26

CHAPTER
Inflammatory Bowel Disease

• There are two forms of idiopathic inflammatory bowel disease (IBD): ulcerative colitis
(UC), a mucosal inflammatory condition confined to the rectum and colon, and
Crohn’s disease (CD), a transmural inflammation of gastrointestinal (GI) mucosa
that may occur in any part of the GI tract. The etiologies of both conditions are
unknown, but they may have a common pathogenic mechanism.

ETIOLOGY AND PATHOPHYSIOLOGY

• Factors that cause IBD include infectious agents, genetics, the environment, and
the immune system. This may involve abnormal regulation of the innate immune
response or a reaction to various antigens. The microflora of the GI tract may pro-
vide an environmental trigger to activate inflammation in genetically susceptible
individuals and is highly implicated in the development of IBD.
• Suspect infectious agents include viruses, protozoans, mycobacteria such as Mycobac-
terium paratuberculosis or avium, and other bacteria such as Ruminococcus gnavus,
Ruminococcus torques, Listeria monocytogenes, Fusobacterium varium, Chlamydia
trachomatis, and Escherichia coli. Patients with CD typically have circulating antibod-
ies to Saccharomyces cerevisiae, which demonstrates some immunologic response to
intestinal organisms.
• Genetic factors play a significant role in the predisposition to IBD. First-degree rela-
tives of patients with IBD may have up to a 20-fold increase in the risk of disease and
risk is extended to second- and third-degree relatives.
• Th1 cytokine activity is excessive in CD, and increased expression of interferon-γ in
the intestinal mucosa and excess production of IL-12, IL-17A, and IL-22 are features
of the immune response in CD. In contrast, Th2 cytokine activity is excessive with
UC. Tumor necrosis factor-α (TNF-α) is a pivotal proinflammatory cytokine that is
increased in the mucosa and intestinal lumen of patients with CD and UC.
• Antineutrophil cytoplasmic antibodies are found in a high percentage of patients
with UC and less frequently with CD.
• Smoking appears to be protective for UC but is associated with increased frequency
and severity of CD. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) may trig-
ger disease occurrence or lead to disease flares.
• UC and CD differ in two general respects: anatomical sites and depth of involvement
within the bowel wall. There is, however, overlap between the two conditions, with a
small fraction of patients showing features of both diseases (Table 26-1).

ULCERATIVE COLITIS
• UC is confined to the colon and rectum and affects primarily the mucosa and
the submucosa. The primary lesion occurs in the crypts of the mucosa (crypts of
Lieberkühn) in the form of a crypt abscess.
• Local complications (involving the colon) occur in the majority of patients with UC.
Relatively minor complications include hemorrhoids, anal fissures, and perirectal
abscesses.
• A major complication is toxic megacolon, a severe condition that occurs in up to
7.9% of UC patients admitted to hospitals. Patients with toxic megacolon usually
have a high fever, tachycardia, distended abdomen, elevated white blood cell count,
and a dilated colon.
• The risk of colonic carcinoma is much greater in patients with UC than in the general
population.
• Patients with UC may have hepatobiliary complications, including fatty liver, peri-
cholangitis, chronic active hepatitis, cirrhosis, sclerosing cholangitis, cholangiocar-
cinoma, and gallstones.

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 Inflammatory Bowel Disease | CHAPTER 26

TABLE 26-1 Comparison of the Clinical and Pathologic Features of Crohn’s Disease and
Ulcerative Colitis
Feature Crohn’s Disease Ulcerative Colitis
Clinical
Malaise, fever Common Uncommon
Rectal bleeding Common Common
Abdominal tenderness Common May be present
Abdominal mass Common Absent
Abdominal pain Common Unusual
Abdominal wall and internal fistulas Common Absent
Distribution Discontinuous Continuous
Aphthous or linear ulcers Common Rare
Pathologic
Rectal involvement Rare Common
Ileal involvement Very common Rare
Strictures Common Rare
Fistulas Common Rare
Transmural involvement Common Rare
Crypt abscesses Rare Very common
Granulomas Common Rare
Linear clefts Common Rare
Cobblestone appearance Common Absent

• Arthritis commonly occurs in patients with IBD and is typically asymptomatic and
migratory. Arthritis typically involves one or a few large joints, such as the knees,
hips, ankles, wrists, and elbows.
• Ocular complications including dry eye, blepharitis, iritis, uveitis, episcleritis, and
conjunctivitis occur in up to 29% of patients with IBD occur in some patients. Skin
and mucosal lesions associated with IBD include erythema nodosum, pyoderma
gangrenosum, aphthous ulceration, and Sweet syndrome.

