dies ist der titel der präsentation - mucosal immunology€¦ · 29 january 2015 prof. harry...

Gastroenterologie, Inselspital

29 January 2015 Prof. Harry Sokol, Paris

IBD Masterclass

Moderator: Pascal Juillerat, MD, MSc.

http://www.google.ch/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.europeish.com/paris/&ei=_yTJVJPAMMO3OPzUgWA&bvm=bv.84607526,d.d2s&psig=AFQjCNGhB16CqkvcWKIZmP0quxxXLOlgIw&ust=1422554675443363

IBD Masterclass, Prof. H. Sokol , Paris 29 January 2015 2

Universität für viszeral Chirurgie und Medizin, Gastroenterologie

Case 1

• Dr. med. A. Kugener



SM, female, 40yo • Fistulizing ileocolic Crohn's disease, montréal L3 B3 + P

03/2013: perforated appendicitis with suspicion of ileitis

Personal history

– Smoking

– Overweight BMI 27.5

– 2 sectio caesarea

• Family history: uneventful



Past history / Crohn‘s disease diagnosis

• 02/2014 colonoscopy:

– ileal involvement, stenosis C. descendens & ileocaecal valve

– fistula: prox. anal canal, C.ascendens & ileocaecal valve

• MRI 02/2014: normal, no fistulas

• MRI 04/2014: wall thickening C.descendens & sigma

• Medication: Imurek 150mg/d, prednison (max. 50mg/d)



Complications

• Iron deficiency anemia

• Vitamin B12-deficiency

• CT-scan 09/2014: jejunocolic fistula C. descendens & paracolic

abscess

Referred by GI-collegue from external hospital due to

complicated course 11/2014



CT scan 09/2014



1st presentation outpatient clinic, Inselspital Berne

• Stool frequency 2x/d, no mucus, no blood

• Weight loss 5kg and inappetence since second flare 09/2014

• Physical exam: leftsided flank pain, no fever or rash

• CRP 70->100mg/l under iv-antibiotics (ciprofloxacine &

metronidazole)

• CT-scan 04.11.2014: progredient paracolic abscess &

jejunocolic fistula



CT-scan 04.11.2014:

• progredient paracolic abscess & jejunocolic fistula



What next ?

• Continue azathioprine/prednisone?

– no

• Antibiotics ?

– iv-antibiotics and enteral nutrition support

• Switch to anti-TNF?

–which one? Infliximab in combination with

azatioprine

–When? Later in course,. If new imaging (after 2-3

weeks) shows abscess <1cm

• Surgery?

– Abscess drainage if possible

– Surgery should be delayed at least 2 weeks after

beginning enteral nutrition support



1st surgery and clincal course

• median laparotomie :

– with sigmaresection (10cm)

– small bowel resection (40cm distal Treitz)

– ileocaecal resection (30cm terminal ileum)

• Postoperative course without signs of abdominal pain, fever,

nausea or vomiting. But 4 kg weight loss

• Persistent elevated CRP ~170mg/l

• Sonography 2 weeks later due to suspicion of abdominal abscess



CT-scan 2.12.2014: • abdominal wall abscess, left lower

quadrant, paracolic

Percutaneous drainage & Tazobac

Microbiology: E.coli, S.milleri

• Metronidazole & ciprofloxacine -> switch

to Ceftriaxon & metronidazol (resistance)



Colonoscopy 4.2.2014 • fistula of distal anastomosis,

• inflammation prox. Colon & ulceration,

• pseudopolyps



What to do next ?

• Conservative management? (ATB, drainage)

– No, surgical-related problem. End-to-end anastomosis in severe colitis

(1st surgery) not recommended due to high postoperative complicaton

rate -> revision of anastomosis & ileoprotectice stoma

• Start Immunosuppression with anti-TNFs / restart Imurek?

– No, no hint for Crohn relapse. Surgical problems not resolved

• Fistula resection?

– yes

• Protective ileostoma?

– yes



2nd surgery

• 09.12.2014: DIVERSION (Split-Stoma)

• Resection of ileotransversostomie, split-ileotransversostomie

• Sepsis after 5d, stool in wound drainage (anastomotic insufficiency?)

