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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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
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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
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• 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
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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)
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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
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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)
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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
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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
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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 !