SOAP. – Crohn’s Disease – SỔ TAY LÂM SÀNG

Kathy R. Reese and Cheryl A. Glass

Definition

A.Crohn’s disease (CD) is a chronic, progressive, destructive inflammatory bowel disorder with both intestinal and extraintestinal manifestations. It produces focal, asymmetric, transmural inflammation, ulceration, and fibrosis, resulting in malabsorption. CD can involve any segment of the gastrointestinal (GI) tract from the mouth to the anus; the terminal ileum and colon are the most common sites:

1.CD is subclassified based on age, location (ileal, colonic, ileocolonic, or upper GI), and clinical presentation (nonstricturing/nonpenetrating to penetrating) using the Montreal classification.

2.Elderly patients with inflammatory bowel disease (IBD) can be subdivided into two groups:

a.Elderly patients with onset of IBD at a late age (late-onset IBD).

b.Elderly patients with long-standing IBD; first diagnosed as having IBD at a younger age (long-standing IBD).

B.The disease is chronic, relapsing, and incurable. CD is characterized by episodes of remission and exacerbation. The most frequent cause of death in persons with IBD is the primary disease, followed by malignancy and thromboembolic disease. Symptoms of CD do not correlate well with the presence of active inflammation, and therefore should not be the sole guide for therapy. The diagnosis is usually established by objective evaluation with endoscopic finding in a patient with a compatible clinical history. Objective evidence for disease activity should be sought before administering medication that may have significant adverse effects.

C.Up to 80% of patients with CD undergo surgery at some point during their clinical course. Indications for surgery include stricture, intractable or fulminant disease, anorectal disease, and intra-abdominal abscess. Surgical procedures include bowel resection and ileal pouch–anal anastomosis (IPAA). The 10-year cumulative risk of a major abdominal surgery in CD is 30% in the biologic era of treatment. The 10-year risk of a second resection after the first is 30% to 35%

D.The lifetime risk of fistula development is 20% to 40%.

E.The incidence of adenocarcinoma in patients with CD is higher than in the general population. Lymphoma is also increased, especially for patients with IBD treated with azathioprine (AZA; 6-mercaptopurine [6-MP]).

Incidence

A.The incidence rate ranges from 3.1 cases per 100,000 to 20.2 cases per 100,000. An estimated one to two million people in the United States have ulcerative colitis (UC) or CD. The incidence of IBD has been reported to be highest in Jewish populations. IBD is very prevalent among the American Jewish population—four to five times that of the general population.

B.The peak incidence of CD is most common in late adolescence to the third decade of life. Another peak occurs in persons aged 50 to 80 years. It is arguable if the increased incidence later in life is due to prior misdiagnosis or actual development of new disease. Ten to fifteen percent of cases of IBD are diagnosed in patients older than 60 years of age.

C.CD may involve the entire GI tract; note the incidence according to the location:

1.80% have small bowel involvement, usually in the distal ileum. In severe cases of ileitis, complications may include fistulas or an abscess in the right lower quadrant (RLQ) of the abdomen.

2.50% have ileocolitis (involving both the ileum and colon). This type is associated with significant weight loss.

3.20% have disease limited to the colon, with roughly one-half having sparing of the rectum.

4.A small percentage has predominant involvement of the mouth (aphthous ulcers) or gastroduodenal area; fewer have involvement of the esophagus (odynophagia and dysphagia) and proximal small bowel.

5.One-third have perianal disease (perianal pain, drainage from large skin tags, anal fissures, perirectal abscesses, and anorectal fistulae).

6.15% to 20% have arthralgias. Arthritis is the most common complication.

Pathogenesis

A.Pathogenesis is multifactorial and remains unclear. Dysregulation of the immune system, changes in the composition of intestinal flora, and presence of genetic susceptibility combines to produce inflammation of the mucosal lining of the intestinal tract, resulting in ulceration, edema, bleeding, and fluid and electrolyte loss.

B.The 2018 American Gastroenterology Association (AGA) guidelines note genetic testing is not indicated to establish the diagnosis of CD. There are currently 200 genetic foci that are being studied to determine their role in the pathogenesis of IBD. CD and UC share approximately 70% of their genes indicating a close relationship between the two processes.