-> surgery: peritonitis and small bowel perforation

– Small bowel resection (10cm)

– Ileostomie & transversostomie

– VAC

• Tazobac



Complicated course & 3rd surgery

• Pleural effusion, new fluid collection left upper abdomen

• Punction: E.feacium, candida

• Tazobac stop-> ceftriaxon, metronidazol, vancomycin, diflucan

• No percutaneous drainage possible

-> Revision laparotomy:

– abscess drainage

– peritonitis and small bowel perforation 10cm prox ileostomie

• Starting Entocort 9mg/d



Rehab‘ period

• Psychic decompensation

• 13.1.2015: ileoscopy (45 cm ): no signs of inflammation

(macroscopic & microscopic) on Entocort .

• Following 3 weeks progressive improvement, discharged on

Jan. 20 2015

• Reevaluation in outpatient clinic february 2015



• Aetiologie of smal bowel perforation (twice) unclear ?

– Consequence of active uncontrolled crohn's disease ?

( after 3 weeks postop?) spontaneous small bowel perforation

unusual in Crohn’s disease

– or surgery (leakage – persistent high CRP-)? ileo-protective

stoma recommended in first surgery in severe colitis

• no MR enteroclysis, mandatory in initial work-up? Should

be performed during workup in initial diagnosis

• How to influence / Improve recovery?

(apart from) smoking cessation

–elemental diet? No, enteral nutrition support sufficient

–Entocort or other medications perioperatively, or earlier? Entocort not recommended

• Immunosupressive medication? When ? Which? How?

Yes, later in course (anti-TNF & AZA) after acute infection healed. No anti-

TNF as long as VAC i situ or bowel continuity



Case 2

• Tobias Ernst



Course of disease:

17 years old female patient

• Symptoms at initial presentation:

– chronic watery diarrhea up to 2x/d without blood in the stool

– lower abdominal pain

• laboratory values:

– hemoglobin (104 g/l), CRP 13 mg/l, ferritin 7 µg/l,

transferrin saturation 9%, fecal calprotectin 623 mg/kg,

neg. c-ANCA, neg. p-ANCA, pos. PAB

• examination:

– gastroduodenoscopy & colonoscopy aphthous lesions

in duodenal bulb and terminal ileum, no particular

histopathological findings

– abdomen MRI and no particular echographic findings

• therapy:

– initially Salofalk® 2x1 g per day because of a high

degree of psychological strain, additional iron replacement

– side effects: headache, nausea & symmetrical distal arm- and

leg disorder therefore therapy changed to 9 mg Budesonide

08/2012 – 1st flare



Course of disease: 12/2012 – 2nd flare

• symptoms:

– after reduction and hold of Budesonide, patient complaints increase without

extraintestinal manifestations


– hemoglobin (132 g/l), CRP 3 mg/l, fecal calprotectin 1087 mg/kg

• therapy:

– Budesonide 9mg/d restarted

• procedure:

– Tapering of Budesonide and combination with Modulen®

• conclusion:

– at that stage: a functional component is considered because of negative results in

endoscopy, MRI and US begin with relaxation technique



Course of disease: 05/2013 – 5 months later

• symptoms:

– patient feels well


– normal hemoglobin, CRP 4 mg/l, fecal calprotectin 144 mg/kg, normal values of

vitamin b12, 25-hydroxy-vit d3 and folic acid

no absorption disorder and decrease of inflammation

• therapy:

– Modulen® monotherapy

• procedure:

– next control in 6 months



Course of disease: 09/2013 – 3rd flare

• symptoms:

– increase of abdominal pain and defecation frequency to 3x/d in the past 3 weeks

– but no pain and normal defecation frequency at the moment


– CRP 13 mg/l, fecal calprotectin 244 mg/kg

• therapy:

– Budesonide 9 mg per day by self medication since 3 weeks before

• procedure:

– begin with azathioprin (Imurek®) 50 mg

– To enable Entocort sparing

http://www.ibdetermined.org/ibd-information/ibd-treatment/ibd-

medication.aspx



Course of disease: 05/2014 – 4th flare

• symptoms:

– relapse after stopping Budesonide despite therapy with azathioprin (Imurek®) 100 mg