CROHN’S DISEASE
• CD is a transmural inflammatory process. The terminal ileum is the most common
site, but it may occur in any part of the GI tract. Most patients have some colonic
involvement. Patients often have normal bowel separating segments of diseased
bowel; that is, the disease is often discontinuous.
• Complications of CD may involve the intestinal tract or organs unrelated to it.
Small bowel stricture with subsequent obstruction is a complication that may
require surgery. Fistula formation is common and occurs much more frequently
than with UC.
• Systemic complications of CD are common and similar to those found with UC.
Arthritis, iritis, skin lesions, and liver disease often accompany CD.
• Nutritional deficiencies are common with CD (including deficiencies of folate, vita-
min B12, vitamins A to D, calcium, magnesium, iron, and zinc).

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CLINICAL PRESENTATION AND DIAGNOSIS

ULCERATIVE COLITIS
• There is a wide range of presenting symptoms in UC, from mild abdominal cramping
with frequent small-volume bowel movements to profuse diarrhea. Many patients
have disease confined to the rectum (proctitis).
• Most patients with UC experience intermittent bouts of illness after varying intervals
of no symptoms.
• Mild disease, which afflicts two-thirds of patients, has been defined as fewer than
four stools daily, with or without blood, with no systemic disturbance and a normal
erythrocyte sedimentation rate (ESR <30 mm/h).
• Patients with moderate disease have more than four stools per day but with minimal
systemic disturbance.
• With severe disease, the patient has more than six stools per day with blood, with
systemic manifestations of fever, tachycardia, anemia, or ESR greater than 30 mm/h
(8.3 µm/sec). With fulminant disease, there are more than 10 bowel movements per
day with continuous bleeding, toxicity, abdominal tenderness, requirement for trans-
fusion, and colonic dilation.
• Signs and symptoms
✓ Abdominal cramping
✓ Frequent bowel movements, often with blood in the stool
✓ Weight loss
✓ Fever and tachycardia in severe disease.
✓ Blurred vision, eye pain, and photophobia with ocular involvement
✓ Arthritis
✓ Raised, red, tender nodules that vary in size from 1 cm to several centimeters
• Physical examination
✓ Hemorrhoids, anal fissures, or perirectal abscesses may be present
✓ Iritis, uveitis, episcleritis, and conjunctivitis with ocular involvement
✓ Dermatologic findings with erythema nodosum, pyoderma gangrenosum, or
aphthous ulceration
• Laboratory Tests
✓ Decreased hematocrit/hemoglobin
✓ Increased ESR, CRP, and fecal calprotectin
✓ Leukocytosis and hypoalbuminemia with severe disease
✓ (+) perinuclear antineutrophil cytoplasmic antibodies

CROHN’S DISEASE
• As with UC, the presentation of CD is highly variable. A patient may present with
diarrhea and abdominal pain or a perirectal or perianal lesion. Patients with mild-
to-moderate CD are typically ambulatory and have no evidence of dehydration,
systemic toxicity, less than 10% loss of body weight, or abdominal tenderness, mass,
or obstruction.
• The course of CD is characterized by periods of remission and exacerbation. Some
patients may be free of symptoms for years, whereas others experience chronic prob-
lems despite medical therapy.
• The Crohn’s Disease Activity Index (CDAI) is used to gauge response to therapy and
determine remission. Disease activity may be assessed and correlated by evaluation
of serum C-reactive protein concentrations.
• Signs and Symptoms
✓ Malaise and fever
✓ Abdominal pain
✓ Frequent bowel movements

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 Inflammatory Bowel Disease | CHAPTER 26

