INFLAMMATORY BOWEL DISEASE - ACCP
Abbreviations
INFLAMMATORY
BOWEL DISEASE
Jeffrey F. Binkley, Pharm.D., BCNSP
Reviewed by Michelle M. Chapman, Pharm.D., FCCP, BCPS; Joseph T. DiPiro, Pharm.D., FCCP; and
Karen Whalen, R.Ph., BCPS
Learning Objectives
1.
2.
3.
4.
5.
6.
7.
8.
is complex and has not been fully elucidated, both have
distinct and overlapping clinical manifestations and
pathology. These disease processes can have broad social,
economic, and health-related quality of life influences that
significantly impact patients and their families. Treatment
options include medical and surgical interventions, but
results are variable, depending on the type, severity, and
location of disease. This chapter addresses the pathogenesis
and treatment of these two potentially debilitating diseases,
offering guidance to pharmacists who can help patients
achieve optimal pharmacological therapy and improve their
quality of life. Comparisons of UC and CD will be made
throughout the chapter, noting similarities and highlighting
differences in manifestations, diagnosis, and treatment of
these disorders.
Based on a patient¡¯s signs and symptoms, history, and
diagnostic findings, distinguish between the
characteristics of Crohn¡¯s disease (CD) and ulcerative
colitis (UC) and understand how the site and type of
disease can influence treatment options.
Given patient-specific parameters and indicators, assess
a patient¡¯s severity of CD or UC and risk of disease
progression or cancer development.
Based on a patient¡¯s history, symptoms, and type and
site of disease, design and implement the best
pharmacological interventions using antibiotic
drugs, anti-inflammatory drugs, corticosteroids,
immunomodulators, and adjunctive drugs to treat CD
or UC and evaluate the effectiveness of treatment.
Evaluate and justify the appropriate use of infliximab to
treat CD based on the efficacy, toxicity, and
cost-effectiveness.
Design appropriate pharmacological therapies to
maintain remission for patients with inflammatory
bowel disease (IBD).
Given patient-specific information, design appropriate
nutritional interventions for patients with IBD.
Given patient information regarding response to
pharmacotherapy, design appropriate monitoring plans and
evaluate appropriate counseling requirements to optimize
treatment outcomes and prevent treatment failures.
Based on patient-specific needs, recommend resources
for patients with treatment, economic or psychological
challenges due to refractory IBD.
Pathophysiology of IBD
Definitions
Although there are many similarities between UC and
CD, the basic defining differences involve the location of
disease and the extent of inflammation. Ulcerative colitis is
characterized by inflammation limited to the superficial
mucosal layer of the colon and does not affect other areas of
the gastrointestinal tract. Crohn¡¯s disease is characterized by
transmural, or deeper, mucosal inflammation and can be
present throughout the gastrointestinal tract. Other
distinguishing characteristics for UC and CD are listed in
Table 1-1.
For patients with UC, the rectum is almost always
affected, but disease also may extend proximally and
continuously to involve other locations within the large
bowel. When only the rectum is inflamed, the disease is
known as ulcerative proctitis. Distal colitis or
proctosigmoiditis describes disease extending into the
midsigmoid colon. Left-sided UC reaches the splenic
flexure. Disease involving the entire colon, including
Introduction
Inflammatory bowel disease (IBD) is a grouping of two
similar disorders: ulcerative colitis (UC) and Crohn¡¯s
disease (CD). Although the pathogenesis of these disorders
Pharmacotherapy Self-Assessment Program, 5th Edition
69
Inflammatory Bowel Disease
Abbreviations
predominance in CD has been observed in women, but
predominance has been noted in men with UC.
Abbreviations in this
Chapter
CD
IBD
pANCA
Th1
TNF
UC
Etiology
The pathogenesis of IBD is not known; however, three
components have been established as major contributors:
genetic predisposition, environmental factors, and
immunologic influences. Disease development may be a
result of complex interactions of all three of these
influences; however, further investigation is required to
fully understand the intricacies of these interactions.
Crohn¡¯s disease
Inflammatory bowel disease
Perinuclear antineutrophilic
cytoplasmic antibody
Type 1 helper T cell
Tumor necrosis factor
Ulcerative colitis
Genetic Influences
Genetic factors may influence susceptibility to IBD. The
majority of patients with IBD have no family history of
IBD; however, in patients who have a positive family
history, the most common occurrence is in first-degree
relatives. Evidence derived from studies of identical twins
indicates stronger genetic influences for CD than for UC.
