Ms. S is a 28-year-old White female with no significant past medical history. She presents to the nurse practitioner's (NP) office with abdominal pain, stating that the pain started around 6 a.m. and was accompanied by nausea and two episodes of bilious vomiting. Her last bowel movement was this morning and was bloody, watery, and painful. She also states that she has had periods of constipation in the past but has never experienced her current pain level, which she rates as 8/10 on a scale of 0 to 10. She reports a poor appetite for the past few months and has lost 15 lb (6.81 kg) over the past 2 months. She states that she has been increasingly fatigued and is afraid that she has cancer. Ms. S denies recent travel, and her last meal (yesterday) was grilled chicken and salad.
Ms. S is single, lives with her parents, and is a nursing student in her last year. She denies drug and alcohol use but has been smoking 10 cigarettes per day for about 4 years. She is of Ashkenazi Jewish heritage and has a significant family history for Crohn disease (CD) on her mother's side.
Vital signs: Temperature 101.2° F (38.4° C), pulse 110, respirations 18, BP 98/56 sitting and 90/50 standing (orthostatic), weight 108 lb (48.98 kg), height 64 in (162.56 cm).
General: 28-year-old woman in moderate distress, pale, and diaphoretic.
Physical exam: Head, ears, eyes, nose, and throat: two ulcerated lesions to buccal mucosa, the rest of the exam within normal limits (WNL).
Cardiac—WNL S1S2 with no murmurs, gallops, or rubs
Pulmonary—lungs clear to auscultation bilaterally
Abdomen—distended with hyperactive bowel sounds (BS), (-) rebound, (+) guarding, (-) psoas sign, (-) McBurney sign.
Lab and X-ray results:
Complete blood count (CBC): Hemoglobin—10 g/dL; hematocrit—32.2%; white blood cell count 11,000/cells/mm3
Erythrocyte sedimentation rate (ESR): 48 mm/hour; chemistry: blood urea nitrogen—40 mg/dL, creatinine—1.0 mg/dL, and amylase, lipase, and liver function tests WNL
Urinalysis (U/A): WNL
Human chorionic gonadotropin (Urine HCG): negative
Abdominal X-Ray: flat and upright, narrowing at distal ileocecal region
Inflammatory bowel disease (IBD) is divided into two major categories: Ulcerative colitis (UC) and CD. UC and CD are autoimmune diseases with an unknown etiology and are known to affect approximately 1.4 million people worldwide.1 This article will focus on the diagnosis and management of patients with CD.
CD in North America is estimated to vary between 44-201/100,000, while in Europe, it is estimated at 8-214/100,000.2 The highest incidence of CD in North America tends to be in Canada and northern parts of the United States as compared to the southern areas of the continent. Although the cause is unknown, it appears that environment and genetics play a role in the development of the disease. In families where one member has CD, first-degree relatives and twins have a higher incidence of the disease.2,3 CD occurs primarily in the 20- to 30-year age group; however, it can present at any age. There seems to be a higher risk in women, and Blacks are affected with CD two-thirds more often than Whites. There are lower rates of CD in Hispanic and Asian populations in comparison with non-Hispanic Whites. A high incidence of CD occurs in Ashkenazi Jews.4 Environmental factors such as active smoking increase and aggravate the course of CD. In addition, CD is strongly correlated to obesity due to diets containing high-saturated fats.5
While the etiology of CD is unknown, it has been widely considered to be a nonspecific autoimmune disease targeting the gastrointestinal (GI) tract. Approximately 30% of the patients affected with CD have lesions within the small intestine, 30% in the colon, and the remaining 40% involve both the colon and small intestine.6 The lesions in CD can result in ulceration, bleeding, diarrhea, nausea, vomiting, and weight loss.6
Inflammation in CD extends through all the layers of the colon (transmural involvement) resulting in abscess, perforation, and fistula formation. Ulcers begin to appear as a result of an intestinal infection and an altered immune response. The abnormal immune response of proinflammatory cytokines, interleukins, and tissue necrosis factor produces tissue damage beginning with edema and thickening of the mucosal wall.7,8 This altered inflammatory response produces transmural lesions with intervening mucosal edema and granulomatous projections; these cause the typical cobblestone appearance (nodular formation in the mucosa) seen in CD. As the disease progresses, the transmural inflammation thickens the bowel and mesentery wall—causing hypertrophy and fibrosis—which leads to a narrowed lumen with the potential for obstruction.7,8