✓ Hematochezia
✓ Fistula
✓ Weight loss and malnutrition
✓ Arthritis
• Physical examination
✓ Abdominal mass and tenderness
✓ Perianal fissure or fistula
• Laboratory tests
✓ Increased white blood cell count, ESR, CRP, and fecal calprotectin
✓ (+) anti–Saccharomyces cerevisiae antibodies

TREATMENT
• Goals of Treatment: Resolution of acute inflammatory processes, resolution of atten-
dant complications (eg, fistulas or abscesses), alleviation of systemic manifestations
(eg, arthritis), maintenance of remission from acute inflammation, or surgical pal-
liation or cure.
• Treatment often involves use of specific targets, such as mucosal healing and endo-
scopic remission, or resolution of symptoms such as abdominal pain and diarrhea, as
the main indicators of treatment efficacy (referred to as “Treat to Target”).

NONPHARMACOLOGIC TREATMENT
• Patients with IBD have a five-fold higher risk of malnutrition compared to those
without IBD. Patients should be screened for malnutrition upon diagnosis and
assessed intermittently for the presence of micronutrient deficiencies.
• Elimination of specific foods that appear to exacerbate symptoms can be tried;
however, exclusion diets are generally not endorsed, even in the setting of severe
disease.
• Parenteral nutrition is generally reserved for patients with severe malnutrition or
those who fail enteral therapy or have a contraindication to receiving enteral therapy,
such as perforation, protracted vomiting, short bowel syndrome, or severe intestinal
stenosis.
• While probiotics are considered to be generally safe in patients with IBD, the
added cost and requirement to often take multiple doses per day, coupled with
the lack of quality data to support their use, should weigh into the decision to use
them in IBD.
• Colectomy may be necessary for UC patients with disease uncontrolled by maximum
medical therapy or when there are disease complications such as colonic perforation,
toxic megacolon, uncontrolled colonic hemorrhage, or colonic strictures.
• Surgery in patients with CD is usually reserved for patients with intractable hemor-
rhage, perforation, persistent or recurrent obstruction, abscess, dysplasia, cancer, or
medically refractory disease. CD has a high recurrence rate after surgery.

PHARMACOLOGIC THERAPY
• The major drug therapies used in IBD are aminosalicylates; corticosteroids; immu-
nomodulators (azathioprine, mercaptopurine, and methotrexate); immunosup-
pressive agents (cyclosporine and tacrolimus); antimicrobials (metronidazole and
ciprofloxacin); and agents to inhibit TNF-α (anti–TNF-α antibodies), leukocyte
adhesion and migration (natalizumab and vedolizumab), interleukin function
(ustekinumab), or Janus kinase function (tofacitinib).
• Sulfasalazine combines a sulfonamide (sulfapyridine) antibiotic and mesalamine
(5-aminosalicylic acid) in the same molecule. Oral mesalamine derivatives are alter-
natives to sulfasalazine for treatment of mild-to-moderate UC with similar rates of
efficacy. Mesalamine-based products are listed in Table 26-2.

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TABLE 26-2 Agents for the Treatment of Inflammatory Bowel Disease