– high stool frequence with bloody stool

– PCAI-score=20


– fecal calprotectin 600 mg/kg

• procedure:

– repeat ileocolonoscopy just minimal inflammation in the cecum without histopathological stigmata

based on symptoms and course of disease: Crohn’s disease A1 L1+L4 B1




• symptoms:

– normal stool frequency, no blood after an increase of azathioprin (Imurek®) 125 mg, but

still abdominal pain

– lactose-free diet without success


– fecal calprotectin 611 mg/kg

• examination:

– positive fructose breathing test

– DD: SIBO (small intestinal bowel overgrowth) therapy with metronidazol 2x500 mg/d

• procedure:

– testing of 6-thioguanine (6-TGN) and 6-mercaptopurine (6-MMP)




• symptoms:

– still abdominal pain


– still elevated fecal calprotectin

– 6TGN=314 pmol/8x108 (09/2014)

– 6-MMP=3134 pmol/8x108 (09/2014)

• procedure:

– dose escalation with azathioprin (Imurek®) 150 mg




• symptoms: – still abdominal pain and high stool frequency


– fecal calprotectin 91 mg/kg (improvement!) on Imurek 150 mg/d

What to do?




What to do?

• procedure:

– reduce azathioprin (Imurek®) to 75 mg – suspicion of AE

– Re-Test 6TG /6MMP

– ileo-colonoscopy and gastroscopy MRI enteroclysis: if lesion start Anti-TNF

results !!!!



• examination

– gastroduodenoscopy & colonoscopy without any signs of inflammation

– MRI: no lesions

• therapy:

– 25 mg azathioprin (Imurek®)

– 100 mg allopurinol




• symptoms:

– patient feels well without any symptoms


– CRP 12 mg/l, ESR (erythrocyte sedimentation rate) 22 mm/h

Current situation 01/2015



Summary

17 year old female patient with Crohn’s disease

• symptom onset 08/2012: elevated CRP, anemia and chronically watery

diarrhea without extraintestinal manifestations

• late diagnosis in 05/2014, after almost 4 flares

• 2 gastro-duodenoscopies /3 ileo-colonoscopies

• different doses of azathioprin (Imurek®) tried from 25 mg up to 150 mg

• present condition: asymptomatic after dose reduction of azathioprin

(Imurek®) and beginning of allopurinol therapy



Discussion

• How do you distinguish between abdominal pain caused by Crohn’s disease and

abdominal pain caused azathioprin?

– It is very difficult to distinguish. Sometimes the time connection with the beginning of azathioprin

therapy may help you.

• How do you define a flare?

– An increase in subjective symptoms and increase in laboratory values.

• Should TPMN-activity be tested by default?

– If there are no problems with a therapy with azatioprin, you don’t have to test it. We don’t test it

by default.

• When should you check 6-TGN and 6-MMP?

– In our hospital we don’t measure these, but if unexplainable problems in context with a therapy

with azathioprin occur, you should test them.

• What increase is typical for this type of liver cytotoxicity (DD: EBV, Hepatitis)?

– You can’t differ between the cause by evaluating the elevated liver enzyms.

• When do you use allopurinol in this context and what are the most important side

effects?

– We don’t use allopurinol in this context, but there are the same side effects as in therapy of gout.



• retrospectively :

– TMTP-activity: 53 nmol/gHb*h = hypermetaboliser

Discussion

normally 2-3 mg/kg 100-

150mg/d



6MMP / 6TG / 6MMP ratio

• without allopurinol:

– 09/2014 : 3134 / 314 = 10

– 11/2014 : 5452 /174 = 31

• post allopurinol:

– 01/ 2015 : 122 / 314 = 0.388

remember: optimal

treatment:

6-MMP/6-TGN ratio

<30 > 5000 : liver- toxicity



Discussion • consequences of increased TPMT activity

Bible Class on Thiopurine Use in IBD, February 6th, 2013, Dr med P. Juillerat,

M.Sc.



Discussion • effects of adding allopurinol

Bible Class on Thiopurine Use in IBD, February 6th, 2013, Dr med P. Juillerat,

M.Sc.



