ibd masterclass - mucosal immunology€¦ · •09/2015 consultation: good response to the...

Gastroenterologie, Inselspital

19 November 2015 Prof. Arie Levine, Tel Aviv

IBD Masterclass

Moderator: Pascal Juillerat, MD, MSc.

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CASE N° 1

• Dr. med. Maude Grueber

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46 yo male

• Colitis ulcerosa (diagnosed 2006): – Colonoscopy: Rectosgmoiditis

– Entocort Enema1x/day for 4 weeks and Salofalk 3x1g/day during a year

• 2012: macroscopic and microscopic remission

• 11/2014: moderate flare (bloody diarrhea 3-4x/day, tenesmus)

• 11/2014-02/2015: Salofalk enemas1x/day, Salofalk gran 1.5g 2x/day and Budenofalk enema

• 06/2015 (family doctor): persistant moderate flare (bloody diarrhea 3-4x/day, tenesmus), CRP<3, Lc 8.0, Calprotectin 684 mg/kg.

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Emergency consultation

• 13.07.2015: severe flare (bloody diarrhea 30x/day, abdominal pain,

stool at night, -4kg in 1 Month) => hospitalisation

• RX Abdomen: no distension, unspecific distribution of gas

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5

Workout

• Stool: C.difficile negative, bact. negative, parasites negative.

Calprotectine 850 mg/kg, CRP 14, Lc 9.7, albumin 30

• Rectosigmoidoscopy severe relapse Mayo score 3. biopsies:

CMV/HSVnegative

• Therapy: Solumedrol 60mg iv (14-16.07)

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Question 1

• Albumin of 30g/l

Is it a good way of assessing malnutrition in IBD patients?

Albumin is not a good way of assessing nutrition in most patients and

although in IBD patients. A better way to assess nutrition is the weight

loss and measures such as skinfold.

How would you optimize the nutrition among IBD

patients?

A try with protein supplemented fluids (such as Fresubin). The use of

NSJ tube is not clearly recommended.

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Ileo-Colonoscopy

• 15.07.2015: continuous pancolitis (till colon ascendens), Mayo 2. Ileum normal

• Therapy: Stop Salofalk enemas, further Salofalk 1.5g 2x/d po, slow weaning of steroids.

• HBV/HCV, HIV, Quantiferon negativ.

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Follow up

• Consultation (end July ): Improvement of symptoms (stool 6-8x/day, less

blood). Azathioprine started, slow weaning of steroids (not possible

under 20 mg/g).

• Consultation (end Aug.): 150mg/d Imurek, Prednison 20mg. Worsening

=> bloody diarrhea 6-8x/day also at night, abdominal pain. CRP 15, Lc

normal but with left deviation. C.difficile stool again negative.

Imurek 200mg and Prednison 40mg.

• Consultation (beginning September): deterioration of symptoms : bloody

diarrhea 28x/day, abdominal pain, no fever. CRP 40

=> Hospitalisation and begin with antibiotics, Spiricort 60mg iv

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Recto-sigmoidoscopy

• Rectosigmoidoscopy : Left Colitis Mayo 3.

• Biopsies for CMV/HSV.

• Stool culture : C.difficile negativ,

• Aeromonas species, Salmonelle, Shigelles and Campylobacter

negativ.

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• Biopsy Colon:

– Histology: acute activity of the CU, no signs for a pseudomembranous colitis, no

typical cell changes for a viral infection.

– Immunohistochemistry positive for CMV.

– PCR CMV positive with 16 mio copies/ml.

– Blood: 5516 Copies/ml.

CMV Colitis!!

• Begin with Valgancyclovir since 09.09 for 3 weeks, quick weaning of

steroids, Azathioprine 175mg/day, Salofalk po + enema.

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Question 2

• Link between malnutrition and CMV-Colitis? The link is among patients with severe flares of CU and refractory diseases to steroids so that these patients are also often malnourished.

• How do you diagnose it ? The blood serology helps only to know the risk for a CMV reactivation but doesn’t diagnose the disease. The tools are biopsies of the colon (histology, immunohistochemistry, +/- PCR).

• What to do with the steroids and Azathioprine in case of CMV Colitis?

In the literature, there are often change of minds, but in practice steroids should be stopped, Azathioprine could be maintained in case of local disease.

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Evolution / drug managment

• 09/2015 consultation: good response to the antiviral

therapy with improvement of symptoms

• Development of a Azathioprin-induced hepatopathie with a

dosis of 175mg/day (bilirubin normal, ASAT 202, ALAT

178, GGT 2413, amylase/lipase normal).

• Increase of 6TG (710 pmol) and 6MMP (5970 pmol)

=> Suspicion of OVERDOSE!

• 29.09: Stop azathioprine! Prednison was at 15 mg =>

again increase at 20mg.

