Introduction

Crohn’s disease (CD), also referred to as regional enteritis, is one of the two major subtypes of inflammatory bowel disease (IBD). CD can affect any component of the gastrointestinal tract, involving a complex interplay between environmental factors, dysbiosis of the gastrointestinal microbiome, and immunologic dysfunction. The subsequent inflammation is transmural in nature and endoscopically can range from erythema and granularity with shallow aphthous lesions to deep, serpiginous ulceration with edematous adjacent mucosa, forming the classic “cobblestone” appearance that is a hallmark of the disease. The inflammatory process in CD is non-contiguous, resulting in “skip lesions,” or areas of active mucosal involvement directly adjacent to normal segments. The most common site of involvement is the terminal ileum, with ileocolonic involvement being the second most common phenotype.

The clinical presentation of CD is protean in nature and is dependent on the location and the severity of the inflammation. Small bowel inflammation can result in diarrhea, hematochezia, and in more severe cases, anemia, micronutrient deficiencies, and protein-losing enteropathy. Extraintestinal manifestations of the disease can include erythema nodosum, pyoderma gangrenosum, polyarthropathies and spondyloarthropathy, iritis and uveitis, nephrolithiasis and nephritis, and primary sclerosing cholangitis [1].

Several epidemiologic studies have demonstrated an increasing incidence of CD throughout the world, particularly over the past half century. The incidence of CD appears to be higher in northern latitudes, more modernized nations, and in urban centers, although recent data examining worldwide trends has demonstrated that rates are also increasing in regions with historically low rates of the disease [2•, 3].

As the prevalence of this disorder continues to increase, so has the armamentarium of available therapies to treat CD. The initial therapies recommended to treat Crohn’s disease were the glucocorticoids and 5-aminosalicylates (5-ASAs), which include sulfasalazine and mesalamine. In 1971, the first clinical trials demonstrating the efficacy of thiopurines were published by Willoughby and colleagues [4], marking the availability of the first steroid-sparing therapy for the disorder. In 1995, the first study demonstrating the efficacy of another immunomodulator, methotrexate, was published by Feagan and colleagues [5]. This was followed shortly by the emergence of monoclonal anti-bodies against tumor necrosis factor-alpha (anti-TNFs), first with infliximab in 1998, and later adalimumab and certolizumab pegol. Another class of biologic therapies, known as anti-integrin therapies, which include natalizumab and vedolizumab target leukocyte adhesions that also gained regulatory approval for CD [6, 7]. Biologic therapies have been FDA approved for the treatment of moderate to severe CD and, alone or in combination with immunomodulators, have become the mainstay of therapy for moderate to severe CD [8–15]. With their increasing efficacy, however, come rare but increased risks of infection, hematologic dyscrasias, lymphoma and skin cancers, hepatitis, and pancreatitis. Therefore, these medical therapies are often reserved for those with moderate to severe CD. In this review, we will discuss the current recommended evaluation and therapeutic options for those individuals with mild CD.

Identifying Patients with Mild Crohn’s Disease

The availability of multiple clinical indices, endoscopic scores, and radiographic scoring systems has left clinicians with numerous options for determining disease severity [16]. Scoring systems, such as the Crohn’s Disease Activity Index (CDAI), Harvey Bradshaw Index, and IBD-Questionnaire (IBDQ), are all useful tools in the setting of clinical trials but can be challenging to employ while directly caring for patients and making clinical decisions (Table 1). While a CDAI of 150–220 is generally considered to be consistent with mild disease, combining the eight factors, including number of liquid stools, abdominal pain, general well-being, presence of extraintestinal manifestations, the use of anti-diarrheal agents, the presence of an abdominal mass on physical exam, weight loss, and the presence of anemia to calculate the score is overly cumbersome in the clinical setting [18]. Fortunately, there are several well-known clinical factors that can be used to more readily distinguish mild CD from more moderate-to-severe CD. As described in the American College of Gastroenterology and European Crohn’s and Colitis Organization (ECCO) guidelines for the management of CD in adults, individuals with mild disease are typically ambulatory, tolerating oral intake, and lack systemic symptoms of disease, such as fever, tachycardia, hypotension, tenderness to palpation on abdominal exam, weight loss, or signs or symptoms of obstruction [19, 20]. In addition, ECCO requires a C-reactive protein (CRP) above the upper limit of normal. The American Gastroenterological Association (AGA) Institute’s decision support tool stratifies CD by low or moderate/high risk; those who are considered low risk are diagnosed after age 30, have limited anatomic involvement, do not have perianal disease, and lack severe rectal, penetrating, or stricturing disease. These patients possess superficial ulcerations on colonoscopy and have had no prior surgeries [21].

