Crohn's disease resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mugilan Poongkunran M.B.B.S [2]

Overview

Crohn’s disease (CD) is an inflammatory condition of unknown etiology primarily affecting the gastrointestinal (GI) tract from mouth to perianal region, with specific clinical and pathological features characterized by focal, asymmetric, transmural, and occasionally, granulomatous inflammation and with a potential to cause systemic and extraintestinal complications.

Causes

Life Threatening Causes

Crohn’s disease (CD) can be a life-threatening condition and must be treated as such irrespective of the underlying cause.

Common Triggers

Common factors recognized to exacerbate CD are

• Campylobacter
• Clostridium difficile infection
• Lactose intolerance
• NSAIDS
• Salmonella
• Shigella
• Smoking
• Upper respiratory tract infection

Management

The algorithm is based on the American Journal of Gastroenterology guidelines for management of Crohn's disease in adults.

Characterize the symptoms: ❑ Abdominal pain ❑ Chronic diarrhea or nocturnal diarrhea (onset, duration, pattern, bloody, mucous or watery) ❑ Nausea ❑ Vomiting ❑ Abdominal distention ❑ Fever ❑ Loss of appetite ❑ Loss of weight ❑ Mental status change ❑ Rectal bleeding ❑ Painful defecation Extraintestinal symptoms: ❑ Skin lesions ❑ Oral pain ❑ Odynophagia and dysphagia ❑ Joint pains ❑ Burning micturition ❑ Cough, breathlessness ❑ Eye pain, blurring of vision Obtain detailed history: ❑ Recent travel H/O ❑ Recent drug H/O ❑ Abdominal or pelvic radiation H/O ❑ Family H/O ❑ Systemic illness H/O

Assess volume status: ❑ General condition ❑ Thirst ❑ Pulse ❑ Blood pressure ❑ Eyes ❑ Mucosa Examine the patient: ❑ Skin (swelling, pain, erythema or ulceration) ❑ Oral cavity (ulcers) ❑ Respiratory system (wheezing or crackles) ❑ Cardiovascular system ❑ Abdomen (mass, distension or tenderness) ❑ Anorectal (perianal skin tags, sinus tracts or bleeding) ❑ Eye (swelling, pain, edema or vision loss) ❑ Musculoskeletal (Axial, large and small joints)

Order tests: ❑ Complete blood count (CBC) ❑ Erythrocyte sedimentation rate (ESR) ❑ C-reactive protein (CRP) ❑ Serum electrolytes ❑ Serum iron and vitamin B12 levels ❑ Stool analysis (occult blood, WBC's, calprotectin, lactoferrin, culture, ova and parasites) ❑ Stool for Clostridium difficile toxin ❑ Urinalysis ❑ BUN ❑ Creatinine ❑ Serum glucose ❑ Liver function tests

Confirmatory diagnostic tests: ❑ Colonoscopy and biopsy ❑ Upper GI scopy and biopsy ❑ Computed tomography (CT) ❑ Barium enema (length and location of strictures) ❑ Upper gastrointestinal series with small bowel follow through (SBFT) ❑ Magnetic resonance imaging (enterography) ❑ Wireless capsule endoscopy

Findings suggestive of Crohn's disease: ❑ Discontinuous lesions ❑ Biopsy (Transmural inflammation, noncaseating granuloma) ❑ Cobblestoning (Serpiginous and linear ulcer) ❑ Normal rectum ❑ Isolated terminal ileum involvenent ❑ Aphthous ulcers ❑ Negative stool examination for infectious causes

Assessment of severity

Mild to moderate ❑ Ambulatory patients ❑ Tolerating oral diet ❑ No dehydration ❑ No toxicity ❑ No abdominal tenderness or mass ❑ No obstruction ❑ Weight loss <10 percent

Moderate to severe ❑ Fever ❑ Intermittent nausea or vomiting ❑ Mild to moderate dehydration ❑ Anemia ❑ Abdominal pain and tenderness ❑ No obstruction ❑ Weight loss > 10 percent

