Int J Colorectal Dis (2014) 29:645–651 DOI 10.1007/s00384-014-1880-4
REVIEW
Therapy of complicated Crohn’s disease during pregnancy—an interdisciplinary challenge C. Seifarth & J. P. Ritz & U. Pohlen & A. J. Kroesen & B. Siegmund & B. Frericks & H. J. Buhr
Accepted: 18 April 2014 / Published online: 4 May 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Background Severe courses of Crohn’s disease (CD) during pregnancy are rare. However, if occurring, the risk of miscarriage and low birth weight is increased. At present, only limited data is available on the treatment of CD during pregnancy. In particular, there are no standard guidelines for surgical therapy. Nevertheless, surgery is often unavoidable if complications during the course of the disease arise. Purpose This study provides a critical overview of conventional and interventional treatment options for CD complications during pregnancy and analyses the surgical experience gained thus far. For illustrative purposes, clinical cases of three young women with a severe clinical course during pregnancy are presented.
C. Seifarth (*) : H. J. Buhr Department of General, Visceral and Vascular Surgery, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany e-mail: [email protected] J. P. Ritz Center of General and Visceral Surgery, Helios Kliniken, Schwerin, Germany U. Pohlen Department of General, Visceral and Vascular Surgery, Ortenau Klinikum, Offenburg-Gengenbach, Germany A. J. Kroesen Department of Gereral, Visceral Surgery and Traumatology, Krankenhaus Porz am Rhein, Koeln, Germany B. Siegmund Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité – Universitätsmedizin Berlin, Berlin, Germany B. Frericks Department of Radiology, DRK Klikum Westend, Berlin, Germany
Methods After treatment-refractory for conservative and interventional measures, surgery remained as the only treatment option. In all cases, a split stoma was created after resection to avoid anastomotic leaks that would endanger the lives of mother and child. The postoperative course of all three patients was uneventful, and pregnancy remained intact until delivery. No further CD specific medication was required before birth. Conclusions The management of CD patients during pregnancy requires close interdisciplinary co-operation between gastroenterologists, obstetricians, anaesthetists and visceral surgeons. For the protection of mother and child treatment should thus be delivered in a specialised centre. This article demonstrates the advantages of surgical therapy by focusing on alleviating CD complaints and preventing postoperative complications. Keywords Crohn’s disease . Pregnancy . Surgery . Interventional therapy . Conservative therapy . Case report
Introduction Like ulcerative colitis, Crohn’s disease (CD) is a chronic inflammatory bowel disease. It can affect all segments of the gastrointestinal tract but occurs most often in the small bowel, the terminal ileum and the colon [1, 2]. Typical symptoms include tiredness, lower abdominal pain, fever and diarrhoea. The disease may also take a complicated course involving the formation of fistulas, abscesses and strictures [3]. The described symptoms and complications occur in both pregnant and non-pregnant patients. Preference is given to drug therapy in both groups of patients. Lately, the focus has shifted to interventional and surgical treatment measures in patients with a complicated case of the disease. However, several points must be considered in association with pregnancy. The initial
646
manifestation of CD mainly affects young women of childbearing age. Many experience anxiety about a possible pregnancy and an attack of CD with its associated risks. Patients often fear that pregnancy might induce an attack [4]. Furthermore, therapy during an acute CD attack in pregnancy is problematic. Here, it is crucial to consider the advantages and disadvantages of conservative, interventional and surgical therapy and their respective risks. This study presents a critical overview of the distinctive features and therapy of complicated CD cases during pregnancy. It discusses diagnostic clarification as well as conservative, interventional and surgical therapy with reference to the existing pregnancy in each case.
Fertility and course of pregnancy A favuorable time for conception is a phase of spontaneous or drug-induced remission. Whilst patients in remission do not seem to have impaired fertility, active cases of CD are associated with reduced fertility [5, 6]. Various causal factors play a role here: inflammation affecting the fallopian tubes and ovaries or perianal involvement resulting in dyspareunia and loss of libido [7]. Furthermore, depression has been linked to young women with CD and loss of libido [8]. Inflammatory bowel diseases (IBD)-associated dyspareunia, vaginal infections and problems with lubrication can reduce sexual activity and are also associated with depressions [8]. Decisive for the course of pregnancy is the disease activity at its onset. Women who conceive during remission have the same risk of an acute case as non-pregnant women [9]. The risk of an active disease course during pregnancy is higher in those who conceive during active disease, with complications developing in two thirds of all patients [5, 10]. Various studies describe an increased risk of low birth weight and premature delivery in mothers with CD, particularly if an acute case occurs [11, 12]. The first manifestation of the disease also appears to be associated with an increased risk of premature delivery [13]. A complicated course of CD during pregnancy is, however, rare. Complications of CD occur with the same probability as in non-pregnant patients [14]. Pregnant women with CD tend to show a reduced disease activity. Thus, pregnancy exerts an inhibitory influence on CD activity [15]. There seems to be a reduced disease activity in the year after pregnancy in comparison to the time before. Immunomodulatory effects during pregnancy can explain this [16]. However, other studies have shown an increase of disease activity during pregnancy, above all, during the last trimester or post partum. This might be explained by the decrease of endogenous corticoid production after birth [17, 18]. In summary, women conceiving during remission will most likely experience pregnancy without worsening disease activities [19].
Int J Colorectal Dis (2014) 29:645–651
Conservative therapy Initially, conservative measures are available for treating uncomplicated courses of Crohn’s disease in both pregnant and non-pregnant patients [4, 20, 21]. The literature on pregnancy and inflammatory bowel diseases (IBD) has thus far been largely restricted to conservative drug therapy. In accordance with guidelines, drugs used during pregnancy are classified as safe, probably safe and contraindicated [22]. With regard to a possible conception, the induction or continuation of remission is at the centre of attention. Meanwhile, it is well recognised that an active disease results in higher risk for mother and child than medical therapy [22]. A complicated course of disease with fistulas or abscesses caused by insufficient medical treatment endangers the course of pregnancy more than adequate medication [5]. The inadequate data available on side effects of drugs during pregnancy is often based on animal experiments. There have been no prospective studies in pregnant CD patients. Nevertheless, patients are warned against toxic side effects during pregnancy in medication information leaflets. It is, however, essential to maintain remission or a relatively inactive disease both during planning parenthood and pregnancy. The risks of an attack on the fetus and mother must be weighed against possible side effects of any drugs (Table 1).
Safe medication High-dose cortisone therapy is initially prescribed when an acute case occurs during pregnancy. Steroids are regarded as safe during pregnancy [23, 24]. An increased risk of lip and palate cleft has only been reported in the first trimester [25]. However, minimising the risks of a severe case for the unborn child is crucial. No data on pregnancy complications or malformations for anti-TNF-alpha antibodies has thus far been published [26, 27]. In the case of many newer drugs, longterm effects on the immune system remain to be inconclusive. Though, it has been noticed that continuing infliximab therapy soon after surgery could decrease the need for further Table 1 Analogous to S3 guidelines on the diagnosis and treatment of Crohn’s disease, 2008 and to The Second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: Special Situations, 2009 Safe
Probably safe
Contraindicated
Mesalazine Anti-TNF-alpha Steroids
Budesonide Thiopurine Cyclosporine, tacrolimus Metronidazole, ciprofloxacin
MTX
Tetracycline, sulfonamides
Int J Colorectal Dis (2014) 29:645–651
operations [28, 29]. Several points must be considered even for drugs regarded as safe. Folic acid substitution is important when administering aminosalicylates like mesalazine or sulfasalazine as folic acid antagonists [19]. Probably safe medication Azathioprine is also regarded a safe drug during pregnancy. The increased risk of low birth weight could only be demonstrated in animal experiments. However, high doses of azathioprine were found to cause malformations in animal experiments [30, 31]. Clinical experience, however, has thus far been limited to the field of rheumatology [32]. There are also two retrospective studies that failed to detect any influence of azathioprine or 6-mercaptopurine on the course of pregnancy [33, 34]. Based on the available data, it is assumed that patients can continue to take azathioprine, if medically prescribed, both during conception and pregnancy. Administering azathioprine during pregnancy is advised should this be the only option to maintain stability. Cyclosporine and tacrolimus are associated with an increase in rates of premature deliveries and low birth weights [35, 36]. Research is yet to determine whether these risks are attributable to heightened disease activity or to medication. Ciprofloxacine and metronidazole belong to the main common antibiotics and are regarded as sufficiently safe during pregnancy. Risks like arthropathies or muscolosceletal malformations were only found in animal experiments, but not in humans. Nevertheless, these antibiotics should only be applied if necessary after the first trimester [37, 38]. Contraindicated medication Methotrexate (MTX) cannot be administered due to its teratogenicity in early pregnancy [32]. Thus, its use is generally avoided in young women, being restricted to those with additional joint involvement. MTX has a long half-life and should therefore be discontinued 3 months before pregnancy commences [39]. However, several studies investigating pregnant rheumatoid arthritis patients under MTX therapy have failed to demonstrate damage such as neural canal defects and deformities of the skull or skeleton [40, 41]. Diagnosis and interventional therapy Diagnosing CD often occurs late because of unspecific symptoms like diarrhoea, stomach ache or weight loss. Especially during pregnancy, nausea, vomiting or stomach ache can feign general pregnancy symptoms and thus, might be misinterpreted. Therefore, an ultrasound or MRI should be applied as examination methods to avoid radiation by conventional X-ray or CT [42, 43].
