University of Wyoming (Casper) Program Family Medicine Residency
Crohn's Disease: Diagnosis and Management
Am Fam Dr.. 2018 Dec 1;98(11):661-669.
Patient information: See related handout on Crohn'south affliction, written past the authors of this commodity.
This clinical content conforms to AAFP criteria for continuing medical instruction (CME). Come across the CME Quiz Questions.
Author disclosure: No relevant financial affiliations.
Article Sections
- Abstract
- Adventure Factors
- Clinical Findings
- Diagnostic Studies and Monitoring
- Diagnostic Approach
- Direction
- Perianal and Fistulizing Disease
- Surgical Handling
- Preventive Measures
- References
Crohn's disease is a chronic inflammatory condition that affects the gastrointestinal tract. It can cause lesions from mouth to anus and may result in extraintestinal complications. The prevalence of Crohn's disease is increasing in adults and children. Genetic predispositions to Crohn's disease have been identified, and specific environmental factors have been associated with its development. Mutual presenting symptoms include diarrhea, abdominal pain, rectal bleeding, fever, weight loss, and fatigue. Concrete exam should identify unstable patients requiring immediate intendance, include an anorectal examination, and expect for extraintestinal complications. Initial laboratory evaluation identifies inflammation and screens for culling diagnoses. Measurement of fecal calprotectin has value to rule out disease in adults and children. Endoscopy and cantankerous-sectional imaging are used to confirm the diagnosis and determine the extent of disease. Handling decisions are guided by disease severity and run a risk of poor outcomes. Patients commonly receive corticosteroids to treat symptom flare-ups. Patients with higher-run a risk disease are given biologics, with or without immunomodulators, to induce and maintain remission. For children, enteral nutrition is an option for induction therapy. All patients with Crohn's disease should exist counseled on smoking avoidance or cessation. Patients with Crohn's affliction are at increased risk of cancer, osteoporosis, anemia, nutritional deficiencies, depression, infection, and thrombotic events. Maximizing prevention measures is essential in caring for these patients.
Crohn's disease is a chronic inflammatory condition affecting the alimentary canal that often causes extraintestinal complications. Inflammation may occur at any point from mouth to anus (Table iane). Specific clinical and diagnostic characteristics distinguish Crohn's disease from ulcerative colitis1,ii (Table iione). In the United States, the prevalence is estimated at 58 per 100,000 children and 119 to 241 per 100,000 adults, and is increasing for both groups.3,4 Most cases are diagnosed in the 20s to 40s, but new cases do occur later.5 White race and higher education levels are associated with increased prevalence.4 The estimated annual economic brunt to U.S. wellness intendance is $half-dozen.three billion.6
SORT: Primal RECOMMENDATIONS FOR Do
| Clinical recommendation | Show rating | References |
|---|---|---|
| Fecal calprotectin is a useful test for ruling out Crohn's disease in adults. | C | 14 |
| Cross-sectional imaging techniques (i.e., computed tomography, magnetic resonance imaging, and ultrasonography) are the imaging studies of choice for evaluating Crohn'due south illness. | C | twenty, 21 |
| Smoking abeyance reduces complications experienced past patients with Crohn's disease, and all patients should be counseled not to smoke and offered cessation assistance. | B | 42 |
| Corticosteroids care for symptom flare-ups and may induce remission of Crohn'southward disease. | C | ii, 24 |
| Biologics, with or without immunomodulators, induce and maintain remission of Crohn's illness in moderate- to high-take a chance patients. | C | 2 |
TABLE 1
Location of Crohn's Illness and Associated Symptoms
| Location | Symptoms | Comments | Frequency (%) |
|---|---|---|---|
| Ileum and colon | Diarrhea, cramping, abdominal hurting, weight loss | Most common grade | 35 |
| Colon only | Diarrhea, rectal bleeding, perirectal abscess, fistula, perirectal ulcer | Skip lesions and arthralgias more mutual | 32 |
| Small bowel only | Diarrhea, cramping, abdominal pain, weight loss | Complications may include fistula or abscess germination | 28 |
| Gastroduodenal region | Anorexia, weight loss, nausea, airsickness | Rare form may crusade bowel obstruction | 5 |
TABLE two
Characteristics of Crohn's Disease and Ulcerative Colitis
| Characteristic | Crohn'south disease | Ulcerative colitis |
|---|---|---|
| Location | Any area of alimentary canal | Continuous lesions starting in rectum |
| Generally occurs just in the colon | ||