Predisposing Factors

A.Age between 15 and 35 years and another peak 50 to 80 years.

B.Genetic predisposition/family history of CD:

1.First-degree relative five- to 20-fold increased risk.

2.70% incidence in identical twins versus 5% to 10% in nonidentical twins.

3.Jewish populations.

C.Smoking exacerbates disease activity and accelerates disease recurrence.

D.Obesity—unclear if there is increased risk but complications are more severe and frequent.

E.Physical activity—lower risk in active individuals.

F.Dysbiosis—antibiotic use (particular metronidazole and quinolones); presence of infection.

G.Breastfeeding history—three to four times increased risk in patients that were not breastfed.

H.Medications: Use of tretinoin, nonsteroidal anti-inflammatory drugs (NSAIDs), and oral contraceptives have all been implicated in the development of Crohn’s although the relationship remains unclear.

I.History of appendectomy—some studies show a protective benefit after appendectomy.

J.Psychosocial factors.

K.Sleep duration.

Common Complaints

The following hallmark/cardinal symptoms occur in about 80% of patients.

A.Abdominal pain, the classic location being in the RLQ (appendicitis-like):

1.Abdominal pain often worsens postprandially.

B.Diarrhea, chronic or nocturnal.

C.Fatigue—very prevalent; thought to arise from inflammation, anemia, vitamin and mineral deficiencies.

D.Constitutional symptoms at presentation:

1.Fever.

2.Weight loss/anorexia.

3.Growth failure (Younger ages).

Other Signs and Symptoms

Symptoms vary, depending on the location of the intestinal tract and extent of disease.

A.Constipation: Early sign.

B.Bowel urgency and sense of incomplete evacuation.

C.Rectal bleeding.

D.Abdominal mass.

E.Night sweats.

F.Pallor/anemia.

G.Perianal discomfort or soft or semiliquid irritating rectal discharge.

H.Recurrent fissures and fistulas, abscesses sometimes extending to skin.

I.Folate deficiency.

J.Menstrual irregularites/amenorrhea.

K.Extraintestinal symptoms—classic:

1.Arthropathy (both axial and peripheral).

2.Dermatological:

a.Pydoderma gangrenosum.

b.Erythema nodosum.

3.Ocular:

a.Uveitis.

b.Scleritis.

c.Episcleritis.

4.Hepatobiliary disease:

a.Primary sclerosing cholangitis (PSC).

5.Other extraintestinal complications:

a.Thromboembolic (venous and arterial).

b.Metabolic bone diseases.

c.Osteonecrosis.

d.Cholelithiasis.

e.Nephrolithiasis.

L.Other immune-mediated disease associated with CD includes asthma, chronic bronchitis, pericarditis, psoriasis, celiac disease, rheumatoid arthritis, and multiple sclerosis.

Subjective Data

A.Ask about onset, duration, and course of symptoms. Have any of the presenting symptoms occurred at any time in the past (flares of CD may have gone undiagnosed in the past)?

B.Review the patient’s history and extent of diarrhea, including frequency, consistency, color, quantity, and odor of stools. Evaluate if there is blood, mucus, pus, or food particles in the stools.

C.Inquire about recent travel to foreign countries.

D.Ask the patient if diarrhea represents a change in bowel habits. Is there nocturnal diarrhea?

E.Ask the patient what makes the diarrhea worse or better.

F.Inquire about previous GI surgery.

G.Review the patient’s usual weight and any history of weight loss. If weight loss has occurred, how many pounds? How is the patient’s appetite?

H.Review family history of CD, colon cancer, UC, and malabsorption syndrome.

I.How has the duration of current complaints affected the patient’s work or usual social activities?

J.Review for duration and extraintestinal symptoms, including the following:

1.Urinary complications: Renal calculi.

2.Sclerosing cholangitis: Fatigue and jaundice.

3.Skin diseases:

a.Erythema nodosum: Painful, tender, raised, purple lesion on the tibia.

b.Pyoderma gangrenosum: Inflamed patch of skin that has progressed to ulceration.

c.Herpetic lesions related to immune suppression.