647
Interventional therapy is gaining impetus, particularly for the typical CD complications, such as abscesses. Formerly, complications were extensively treated by laparotomy with abscess removal and drainage, flowed by many patients receiving bowel resection or even colostomy. Ultrasoundguided abscess puncture and drainage have become vital interventional therapies over the last two decades. Although, this only applies to abscess formations identified as being accessible to puncture. This intervention can improve the patient’s general condition for later elective surgery. Tissues showing marked inflammatory changes are known to have a higher complication rate through relapse and anastomotic leaks [44]. Abscess drainage results in decreasing inflammation and patient regeneration. Thus, operations may be postponed to a later date. Nevertheless, it is often difficult to decide between applying percutaneous drainage or a laparotomy. Only a few studies have examined the success rates of percutaneous drainage [45–49]. One study demonstrates successful percutaneous abscess drainage in 65 % in cases of spontaneous (not postoperative) abscesses [50]. In another study, the success rate was even 96 % (51 of 53 patients). Thus, surgery could be delayed in 50 % of all cases [51]. The extensive variance in these results may be interpreted as difference in location and type of abscess (singular or combined). In case of pregnant patients failing to respond to conservative therapy, interventional procedures should be chosen, allowing for postnatal surgery once abscesses have been successfully drained. To avoid radiation, an ultrasound-assisted drainage should be conducted. Real-time imaging enables continuous puncture control, and results are comparable to CT-assisted drainage [42]. Limitations of the ultrasoundassisted drainage can result from an inadequate display, e.g. because of gas overlapping [52, 53]. During the first and second trimester (during organogenesis), the unborn child is especially sensitive to radiation. Therefore, in this phase, the indication for CT is very strict. Alternatively, in some centres, MRI-assisted procedures are applied. However, because of adverse room conditions, expensive equipement and longer examination, MRI is more challenging and regarded as suboptimal. Role of surgery Though interventional treatment procedures are becoming increasingly important for typical complications like fistulas, abscesses or perforations, they are not adequate in difficult cases. Here, a surgical approach will have to be considered [54]. To date, studies researching possible surgical interventions in pregnant women with a complicated course of CD have been scarce. These have been mainly case studies involving only a small number of patients [55–57]. The difficulty lies in weighing the risks of a complicated case of CD
648
against those emerging from surgery. Finally, typical complications must be expected particularly during active disease [58]. Indications for surgical interventions are identical to those in non-pregnant patients and include obstruction, perforation, abscesses and fistulas [57, 59]. The stage of pregnancy must always be considered when choosing the access path. In advanced pregnancies, mechanical problems like a high uterus and fetal growth are risk factors for intraoperative complications. Bowel resection is often unavoidable in patients with strictures and fistulas [60]. Postoperative complications like anastomotic leaks can be avoided by creating a protective stoma upstream of the primary anastomosis after bowel resection [39]. The general risk for anastomic leak in pregnant patients is between 3.4 and 6 % [61, 62]. However, there is still a residual risk of suture-line leaks. This can increase in cases of particularly severe bowel involvement with purulent peritonitis. Diverting the bowel ends as a split stoma is the safest way to avoid anastomotic leaks that would endanger the lives of mother and child (see subsequent case reports). A caesarean section is recommended if extensive bowel resection is necessary and the unborn child is viable [63]. It is noteworthy that surgical interventions in patients with anorectal fistulas and abscesses have an impact on fertility [64]. As such, the decision is often made to create an enterostoma in order to reduce anorectal CD activity and preserve fertility [56]. There are only a few stoma complications associated with pregnancy, e.g. stoma prolapse, intestinal obstruction and parastomal hernias [65, 66]. Complications of active CD put the lives of mother and child in great jeopardy [59]. As a result, surgical therapy should be performed, if indicated, using an interdisciplinary approach. Role of anaesthesia When surgery is decided, anxieties may arise that are not restricted to the operation as such. Certain risks are associated with anaesthesia during pregnancy. Potential toxic effects of some anaesthetics have been described. These play a role particularly during the first trimester. Surgery should possibly be postponed until the second or third trimester. In these instances, interventional procedures gain momentum. Intraoperative complications in advanced pregnancy are mainly caused by mechanical problems like a high uterus and fetal growth.
Int J Colorectal Dis (2014) 29:645–651
directly ventral to the iliac muscle and directly lateral to the psoas muscle (Fig. 1). Ultrasound-guided pigtail catheter drainage of the pronounced abscess system was not successful (Fig. 2). Consequently, the indication for surgery was established after careful consideration and discussion with the gastroenterologists and obstetricians as well as with the patient herself. Intraoperative inspection revealed chronic inflammatory changes in parts of the terminal ileum with a pronounced fistula system and multilocular abscesses. All abscesses and fistulas were individually opened and debrided, and ileocecal resection was performed. Because of the extensive findings, a split stoma was created to avoid anastomotic leaks. The intraand postoperative course was uneventful. During and after surgery, the fetus was in good condition with regular heart sounds at all times. A follow-up by the gynaecologist also yielded regular findings prior to discharge. There was no need for further prenatal CD specific medication. The patient gave birth to a healthy girl by primary caesarean section. The restoration of bowel continuity was discussed with the patient after the lactation period.
Case 2 A 26-year-old CD patient in the 19th week of gestation was also admitted to our department, with a long disease course in various hospitals and various departments. Conservative management with antibiotic therapy (sultamicillin) was first initiated due to a morphological image analysis raising suspicion of severe inflammatory changes in the terminal ileum with interenteric fistulas and abscess formation (Fig. 3). Abscess drainage was first performed under ultrasound guidance, and antibiotic therapy with sultamicillin was continued. Surgery was indicated, since CD took a progressive course and was refractory to conservative management with antibiotic therapy and pigtail catheter drainage. The obstetricians and
Case 1 A 32-year-old CD patient in the 23rd week of gestation presented herself to the emergency room because of high temperatures and right lower abdominal pain. Conservative (drug) therapy was initially applied after a long disease course with recurrent abscesses and fistulas. However, pelvic imaging (MRI) revealed a striking multilocular abscess system
Fig. 1 Multilocular abscess system directly ventral to the iliac muscle and directly lateral to the psoas muscle. (MRI)
Int J Colorectal Dis (2014) 29:645–651
Fig. 2 Ultrasound-guided pigtail catheter drainage of the pronounced abscess system was not successful. (MRI)
anaesthesiologists were consulted for the perioperative care and surgical planning. On the day of surgery, the obstetrician immediately before surgery performed dose-adjusted tocolysis. Intraoperative inspection revealed severe inflammatory changes in the terminal ileum with interenteric fistulas to the sigmoid colon and abscess formation. Thus the decision was made to perform a terminal ileum resection. A continuity-preserving resection was not considered feasible due to the severity of the findings and the associated risk of an anastomotic leak. A split stoma was created instead. The patient recovered well in the postoperative phase. Stoma transit was rapid. The pregnancy always remained intact. As well as with the previous case, no further prenatal CD medication was required. The patient gave birth to a healthy child by primary caesarean section. The restoration of bowel continuity was successfully performed a year later without further complications since. Case 3 A 32-years-old CD patient was presented in the 21st week of gestation. In an external gastroenterological unit, a blind-
Fig. 3 Severe inflammatory changes in the terminal ileum with interenteric fistulas and abscess formation. (MRI)
649
ending fistula with a retroperitoneal small abscess due to a tight stenosis of the terminal ileum was detected. Within MRI and ultrasound, the small bowel oral to the stenosis was dilated up to 12 mm in diameter. Prednisolone and azathioprine had no effect. As a last resort, a nutritional therapy with enteral feeding was initiated. However, this was to no avail. A decision for surgery was inevitable. The operation was started by laparoscopy. Due to the vast dilatation of the terminal ileum, a sufficient overview was impossible. After conversion to an open procedure, the caecum was mobilised via a small midline incision, the fistula has been cut out of the retroperitoneal tissue; after resection of the Crohn-affected segment, the two bowel ends were extraterritorised through the right lower abdomen as a split stoma under anastomosing the posterior wall. The patient recovered well from surgery and the pregnancy was continued without any further disturbances.