Table 1 Definitions of mild CD per clinical and endoscopic criteria
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In those patients where mild CD is suspected, endoscopic evaluation via ileocolonoscopy should also be employed to assess disease location and severity. In general, involvement of multiple segments of the small bowel and colon, as well as involvement of the upper gastrointestinal tract, are considered to be consistent with more severe disease. Endoscopic disease activity has been demonstrated to clearly correlate with patient’s future risk of surgery: In one retrospective cohort study, the presence of deep ulceration involving at least one segment of the colon and covering 10 % of the mucosal surface was associated with a 31 % probability of colectomy at 1 year and 62 % risk at 5 years [22]. Several disease activity indices have been developed for CD, including the Crohn’s Disease Endoscopic Index of Severity (CDEIS), which includes the presence of superficial and deeper ulceration, the presence of stenosis, and the percentage of surface involvement for each segment of the colon [23]. As with the CDAI, this index has been deemed cumbersome to employ and has not gained considerable traction in clinical practice. Another index, the Simple Endoscopic Score (SES-CD) has also been validated, correlates well with the CDEIS and serum markers of inflammation such as CRP, and is easier to use [24]. This score focuses on ulcer characteristics and luminal narrowing. It remains unclear how often this simpler index is being used in clinical practice. In general, as per the American College of Gastroenterology (ACG) and ECCO guidelines, endoscopically mild disease consists of superficial ulceration, without evidence of deep ulceration, fistulae, or stricturing [19, 20].

While ileocolonoscopy is the gold standard for Crohn’s disease activity assessment in the colon and terminal ileum, it is also important to assess for signs of active inflammation in the remaining small bowel. The most commonly employed cross-sectional imaging modalities used today are computed-tomography enterography (CTE) and magnetic resonance enterography (MRE). Both technologies have demonstrated efficacy in detecting small bowel CD and are capable of appreciating penetrating or structuring complications that may not be appreciated endoscopically [25]. They are also capable of assessing for the presence of active disease proximal to the terminal ileum, which may not be easily accessed via conventional endoscopic techniques. Each technology has its advantages and disadvantages: CTE can often be obtained more quickly with higher resolution images but requires radiation exposure, whereas MRE can produce images that are often adequate with no radiation exposure but costs more and may not be available at all institutions [26]. There have been limited head-to-head clinical trials of the two modalities, and those that have been conducted demonstrated that the two technologies are relatively equivalent, though they have had small sample sizes [27]. Video capsule endoscopy (VCE) also represents another attractive modality for better characterizing CD activity [28, 29]. In a recently published study comparing VCE to MRE to the combination of both modalities in a cohort of patients with CD, 26 % of patients were reclassified to a more advanced phenotype per Montreal classification with MRE compared to 11 % with VCE. However, combining both modalities offered the greatest opportunity for most, fully characterizing the burden of active disease, with 62 % of individuals being identified with a more advanced phenotype per Montreal classification [30]. While further research is required to assess combinations of multiple modalities for evaluating disease activity, both VCE and cross-sectional imaging are useful tools to measure the extent of inflammation and ensure that those with clinically mild CD do not have findings such as multifocal disease, stenosis, or penetrating complications that would prompt more aggressive therapies.

Factors Associated with Poor Prognosis

When determining disease activity to ensure that an individual with clinically mild disease is not at increased risk for a more severe disease course, clinicians should survey for several additional factors in the history, laboratory parameters, and imaging that may predict a more severe or complicated subsequent disease course. Several prognostic factors associated with an increased risk of disabling disease course were summarized in a recent systematic review by Peyrin-Biroulet and colleagues [17]; these factors included the requirement for systemic steroids at initial diagnosis, age <40 at diagnosis, and the presence of perianal disease. Several factors were also demonstrated to be associated with an increased risk of surgical intervention, including age <40 at diagnosis, weight loss >5 kg at diagnosis, ileocolonic or upper GI tract disease location, perianal or structuring disease at diagnosis, and tobacco use. Laboratory assessment should assess for the presence of anemia or leukocytosis, which is suggestive of higher disease burden and potential complications as well. Collectively, these prognostic factors are useful in determining those for whom gastroenterologists would want to carefully consider more aggressive, steroid-sparing therapies, even when the clinical signs and symptoms may be consistent with mild disease.

