1 Inflammatory Bowel Disease in the Primary Care Setting Lisbeth Selby, MD Assistant professor Ui it fK t k University of Kentucky Department of Internal Medicine Division of Digestive Diseases and Nutrition Outline • Define IBD D ib 2 i • Treatment issues i • Describe 2 main types – clinical features, course • Issues common to both • prognosis • Diagnostic issues • Supplementary material – genetics – reproductive issues
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Inflammatory Bowel Disease in the Primary Care Setting
Lisbeth Selby, MDAssistant professorU i it f K t kUniversity of KentuckyDepartment of Internal MedicineDivision of Digestive Diseases and Nutrition
Outline
• Define IBD
D ib 2 i
• Treatment issues
i• Describe 2 main types – clinical features, course
• Issues common to both
• prognosis
• Diagnostic issues
• Supplementary material– genetics
– reproductive issues
2
Inflammatory Bowel Diseases (IBDs)
Ulcerative Colitis (UC) Crohn’s Disease (CD)
INFLAMMATORY BOWEL DISEASE
Transmural Inflammation
UpperGastrointestinal
ColonicSmall Bowel
Mucosal Ulceration in Colon
Proctitis Left-sided Colitis
Extensive Colitis
Anorectal
Stenson WF, et al. Inflammatory bowel disease. In: Yamada T et al., eds. Textbook of GastroenterologyPhiladelphia, PA: Lippincott Williams & Wilkins;4th Ed. 2003:1699.
Features Supportive of CD vs. UC
• involvement of the small bowel
• sparing of the rectum
• absence of gross bleeding
• presence of bothersome perianal disease
• focality of gross and microscopic lesions
• presence of granulomas
• occurrence of fistulae
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• Diarrhea, typically bloody and with mucus
Abd i l i d t d
Clinical Presentation of Ulcerative Colitis
• Abdominal pain and tenderness
• Loss of appetite and weight
• Fever
• Fatigue
• Urgency for bowel movement• Urgency for bowel movement
• Colon or rectal cancer• Malnutrition• Colon or rectal cancer• Growth failure in children
Stenson WF, et al. Inflammatory bowel disease. In: Yamada T et al., eds. Textbook of Gastroenterology Philadelphia, PA: Lippincott Williams & Wilkins;4th Ed. 2003:1699.
Extraintestinal Manifestations of IBD
• Peripheral arthritis
– Arthralgia more prevalent in subjects with CD g p j
• Axial arthritis
– Ankylosing spondylitis more prevalent in subjects with UC
• Osteoporosis
– Risk is greater in subjects with CD
• Renal
• Dermatological
Miller MM. Prim Care. 1984;11:271.Stenson WF, et al. Inflammatory bowel disease. In: Yamada T et al., eds.
Textbook of Gastroenterology Philadelphia, PA: Lippincott Williams & Wilkins;4th Ed. 2003:1699.
Dermatological
• Eye
• Thromboembolic
• Hepatic complications
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Ulcerative Colitis and Increased Risk of Colorectal Cancer
%) 2525
mu
lati
ve p
rob
abili
ty (
%
UCUC
2020
1515
1010
55
Eaden JA, et al. Gut. 2001;48:526.
Cu
m
Time from diagnosis (years)
UCUC55
11
00 55 1010 1515 2020 2525 3030
• Overall prevalence of CRC in any UC patient is 3.7%• Pancolitis > more limited forms
B12
• Crohn’s disease patients with ileali l t il l ti iinvolvement or ileal resection require lifelong parenteral B12 (usually monthly)
• Levels not reliable to determine need either early on or during parenteral therapy
• Very small minority of CD pts have had• Very small minority of CD pts have had gastric resections– They also require B12
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Folic Acid(Also Called Folate)• Anemia can develop with low body amounts
• All women who could possibly get pregnantAll women who could possibly get pregnant should take 400 micrograms of folic acid every day in a vitamin or in foods that have been enriched with it
C bi ti d t l iCombination dermatologicand cardiopulmonary reactions 0.1%
Serious reactions 0.5%
Schaib le T. Can J Gastroenterol. 2000;14:29C.
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Infections with Anti-TNF Agents
• Opportunistic
• TB– Often disseminated or extra-pulmonary
• Pneumonia, histoplasmosis, coccidioidomycosis, listeriosis and pneumocystosispneumocystosis
• Bacterial infections including sepsis
• Should not be given to patients with a clinically important, active infection
Other Issues with TNF Inhibition
• HBV reactivation
• Contraindication in class III/IV CHF• Contraindication in class III/IV CHF
• Caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD)
• Demyelinating disorders
• Consider discontinuation for significant CNS adverse reactions
• Hepatic reactions
• Lupus-like syndrome
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UC Treatments
Therapeutic Pyramid for Active UC
SevereSevereSurgerySurgery
ModerateModerate
Systemic CorticosteroidsSystemic Corticosteroids
SurgerySurgery
AZA/6AZA/6--MPMP
CyclosporineCyclosporine
Infliximab Infliximab
MildMild
AminosalicylatesAminosalicylates
Oral SteroidsOral Steroids
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Smoking and Ulcerative Colitis
• Cigarette smokingH t ti ff t d l t d f– Has protective effect on development and course of UC including extraintestinal and postsurgical events
– Nicotine therapy (gum, patch, enema) has mixed results
– Restart smoking in severe or refractory colitis?
E k lik l t d l t i UC
Hanauer SB. Nat Clin Pract Gastroenterol Hepatol. 2004;1:26.Ingram JR, et al. Aliment Pharmacol Ther 2004;20:859.