Discussion It is often difficult to choose between conservative drug treatment, interventional therapy and surgical management. This highlights the significance for discussing such decisions in an interdisciplinary team, thus requiring a specialised center for inflammatory bowel diseases. Initially, conservative measures are available for treating uncomplicated courses of Crohn’s disease [4]. However, if the patient develops typical CD complications like abscesses and fistulas, other treatment options must be considered. Interventional therapy becomes a central tenet. Successful abscess decompression can be achieved by ultrasound-guided punctures, and surgical therapy can be postponed to a later time—after delivery, if possible. However, it is preferable to perform ultrasound puncture in order to avoid CT radiation exposure. CT-guided puncture should be reserved for emergency cases [52, 53]. Interventional treatment procedures are not adequate in difficult cases, and a surgical approach will have to be considered. Surgery is often unavoidable in patients with recurrent complicated CD attacks. The difficulty lies in determining the risks of a complicated attack of CD against those of surgery. Indications for surgical interventions are identical to those in non-pregnant patients and include obstruction, perforation, abscesses and fistulas [57, 59]. Complicated CD puts the lives of mother and child in great jeopardy. Consequently, indicated surgery should not be postponed. The risk of an anastomotic leak that would endanger the lives of mother and child can be avoided by creating a split stoma while concomitantly eliminating the CD complication. As such, expert mother care in an interdisciplinary setting usually results in wellbeing for the child as well.
650 Acknowledgments The authors thank Susann Power for translational support of the manuscript.
References 1. Cao Y, Gao F, Liao C, Tan A, Mo Z (2009) Meta-analysis of medical treatment and placebo treatment for preventing postoperative recurrence in Crohn’s disease (CD). Int J Colorectal Dis 24:509 2. Zhang C, Shen Z, Yu C, Li Y (2009) Avoiding misdiagnosis of upper gastrointestinal Crohn’s disease. Int J Colorectal Dis 24:121 3. Garcia-Olmo D, Herreros D, Pascual M, Pascual I, De-La-Quintana P, Trebol J, Garcia-Arranz M (2009) Treatment of enterocutaneous fistula in Crohn’s disease with adipose-derived stem cells: a comparison of protocols with and without cell expansion. Int J Colorectal Dis 24:27 4. Siegmund B, Zeitz M (2009) Inflammatory bowel disease and pregnancy. Z Gastroenterol 47:1069 5. Khosla R, Willoughby CP, Jewell DP (1984) Crohn’s disease and pregnancy. Gut 25:52 6. Hudson M, Flett G, Sinclair TS, Brunt PW, Templeton A, Mowat NA (1997) Fertility and pregnancy in inflammatory bowel disease. Int J Gynaecol Obstet 58:229 7. Fonager K, Sørensen HT, Olsen J, Dahlerup JF, Rasmussen SN (1998) Pregnancy outcome for women with Crohn’s disease: a follow-up study based on linkage between national registries. Am J Gastroenterol 93:2426 8. Timmer A, Bauer A, Dignass A, Rogler G (2007) Sexual function in persons with inflammatory bowel disease: a survey with matched controls. Clin Gastroenterol Hepatol 5:87 9. Miller JP (1986) Inflammatory bowel disease in pregnancy: a review. J R Soc Med 79:221 10. Alstead EM (2002) Inflammatory bowel disease in pregnancy. Postgrad Med J 78:23 11. Moser MA, Okun NB, Mayes DC, Bailey RJ (2000) Crohn’s disease, pregnancy, and birth weight. Am J Gastroenterol 95:1021 12. Kornfeld D, Cnattingius S, Ekbom A (1997) Pregnancy outcomes in women with inflammatory bowel disease–a population-based cohort study. Am J Obstet Gynecol 177:942 13. Heetun ZS, Byrnes C, Neary P, O’Morain C (2007) Review article: reproduction in the patient with inflammatory bowel disease. Aliment Pharmacol Ther 26:513 14. Wulfeck D, Williams T, Amin A, Huang TY (1994) Crohn’s disease with unusual enterouterine fistula in pregnancy. J Ky Med Assoc 92: 267 15. Castiglione F, Pignata S, Morace F, Sarubbi A, Baratta MA, D’Agostino L, D’Arienzo A, Mazzacca G (1996) Effect of pregnancy on the clinical course of a cohort of women with inflammatory bowel disease. Ital J Gastroenterol 28:199 16. Buyon JP (1998) The effects of pregnancy on autoimmune diseases. J Leukoc Biol 63:281 17. Gennuso R (1985) Crohn’s disease and pregnancy: a literature study. Mt Sinai J Med 52:398 18. Sorokin JJ, Levine SM (1983) Pregnancy and inflammatory bowel disease: a review of the literature. Obstet Gynecol 62:247 19. Caprilli R, Gassull MA, Escher JC, Moser G, Munkholm P, Forbes A, Hommes DW, Lochs H, Angelucci E, Cocco A, Vucelic B, Hildebrand H, Kolacek S, Riis L, Lukas M, de Franchis R, Hamilton M, Jantschek G, Michetti P (2006) u. a. European evidence based consensus on the diagnosis and management of Crohn’s disease: special situations. Gut 55(Suppl 1):i36 20. Kraemer M, Kirschmeier A, Marth T (2008) Perioperative adjuvant therapy with infliximab in complicated anal Crohn’s disease. Int J Colorectal Dis 23:965
Int J Colorectal Dis (2014) 29:645–651 21. Rizzo G, Armuzzi A, Pugliese D, Verbo A, Papa A, Mattana C, Rapaccini GL, Guidi L, Coco C (2011) Anti-TNF-alpha therapies do not increase early postoperative complications in patients with inflammatory bowel disease. An Italian single-center experience. Int J Colorectal Dis 26:1435 22. Hoffmann JC, Preiss JC, Autschbach F, Buhr HJ, Häuser W, Herrlinger K, Höhne W, Koletzko S, Krieglstein CF, Kruis W, Matthes H, Moser G, Reinshagen M, Rogler G, Schreiber S, Schreyer AG, Sido B, Siegmund B, Stallmach A (2008) u. a. [Clinical practice guideline on diagnosis and treatment of Crohn’s disease]. Z Gastroenterol 46:1094 23. Beaulieu DB, Ananthakrishnan AN, Issa M, Rosenbaum L, Skaros S, Newcomer JR, Kuhlmann RS, Otterson MF, Emmons J, Knox J, Binion DG (2009) Budesonide induction and maintenance therapy for Crohn’s disease during pregnancy. Inflamm Bowel Dis 15:25 24. Norjavaara E, de Verdier MG (2003) Normal pregnancy outcomes in a population-based study including 2,968 pregnant women exposed to budesonide. J Allergy Clin Immunol 111:736 25. Koren G, Pastuszak A, Ito S (1998) Drugs in pregnancy. N Engl J Med 338:1128 26. Berthelot J-M, De Bandt M, Goupille P, Solau-Gervais E, Lioté F, Goeb V, Azaïs I, Martin A, Pallot-Prades B, Maugars Y, Mariette X (2009) Exposition to anti-TNF drugs during pregnancy: outcome of 15 cases and review of the literature. Joint Bone Spine 76:28 27. Mishkin DS, Van Deinse W, Becker JM, Farraye FA (2006) Successful use of adalimumab (Humira) for Crohn’s disease in pregnancy. Inflamm Bowel Dis 12:827 28. Yamamoto T, Watanabe T (2013) Strategies for the prevention of postoperative recurrence of Crohn’s disease. Color Dis 43:1141 29. Sakuraba A, Sato T, Matsukawa H, Okamoto S, Takaishi H, Ogata H, Iwao Y, Hibi T (2012) The use of infliximab in the prevention of postsurgical recurrence in polysurgery Crohn’s disease patients: a pilot open-labeled prospective study. Int J Colorectal Dis 27:947 30. Mosesso P, Palitti F (1993) The genetic toxicology of 6mercaptopurine. Mutat Res 296:279 31. Platzek T, Bochert G (1996) Dose-response relationship of teratogenicity and prenatal-toxic risk estimation of 6-mercaptopurine riboside in mice. Teratog Carcinog Mutagen 16:169 32. Bermas BL, Hill JA (1995) Effects of immunosuppressive drugs