Specific genes responsible for the genetic risk of IBD have
not been fully identified; however, multiple genes probably
contribute to the complex IBD phenotype in humans.
Animal models with modified genes have indicated that
colitis may result from alterations in many genes. Many
gene alterations may impact changes in the mucosal
immune system. Animal models with genetic alterations
demonstrated a lack of disease when the animals were
maintained in germ-free environments. This observation
suggests the role of environmental factors in disease
development.
sections beyond the splenic flexure, is described as
pancolitis.
For patients with CD, the severity of mucosal
inflammation may lead to the development of fibrosis,
which may result in obstructive symptoms, which are not
seen in patients with UC. Sinus tracts may burrow and
penetrate the serosa, giving rise to bowel perforations and
fistula formation. Crohn¡¯s disease may involve any area of
the gastrointestinal tract from the mouth to the anus, and
areas of involvement may be patchy and affect multiple,
discontinuous areas. The majority of patients with CD have
some small bowel involvement, usually in the distal ileum;
about 66% of patients with CD exhibit colonic disease.
Crohn¡¯s disease of the colon sometimes spares the rectum,
unlike UC which usually involves the rectum. Fewer
patients have disease involvement in other areas of the
gastrointestinal tract, such as the mouth, esophagus,
stomach, and duodenum. Sometimes interchangeable
terminology is used to describe CD in a specific location,
such as Crohn¡¯s colitis or Crohn¡¯s ileitis. Patients who have
involvement of both the ileum and colon are said to have
ileocolitis.
Remission for IBD defined as the absence of symptoms
of disease without the continued use of significant drugs,
such as corticosteroids. Maintenance therapy is
pharmacological intervention used to maintain remission
and reduce the incidence of disease exacerbation or
recurrence.
Environment Influences
It has been suggested that environmental triggers play a
role in the pathogenesis of IBD. Cigarette smoking, the use
of oral contraceptives, nutritional deficiencies, and the
presence of infectious agents have been suggested as
environmental factors that possibly contribute to disease
progression in susceptible patients. Although several studies
have shown a negative correlation between smoking and
UC, a positive correlation between smoking and CD
recurrence has been demonstrated. A clear association
between oral contraceptive use and IBD incidence has not
been established. No specific causative factor has been
identified in the diets of patients with IBD. In the setting of
an underlying genetic or immune defect, pathogenic
bacteria may play a role in the pathogenesis of IBD.
Although some evidence has linked Mycobacterium species
with CD, no single pathogen has been identified to have a
consistent association with IBD. Microorganisms suggested
as potential IBD pathogens include viruses, mycoplasmata,
Chlamydia, and other bacteria. Limited evidence suggests
that stress can worsen the symptoms of IBD, but the
mechanism underlying this observation is unclear.
Epidemiology
In North America, the incidence for UC ranges from
2.2/100,000 to 14.3/100,000 person-years, and prevalence
ranges from 37/100,000 to 246/100,000 people. The
incidence for CD in North America ranges from
3.1/100,000 to 14.6/100,000 person-years, and prevalence
ranges from 26/100,000 to 199/100,000 people. A higher
incidence of IBD is observed in Jewish and Caucasian
populations, and lower rates are seen in African-American,
Hispanic-American, and Asian-American populations;
however, studies suggest that the incidence of IBD in
African Americans is approaching that of white Americans.
The incidence of IBD is higher in urban areas. Although
IBD can present at any age, peak incidence is observed in
late adolescence and early adulthood; in addition, a second
peak occurs between 50 and 80 years of age. A slight
Inflammatory Bowel Disease
Immunologic Influences
In addition to genetic and environmental factors, altered
immune response has been implicated in the pathogenesis
of both UC and CD. Investigation has revealed two major
areas of immune system involvement: an abnormal
immune system against dietary or microbial antigens and
possible alterations in mucosal barrier function.
70
Pharmacotherapy Self-Assessment Program, 5th Edition
Abbreviations
antibodies are directly involved in the development of IBD,
and titers of pANCA are not indicative of disease activity.