4.Arthritic symptoms.

K.Review medications, especially antibiotics and NSAIDs.

L.Review the patient’s current tobacco/cigarette use.

Physical Examination

A.Check temperature, pulse, respirations, blood pressure (BP). Measure height and weight to calculate body mass index (BMI).

B.Inspect:

1.Observe general appearance, noting pallor, wasting, cachectic appearance, ecchymosis, skin ulcerations, jaundice, and signs of Kaposi’s sarcoma.

2.Inspect the head and neck for aphthous ulcers, glossitis, stomatitis, and poor dentition.

3.Inspect the abdomen for surgical scars.

4.Order eye examination for uveitis.

5.Inspect joints for warmth and redness.

C.Auscultate the abdomen for altered bowel sounds (obstruction).

D.Palpate:

1.Palpate the neck for goiter and lymphadenopathy.

2.Palpate the abdomen for distension, ascites, tenderness rebound, guarding, and masses.

3.Palpate for hepatomegaly in RLQ.

4.Palpate the joints for tenderness.

E.Rectal exam:

1.Check anal sphincter for tags, control, and discharge.

2.Palpate for masses, fissures, fistulas, and inflammation.

3.Perform digital rectal examination to assess for anal strictures and rectal mass.

F.Neurologic exam: Assess for signs of vitamin B12 deficiency, including tingling sensation and numbness in hands or feet.

Diagnostic Tests

A.Laboratory tests:

1.Complete blood count (CBC) with differential.

2.Electrolytes and albumin.

3.Erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP).

4.Serum cobalamin (vitamin B12).

5.Serum iron studies.

6.Folate.

7.Liver enzymes and functioning tests (international normalized ratio [INR]) and bilirubin.

8.HIV.

9.Celiac antibody testing should be considered.

10.Thiopurine methyltransferase (TPMT) activity should be assessed before AZA or MP.

B.Stool studies:

1.Fecal calprotectin should be considered to help differential the presence of IBD from irritable bowel syndrome (IBS).

2.Guaiac.

3.Stool culture.

4.Clostridioides difficile toxin assay.

5.Ova and parasites.

C.Imaging:

1.Abdominal flat plate radiography; assess dilated loops of bowel.

2.Barium enema (BE):

a.Classic string sign: Narrow band of barium flowing through an inflamed or scarred area in terminal ileum; differentiates CD from UC.

b.Rectal sparing: Suggests CD in the presence of inflammatory changes in other parts of the colon.

c.Thumbprinting: Indicates mucosal inflammation (may be seen on flat plate of abdomen).

d.Skip lesions: Areas of inflammation with normal-appearing areas.

3.Small bowel follow-through GI series.

4.Fistulogram: Used to guide the surgical correction.

5.CT or MRI scan of the abdomen and pelvis (limited use in IBD but may detect fistulae).

D.Procedures with/without biopsy:

1.Colonoscopy: Mucosa has characteristic cobblestone appearance.

2.Flexible sigmoidoscopy with biopsy: Reveals skip areas in colon, significant small bowel involvement, fistulas, and granulomas.

3.Upper endoscopy: Aphthous ulcerations occur in the stomach and duodenum in 5% to 10% of patients.

4.Capsule enteroscopy: The major risk is the potential for the camera to become lodged at the point of stricture and require operative intervention.

5.Skin biopsy.

E.Tuberculin PPD skin test—prior to initiation of biologic therapy.

Differential Diagnoses

A.CD.

B.UC.

C.Appendicitis.

D.Colon cancer.

E.IBS.

F.Anorexia nervosa.

G.Perianal abscess.

H.Intestinal protozoan and bacterial etiologies.

I.Food poisoning.

J.Cytomegalovirus (CMV).

K.Intestinal tuberculosis (TB).

L.Diverticulitis with colitis.

Plan

A.CD should be managed jointly with a gastroenterologist, colorectal surgeon, and specialists such as a rheumatologist, pharmacist, and nutritionist.

B. See Section III: Patient Teaching Guide Crohn’s Disease.

C.See Section III: Patient Teaching Guide Nicotine Dependence.