during pregnancy. Arthritis Rheum 38:1722 33. Alstead EM, Ritchie JK, Lennard-Jones JE, Farthing MJ, Clark ML (1990) Safety of azathioprine in pregnancy in inflammatory bowel disease. Gastroenterology 99:443 34. Francella A, Dyan A, Bodian C, Rubin P, Chapman M, Present DH (2003) The safety of 6-mercaptopurine for childbearing patients with inflammatory bowel disease: a retrospective cohort study. Gastroenterology 124:9 35. Bar Oz B, Hackman R, Einarson T, Koren G (2001) Pregnancy outcome after cyclosporine therapy during pregnancy: a metaanalysis. Transplantation 71:1051 36. Radomski JS, Moritz MJ, Muñoz SJ, Cater JR, Jarrell BE, Armenti VT (1995) National Transplantation Pregnancy Registry: analysis of pregnancy outcomes in female liver transplant recipients. Liver Transpl Surg 1:281 37. Burtin P, Taddio A, Ariburnu O, Einarson TR, Koren G (1995) Safety of metronidazole in pregnancy: a meta-analysis. Am J Obstet Gynecol 172:525 38. Loebstein R, Addis A, Ho E, Andreou R, Sage S, Donnenfeld AE, Schick B, Bonati M, Moretti M, Lalkin A, Pastuszak A, Koren G (1998) Pregnancy outcome following gestational exposure to fluoroquinolones: a multicenter prospective controlled study. Antimicrob Agents Chemother 42:1336 39. Kane P (2000) Reproductive health needs worldwide: constraints to fertility control. Reprod Fertil Dev 12:435 40. Kozlowski RD, Steinbrunner JV, MacKenzie AH, Clough JD, Wilke WS, Segal AM (1990) Outcome of first-trimester exposure to low-
Int J Colorectal Dis (2014) 29:645–651
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
dose methotrexate in eight patients with rheumatic disease. Am J Med 88:589 Martínez Lopez JA, Loza E, Carmona L (2009) Systematic review on the safety of methotrexate in rheumatoid arthritis regarding the reproductive system (fertility, pregnancy, and breastfeeding). Clin Exp Rheumatol 27:678 Maconi G, Sampietro GM, Sartani A, Bianchi Porro G (2008) Bowel ultrasound in Crohn’s disease: surgical perspective. Int J Colorectal Dis 23:339 Shoenut JP, Semelka RC, Silverman R, Yaffe CS, Micflikier AB (1993) MRI in the diagnosis of Crohn’s disease in two pregnant women. J Clin Gastroenterol 17:244 Yamamoto T, Allan RN, Keighley MR (2000) Risk factors for intraabdominal sepsis after surgery in Crohn’s disease. Dis Colon Rectum 43:1141 Bafford AC, Coakley B, Powers S, Greenwald D, Ha CY, Weintraub J, Chessin DB, Gorfine SR, Bauer JJ (2012) The clinical impact of preoperative percutaneous drainage of abdominopelvic abscesses in patients with Crohn’s disease. Int J Colorectal Dis 27:953 Gutierrez A, Lee H, Sands BE (2006) Outcome of surgical versus percutaneous drainage of abdominal and pelvic abscesses in Crohn’s disease. Am J Gastroenterol 101:2283 Golfieri R, Cappelli A, Giampalma E, Rizzello F, Gionchetti P, Laureti S, Poggioli G, Campieri M (2006) CT-guided percutaneous pelvic abscess drainage in Crohn’s disease. Tech Coloproctol 10:99 Müller-Wille R, Iesalnieks I, Dornia C, Ott C, Jung EM, Friedrich C, Schill G, Hoffstetter P, Zorger N, Schreyer AG (2011) Influence of percutaneous abscess drainage on severe postoperative septic complications in patients with Crohn’s disease. Int J Colorectal Dis 26:769 Xie Y, Zhu W, Li N, Li J (2012) The outcome of initial percutaneous drainage versus surgical drainage for intra-abdominal abscesses in Crohn’s disease. Int J Colorectal Dis 27:199 Da Luz MA, Stocchi L, Tan E, Tekkis PP, Fazio VW (2009) Outcomes of Crohn’s disease presenting with abdominopelvic abscess. Dis Colon Rectum 52:906 Gervais DA, Hahn PF, O’Neill MJ, Mueller PR (2002) Percutaneous abscess drainage in Crohn disease: technical success and short- and long-term outcomes during 14 years. Radiology 222:645 Gervais DA, Brown SD, Connolly SA, Brec SL, Harisinghani MG, Mueller PR (2004) Percutaneous imaging-guided abdominal and pelvic abscess drainage in children. Radiographics 24:737
651 53. Clark RA, Towbin R (1983) Abscess drainage with CT and ultrasound guidance. Radiol Clin N Am 21:445 54. Scarpa M, Mescoli C, Rugge M, D’Incà R, Ruffolo C, Polese L, D’Amico DF, Sturniolo GC, Angriman I (2009) Restorative proctocolectomy for inflammatory bowel disease: the Padova prognostic score for colitis in predicting long-term outcome and quality of life. Int J Colorectal Dis 24:1049 55. Da Fonseca LM, Castro FV, Celani MFS, da Silva RG, Lacerda-Filho A (2008) Ileo-uterine fistula during pregnancy in a patient with Crohn disease: an uncommon complication. ANZ J Surg 78:1142 56. Takahashi K, Funayama Y, Fukushima K, Shibata C, Ogawa H, Kumagai E, Sasaki I (2007) Pregnancy and delivery in patients with enterostomy due to anorectal complications from Crohn’s disease. Int J Colorectal Dis 22:313 57. Hill J, Clark A, Scott NA (1997) Surgical treatment of acute manifestations of Crohn’s disease during pregnancy. J R Soc Med 90:64 58. Egberts J-H, Stroeh A, Alkatout I, Goumas FA, Brand PA, Schafmayer C, Becker T, Schniewind B (2011) Preoperative risk evaluation of postoperative morbidity in IBD patients—impact of the POSSUM score. Int J Colorectal Dis 26:783 59. Subhani JM, Hamiliton MI (1998) Review article: the management of inflammatory bowel disease during pregnancy. Aliment Pharmacol Ther 12:1039 60. Rink AD, Fischer IR, Vestweber B, Vestweber K-H (2013) Longterm outcome of laparoscopic ileocecal resection for Crohn’s disease before the era of biologics. Int J Colorectal Dis 29:127 61. Alves A, Panis Y, Bouhnik Y, Pocard M, Vicaut E, Valleur P (2007) Risk factors for intra-abdominal septic complications after a first ileocecal resection for Crohn’s disease: a multivariate analysis in 161 consecutive patients. Dis Colon Rectum 50:331 62. Isbister WH (2001) Anastomotic leak in colorectal surgery: a single surgeon’s experience. ANZ J Surg 71:516 63. Katz JA, Pore G (2001) Inflammatory bowel disease and pregnancy. Inflamm Bowel Dis 7:146 64. Wikland M, Jansson I, Asztély M, Palselius I, Svaninger G, Magnusson O, Hultén L (1990) Gynaecological problems related to anatomical changes after conventional proctocolectomy and ileostomy. Int J Colorectal Dis 5:49 65. Nicholl MC, Thompson JM, Cocks PS (1993) Stomas and pregnancy. Aust N Z J Obstet Gynaecol 33:322 66. Van Horn C, Barrett P (1997) Pregnancy, delivery, and postpartum experiences of fifty-four women with ostomies. J Wound Ostomy Continence Nurs 24:151
REVIEW
Therapy of complicated Crohn’s disease during pregnancy—an interdisciplinary challenge C. Seifarth & J. P. Ritz & U. Pohlen & A. J. Kroesen & B. Siegmund & B. Frericks & H. J. Buhr
Accepted: 18 April 2014 / Published online: 4 May 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Background Severe courses of Crohn’s disease (CD) during pregnancy are rare. However, if occurring, the risk of miscarriage and low birth weight is increased. At present, only limited data is available on the treatment of CD during pregnancy. In particular, there are no standard guidelines for surgical therapy. Nevertheless, surgery is often unavoidable if complications during the course of the disease arise. Purpose This study provides a critical overview of conventional and interventional treatment options for CD complications during pregnancy and analyses the surgical experience gained thus far. For illustrative purposes, clinical cases of three young women with a severe clinical course during pregnancy are presented.