Severe to fulminant ❑ High fever ❑ Persistent vomiting ❑ Severe dehydration ❑ Significant peritoneal signs ❑ Evidence of abscess ❑ Intestinal obstruction ❑ Cachexia

Management of Mild to Moderate Crohn's Disease

❑ Outpatient therapy ❑ Start altered diet ❑ Start oral rehydration therapy

Ileitis and colitis

Oral lesion

Gastroduodenal disease

❑ Illeitis and Rt side colitis: Oral budesonide (9 mg/day) ❑ Distal colitis : Topical mesalamine or topical steroids (enemas or suppositories) ❑Other site : Oral mesalamine (4 g/day) or oral sulfasalazine (3-6 g/day)

triamcinolone acetonide

❑ PPI or H2 antagonist, or sucralfate ❑ Oral mesalamine (Pentasa: 2 g/day)

Response to treatment in 3-4 wks

Yes

No

Oral metronidazole (10-20 mg/kg/day)

Significant response

No response

Maintenance therapy ❑ Proctitis: Mesalamine suppositories OR ❑ Distal colitis : Mesalamine enemas OR ❑ Others: Oral sulfasalazine or olsalazine or mesalamine(3-3.6 g/day) or balsalazide

Treat as moderate to severe disease

Azathioprine or 6-mercaptopurine for inadequate response

Management of Moderate to Severe Crohn's Disease

❑ Inpatient therapy ❑ Start oral rehydration therapy or intravenous fluids based upon hydration status

No steroid contraindication

Steroid contraindicated

Oral prednisone (40-60 mg/day) with or without mesalamine

Consider methotrexate therapy ❑ A baseline CBC, CXR and LFT ❑ Methotrexate (25 mg/wk i.m and once improvement 15 mg/wk i.m or oral or s.c) OR Consider anti-TNF monoclonal antibody therapy ❑ A baseline PPD and CXR (Rule out TB) ❑ Infliximab (5 mg/kg i.v at 0, 2 and 6 wks) OR ❑ Adalimumab (160 mg s.c at 0 wk and 80 mg/2 wks) OR ❑ Certolizumab pegol (400 mg/4wk s.c) OR Consider Azthioprine or 6 MP therapy ❑ A baseline CBC and LFT ❑ Azathioprine (2-3 mg/kg/day) OR ❑ 6-mercaptopurine (1-1.5 mg/kg/day)

Response to treatment

Response to treatment

No

Yes

Yes

No

Treat as severe to fulminant disease or consider managing as steroid contraindicated CD treatment

❑Taper steroids by 5-10 mg/wk until 20 mg and then by 2.5-5 mg/wk until discontinuation of therapy ❑ Baseline DEXA scan ❑ Oral calcium, vitamin D or bisphosphonates based on DEXA scan

Maintenance therapy ❑ Infliximab montherapy OR ❑ Combined infliximab and azathioprine therapy OR ❑ Methotrexate therapy (15 mg/wk i.m): For methotrexate induced remissions OR ❑ Adalimumab therapy (40 mg/wk s.c): For adalimumab induced remissions OR ❑ Certolizumab pegol therapy (400 mg/ 4wk s.c): For certolizumab pegol induced remissions OR ❑ Natalizumab therapy (300 mg/ 4wk s.c): For natalizumab induced remissions ❑ Monitor CBC every 3 months ❑ Monitor periodically for side effects

Surgical consultation (ileocolonic resections / perioperative antibiotics)

Steroid dependent (Flare up of symptoms on tapering steroids)

Steroid independent (No flare up of symptoms on tapering steroids)

Manage as steroid contraindicated CD treatment ❑ Consider methotrexate therapy OR ❑ Consider anti-TNF monoclonal antibody therapy OR ❑ Consider Azthioprine or 6 MP therapy PLUS ❑ Maintenance therapy or surgical consultation according to Rx response