| Thickness | Transmural interest | Mucosa and submucosa only |
| Colonoscopy findings | Skip lesions, cobble-stoning, ulcerations, strictures | Pseudopolyps, continuous areas of inflammation |
| Anemia | + | ++ |
| Intestinal hurting | ++ | + |
| Rectal bleeding | + | ++ |
| Colon cancer adventure | ++ | ++++ |
Risk Factors
- Abstract
- Risk Factors
- Clinical Findings
- Diagnostic Studies and Monitoring
- Diagnostic Approach
- Management
- Perianal and Fistulizing Affliction
- Surgical Treatment
- Preventive Measures
- References
Current data suggest an interplay between genetic susceptibility and environmental factors in the development of Crohn'southward disease. Genetic loci have been identified that increase risk. For example, homozygosity for the NOD2 cistron has shown a 20- to 40-fold increased risk of developing Crohn's disease.five Ecology factors associated with increased risk include smoking, oral contraceptive use, antibiotic use, regular use of nonsteroidal anti-inflammatory drugs, and urban surroundings.5,7 Factors associated with decreased adventure include exposure to pets and farm animals, bedchamber sharing, having more than 2 siblings, high fiber intake, fruit consumption, and concrete activity.5,viii Vaccines have not been associated with the development of Crohn'south illness.ix
Clinical Findings
- Abstruse
- Adventure Factors
- Clinical Findings
- Diagnostic Studies and Monitoring
- Diagnostic Approach
- Management
- Perianal and Fistulizing Affliction
- Surgical Treatment
- Preventive Measures
- References
HISTORY AND PHYSICAL EXAMINATION
Crohn's affliction nigh oftentimes presents insidiously but can present every bit an acute toxic illness. Common symptoms include diarrhea, abdominal pain, rectal bleeding, fever, weight loss, and fatigue.ane,two A case review of 201 participants compared patients with Crohn's disease and patients without Crohn's illness who had irritable bowel syndrome or were otherwise healthy. The study identified eight red flag findings for Crohn's disease in adults. In order of strength of clan, the findings were perianal lesions other than hemorrhoids, a kickoff-degree relative with inflammatory bowel disease, weight loss (v% of usual body weight) in the past three months, intestinal pain for longer than three months, nocturnal diarrhea, fever, no abdominal pain for thirty to 45 minutes after meals, and no rectal urgency.x A example review of 606 children with chronic abdominal hurting identified 3 carmine flag findings for children: anemia, hematochezia, and weight loss.xi The history should identify findings specific for Crohn's disease, identify culling diagnoses (Table 31,2,12), and search for extraintestinal findings (Table 4one). Important areas to embrace are nocturnal symptoms; urgency findings; nutrient intolerance; travel; medications (including antibiotic exposure); smoking status; family history of inflammatory bowel disease; and middle, articulation, or peel symptoms.
Tabular array 3
Differential Diagnosis for Crohn's Affliction
| Celiac disease |
| Chronic pancreatitis |
| Colorectal cancer |
| Diverticulitis |
| Infection (e.thousand., Yersinia, Mycobacterium) |
| Irritable bowel syndrome |
| Ischemic colitis |
| Lymphoma of small bowel |
| Sarcoidosis |
| Ulcerative colitis |
TABLE 4
Prevalence of Extraintestinal Manifestations of Crohn's Disease
| Extraintestinal manifestation | Prevalence (%) |
|---|---|
| Anemia | ix to 74 |
| Anterior uveitis | 17 |
| Aphthous stomatitis | 4 to twenty |
| Cholelithiasis | xiii to 34 |
| Episcleritis | 29 |
| Erythema nodosum | 2 to twenty |
| Inflammatory arthropathies | x to 35 |
| Nephrolithiasis | eight to 19 |
| Osteoporosis | 2 to 30 |
| Pyoderma gangrenosum | 0.5 to 2 |
| Scleritis | eighteen |
| Venous thromboembolism | ten to xxx |
The physical examination should beginning place unstable patients that need immediate attention. Pulse, blood pressure, temperature, respiratory rate, and body weight should be measured. Abdominal examination findings can include tenderness, distention, and/or masses.ane,2 An anorectal exam is required, and a pelvic examination should be considered considering abscesses, fissures, or fistulas are common in Crohn'due south disease.ane,2 Perianal findings (e.g., fistulas, abscesses) increase the likelihood of Crohn's illness.ten
EXTRAINTESTINAL FINDINGS
The inflammatory effects of Crohn's illness tin can extend across the intestinal lumen, causing abscesses, fissures, and/or fistulas, and can affect organs outside of the intestinal tract. Patients tin present with extraintestinal findings before gastrointestinal symptoms are prominent. Areas afflicted include, but are non limited to, the eyes, hematologic organization, joints, and skin (Tabular array four1). History, physical examination, laboratory testing, and imaging are important in identifying these manifestations.1,13