Assessment and associated clinical findings
An in-depth patient history is crucial in guiding the NP toward a focused and detailed physical exam. This patient history enables the NP to arrive at an appropriate working diagnosis, as well as detail the subtle nuances that are often overlooked if the patient history is rushed or abbreviated. In the case study, important factors such as risk stratification (clinical presentation and pertinent findings), identification of predisposition to CD, and family history are critical elements requiring careful attention.5,9,10 The family history will most likely be the most contributory to the development of a working diagnosis of CD because the presenting symptoms may mimic other acute abdominal pathology such as gastroenteritis, infectious diarrhea, or UC. The most common physical complaints and presenting symptoms for patients with CD are bilateral lower quadrant (LQ) abdominal pain, fever, diarrhea, watery stools (with or without blood), weight loss, fatigue, nausea, vomiting, and postprandial abdominal pain.11
On physical exam, the patient may or may not have a palpable mass, which may be indicative of a dilated bowel or stool. A common physical finding is positive right LQ or bilateral LQ abdominal pain with tenderness on light palpation but more pronounced on deep palpation.3 In addition, the patient will usually have negative peritoneal signs (McBurney or psoas sign), which is an essential negative finding to rule out acute appendicitis; however, this is not an absolute. Abdominal distension may be present due to increased peristaltic activity or obstructive process, and normoactive BS are commonly found. Careful inspection of the rectum and vagina for leakage of stool, pus, or other drainage should be included in the physical exam—this may indicate fistula development. A digital rectal exam should also be performed to detect the presence of rectal masses or abscesses. In addition, a guaiac test for blood should be performed. It is essential to differentiate CD from other similar acute abdominal pathology such as abdominal obstruction, cholecystitis, diverticulitis, ectopic pregnancy, and acute appendicitis. Radiographic imaging is a critical component to rule out other pathology and confirm the diagnosis of CD.
Since CD is considered to be of autoimmune etiology, immunologic findings may also be suggestive of it and should be explored to rule out other autoimmune and extraintestinal conditions.12,13 Physical findings such as joint tenderness and swelling normally associated with arthritis can be found in patients with CD as well as psoriatic lesions, both of which have immunologic underpinnings.13
Lab testing should primarily focus on evaluation for the presence of anemia, inflammation, infection, and abnormalities associated with nutritional deficit and compromise. The CBC is performed to detect anemia (demonstrated by decreases in hemoglobin and hematocrit) and infection (elevation in white blood cell count). A complication of CD in about 1% of patients can be primary sclerosing cholangitis; therefore, liver function tests, amylase, and lipase are performed to detect liver and pancreatic abnormalities.1 A Comprehensive Metabolic Panel (CMP) is performed to evaluate fluid and electrolyte hemostasis, as well as identify renal compromise, evidenced by the elevated creatinine levels. Since inflammation is a major component of CD, the ESR will provide the NP with the appropriate data to suggest the presence of an existing inflammatory process. A U/A should also be performed to rule out infection or detect the presence of blood or protein, which may be suggestive of renal tubular pathology. In addition, pregnancy testing and Urine HCG should be performed in female patients in childbearing years. Stool samples for culture, ova, and parasite (O&P) fungal infections are also collected to evaluate the patient for intestinal infection.14 Current studies on CD are exploring protein profiles of mononuclear cells as potential biomarkers for predicting CD and UC.15 In a study conducted by Hatsugai et al., these protein biomarkers were strongly correlated to the diagnosis of CD and may be useful in differentiating between CD and UC.15