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Follow up endoscopy

• Control rectosigmoidoscopy (29.09) because of abdominal pain =>

persistance of a severe CU, Mayo 3. Biopsies of the colon show 6382

copies/ml.

• Prolongation of the treatment with Valgancyclovir for 2 weeks, control

rectoscopy in 2 weeks, plan: start biologic (anti –TNF or anti-integrin)

treatment

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• Control rectoscopy (12.10): persistance of a severe colitis ulcerosa

Mayo 3. Immunochemistry negative for a CMV. CMV PCR increased

again with 421‘295 copies/ml. Symptoms with diarrhea 10-15x/day.

=> Persistant CMV Colitis

• NEXT STEP => Valgancyclovir iv (refused by patient) and CMV

blood resistance test.

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QUESTION 4

• SUGGESTIONS ….

To evaluate the duration of the CMV colitis/good response to anti-viral

therapy, the follow-up would rather be clinical based on symptoms than

on the re-endoscopies with PCR.

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CASE N° 2

• Dr. med. Ioannis Kapoglou

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Patient: Mr. P.R. 36 yo

Ileocolonic Crohn’s disease

Montréal Classification A2 L3 B1, FD 2007

- Recurrent perianal fistulae

- Seronegative Sacroileitis 2010

- Prednisone 20mg 2-0-0 from 12.2.15 until 17.02.15 (Puls therapy)

M.Crohn therapy:

• Mesalamine Gran 1.5g 2-0-0

• Humira 40mg/0.8ml every 2 W

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Acute complication

• Presentation with anal pain 28.1.15 at Solothurn hospital

–Anal fissure SSL 6 , possible fistula

– Sub febrile temperature

– AB with amoxicillin and clavulanic acid

–Fissurectomy and partial Fistulotomy 29.1.15

–Coloscopy 09.02.2015: moderate to severe active CD Colon

asc./desc., sigmoid and rectum

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17.2.15

• Presented at ER University Hospital Bern

–Diarrhea, anal pain, fever (38°C)

–WBC: 16.4G/L, CRP 85 mg/L (2 weeks post-op)

–MRI: no new fistula or abscess

•Severe Proctosigmoiditis

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Question 1:

•Need for a change in current therapy?

•Antibiotics?

•Immunomodulators (AZA?)

•Other Anti-TNF?

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Answer

• Adalimumab trough levels as well as Adalimumab-Ab

should be measured

• A re-induction with Adalimumab can be considered as an

treatment option

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17.2.15

Decision for a change in therapy Induction with

Infliximab

+ Budesonide foam locally

-Initially good response

Healing of the fistulae

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August 2015 – new referal (2nd Opinion)

• Diarrhea : 5-6 bowel movements per day without blood,

• Spondylarthritis newly active

• Coloscopy + EUS 21.08.2015: moderate to severe active

segmental Colitis with perianal Fistula and intrasphincteric

abscess.

• Fistulectomie 24.08.2015 by fistula SSL 12.

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What to do / suspected Diagnosis ?

• Levels of Infliximab in Serum / Infliximab-Ab

• Infliximab levels: 1µg/L

• Infliximab-Ab: 96,9 UA/ml

-->Loss of response to Infliximab (high AB-Titer)

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1.9.15. Current Therapy (post op)

• AB: Ciprofloxacin and Metronidazole

• Prednisone 40mg per day

• Mesalamine 3g per day

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Question 2

•How to proceed?

•Reduction of corticosteroids dosage

reasonable?

•Immunomodulators?

•Other Anti-TNF (Certolizumab)?

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Answer

• Try to reduce/stop steroids (disrupt healing rate in

penetrating disease).

• A re-induction with Adalimumab +- MTX can be considered

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1.9.15

• Decision for a new induction with Adalimumab

–After induction injection every 2w

• Amelioration of all the symptoms (Stool 3-4x per day)

–Fistula healed, no sign of recurrence

3.11.15

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Question 3

•Alternative therapy in case of new flare

/ dev. of fistula?

–Tacrolimus?

–Certolizumab?

–Sargramostim?

–Diverting stoma and continued

medication?

–Adsorptive carbon?S

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Answer

• A diverting Stoma and continued medication should be

considered in case of a new flare.