Diagnostic Studies and Monitoring
- Abstract
- Risk Factors
- Clinical Findings
- Diagnostic Studies and Monitoring
- Diagnostic Approach
- Management
- Perianal and Fistulizing Disease
- Surgical Treatment
- Preventive Measures
- References
LABORATORY TESTING
Laboratory testing has multiple purposes for the evaluation of Crohn'southward disease, including diagnosis, monitoring of disease activity, and tracking adverse effects and effectiveness of medications. Fecal calprotectin is a reasonable exam to dominion out Crohn's illness for adults (sensitivity of 83% to 100%; specificity of threescore% to 100%) and children (sensitivity of 95% to 100%; specificity of 44% to 93%) with equivocal symptoms, and may spare them from more than invasive testing.2,xiv When the diagnosis of Crohn'due south illness is considered, a consummate blood count; a complete metabolic panel; pregnancy exam; C-reactive protein level; erythrocyte sedimentation rate; and stool studies for Clostridium difficile, ova and parasites, and civilization may exist useful. Results tin can provide information to support the diagnosis, place the severity of disease, or determine culling diagnoses.one,2 Measurement of C-reactive protein, fecal calprotectin, and stool lactoferrin can help appraise disease activeness and potentially limit the demand for endoscopy in affliction direction decisions.15
Anemia is mutual, and then hemoglobin and hematocrit should be monitored periodically. Deficiencies of folate, iron, and 25-hydroxyvitamin D are also mutual; thus, screening is prudent. Patients with extensive bowel resection have increased take chances of vitamin B12 deficiency and should be screened.16 Tuberculosis screening should be considered before using biologic agents. A complete blood count and renal and hepatic function testing should exist done periodically when methotrexate, thiopurines, and/or biologic agents are used for handling.16 Therapeutic drug monitoring tin can guide therapy.17
ENDOSCOPY AND IMAGING
Endoscopy and imaging are essential tools for diagnosing and monitoring Crohn's disease. Endoscopic procedures allow direct visualization of and access to the bowel lumen. Direct visualization allows for identification of characteristic lesions, monitoring the success or failure of therapy, and screening for colorectal cancer. Endoscopic procedures (except capsule endoscopy) also allow for biopsy and therapeutic interventions (Table 52,13,eighteen,19).
Table 5
Endoscopic Procedures for Diagnosis and Management of Crohn's Disease
| Procedure | Comments |
|---|---|
| Ileocolonoscopy | Starting time procedure to pursue for diagnosis* |
| Can obtain biopsy | |
| Can provide intervention | |
| Used for colon cancer surveillance | |
| Capsule endoscopy | Noninvasive |
| Tin examine unabridged modest bowel | |
| Very good negative predictive value | |
| Unable to biopsy | |
| Unable to provide intervention* | |
| Take a chance of retention | |
| Esophagogastroduodenoscopy | Non routine for adults |
| Tin obtain biopsy | |
| Can provide intervention* | |
| More mutual to take isolated upper gastrointestinal lesions in children, so may exist considered as part of initial workup in children | |
| Enteroscopy | Ordinarily not part of initial evaluation |
| Imaging and/or capsule endoscopy often guides apply | |
| Can obtain biopsy | |
| Tin can provide intervention* |
Cross-sectional imaging techniques, including computed tomography (CT), magnetic resonance imaging, and ultrasonography, take come up to the forefront in the management of Crohn's disease. These techniques are all useful and provide like accuracy for making the initial diagnosis, monitoring illness activeness, and identifying complications (e.g., fistulas, abscesses).20,21 They complement endoscopy because they tin can identify extraluminal pathology and examine the gastrointestinal tract not accessible to endoscopic procedures. If the patient tin tolerate the dissimilarity load, CT and magnetic resonance enterography are preferred to standard CT and magnetic resonance imaging protocols. CT studies provide the near consistent results simply have the downside of radiation exposure. Magnetic resonance studies take no radiation exposure, simply are expensive, may accept limited availability, and are more difficult for patients to tolerate. Ultrasonography is readily available and has no radiation exposure, but it is highly operator dependent and can be limited by body habitus. Choosing which modality to pursue depends on the patient's age, pregnancy condition, electric current clinical condition, local expertise, and availability13,20,21 (Table 613,21,22).
