMT, thio- 0 A D 5 A I purine S-methyltransferase; URI, upper respiratory infection. a Approved for ulcerative colitis only. (C CA b Approved for multiple sclerosis. c Depending on exposure risk, annual tuberculosis testing may be appropriate. A A D d Consider if vaccination likely done, but no records available. , 4 CA 2 D A E4 CA D 5 A / A A5 4 A. E4 5 Inflammatory Bowel Disease 417 418 Bruner et al pregnancy complications.9 There are minimal data on the small molecules, and some animal models have shown potential fetal harm. Methotrexate should be discontinued at least 3 months before conception, and alternatives to methotrexate should be considered in women of child-bearing age. Consultation with Maternal Fetal Medicine can be helpful. HEALTH MAINTENANCE IBD independently increases risks for other medical conditions, such as infections, CVD, anxiety, and depression, as well as some cancers.10 Many patients with IBD are also on immunosuppressive therapies, resulting in further increased risks for certain infections and malignancies. Rates of standard screenings and vaccinations are suboptimal in patients with IBD,11,12 and intensification of some health mainte- nance practices is needed to improve outcomes10,13 (Table 5). PCPs and gastroenter- ologists are sometimes unsure which specific screenings and vaccines are indicated, so systematic education and resources are needed to increase rates. Disease Prevention and Treatment Advances in treatment have markedly increased the quality of life of patients with IBD owing to higher rates of symptom resolution and mucosal healing. However, many of these newer immunosuppressive therapies also increase risks for viral and bacterial infections, many of which can be minimized with vaccination. Some of the immuno- suppressive therapies, especially corticosteroids and TNF-a inhibitors, can also blunt the immune response to many of the vaccines, including influenza, hepatitis B, human papillomavirus (HPV), herpes zoster (HZ), and pneumococcal, making them less effec- tive. Vaccination before the start of immunosuppressive therapy is preferred, although necessary IBD treatment should not be delayed for vaccinations. Patients with IBD who are not on immunosuppressive therapy should receive all age-appropriate and condition-specific vaccinations based on Centers for Disease Control and Prevention (CDC) (Advisory Committee on Immunization Practices [ACIP]) guidelines.14 However, in patients on immunosuppressive therapy, live vacci- nations (measles, mumps, and rubella [MMR], varicella, and intranasal influenza) are contraindicated. Patients who are already on immunosuppressive therapy should still receive all recommended non-live vaccines, although immune responses may not be as robust. The rationale for disease prevention and treatment adjustments in persons with IBD is reviewed in later discussion, and specific recommendations are summa- rized in Table 5. Influenza Patients with IBD are at higher risk for influenza infections and resultant hospitaliza- tions compared with the general population,10 making annual vaccination important. These risks are particularly high for patients on corticosteroids. The high-dose trivalent formulation of the influenza vaccine is preferred for those with IBD on immunosup- pressive therapy and those "65 years old.13 With increased risk for complications from influenza, patients on immunosuppression also fall into a CDC priority group for antiviral treatment of suspected or confirmed infections. COVID-19 Patients with IBD with active disease and those on immunosuppression with high- dose corticosteroids and certain medication combinations are at increased risk for se- vere COVID-19.15 They should be vaccinated with the COVID-19 primary series as well as boosters based on the CDC recommendations for immunosuppressed persons. A4 5 ( CA 2A / (C CA 2 D A. E4 5 ) 4 A A D 0 CA A E4 CA D / A A CA A A C 4 ) I A D , 4 5 A A5 4 A A D 5 A  Inflammatory Bowel Disease 419 Table 5 Specialized health maintenance for patients with inflammatory bowel disease Disease prevention and treatment Influenza Give annual high-dose trivalent vaccine for any age on TNF-a inhibitors and those "65 y.13 Give all others annual quadrivalent vaccine. Avoid live attenuated nasal vaccine in immunosuppressed Treat immunosuppressed patients with antiviral therapy for confirmed or suspected influenza infection (#48 h