Drug Brand Name Initial Dose (g) Usual Range
Sulfasalazine Azulfidine 500 mg–1 g 4–6 g/day
Azulfidine EN 500 mg–1 g 4–6 g/day
Mesalamine Canasa 1g 1 g daily to three
suppository times weekly
Mesalamine enema Rowasa 4g 4 g daily to three
times weekly
Mesalamine (oral) Asacol HD 1.6 g/day 2.8–4.8 g/day
Apriso 1.5 g/day 1.5 g/day once daily
Lialda 1.2–2.4 g/day 1.2–4.8 g/day once
daily
Pentasa 2 g/day 2–4 g/day
Delzicol 1.2 g/day 2.4–4.8 g/day
Olsalazine Dipentum 1.5 g/day 1.5–3 g/day
Balsalazide Colazal 2.25 g/day 2.25–6.75 g/day
Azathioprine Imuran, Azasan 50–100 mg 1–2.5 mg/kg/day
Cyclosporine Gengraf 2–4 mg/kg/day IV 2–4 mg/kg/day IV
Neoral, 2–8 mg/kg/day oral
Sandimmune
Mercaptopurine Purinethol 50–100 mg 1–2.5 mg/kg/day
Methotrexate No branded IM 15–25 mg IM weekly 15–25 mg IM weekly
injection
Adalimumab Humira 160 mg SC day 1 80 mg SC 2 (day 15),
Adalimumab-atto Amjevita and then 40 mg
every 2 weeks
Adalimumab-abdm Cyltezo
Adalimumab-adaz Hyrimoza
Adalimumab-afzb Adriladaa
Adalimumab- Adalimumab-
bwwd bwwd Hadlimaa
Certolizumab Cimzia 400 mg SC 400 mg SC weeks 2
and 4, and then
400 mg SC monthly
Infliximab Remicade 5 mg/kg IV 5 mg/kg weeks 2 and
Infliximab-dyyb Inflectra 6, 5–10 mg/kg
every 8 weeks
Infliximab-abda Renflexis
Infliximab-qbtx IXIFI
Infliximab-axxq AVSOLA
Natalizumab Tysabri 300 mg IV 300 mg IV every
4 weeks
Budesonide Entocort EC 9 mg orally once daily 6–9 mg daily
capsule, Uceris
tablet
Uceris rectal foam 2 mg twice daily 2 mg daily
(Continued)

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TABLE 26-2 Agents for the Treatment of Inflammatory Bowel Disease (Continued)
Drug Brand Name Initial Dose (g) Usual Range
Vedolizumab Entyvio 300 mg IV 300 mg IV weeks 2
and 6 and then
every 8 weeks
Golimumab Simponi 200 mg SC 100 mg SC weeks
2 and 4
Ustekinumab Stelara Weight-based initial IV 90 mg SC every
dose <55 kg (260 mg), 8 weeks
55–85 kg (390 mg),
>85 kg (520 mg)
Tofacitinib Xeljanz 10 mg twice daily for 5 mg twice daily
8 weeks; may continue
for maximum of
16 weeks
Ozanimod Zeposia 0.23 mg orally once 0.92 mg orally once
daily days 1–4, then daily starting day
0.46 mg once daily 8 of therapy
days 5–7
a
Not available until 2023
IM, intramuscular; SC, subcutaneous.

• Oral corticosteroids in doses of 40–60 mg/day prednisone equivalent can be used

for patients with moderate-to-severe active disease who are refractory to oral amino-
salicylates or require more rapid control of symptoms.
• Immunomodulators such as azathioprine, mercaptopurine (a metabolite of azathio-
prine), methotrexate, or cyclosporine are used in the long-term treatment of IBD.
These agents are generally reserved for patients who fail aminosalicylate therapy or
are refractory to or dependent on corticosteroids.
• Cyclosporine has a short-term benefit in the treatment of acute, severe UC to avoid
colectomy in patients failing corticosteroids but has little efficacy in CD.
• Methotrexate 15–25 mg intramuscularly or subcutaneously once weekly is useful for
treatment and maintenance of CD and may be steroid sparing.
• Antimicrobial agents have limited roles as adjunctive therapies in IBD. Metroni-
dazole can be used as adjunctive therapy for simple perianal fistulaes and may be
combined with infliximab.
• Infliximab is an anti-TNFα antibody that is useful in moderate-to-severe active
CD and UC as well as steroid-dependent or fistulizing disease, both as induction
and maintenance therapy. Adalimumab is another anti-TNFα (fully humanized)
antibody that is an option for patients with moderate-to-severe active CD or UC
previously treated with infliximab who have lost response.
• Natalizumab and vedolizumab are leukocyte adhesion and migration inhibitors that
are used for patients with CD who are unresponsive to other therapies.

Ulcerative Colitis
Mild-to-Moderate Active Disease
• Most patients with mild-to-moderate active UC can be managed on an outpatient
basis with oral and/or topical aminosalicylates (Fig. 26-1). For patients with exten-
sive disease, oral once-daily mesalamine is generally preferred in doses of 2–3 g/day.
Doses greater than 3 g/day can be used in patients who are unresponsive to standard
doses and generally should be combined with a rectal mesalamine formulation at a
dose of 1 g/day.