Tabular array 6
Imaging Modalities Used in Crohn's Illness
| Imaging modality | Comments |
|---|---|
| CT enterography | Preferred for initial evaluation |
| Preferred CT technique | |
| Loftier volume of dissimilarity media might not exist tolerated by acutely ill patient | |
| High radiations exposure | |
| Magnetic resonance enterography | Preferred magnetic resonance technique |
| Preferred for children | |
| Preferred for surveillance | |
| Differentiates inflammatory from fibrotic strictures | |
| No radiations exposure | |
| More variability in quality of examinations than CT | |
| More decumbent to artifact than CT | |
| High volume of contrast media might not be tolerated by acutely ill patient | |
| Magnetic resonance requirements might not be tolerated past acutely ill patient | |
| Availability may exist limited | |
| Abdominal/pelvic ultrasonography | No radiation exposure |
| Readily available | |
| Highly operator dependent | |
| Quality can be limited by trunk habitus | |
| Standard abdominal/pelvic CT with intravenous contrast media | Preferred study for acutely ill patient non able to comply with magnetic resonance requirements or tolerate contrast media book for enterography |
| High radiation exposure | |
| Standard abdominal/pelvic MRI with and without intravenous contrast media | Option for patients not able to receive iodinated contrast media for CT |
| Study of choice to evaluate perianal disease | |
| Availability may be limited | |
| Standard intestinal/pelvic MRI without contrast media | Preferred for pregnant patients |
| No radiation exposure | |
| Availability may exist limited | |
| Fluoroscopic contrast examinations with minor bowel follow-through | Cross-sectional studies preferred because more than accurate for active disease |
| Less likely to identify extramural complications | |
| May assist surgeon for preoperative planning | |
| Scintigraphy | Cross-sectional studies preferred for initial evaluation |
| Potential limited role for surveillance; however, cross-sectional studies preferred | |
| Abdominal radiography | Only function is to notice bowel perforation for acutely ill patient |
Diagnostic Approach
- Abstract
- Risk Factors
- Clinical Findings
- Diagnostic Studies and Monitoring
- Diagnostic Approach
- Management
- Perianal and Fistulizing Illness
- Surgical Treatment
- Preventive Measures
- References
The diagnosis of Crohn's illness results from clinical findings coupled with endoscopic, histologic, radiologic, and/or biochemical testing. History, physical examination, and basic laboratory findings drive the decision to pursue the diagnosis. If the patient has a toxic presentation, standard CT should exist the beginning exam. If the patient does not have a fulminant presentation, ileocolonoscopy with biopsy should be the first examination, and esophagogastroduodenoscopy should be considered for children. Cross-sectional imaging should follow and then that the full extent of disease seen by endoscopy can be adamant or to identify disease not visualized by endoscopy. Identifying the complete extent of affliction is of import for developing a handling plan. When ileocolonoscopy and cantankerous-sectional imaging are negative and concern for Crohn's disease is still high, sheathing endoscopy would be the next step. If this study is negative, it is moderately certain that the affliction is non present1,two,thirteen,20,21 (Figure 1 ane,two,13,fourteen,xviii,19,21).
FIGURE ane
Algorithm for diagnosing Crohn's disease.
*—Esophagogastroduodenoscopy may be considered, specially for children and/or in the presence of upper gastrointestinal symptoms.
†—Pick of cross-exclusive imaging technique depends on several factors. Refer to Table 6 for details.
Data from references one, two, 13, xiv, 18, 19, and 21.
Management
- Abstract
- Risk Factors
- Clinical Findings
- Diagnostic Studies and Monitoring
- Diagnostic Approach
- Management
- Perianal and Fistulizing Affliction
- Surgical Treatment
- Preventive Measures
- References
Management has two aims. Kickoff is treating the inflammatory process and its associated complications (e.g., abscesses, fistulas, strictures, abdominal obstructions) with the goal of achieving and maintaining remission. 2nd is minimizing the negative health impacts from Crohn's disease itself and the therapies used to treat it.xiii,sixteen,22,23
MEDICAL Handling
Treatment decisions are guided by age, comorbidities, symptoms, inflammation status, illness location and extent, and overall run a risk of more than astringent and complicated disease (Table 72,24). More severe illness and the presence of risk factors that predict poor prognosis justify the utilise of high-risk medications.2,24
TABLE seven
Run a risk Stratification to Guide Treatment Decisions in Patients with Crohn's Disease
| Depression take a chance | Moderate to loftier adventure |
|---|---|
| Historic period at initial diagnosis > thirty years | Age at initial diagnosis < xxx years |
| Limited anatomic interest | Extensive anatomic involvement |
| No perianal and/or severe rectal disease | Ileal/ileocolonic involvement |
| Perianal and/or astringent rectal disease | |
| Superficial ulcers | Deep ulcers |
| No previous surgical resection | Previous surgical resection |
| No stricturing and/or penetrating behavior | Stricturing and/or penetrating beliefs |
Pregnant advancements take been made in handling. Whereas v-aminosalicylates were once commonly used and are however prescribed for symptom management in mild to moderate disease, mucosal healing has non been demonstrated.2 Antibiotics, also widely used, should exist limited to treating complications such as abscesses and fistulas.two,25,26
Medication direction includes corticosteroids, immunomodulators, and biologics (eTable A). Each plays an important role in inducing or maintaining remission.