from symptom onset) COVID-19 Vaccinate all with primary series and booster doses based on current CDC recommendations for immunosuppressed persons Give immunosuppressed patients early treatment for COVID-19 Hepatitis B Screen for infection (HBsAg and HBcAb) at diagnosis and before starting TNF-a inhibitors Give complete hepatitis B series if no infection and not previously vaccinated16 Only if immunosuppressed, check for immunity (HBsAb titer) "1 mo after series completion. Further doses indicated if not immune17 HPV Give HPV vaccine series between ages 9 and 26 y. Still strongly consider vaccination between ages 27 and 45 y if not previously vaccinated If immunosuppressed, give 3-dose rather than 2-dose series even if series started before age 15 y Pneumococcal disease If no previous PCV13, PCV15, or PCV20 as an adult, give either one dose PCV20 or one dose of PCV15 followed by PPSV23 1 y later. No further pneumococcal vaccines are needed at age 65 y19 If PCV13 previously received (with or without PPSV23), complete series for immunocompromised patients per ACIP recommendations14 Measles, mumps, and rubella Assess for immunity to MMR (receipt of 2 doses of MMR). (MMR)13 If no immunization record, check antibody titers If nonimmune, consider 2 doses of live attenuated MMR, with a minimum interval of 4 wk. Hold high-dose steroids and biologics for 3 mo prior and 4 wk after vaccination Varicella-zoster virus Assess for immunity to varicella.a If criteria not met, check antibody titers20 If nonimmune, consider 2 doses of live attenuated VAR, with a minimum interval of 4 wk. Hold high-dose steroids and biologics for 3 mo before and 4 wk after vaccination13 Herpes zoster Give 2 doses RZV, with a minimum interval of 4 wk, to all adults with history of varicella infection or receipt of 2 doses VAR21 (continued on next page) A4 5 ( CA 2A / (C CA 2 D A. E4 5 ) 4 A A D 0 CA A E4 CA D / A A CA A A C 4 ) I A D , 4 5 A A5 4 A A D 5 A 420 Bruner et al Table 5 (continued ) Follow standard recommendations for other vaccines, including Tdap, meningococcal, and hepatitis A vaccines Cancer screenings Colorectal cancer Increase frequency of surveillance/treatment. Refer back to GI if no follow-up in the last year Cervical cancer Follow guidelines for persons living with HIV: annual (immunosuppressed only) cytology for 3 y (starting within 1 y of sexual debut), then cytology every 3 y if normal (switch to cytology/ HPV cotesting at age 30 y)25 Colposcopy referral is triggered earlier for atypical squamous cells of undetermined significance with high-risk HPV or any cervical dysplasia (low-grade squamous intraepithelial lesion or higher) Skin cancer Visually examine skin annually Follow other standard cancer screening recommendations, including those for breast, prostate, and lung cancer Other screenings Cardiovascular disease Screen for and aggressively treat CVD risk factors with (CVD) risk increased CVD risk Achieve and maintain good control of IBD Depression Screen annually and as needed and treat accordingly to improve outcomes Anxiety Screen annually and as needed and treat accordingly Follow other standard screening recommendations, including those for osteoporosis, hepatitis C, and HIV Modifiable lifestyle factors Smoking cessation Use evidence-based strategies for smoking cessation counseling to improve outcomes in CD10 Diet Assess for malnutrition/undernutrition, and supplement and/or refer to a dietician if present With limited data, a Mediterranean diet with avoidance of highly processed foods and artificial sweeteners may be reasonable in IBD given additional known health benefits29,30 Watch for vitamin B12 deficiency as well as iron or folate deficiency with active disease and/or ileal resection Exercise Encourage regular physical activity as safe and probably beneficial31 Sun protection Recommend sun-protective practices with increased skin cancer risk Contraception Recommend highly efficacious contraception for patients who do not desire pregnancy and are taking medications that may increase neonatal adverse effects Abbreviations: PCV13 (15 or 20), 13 (15 or 20)-valent pneumococcal conjugate vaccine; PPSV23, 23- valent pneumococcal polysaccharide vaccine; Tdap, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis; VAR, live attenuated varicella vaccine. a Varicella immunity 5 Vaccine record of age-appropriate 2-dose series, laboratory confirmation of