D.Dietary management:

1.Adequate nutrition is critical to promotion of healing. Sufficient protein and calories limit the stress on an inflamed and often strictured bowel.

2.Patients with cramps and diarrhea should alter the fiber content of their diets. Diet should include high fiber, low fat (see Appendix B: Dietary Recommendations).

3.Those with steatorrhea benefit from decrease in fat intake to less than 80 g/d. Give the patient a copy of the low-fat/low-cholesterol diet (see Appendix B: Dietary Recommendations).

4.An empiric trial of restricting milk products may terminate diarrhea due to lactase deficiency.

5.Patients with severe diarrhea may require partial bowel rest, which removes the stimulus that food has on bowel motility and secretion.

6.Elemental diet preparations, such as Ensure, Sustacal, or Isocal, have been found to induce remission, improve symptoms, and decrease disease activity in patients with acute disease.

7.Total parenternal nutrition (TPN) is used when the patient’s oral intake is not adequate or when surgery is indicated.

8.Pretreatment screening for TB, using Mantoux (a PPD) skin testing, is needed prior to initiation of immunomodulators and thiopurines.

9.Immunization status: International consensus guidelines recommend vaccinating patients on or likely to begin immunosuppressive therapy for control of their IBD.

a.Immunizations with inactivated vaccines should be brought up to date and rigorously maintained during treatment, including a yearly inactivated influenza, meningococcus, hepatitis B if not immune, and pneumococcal vaccine given periodically (5-yearly).

b.Check varicella titers prior to treatment with immunomodulators and reimmunize if titers are low.

c.If required, live vaccines (polio, rubella, and yellow fever) should be given at least 3 weeks before immunosuppressive therapy or 3 months after stopping the therapy.

d.Medical and surgical management.

10.Surgery does not cure the patient and is reserved for intractable disease, perforation, obstruction, or severe bleeding.

11.The objective of surgery is to remove grossly involved bowel and to spare as much normal-appearing bowel as possible.

12.Postoperative recurrence rates are estimated at 30% to 50% per decade and are inversely related to preoperative disease duration.

E.Pharmaceutical therapy.

The medical management of CD can be divided into treatment of mild Crohn’s and moderate to severe Crohn’s and further subdivided into management of an acute exacerbation and maintenance of remission. In acute exacerbation, triggers such as underlying infection, fistula, perforation, and other pathology must be ruled out prior to the intravenous (IV) administration of glucocorticoids. The goal of chronic therapy is the remission of bowel inflammation. Therapies include the following:

1.Vitamin, mineral, and folic acid supplements are necessary for proper healing and avoidance of secondary complications, such as bone disease and anemia:

a.Patient should take a multiple vitamin containing about five times the normal daily vitamin requirements.

b.Sulfasalazine is effective for treating symptoms of CD. Folic acid supplementation is required for patients on sulfasalazine because it impairs folic acid absorption.

c.Vitamin B12 replacement is required for patients who have ileal surgery.

d.Vitamin D, 4,000 international unit (IU), is required for patients with steatorrhea.

2.Loperamide is recommended for symptomatic relief of diarrhea that occurs either prior to maintenance of remission or during acute flares only for mild CD.

3.Stepwise medication approach (see Table 14.6):

a.Aminosalicylates (5-ASA) are a mainstay of therapy for mild CD because of their anti-inflammatory activities and rapid absorption throughout the small intestines. Several formulations are available for targeting a specific region of the bowel.

b.Corticosteroids are used if IBD fails to respond to 5-ASA. Corticosteroids should be tapered as rapidly as possible as they do not have a role in maintaining remission. The 2018 AGA guidelines recommend controlled ileal release budesonide at a dose of 9 mg once daily is effective and should be used for induction of symptomatic remission for patients with mild-to-moderate ileocecal CD. However, budesonide should not be used to maintain remission of CD beyond 4 months.

c.Immunomodulatory agents may be initiated for moderate or severe Crohn’s refractory to corticosteroids or in Crohn’s that exhibits frequent flares that require steroids. These agents require monitoring of blood counts due to hematological toxicity. A 3% incidence of pancreatitis, allergic reactions, infections, and marrow toxicity is associated with their use. The main drawback to the use of AZA and 6-MP is their slow onset. The effect of therapy is noted after 3 to 6 months of treatment. The 2018 AGA guidelines recommend TPMT testing should be considered befor initial use of AZA or 6-MP.

d.Biologic agents.