eTABLE A
Pharmacologic Therapies for Patients with Crohn'south Disease
| Drug | Dosage | Agin furnishings | FDA boxed warning | Monitoring | Price* |
|---|---|---|---|---|---|
| Corticosteroids | |||||
| Prednisone | 40 to 60 mg past rima oris daily | Hypertension, fluid retention, weight gain, hypernatremia, elevated blood glucose, osteoporosis, mood disorder, increased risk of infection, narrow angle glaucoma | None | Claret pressure, electrolyte panel, blood glucose level, mental status, ophthalmic examination (with prolonged therapy), dual energy ten-ray absorptiometry, signs and symptoms of hyperadrenocorticism | $15 |
| Budesonide (Entocort EC) | 9 mg past mouth every morn for up to 8 weeks | Diarrhea, nausea, arthralgias, headache, respiratory tract infection, sinusitis | None | Signs and symptoms of hyperadrenocorticism and adrenal suppression with long-term therapy | $600 ($ii,100) |
| Immunomodulators | |||||
| Azathioprine (Imuran) | 50 mg by oral fissure daily (maximum: 2.5 mg per kg per day) | Gastritis, nausea, vomiting, lymphoma, fever May cause pancreatitis, leukopenia, anemia, thrombocytopenia | Chronic immunosuppression increases risk of neoplasia | Creatinine level at baseline Complete blood count weekly for ane month, then every 2 weeks for two months, so monthly and when dosage changes Liver enzyme tests TPMT to guide dosing and TDM in select cases | $20 ($200) |
| 6-mercaptopurine | l mg by rima oris daily (maximum: 1.5 mg per kg per day) | Myelosuppression, hepatic toxicity, immunosuppression, hepatic encephalopathy, pancreatitis, rash, hyperpigmentation, lymphoma, fever | None | Creatinine level at baseline Complete blood count with differential weekly during induction Liver enzyme tests weekly during induction TPMT and TDM in select cases | $45 |
| Methotrexate | 25 mg subcutaneously or intramuscularly per week | Alopecia, photosensitivity, rash, diarrhea, anorexia, nausea, airsickness, stomatitis, leukopenia, pneumonitis May also crusade hyperuricemia, gastrointestinal hemorrhage, myelosuppression, hepatotoxicity, lung fibrosis, renal failure | Fetal death and congenital abnormalities (non recommended for utilize in women of childbearing historic period), hepatotoxicity Fibrosis and cirrhosis with prolonged utilise Malignant lymphoma may occur | Chest radiography at baseline Complete blood count with differential and platelet count at baseline, then monthly Blood urea nitrogen measurement, creatinine level, and liver enzyme tests at baseline, then every 4 to 8 weeks | $xx |
| Biologics | |||||
| Anti-TNF agents | |||||
| Adalimumab (Humira) | 160 mg subcutaneously once at week 0, then 80 mg once at week two, then twoscore mg every ii weeks | Injection site reactions (east.g., erythema, itching, hemorrhage, pain, swelling), infection, tuberculosis, malignancies (east.m., lymphoma), autoantibodies/lupus-like syndrome | Agile tuberculosis, reactivation of latent tuberculosis, invasive fungal infections (may include histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystis pneumonia) | Purified protein derivative examination and chest radiography at baseline Signs and symptoms of tuberculosis and active hepatitis B (in those who are carriers of hepatitis B virus) Complete blood count, blood urea nitrogen, creatinine level, and hepatic office tests at baseline and periodically TDM in select cases | NA ($20,000) |
| Certolizumab pegol (Cimzia) | 400 mg subcutaneously in one case at weeks 0, 2, and 4, and so 400 mg every 4 weeks | Injection site reactions, upper respiratory tract infection, headache, hypertension, rash, infections, autoantibodies/lupus-like syndrome | Agile tuberculosis, reactivation of latent tuberculosis, invasive fungal infections, lymphoma and other malignancies | Purified poly peptide derivative test and breast radiography at baseline Signs and symptoms of tuberculosis and active hepatitis B (in those who are carriers of hepatitis B virus) Complete blood count, claret urea nitrogen, creatinine level, and hepatic function tests at baseline and periodically TDM in select cases | NA ($12,000) |
| Infliximab (Remicade) Infliximab dyyb (Inflectra) | v mg per kg intravenously in one case at weeks 0, 2, and vi, then 5 mg per kg every 8 weeks | Infusion-related reactions (e.g., dyspnea, flushing, headache, rash, chest pain, hypotension, pruritus, urticaria, anaphylaxis), delayed reaction (e.g., serum sickness, myalgia, arthralgia), infections, pneumonia, cellulitis, abscess, skin ulceration, sepsis, bacterial infection, autoantibodies/lupus-like syndrome, lymphoma | Active tuberculosis, reactivation of latent tuberculosis, invasive fungal infections, hepatosplenic T-cell lymphoma | Purified protein derivative test and chest radiography at baseline Signs and symptoms of tuberculosis and agile hepatitis B (in those who are carriers of hepatitis B virus) Dermatologic examination in patients with psoriasis Complete blood count, blood urea nitrogen, creatinine level, and hepatic role tests at baseline and periodically TDM in select cases | NA ($5,000; based on 75-kg [165-lb] male) NA ($4,000; based on 75-kg male) |