immunity, or diagnosis or verification of a varicella infection or herpes zoster by a health care provider. A4 5 ( CA 2A / (C CA 2 D A. E4 5 ) 4 A A D 0 CA A E4 CA D / A A CA A A C 4 ) I A D , 4 5 A A5 4 A A D 5 A  Inflammatory Bowel Disease 421 Those with IBD on immunosuppression are also candidates for early COVID-19 treat- ment. It is important to continue IBD treatment during a COVID-19 infection because discontinuation could precipitate a flare. Hepatitis B Reactivation of hepatitis B can have serious consequences, including fulminant liver failure and death. Although it is not clear to what extent reactivation of hepatitis B oc- curs in patients with IBD on immunosuppression, potential consequences are serious enough that screening for infection is recommended at diagnosis and before starting TNF-a inhibitors. Further workup is needed before therapy for positive screens. Give the complete hepatitis B vaccine series to all patients with IBD who have not been pre- viously vaccinated.16 For those on immunosuppression at the time of vaccination, the ACIP recommends testing for immunity more than 1 month after series completion (hepatitis B surface antibody, HBsAb) owing to potentially reduced immune response. If HBsAb is less than 10 mIU/mL (nonimmune), a repeat series or a challenge dose fol- lowed by recheck for immunity is recommended.17 Human papillomavirus Patients with IBD on immunosuppressive therapy have increased rates of cervical cancer,18 and HPV vaccination given before exposure to high-risk HPV subtypes is highly effective at preventing cervical cancer and likely other HPV-associated cancers. Three, rather than two, doses of HPV vaccine should be given to patients on immuno- suppression even if the series is started before age 15. Although vaccination starting at age 9 and before immunosuppression is ideal, it is recommended for all men and women up to age 26 and is approved for use between the ages of 27 and 45 with shared decision making. Vaccination even in the older age range should be strongly considered, given the increased risks for patients with IBD. Pneumococcal disease Patients with IBD are at increased risk of pneumococcal infection before and after diagnosis. Treatment with immunosuppressive therapies, including corticosteroids and TNF-a inhibitors, further increases risk of pneumonia, the infection causing the greatest increase in mortality in patients with IBD.13 All patients 19 years old or older with underlying conditions like IBD need extra pneumococcal vaccination (see Table 5).14,19 Measles, mumps, and rubella With recent measles outbreaks, there has been concern that patients on immunosup- pression might be vulnerable to infection. Patients with IBD should be assessed for immunity to MMR, as evidenced by receipt of 2 doses of MMR after 12 months of age.13 Because of risk of false negative testing, the ACIP does not recommend check- ing antibody titers in those with IBD on immunosuppression who have previously been immunized. If patients have not been immunized or are tested and found to be nonim- mune, the live attenuated MMR vaccination should be considered, but is contraindi- cated with immunosuppression. Live vaccines should be given at least 4 weeks before starting immunosuppression, or if already on immunosuppression, therapy must be held for at least 3 months before the vaccination and 4 weeks after the vacci- nation.13 Delaying or interrupting immunosuppressive treatment to administer live vaccines comes with risks of disease progression with possible emergency depart- ment visits, hospitalizations, and surgery, so it should only be done in consultation with gastroenterology. A4 5 ( CA 2A / (C CA 2 D A. E4 5 ) 4 A A D 0 CA A E4 CA D / A A CA A A C 4 ) I A D , 4 5 A A5 4 A A D 5 A 422 Bruner et al Varicella-zoster virus Patients with vaccine records showing an age-appropriate 2-dose series of varicella vaccine, laboratory confirmation of immunity, or diagnosis of a varicella infection or HZ by a health care provider are considered to have evidence of immunity and do not need further vaccination. Patients meeting these criteria should not undergo lab- oratory screening for immunity because commercial tests have significant false nega- tive rates, especially for vaccine-induced immunity.13 Patients with IBD not meeting criteria for varicella immunity should have varicella-zoster immunoglobulin G titers