Case 3

• Roseline Ruetsch



38 years old patient, female

Colitis ulcerosa, diagnosed 2008

• Non-smoker status

• Family history: grandfather and one cousin affected by UC,

siblings with IBS

• Initial presentation: proctocolitis with segmental

presentation in colon descendens

• Extraintestinal manifestations:

- Axial and peripheral spondylarthropathy

- Recurrent episodes of iridozyklitidis (prior to

gastrointestinal manifestation !)




Colitis ulcerosa, diagnosed 2008

• Initially steroid dependent course with glucocorticoid

treatment 12/2008-2012

severe osteopenia

• Azathioprin since 01/2009

• Infliximab 01/2011 -09/2011

• Adalimumab 01/2011 – 04/2013 (stopped due to extra-

intestinal symptoms – lupus-like and fever)

• 04/2014 salofalk 3g and azathioprin 100mg with clinically

remission




New Flare 08/2014 – clinical presentation:

• Recurrent diarrhea with urgency, tenesmus and abdominal

cramps, bloody diarrhea (up to 20x day; 6x nights), fever

(38°C), weight loss: 5kg.

• NB: change of hormonal contraception just before new

flare (Gynera -Gestodenum, Ethinylestradiolum- / Cerazette Desogestrelum( Progesteron)




New Flare 08/2014 2014 – treatment (extern):

• No response after 2 weeks prednison oral (50mg )

• Colonoscopy (extern) proctocolitis ulcerosa with segmental

pattern

• Infliximab 09/2014 (1 shot) without clinicial response

• 10/10/14 rectoscopy: progressive course with new

continious pattern rectum- 45cm ab ano

• Beginn Golimumab 16/10/14 100mg, 30/10 50mg

No response patient referred to University center.



Colonoscopy 28/11/2014



Pancolitis ulcerosa, macroscopically signs of moderate activity

(Mayo 2), with focal erosionen and fissur/ulceration (high

activity) with signs of reepithelialization (healing process)

up to to distal colon transversum.

Colonoscopy 28/11/2014



Question

• 38 year old woman with complicated course of UC, already

treated with all anti TNF agents (1AE, 2 primary non

responder) in outpatient care

• Refered to universitary center from her gastroenterologist

• Endoscopically & histology: moderately active

What would you do at that point ??? GLM induction shema to low at the first time augmentation of the

dosage

Retry strategie induction with IFN was acceptable as 50% of patients reach

remission, BUT do not stop after just 1. shot

Prefer always combo therapy (better response / remission outcome)

GLM: if after a few days no acceptable response that possibility of 2. shot

after a few days for intensive induction

Contact surgery and discuss colectomy



• Treatment proposition at this time:

Hypothesis of inadequately conducted induction with

golimumab so:

New induction regimen with golimumab,

initially 200mg (19.11.2014), than 100mg

(30.11.2014)(26.12.2014) at outpatient clinic





• A few days later:

07.12.15: Beginn with Valcyte 900mg qid (until

06.01.15)

Valcyte: treat even if low PCR

copys, as an option to stop

any pro-inflammatory process

, cave offen with negativ

histology, even

immunohistochemistry !!! So

do not only trust histo

Cave, different if PCR in blood positive then of course treat with antiviral tt

but then reduce immunosuppression because sign an systemic infection !!

CMV+IBD colitis trigger for inflammation and inversely treat both (IS+antiviral)




• Initial clinical improvement with clearly improvement of the

abdominal cramps, less diarrhea, less tenesmus.

• BUT, new pejoration after 3. Godulimab 23.12.2014

with high diarrhea frequency (20x), bloody bowel movement,

increased pain, important night symptoms

Lab values: hypoalbuminemia, high CRP



endoscopy 08.01.2015

Mayo endoscopic classification 3



Question

What would you do at that point ???