An effective mucosal barrier function requires an intact
intestinal epithelium, surface mucus, normal peristalsis, and
the secretion of numerous protective factors. Epithelial cells
provide the first barrier against pathogens crossing the
gastrointestinal tract. Alterations in epithelial cells or in
intestinal mucus, high concentrations of bacteria within
mucus, and increased intestinal permeability may play
contributing roles in the pathogenesis of IBD. Intestinal
growth factors regulate the growth and differentiation of
intestinal epithelial cells and may be involved in IBD
pathogenesis. Excess arachidonic acid and its by-products,
reactive oxygen and nitrogen products, have been
implicated in IBD pathogenesis because of their potential
effects on the mucosal barrier.
Clearly, researchers will continue to investigate the
pathogenesis of IBD; however, the mechanisms of disease
likely involve a matrix of interactions among these genetic,
environmental, and immunologic influences.
Table 1-1. Distinguishing Characteristics of Crohn¡¯s
Disease Versus Ulcerative Colitis
Characteristics
Crohn¡¯s Disease
Ulcerative
Colitis
Pattern
of inflammation
and ulceration
Patchy, ¡°cobblestone¡± Continuous and
appearance
superficial
Histology
Transmural lesions
and granulomas
Nontransmural and
crypt abscesses
Location within
Any location
the gastrointestinal from mouth to anus
tract
Limited to colon
and/or rectum
Presenting
symptoms
Fatigue, diarrhea,
abdominal pain,
and fever
Rectal bleeding
and bloody or
watery diarrhea
Potential
complications
Perineal disease,
abscesses, and
fistula development
Toxic megacolon
Response
to surgery
Variable, not curative
Curative
Clinical Characteristics and Complications
Ulcerative Colitis
Clinical Manifestations of UC
The severity of symptoms associated with UC usually
correlates with the extent of colonic involvement. Initial
presentation often includes an insidious onset of symptoms,
often preceded by a history of self-limited, intermittent
rectal bleeding. Other physical findings include abdominal
tenderness, fever, weight loss, and pallor. In general,
patients can be classified as having mild, moderate, or
severe disease based on their symptoms and diagnostic
studies.
About 33% of patients with UC experience mild disease,
limited to the rectum and sigmoid colon, known as proctitis
or distal colitis. Presentation of mild disease usually
includes intermittent rectal bleeding, passage of mucus, and
development of about four episodes of mild diarrhea daily.
Tenesmus, or difficulty defecating despite urgency, mild
abdominal pain, and periods of constipation are also
common for patients with mild disease.
Patients with moderate UC usually have disease
extending beyond the distal colon. These patients
experience frequent loose bloody stools, mild anemia,
moderate abdominal pain, and low-grade fever.
Patients with severe disease demonstrate extensive
colonic involvement, often pancolitis. In general, these
patients have frequent loose stools (as many as 10 stools/day
or more) with severe abdominal cramping, fever, and
significant bleeding. They also may experience rapid weight
loss and malnutrition. Toxic megacolon is a condition that
may occur in severely ill patients when colonic motility is
impaired, the colon is dilated, and the patient¡¯s bowel
movements decrease or cease. Serious consequences may
result, including colonic perforation, peritonitis, and even
death.
During normal absorptive processes, the intestine has an
effective barrier that uses both innate and acquired immune
systems to discriminate harmless food antigens from
infectious or toxic agents.
The innate immune system provides the initial response
to a foreign antigen exposure and is composed of
phagocytes and natural killer cells. The acquired immune
system involves both humoral and cell-mediated
mechanisms and includes B and T lymphocytes which
provide specific immunity. Humoral immunity is mediated
within the gastrointestinal tract by antibody-secreting B
cells, primarily of the immunoglobulin A class. Cellular
immunity is mediated by T lymphocytes, which include
both CD4+ helper T cells and CD8+ suppressor T cells.
CD4+ helper T cells include both type 1 (Th1) and type 2
(Th2) helper T cells. Inducers of cell-mediated immunity
such as interferon-gamma, tumor necrosis factor-alpha
(TNF-¦Á), interleukin-2, and interleukin-12 are secreted by
Th1 cells. B cell differentiation is regulated by Th2 cells by
secreting interleukin-4, interleukin-5, interleukin-6, and
interleukin-10. Animal studies suggest additional CD4+
subsets, which produce ¡°down-regulatory¡± cytokines.
Studies show abnormally secreted immunoregulatory
and inflammatory cytokines correlate with active IBD.