checked. If nonimmune, varicella-zoster vaccine should be considered with the same constraints as MMR with regard to live vaccines and immunosuppression.20 Herpes zoster Patients with IBD are at increased risk for HZ even without immunosuppressive ther- apy. In fact, HZ is the most frequent serious infection in patients with IBD.13 In addi- tion, patients on immunosuppressive therapy are at higher risk of more severe disease with complications, making prevention by vaccination key. Adults with IBD who have either had varicella or received 2 doses of varicella vaccine are at risk for HZ and should receive recombinant zoster vaccine (RZV), preferably before starting immunosuppressive therapy, and should not wait until age 50.21 Live attenuated her- pes zoster vaccine (ZVL) is no longer recommended, and RZV should be given even if patients previously received ZVL. Vaccination of household members of patients with inflammatory bowel disease on immunosuppression Immunocompetent household contacts should be vaccinated with all non-live vac- cines to help prevent transmission of diseases to the immunosuppressed family mem- ber. Live vaccines can also be given as recommended with a few adjustments. The inactivated influenza vaccine is recommended over the live attenuated version in household contacts owing to the theoretical risk of live-virus transmission. MMR and varicella live attenuated vaccines can be safely given to immunocompetent household contacts, but if a postvaccination rash develops with varicella vaccine, contact with persons who are immunosuppressed should be avoided until the rash re- solves.5 Infants born to mothers on immunosuppressive therapy should not receive live rotavirus vaccine because of relative immunosuppression for up to 6 months from medications crossing the placenta. Similarly, highly immunocompromised per- sons should ideally avoid contact with stool from infants vaccinated against rotavirus or at least be vigilant about handwashing in the 4 weeks after vaccination.5 Cancer Screening IBD is associated with an overall increased risk of malignancy, with moderate epide- miologic evidence of association with 15 cancer types, GI cancers (including colo- rectal and mouth to terminal ileum [CD]) as well as extraintestinal cancers (including bile duct and liver, intrahepatic cholangiocarcinoma [in PSC], nonmelanoma skin can- cer, kidney [CD], and thyroid).22 Intestinal inflammation from IBD itself is known to in- crease risks of GI cancers, and although immunosuppressive therapy for IBD decreases the risk of these cancers, there is some evidence of increased risk of extra- intestinal cancers, such as lymphomas, acute myeloid leukemia and myelodysplastic syndromes, urinary tract cancers, skin cancers,23 and cervical cancer.18 Patients with IBD should follow the standard screening recommendations for breast, prostate, and lung cancer, but need increased screening for colorectal cancer, cervical cancer (if immunosuppressed), and skin cancer (see Table 5). A4 5 ( CA 2A / (C CA 2 D A. E4 5 ) 4 A A D 0 CA A E4 CA D / A A CA A A C 4 ) I A D , 4 5 A A5 4 A A D 5 A  Inflammatory Bowel Disease 423 Colorectal cancer IBD has long been associated with an increased risk of colorectal cancer, with GI typi- cally directing and performing colorectal dysplasia surveillance. The PCP role in colo- rectal cancer screening is largely one of coordination to ensure regular GI follow-up, even if disease symptoms are minimal and/or patients are not on immunosuppression. Cervical cancer There are data suggesting that cervical cancer screening rates in patients with IBD are not optimal.18 Although there is no convincing evidence to date that UC or CD by themselves increases the risk of cervical cancer, immunosuppressive IBD treatment does seem to increase the risk of both cervical dysplasia and cervical cancer. Because of this, patients with IBD on immunosuppression should follow the more frequent screening schedule recommended for persons living with HIV.24,25 Given the increased risks and that oncogenic HPV causes cervical cancer, universal child- hood HPV vaccination should be a priority. Skin cancer There is an increased risk of skin cancer, including melanomas as well as squamous and basal cell carcinomas, in patients with IBD as compared with the general popula- tion.22 This is thought to be largely, but not entirely, due to immunosuppressive ther- apy. For