So now situation of pancolitis pejoration of the situation

Refer to surgery for colectomy, also to reduce the neoplasia risk

secondary to continued high inflammatory activity by a patient with

disease history >8Y

Cyclosporin could be an option, as also Vedolizumab (but cave delayed

activity so perhaps not in these high acute situation with high

inflammation)

Hospitalization on the 08.01.2015 for intraveinous steroid

application




CRP evolution

Albumin evolution

Calprotectin

evolution



Campylobacter concisus facultative pathogenic germ,

mainly by IBD and immunosuppresion Cipro 500mg

2x/day 10 days



Hospital course:

• Initial empiric antibiotic treatment with Metro/Cipro and

again trial with valcyte (08.01-12.01) by suspiscion of

superinfected colitis

• New antibiotical course (Campylobacter Consisius)

• IV steroid (Solumedrol 60mg 08.01 -22.01) Don’t stop the iv therapy to quikly, otherwise high risk for relapse, oral

form not so well absorbed, mainly because of the hypoalbuminemia (less

because of colitis) even if initial evolution very positive !!! Better

prolongate hospitalization with iv steroids

• Topical therapy with Salofalk 1gr und Budenofalk 2mg with

good tolerance and clinical response

• Azathioprine initiated, then stopped because of suspiscion

of induction of new pejoration



Evolution

• After 3 weeks hospitalization clinical amelioration

• First contact with visceral surgery

• iv corticoids oral steroids

• Pejoration after adjunction of azathioprin stop actually

• Oral nutrition support with special nutrition drinks

• Last clinical evolution: 26/01/15 significant reduced pain,

bowel mouvement. Hypophosphatemia. Hypoalbuminemia.

• Patient discharged in good condition with oral prednisone

60mg/day

• Plan for further treatment: oral tapered steroid treatment,

start in a trial setting with anti-integrin agent



Discussion

• Optimal time for hospitalization ?

• Which treatment ?



Discussion

• When should we consider surgical treatment ? Should we

try again whith cyclosporine / tacrolimus ?

Remain delicate, especially in young patient, psychological acceptance with

this project needed, also difficult for the gastroenterologist to give up after a so

long trial with medical treatment



Case 4

• Claudia Münger



55 year old female patient

• Crohn‘s disease, diagnosed in 2010:

isolated terminal ileitis

• Positive family history (sister died of the complications of

Crohn‘s disease, at age 39!)

Treatment

–5-ASA

–Systemic steroids

– Intolerance for multiple medications: Thiopurines stopped

because of nausea; budenoside…



• Patient wishes a stool transplantation

Colonoscopy 11/2013:

Known terminal ileitis with moderate activity over 2-3cm. No

stenosis.

application of donor stool during the colonoscopy



• Follow-up: clinical improvement for about 2 weeks, then

the comeback of the symptoms (abdominal pain)

• We suggested a second stool transplantation with a

different method: via jejunal tube



• Follow-up: only slight improvement of the bloating and

diarrhea.

• Calprotectin 525 mg/kg

Treatment with anti-TNF (Adalimumab)



• Follow-up under anti-TNF

– Improvement of the abdominal pain and of the diarrhea, stool

frequency 4-5x/d

–Normalisation of the CRP and calprotectin (47 mg/kg)



Case 5

• Lorenzo Macchia



Female, 78 years old

• Atrial fibrillation on anticoagulants

• Biological aortic valve replacement

many antibiotics in the past due to recurrent

cystitis and as prophylaxis before visiting the dentist at

least twice a year.

• Diverticulosis

History



Female, 78 years old

December 2013: recurrent diarrhea

Diagnosis: Clostridium Difficile colitis

Therapy: Metronidazole, 2 per day for 7 days

Diarrhea stops

Initial presentation



10 January 2014: patient brakes her wrist

Diarrhea starts again

Therapy: Metronidazole, for 9 days

Diarrhea stops

Previous

New episode



24 January 2014: subdural hematoma


Therapy: Vancomycin, 4 per day until 10 March 2014

Diarrhea stops

Previous

New episode



18 March 2014: 8 days after the end of the previous therapy cycle


Therapy: Vancomycin, tapering process

Diarrhea stops

Previous

New episode



28 April 2014: before the end of the previous therapy cycle


Therapy: Vancomycin, 4 per day

Diarrhea stops and stool test becomes negative

Previous

New episode



June 2014


Therapy: Fidaxomicin; continue Vancomycin, 4 per day

Diarrhea stops

Previous

New episode



29 July 2014: 6 days after the end of the previous therapy cycle

Diarrhea starts again and stool test becomes positive

Therapy: Vancomycin, 4 per day

Diarrhea stops

Previous

New episode



26 August 2014

Stool transplantation

Therapy



2 September 2014: one week after the stool transplantation

Fever

Previous

New episode



Bacterial translocation?