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 SECTION 5 | Gastrointestinal Disorders

Distal Consider reducing oral

Disease severity
Oral sulfasalazine or mesalamine or
mesalamine, or mesalamine Remission sulfasalazine dose to
Mild enema (2–3 g/day left sided), or 2–3 g/day, or mesalamine
suppository 1 g/day (proctitis) enema 4 g every 1–2 days,
or suppository 1 g every
1–2 days
Extensive
oral mesalamine 2–3 g/day Reduce sulfasalazine or
or Remission mesalamine dose to
controlled release 2–3 g/day or
Moderate budesonide 9 mg/day continue budesonide for
up to 8 weeks

Taper prednisone,
Budesonide MMX 9 mg/day or Remission then after 1–2 mo or
prednisone 40–60 mg/day continue Budesonide
for 8 weeks
Severe
Infliximab plus azathioprine,
Inadequate or no response OR certolizumab, adalimumab,
vedolizumab, tofaciitinib
or ozanimod. Avoid switching
to the biosimilar of the original
agent. Ustekinumab for
anti-TNF failure or intolerance.

Methylprednisolone 40–60 mg Remission

or hydrocortisone IV Change to prednisone
100 mg every 6–8 h
Fulminant
No response in 3–5 days Add azathioprine,
Infliximab mercaptopurine, infliximab,
or cyclosporine IV certolizumab, adalimumab,
4 mg/kg/day vedolizumb or tofacitinib
attempt to withdraw
Remission steroids after 1–2 mo
Change to oral cyclosporine Remission
and add AZA/MP or
vedolizumab OR continue Maintain TNF-α inhibitor
Infliximab or immunomodulator

AZA, Azathioprine; MMX, Multi-matrix system; MP, mercaptopurine, and TNF, tumor necrosis factor.
FIGURE 26-1. Treatment approaches for ulcerative colitis.

• Oral mesalamine derivatives (see Table 26-2) are reasonable alternatives to sulfasala-
zine for treatment of UC because they are better tolerated. Topical mesalamine in an
enema or suppository formulation is more effective than oral mesalamine or topical
steroids for distal disease.
• Budesonide 9 mg/day is preferred for patients who are unresponsive to optimized
doses of mesalamine.

Moderate-to-Severe Active Disease

• While oral mesalamine products may be effective for moderately severe UC, oral
budesonide MMX is the preferred alternative prior to use of more systemic cortico-
steroids and for moderate disease.

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 Inflammatory Bowel Disease | CHAPTER 26

• Steroids have a place in the treatment of moderate-to-severe UC or in patients who

are unresponsive to maximal doses of oral and topical mesalamine. Oral cortico-
steroids in doses of 40–60 mg prednisone equivalent daily are recommended for
adults.
• TNF-α inhibitors are an option for patients with moderate-to-severe disease who are
unresponsive to aminosalicylates or corticosteroids, or are corticosteroid dependent,
and are more effective than immunomodulator monotherapy for induction of remis-
sion. For treatment-naive patients, infliximab or vedolizumab in combination with
an immunomodulator (eg, azathioprine) is recommended preferentially.

Active Severe or Fulminant Disease

• Patients with uncontrolled acute severe UC or incapacitating symptoms require
hospitalization for effective management. Most medications are given parenterally.
Patients should be tested for Clostridoidies difficile infection and receive venous
thromboembolism (VTE) prophylaxis.
• Methylprednisolone IV at a dose of 40–60 mg daily is considered a first-line agent. A
trial of corticosteroids is warranted in most patients before proceeding to colectomy,
unless the condition is grave or rapidly deteriorating.
• Patients who are unresponsive to parenteral corticosteroids can receive cyclosporine
or infliximab. A continuous IV infusion of cyclosporine 2–4 mg/kg/day is the typical
dose range used and may delay the need for colectomy.