the general population, there is insufficient evidence to recommend visual surveillance for skin cancer; however, the risks are higher in the IBD population, and it should be considered.10 Other Screenings and Prevention Patients with IBD should receive all other recommended screenings, including HIV, hepatitis C, and osteoporosis screening. These patients have increased rates of oste- oporosis and fractures, but this appears to be explained by confounders, including glucocorticoid use and low body mass index. Given this, patients with IBD should follow the standard recommendations for osteoporosis screening, paying special attention to the indications for early screening based on individual risk factors.10 Addi- tionally, the screening and treatment of CVD risk, venous thromboembolism (VTE) risk, depression, and anxiety may need to be intensified (see Table 5). Cardiovascular diseases Patients with IBD have increased risk of CVD when compared with those without IBD, including ischemic heart disease (RR, 1.24), cerebrovascular accidents (OR, 1.18), premature atherosclerotic CVD (OR, 1.27), extremely premature atherosclerotic CVD (OR, 1.61), heart failure (HR, 2.03), and atrial fibrillation (HR, 2.26).26 These risks are highest during acute IBD flares and corticosteroid use as well as during long pe- riods of disease activity. The mechanisms of increased CVD risk are not completely understood, but may involve a combination of chronic inflammation as well as endo- thelial dysfunction, dyslipidemia, thrombocytosis, and dysbiosis of gut microbiota.26 As a result, IBD control is important, as is screening for and aggressively managing CVD risk factors, including calculating atherosclerotic CVD risk and prescribing statins when indicated. Venous thromboembolism Patients with IBD are at 2- to 3-fold higher risk of VTE than the general population, with greatest risk with active disease, more extensive disease, hospitalization, IBD-related surgery, pregnancy, and corticosteroid use.27 Pharmacologic VTE prophylaxis is rec- ommended for patients hospitalized with an IBD flare, even those with hematochezia, A4 5 ( CA 2A / (C CA 2 D A. E4 5 ) 4 A A D 0 CA A E4 CA D / A A CA A A C 4 ) I A D , 4 5 A A5 4 A A D 5 A 424 Bruner et al and is safe and effective as long as bleeding is not hemodynamically significant. How- ever, adherence to these guidelines remains low, and education is needed to improve outcomes.27 Depression and anxiety Among patients with IBD, rates of anxiety and depression are high and exceed those in the general population, with overall prepandemic pooled prevalences of 32.1% and 25.2%, respectively.28 The US Preventive Services Task Force currently recommends that all adolescents and adults be screened for depression, and all persons aged 8 to 64 be screened for anxiety. Appropriate intervals for screening have not been deter- mined, but those at higher risk, including those with IBD, may benefit from more frequent screening. Positive results on screening instruments should be followed up with further assessment for diagnosis and evaluation of comorbid conditions. Patients with depression have worse IBD outcomes, and psychological stress can also worsen disease. Treatment of depression with antidepressants seems to improve psycholog- ical and somatic symptoms of IBD and reduce disease activity as well as medical sys- tem utilization.10 Recognition and treatment of anxiety may also be helpful. Modifiable Lifestyle Factors PCPs are experienced at counseling patients on modifiable lifestyle changes to improve health. Smoking cessation, diet, exercise, sun protection, and contraceptive counseling warrant additional focus in those with IBD. Smoking cessation In addition to the other risks of tobacco use, smoking has been shown to increase the development of CD, speed disease progression, and result in poorer medical and sur- gical outcomes. Smoking cessation improves outcomes, making counseling and treatment a key focus for those with CD who smoke.10 In contrast, smoking is actually protective against the development of UC, but given the balance of benefits and risks, patients with UC should still be counseled to stop smoking. Diet Some vitamin and nutritional deficiencies can occur owing to active disease and treat- ment interventions (see Table 5). In terms of dietary recommendations, there is little prospective research in the IBD realm. Patients