The flat, upright X-ray and upper and lower GI series with small bowel follow-through (visualization past the duodenum) are the most effective imaging studies for the diagnosis of CD. The latter exam employs the use of barium, which is helpful in visualizing early mucosal changes. Both studies should be part of the first-line testing for the initial work-up of CD.1 In addition, esophagogastroduodenoscopy and colonoscopy are also employed to discern CD as opposed to UC or other colonic and intestinal pathology.16 When studies such as endoscopy and/or colonoscopy are performed, the gastroenterologist will frequently biopsy areas of the GI tract to rule out carcinoma, infectious processes such as Helicobacter pylori, or remove precancerous lesions such as polyps. Computed tomography (CT) is also a useful imaging study that can visualize areas of transmural inflammation, bowel thickening, and extraintestinal pathology.17,18 CT is also employed when a rapid diagnosis of appendicitis needs to be made, when delay to diagnosis and treatment may have higher morbidity, and mortality due to complications of appendicitis such as rupture. Magnetic resonance imaging (MRI), although not a baseline imaging study, has been gaining increased use and value when other pathology is suspected. MRIs are extremely useful when the need for visualization of tissue perfusion as an indicator for disease activity is critical, where CT or radiography are unable to capture other data such as location, and when fistulas and abscesses are present.17,18 The use of video capsule endoscopy has grown in popularity over the past few years. The video capsule endoscopy procedure employs the use of a small capsule that the patient swallows. The capsule travels through the small intestine, visualizes the bowel, and captures various pathologies. This is a favorable diagnostic method because it is noninvasive and does not require sedation or anesthesia like conventional endoscopy. Noted complications to video capsule endoscopy are a retained capsule and possible bowel perforation.19 Conventional endoscopy is still the first choice in diagnostic evaluation.
Diagnostic findings in CD
On plain film X-ray with flat and upright views, strictures, dilation of bowel loops, and bowel obstruction can be visualized. The more definitive test is the upper and lower GI series where barium is used to enhance visualization of the bowel mucosa. When performing upper and lower GI series with barium and small bowel follow-through, aphthous ulcers, gut edema, skip lesions (noncontinuous bowel lesions), and cobblestoning—which are all considered to be early mucosal changes—are visualized.17,18 Cobbelstoning is a term used to describe a condition of the bowel where increasing nodularity occurs in the bowel mucosa, and aphthae (series of aphthous ulcers) begin to merge. Cobblestoning of the mucosa also leads to the development of fistulas, which is why it is important to detect mucosal changes early (see Characteristic mucosal features of CD). The upper GI study with barium is the gold standard because these early findings can be lost on CT even with contrast.17,18 Strictures, dilation of bowel loops, narrowing of bowel loop (string sign), delayed filling, ulcerations, and other mucosal changes are also well-visualized with barium. Findings of a particular note are skip lesions and bowel loop narrowing (also known as positive string sign). Skip lesions (or noncontinuous lesions) are typical for CD where the bowel will have areas that are unaffected by disease. This is an essential finding when differentiating between UC and CD (see Distribution patterns of disease in CD and UC). Entire sections of the bowel will commonly be affected in patients with UC, and the skip lesion pattern, as typically seen in CD, would be absent. Bowel narrowing and strictures are a major complication of CD with the potential for bowel obstruction. The term “string sign” is used because the section of the bowel on radiography resembles a frayed piece of cotton or string. Strictures, fissures, bowel wall thickening, abscesses, edema, and mural/mucosal changes are visualized on CT scan (although earlier mucosal changes are not always seen on CT scan).18
Lab findings in CD
