Transcript presentation ( format)

Crohn’s and the College Student
Evelyn Wiener, MD
Student Health Service
University of Pennsylvania
Disclosures
• I have NO actual or potential conflict of
interest in relation to this presentation.
• Some medications are used off-label in
treatment of Crohn’s disease
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Objectives
• Explain etiology & mechanism of Crohn’s disease
• Discuss diagnosis of Crohn’s disease
• Describe management of Crohn’s disease
• Identify resources to support social, emotional and
academic needs of students with Crohn’s disease
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Overview
• Chronic inflammatory bowel disease
• Marked by diarrhea and abdominal pain
• Similar to ulcerative colitis but can affect entire GI
tract
• Patients are at risk for obstruction, fistula
formation, nutritional deficits
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Let’s do the numbers
US: 500,000 to 700,000
Peak age of onset 15 to 30 years
10% occur in individuals < 18 years
Familial disease in 5 – 10 %
50% of patients with Crohn’s are sick at any one time
Up to 70% patients require surgery at some point
30% recur within 3 years, 60% recur within 10 years
Total direct cost in US in 1998: $1.7 billion
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Figure 1 Interaction of various factors contributing to chronic intestinal inflammation in
a genetically susceptible host
Sartor RB (2006) Mechanisms of Disease: pathogenesis of Crohn's disease and ulcerative colitis
Nat Clin Pract Gastroenterol Hepatol 3: 390–407 doi:10.1038/ncpgasthep0528
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Genetic susceptibility
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Xavier r, Nature 474, 2011
Intestinal microbiome
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Intestinal microbiome
Intestinal
microbiome
Walker et al, Pharmacological Res 2012
DIET
Genetics
Environment
Gut
microbiota
Antibiotics
Inflammation
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Environmental triggers
Known
Probable
Speculative
Smoking
Antibiotic use
Hygiene
NSAIDS
Vitamin D
Exercise
Appendectomy
Childhood infections
Stress
Breastfeeding
Furry pets
Diet (?)
Oral contraceptives
Periodontitis
Air pollution
Eczema
Immune response
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Immune response
Table 2 Cytokines associated with inflammatory bowel diseases
Sartor RB (2006) Mechanisms of Disease: pathogenesis of Crohn's disease and ulcerative colitis
Nat Clin Pract Gastroenterol Hepatol 3: 390–407 doi:10.1038/ncpgasthep0528
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Pathogenesis of Inflammatory Bowel Disease.
Podolsky DK. N Engl J Med 2002;347:417-429.
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Newman
Julia
Marda
20 yo male undergrad
24 yo female grad student
19 yo female undergrad
Progressively severe RLQ pain
over course of day
Two episodes severe
abdominal pain, diarrhea and
emesis over past week
Recurrent vomiting and
abdominal pain x 7 years,
admitted for recurrent pain
PMH unremarkable
PMH unremarkable
Capsule endoscopy in past
suggestive of Crohn’s
Symptomatic improvement on
pentasa and prednisone
CTAP:
CTAP:
• No evidence of appendicitis • 2 cm length of thickening
• Thickening and hyperemia
and inflammation of
of terminal ileum
terminal ileum with partial
• Partial small bowel
SBO, unable to exclude
obstruction
enteroenteric fistulization
CTAP:
• Circumferential thickening
of terminal ileum
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Diagnosis
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Clinical presentation
Laboratory tests
Radiology
Endoscopy
Pathology
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Barium studies
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CTAP
Radiology Tutorials. 20
com
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Newman
Julia
Marda
20 yo male undergrad
24 yo female grad student
19 yo female undergrad
CTAP:
CTAP:
• No evidence of appendicitis • 2 cm length of thickening
• Thickening and hyperemia
and inflammation of
of terminal ileum
terminal ileum with partial
• Partial small bowel
SBO, unable to exclude
obstruction
enteroenteric fistulization
CTAP:
• Circumferential thickening
of terminal ileum
Colonoscopy:
• Significant inflammation
and ulceration terminal
ileum
Colonoscopy:
• Cobblestoning of distal
ileum
Colonoscopy:
• Colon and terminal ileum
normal in appearancE
Biopsy:
• Inflammation and
ulceration of terminal
ileum consistent with
Crohns
Biopsy:
• Hypertrophic Peyer’s
patches, likely reactive
Biopsies negative
SBFT:
• Terminal ileum
UGI/SBFT
• Normal UGI tract and small
bowel; no radiographic
evidence of Crohn’s 24
Nora
Joe
Damien
27 yo female graduate
student
19 yo male sophomore
19 yo male freshman
Diagnosed with Crohn’s
disease at age 15
Presents to SHS c/o cramping
pain in calves x two months,
treated with ibuprofen, then
onset of “digestive issues”
Describes “significant GI
history for years”, diagnosed
with Crohn’s summer before
starting college
Now receiving Remicade
infusions every two month
Diagnosed with Crohn’s
disease, started on pentasa
with clinical response
Started on budesonide and
pentasa with benefit, changed
to prednisone and 6MP
Continue symptoms, switched
to Humira
Presents to SHS for ….