Secretion of interferon-gamma and TNF-¦Á by Th1 cells has
a significant proinflammatory effect, whereas the secretion
of interleukin-10 by Th2 cells suppresses the Th1-mediated
responses. CD4+ T lymphocytes isolated from patients with
CD secrete large amounts of interferon-gamma and TNF-¦Á,
implicating Th1 cells in the pathogenesis of IBD.
Abnormal B cell regulation may be a factor in IBD
development. An increase in circulating B cells, perinuclear
antineutrophilic cytoplasmic antibodies (pANCAs), and
other autoantibodies have been observed in patients with
IBD. Studies have not shown that production of these
Pharmacotherapy Self-Assessment Program, 5th Edition
Complications of UC
Ulcerative colitis can include both local and
extraintestinal complications. Local complications of UC
include massive hemorrhage, fulminant colitis, toxic
71
Inflammatory Bowel Disease
Abbreviations
Crohn¡¯s Disease
Clinical Manifestations of CD
In contrast to the common features found in patients with
UC, the clinical manifestations of CD may vary greatly
based on the extent of disease. Hallmark characteristics of
CD include fatigue, prolonged diarrhea with abdominal
pain, weight loss, and fever. Bleeding may or may not be
present. Some patients may develop a fistula or abdominal
abscesses.
Diarrhea may result from excessive fluid secretion and
impaired fluid absorption, from bacterial overgrowth, or
from bile salt malabsorption. Abdominal pain often is due to
fibrotic strictures, which may lead to bowel obstruction.
Bleeding may be present in Crohn¡¯s colitis, but typically
is observed less frequently than in UC. Diarrhea without
bleeding, but with other features of IBD such as skin, eye,
or joint problems, or a family history of IBD may aid in
diagnosing CD.
Patients with CD are predisposed to sinus tract formation
with potential bowel wall perforation resulting in acute
peritonitis characterized by fever, abdominal pain and
tenderness, and often a palpable mass. Fistula tracts can
develop at various anatomical locations adjacent to the
diseased bowel, and symptoms may vary accordingly.
Patients with an enterocutaneous fistula have bowel
contents draining to the skin surface. Enteroenteric fistulae
may be asymptomatic or present as a palpable mass on
physical examination. Enterovesical fistulae (bowel to
bladder) lead to recurrent urinary tract infections often
caused by multiple organisms and a complaint of
pneumaturia, or the passage of air in urine. Passage of gas or
feces through the vagina indicates presence of an
enterovaginal fistula.
About 33% of patients with CD develop perianal disease.
Signs and symptoms include perianal pain and drainage
from large skin tags, anal fissures, perirectal abscesses, and
anorectal fistulae.
Systemic symptoms in CD include fatigue, weight loss
and fever. Weight loss often is related to decreased food
intake because patients¡¯ symptoms are lessened when they
do not eat. Weight loss also may result from malabsorption.
Fever may be due to the inflammatory process or due to
bowel infection.
Patients with mild to moderate CD are ambulatory and
able to tolerate an oral diet without dehydration, toxicity,
abdominal tenderness, mass, or obstruction. Patients with
moderate to severe CD exhibit mild to moderate disease or
present with prominent symptoms such as fever, weight
loss, abdominal pain and tenderness, intermittent nausea or
vomiting, or anemia. Patients with severe fulminant disease
have persisting symptoms despite treatment with
corticosteroids or exhibit high fever, persistent vomiting,
intestinal obstruction, rebound tenderness, cachexia, or an
abscess. Patients in remission become asymptomatic either
spontaneously or after medical or surgical intervention.
Patients requiring corticosteroids to remain asymptomatic
are not considered to be in remission.
Table 1-2. Extraintestinal Complications of
Inflammatory Bowel Disease
Eye involvement
Uveitis
Episcleritis
Skin disorders
Erythema nodosum
Pyoderma gangrenosum
Joint disease
Peripheral arthritis (usually involves large joints with no
synovial destruction)
Ankylosing spondylitis (may be the presenting manifestation
of ulcerative colitis)
Sclerosing cholangitis (presents with an elevation in serum
alkaline phosphatase and gamma glutamyltranspeptidase)
Venous and arterial thromboembolism
megacolon, intestinal perforation or stricture, and the
development of colon cancer. Extraintestinal manifestations
of UC can include eye involvement, skin disorders, joint
disease, primary sclerosing cholangitis, and venous and
arterial thromboembolism as described in Table 1-2.
Potential development of colon cancer is a major concern
for patients diagnosed with UC. The risk of colon cancer is
related both to the extent and duration of the disease.