Maintenance of Remission
• Once remission from active disease has been achieved, the goal of therapy is to main-
tain the remission for as long as possible.
• For patients with previously mildly active extensive or left-side disease, the oral ami-
nosalicylate agents are preferred for maintenance therapy at a dose of at least 2 g/day.
The newer mesalamine derivatives are generally better tolerated than sulfasalazine
and are associated with fewer adverse effects, making them a preferred choice.
• The TNF-α inhibitors, vedolizumab, ustekinumab, or tofacitinib are all options for
maintenance in patients with moderate-to-severe UC following successful induction
of remission, and in those who are steroid-dependent or have failed azathioprine.
• Steroids do not have a role in the maintenance of remission with UC because they
are ineffective. Steroids should be withdrawn gradually over 2–4 weeks after remis-
sion is induced.

Crohn’s Disease
• Sulfasalazine has marginal efficacy in mild-to-moderate CD. The newer mesalamine
derivatives are generally considered to have minimal efficacy.
• Mesalamine derivatives that release mesalamine in the small bowel (eg, Pentasa) may
be more effective than sulfasalazine for ileal involvement.
• Systemic corticosteroids are frequently used for treating moderate-to-severe active
CD; however, controlled-release budesonide (Entocort) 9 mg daily is a preferred
first-line option for patients with mild-to-moderate ileal or right-sided (ascending
colonic) disease.
• Oral corticosteroids, such as prednisone 40−60 mg/day, are generally considered
first-line therapy and are frequently used for moderate-to-severe active CD unre-
sponsive to aminosalicylates.
• Metronidazole 10−20 mg/kg/day orally in divided doses may be useful in some
patients with CD, particularly for patients with colonic or ileocolonic involvement,
those with perineal disease, or those who are unresponsive to sulfasalazine.
• Azathioprine, mercaptopurine, and methotrexate are not recommended to induce
remission in moderate-to-severe CD; however, they are effective in maintaining
steroid-induced remission and are generally limited to use for patients not achiev-
ing adequate response to standard medical therapy or in the setting of steroid
dependency.

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 SECTION 5 | Gastrointestinal Disorders

• Clinical response to azathioprine and mercaptopurine may be related to whole-blood

concentrations of the metabolite 6-thioguanine (TGN). Concentrations of TGN
greater than 230−450 pmol/8 × 108 erythrocytes have beneficial effects, but moni-
toring is not routinely performed or may not be available at some sites.
• Methotrexate given weekly intramuscularly or subcutaneously in doses of 15−25 mg
is effective in reducing steroid dependency and maintaining remission, and may be
considered as an alternative to azathioprine or mercaptopurine.
• The TNF-α inhibitors are the most effective and thus the preferred agents in man-
aging moderate-to-severe CD. All agents in this class, with the exception of golim-
umab, which is not approved for use in CD in the United States, have similar rates of
efficacy. The use of TNF-α inhibitors in combination with thiopurines has quickly
become the preferred approach to treatment of moderate-to-severe CD.
• The integrin antagonists are options for patients who do not respond to steroids
or TNF-α inhibitors, and vedolizumab is also considered a first-line alternative to
TNF-α inhibitors for moderate-to-severe disease.

Maintenance of Remission
• Prevention of recurrence of disease is more difficult with CD than with UC. There is
minimal evidence that sulfasalazine and oral mesalamine derivatives are effective for
maintenance of CD remission following medically induced remission, and therefore
these agents are not preferred (Fig. 26-2).
• Systemic steroids have no role in the maintenance of remission or prevention of
recurrence of CD; these agents do not appear to alter the long-term course of the
disease. Budesonide can be considered for maintenance therapy for up to 4 months.
• All of the TNF-α inhibitors currently approved for use in CD are viable options for
maintenance of remission. Combination therapy with a thiopurine should be highly
considered to further improve efficacy and to extend the duration of TNF-α inhibitor
efficacy by reducing immunogenicity.
• Methotrexate may be considered as an alternative to thiopurines to maintain corti-
costeroid-induced remission.

Disease severity
Mild
Perianal Small bowel
Metronidazole Budesonide 9 mg/day for
Sulfasalazine 3–6 g/day up to 10–20 mg/kg/day terminal ileal or ascending
+/– infliximab colonic disease

Response Taper prednisone

Moderate after 2–4 weeks

Prednisone + infliximab, adalimumab, Add azathioprine, mercapto-

certolizumab, vedolizumab +/– purine, or methotrexate if not
methotrexate, azathioprine, or already receiving; change to
mercaptopurine. natalizumab or vedolizumab
if no response to TNF-α
inhibitor + immunomodulator.
Inadequate Consider TNF-α trough
Severe
or monitoring. Ustekimumab
no response may be considered
as a last line option.