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CASE N° 3

• Cand. med. Stefanie Heyne

26 yo male, diagnosed with Crohn’s disease in 2005: Montreal classification: A1, L1, B3p

2005: • Initial: diarrhea for 2 months and anal abscess excision

• Extraintestinal manifestation: arthritis (ankles, wrists)

• Colonoscopy: chronic inflammation of the terminal ileum

• Therapy: - antibiotics, high dose cortisone tapering

- Azathioprine (2005-2007) good tolerance, stopped in 2007 (patients

wish due to subjective well-being)

2006: multiple flares • Therapy: short courses of steroids (20mg) when disease relapsed (with GP)

2009: severe flare with diarrhea and strong pain in the right LQ • Colonoscopy: severe stenosis in the terminal ileum

• Therapy: Morphine, Azathioprine restarted (2009-2011) stopped by patient due to

subjective well-being and suspect skin lesions

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Course I

2011: recurrence of right LQ pain with local tenderness on palpation

• Therapy: Adalimumab (06/2011-11/2011) stopped due to no improvement

• Colonoscopy: impassable severe stenosis of the terminal ileum,

histopathological slight inflammation and fibrosis

• Gastroscopy: small axial hernia, reflux disease grade I, chronic gastritis, H.p.-positive

11/2011-12/2011: repeated hospitalization due to pain progression

• Therapy: high dose cortisone and antibiotics no improvement

• Final diagnosis: ulcerophlegmonous appendicitis with peritonitis appendectomy

01/2012-02/2012: pain attack, fever, increasing of CRP, cortisone 20mg

• CT-Abdomen: multiple intraabdominal abscesses, 9,5x4,8cm necrotic liver

abscess-segment VIII,V,I, portal vein thrombosis

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Course II

• Therapy: - Punction of the abscesses: left upper abdomen beta-haem. Strept. F,

liver abscess Strept. anginosus, pancreas exsudate Strept. constellatus

Meropenem

- tapering of cortisone

- portal vein thrombosis Marcoumar

08-10/2012: • Sonography: total regression of abscesses, consisting portal vein thrombosis

with cavernous transformation, progressing splenomegaly

• Lab values: persistent cholestasis (DD PSC?)

• MRT liver and cholangiopancreaticography:

portal vein thrombosis with cavernous transformation cirrhosis, central stricture of

the left ductus hepaticus no confirmation of PSC

• New diagnosis: IgA-deficit no treatment

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Course III

2012:

• MR-Sellink: known stenosis of the terminal ileum, no fistula

• Therapy: Induction of Infliximab (07/2012-01/2013) clinical improvement

02/2014:

• Gastroscopy: esophagus varices grade I, reflux disease, histological slight active

H.p.-gastritis. Therapy: PPI

• Colonoscopy: chronic anal fissure, persistent severe fibrotic stenosis in the

terminal ileum, histopathological no active Crohn`s disease

07/2015:

• CT-Abdomen: long segment wall thickening in the terminal ileum and cecum,

adherent small destine loops at the inflammation conglomerate, no

fistula, no ileus, known portal vein thrombosis with cavernous

transformation and collateral circulation

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Course IV

10/2015: Hospitalized for an acute severe flare • Since 5d mucous diarrhea with blood, 20/d, recurrence of pain in the right LQ, repeatedly

vomiting

• Acute therapy by GP: 125mg SoluMedrol

• Clinical exam: normal vital signs, T. 37.3°C, local tenderness defense in the right LQ,

no releasing pain, active peristalsis

• Lab values 28/10/2015: with Marcoumar INR>5, Quick<10%, CRP 115mg/L,

leukocytes 21 G/L, deficit of folic acid

Anamnestic development of flares since 2013: • Short pain attacks every 3 months, triggered by stress, always mucous watery stools

• Therapy: short courses of steroids (20mg) and Morphine when disease relapsed

(controlled by GP)

• Side-effects of steroids: ostealgia, defects of dental enamel, increase in weight (22kg/6y)

29kg/3y weight loss by physical training and dietary change

• Smoking: 5-10cig./d since 10y, no alcohol, no allergy

• Family anamnesis: father died by perforation of abdominal aneurysm

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Current situation

CT-Abdomen I

• Wall thickening of the

terminal ileum, imbibing

of the circumfluent fat

tissue

• Adjacent 4,8x5,0x5,6cm

polyseptate collection

with frame enhancement

• Multiple mesenterial

lymph nodes >11mm

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CT-Abdomen II

• Known portal vein thrombosis with

cavernous transformation,

collateral circulation, slightly

extended biliary tract DD portal

biliopathy, splenomegaly

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• Secondary finding: partial

ancolysis of the left SIJ,

longitudinal fracture of the left

part of os sacrum DD SpA,

osteoporosis due to steroid

therapy

Question 1: What is the right management of

the current flare?

Base therapy: • INR>5: Anticoagulation ? necessary by portal vein thrombosis, stopping

Marcoumar, change to Heparin

• Marked weight loss, deficit of folic acid: Nutrition ? substitution of folic acid, EEN/PEN?

Management of the ileocecal inflammation: • Steroids ? tapering SoluMedrol, no change to Budesonid

• Antibiotics ? Metronidazole

• Immunosuppression (Azathioprin) ? not in infect situation

• Other therapy (Anti-TNF-alpha) ? not in infect situation

• Colonoscopy with endoscopic dilatation ? next diagnostic step

• Emergency surgery ? yes, emergency treatment in insecure situation

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Question 1: What is the right management of

the current flare?