Presents to SHS for ….
Presents to SHS for ….
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Management
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Disease severity
Induction
Maintenance
Management of flares
Management of complications
Prevention of recurrence
Quality of life
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Crohn’s Disease Activity Index
Variable
Weighting factor
Number of liquid or soft stools each day for 7 days
X2
Abdominal pain (graded 0-3) each day for 7 days
X5
General well being each day for 7 days
from 0 (well) to 4 (terrible)
X7
Total score
Presence of complications (one point for each)
Joint pain or frank arthritis
E. nodosum, pyoderma gangrenosum, apthous ulcers
Anal fissues, fistule or abscesses
Other fistulae
Fever during previous week
X20
Taking Lomotil or opiates for diarrhea
X30
Presence of abdominal mass
(0 as none, 2 as questionable, 5 as definite)
X10
Hematocrit <47 in men, <42 in women
X6
Percentage deviation from standard weight
X1
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Pharmacologic management
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Antibiotics
5-ASA
Steroids
Immune modulators
Biologics, aka anti-TNF inhibitors
Anti-alpha 4
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Antibiotics in Crohn’s
• Proposed mechanisms of action
– Alteration of gut flora
– Treatment of bacterial overgrowth
– Treatment of unrecognized infection, microperforation or abscess
– Decrease tissue invasion
• Use in Crohn’s disease
– Adjunctive treatment
– Prevention of post-op recurrences
– Treatment of perianal disease
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5-aminosalicylates
what-when-how
In Depth Tutorials and Information
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Steroids
• Mainstay of treatment
– Especially useful for acute flares, severe disease or
mild-moderate disease that does not respond to
treatment
• Prednisone versus budesonide
• Dosing of prednisone
– 40 to 60 mg daily for two to three weeks
– Then taper by 5 mg daily each week to 20 mg daily,
then by 2.5 mg daily each week or every other week
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Side effects of steroids
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Immune suppression
Adrenal suppression
Hyperglycemia
Osteoporosis
Osteonecrosis
Acne
Abdominal striae
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Immune modulators
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Azathioprine (AZA)
6-mercaptopurine (6-MP)
Methotrexate (MTX)
Cyclosporine
Tacrolimus?
Sirolimus ?
Everolimus?
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TNF inhibitors
• Infliximab (Remicade®
• Adalimubab (Humira®)
• Certolizumab (Cimzia®)
• Etanercept enbrel®)
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Side effects of TNF inhibitors
• Infections, including serious and opportunistic
infections
• Drug-induced lupus
• Injection site reactions
• Demyelination
• Non-Hodgkin’s lymphoma
• Long-term safety concerns
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Immunologic sequelae of TNF inhibitors
• Development of neutralizing antibodies
– Potential for allergic reactions
– Potential loss or lack of efficacy
• Development of autoantibodies
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Anti-alpha 4 inhibitor
• Natalizumab (Tysabri®)
– Humanized monoclonal antibody
• Mechanism of action
• Indicated for moderate to severe Crohn’s
disease that has failed alternative therapies
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Management of Recent-Onset CD:
A controlled, randomized trial comparing
step up and top down therapy
Newly diagnosed*
Crohn’s disease (n=130)
+ IFX
+ AZA
MTX
Steroids
Steroids
Top down (n=65)
IFX (0/2/6) + AZA
IFX + AZA
+ (episodic)
IFX
Steroids
Step up (n=65)
Steroids
*within 4 years
D’Haens G et al Lancet 2008;371:660-667
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Non-pharmacologic management
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Diet
Probiotics
Exercise
Stress reduction
Tobacco
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Life style/behaviors
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Nora
Joe
Damien
Remicade every two months
Starts pentasa with response
On Humira, 6MP, pentasa, etc
Presents for referral to GI
Two months later:
• Develops myocarditis
• Followed by massive left
hemispheric CVA
• Takes one year leave
Seen by GI at hospital
Referral provided, told to return
to primary care as needed
Sees gastroenterologist once,
does not care for him
Continues Remicade for next 18
months but no follow up visits to
GI or to SHS primary care (does
see women’s health regularly)
Admitted to hospital for flare one
week after graduating
Returns to school for summer
session, has flare
• Takes leave x one semester
• Initially responds to Remicade
• Switched to Humira for
worsening symptoms
Returns to school
• Hospitalized two weeks later
for flare
• Discharged on Humira, MTX
and prednisone
• Followed closely at SHS & GI
• Stable until end of semester
• Develops fever, chills,
orthostasis
Comes to SHS to establish care
Referred to nutritionist and
advised to return to primary care
as needed
Continues to see GI
Sees UPHS internist to establish
care, assess ongoing fatigue
Sees Counseling Service for
depression, started on citalopram
(Celexa)
Has seizure, seen in ED/neurology
Depression worsens, admitted to
in-patient psychiatry
Takes leave of absence
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Strategies to support students
• Clinical care
– Primary care
– Coordinating GI, other
• Coordinating support/school resources
– Housing
– Academics
– Financial
– Counseling/emotional
– Relationships
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