Tumor necrosis factor (TNF)-alpha blocker—initial biologic. Infliximab and adalimumab are indicated for both remission induction and maintenance of remission:

i.Infliximab (Remicade).

ii.Adalimumab (Humira).

iii.Certolizumab—not indicated to induce remission.

iv.Anti-interleukin 12/23—ustekinumab (Stelara): alternative to TNF-alpha blocker.

v.Anti-integrin.

vi.Vedolizumab (Entyvio)—useful in patients over 60.

vii.Natalizumab (Tysabri).

e.Antibiotics are utilized in adults for management of perianal disease or inflammatory mass (metronidazole, ciproflxacin). Metronidazole and ciprofloxacin should not be used as primary therapy for luminal inflammatory CD.

f.NSAIDs may exacerbate disease activity and should be avoided when possible.

Follow-Up

A.Have the patient record his or her weight daily to monitor changes.

B.Assess frequency and consistency of stools to evaluate volume losses and effectiveness of therapy.

C.Instruct patients on self-medication and to call a physician if fever develops, diarrhea worsens, bleeding occurs, or abdominal pain becomes marked.

D.Monitoring patients on 5-ASA should include CBC at least twice a year and urinalysis at least annually.

E.Monitoring patients on 6-MP requires frequent monitoring, including CBC and aminotransferase levels (alanine transaminase [ALT] and AST) before treatment, and again at 2, 3, 8, and 12 weeks after initiating therapy. When stable, monitor every 3 months thereafter, and 2 to 3 weeks after a change in dosage.

F.Monitoring patients on methotrexate (MTX) includes a CBC and aminotransferases as with 6-MP/thiopurine therapies.

G.Periodic bone mineral density assessment is recommended for patients on long-term corticosteroid therapy (longer than 3 months). Osteopenia should be treated aggressively. The primary intervention includes dietary counseling and supplementation to ensure adequate intake of vitamin D and calcium.

H.Annual ophthalmologic examinations are recommended for patients on long-term corticosteroids.

I.Patients who are using corticosteroids should be monitored for glucose intolerance and other metabolic abnormalities.

Consultation/Referral

A.Refer the patient to a gastroenterologist initially for evaluation. Treatment requires multidisciplinary management with a gastroenterologist and other subspecialists, including a nutritionist, surgeon, rheumatologist, ophthalmologist, and social workers.

B.Promptly hospitalize for parenteral management patients who are toxic, bleeding heavily, in severe pain, or too sick to obtain adequate nutrition orally.

Individual Considerations

A.Pregnancy:

1.Active disease at time of conception is associated with increased incidence of miscarriage and postpartum exacerbation. It may also predispose the patient to other maternal and prenatal risks, such as premature labor, small-for-gestational-age babies, and stillbirth.

2.Sulfasalazine and steroids are safe and effective during nursing or pregnancy.

3.Women on prednisone should receive supplementary steroids during labor and delivery as well as during other highly stressful times.

4.Counsel women to attempt pregnancy only when the disease has been quiescent for several months.

5.Withholding sulfasalazine for 2 to 3 days before delivery may be advisable to minimize neonatal jaundice due to bilirubin displacement.

6.MTX is a U.S. Food and Drug Administration (FDA) category X drug.

B.Geriatrics:

1.Unexplained diarrhea, weight loss, and perianal disease in the elderly should arouse suspicions regarding CD. Elderly patients have worse outcomes because of delayed presentation and comorbid conditions. The elderly patient is more likely to be more malnourished, anemic, and hypovolemic with higher transfusion requirements, and with longer postoperative hospital stays especially after surgery. Dehydration is more common in the elderly. Signs of dehydration include confusion, muscle weakness, fever, dizziness, poor skin turgor, hypotension, and

tachycardia.