Our management:

• Stopping of Marcoumar Heparin full dose

• SoluMedrol slowly tapered

• Rocephin and Metronidazole Piperacillin/Tazobactam

• Microbiology: blood and stool cultures without pathological findings, serology: CMV

IgG +, IgM –

• Colonoscopy and histopathology if possible: endoscopic dilation

• No emergency surgery

• Decision for surgical intervention dependent on colonoscopy results

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Colonoscopy

• No activity of the Crohn`s disease, multiple pseudopolyps in the cecum,

impassable stenosis in the terminal ileum, no erosions on the Bauhin`s valve

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Summery:

• CT-Abdomen: 4,8x5,0x5,6cm polyseptate collection at the ileocecal area

• Colonoscopy: impassable stenosis in the terminal ileum

• Clinical improvement by antibiotics

Question 2: Conservative or surgical therapy of

the abscess?

Options:

Conservative: • Continuation of antibiosis, after regression of inflammation elective decision about

surgical intervention ? possible, but early surgical treatment recommended

• Steroids ? no benefit for the stenosis

• Immunosuppression (Azathioprin) ? not in infect situation

• Other therapy (Anti-TNF-alpha-Inhibitors) ? not in infect situation

• Endoscopic dilation ? no retry

Surgical therapy:

• Laparoscopic ? only way of eliminating the stenosis, decision by the surgeon

• Laparotomy ?

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Question 2: Conservative or surgical therapy of

the abscess?

laparoscopic ileocecal resection

Our management – important factors for decision making:

• Crohn`s disease activity: 10y

• Localized ileal disease

• Stenosis known since 2009, slowly progression and penetrating behavior (abscess)

• Without base therapy since 2013, steroids in flares

• Compliance? stopping of the therapy in the past due to subjective well-being

• Patient`s request? early excision

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Ileocecal resection and short intersegmental resection of small intestine:

Started laparoscopically, conversion to laparotomy due to severe adhesions, ileocecal

fistula, abscess attached and fistulous to small intestine loops (90cm from ileocecal

region)

Intervention I

16cm long resectate of the ileocecal region

Small intestine segment

adherent to the abscess

collection

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Intervention II

Abscess adhesion at the small

intestinal loops, with fistula

• Macroscopic: injected serosa, «Creeping fat-sign», mucosa edema , Bauhin-Valve

edema, multiple «snail train-ulcera» in the terminal ileum, pseudopolyps,

transmural ileocecal fistula behind the Bauhin-Valve

• microscopic: severe chronic inflammation

activity of Crohn’s disease,

ulcera, fissures, fistula in

the terminal ileum

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Histopathology

Question 3: Which postinterventional therapy

do we choose?

Options for induction of remission and maintenance:

• Prednisolone / Budesonid (further) ? no prophylactic effect

• «Wait-and-see» ? best choice: at the moment «remission» after surgical

treatment of the local ileal disease, control by consultations

and colonoscopy every 6-12month

• Azathioprine / 6-Mercaptopurin ? by new severe flare: induction of Azathioprine

• Methotrexat ? not the first choice

• Adalimumab / Infliximab / Certolizumab ? if Azanthioprine shows no clinical

improvement Induction of Infliximab

Our management: «Wait-and-see»

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CASE N° 4

• Dr. med. Bernhard Friedli

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Male patient 17 y

Ulcerative colitis (diagnosed 2012)

• Initial symptoms: rectal bleeding, anemia, weight loss and

fever

• 2/2012 colonoscopy: ulcerative pancolitis

• Mesalazin 2/2012-3/2013

• Initial insufficient response to steroids, rescuetherapy with

Infliximab 6/2012 – 12/14, stop due to Infliximab antibodies

• Mesalazin again from 12/2014

• 1/2015 Colonoscopy: mild proctitis, – Histology: chronic moderate active Colitis

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Current history

• 8/2015 sinus pilonidalis infection

– co-amoxicillin several weeks

– Excision 22.9.15

– Postoperative co-amoxicillin due to fever

• 9/2015 admission due to abdominal cramps, bloody

diarrhea (5x/d)

– Abdomen was weak with tenderness on palpation

– Samples of blood and stool

– CRP 81mg/l, Lc 16G/l, T 36°C

– X-ray: no toxic megacolon

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Sigmoidoscopy

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Severe ulcerative colitis, Mayo 3

Histology: Severe acute ulcerative colitis,

- immunohistology: CMV negative

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Therapeutic management

• Methylprednison 60mg/d i.v

• Metronidazol to treat C. diff. (high clinical

suspicion)

• Day 3: CRP 66mg/l, Lc 14 G/l,

Diarrhea 1-2x bloody /d

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Evolution

• Day 6 of hospitalisation

• Increase in abdominal pain

• Raise in CRP (110mg/ml) and Lc (23G/l)

• Increase in bloody diarrhea

• Rescuetherapy Ciclosporin 4mg/kg – 8mg/kg i.v.