| Anti-integrin agents | |||||
| Vedolizumab (Entyvio) | 300 mg intravenously once at weeks 0, 2, and 6, and then every 8 weeks thereafter | Nasopharyngitis, headache, arthralgias, nausea, pyrexia, upper respiratory infection and other infections, hypersensitivity reactions, anaphylaxis, lupus-like syndrome | None | Hepatic office tests New onset or worsening of neurologic signs and symptoms Consider screening for tuberculosis TDM in select cases | NA ($12,000) |
| Natalizumab (Tysabri) Just available through REMS CD Bear on prescribing programme | 300 mg intravenously every 4 weeks | Headache, fatigue, upper or lower respiratory and other infections, nausea, arthralgia, low, infusion-related reaction | Fatal or disabling PML; not to exist used with immunomodulators or anti-TNF agents | Anti–John Cunningham virus antibody Signs and symptoms suggestive of PML Hepatic role tests Hypersensitivity reactions Signs and symptoms of astute retinal necrosis | |
| Anti-interleukin 12/23p40 antibody therapy | |||||
| Ustekinumab (Stelara) | Weight-based dosing initially by intravenous infusion Upwardly to 55 kg (121 lb): 260 mg > 55 kg to 85 kg (187 lb): 390 mg > 85 kg: 520 mg Maintenance dosing: 90 mg subcutaneously eight weeks afterward initial dose, and so every 8 weeks thereafter | Vomiting, nasopharyngitis, injection site erythema, infections, pruritus | None | Purified poly peptide derivative test and chest radiography at baseline and periodically Consummate claret count Signs and symptoms of infection or reversible posterior leukoencephalopathy syndrome TDM in select cases | |
CORTICOSTEROIDS
Corticosteroids are oftentimes used for symptom management.2,24 Tapering courses of prednisone, with initial doses of 40 to lx mg based on disease severity, are recommended. Depending on response and how quickly remission is achieved, first tapering by 5 mg per calendar week until the patient reaches a dose of 20 mg, and then tapering by ii.5 to 5 mg weekly until discontinuation is an advisable strategy.2 When disease is lengthened or located in the left colon, prednisone is preferred; nonetheless, formulations of controlled ileal-release budesonide (Entocort EC) are an option for affliction affecting the ileum and/or proximal colon and may be preferred because of their unique delivery specifically to that area.2 Budesonide undergoes significant first-pass metabolism in the liver, resulting in improved tolerability.26 Considering corticosteroids do not maintain remission, adverse furnishings are mutual, and considering perforating complications are higher in patients who accept corticosteroids, they are most ofttimes used to treat symptom flare-ups while patients transition to more effective therapies.
IMMUNOMODULATORS
Thiopurines and methotrexate are the immunomodulators used in Crohn's illness. Azathioprine (Imuran) and half-dozen-mercaptopurine are no more than constructive than placebo in inducing remission, and therefore, take limited apply as monotherapy.2 Immunomodulators have a relatively slow onset of activity, merely they are often used adjunctively for their steroid-sparing effects. In moderate- to high-risk patients, azathioprine combined with anti–tumor necrosis gene (TNF) agents, such equally infliximab (Remicade), demonstrated improved effectiveness over either agent used alone.2 This combination decreases corticosteroid exposure, resulting in fewer adverse effects, and reduces the rate of immunogenicity against anti-TNF agents.ii,27 Based on more than limited prove, methotrexate may besides be used for consecration or maintenance of remission; still, fourth dimension to clinical response should exist considered.2,24,28,29
BIOLOGICS
Several monoclonal antibodies accept been approved for the treatment of Crohn's disease: anti-TNF agents, anti-integrin agents, and anti-interleukin-12/23p40 antibody therapy. Whichever agent induces remission should exist connected for maintenance. All monoclonal antibodies increase the gamble of certain cancers and infections, including reactivation of tuberculosis.1,30,31 Despite these risks, a contempo meta-assay indicates that patients are more likely to keep treatment with biologics than immunomodulators because of improved effectiveness and tolerability.32
Anti-TNF agents, such as certolizumab pegol (Cimzia), adalimumab (Humira), and infliximab, induce and maintain remission in moderate- to high-take chances patients, or in patients with inadequate response to corticosteroids and immunomodulators. Onset of action and clinical benefit are often seen within two weeks of therapy initiation. The overall effectiveness of anti-TNF agents is greatest when given within two years of disease onset.ii
