SEVERE ULCERATIVE COLITIS DURING PREGNANCY

M. Stoupaki, V. Gkagkari, G. Axiaris, G. Leonidakis, A. Karlaftis,

E. Zampeli, S. Michopoulos

Gastrenterology Department, Hospital Alexandra, Athens

Introduction

• Acute severe UC (ASUC) is a medical emergency that requires prompttreatment, early identification of therapeutic response andmultidisciplinary management in specialized centers.

• Intravenous steroids are the mainstay of therapy, but up to 40% ofpatients will fail to respond to steroids (SR-UC) requiring quickprogression to second-line therapy with either cyclosporine (CsA) orinfliximab (IFX).

•Woude, Ecco 2015•Dulai, Therapeutic adv Chrnonic Dis 2018

Clinical Case

• Caucasian female (DoB:13/11/1982)

• Family History: Father: UC (?), Mother: Lupus

• No surgeries

• Smoker

• Ulcerative Colitis:

Diagnosis 2014 : extensive colitis (moderate severity)

Total Mayo Score: 5

Treatment: Mesalazine 3.6 gr oral

Mesalazine topicalRemission for 4 yrs

• 27/01/2018 – 3 months before pregnancy:

• Total colonoscopy: No pathology (Mayo 0)

• Normal bowel motions, no abdominal pain

• Inflammatory biomarkers normal

• Treatment mesalazine oral and topical

• Disease in remission at the time of conception

Clinical Case

Is it safe to discontinue treatment during pregnancy if the patient is in

deep remission?

# Question 1

Clinical Case: Disease flare

• 10 wk: She discontinued treatment (on gynecologist advice), stopped smoking

Gradual increase of bowel motions /day (5),

No abdominal pain, Inflammatory biomarkers normal

• 16 wk: Reintroduction of mesalazine 3gr/day oral and topical

• 29 wk: Deterioration - Abdominal pain, fatigue

Truelove score: 5 bloody diarrheas/day, 80 bpm, 37 oC , HGB 12.4 g/dL, ESR 70 mm/h,

CRP 0,4 mg/L (<5)

Introduction of corticosteroids

(prednisolone) 40 mg/day oral

30 wk: Admission in hospital - Acute severe ulcerative colitis – Total Mayo Score = 11

• Factors of risk: cortico-resistance, pregnancy, weight loss, abdominal pain

•Truelove score: >10 bloody diarrheas/day, 67 bpm, 37 oC , HGB 11 g/dL,

ESR 45 mm/h, CRP 46 mg/L (<5).

• Unprepared flexible sigmoidoscopy: ulcers (mayo 2) and

CMV Immunohistopathology Negative

• Ultrasound to exclude toxic megacolon

• Stool culture (-), C. difficle toxins (-), parasites (-)

• Check list for the prevention of infection: mantoux test (-), anti Hbs (+), HCV(-), HIV(-), HAV-IgG(-), HSV-IgG(+),VZV-IgG(+), CMV-IgG(+)/IgM(-)

• WBC=6.700,Ur=20 mg/dL, Cr=0,41 mg/dL, Mg=1,7 mg/dL, P=2,7 mg/dL,

Ca=8,5 mg/dL, TP=6,5 g/dL, ALB=3,2 g/dL, INR=1,1, UA=3,6 mg/dL, TC=167 mg/dL, TG=205 mg/dL, HDL=80 mg/dL, LDL=mg/dL, AST=17 U/L, ALT=15 U/L, γGT=19 U/L, ALP= U/L, Tbil=0,30 mg/dL

Clinical Case: Hospital admission

Assessment of Acute severe ulcerative colitis

•Day 0• IV steroids (prednisolone 50 mg /day)

• Calcium and vitamin D supplements

• Thrombosis prophylaxis (subcutaneous LMWH) - ECCO Statement 7D

• Intravenous fluids and electrolyte replacement (especially K+ and Mg++)

• Adjunctive mesalazine (oral and topical)

• Inform colo-rectal surgical team (surgical consultation on daily basis)

• Regular clinical review/12h

• Blood tests /24 h

• Stool chart

• Obstetrician consultation and NST test on daily basis

• Nutrition assessment – oral nutrition

• Treatment:

• Assessment:

Algorithm for treatment decisions for Acute Severe UC on intensive steroid therapy