• Change metronidazol to vancomycin due to progression

of inflammation

• Prof. A Levine: Other Rescuetherapy possible, i.e.

Adalimumab

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Day 16 - abdominal MR

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Inflamation of the entire colon,

little acites , no collection

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Day 21 - Colonoscopy

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Mayo 2-3

Histology: Severe flare of ulcerativ colitis, no CMV or HSV

Microbiology 600’000 copy’s CMV

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Evolution

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• Due to therapy refractery severe flare of ulcerative colitis

decision to colectomy, performed 16.10.15

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Questions

• Other rescue therapy (e.g. adalimumab)

• Answer: Due to guidelines not a second rescuetherapie should be given. In this case with not very severe evolution maybe second rescuetherapie with adalimumab could be tried

• Treatment of CMV before operation ?

• Answer: The evolution is not likely due to CMV-infection but to a therapierefactory UC.

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CASE N° 5

• Dr. med. Miriam Flückiger

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46 year old female

Crohn`s disease (diagnosis 01/2014)

• Initial presentation with ileitis

• Montreal classification A3 L1 B1

• Colonoscopy 01/2014: ulcerous ileitis terminalis, 2

serrated adenomas & 2 hyperplastic polyps

hyperplastic polyposis syndrome

• Gastroscopy 01/2014: helicobacter pylori gastritis

• MR enteroclysis 01/2014: wall thickening of terminal

ileum

• Chronic arthralgias

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Initial colonoscopy 01/2014

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Therapy

• Budesonide 9 mg/day 01/2014 – 03/2014

– Persistent abdominal pain, fever and ileitis

• Corticosteroids and Azathioprine 03/2014 – 04/2014

– New epigastric pain, nausea & vomiting, elevated liver enzymes

(no pancreatitis) under Imurek stop

– TPMT activity intermediate, no genetic mutation

• MTX 04/2014 – 05/2015, low dose steroids (asthma)

– Initially Remission in 05/2014

– BUT: Diffuse musculoskeletal symptoms/fibromyalgia with

immobilisation (Rheumatology: no typical IBD arthropathy) and

local reactions & nausea after injection of MTX

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Colonoscopy after 1 year 02/2015

Persistent slight Ileitis

NO mucosal healing 2 polyps & serrated adenoma

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Question 1

• Which medication?

–No treatment

–Budenoside

–5-ASA agents

–Biologics (Anti-TNFs)

–Vedolizumab (Entyvio)?

–Surgery

Dietary therapy suggested

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Therapy

• Start with Infliximab in 05/2015

–Reasons: persistent ileitis, intolerance for MTX,

musculoskeletal symptoms

–Intervall: 600 mg every 8 weeks, premedication with

Solumedrol (multiple allergies)

–After 2nd injection: edema, pain & pruritus, DD

Infliximab-associated reaction vs. steroid-induced

reaction

–3rd injection without steroid premedication

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After 3rd injection

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After 3rd injection

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Infliximab-associated psoriasiform-

eczematiform reaction

• Head, trunk, genital area

• Dermatology: Punch biopsy (feet, shoulder)

– Psoriasiform-spongiform dermatitis

• Topical corticosteroid therapy, PUVA & Neotigason

• Continuation of infliximab

– No symptoms of Crohn’s disease

– Musculoskeletal symptoms better

– Skin under control

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Questions 2

• Class effect ? Yes, it is a class effect

• In case of exacerbation (skin): change therapy again? Not necessarily

• New medication (Ustekinumab or Vedolizumab?) Not indicated at this stage, Crohn`s disease is very mild

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CASE N° 6

• Dr. med. Ioannis Linas

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25 yo Male

• Ulcerative pancolitis with backwash Ileitis (ED 02/2013, EM 2011)

• Montréal Classification E3

• initial manifestation 2011: elevated stool frequency, later bloody

stools

• No extraintestinal, no perianal manifestation

• Non smoker

• Negative IBD Family history

Initial Therapy (02/2013): Mesalazine, Budesonide

• No response

Steroid tapper (03/2013)

• No response

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• 4 cycles of Infliximab

• No response

Adalimumab 09-10/2013

• No response

Patient frustrated

Alternative medicine 10/2013 – mid 2014

• No response

Colonoscopy 05/2014: Ulcerative pancolitis with backwash Ileitis

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• Steroid induction + Azathioprine maintenance therapy

• No response

Golimumab 05/2015

• Subjectively partial response

• No blood, no abdominal pain, no arthralgia

But…

• Persistent diarrhea > 5-6x/d, stool urgency

• Under golimumab intermittent gingival bleeding

• Calprotectin > 1800mg/Kg

07/2015 Golimumab every 3 weeks and referral to us

76

Work up

• Partial clinical response, 5-6x/d diarrhea good condition

• Calprotectin > 1800 mg/Kg, CRP<3 mg/L, WBC: 4.6 G/L,

• Negative stool microbiology, parasites

• No extraintestinal manifestation

• Colonoscopy: ulcerative pancolitis with sparse ulcera but

spontaneous mucosal bleeding and backwash Ileitis.