Therapeutic Strategies in Mild CD

After thorough initial evaluation to ensure that an individual’s Crohn’s disease is limited to mild disease without concerning features for moderate to severe disease or poor prognostic indicators of an aggressive disease course, appropriate therapies can be selected. As opposed to moderate to severe disease, therapies in mild disease have historically been focused on alleviating or controlling symptoms while exposing the patient to minimal risks. From a therapeutic standpoint, the two most assessed modalities for the therapy of mild CD include mesalamine-based compounds and oral budesonide [31]. 5-ASA-based therapies were one of the first classes of agents to be employed in the management of CD. However, a recent meta-analysis examined 19 clinical trials of 5-ASA-based compounds [32]. Both low-dose (RR 1.46, 95 % CI 0.89–2.40) and high-dose mesalamine (RR 2.02; 95 % CI 0.75–5.45) were not significantly more effective than placebo. Sulfasalazine demonstrated modest benefit when compared to placebo in those with isolated colitis (RR 1.38; 95 % CI 1.02–1.87). This endpoint was based on a post hoc analysis. However, it is important to note that this agent is often poorly tolerated, with side effects that can include fever, agranulocytosis, and methemoglobinemia. Furthermore, sulfasalazine was found to be inferior to glucocorticoids (RR 0.66; 95 % CI 0.53–0.81) in this meta-analysis.

Despite the non-significant effect estimates of mesalamine in meta-analyses, they have remained part of the armamentarium for many clinicians in Crohn’s disease given their favorable safety profile. However, in their 2009 guidelines, the ACG recommends that there is no significant evidence to support the use of mesalamine in CD at this time [19]. Similarly, guidelines published by ECCO state that the likely benefit of 5-ASAs is limited [33]. The AGA clinical care pathway for CD also does not include mesalamine in their management algorithm for low-risk disease [21].

Enteric-coated budesonide (ileal-release) has become the primary recommended therapy by the ACG, AGA, and ECCO for mild ileal CD and right colonic CD [19, 20, 33]. This medication is taken orally, typically starting at 9 mg daily followed by a taper after 8 weeks. The initial formulation of this medication is designed to be released in a time-dependent manner, with greatest rates of release in the terminal ileum and proximal colon. There, it locally treats active mucosal inflammation while being absorbed into the hepatic portal system. Upon arrival in the liver, budesonide is primarily broken down by the cytochrome P450 CYP3A4 pathway [34]. This high rate of “first-pass” metabolism results in decreased rates of systemic glucocorticoid side effects.

The efficacy of budesonide has been demonstrated for both induction and short-term maintenance of clinical remission. In a recent meta-analysis of 14 randomized controlled trials, budesonide clearly demonstrated efficacy compared to conventional steroids, placebo, or mesalamine in the induction of remission. On pooled analysis, 47 % (115/246) of individuals receiving budesonide 9 mg daily were in clinical remission compared to 22 % (29/133) receiving placebo (RR 1.93, 95 % CI 1.37–2.73). There was significant heterogeneity in the two available clinical trials comparing budesonide to mesalamine, with one study by Thomsen and colleagues demonstrating that budesonide was superior to mesalamine at 8 weeks (RR 1.63, 95 % CI 1.23–2.16), while another study by Tromm and colleagues demonstrated no significant benefit (RR 1.12, 95 % CI 0.95–1.32) [35•, 36, 37]. Interestingly, when compared to systemic corticosteroids, budesonide was noted to be inferior in inducing remission (52 vs 61 %, RR 0.85, 95 % CI 0.75–0.97). This was noted to be particularly true when considering more severe disease. However, patients receiving budesonide were also less likely to experience significant steroid-related side effects during induction (RR 0.64, 95 % CI 0.54–0.76). These data highlight the unique properties of budesonide in inducing clinical remission while minimizing the potential side effect profile for patients with milder symptomatology and no high-risk features.