Patients with UC who have proximal disease involvement or
who have a family history of colon cancer are at increased
risk of developing colon cancer. In addition, patients with
UC and primary sclerosing cholangitis may be at increased
risk for colorectal cancer compared to those without primary
sclerosing cholangitis. Compared to an age-matched
population, the risk of colorectal cancer begins to increase
8¨C10 years after the onset of symptoms. The incidence of
colorectal cancer is about 5¨C10% after 20 years and 12¨C20%
after 30 years of disease.
Patients with UC should undergo surveillance
colonoscopy, although the timing and the optimal number
and location of biopsies that should be obtained are
uncertain. Although specific recommendations regarding
screening differ from various professional organizations, all
agree that screening for cancer should occur in patients with
UC who have not had a total colectomy. The timing of these
screenings should be a collaborative decision between the
patient and physician. The American Gastroenterological
Association recommends that surveillance colonoscopy
should begin 8 years after initial diagnosis of pancolitis, and
15 years after initial diagnosis of colitis involving the left
colon. Colonoscopy should then be repeated every
1¨C2 years. The American College of Gastroenterology
recommends annual surveillance colonoscopy beginning
after 8¨C10 years of disease in patients who have not
undergone colectomy. The American Society for
Gastrointestinal Endoscopy recommends that patients with
UC who have pancolitis begin surveillance colonoscopy
after 8 years of disease. Four biopsies should be obtained
every 10 cm from the cecum to the rectum. Suspicious
lesions or masses should be biopsied. Colonoscopy should
be repeated every 1¨C3 years. Colectomy is indicated if
carcinoma, high-grade dysplasia, or dysplasia with lesions
or a mass is found on surveillance.
Inflammatory Bowel Disease
Complications of CD
Crohn¡¯s disease is associated with both local,
extraintestinal, and malabsorption complications. Local
72
Pharmacotherapy Self-Assessment Program, 5th Edition
Abbreviations
increased relative risk of colon cancer in CD, the absolute
number of patients at risk is relatively small because many
patients with extensive colitis undergo colectomy early in
the course of disease. Surveillance guidelines are similar for
CD and UC. The American Gastroenterological Association
concluded that the risk of colorectal cancer associated with
UC and Crohn¡¯s colitis is similar for comparable extent,
duration, and age of onset of inflammatory disease. As a
result, the surveillance strategy previously discussed for UC
also applies for Crohn¡¯s colitis. The American College of
Gastroenterology recognizes the evidence of the
carcinogenic potential of long-standing CD but does not
provide specific guidelines for surveillance. The American
Society for Gastrointestinal Endoscopy also recognizes that
the risk of colorectal cancer is increased in Crohn¡¯s colitis.
Surveillance colonoscopy and biopsy for dysplasia should
be offered to patients with longstanding Crohn¡¯s colitis.
complications include intestinal obstruction, severe
hemorrhage, acute perforation, the development of fistulae
and abscesses and toxic megacolon. Patients with CD may
exhibit extraintestinal manifestations related to
inflammatory bowel disease activity as described in
Table 1-2.
Malabsorption due to CD can have serious consequences,
including weight loss, steatorrhea, calcium oxalate and uric
acid stone formation, and vitamin B12 deficiency. Bile acid
malabsorption can occur in patients with distal ileal CD or
who have had surgical resection of the distal ileum. Milder
degrees of bile acid malabsorption may result in watery
diarrhea, but more profound degrees of bile acid
malabsorption impair micelle formation for fat absorption
and can lead to development of steatorrhea. In addition, bile
acid malabsorption often results in formation of gallstones
because of build up of biliary sludge.
Steatorrhea can lead to severe malnutrition, clotting
abnormalities,
osteomalacia,
osteoporosis,
and
hypocalcemia. Diarrhea and fat malabsorption due to
steatorrhea may ultimately lead to weight loss and a
decrease in absorption of key nutrients, such as fat-soluble
vitamins. Calcium abnormalities lead to clotting disorders,
osteomalacia, and osteoporosis. Primary bone density loss is
related to corticosteroid use; however, alterations in calcium
absorption also can occur in the setting of steatorrhea.
Steatorrhea increases oxalate absorption and results in
hyperoxaluria and can lead to calcium oxalate and uric acid
kidney stone formation. Free calcium binds to fatty acids in
the intestinal lumen, allowing free oxalate to be absorbed.