Hydrocortisone 100 mg Consider infliximab prior

IV every 6–8 hr No response in to surgery as last option
Fulminant 5–7 days

FIGURE 26-2. Treatment approaches for Crohn’s disease.

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 Inflammatory Bowel Disease | CHAPTER 26

SELECT COMPLICATIONS
Toxic Megacolon
• The treatment required for toxic megacolon includes general supportive measures
to maintain vital functions, consideration for early surgical intervention, and drug
therapy.
• Aggressive fluid and electrolyte management are required for dehydration. When the
patient has lost significant amounts of blood (through the rectum), blood transfusion
may be necessary.
• Steroids in high doses (eg, hydrocortisone 100 mg every 8 hours) should be adminis-
tered IV to reduce acute inflammation.
• Broad-spectrum antimicrobials that include coverage for gram-negative bacilli and
intestinal anaerobes should be used as preemptive therapy if perforation occurs.

Extraintestinal Manifestations
• For arthritis, aspirin or another NSAID may be beneficial, as are corticosteroids.
However, NSAID use may exacerbate the underlying IBD and predispose patients
to GI bleeding.
• Anemia secondary to blood loss from the GI tract can be treated with oral ferrous
sulfate. Vitamin B12 or folic acid may also be required.
• If the patient is deemed high risk for osteoporosis or exhibits a reduced serum
vitamin D concentration, vitamin D and calcium should be administered. If
osteoporosis is present, then calcium, vitamin D, and a bisphosphonate or possibly
teriparatide are recommended.

EVALUATION OF THERAPEUTIC OUTCOMES

• See Table 26-3 for drug monitoring guidelines.
• Patients receiving sulfasalazine should receive oral folic acid supplementation
because sulfasalazine inhibits folic acid absorption.
• The success of therapeutic regimens to treat IBDs can be measured by patient-
reported complaints, signs and symptoms, direct physician examination (including
endoscopy), history and physical examination, select laboratory tests, and quality of
life measures.
• Adverse effects of corticosteroids include hyperglycemia, hypertension, osteoporosis,
acne, fluid retention, electrolyte disturbances, myopathies, muscle wasting, increased
appetite, psychosis, infection, and adrenocortical suppression. To minimize corti-
costeroid effects, clinicians may use alternate-day steroid therapy; however, some
patients do not do well clinically on the days when no steroid is given.
• To create more objective measures, disease-rating scales or indices have been created.
CDAI is a commonly used scale, particularly for evaluation of patients during clinical
trials. The scale incorporates eight elements: (1) number of stools in the past 7 days,
(2) sum of abdominal pain ratings from the past 7 days, (3) rating of general well-
being in the past 7 days, (4) use of antidiarrheals, (5) body weight, (6) hematocrit,
(7) finding of abdominal mass, and (8) a sum of symptoms present in the past week.
• Standardized assessment tools have also been constructed for UC. Elements in these
scales include: (1) stool frequency; (2) presence of blood in the stool; (3) mucosal
appearance (from endoscopy); and (4) physician’s global assessment based on physi-
cal examination, endoscopy, and laboratory data.

See Chapter 52, Inflammatory Bowel Disease, authored by Brian A. Hemstreet, for a more
detailed discussion of this topic.

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276

SECTION 5
TABLE 26-3 Drug Monitoring Guidelines
Drug(s) Adverse Drug Reaction Monitoring Parameters Comments
Sulfasalazine Nausea, vomiting, headache Folate, complete blood count Increase the dose slowly, over 1−2 weeks
Rash, anemia, pneumonitis Liver function tests, Scr, BUN