Differential diagnosis

Port-a-cath infection?

Urinary tract infection?

Endocarditis?



Positive for Proteus Mirabilis

Blood culture



No focus of infection

Abdomen CT scan



No focus of infection or infiltration

Chest X-ray



Therapy: Ciprofloxacin 1 per day until 15 September 2014

Previous

2 September 2014: one week after the stool transplantation

Fever

New episode



Therapy: Ciprofloxacin 1 per day for one week

Fever continues

Previous

17 September 2014: 2 days after the end of the therapy cycle

Fever with negative blood culture

New episode



Persistent fever



Therapy: Removal of Port-a-cath,

Followed by Augmentin and then Ciprofloxacin

Previous

1 October 2014

Positive Port-a-cath blood culture

New episode



The patient is finally better!

No recurrence of Clostridium Difficile

infection

Negative blood culture



Questions

• Should the fecal transplantation have been considered

before? Once the recurrence of the infection had been seen, fecal

transplantation should have been considered

• Through which mechanisms does fecal transplantation

help in the treatment of recurrent colitis and IBD? It re-

establishes the balance between the bacteria populations thus creating a less

favorable environment for C. Difficile

• Are there other ways of re-establishing the balance in the

bacterial flora? There are a few possible alternatives which are being

studied and compared: one is Perenterol and the other one consists in 15

capsules containing treated fecal matter, to be given orally



Questions

• What are the risks of fecal transplantation? Fecal transplantation

is a very safe procedure. Very few complications have been reported.

• Does this situation occur frequently in your experience? The

post-procedure complication in this patient were independent from the fecal

transplantation, which is very safe.

• What are the risks in patients with multiple morbidities? See

above (very safe procedure)

• Should we use another Stool transplantation method in

these patients? (e.g. enema) Prof. Sokol always uses the enema

method for all patients



Case 6

• Markus Herzig

http://www.google.ch/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.parisdigest.com/monument/sacrecoeur.htm&ei=tWfJVOv7C4L9PMGTgLAI&bvm=bv.84607526,d.bGQ&psig=AFQjCNEtHwU1AgYpycFDyAiD7mG4pjZEsg&ust=1422571826761005



55 year old male patient

Ulcerative colitis E3

• First diagnosed 2003, pancolitis

• Initially diagnosed as Crohn’s disease due to granulomas

on histology, diagnosis changed to ulcerative colitis 2013

• ANCA, ASCA and PAB negative

• No extraintestinal manifestations



Course of disease

• Flare 02/2004 despite steroids, start azathioprine

• Azathioprine intolerance: elevated transaminases,

lymphopenia, impaired renal function

• Start with MTX

• 1-2 flares/year, remission on steroids



Course of disease

• 2007 only partial remission on steroids

• 2007-2011 4 doses of Infliximab and MTX, complete

remission

• Patient lost to follow up 2011-2013

• 2013 flare: bloody diarrhea, abdominal pain,

• Calprotectin >600mg/kg



Colonoscopy 2013

Pancolitis, no CMV



Course of disease

• Mesalazine granulate and enema no effect

• Prednisone 30 mg/d 4 weeks 6-7 bowel movements,

bloody stool

• MTX 15mg s.c. 1x/week 4 weeks no effect



Sigmoidoscopy February 2014

Pancoltits, no CMV



Course of disease

• Start Infliximab 07.02.2014: rapid response after first

infusion, MTX stopp

• 21.02.2014 second Infliximab-Infusion: anaphylaxis

(exanthema, bronchospasm, collapse)

• 6-7 bloody bowel movements daily



Discussion

• WHAT TO DO ?

• Further combination of Metothrexate with an anti-TNF, p.e.

Adalimumab

• Alternative: switch to Golimumab



Course of disease

• 20.03.2014 Start Adalimumab initial rapid

response

• after 4 weeks of Adalimumab: 5 bowel

movements, intermittent bloody stool

• 14.07.2014 colonoscopy: Colitis of rectum and

sigma



TL and ABs

• Adalimumab trough-level: <0.024ug/ml

• Adalimumab antibody: 218.2 UA/ml



Discussion

• WHAT TO DO ?