Ahuja, Tropical Gastroenetrology 2008

DAY 3

DAY 5

• Day 3, 30wk3d pregnancy: No clinical benefit Stool GDH (+) & Toxin B Cl.difficile (+). Vancomycin 125 mg X 4 oral was commenced without any clear improvement Re-evaluation: >8 bloody diarrheas/day, 95 bpm, 37.2 oC , HGB 10.1 g/dL, ESR 87 mm/h, CRP 118 mg/L

abdominal pain, weight loss, vomiting

•Day 5, 30wk5d pregnancy: 2nd line therapyAt this point salvage treatment was discussed with the patient whilst surgical advice was requested. Between infliximab and cyclosporine, the patient chose the latter. Cyclosporin (Calcineurin inhibitor) was initiated with close monitoring of drug levels (2mg/kg/day through pump-controlled IV infusion over 24 hours).

Clinical Case: Rescue therapy

# Question 2

Cyclosporine and Infliximab:

Are they of comparable effectiveness and safety?

Does pregnancy make any difference?

The incidence of colectomy and the time of colectomy did not differ between the cyclosporine and infliximab group

Laharie, Lancet 2012

Cyclosporine was commenced at week 30 of pregnancy

Cyclosporine during pregnancy

•Kombluth, Am J Gastroenterology 1997•Arts, J Inflamm Bowel Dis 2004

CsA Side effects

• Vascular:

- Hypertension- Renal Injury (acute tubular necrosis)

• Neurological :- Headache- Seizures (Mg, Cholesterol)- Paresthesias

• Opportunistic Infections- Pneumocystis jirovecii- Aspergilus Fumigatus

CsA Monitoring

• Trough levels/48 h (150-250 μg/L)

• Blood pressure c/8h

• Kidney & liver function

• Cholesterol and Magnesium

# Question 3

Should we have given Pneumocystis jiroveci prophylaxis with Co-trimoxazole ?

30 wk5d 32 wk 34 wk 35 wk

Bowel motions 10 4 3 2

Blood in stool All 1 no No

CRP mg/L 118 75 32 7,8

Sigmoidoscopymayo

2 - 0 -

CsA (μg/L) 134 225 192 180

CsA dose (mg/d) 100 IV 200 IV 300 oral 300 oral

After the initiation of Cyclosporine and steroids tapering, the patient’s symptoms gradually improved in

accordance with normalization of blood tests and biomarkers:

•2 bowel motions /day, 66 bpm, 36,8 oC, HGB 9,1 g/dL CRP 7,8 mg/L, Alb 3,8 g/dL ,

•Endoscopy confirmed the improvement mayo 0, total mayo 4

Clinical Case: Disease course on Cyclosporine

Bacteremia(P. Aeroginosa)

Preeclampsia

Acute chorioamnionitis

Stool number

30w5d 32w 34w 35w

Cesarean

section

Complications

10

4

3

2

CsA

CsA225 μg/L

CsA192 μg/L

CsA180 μg/L

Time

Disease course after the initiation of Cyclosporine CsA

Transfer to High Risk Pregnancy Unit

Bacteremia(P. Aeroginosa)

# Question 4

Given the fact that bacteremia ensued , should we have withdrawn immunosuppression?

Bacteremia(P. Aeroginosa)

Preeclampsia

Acute chorioamnionitis

Stool number

30w5d 32w 34w 35w

Cesarean

section

Complications

10

4

3

2

CsA

CsA225 μg/L

CsA192 μg/L

CsA180 μg/L

Time

Disease course after the initiation of Cyclosporine CsA

Transfer to High Risk Pregnancy Unit

• 35 wk: Cesarean section The newborn was premature and underweight but recovered after 30 days in the incubator.

• A week after delivery the patient was discharged • Cyclosporine was discontinued and replaced by adalimumab 30 days later • Six months later the patient is still in remission

Rahier, J Crohn's and Colitis,2014

Clinical Case: Pregnancy outcomes

# Questions

1. Is it safe to discontinue treatment if the patient is in deep remission?

2. What is your first option as rescue therapy in pregnant patients with acute severe UC? Cyclosporine or Infliximab?

3. Should we have done something differently in order to avoid the advent of infections in this patient?

4. What about vaccination of newborn?

Thank You