C. Seifarth (*) : H. J. Buhr Department of General, Visceral and Vascular Surgery, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany e-mail: [email protected] J. P. Ritz Center of General and Visceral Surgery, Helios Kliniken, Schwerin, Germany U. Pohlen Department of General, Visceral and Vascular Surgery, Ortenau Klinikum, Offenburg-Gengenbach, Germany A. J. Kroesen Department of Gereral, Visceral Surgery and Traumatology, Krankenhaus Porz am Rhein, Koeln, Germany B. Siegmund Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité – Universitätsmedizin Berlin, Berlin, Germany B. Frericks Department of Radiology, DRK Klikum Westend, Berlin, Germany
Methods After treatment-refractory for conservative and interventional measures, surgery remained as the only treatment option. In all cases, a split stoma was created after resection to avoid anastomotic leaks that would endanger the lives of mother and child. The postoperative course of all three patients was uneventful, and pregnancy remained intact until delivery. No further CD specific medication was required before birth. Conclusions The management of CD patients during pregnancy requires close interdisciplinary co-operation between gastroenterologists, obstetricians, anaesthetists and visceral surgeons. For the protection of mother and child treatment should thus be delivered in a specialised centre. This article demonstrates the advantages of surgical therapy by focusing on alleviating CD complaints and preventing postoperative complications. Keywords Crohn’s disease . Pregnancy . Surgery . Interventional therapy . Conservative therapy . Case report
Introduction Like ulcerative colitis, Crohn’s disease (CD) is a chronic inflammatory bowel disease. It can affect all segments of the gastrointestinal tract but occurs most often in the small bowel, the terminal ileum and the colon [1, 2]. Typical symptoms include tiredness, lower abdominal pain, fever and diarrhoea. The disease may also take a complicated course involving the formation of fistulas, abscesses and strictures [3]. The described symptoms and complications occur in both pregnant and non-pregnant patients. Preference is given to drug therapy in both groups of patients. Lately, the focus has shifted to interventional and surgical treatment measures in patients with a complicated case of the disease. However, several points must be considered in association with pregnancy. The initial
646
manifestation of CD mainly affects young women of childbearing age. Many experience anxiety about a possible pregnancy and an attack of CD with its associated risks. Patients often fear that pregnancy might induce an attack [4]. Furthermore, therapy during an acute CD attack in pregnancy is problematic. Here, it is crucial to consider the advantages and disadvantages of conservative, interventional and surgical therapy and their respective risks. This study presents a critical overview of the distinctive features and therapy of complicated CD cases during pregnancy. It discusses diagnostic clarification as well as conservative, interventional and surgical therapy with reference to the existing pregnancy in each case.
Fertility and course of pregnancy A favuorable time for conception is a phase of spontaneous or drug-induced remission. Whilst patients in remission do not seem to have impaired fertility, active cases of CD are associated with reduced fertility [5, 6]. Various causal factors play a role here: inflammation affecting the fallopian tubes and ovaries or perianal involvement resulting in dyspareunia and loss of libido [7]. Furthermore, depression has been linked to young women with CD and loss of libido [8]. Inflammatory bowel diseases (IBD)-associated dyspareunia, vaginal infections and problems with lubrication can reduce sexual activity and are also associated with depressions [8]. Decisive for the course of pregnancy is the disease activity at its onset. Women who conceive during remission have the same risk of an acute case as non-pregnant women [9]. The risk of an active disease course during pregnancy is higher in those who conceive during active disease, with complications developing in two thirds of all patients [5, 10]. Various studies describe an increased risk of low birth weight and premature delivery in mothers with CD, particularly if an acute case occurs [11, 12]. The first manifestation of the disease also appears to be associated with an increased risk of premature delivery [13]. A complicated course of CD during pregnancy is, however, rare. Complications of CD occur with the same probability as in non-pregnant patients [14]. Pregnant women with CD tend to show a reduced disease activity. Thus, pregnancy exerts an inhibitory influence on CD activity [15]. There seems to be a reduced disease activity in the year after pregnancy in comparison to the time before. Immunomodulatory effects during pregnancy can explain this [16]. However, other studies have shown an increase of disease activity during pregnancy, above all, during the last trimester or post partum. This might be explained by the decrease of endogenous corticoid production after birth [17, 18]. In summary, women conceiving during remission will most likely experience pregnancy without worsening disease activities [19].
Int J Colorectal Dis (2014) 29:645–651
Conservative therapy Initially, conservative measures are available for treating uncomplicated courses of Crohn’s disease in both pregnant and non-pregnant patients [4, 20, 21]. The literature on pregnancy and inflammatory bowel diseases (IBD) has thus far been largely restricted to conservative drug therapy. In accordance with guidelines, drugs used during pregnancy are classified as safe, probably safe and contraindicated [22]. With regard to a possible conception, the induction or continuation of remission is at the centre of attention. Meanwhile, it is well recognised that an active disease results in higher risk for mother and child than medical therapy [22]. A complicated course of disease with fistulas or abscesses caused by insufficient medical treatment endangers the course of pregnancy more than adequate medication [5]. The inadequate data available on side effects of drugs during pregnancy is often based on animal experiments. There have been no prospective studies in pregnant CD patients. Nevertheless, patients are warned against toxic side effects during pregnancy in medication information leaflets. It is, however, essential to maintain remission or a relatively inactive disease both during planning parenthood and pregnancy. The risks of an attack on the fetus and mother must be weighed against possible side effects of any drugs (Table 1).
Safe medication High-dose cortisone therapy is initially prescribed when an acute case occurs during pregnancy. Steroids are regarded as safe during pregnancy [23, 24]. An increased risk of lip and palate cleft has only been reported in the first trimester [25]. However, minimising the risks of a severe case for the unborn child is crucial. No data on pregnancy complications or malformations for anti-TNF-alpha antibodies has thus far been published [26, 27]. In the case of many newer drugs, longterm effects on the immune system remain to be inconclusive. Though, it has been noticed that continuing infliximab therapy soon after surgery could decrease the need for further Table 1 Analogous to S3 guidelines on the diagnosis and treatment of Crohn’s disease, 2008 and to The Second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: Special Situations, 2009 Safe
Probably safe
Contraindicated
Mesalazine Anti-TNF-alpha Steroids
Budesonide Thiopurine Cyclosporine, tacrolimus Metronidazole, ciprofloxacin
MTX
Tetracycline, sulfonamides
Int J Colorectal Dis (2014) 29:645–651
operations [28, 29]. Several points must be considered even for drugs regarded as safe. Folic acid substitution is important when administering aminosalicylates like mesalazine or sulfasalazine as folic acid antagonists [19]. Probably safe medication Azathioprine is also regarded a safe drug during pregnancy. The increased risk of low birth weight could only be demonstrated in animal experiments. However, high doses of azathioprine were found to cause malformations in animal experiments [30, 31]. Clinical experience, however, has thus far been limited to the field of rheumatology [32]. There are also two retrospective studies that failed to detect any influence of azathioprine or 6-mercaptopurine on the course of pregnancy [33, 34]. Based on the available data, it is assumed that patients can continue to take azathioprine, if medically prescribed, both during conception and pregnancy. Administering azathioprine during pregnancy is advised should this be the only option to maintain stability. Cyclosporine and tacrolimus are associated with an increase in rates of premature deliveries and low birth weights [35, 36]. Research is yet to determine whether these risks are attributable to heightened disease activity or to medication. Ciprofloxacine and metronidazole belong to the main common antibiotics and are regarded as sufficiently safe during pregnancy. Risks like arthropathies or muscolosceletal malformations were only found in animal experiments, but not in humans. Nevertheless, these antibiotics should only be applied if necessary after the first trimester [37, 38]. Contraindicated medication Methotrexate (MTX) cannot be administered due to its teratogenicity in early pregnancy [32]. Thus, its use is generally avoided in young women, being restricted to those with additional joint involvement. MTX has a long half-life and should therefore be discontinued 3 months before pregnancy commences [39]. However, several studies investigating pregnant rheumatoid arthritis patients under MTX therapy have failed to demonstrate damage such as neural canal defects and deformities of the skull or skeleton [40, 41]. Diagnosis and interventional therapy Diagnosing CD often occurs late because of unspecific symptoms like diarrhoea, stomach ache or weight loss. Especially during pregnancy, nausea, vomiting or stomach ache can feign general pregnancy symptoms and thus, might be misinterpreted. Therefore, an ultrasound or MRI should be applied as examination methods to avoid radiation by conventional X-ray or CT [42, 43].