• Ex-smokers more likely to develop extensive UC (second age peak > 40 years)
Majority of patients had UC; other diseases included Crohn’s disease, indeterminate colitis, familial polyposis, and cancer
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Ileal Pouch:Cumulative Incidences Pregnancy
M thControls
Before C l t
After IPAAMonths
Controls (n=914)
Colectomy (n=84)
IPAA (n=149)
12 75% 78% 18%*
24 82% 85% 27%*
60 88% 90% 36%*
*P<0.001 vs. Controls
Olsen KO, et al. Gastroenterology. 2002;122:15-19.
Crohn’s disease treatment
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Maintenance Therapies for Ulcerative Colitis
A i li l• Aminosalicylates
• Azathioprine/6-MP
• Infliximab (Remicade®)
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Mortality and IBD
• IBD patients have an elevated mortality rate of 0.5% per year
• Extensive colitis and higher age (> 50 years) at diagnosis increase• Extensive colitis and higher age (> 50 years) at diagnosis increase the risk for a fatal outcome in UC
• Greatest hazard ratio (HR)
– UC – age group 40 to 59 years (HR 1.79)
– CD – age group 20 to 39 years (HR 3.82)
• IBD is associated with an overall small increase in mortality rate greatest in relative terms in younger subjects but in absolute terms in the elderly
Card T, et al. Gastroenterology. 2003;125:1583.Winther KV, et al. Gastroenterology. 2003;125:1576.
Final Points• There is no “one size fits all” to IBD therapy
– Therapy and decision making are tailored to the individual
• Algorithms are based upon available evidenceAlgorithms are based upon available evidence
– Evidence is in constant flux
• Success of algorithms depends upon optimization of each step of therapy and considerable judgment about each outcome
– Skillful application of medical therapy makes all the diff i tdifference in outcomes
• Need for better treatments since many only work about 50% of the time
• Success of newer medications have opened new doors for investigation
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When to Suspect IBDInstead of IBS
• Red flags
If d fl IBD lik l• If no red flags, IBD unlikely
• Even if IBD present in some sort of subclinical state such that “red flags” are negative, hard to justify more than symptomatic rx
• … and that means GI specific care not needed itheither
• Kids are slightly different and need close attention and f/u to growth
*
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Do Not Use the Panelsthat are Marketed
to Distinguish IBS from IBD (Prometheus)
• Useless in this setting
• Main utility is persons with indeterminate colitis who require surgery and may need a permanent ileostomy if disease is more C h ’ likCrohn’s-like
• I have not ordered one in years
Supplementary Materials
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Genetics Issues
Familial Patterns of Inheritance in IBD
• Relative risk 14-15 times higher among first-degree relatives than the general population
– Prevalence in family members
• 4.6% parents
• 2.6% siblings
• 1.9% children
• Concordance in affected parent-child pairs
– 75% disease type
Sands BE. Crohn’s Disease. In: Feldman M, Friedman LS, Sleisenger MH, eds. Sleisenger & Fordtran’s Gastrointestinal and Liver Disease. Philadelphia, PA: Saunders; 7th ed. 2002:2009.
Satsangi J, et al. Gut. 1996;38:738. Lashner BA, et al. Gastroenterology. 1986:91:1396.
– 63% extent
– 70% extraintestinal manifestations
– 85% smoking history
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Genetics and IBD
• Greater concordance for CD than for UC
Twin Studies Concordance
Identical Fraternal
CD 58% 0%
UC 18% 4%
Stenson WF, et al. Inflammatory bowel disease. In: Yamada T et al., eds. Textbook of Gastroenterology. Philadelphia, PA: Lippincott Williams & Wilkins; 4th Ed. 2003:1699.
Orholm M, et al. Scand J Gastroenterol. 2000;35:1075.
Miscellaneous Reproductive and Sexual Health Issues
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Gender-Related Considerations in IBD
Slide courtesy of Dr. Sunanda Kane, Mayo Clinic
Women Men
Reproductive issues
fertility after IPAA or proctocolectomy
risk of relapse if disease active at
time of conception
fertility with sulfasalazine
Disease-related concerns
concern re: body stigma,
loss of bowel control
—
Sexuality sexual activity because of dyspareunia,
abdominal pain, depression, etc
libido and sexual satisfaction after proctocolectomy; depression effects
Women with Restorative Proctocolectomies:
Satisfaction With Sexual Relationships
• 22% improved
• 51% unchanged
• 26% less satisfactory
• Overall 86% moderately to extremely % y ysatisfied
Bambrick M, et al. Bambrick M, et al. Dis Colon Rectum.Dis Colon Rectum. 1996;39:6101996;39:610--614.614.
Slide courtesy of Dr. Sunanda Kane, Mayo Clinic
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Pouch Function and Pregnancy
• Questionnaire study of women with IPAA– 49 deliveries in 29 women (25 vaginal)
– 6 pouch-related complications (2 during pregnancy)
– Increased stool frequency reported during pregnancy
– Delivery method did not influence incontinence, stool frequency
Ravid A. Dis Colon Rectum 2002; 45:1283-88.
Slide courtesy of Dr. Sunanda Kane, Mayo Clinic
Pregnancy on IBD:Does Pregnancy Change Course?
• European cohort followed over 10 years
• 580 pregnancies, 403 prior to, 177 after diagnosis of IBD
• Rate of spontaneous Ab higher after dx
• C section rate higher after IBD dx
• Rate of relapse decreased in years following pregnancy in both UC and CD
Riis L. Am J Gastroenterol 2006; 101:1539-45.
Slide courtesy of Dr. Sunanda Kane, Mayo Clinic
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Summary: Safety of IBD Medications During Pregnancy