2.Diagnostic delay is more common in the elderly. The differential diagnosis for older patients includes the following:

a.Diverticulitis and diverticular bleeding.

b.Ischemic colitis.

c.Microscopic colitis.

d.Infectious colitis.

e.NSAID-induced ulcerations, strictures, and perforation.

f.Radiation colitis (most commonly gynecological, rectal, and prostate cancers).

3.Elderly patients tend to have CD confined to the distal colon, with only 40% having proctitis.

4.With an increase in cancers in elder patients with CD, it is imperative to evaluate and exclude cancer before beginning immunosuppressant or biologic therapies. Older patients with CD are at increased risk for cancers, including those cancers found in the following:

a.Small intestines.

b.Pancreas.

c.Endocrine glands.

d.Kidney

e.Stomach.

f.Lung and non-Hodgkin’s lymphoma (NHL) and nonmelanoma skin cancer.

5.Review CD therapies, with comorbid conditions in mind, due to side effects, interactions between medications, need for increased laboratory monitoring (e.g., INR as well as digoxin levels and phenytoin levels), and risk of infections.

6.Anti-TNF-alpha agents are contraindicated in patients with New York Heart Association (NYHA) class III and IV heart failure (HF).

7.Age is currently not a contraindication for performing an IPAA. Elderly patients with good anal sphincter function and adequate cognitive ability are better surgical candidates for the IPAA procedure.

8.The incidence of a deep vein thrombosis (DVT) is higher in the elderly.

9.Due to polypharmacy a full review of medications, herbals, and over-the-counter (OTC) drugs should be undertaken to identify medications that should be avoided in the geriatric population, duplicate medications, and medications that are able to be to be decreased or deprescribed. (Refer to section Deprescribing of Chapter 3.)

10.For the older adult with existing CD, nurse practitioner (NPs) should practice special consideration of the following geriatric syndromes:

a.Delirium is a common early sign of acute illness or infection in the elderly. It is more common in patients with existing cognitive impairment. At a minimum, patients and family should be asked if the patient has experienced episodes of altered mental status:

i.The bCAM is a well-documented assessment for delirium. It is available at www.mnhospitals.org/Portals/0/Documents/ptsafety/LEAPT%20Delirium/HELP%20Program%20CAM%20Flowsheet.pdf.

b.Pain—poorly relieved pain is an important cause of functional impairment at any age group:

i.Elderly patients have a diminished sensorium, allowing pathology to advance to a dangerous point prior to symptom development.

ii.Elderly with abdominal pain may present with altered mental status. Cognitive impairment can make assessment and diagnosis of pain more difficult.

For dementia or noncommunicative patients: The American Medical Directors Association has endorsed the Pain Assessment in Advanced Dementia (PAINAD) Scale scores for the following items:

•Breathing: Examples include normal, labored, hyperventilation.

•Negative vocalization: Examples include moaning, negative language, crying.

•Facial expression: Examples include smiling, frowning, grimacing.

•Body language: Examples include relaxed, tense, rigid, or striking out.

•Consolability: Examples include extent to which a caregiver is able to console, distract, or reassure.

c.Weight loss/appetite suppression: Weight loss is a predictor of mortality. Clinically significant weight loss is considered to be 5% loss of usual body weight in 3 months or 10% in 6 months.

i.Monitor weight patterns/BMI. (Caution: BMI is not used to identify loss of muscle mass.)

ii.Monitor both serum albumin and anemia: Hypoalbuminemia and anemia is not necessarily associated with low bodyweight. It can be caused by decreases in liver protein synthesis:

•Serum albumin concentration is commonly recommended.

•Hemoglobin (Hgb), prealbumin, and transferrin.

•Cholesterol.

d.Depression: Anxiety and depression are common in IBD and are factors that lead to decreased health-related quality of life. A depression screen should be done at each office visit:

i.An online Patient Health Questionnaire-9 (PHQ-9) is available at www.mdcalc.com/phq-9-patient-health-questionnaire-9.

ii.The Geriatric Depression Scale, short form, a 15-item questionnaire that can be quickly applied in the clinical setting, is available at web.stanford.edu/~yesavage/GDS.english.short.html.

Resource

Crohn’s and Colitis Foundation of America: www.ccfa.org.