|
Hepatotoxicity, nephritis

Gastrointestinal Disorders
Thrombocytopenia, lymphoma
Mesalamine Nausea, vomiting, headache GI disturbances
Corticosteroids Hyperglycemia, dyslipidemia Blood pressure, fasting lipid panel Avoid long-term use if possible or consider
Osteoporosis, hypertension, acne Glucose, vitamin D, bone density budesonide
Edema, infection, myopathy,
psychosis
Azathioprine/Mercaptopurine Bone marrow suppression, Complete blood count Check TPMT activity or NUDT15 phenotype
pancreatitis, Lymphoma Scr, BUN, liver function tests, genotype/ May monitor TGN
Liver dysfunction, rash, arthralgia phenotype
Methotrexate Bone marrow suppression, Complete blood count, Scr, BUN Check baseline pregnancy test
pancreatitis Liver function tests Chest x-ray
Pneumonitis, pulmonary fibrosis,
hepatitis
Infliximab Infusion-related reactions Blood pressure/heart rate (infliximab) Need negative PPD and viral serologies
Adalimumab (infliximab), infection Neurologic exam, mental status
Certolizumab Heart failure, optic neuritis, Trough concentrations (infliximab)
demyelination, injection site
Golimumab reaction, signs of infection Antidrug antibodies (all agents)
Natalizumab Infusion-related reactions Brain MRI, mental status, progressive Vedolizumab not associated with PML
multifocal leukoencephalopathy
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Vedolizumab

Ustekinumab Infections, skin cancers Signs/symptoms of infection, annual Rare instances of reversible posterior
skin exam leukoencephalopathy syndrome (RPLS)
Avoid live vaccines
Tofacitinib Infection, thrombosis, lymphoma, Symptoms of infection or thrombosis Avoid live vaccines
elevated cholesterol, CK, LFTs, Screen for baseline TB
lymphopenia, neutropenia,
anemia Do not initiate in patients with lymphocytes
<500/mm3, ANC <1000/mm3, or
hemoglobin <9 g/dL
 Liver function tests Chest x-ray
Pneumonitis, pulmonary fibrosis,
hepatitis
Infliximab Infusion-related reactions Blood pressure/heart rate (infliximab) Need negative PPD and viral serologies
Adalimumab (infliximab), infection Neurologic exam, mental status
Certolizumab Heart failure, optic neuritis, Trough concentrations (infliximab)
demyelination, injection site
Golimumab reaction, signs of infection Antidrug antibodies (all agents)
Natalizumab Infusion-related reactions Brain MRI, mental status, progressive Vedolizumab not associated with PML
Vedolizumab multifocal leukoencephalopathy
27_Schwinghammer_ch26.indd 277

Ustekinumab Infections, skin cancers Signs/symptoms of infection, annual Rare instances of reversible posterior
skin exam leukoencephalopathy syndrome (RPLS)
Avoid live vaccines
Tofacitinib Infection, thrombosis, lymphoma, Symptoms of infection or thrombosis Avoid live vaccines
elevated cholesterol, CK, LFTs, Screen for baseline TB
lymphopenia, neutropenia,
anemia Do not initiate in patients with lymphocytes
<500/mm3, ANC <1000/mm3, or
hemoglobin <9 g/dL
Monitor lipids and LFTs every 4−8 weeks
Gastrointestinal perforation has been reported
with use of the XR formulation
Drug interactions with CYP3A4 and 2C19

Inflammatory Bowel Disease | CHAPTER 26

inhibitors
Ozanimod Infection, heart rate, blood pressure, Symptoms of infection or respiratory Need baseline ECG, WBC, LFTs, ophthalmic
LFTs, respiratory rate, fetal dysfunction, changes in vision assessment, and testing for varicella zoster
abnormalities, macular edema, antibodies. Contraindicated if patient has
headache experienced MI, unstable angina, stroke,
TIA, decompensated heart failure, or Mobitz
type II second- or third-degree AV block,
sick sinus syndrome in the last 6 months,
presence of sleep apnea, and concomitant
use of MAOI. Women of childbearing age
should use effective contraception during
and for 3 months after use
ANC, absolute neutrophil count; BUN, blood urea nitrogen; CK, creatine kinase; GI, gastrointestinal; LFTs, liver function tests; MRI, magnetic resonance imaging; PML, progressive multifocal
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leukoencephalopathy; PPD, purified protein derivative; SCr, serum creatinine; TGN, thioguanine; TPMT, thiopurine methyltransferase; XR, extended-release.
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