Exposure to unabsorbed bile salts increases colonic
permeability to small molecules such as oxalate. Volume
depletion and metabolic acidosis can lead to a reduction in
the urinary excretion of citrate, a process that normally
inhibits oxalate stone formation. Dehydration and acidosis
also increases uric acid kidney stone formation because
acidic urine decreases uric acid solubility.
Vitamin B12 is absorbed in the distal ileum; consequently,
severe ileal disease or ileal resections can lead to vitamin
B12 malabsorption and deficiency, which may lead to
pernicious anemia. Serum vitamin B12 concentrations
should be monitored in patients with ileal CD or in patients
with a history of ileal resection.
Other nutrients commonly malabsorbed in patients with
CD are folate, zinc, and iron. Folate deficiency may occur
because of a decreased intake or because of treatment with
sulfasalazine, which interferes with folate absorption. In
general, other water-soluble vitamins are rarely deficient in
CD. Zinc deficiency usually is caused by excessive wasting
in diarrhea or by enteric fistulae. Iron deficiency frequently
can be caused by a decreased intake, by rectal bleeding, and
by decreased absorption in the gastrointestinal tract.
Patients with a long history of CD are at increased risk of
colon cancer, and to a lesser extent small bowel cancer. In a
population-based study from Sweden, the relative risk of
colon cancer was 2.5 overall in patients with CD and 5.6 in
those with only colonic disease. The relative risk was even
greater in patients who were younger than 30 years of age at
the time of diagnosis. Similar to UC, risk is related to the
extent and duration of disease. Colorectal cancer in CD is
observed in a similar time frame as that in UC. Despite the
Pharmacotherapy Self-Assessment Program, 5th Edition
Diagnostic Approach and Tools
The clinical presentations of UC and CD are similar to
many other diseases or conditions as listed in Table 1-3.
Infection or adverse drug reactions must be ruled out both at
diagnosis and during symptomatic periods. About 5¨C15% of
patients are initially diagnosed with ¡°indeterminate¡± colitis,
because neither UC nor CD can be definitively diagnosed.
The diagnosis of IBD involves both subjective and
objective parameters. Clinical history, family history, and
patient physical examination often are as important as
radiographic and endoscopic evaluations. A family history
of IBD is associated with an earlier age of diagnosis in
affected patients. Because of differences in treatment
options, UC must be distinguished from Crohn¡¯s colitis.
Ulcerative colitis usually is diagnosed by characteristic
clinical history, endoscopic mucosal findings, and histology
from colonic biopsy. Presence of family history may aid in
Table 1-3. Differential Diagnosis for Ulcerative Colitis
and Crohn¡¯s Disease
Mild disease
Lactose intolerance
Irritable bowel disease
Colonic disease
Radiation colitis
Ischemic colitis
Diverticular colitis
Infectious disease
Salmonella
Shigella
Campylobacter
Aeromonas
Escherichia coli
Clostridium difficile colitis
Cytomegalovirus
Tuberculosis
Amebiasis
Adverse drug reactions
Antibiotic drugs
Nonsteroidal anti-inflammatory drugs
Retinoic acid
Oral contraceptives
Penicillin-induced segmental hemorrhagic colitis
73
Inflammatory Bowel Disease
................
................
In order to avoid copyright disputes, this page is only a partial summary.
To fulfill the demand for quickly locating and searching documents.
It is intelligent file search solution for home and business.
Related download
- inflammatory bowel disease part i pathophysiology and conventional and
- inflammatory bowel disease incidence and treatment
- inflammatory bowel disease
- vedolizumab for the treatment of inflammatory bowel diseases
- for inflammatory bowel disease msgh
- study points to potential new treatment for inflammatory bowel diseases
- new study identifies potential treatment for inflammatory bowel disease
- inflammatory bowel disease treatment university of cape town
- treatment of inflammatory bowel disease ibd
- nutrition in inflammatory bowel disease queensland health
Related searches
- inflammatory muscle disease symptoms
- inflammatory muscle disease mayo clinic
- inflammatory airway disease icd 10
- ischemic bowel disease icd 10
- icd 10 inflammatory bowel disease
- types of inflammatory bowel disease include
- irritable bowel disease icd 10
- inflammatory bowel disease icd 10 code
- medication for inflammatory bowel disease
- inflammatory bowel disease icd 10
- icd 10 for inflammatory bowel disease
- inflammatory brain disease symptoms