Natalizumab (Tysabri) and vedolizumab (Entyvio) are anti-integrin agents that target leukocyte trafficking. Natalizumab is associated with progressive multifocal leukoencephalopathy and should simply be used in patients who are not seropositive for anti–John Cunningham virus antibody; progressive multifocal leukoencephalopathy has not been observed in patients treated with vedolizumab. Vedolizumab is preferred considering of its specificity to leukocyte trafficking in the gut, and has demonstrated effectiveness in achieving clinical response, remission, and corticosteroid-free remission.two
Anti-interleukin-12/23p40 antibody therapy (ustekinumab [Stelara]) is an emerging handling selection for patients when standard therapies have been ineffective.2 The U.S. Food and Drug Administration canonical the use of ustekinumab for Crohn's disease in September 2016. Although ustekinumab has been shown to be better than placebo for achieving remission and decreasing symptoms of Crohn'south disease, no head-to-head studies accept demonstrated the effectiveness of ustekinumab over other therapies, and clinical feel is express.ii,33,34
OTHER THERAPIES
Enteral nutrition is first-line therapy to induce remission in children.23,35 Pocket-sized studies also show benefit for enteral nutrition for maintenance therapy in adults, and then information technology may be considered when medications are contraindicated or refused.13,36 Current evidence does not support the use of probiotics or omega-iii fat acids.13
Perianal and Fistulizing Illness
- Abstract
- Risk Factors
- Clinical Findings
- Diagnostic Studies and Monitoring
- Diagnostic Approach
- Management
- Perianal and Fistulizing Illness
- Surgical Treatment
- Preventive Measures
- References
These complex situations are associated with worse outcomes37 and are all-time managed past a multidisciplinary approach involving subspecialty intendance from gastroenterologists and surgeons. Perianal disease is best evaluated past contrast-enhanced magnetic resonance imaging. Endoscopic anorectal ultrasonography and clinical examination nether anesthesia are besides useful diagnostic procedures.21,22
Perianal fistulization is classified as unproblematic or circuitous. Simple affliction is managed with surgical drainage of abscesses and antibody therapy (commonly metronidazole [Flagyl] with or without ciprofloxacin). Complex disease get-go requires surgical drainage of abscesses followed by therapy with an anti-TNF agent (i.e., infliximab or adalimumab). The improver of ciprofloxacin or thiopurines can raise the effect of anti-TNF agents. Evidence for the direction of other fistulas (e.thousand., enterocutaneous, enteroenteric, enterovesical, enterogynecologic) is limited. When treatment is necessary, they usually require surgical intervention. Anti-TNF agents, thiopurines, and tacrolimus (Prograf; enterocutaneous fistulas) may as well provide benefit.2,22
Surgical Treatment
- Abstract
- Take a chance Factors
- Clinical Findings
- Diagnostic Studies and Monitoring
- Diagnostic Approach
- Management
- Perianal and Fistulizing Disease
- Surgical Treatment
- Preventive Measures
- References
The need for surgery is mutual, with up to 57% of patients requiring at least ane surgery.38 Surgery is oftentimes needed to treat fistulas, abscesses, and perianal illness. Other indications include medically resistant disease, perforation, obstruction, strictures, uncontrolled bleeding, dysplasia, and malignancy.1,22,26 Early resection may be an choice for patients with illness bars to the ileocecal region who wish to minimize agin furnishings of medical therapy.23,39 If resection is required for colonic illness, segmental, as opposed to total, is preferable.22 Strictureplasty and endoscopic dilatation are alternatives to resection for the treatment of strictures. Strictureplasty is non recommended in the colon.22,23
After surgical resection, prophylactic therapy should be considered to prevent recurrence.ii,22,23 Current data show that anti-TNF agents are almost effective.2 Nitroimidazole antibiotics (metronidazole), mesalamine, and thiopurines are as well useful in preventing postoperative recurrence.two,22,40
Preventive Measures
- Abstract
- Take a chance Factors
- Clinical Findings
- Diagnostic Studies and Monitoring
- Diagnostic Arroyo
- Management
- Perianal and Fistulizing Disease
- Surgical Handling
- Preventive Measures
- References
Crohn's illness itself and treatments for the disease are associated with medical comorbidities. Preventive measures tin mitigate these complications. Patients with Crohn'southward disease are at increased risk of cancer, osteoporosis, anemia, nutritional deficiencies, depression, infection, and thrombotic events16,41 (Tabular array 816,41–51 and eTable B).