647
Interventional therapy is gaining impetus, particularly for the typical CD complications, such as abscesses. Formerly, complications were extensively treated by laparotomy with abscess removal and drainage, flowed by many patients receiving bowel resection or even colostomy. Ultrasoundguided abscess puncture and drainage have become vital interventional therapies over the last two decades. Although, this only applies to abscess formations identified as being accessible to puncture. This intervention can improve the patient’s general condition for later elective surgery. Tissues showing marked inflammatory changes are known to have a higher complication rate through relapse and anastomotic leaks [44]. Abscess drainage results in decreasing inflammation and patient regeneration. Thus, operations may be postponed to a later date. Nevertheless, it is often difficult to decide between applying percutaneous drainage or a laparotomy. Only a few studies have examined the success rates of percutaneous drainage [45–49]. One study demonstrates successful percutaneous abscess drainage in 65 % in cases of spontaneous (not postoperative) abscesses [50]. In another study, the success rate was even 96 % (51 of 53 patients). Thus, surgery could be delayed in 50 % of all cases [51]. The extensive variance in these results may be interpreted as difference in location and type of abscess (singular or combined). In case of pregnant patients failing to respond to conservative therapy, interventional procedures should be chosen, allowing for postnatal surgery once abscesses have been successfully drained. To avoid radiation, an ultrasound-assisted drainage should be conducted. Real-time imaging enables continuous puncture control, and results are comparable to CT-assisted drainage [42]. Limitations of the ultrasoundassisted drainage can result from an inadequate display, e.g. because of gas overlapping [52, 53]. During the first and second trimester (during organogenesis), the unborn child is especially sensitive to radiation. Therefore, in this phase, the indication for CT is very strict. Alternatively, in some centres, MRI-assisted procedures are applied. However, because of adverse room conditions, expensive equipement and longer examination, MRI is more challenging and regarded as suboptimal. Role of surgery Though interventional treatment procedures are becoming increasingly important for typical complications like fistulas, abscesses or perforations, they are not adequate in difficult cases. Here, a surgical approach will have to be considered [54]. To date, studies researching possible surgical interventions in pregnant women with a complicated course of CD have been scarce. These have been mainly case studies involving only a small number of patients [55–57]. The difficulty lies in weighing the risks of a complicated case of CD
648
against those emerging from surgery. Finally, typical complications must be expected particularly during active disease [58]. Indications for surgical interventions are identical to those in non-pregnant patients and include obstruction, perforation, abscesses and fistulas [57, 59]. The stage of pregnancy must always be considered when choosing the access path. In advanced pregnancies, mechanical problems like a high uterus and fetal growth are risk factors for intraoperative complications. Bowel resection is often unavoidable in patients with strictures and fistulas [60]. Postoperative complications like anastomotic leaks can be avoided by creating a protective stoma upstream of the primary anastomosis after bowel resection [39]. The general risk for anastomic leak in pregnant patients is between 3.4 and 6 % [61, 62]. However, there is still a residual risk of suture-line leaks. This can increase in cases of particularly severe bowel involvement with purulent peritonitis. Diverting the bowel ends as a split stoma is the safest way to avoid anastomotic leaks that would endanger the lives of mother and child (see subsequent case reports). A caesarean section is recommended if extensive bowel resection is necessary and the unborn child is viable [63]. It is noteworthy that surgical interventions in patients with anorectal fistulas and abscesses have an impact on fertility [64]. As such, the decision is often made to create an enterostoma in order to reduce anorectal CD activity and preserve fertility [56]. There are only a few stoma complications associated with pregnancy, e.g. stoma prolapse, intestinal obstruction and parastomal hernias [65, 66]. Complications of active CD put the lives of mother and child in great jeopardy [59]. As a result, surgical therapy should be performed, if indicated, using an interdisciplinary approach. Role of anaesthesia When surgery is decided, anxieties may arise that are not restricted to the operation as such. Certain risks are associated with anaesthesia during pregnancy. Potential toxic effects of some anaesthetics have been described. These play a role particularly during the first trimester. Surgery should possibly be postponed until the second or third trimester. In these instances, interventional procedures gain momentum. Intraoperative complications in advanced pregnancy are mainly caused by mechanical problems like a high uterus and fetal growth.
Int J Colorectal Dis (2014) 29:645–651
directly ventral to the iliac muscle and directly lateral to the psoas muscle (Fig. 1). Ultrasound-guided pigtail catheter drainage of the pronounced abscess system was not successful (Fig. 2). Consequently, the indication for surgery was established after careful consideration and discussion with the gastroenterologists and obstetricians as well as with the patient herself. Intraoperative inspection revealed chronic inflammatory changes in parts of the terminal ileum with a pronounced fistula system and multilocular abscesses. All abscesses and fistulas were individually opened and debrided, and ileocecal resection was performed. Because of the extensive findings, a split stoma was created to avoid anastomotic leaks. The intraand postoperative course was uneventful. During and after surgery, the fetus was in good condition with regular heart sounds at all times. A follow-up by the gynaecologist also yielded regular findings prior to discharge. There was no need for further prenatal CD specific medication. The patient gave birth to a healthy girl by primary caesarean section. The restoration of bowel continuity was discussed with the patient after the lactation period.
Case 2 A 26-year-old CD patient in the 19th week of gestation was also admitted to our department, with a long disease course in various hospitals and various departments. Conservative management with antibiotic therapy (sultamicillin) was first initiated due to a morphological image analysis raising suspicion of severe inflammatory changes in the terminal ileum with interenteric fistulas and abscess formation (Fig. 3). Abscess drainage was first performed under ultrasound guidance, and antibiotic therapy with sultamicillin was continued. Surgery was indicated, since CD took a progressive course and was refractory to conservative management with antibiotic therapy and pigtail catheter drainage. The obstetricians and
Case 1 A 32-year-old CD patient in the 23rd week of gestation presented herself to the emergency room because of high temperatures and right lower abdominal pain. Conservative (drug) therapy was initially applied after a long disease course with recurrent abscesses and fistulas. However, pelvic imaging (MRI) revealed a striking multilocular abscess system
Fig. 1 Multilocular abscess system directly ventral to the iliac muscle and directly lateral to the psoas muscle. (MRI)
Int J Colorectal Dis (2014) 29:645–651
Fig. 2 Ultrasound-guided pigtail catheter drainage of the pronounced abscess system was not successful. (MRI)
anaesthesiologists were consulted for the perioperative care and surgical planning. On the day of surgery, the obstetrician immediately before surgery performed dose-adjusted tocolysis. Intraoperative inspection revealed severe inflammatory changes in the terminal ileum with interenteric fistulas to the sigmoid colon and abscess formation. Thus the decision was made to perform a terminal ileum resection. A continuity-preserving resection was not considered feasible due to the severity of the findings and the associated risk of an anastomotic leak. A split stoma was created instead. The patient recovered well in the postoperative phase. Stoma transit was rapid. The pregnancy always remained intact. As well as with the previous case, no further prenatal CD medication was required. The patient gave birth to a healthy child by primary caesarean section. The restoration of bowel continuity was successfully performed a year later without further complications since. Case 3 A 32-years-old CD patient was presented in the 21st week of gestation. In an external gastroenterological unit, a blind-
Fig. 3 Severe inflammatory changes in the terminal ileum with interenteric fistulas and abscess formation. (MRI)
649
ending fistula with a retroperitoneal small abscess due to a tight stenosis of the terminal ileum was detected. Within MRI and ultrasound, the small bowel oral to the stenosis was dilated up to 12 mm in diameter. Prednisolone and azathioprine had no effect. As a last resort, a nutritional therapy with enteral feeding was initiated. However, this was to no avail. A decision for surgery was inevitable. The operation was started by laparoscopy. Due to the vast dilatation of the terminal ileum, a sufficient overview was impossible. After conversion to an open procedure, the caecum was mobilised via a small midline incision, the fistula has been cut out of the retroperitoneal tissue; after resection of the Crohn-affected segment, the two bowel ends were extraterritorised through the right lower abdomen as a split stoma under anastomosing the posterior wall. The patient recovered well from surgery and the pregnancy was continued without any further disturbances.