Maintenance therapy ❑ Azathioprine (2-2.5 mg/kg) OR ❑ 6-mercaptopurine (1.5 mg/kg) ❑ Monitor CBC every 3 months ❑ Monitor periodically for side effects

Maintenance therapy ❑ Natalizumab therapy (300 mg/ 4wk s.c) OR ❑ Infliximab montherapy (1.5 mg/kg) ❑ Monitor CBC every 3 months ❑ Monitor periodically for side effects

Management of Severe to Fulminant Crohn's Disease

❑ Inpatient therapy ❑ NPO ❑ Start intravenous fluids ❑ Consider total parental nutrition

Abscess or peritonitis or severe intestinal obstruction or refractory/severe painful fistulas

No abscess or partial intestinal obstruction

Surgical consultation (ileocolonic resections / abscess drainage / perioperative antibiotics)

Intravenous prednisone (40-60 mg/day)

Maintenance therapy ❑ Natalizumab therapy (300 mg/ 4wk s.c) OR ❑ Infliximab montherapy (1.5 mg/kg) ❑ Monitor CBC every 3 months ❑ Monitor periodically for side effects

No response to Rx

Significant response to Rx

Intravenous cyclosporine or tacrolimus

❑ Gradually switch to oral steroids and monitor the response ❑ Taper the dose of steroids as mentioned above ❑ Monitor for any relapses and treat accordingly ❑ Start the patient on maintenance therapy as above

No response to Rx

Significant response to Rx

Surgical consultation (ileocolonic resections / abscess drainage / perioperative antibiotics)

Bridging therapy ❑ Switch to oral cyclosporine ❑ Taper off the glucocorticoids over the first 4-6 weeks ❑ Taper off cyclosporine microemulsion over the next 6-8 weeks ❑ Start then 6-mercaptopurine (6-MP) or azathioprine

Maintenance therapy ❑ Natalizumab therapy (300 mg/ 4wk s.c) OR ❑ Infliximab montherapy (1.5 mg/kg) ❑ Monitor CBC every 3 months ❑ Monitor periodically for side effects