• Mayo 3, maximal manifestation in rectum.

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Histopathology:

• Chronic ulcerative pancolitis

• Minimal signs of inflammatory activity

• No CMV (IHC / PCR)

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Question 1: What would you do next?

• Other anti-TNF?

• Combination therapy?

• Anti-integrin?

• Calcineurin inhibitors?

Answer: I would consider the maximum

dosis of Mesalazin per os combined

with Enemas and keep Golimumab,

since the patient never had this therapy

and the activity seems to be minimal

with good general condition

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Our decision:

• Combination golimumab + azathioprine

• Local therapy with alternating budesonide and

mesalazine for stool urgency

But then……

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03/10/2015

81

• 2x Punch biopsy, Microbiology, direct immunofluorescence

• Pemphigus vegetans type hallopeau associated with the anti-

TNF therapy

• Superinfection with S. aureus

• Azathioprine stopped by the patient,

• Local steroids, antiseptics and antibiotics

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Question 3: What do we do next?

• Calcineurin inhibitors?

• Vedolizumab?

• Ustekinumab?

• Surgery?

Answer: Again I would try the combination of 5-ASA per

os and enemas. I would not try another anti-TNF since 3

have already failed. Vedolizumab would be another

possibility. Personally am no fan of calcineurin

inhibitors, though theoretically they are another option.

Question 2: In your experience anti-TNF associated

with autoimmune bullous skin disease?

Answer: I am not familiar with any relevant cases.

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Our decision: vedolizumab

Question 4: After those adverse effects would a combination

with azathioprine still be an option in the future?

Answer: Because of the limited experience in the literature and

the unknown pathophysiology I would rather avoid azathioprin

as well

85

CASE N° 7

• Dr. med. Stefan Schlosser

86

Patient: Ms. G.M. 56 yo

Ileocolonic Crohn’s disease

Montréal Classification A1 L3 B3 P, diagnosed 1970

Referral by GP for second opinion

- nutrition & therapy?

- multiple bowel resections (enteroenteric fistulae, adhesiolysis,

reversed transversostomy)

- multiple perianal abscesses, transspincteric fistula, last 2006

- recurrent ileus/subileus, last 2009

- 2014 vaginal & anal fistula (w/o inflammation)

- diet: since years only Fresubin (normal diet > pain LLQ for days,

flatulence, diarrhoe)

- smoker (10cig/d), sec. osteoporosis (ED 1995)

87

Patient: Ms. G.M. 56 yo

Ileocolonic Crohn’s disease

Montréal Classification A1 L3 B3 P, diagnosed 1970

Therapy:

• Remicade (Infliximab) 2001-2007, stopped in remission

• Opioids (> abd. Cramps, pain)

– Durogesic (Fentanyl) TTS 100mcg/h q/72hrs

– MST cont ret. (Morphin 60mg) q/8hrs

• Lexotanil (Bromazepam) 3mg q/8hrs

• Deanxit (Melitracen/Flupentixol) q/12hrs

• Prolia (Denosumab) 60mg q/6mo

88

Work up

• Clinical exam: 54kg, 165kg, BMI 20, anal fistula,

hemorrhoids, soft abdomen, normal bowel sounds, no

rectal exam.>pain

• IgM slightly increased

• Alpha1 globulin decreased

• Calprotectin 805 mg/kg, CRP <3 Lc <10, Alb 37

• Negative: rheumatoid factor, ANA, Anti-tG IgA

• Infliximab AB: 18.2 ng/ml (<10)

89

MR enteroclysis 6/17/15

• small bowel loops

completely shifted right

hemiabdomen w kinking

of ascending

duodenum) with

contrast to the cecum

• dilated gas-filled colon

(9 cm)

• no clear stenosis

• no active inflammatory

bowel changes.

MR-E

90

06/15

•Picture of a type C gastritis

•findings consistent with diffuse

motility disorder

Histology:

•duodenal bulb: wo

histopathological changes.

•Antrum&corpus: wo

histopathological changes. No

chronic or active inflammation.