TABLE viii
Preventive Measures for Managing Crohn'south Disease
| Conditions to monitor | Comments | Clinical considerations |
|---|---|---|
| Anemia | Nigh common extraintestinal manifestation Nutritional deficiencies and chronic disease are the main contributors | Screen every 3 to 12 months Consider the following for diagnostic workup: complete claret count, scarlet blood jail cell indices, reticulocyte count, ferritin, transferrin saturation, vitamin B12, folate, haptoglobin, lactate dehydrogenase, and creatinine Replace iron deficiency Care for underlying disease |
| Cancer Cervical | Immunosuppression increases the risk of cervical cancer | Annual screening if on immunosuppressive therapy; consider human papillomavirus vaccine |
| Colorectal | Increased hazard for those with one-third or more than of the colon involved | Consider screening (eTable B) |
| Skin | Increased take chances of melanoma and nonmelanoma skin cancers Thiopurine use increases the gamble of nonmelanoma cancers; anti-TNF agents increment the gamble of melanomas | Encourage measures to limit and/or protect from sunday exposure Consider periodic skin examinations |
| Upper alimentary canal, modest bowel, intestinal lymphomas, anal, cholangiocarcinoma, lung | All are associated with an increased run a risk of Crohn's affliction Overall incidence is still low | No specific screening recommendations Increased rates may gene into decisions to pursue diagnostic testing |
| Urinary float lymphoma and urinary tract | Associated with the use of thiopurines | Consider in the conclusion to use thiopurines |
| Depression | Patients with Crohn'southward disease have increased rates; associated with increased rates of recurrence | Consider screening for depression Employ standard therapies to care for |
| Nutritional deficiencies | Increased risk from poor intake, intestinal loss, malabsorption, small-scale intestine resection, and medication interactions | Consider screening for iron, vitamin D, folate, and vitamin B12 deficiencies; frequency depends on illness condition and symptoms Intestine resection increases risk of vitamin B12 deficiency |
| Osteoporosis | Increased risk because of corticosteroid use, chronic inflammation, and nutritional deficiencies | Early screening for patients with increased risk (long-term corticosteroid apply) Ensure adequate calcium and vitamin D intake Consider bisphosphonate therapy when osteoporosis is diagnosed |
| Smoking cessation | Smokers accept more complicated disease (increased flare-ups, increased recurrence rates after surgery, increased need for surgery) Quitting smoking reduces the risk of a complicated disease course | Educate patients on the agin effects of smoking on the clinical grade of Crohn'south disease Offer proven intervention for smoking cessation |
| Thrombotic events | Increased risk of venous and arterial thrombotic events | Encourage hazard gene modification for ischemic center disease (no smoking, exercise, lipid direction, weight reduction, blood pressure control) Consider every bit a factor when evaluating for deep venous thrombosis prevention |
| Vaccines | Infections may be more complicated because of underlying disease Immunosuppressive medications make patients more than susceptible to infections | Follow usual Centers for Disease Command and Prevention recommendations for vaccination; encourage annual flu vaccine; patients on immunosuppressive therapy are candidates for PCV13 (Prevnar 13) and PPSV23 (Pneumovax 23) vaccines; avert live vaccines when on immunosuppressive therapy |
eTABLE B
CRC Screening Recommendations for Patients with Crohn's Disease
| Arrangement | Initiation | Follow-upwardly |
|---|---|---|
| American Gastroenterological Association | Screening colonoscopy for all patients no after than 8 years from symptom onset Screening surveillance for those with disease in at least one-third of the colon If PSC is detected, start at the fourth dimension of detection | Patients with PSC should be screened annually Others every 1 to iii years Patients with the post-obit should be screened more than frequently: CRC in a first-degree relative; active inflammation; anatomic abnormalities (e.g., shortened colon, stricture, inflammatory pseudopolyps) |
| American Society for Gastrointestinal Endoscopy | Screening colonoscopy for all patients no later on than 8 years from symptom onset; earlier in patients with PSC and CRC in a commencement-degree relative younger than 50 years Screening surveillance for those with disease in more than one-third of the colon | Annual surveillance for high-risk factors* No definite recommendation for others, but range of one to 3 years Longer interval for 2 or more visually and histologically normal colonoscopies |
| Cancer Council Australia Colonoscopy Surveillance Working Party | Offering colonoscopic surveillance no afterward than 8 years from outset of symptoms with colitis involving more than than one-third of the colon If PSC is detected, first at the time of detection Start earlier when a strong family history is nowadays | Annually† 3 years‡ 5 years§ |
| European Crohn'south and Colitis Organisation | Screening colonoscopy for all patients eight years from symptom onset Ongoing surveillance for those with disease in more than than one colonic segment | High risk||: 1 year Intermediate risk¶: 2 to 3 years Low chance**: v years |
| National Found for Health and Care Excellence (Squeamish) | Offer colonoscopic surveillance x years later symptom onset and with colitis involving more than one segment of the colon | Low take chances††: 5 years Intermediate take chances‡‡: 3 years High chance§§: one year |
Data Sources: Nosotros searched the National Guideline Clearinghouse using the term Crohn disease; PubMed was searched using the terms Crohn disease and toll United States, prevalence of Crohn affliction, and Crohn disease AND prevalence AND U.s., and using the Clinical Queries office with the term Crohn's Disease. Also searched were the Cochrane database and Bandolier database using the term Crohn's, and the Institute for Clinical Systems Improvement database for the term Crohn disease. Essential Testify was also searched. Search dates: November ane, 2016, through July 2, 2018.
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