Lab findings will be consistent with inflammation, anemia, hypoalbuminemia, and infection. The mucosal changes seen with CD alter the absorption of essential nutrients and compromise overall nutritional stability. It is because of these changes that patients often report weight loss and fatigue, while routine blood studies such as the CBC frequently demonstrate anemia. Patients with CD will often have associated iron deficiency anemia due to poor or insufficient small bowel absorption.20 Other key lab studies such as the ESR will be elevated, indicating inflammation. Eosinophils may also be elevated, which again supports the presence of an inflammatory process. Hypoalbuminemia is a common finding due to the decrease in bowel absorption of essential amino acids and protein. In addition, patients frequently experience nausea, vomiting, and anorexia, which will contribute to malnourished states and dehydration. Infections such as Clostridium difficile and Escherichia coli need to be identified and treated in order to prevent life-threatening complications such as sepsis. Stool samples will also detect the presence of parasites and fungal infections (Candida). The patient with CD is most vulnerable to abscesses and toxic megacolon (infectious dilation of the colon) due to the disruption of the integrity in the intestinal mucosa. Early identification of infection will assist in preventing complications.14
The goals of therapy for patients with CD are to decrease inflammation, correct anemia and nutritional deficits, relieve pain, prevent complications (toxic megacolon, abscesses, and fistulas), and improve/preserve quality of life. These goals are accomplished through diet management and nutritional counseling, pharmacotherapeutic regimens, patient support, and surgery. Pharmacotherapy includes 5-aminosalicylic acids, corticosteroids, immunosuppressive agents, anticytokines antibiotics, antidiarrheals, and probiotics.11,20–24
Pharmacotherapy includes the 5-aminosalicylic acids such as sulfasalazine, olsalazine, balsalazide, and mesalamine; they have an FDA indication for UC and are used off-label for treatment of CD. These drugs inhibit production of prostaglandins, interleukin-1, and other enzymes released by the macrophages; this decreases acute inflammation associated with CD. In addition to the 5-aminosalicylic acids, corticosteriods such as prednisone or prednisolone are also used to decrease inflammation during exacerbations. The common adverse reactions of these drugs are mostly GI in nature (abdominal pain, diarrhea, vomiting, and GI irritation). Enteric-coated preparations have been studied for efficacy, and findings indicated that these preparations have been shown to reduce adverse reactions of prednisolone, and were as effective as nonenteric-coated preparations.24 Immunosuppressive drugs such as azathioprine, tacrolimus, and methotrexate are well known for antirejection therapy for posttransplantation. The properties or actions of these drugs are suppression of T-cell activation and interruption of DNA/RNA cell replication, which are normal actions of immunity. These agents interfere with the autoimmune response of Crohn disease, which in turn decreases chronic inflammation.20 Patients receiving these agents have increased susceptibility to infection because of their suppressive properties. It is therefore critical to educate patients with regard to communicable disease prevention through hand washing, maintaining immunization, and avoiding crowds during the cold and flu season. The next category of medications is called anticytokines and includes infliximab, adalimumab, and certolizumab, which serve as antibodies to tumor necrosis factor (TNF). TNF is responsible for the regulation of immune cells. Anticytokines work toward inhibiting TNF, which again will decrease the inflammatory response. Patients with CD frequently require antibiotics such as ampicillin, metronidazole, sulfonamides, and cephalosporins for the treatment of infection related to abscess formation, alterations in gut flora, and immunosuppression.
Antidiarrheals are especially helpful in controlling refractory diarrhea, which increases the risk of dehydration if left untreated.
The use of probiotics has been shown to increase host vitality. It is considered “good” bacteria found in foods such as yogurt; a well-known probiotic is Lactobacillus acidophilus. In addition to probiotic's availability in foods, these preparations are also available in concentrated capsules.23
Pain related to CD is not only limited to the abdominal discomfort generally associated with CD. Arthritic joint pain, skin lesions related to psoriasis, and other “extraintestinal” areas of involvement can cause severe pain and discomfort for patients with CD requiring analgesia. Although the mainstay for many of these types of pain is nonsteroidal anti-inflammatory drugs, this classification of drugs can worsen the GI symptoms (mainly abdominal pain) and increase the risk of bleeding. NPs can offer these patients acetaminophen because it is easily tolerated when taken orally. Patients should be instructed not to exceed the maximum daily dosage of acetaminophen (3,000 mg per day) to prevent liver toxicity.