Unsurprisingly, budesonide also has similar efficacy in maintaining rates of remission as with systemic glucocorticoids. A pivotal retrospective study demonstrated the inability for systemic steroids to maintain remission in CD at 1 year, with 28 % requiring continued steroid use and 38 % requiring surgery at 1 year [38]. A recent meta-analysis assessing the efficacy of budesonide in maintaining clinical remission in CD by Kuenzig and colleagues demonstrated similar findings [39•]. While there was heterogeneity among comparators (placebo, systemic steroids, or azathioprine), formulation (timed ileal release vs pH-modified release mechanisms), and dose, the results among nine pooled studies were consistent. At 6 months, budesonide 6 mg was no more effective than placebo in maintaining clinical remission among five pooled studies (RR 1.15, 95 % CI 0.95–1.39). Similar results were seen at 1 year (RR 1.13, 95 % CI 0.94–1.35). Very similar results were seen with budesonide 3 mg versus placebo at 6 months (3 studies, RR 1.12, 95 % CI 0.83–1.51) and 12 months (five pooled studies, RR 1.08, 95 % CI 0.87–1.34). Similar findings were also appreciated when comparing budesonide 9 mg to prednisolone 40 mg (RR 0.79, 95 % CI 0.55–1.13) and budesonide 6–9 mg to azathioprine 2–2.5 mg (RR 0.81, 95 % CI 0.61–1.08)) at 12 months [39•, 40, 41].

The appropriate therapeutic options for distal mild left colonic disease and more proximal small bowel involvement are less clear at this juncture. For left colonic involvement, it is possible that alternative formulations of budesonide may be efficacious. Budesonide MMX (UCERIS®) was recently FDA approved for the treatment of ulcerative colitis after demonstrating clinical efficacy in several clinical trials [42]. However, this agent has not been assessed in Crohn’s, and extrapolating the efficacy of this agent from UC to CD is problematic. Therefore, systemic steroids may be most appropriate for these patients. Individuals may also respond to mesalamine or sulfasalazine based compounds, as previously noted, although it is important to note that the efficacy of inducing mucosal healing with mesalamine-derived products has not been assessed in patients with CD. For more proximal disease, there are no specific budesonide formulations, and systemic steroids may be required. In each of these instances, careful investigation of disease location and severity should be employed to ensure multifocal disease is not present, which would modify the classification of disease severity.

For those who respond to therapy and enter remission, several options exist per current AGA guidelines [43]. Tapering budesonide and monitoring for disease recurrence as described below are potential options. An alternative strategy would be to use lower-dose budesonide at 6 mg daily for maintenance therapy. However, rates of flare for this option are similar to those seen with systemic steroids. Additionally, “maintenance budesonide” has not been demonstrated to have a long-term maintenance benefit. Lastly, one could consider the addition of azathioprine or 6-mercaptopurine (6-MP). Azathioprine 2.5 mg/kg has been demonstrated to maintain remission in mild to moderate CD, with 42 % of individuals maintaining remission with azathioprine compared to 7 % with placebo [44]. However, thiopurines also carry with them significant risks, including bone marrow suppression, infection, pancreatitis, drug-induced hepatitis, non-melanoma skin cancer, and non-Hodgkin’s lymphoma [43, 45–47]. Therefore, careful consideration and discussion of the risks and benefits of thiopurines is required.

For failure of induction of remission or increased symptoms when attempting to taper budesonide, current guidelines suggest several approaches. Per AGA guidelines, azathioprine could be considered at this juncture. ECCO guidelines also recommend considering thiopurines in the setting of early relapse, with the caveat that careful evaluation for evidence of active inflammation should be performed as well [33]. Another potential option, as per AGA guidelines, are the anti-TNFs, which include infliximab, adalimumab, and certolizumab pegol [21, 48]. Anti-TNFs are more commonly used in moderate to severe CD and have demonstrated efficacy in both inducing and maintaining remission [8, 10].

Monitoring for Disease Recurrence

Monitoring for disease recurrence in mild or asymptomatic CD has traditionally been done by evaluating for symptom recurrence. This approach is problematic; however, a significant proportion of patients with IBD can have symptoms secondary to other etiologies, such as overlap with irritable bowel syndrome. Therefore, the gold standard for evaluation of active disease has been using the same endoscopic and radiographic methods employed when first evaluating patients. This practice has been termed “treat-to-target” [49]. In those with confirmed evidence of recurrence of active inflammation, the appropriate course of action is dependent on disease location, presence of high-risk features, and temporal relationship to the prior flare. Those that have developed high-risk features, such as multi-focal disease, systemic symptoms of disease, or worrisome features, such as deep ulceration on endoscopy, should be re-classified as having moderate-to-severe disease. For those individuals who have required either systemic or second generation glucocorticoids in the past 6 months, one could consider re-initiating an additional course of steroids. However, a recent clinical care pathway suggests that advancing to steroid-sparing therapies is the appropriate course of action in those requiring multiple courses of steroids within this time window [50].