• Switch to Golimumab as an option

• Combination with Metothrexate at least for 6 months.

• Premedication with corticosteroids not recommended

• If Golimumab fails: Vedolizumab in combination with

Metothrexate



Answer

• Start Golimumab and MTX

• Patient in remission on Golimumab and MTX



Summary

• Steroid dependent / refractory pancolitis ulcerosa

• Treatment failure with

–Mesalazine

–AZA

– Infliximab

–Adalimumab

• Response to Golimumab



Discussion

• Continue MTX?

• Premedication with Prednisone, H2-Antagonist ?

• If Golimumab fails: Certolizumab? Vedolizumab?

• Tacrolimus?

• Cross-reaction between anti-TNF?



Case 7

• Susanne Schibli

http://www.google.ch/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.paris-a-nu.fr/une-allee-du-luxembourg-gerard-de-nerval/&ei=fSbJVMzUAsnuPJGxgMAF&bvm=bv.84607526,d.d2s&psig=AFQjCNFsNAnrfdpJMZDQYbm2P5_yNtweEg&ust=1422555094484358



Ulcerative Colitis and bugs

Susanne Schibli Pädiatrische Gastroenterologie, Hepatologie, Ernährung Medizinische Kinderklinik, Inselspital, Bern



L. ML 12 yo

• First presentation 2/2014

• Family holidays in South Africa 12/2013

• Not ill during 4wk trip

• After return, small amounts of fresh blood and

mucus in stool

• 3-4 BM/d, soft stool, once liquid

• Mild abdominal pain, not related to BM

• Normal activity

• Muscle pains in legs, no arthritis

• Previously healthy, normal growth (weight, height P

75)

• Mild asthma, multiple allergies (dust mites, birch)



L. ML 12 yo

• First presentation 2/2014

• Hb 129, MCV 82, Tc 282, Albumin 38, CRP<3, BSR 9

• Calprotectin >600

• Stool positive for

•Blastocystis hominis

•Endolimax nana cysts (reports of bloody diarrhea)

• No response to metronidazol



03/2014



L. ML 12 yo

• 3/2014

• Pancolitis ( - Colon transversum)

• Histology; lympho-plasmacellular infiltrates, mild

chronic changes (crypt distorsion, elongation)

• p-ANCA positive

• DD: infectious, UC

• 5-ASA: orally 2g, topically daily

• 5/2014

• Good response, clinical remission, PUCAI 0,

Calprotectin 58



L. ML 12 yo

• 6/2014

• Flare, bloody diarrhea, Calprotectin 600

• Stool cultures: Camplylobacter concisus

• Ciprofloxacin 2wks, 5-ASA po and enema

• Good response, resolution of bloody diarrhea

• 8-9/2014

• Flare, bloody diarrhea

• Stool cultures: Aeromonas caviae

• Entocort enema (partial response), Ciprofloxacin



L. ML 12 yo

• 10/2014

• 2 days after stop of Ciproxin, again bloody diarrhea

• Holidays in Germany

• Sigmoidoscopy with Pancolitis

• Prednison 50mg, partial response

• Tapering schedule: PDN 30mg, worsening of

diarrhea


• 11/2014

• Colonoscopy under tx with PDN 30mg



11/2014



L. ML 12 yo

• 11/2014

• Mainly nocturnal stools, incontinence, mild pains

• Almost normal daily activity

• Hb 139, MCV 82, Tc 282, Albumin 39, CRP<3, BSR 5

• Calprotectin 529


• Tapering Prednison

• Ciprofloxacin, Metronidazol, Amoxicillin

• Start Mutaflor



L. ML 12 yo

• 12/2014

• Well under triple AB-therapy

• Few days after dc of AB, again soft stools, no blood

• C. diff positive

• Spontaneous improvement

• 1/2015

• Clinically well, PCDAI 15

• Calprotectin 250

• Treatment: Salofalk po and topically, Mutaflor



Discussion

• Ulcerative Colitis

• Campylobacter consicus

• Aeromonas, Endolimax, Blastocystis

• C.diff

• Steroid non-responder

• Treatment options?

dies ist der titel der präsentation - mucosal immunology€¦ · 29 january 2015 prof. harry...

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