Discussion It is often difficult to choose between conservative drug treatment, interventional therapy and surgical management. This highlights the significance for discussing such decisions in an interdisciplinary team, thus requiring a specialised center for inflammatory bowel diseases. Initially, conservative measures are available for treating uncomplicated courses of Crohn’s disease [4]. However, if the patient develops typical CD complications like abscesses and fistulas, other treatment options must be considered. Interventional therapy becomes a central tenet. Successful abscess decompression can be achieved by ultrasound-guided punctures, and surgical therapy can be postponed to a later time—after delivery, if possible. However, it is preferable to perform ultrasound puncture in order to avoid CT radiation exposure. CT-guided puncture should be reserved for emergency cases [52, 53]. Interventional treatment procedures are not adequate in difficult cases, and a surgical approach will have to be considered. Surgery is often unavoidable in patients with recurrent complicated CD attacks. The difficulty lies in determining the risks of a complicated attack of CD against those of surgery. Indications for surgical interventions are identical to those in non-pregnant patients and include obstruction, perforation, abscesses and fistulas [57, 59]. Complicated CD puts the lives of mother and child in great jeopardy. Consequently, indicated surgery should not be postponed. The risk of an anastomotic leak that would endanger the lives of mother and child can be avoided by creating a split stoma while concomitantly eliminating the CD complication. As such, expert mother care in an interdisciplinary setting usually results in wellbeing for the child as well.
650 Acknowledgments The authors thank Susann Power for translational support of the manuscript.
References 1. Cao Y, Gao F, Liao C, Tan A, Mo Z (2009) Meta-analysis of medical treatment and placebo treatment for preventing postoperative recurrence in Crohn’s disease (CD). Int J Colorectal Dis 24:509 2. Zhang C, Shen Z, Yu C, Li Y (2009) Avoiding misdiagnosis of upper gastrointestinal Crohn’s disease. Int J Colorectal Dis 24:121 3. Garcia-Olmo D, Herreros D, Pascual M, Pascual I, De-La-Quintana P, Trebol J, Garcia-Arranz M (2009) Treatment of enterocutaneous fistula in Crohn’s disease with adipose-derived stem cells: a comparison of protocols with and without cell expansion. Int J Colorectal Dis 24:27 4. Siegmund B, Zeitz M (2009) Inflammatory bowel disease and pregnancy. Z Gastroenterol 47:1069 5. Khosla R, Willoughby CP, Jewell DP (1984) Crohn’s disease and pregnancy. Gut 25:52 6. Hudson M, Flett G, Sinclair TS, Brunt PW, Templeton A, Mowat NA (1997) Fertility and pregnancy in inflammatory bowel disease. Int J Gynaecol Obstet 58:229 7. Fonager K, Sørensen HT, Olsen J, Dahlerup JF, Rasmussen SN (1998) Pregnancy outcome for women with Crohn’s disease: a follow-up study based on linkage between national registries. Am J Gastroenterol 93:2426 8. Timmer A, Bauer A, Dignass A, Rogler G (2007) Sexual function in persons with inflammatory bowel disease: a survey with matched controls. Clin Gastroenterol Hepatol 5:87 9. Miller JP (1986) Inflammatory bowel disease in pregnancy: a review. J R Soc Med 79:221 10. Alstead EM (2002) Inflammatory bowel disease in pregnancy. Postgrad Med J 78:23 11. Moser MA, Okun NB, Mayes DC, Bailey RJ (2000) Crohn’s disease, pregnancy, and birth weight. Am J Gastroenterol 95:1021 12. Kornfeld D, Cnattingius S, Ekbom A (1997) Pregnancy outcomes in women with inflammatory bowel disease–a population-based cohort study. Am J Obstet Gynecol 177:942 13. Heetun ZS, Byrnes C, Neary P, O’Morain C (2007) Review article: reproduction in the patient with inflammatory bowel disease. Aliment Pharmacol Ther 26:513 14. Wulfeck D, Williams T, Amin A, Huang TY (1994) Crohn’s disease with unusual enterouterine fistula in pregnancy. J Ky Med Assoc 92: 267 15. Castiglione F, Pignata S, Morace F, Sarubbi A, Baratta MA, D’Agostino L, D’Arienzo A, Mazzacca G (1996) Effect of pregnancy on the clinical course of a cohort of women with inflammatory bowel disease. Ital J Gastroenterol 28:199 16. Buyon JP (1998) The effects of pregnancy on autoimmune diseases. J Leukoc Biol 63:281 17. Gennuso R (1985) Crohn’s disease and pregnancy: a literature study. Mt Sinai J Med 52:398 18. Sorokin JJ, Levine SM (1983) Pregnancy and inflammatory bowel disease: a review of the literature. Obstet Gynecol 62:247 19. Caprilli R, Gassull MA, Escher JC, Moser G, Munkholm P, Forbes A, Hommes DW, Lochs H, Angelucci E, Cocco A, Vucelic B, Hildebrand H, Kolacek S, Riis L, Lukas M, de Franchis R, Hamilton M, Jantschek G, Michetti P (2006) u. a. European evidence based consensus on the diagnosis and management of Crohn’s disease: special situations. Gut 55(Suppl 1):i36 20. Kraemer M, Kirschmeier A, Marth T (2008) Perioperative adjuvant therapy with infliximab in complicated anal Crohn’s disease. Int J Colorectal Dis 23:965
Int J Colorectal Dis (2014) 29:645–651 21. Rizzo G, Armuzzi A, Pugliese D, Verbo A, Papa A, Mattana C, Rapaccini GL, Guidi L, Coco C (2011) Anti-TNF-alpha therapies do not increase early postoperative complications in patients with inflammatory bowel disease. An Italian single-center experience. Int J Colorectal Dis 26:1435 22. Hoffmann JC, Preiss JC, Autschbach F, Buhr HJ, Häuser W, Herrlinger K, Höhne W, Koletzko S, Krieglstein CF, Kruis W, Matthes H, Moser G, Reinshagen M, Rogler G, Schreiber S, Schreyer AG, Sido B, Siegmund B, Stallmach A (2008) u. a. [Clinical practice guideline on diagnosis and treatment of Crohn’s disease]. Z Gastroenterol 46:1094 23. Beaulieu DB, Ananthakrishnan AN, Issa M, Rosenbaum L, Skaros S, Newcomer JR, Kuhlmann RS, Otterson MF, Emmons J, Knox J, Binion DG (2009) Budesonide induction and maintenance therapy for Crohn’s disease during pregnancy. Inflamm Bowel Dis 15:25 24. Norjavaara E, de Verdier MG (2003) Normal pregnancy outcomes in a population-based study including 2,968 pregnant women exposed to budesonide. J Allergy Clin Immunol 111:736 25. Koren G, Pastuszak A, Ito S (1998) Drugs in pregnancy. N Engl J Med 338:1128 26. Berthelot J-M, De Bandt M, Goupille P, Solau-Gervais E, Lioté F, Goeb V, Azaïs I, Martin A, Pallot-Prades B, Maugars Y, Mariette X (2009) Exposition to anti-TNF drugs during pregnancy: outcome of 15 cases and review of the literature. Joint Bone Spine 76:28 27. Mishkin DS, Van Deinse W, Becker JM, Farraye FA (2006) Successful use of adalimumab (Humira) for Crohn’s disease in pregnancy. Inflamm Bowel Dis 12:827 28. Yamamoto T, Watanabe T (2013) Strategies for the prevention of postoperative recurrence of Crohn’s disease. Color Dis 43:1141 29. Sakuraba A, Sato T, Matsukawa H, Okamoto S, Takaishi H, Ogata H, Iwao Y, Hibi T (2012) The use of infliximab in the prevention