Given the invasive nature of such evaluations, as well as the increased costs and risks of frequent endoscopic evaluation, the development of non-invasive markers of inflammation has been a fervent area of research for many years. There are some limited data on these tests in mild CD. The most commonly used marker has been C-reactive protein (CRP). This test is readily available at most medical centers at low cost. However, it is not specific for intestinal inflammation. While it has been estimated that 60–80 % of patients with CD demonstrate an elevated CRP, some individuals are incapable of demonstrating an elevated CRP even when clinically appropriate due to genetic polymorphisms [51–53]. In a recent systematic review and meta-analysis of nine studies published from 2006 to 2014, CRP had a relatively low pooled sensitivity (sensitivity = 0.49, 95 % CI 0.34–0.64) but was very specific for active inflammation (specificity = 0.92, 95 % CI 0.92 (0.72–0.98)) [53]. However, these results were not stratified by disease activity. Several studies have specifically examined the utility of CRP stratified by disease severity: a study by Fagan and colleagues published in 1982 suggested that those individuals with mild disease typically had lower ranges of CRP, with a median value of 4 mg/L (range 0–65 mg/L), compared to those with moderate or severe disease [54]. A recent study by Solem and colleagues demonstrated that in those with mild CD, 9/25 with active ileocolonoscopic disease had an elevated CRP, compared to only 1 of 13 without active disease endoscopically [54].

Two new fecal markers of active gastrointestinal inflammation have recently become commercially available as well. Fecal calprotectin, a non-specific protein located within the cytosol of neutrophils, is released when these cells are activated. Fecal calprotectin levels can be measured in any bodily fluid where active inflammation is present. Therefore, its presence in stool is relatively specific to inflammation involving the gastrointestinal tract. In a meta-analysis of 16 studies assessing the test characteristics of fecal calprotectin in CD, the pooled sensitivity of fecal calprotectin was 0.88 (95 % CI 0.84–0.92) and specificity was 0.79 (95 % CI 0.68–0.87). Several studies have examined fecal calprotectin specifically in mild CD, though sample sizes have typically been small. In a study conducted in Finland, 77 patients with confirmed CD were evaluated; 38 had mild CD per the CD Endoscopic Index of Severity (CDEIS); mean fecal calprotectin in this group was 170 (95 % CI 99–451), while mean CRP was 0 [55]. Schoepfer and colleagues appreciated an elevated fecal calprotectin (>50 μg/g) in 32/40 (80 %) of patients with mild CD, compared to 11/26 (42 %) with inactive disease. This positivity was mildly reduced compared to moderate disease (89 % fecal calprotectin positive) and severe disease (96 %) [56].

Fecal lactoferrin is an iron-binding protein that can be measured in the stool and is also non-specific marker of inflammation of the gastrointestinal mucosa. In this same meta-analysis of eight studies, the sensitivity of fecal lactoferrin for active inflammation was 0.82 (95 % CI 0.73–0.88), while the specificity was similar to that of fecal calprotectin (0.79, 95 % CI 0.62–0.89). There currently exists a paucity of data on the test characteristics of this assay specifically in those with mild CD.

Collectively, while none of these tests offer perfect test characteristics, they may be particularly useful in determining when further evaluation is no longer necessary when evaluating recurrence of symptoms. Fecal calprotectin may be utilized for ruling out active gastrointestinal inflammation given its superior negative predictive value. Positive test results for any of these markers (CRP, fecal calprotectin, or fecal lactoferrin) should trigger further evaluation and confirmation. However, none of these markers, alone or in combination, can currently supplant mucosal visualization in those with active symptoms if negative. Further research is required to assess the potential of combining these assays to improve their diagnostic accuracy in surveying individuals with active symptoms, particularly in mild CD.