Supportive therapy such as stress management and nutritional counseling (carbohydrate restriction, healthy eating, managing obesity, and increased iron intake) are critical. Referral to a nutritionist for further management would be beneficial and should be part of the treatment plan. Nutritional therapy would also include fluid replacement for dehydration, nutritional supplements such as vitamin C and D, ferrous sulfate, calcium, small, frequent feeds, elemental supplementation, and enteral nutrition. Removing foods that increase symptoms and flares are often recommended, and patients will frequently be instructed to keep a food diary to find patterns/trends of foods that lead to exacerbations or flares. The patient is also instructed to compile a list of the types of foods to avoid in order to assist those (at home) who prepare meals and to guide the patient when eating meals out.20–22
Surgery is indicated when common complications, bowel obstruction, perforation, toxic megacolon, fistulas, abscesses, and excessive bleeding occur. An estimated 60% to 70% of patients with CD will require surgery at some point.1 Surgical procedures may be performed as either an open or laparoscopic procedure depending on the extent of the patient's disease. The most common surgical procedures that are performed include strictureplasty, bowel resection, colectomy, and proctocolectomy. Strictureplasty is indicated when small bowel strictures cause significant obstruction. A strictureplasty is a procedure where a balloon is guided through the intestine to search for areas of resistance. Once an area of resistance is encountered, the stricture is incised in such a way so as to allow for a larger opening in that section, which in turn will relieve the obstruction. In cases where bowel obstruction is either too large or life threatening (as in the case of toxic megacolon), sections of bowel are removed (bowel resection), and then remaining bowel is anastomosed. At times, the entire colon may be affected, and a total colectomy (resection of the entire colon) will be performed if the bowel is extremely friable or persistent bleeding occurs; these portions of the GI tract may be resected. In cases with rectal involvement due to large fistulas or abscesses, the rectum will also be removed (proctocolectomy). However, rectal involvement is uncommon.1,11,24 Small intestine transplantation is another alternative for surgical intervention but is reserved for severe cases of intestinal failure where all other measures and interventions have failed.1
Therapy and treatment for children is primarily based on adult regimens, which are tailored and adjusted for age, medication dosing, adjustment of radiation dosage, symptomatology, and specific manifestations of the disease. Pharmacotherapy is dose-adjusted according to age and weight.21,25
Case study follow-up: Assessment and plan
Based on clinical presentation, family history, physical exam, and preliminary lab results, Ms. S was diagnosed with Crohn disease, which was confirmed via upper and lower GI series with barium. She was admitted to the hospital and was ordered nothing by mouth and received I.V. fluid replacement therapy. She was started on mesalamine, prednisone, and metronidazole. Her stool cultures and O&P were negative, and her overall hospitalization was uneventful. She was discharged and given a one-week follow-up appointment with gastroenterologist, nutritionist, and her primary care provider in order to develop a long-term disease management plan.
CD affects 1.4 million people worldwide. Early diagnosis and treatment are vital in preventing debilitating complications and preserving quality of life. The increased risk of cancer associated with CD can be prevented or detected early on through regular follow-up care with gastroenterology and annual physical checkups with the primary care provider. An in-depth patient history is critical when evaluating patients suspect of IBD, specifically CD because of the strong correlation to familial history and ethnicity. Disease management goals for patients with CD are to prevent disease progression, preserve current functional status, minimize complications associated with exacerbations, and provide supportive care to the patient and family. The NP has an integral role in assisting patients toward achieving their goals and promoting positive outcomes.