of postsurgical recurrence in polysurgery Crohn’s disease patients: a pilot open-labeled prospective study. Int J Colorectal Dis 27:947 30. Mosesso P, Palitti F (1993) The genetic toxicology of 6mercaptopurine. Mutat Res 296:279 31. Platzek T, Bochert G (1996) Dose-response relationship of teratogenicity and prenatal-toxic risk estimation of 6-mercaptopurine riboside in mice. Teratog Carcinog Mutagen 16:169 32. Bermas BL, Hill JA (1995) Effects of immunosuppressive drugs during pregnancy. Arthritis Rheum 38:1722 33. Alstead EM, Ritchie JK, Lennard-Jones JE, Farthing MJ, Clark ML (1990) Safety of azathioprine in pregnancy in inflammatory bowel disease. Gastroenterology 99:443 34. Francella A, Dyan A, Bodian C, Rubin P, Chapman M, Present DH (2003) The safety of 6-mercaptopurine for childbearing patients with inflammatory bowel disease: a retrospective cohort study. Gastroenterology 124:9 35. Bar Oz B, Hackman R, Einarson T, Koren G (2001) Pregnancy outcome after cyclosporine therapy during pregnancy: a metaanalysis. Transplantation 71:1051 36. Radomski JS, Moritz MJ, Muñoz SJ, Cater JR, Jarrell BE, Armenti VT (1995) National Transplantation Pregnancy Registry: analysis of pregnancy outcomes in female liver transplant recipients. Liver Transpl Surg 1:281 37. Burtin P, Taddio A, Ariburnu O, Einarson TR, Koren G (1995) Safety of metronidazole in pregnancy: a meta-analysis. Am J Obstet Gynecol 172:525 38. Loebstein R, Addis A, Ho E, Andreou R, Sage S, Donnenfeld AE, Schick B, Bonati M, Moretti M, Lalkin A, Pastuszak A, Koren G (1998) Pregnancy outcome following gestational exposure to fluoroquinolones: a multicenter prospective controlled study. Antimicrob Agents Chemother 42:1336 39. Kane P (2000) Reproductive health needs worldwide: constraints to fertility control. Reprod Fertil Dev 12:435 40. Kozlowski RD, Steinbrunner JV, MacKenzie AH, Clough JD, Wilke WS, Segal AM (1990) Outcome of first-trimester exposure to low-
Int J Colorectal Dis (2014) 29:645–651
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
dose methotrexate in eight patients with rheumatic disease. Am J Med 88:589 Martínez Lopez JA, Loza E, Carmona L (2009) Systematic review on the safety of methotrexate in rheumatoid arthritis regarding the reproductive system (fertility, pregnancy, and breastfeeding). Clin Exp Rheumatol 27:678 Maconi G, Sampietro GM, Sartani A, Bianchi Porro G (2008) Bowel ultrasound in Crohn’s disease: surgical perspective. Int J Colorectal Dis 23:339 Shoenut JP, Semelka RC, Silverman R, Yaffe CS, Micflikier AB (1993) MRI in the diagnosis of Crohn’s disease in two pregnant women. J Clin Gastroenterol 17:244 Yamamoto T, Allan RN, Keighley MR (2000) Risk factors for intraabdominal sepsis after surgery in Crohn’s disease. Dis Colon Rectum 43:1141 Bafford AC, Coakley B, Powers S, Greenwald D, Ha CY, Weintraub J, Chessin DB, Gorfine SR, Bauer JJ (2012) The clinical impact of preoperative percutaneous drainage of abdominopelvic abscesses in patients with Crohn’s disease. Int J Colorectal Dis 27:953 Gutierrez A, Lee H, Sands BE (2006) Outcome of surgical versus percutaneous drainage of abdominal and pelvic abscesses in Crohn’s disease. Am J Gastroenterol 101:2283 Golfieri R, Cappelli A, Giampalma E, Rizzello F, Gionchetti P, Laureti S, Poggioli G, Campieri M (2006) CT-guided percutaneous pelvic abscess drainage in Crohn’s disease. Tech Coloproctol 10:99 Müller-Wille R, Iesalnieks I, Dornia C, Ott C, Jung EM, Friedrich C, Schill G, Hoffstetter P, Zorger N, Schreyer AG (2011) Influence of percutaneous abscess drainage on severe postoperative septic complications in patients with Crohn’s disease. Int J Colorectal Dis 26:769 Xie Y, Zhu W, Li N, Li J (2012) The outcome of initial percutaneous drainage versus surgical drainage for intra-abdominal abscesses in Crohn’s disease. Int J Colorectal Dis 27:199 Da Luz MA, Stocchi L, Tan E, Tekkis PP, Fazio VW (2009) Outcomes of Crohn’s disease presenting with abdominopelvic abscess. Dis Colon Rectum 52:906 Gervais DA, Hahn PF, O’Neill MJ, Mueller PR (2002) Percutaneous abscess drainage in Crohn disease: technical success and short- and long-term outcomes during 14 years. Radiology 222:645 Gervais DA, Brown SD, Connolly SA, Brec SL, Harisinghani MG, Mueller PR (2004) Percutaneous imaging-guided abdominal and pelvic abscess drainage in children. Radiographics 24:737
651 53. Clark RA, Towbin R (1983) Abscess drainage with CT and ultrasound guidance. Radiol Clin N Am 21:445 54. Scarpa M, Mescoli C, Rugge M, D’Incà R, Ruffolo C, Polese L, D’Amico DF, Sturniolo GC, Angriman I (2009) Restorative proctocolectomy for inflammatory bowel disease: the Padova prognostic score for colitis in predicting long-term outcome and quality of life. Int J Colorectal Dis 24:1049 55. Da Fonseca LM, Castro FV, Celani MFS, da Silva RG, Lacerda-Filho A (2008) Ileo-uterine fistula during pregnancy in a patient with Crohn disease: an uncommon complication. ANZ J Surg 78:1142 56. Takahashi K, Funayama Y, Fukushima K, Shibata C, Ogawa H, Kumagai E, Sasaki I (2007) Pregnancy and delivery in patients with enterostomy due to anorectal complications from Crohn’s disease. Int J Colorectal Dis 22:313 57. Hill J, Clark A, Scott NA (1997) Surgical treatment of acute manifestations of Crohn’s disease during pregnancy. J R Soc Med 90:64 58. Egberts J-H, Stroeh A, Alkatout I, Goumas FA, Brand PA, Schafmayer C, Becker T, Schniewind B (2011) Preoperative risk evaluation of postoperative morbidity in IBD patients—impact of the POSSUM score. Int J Colorectal Dis 26:783 59. Subhani JM, Hamiliton MI (1998) Review article: the management of inflammatory bowel disease during pregnancy. Aliment Pharmacol Ther 12:1039 60. Rink AD, Fischer IR, Vestweber B, Vestweber K-H (2013) Longterm outcome of laparoscopic ileocecal resection for Crohn’s disease before the era of biologics. Int J Colorectal Dis 29:127 61. Alves A, Panis Y, Bouhnik Y, Pocard M, Vicaut E, Valleur P (2007) Risk factors for intra-abdominal septic complications after a first ileocecal resection for Crohn’s disease: a multivariate analysis in 161 consecutive patients. Dis Colon Rectum 50:331 62. Isbister WH (2001) Anastomotic leak in colorectal surgery: a single surgeon’s experience. ANZ J Surg 71:516 63. Katz JA, Pore G (2001) Inflammatory bowel disease and pregnancy. Inflamm Bowel Dis 7:146 64. Wikland M, Jansson I, Asztély M, Palselius I, Svaninger G, Magnusson O, Hultén L (1990) Gynaecological problems related to anatomical changes after conventional proctocolectomy and ileostomy. Int J Colorectal Dis 5:49 65. Nicholl MC, Thompson JM, Cocks PS (1993) Stomas and pregnancy. Aust N Z J Obstet Gynaecol 33:322 66. Van Horn C, Barrett P (1997) Pregnancy, delivery, and postpartum experiences of fifty-four women with ostomies. J Wound Ostomy Continence Nurs 24:151
![[Delirium: an interdisciplinary challenge].](/assets/img/hold.png)
