Chief Rounds 7/12/10 Inflammatory Bowel Disease Ralph Yachoui MD Thomas Judge MD

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Chief Rounds7/12/10Inflammatory Bowel
DiseaseRalph Yachoui MDThomas Judge MD
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The Case

• HPI 35 y/o F presents with
• . Diarrhea x 4 weeks,
• large volume, bloody, 7-8x/day
• () nocturnal
• . Crampy abdominal pain, relieved
  by BM
• . Weight loss 7 lbs x 1month
• . Peripheral arthralgias

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The case ( continued)

• Recent travel to Mexico
• No recent ABx use
• No family history of IBD
• Former smoker, quit 3 months ago
• No PMH or PSH
• No meds
• Allergies Sulfa

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Physical examination
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Labs

• CBC Hb 10 MCV 102
• LFTs normal
• ESR/ CRP elevated

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1- What is the first test to order ?
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R/O infectious disease

• C diff neg
• OP neg
• Culture neg
• WBC neg
• Hem pos

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• 2- How do we confirm the diagnosis?

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Diagnosis

• "skip lesions". Early changes may be only patchy
  erythema (panel A) or aphthoid ulcers (panel B).
  Linear ulcers (panel C) are seen with more
  advanced disease, culminating in very deep and
  long serpiginous ulcers (panel D)

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(No Transcript)
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Pathology

• Ileum Intestinal mucosa showing marked acute and
  chronic inflammation and evidence of non
  caseating granulomas

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Crohns disease

• Transmural inflammation
• Fibrotic strictures leading to obstruction
• Microperforations and fistulae
• Perianal disease

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Clinical manifestations

• Diarrhea, abdominal pain, weight loss, and fever
• Bleeding (less than UC)
• Perforation and fistulae (33 and 50 percent after
  10 and 20 years )

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Antibody tests

• ASCA / pANCA - gtgtgt Crohns
• ASCA - / pANCA gtgtgt UC
• Anti- OmpC and Anti-Cbir 1 possibly correlates
  with a more aggressive Crohns

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Extraintestinal manifestations

• 1- Related to disease activity
• . Uveitis/ episcleritis
• . Erythema nodosum
• . Peripheral arthritis
• 2- Unrelated to disease activity
• . Sacroiliitis / Ankylosing spondylitis
• . Pyoderma gangrenosum
• . Primary sclerosing cholangitis

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3- What other workup prior to initiating
treatment?
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Prior to treatment

• PPD test
• Hep Bs Ag
• TPMT level
• Dexa scan/ vitamin D
• Iron studies/ Folate/ vitamin B12

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General approach

• As a general rule, start with a less potent
  treatment and progress to a more potent in
  patients with refractory disease
• Top-down approach ?

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First line treatment

• Oral 5-ASA or Sulfasalazine
• . Mild or moderate Crohns colitis
• . ? efficacy in ileitis
• . Use in inducing remission and
  maintaining remission
• . Need 3 to 6 weeks to act

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5-ASA

• Anti-inflammatory and immunosuppressive
  properties
• Sulfasalazine 5-ASA sulfapyridine
• . More toxic than 5-ASA
• . As effective than 5-ASA
• . Better in case of arthropathy
• . Mesalamine (Asacol , Pentasa, Lialda , Apriso)
• Other 5-ASA meds Dipentum, Colazal
• . Dose- response relationship ?

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Antibiotics

• Trial of antibiotics ??
• Patients who do not respond to 5-ASA or
  as alternative 1st line therapy
• Flagyl or ciprofloxacin
• alone or in combination ?

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Second line treatment

• Prednisone
• . In severe crohns or unresponsive to
  5-ASA
• . No role in maintaining remission
• . Initial dose 40-60 mg /d. Taper by
  5mg/week until discontinuation

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Prednisone

• Side effects
• . Osteoporosis
• . Steroid myopathy
• . Avascular necrosis
• . Cataract
• . HTN
• . Hyperglycemia
• . Infections
• . Acute adrenal insufficiency

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Budesonide (Entocort)

• An alternative to prednisone
• . Less steroid toxicity due to a high
  first-pass hepatic metabolism
• . Acts primarily on the T.I. and right colon
• . FDA approved as a maintenance treatment
• ( for up to 3 months)

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Third line treatment

• Steroid-refractory and steroid-dependant
• . Steroid-refractory Lack of response to
  prednisone PO within 30 days or IV prednisone
  within 7-10 days
• . Steroid- dependant Relapse when steroids
  are tapered or stopped

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AZT (Imuran) or 6MP (Purinethol)

• Slow-acting Need 3-6 months to act, during
  which steroids are tapered
• Maintenance treatment only
• S.E. Bone marrow suppression and liver toxicity
• Follow TPMT level ( if low, need to decrease the
  dose )
• MTX Parenteral only as effective as anti-TNF
  therapy

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Cyclosporine or Tacrolimus

• Fast-acting Bridging therapy to AZT/6MP
• IV cyclosporine is used in fulminant colitis
  unresponsive to IV steroids in patients refusing
  colectomy
• Significant side-effects
• ? Long-term effectiveness (many still need
  surgery)

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TNF alpha inhibitors

• Mucosal T cells express TNF alpha
• TNF inh. have a lytic effect on mucosal cells
• 3 differents drugs
• . Infliximab (Remicade)
• . Adalimumab (Humira)
• . Certolizumab (Cimzia)

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Infliximab (Remicade)

• Chimeric antibody to TNF
• IV infusion only
• Chimeric gtgtgt Anti-chimeric antibodies
• The only TNF inh. approved in UC
• Use as inducing maintaining remission
• Approved for fistulizing Crohns

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Subcutaneous TNF inhibitors

• 1- Adalimumab (Humira)
• Humanized anti-TNF ab
• Injection every 2 weeks
• 2- Certolizumab (Cimzia)
• Fab fragment
• Monthly injections (2 x 1mL)

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TNF alpha inhibitors

• Side effects
• . Reactivation of TB
• . Reactivation of Hep B ( NOT hep C)
• . Reactivation of MS
• . Can cause heart failure
• . Malignancy
• . Development of ACL, anti-DNA, ANA and
  acute autoimmune hepatitis

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What is the major risk of combination therapy
(TNF inh. Thiopurine drug)
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Hepatosplenic T-cell lymphoma

• Account for less than 1 of non-Hodgkin lymphoma
• Young male
• Increased risk with combination AZT and
  infliximab
• High grade with high mortality

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Integrin-directed therapy

• T cell entry into mucosa dependent on a4b7
  integrin
• Natalizumab (Tybrisi) binds a4 component
• Effective in severe Crohns disease
• Risk of PML secondary to JC virus

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Case 2

• HPI 60 y/o M
• . H/o UC diagnosed 20 y. ago
• . Dysplasia 5 y. ago
• . Underwent proctocolectomy with IPAA (
  ileal pouch- anal anastomosis)
• . Now with tenesmus/ rectal pain/
  bleeding

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Pouchitis

• Flex. Sig. Severe mucosal inflammation with
  erosions
• Pathology Acute on chronic inflammation
• Diagnosis Ileal pouchitis

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J-pouch
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Treatment

• Metronidazole 1-2 g/d for 7 days
• Steroids enemas
• 5ASA enemas
• Anti-TNF therapies

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Thank you