The best approach for monitoring those individuals who are asymptomatic is not as clearly defined. There currently exists a paucity of data regarding the appropriate course in this population. There are data in ulcerative colitis suggesting that histologic findings, such as basal cell plasmacytosis, are strong predictors of future clinical activity, for example [57]. It is not clear that these findings translate to CD: a study examining isolated ileal ulceration demonstrated they only rarely result in clinically active CD [58]. Further evaluation of such findings in asymptomatic CD patients is required.

In those individuals who are in clinical remission, it is possible that serial CRP, fecal calprotectin, or fecal lactoferrin monitoring could represent an attractive, non-invasive option for disease activity monitoring without exposing individuals to repeated invasive endoscopic procedures. There are preliminary data supporting this approach both in the post-operative setting and in Crohn’s colitis. A recent study by Boschetti and colleagues of 86 patients with CD who had undergone ileocolonic resection demonstrated that a cutoff of 100 μg/g of fecal calprotectin had a negative predictive value of 93 % for predicting mucosal recurrence in individuals who were otherwise asymptomatic [59]. In a cohort of 53 individuals with Crohn’s colitis who were in clinical remission, fecal calprotectin levels >340 predicted an 18-fold increased risk of relapse over the next year [60]. Similarly, there are prospective data assessing CRP levels in individuals with asymptomatic CD. In a recent study by Click and colleagues, 351 individuals with asymptomatic CD were followed. In those with an elevated CRP at baseline, subsequent hospitalization rates were twofold higher at 24 months compared to asymptomatic individuals without CRP elevation [61]. Osterman and colleagues demonstrated that increasing 5-ASA dosing in patients with clinically quiescent UC resulted in reduction of FC to <50 μg/g in 26.9 % of patients, compared to only 3.8 % of individuals who maintained their previous dose (P = 0.0496) [62]. As with assessing those with active symptoms, further research is required to assess using these markers prospectively in asymptomatic CD.

General Health Maintenance in Patients with Mild Crohn’s Disease

Gastroenterologists often serve in part as the primary care physician for individuals with CD. In addition to the diagnostic evaluation of and selection of appropriate medical therapy for mild CD, there are currently a number of recommendations physicians should consider when counselling their patients. Growing recognition of this has recently led to successfully incorporating educational sessions at some gastroenterology fellowship programs [63]. Systematic approaches to comprehensive general medical care have been demonstrated to markedly improve adherence in making appropriate recommendations. Therefore, when managing mild, moderate, or severe CD, physicians should also consider employing health maintenance checklists such as those available through the CCFA [64, 65]. While outside the scope of this review, these recommendations include ensuring that vaccinations are up to date, screening for tuberculosis if considering advancing therapy, and monitoring for iron, vitamin B12, and vitamin D deficiency. Those with several courses of steroids in the past should be referred for dual-energy X-ray absorptiometry scanning when appropriate. Tobacco cessation should be recommended to all current smokers given its’ known association with increased risk of flare and progression to surgery in CD. Lastly, those with colonic disease should begin annually to biennially colonoscopy for colorectal cancer screening beginning at 8 years from diagnosis.

Conclusions

In summary, Crohn’s disease is defined as mild in those patients who are ambulatory, with <10 % weight loss, are eating and drinking without abdominal mass, tenderness, obstructive symptoms, or fever, and who have endoscopic findings of superficial ulceration, without evidence of deep ulceration, fistulae, or stricturing. Initial evaluation of mild CD should focus on assessment for high-risk features that may require more earlier aggressive therapy. Once mild disease without high-risk features is confirmed, therapeutic focus should be on symptom management, while exposing the individual to as little medication risk as possible. The standard of care therapy for symptomatic patients with mild ileal and right colonic disease is oral budesonide, while those with left-sided colonic involvement or more proximal disease may require systemic steroids. Those individuals requiring hospitalization for a flare or those patient requiring two or more courses of steroid therapy should be counseled about initiating steroid-sparing agents, such as anti-TNF monotherapy or combination therapy with an anti-TNF and thiopurine. The benefit of therapy in those with isolated ileal inflammation without symptoms is less clear, as many will not develop clinical symptoms. Individuals with mild CD should undergo follow-up with intermittent assessment of inflammatory markers such as CRP or fecal calprotectin, and follow-up endoscopic evaluation at 1 year should also be considered. Lastly, despite their mild disease severity, these individuals still require evaluation to ensure that routine vaccination has occurred, to assess for iron-deficiency anemia and vitamin D deficiency, and to initiate colorectal cancer screening when appropriate.