•esophagus: squamous mucosa w

focal inflammatory activity DD CD,

reflux

Gastroscopy

91

06/15

•pronounced anastomotic stenosis

– w 90°angle @ neoterminal ileum)

– clinical subileus

– ballon dillatation > 12 to 15 mm

•wo ulcers or signs of heavy activity

Histology:

•small intestine: villi&crypts disturbed,

partly erosive active inflammation

•colon: crypts disturbed, mod. active

lymphoplasmacel. inflam., cryptitis

•rectum: less crypts distortion, less

inflammation (neutrophils)

•CMV neg.

Ileo colonoscopy

92

Question 1:

Your recommendations?

Nutrition? Fresubin & what else?

Symptoms - Influence of opioids?

Therapy:

Surgical Reassessment vs. Steroids?

Induction with Infliximab?

93

... Some weeks later 08/15

Symptomatic improvement better after 1st dilation

Discussion: operative revision of ileocoecal

anastomosis (after balloon dilation 12>15mm)

•prestenotic and poststenotic dilation in MR

•patient undecided

Tried to eat solid food > flatulence & abd. cramps

CRP/Lc normal

94

2nd Ileo colonoscopy

09/15 rectal Stenosis at 5cm

use of gastroscope

mucosal lesions & fistula

Colon: no inflammation, 2nd ballon

dilatation of anastomotic stenosis

(neoterminal ileum) > 12 to 15 mm

95

Clinic slightly improved

Ultrasound: distended small bowel to 1.5 cm

... Some weeks later 10/15

96

Question 2:

Your recommendations?

Therapy:

Conventional step care vs. early top

down?

Induction with Infliximab now?

97

Entocort (Budesonid) 3mg/d po

New balloon dilation 12/15

After some weeks Pt decided to stop eating

fruits/vegetables/meat

FODMAP Diet

... Plan

98

Ultrasound 20.10.15: Dilation small bowels 1,5cm

Entocort 3mg/d stopped > severe nausea

Overall much better with FODMAP diet

Can arrange with current situation > does not want further

therapy

... Some weeks later 10/15

99

Question 3:

Further ideas? what`s the influence of FODMAP here?

no maintenance therapy?

does smoking increase symptoms or prevent

remission?

Follow up intervall?

What therapy escalation in case of new events?

Stool transplantation is an option?

Would you screen her son w slight upper GI pain?

100

CASE N° 8

• Dr. med. Vasileios Oikonomou

41 yo male Patient

Ulcerative colitis, diagnosed 06/2003 Montreal classification : E2

2007 – 03/2009 partial clinical remission under steroids + azathioprin 150 mg/day

04/2009 azathioprin + steroids (relativ steroiddependency) stopped from patient mesalazin 1-0-1 gr po mesalazin enema 0-0-0-2 gr started from patient

07/2009

colonoscopy: distal colitis of the rectum and the distal sigma, E2

complete Mayo score: 7 Endoscopy : 2

Rectal bleeding: 1

Stool frequency: 2

Phys.gl.assessment: 2

Therapy?

• 5-ASA dosis increase?

• Combination with budesonid?

• Azathioprin?

• Systemic steroid therapy?

Answer

• Combination of mesalazin with budesonid enema

07/2009

Therapy: mesalazin 1,5 gr 1-1-1 po

mesalazin enema 2-0-0-0 gr

budesonid enema 0-0-0-2,3 gr

partial clinical remission

2010

Therapy reduction : mesalazin 2-0-2 gr po

mesalazin enema 0-0-0-2 g

mild flares

01/2011 Mesalazin 2-2-2 gr po Mesalazin 0-0-0-2 gr enema Colonoscopy: colitis with mild activity in the coecum, ascendens, transversum, descendens, erosiv and more active colitis in sigma and rectum complete MAYO-score: 6 Stool frequency: 2 Rectal bleeding: 0 Endoscopy : 3 Physic. Gl. Assess. : 1

Therapy?

• 5-ASA + azathioprin?

• Steroids?

• Anti-TNF?

Answer

• The next therapy should be really effective,

Azathioprin with mesalazin would be a good idea

02/2011

• azathioprin 50 mg/day

• mesalazin 2-2-2 gr po

• mesalazin enema 0-0-0-2 gr

Evolution:

Azathioprin dosis maximised to 200 mg /day =>

clinical remission =>

hepatotoxicity => ALT: 156 U/L, AST : 54 U/L

05/2011

Dosis reduction to 50 mg /day =>

in 2 weeks clinical progress with diarrhea and rectal bleeding

07/2011

normal transaminases

• azathioprin 100 mg/day => Clinical remission

• 08/2011 Dosis increase to 150 mg/day

• 01/2012 screening colonoscopy : total clinical, endoscopical und biological remission

• 02/2012 dosis increase to 175 mg/day

• 06/2012 dosis reduction to 150 mg/day

• 03/2014 colonoscopy: colitis in sigma und descendens of moderate activity , Mayo II

• Until 06/2015 clinical remission

• The patient stopped the monotherapy with azathioprin because of intolerance- incompliance (gastro-intestinal and systemic AE)

09/2015

flare with high grade activity

E3, Mayo 3

Evolution

• Clinical und biological remission under :

Mesalazin 1-1-1 gr po

Prednison po, up to 40 mg/d., then weaned

Long term Therapy ?