often receive mixed messages regarding dietary modifications, some of which can be extremely difficult to follow. Gluten-free and low FODMAP diets do not appear to be beneficial in IBD without con- current celiac disease or functional GI symptoms.29 Data from studies in other immune-mediated inflammatory diseases, such as psoriasis and rheumatoid arthritis, show some benefits with Mediterranean, vegetarian/vegan, and reduced-calorie/ fasting diets and might have some applicability in IBD.29 A randomized controlled trial compared the anti-inflammatory effect of the Mediterranean diet with the specific car- bohydrate diet, a commonly used, but complex, therapeutic diet with preliminary ev- idence of improved symptoms and reduced inflammation in IBD. The study did not demonstrate an advantage for one over the other in CD.30 With other known health benefits and a wider range of food options, it may be reasonable to recommend a Mediterranean diet. Exercise Exercise is safe and probably beneficial for patients with IBD, although recommenda- tions on duration and intensity are not well-defined.31 Given the increased A4 5 ( CA 2A / (C CA 2 D A. E4 5 ) 4 A A D 0 CA A E4 CA D / A A CA A A C 4 ) I A D , 4 5 A A5 4 A A D 5 A  Inflammatory Bowel Disease 425 cardiovascular risk as well as higher rates of anxiety/depression seen in patients with IBD, exercise may be an important strategy to improve health. Sun protection With an increased risk of skin cancer in patients with IBD on immunosuppressive ther- apy, education and adherence to sun-protective practices are important.10,22 Contraceptive counseling It can be empowering to patients to be asked if they plan to become a parent in the next year. For those who do not desire pregnancy, contraceptive counseling is important, especially if they are on medications that may increase risk for neonatal adverse effects. SUMMARY CD and UC, both forms of IBD, are seen in approximately 1% of the population and are typically characterized by chronic diarrhea (with or without bleeding), abdominal pain, and weight loss. The diagnosis is based on history, physical examination, laboratory studies, and endoscopic evaluation with biopsy. EIMs may coincide with or precede IBD diagnosis. Pharmacologic treatments have markedly advanced in the past decade, resulting in improved outcomes. Chronic inflammation from IBD as well as treatments that induce immunosuppression increases rates for certain conditions, making collab- oration between GI and primary care an integral part of care for the patient with IBD. CLINICS CARE POINTS ! Abdominal computed tomography scans in the absence of acute abdominal symptoms and inflammatory bowel disease antibody panels are not necessary in the workup of inflammatory bowel disease. ! Follow recommendations for increased vaccinations, screenings, and counseling in patients with inflammatory bowel disease, as completion rates are suboptimal. ! Administer recommended non–live vaccines as soon as possible, but avoid live vaccines in those with immunosuppression, and do not delay inflammatory bowel disease treatment to administer live vaccines. ! Given the increased risk of venous thromboembolism, initiate pharmacologic venous thromboembolism prophylaxis in patients admitted to the hospital with an inflammatory bowel disease flare, even in the presence of bloody diarrhea. ! Encourage regular gastrointestinal follow-up for laboratory and endoscopic monitoring for all patients with inflammatory bowel disease, even those who appear well, as disease activity does not always correlate with clinical symptoms. DISCLOSURE Dr L.P. Bruner and Dr A.M. White have nothing to disclose. Dr S. Proksell has given paid educational talks at conferences on inflammatory bowel disease for the Gastrointestinal and Liver Association of the Americas, Baptist Health System Education, and HCP Live. REFERENCES 1. Xu F, Carlson SA, Liu Y, et al. Prevalence of inflammatory bowel disease among Medicare fee-for-service beneficiaries — United States, 2001$2018. MMWR Morb Mortal Wkly Rep 2021;70:698–701. A4 5 ( CA 2A / (C CA 2 D A. E4 5 ) 4 A A D 0 CA A E4 CA D / A A CA A A C 4 ) I A D , 4 5 A A5 4 A A D 5 A 426 Bruner et al 2. Kobayashi T, Siegmund B, Le Berre C, et al. Ulcerative colitis. Nat Rev Dis Prim 2020;6(1):74. 3. Roda G, Chien Ng S, Kotze PG, et al. Crohn’s disease. 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