Do's

• Always assess first the volume status and adequate intravascular volume in CD patients presenting with diarrhea. Correcting fluid and electrolyte disturbances take priority over identifying the causative agent.
• Always consider a diagnosis of underlying Crohn disease in patients with perianal disease that does not resolve with routine management and with unusual presentations such as complex anal fistulas, large indurated hemorrhoids and anal fissures that are not located in the midline.
• Always consider alternative inflammatory bowel diseases (infectious, ischemic, radiation-induced, medication-induced, particularly related to the use of non-steroidal anti-inflammatory drugs), or idiopathic intestinal disorders (ulcerative colitis, celiac disease, or microscopic colitis), and irritable bowel syndrome as differential diagnosis to CD before initiating the treatment.
• Colonoscopy with multiple biopsies (at least two biopsies from five sites including the distal ileum and rectum) is the first line procedure for diagnosing inflammatory bowel disease. Full colonoscopy is not advised in acute severe colitis, however phosphate enema prior to sigmoidoscopy is preferred and considered safe, except in those with colonic dilatation.
• Always decide therapeutic recommendations based upon the disease location, disease severity, and disease-associated complications and always consider maintenance therapy for patients achieving remission.
• Mid to moderate disease can be managed relatively early in the course of the disease with more potent therapies, such as biologic therapy or immunomodulator therapy, even before they receive glucocorticoids and become glucocorticoid dependent.
• Consider symptomatic treatment with loperamide in patients not responding completely to first-line therapy in the absence of warning signs. Cholestyramine can be given for patients with ileal resections who have bile salt diarrhea and non-stenosing ileitis who have chronic watery diarrhea.
• Do a lactose avoidance trial for CD patients with symptoms suggestive of lactase insufficiency and a lactose breath hydrogen test is done in any case of doubt.
• Do C. difficile testing for all patients with IBD who develop diarrhea following recent hospitalization or antibiotic use or in the setting of previously quiescent disease or with a disease flare. Consider the simultaneous treatment for IBD flare and empiric therapy against C. difficile infection among IBD patients who have severe colitis.
• Serological studies evaluating antibodies against S. cerevisiae, antineutrophil cytoplasmic antibodies, antibodies directed against CBir1, OmpC are not sufficiently sensitive or specific to be used as screening tools, but are evolving to provide adjunctive support for the diagnosis of CD.
• Do complete blood cell count and liver function tests at the initiation of 5-ASA therapy with subsequent monitoring every two weeks during the first three months, then monthly for the second three months, and every three months thereafter.
• Do serum blood urea nitrogen and creatinine and urinalysis testing at 6 weeks, 6 months, and 12 months after initiation of 5-ASA therapy and then annually.
• Do hepatitis B screening before initiating infliximab therapy.
• Do complete blood counts, initially every 1-2 weeks and at least every 3 months for patients on azathioprine, 6 mercaptopurine and other immunomodulator therapy to avoid the risk of acute or delayed bone marrow suppression.
• Always determine thiopurine methyltransferase (TPMT), the primary enzyme-metabolizing azathioprine/6-mercaptopurine, activity or genotype prior to initiating treatment with azathioprine or 6-mercaptopurine.
• Do switch patients to an alternative anti-TNF agent who fail to respond to, lose their response to, or are intolerant of one biologic therapy.
• Use metronidazole alone or in combination with ciprofloxacin for CD patients with non-suppurative perianal complications. Monitor patients for any evidence of peripheral neuropathy with long term metronidazole treatment and for tendonitis and tendon rupture with ciprofloxacin therapy.
• Immunomodulator therapy should be considered in patients with symptomatic perianal fistulas who do not respond to antibiotics and local therapy. Do treat patients with fistulae, especially those with actively draining fistulae or high output enteroenteric fistulae, with infliximab 5 mg/kg administered at weeks 0, 2, and 6 alone or in combination with azathioprine.
• Surgical intervention is required in some CD patients to treat intractable hemorrhage, perforation, persisting or recurrent obstruction, abscess (not amenable to percutaneous drainage), dysplasia or cancer, or unresponsive fulminant disease.
• Surgery should also be considered in patients who have active luminal CD and fail to improve within 7-10 days of intensive in-patient medical management.
• Do recommend prophylaxis for venous thromboembolism for all hospitalized patients with IBD.
• Do vaccinate patients on immunosuppresants routinely for influenza, pneumococcal, meningococcus infection, and for tetanus in the appropriate settings.

Don't s

• Don't treat patients with severe diarrheal dehydration using 5% dextrose with 1/4 normal saline, as using solutions with lower amounts of sodium (such as 38.5 mmol/L in 1/4 saline with 5% dextrose ) would lead to sudden and severe hyponatremia with a high risk of death.
• Oral rehydration therapy is contraindicated in the initial management of severe dehydration, in patients with frequent and persistent vomiting (more than four episodes per hour), and painful oral conditions such as moderate to severe thrush.
• Dont continue immunomodulator therapy in the occurrence of any hypersentivity reactions or toxic side effects.
• Dont use narcotic analgesia except for the perioperative setting because of the potential for tolerance and abuse in the setting of chronic disease.
• Dont use live vaccines in patients on immunosuppressants, so if these are required they should be administered at the time of inflammatory bowel disease diagnosis.
• Dont use infliximab in patients with active infection, untreated latent tuberculosis (TB), preexisting demyelinating disorder or optic neuritis, moderate to severe congestive heart failure, or current or recent malignancies.
• Dont treat patients with decompensated heart failure with infliximab because of the risk of further decline in cardiac function.
• Dont use medications with anticholinergic or narcotic properties in patients with either toxic signs (fever, leukocytosis, or worsening symptoms) or megacolon, due to possibility of worsening colonic atony or dilatation, as increased colonic and small intestinal gas is a predictor of a poor outcome to medical therapy.