• 5-ASA ?

• Puri – Nethol ?

• Methotrexate ?

• Biologics ?

Answer

• Suggestion for a sigmoidoscopy with biopsies

• The therapy should depend on the result of the sigmoidoscopy and the clinic

117

CASE N° 9

• Dr. med. André Kugener

118

DK, 1991, female - history

• Hospitalisation 05.2015: acute

appendicitis, probably perforated

• Laparoscopic appendectomy

05.2015

–Histology appendix: acute erosive

appendicitis with acute fibrinous

periappendicitis; no perforation

• Sonography 1.6.2015: small

abscess lower right abdomen

• Discharged on the 3rd day

–Co-Amoxicillin for 7 days

119

Postoperative follow-up

• 16.06.2015: Little pain lower right quadrant, doing well

• 25.06.2015: pain lower right quadrant, subfebrile, CRP

103mg/l

–Co-Amoxicillin 2x1g/d for 2 weeks

• 29.06.2015 sonography : terminal ileitis, colitis cecum &

ascending colon, residual abscess

• 01.07.2015: CRP regredient, feels better

• Referral to gastroenterology

120

Outpatient clinic

• No blood, mucous in stool, no diarrhea, no fever

• Persistent slight lower right abdominal pain, palpable

resistance, abdomen soft

• No nicotine, seldom alcohol

• No allergies

• Uncle (fatherside) with Crohn‘s disease

• CRP 35mg/l, Lc 5.7 G/l; (iron, lab chemistry and blood

count normal)

• Calprotectin 1384mg/kg

121

Colonoscopy 17.07.2015

• Edematous stenosis

colon at 60cm

• Passage with

colonoscope not

possible

• histology: no signs of

chronic inflammation,

no hints for Crohn‘s

disease; probably

infectious nature

122

Therapy?

• Further investigation?

• Initiate therapy? If yes, which one, and why

• Empiric steroids 50mg/d & Amoxicillin, MR-enteroclysis

123

MR-enteroclysis 07/2015

• Terminal ileitis with

prececal abscess

• No stenosis, no

proximal colon dilation

124

Further work-up

• Yersinia-serology 07/2015: pos. IgM, neg. IgG

–Steroid stopped after 5 days

–Ciprofloxacin for 3 weeks

• Patient feels fine, oligosymptomatic

– no change in stool behaviour, no diarrhea, slight abdominal

pain right lower quadrant on deep palpation

• Close case? Control needed?

125

FU after treatment of yersinia-enterocolitis

• Stool culture negative, no yersinia

• CRP 39mg/l, abdominal pain, no diarrhea, no blood

• Calprotectin: 148 mg/kg

• Abdominal sonography 08/2015: ileitis terminalis over 6cm,

colitis of cecum and ascending colon

Steroids 50mg/d & colonoscopy (w/o dilatation)

126

Colonoscopy 20.08.2015

• Edematous stenosis colon at 60cm

• Passage with colonoscope not possible

• Not possible to advance wire under radiologic control (for dilatation)

• Contrast agent with delayed flow into cecum

• Histology: moderate active erosive inflammation, probably infectious

127

Interdisciplinary discussion

• Surgeon: – probably postoperative

alterations one often sees after retrocecal appendicitis

– Operation situs without signs of inflammation of ascending colon

• Gastroenterologists: – Crohn most likely, diagnostic

measures limited

– Oligosymptomatic patient

• Consenus: – Wait with diagnostic

laparoscopy

– Repeat colonoscopy after 3 weeks syst. steroids (50mg, tapering dose)

128

Colonoscopy 29.09.2015 – after 5 weeks steroids

• Edematous stenosis colon at 60cm

• Passage with colonoscope not possible

• Histology: no granuloma, could be Crohn‘s disease or Yersinia-colitis

• Yersinia-serology 09/15: IgG & IgA neg.

129

How to proceed ...

• No definite diagnosis ... after 3 colonoscopies

• Crohn most likely in an oligosymptomatic young woman

• Further investigation?

• Diagnostic laparoscopy?

• No medication?

• Budesonid?

• Continue systemic steroids?

• Immunmodulator?

130

Our plan

• Budesonide 9mg/d for 8 weeks and afterwards dose

tapering; regular clinical & sonographic controls

• If symptoms recur -> diagnostic laparoscopy and right

hemicolectomy with evaluation of imurek

• Telephone call this week: no abdominal pain, no diarrhea,

doing well; little fatigue

131

THANK YOU FOR THIS EXCELLENT MASTERCLASS !