Differenzialdiagnosen von Kolitiden

Neben chronisch-entzündlichen Darmerkrankungen sind die mikroskopische Kolitis (kollagene und lymphozytäre Kolitis), die NSAR-induzierte Kolitis und die Checkpoint-Inhibitor-induzierte Kolitis weitere Kolitis-Differenzialdiagnosen, die sich durch eindeutige histologische Befunde bzw. durch definierte ätiologische Auslöser auszeichnen. Wir geben einen Überblick über Pathogenese, diagnostisch wegweisende Kriterien und empfohlene Therapieansätze.

Kernaussagen

Mikroskopische Kolitis

• Das Leitsymptom der mikroskopischen Kolitis ist die wässrige, typischerweise nachts auftretende Diarrhö.

• Pathognomisch für die LC ist eine Infiltration der Mukosa mit > 20 IEL pro 100 Epithelzellen. Die CC ist durch ein > 10 µm messendes subepitheliales Kollagenband definiert.

• Die enterale Anwendung von Budesonid führt meist zu einer raschen klinischen und histologischen Remission. Es besteht allerdings ein erhebliches Rezidivrisiko nach Absetzen der Therapie.

NSAR-induzierte Kolitis/Enteropathie

• Bei ungeklärten Diarrhöen und (zurückliegendem) NSAR-Gebrauch sollte stets eine NSAR-induzierte Kolitis/Enteropathie differenzialdiagnostisch miteinbezogen werden.

• Schwerpunktmäßig ist neben distalen Dünndarm und Kolon die Ileozäkalregion miteinbezogen. Es können neben entzündeter Schleimhaut demarkierte Ulzerationen vorhanden sein.

• Residuelle narbige Stenosen sollten, sofern zugänglich, bevorzugt endoskopisch mittels TTS-Ballondilatation oder Nadelmesser interveniert werden.

CPI-induzierte Kolitis

• CPI-assoziierte Diarrhöen treten durchschnittlich bei 10 von 100 mit PD1- oder PD-L1-Inhibitoren behandelten Patienten auf. Die Prävalenz sowohl von Diarrhöen als auch Kolitis ist im Gefolge einer Therapie mit dem CTLA4-Inhibitor Ipilimumab höher.

• Für die Diagnosestellung sind zeitlicher Zusammenhang zu einer CPI-Therapie, Ausschluss einer infektiösen Genese und endoskopisch-bioptischer Befund entscheidend.

• Bei milden Verläufen (CTCAE Grad 1) ist die Pausierung der CPI-Therapie optional; bei schweren Verläufen (CTCAE Grad 3 und 4) sollte die CPI-Therapie dauerhaft beendet werden.

• Bei moderaten und schweren Verläufen (CTCAE Grad 2 – 4) ist eine systemische Kortikosteroidtherapie unumgänglich. In steroidrefraktären Fällen kann als „Rescue“-Maßnahme eine Biologikatherapie mit Infliximab oder Vedolizumab in Abhängigkeit von Alter, individuellem Infektrisiko und hämatologischen Begleiterkrankungen erfolgen.

Schlüsselwörter

Mikroskopische Kolitis; NSAR-induzierte Enteropathie; Checkpoint-Inhibitor-induzierte Kolitis

Publication History

Article published online:
16 October 2024

• Literatur

• 1 Tong J, Zheng Q, Zhang C. et al. Erratum: Incidence, prevalence, and temporal trends of microscopic colitis: A systematic review and meta-analysis. Am J Gastroenterol 2015; 110: 1121
• 2 Davidson S, Sjöberg K, Engel PJH. et al. Microscopic colitis in Denmark and Sweden: incidence, putative risk factors, histological assessment and endoscopic activity. Scand J Gastroenterol 2018; 53: 818-824
• 3 Verhaegh BP, Jonkers DM, Driessen A. et al. Incidence of microscopic colitis in the Netherlands. A nationwide population-based study from 2000 to 2012. Dig Liver Dis 2015; 47: 30-36
• 4 Fumery M, Kohut M, Gower-Rousseau C. et al. Incidence, clinical presentation, and associated factors of microscopic colitis in Northern France: A population-based study. Dig Dis Sci 2017; 62: 1571-1579
• 5 Westerlind H, Mellander MR, Bresso F. et al. Dense genotyping of immune-related loci identifies HLA variants associated with increased risk of collagenous colitis. Gut 2017; 66: 421-428
• 6 van Hemert S, Skonieczna-Żydecka K, Loniewski I. et al. Microscopic colitis-microbiome, barrier function and associated diseases. Ann Translat Med 2018; 6: 39
• 7 Kumawat AK, Strid H, Tysk C. et al. Microscopic colitis patients demonstrate a mixed Th17/Tc17 and Th1/Tc1 mucosal cytokine profile. Mol Immunol 2013; 55: 355-364
• 8 Bürgel N, Bojarski C, Mankertz J. et al. Mechanisms of diarrhea in collagenous colitis. Gastroenterology 2002; 123: 433-443
• 9 Escudero-Hernández C, Münch A, Østvik AE. et al. The water channel aquaporin 8 is a critical regulator of intestinal fluid homeostasis in collagenous colitis. J Crohns Colitis 2020; 14: 962-973
• 10 Fernandez-Bañares F, Esteve M, Salas A. et al. Bile acid malabsorption in microscopic colitis and in previously unexplained functional chronic diarrhea. Dig Dis Sci 2001; 46: 2231-2238
• 11 Günther U, Schuppan D, Bauer M. et al. Fibrogenesis and fibrolysis in collagenous colitis. Patterns of procollagen types I and IV, matrix-metalloproteinase-1 and -13, and TIMP-1 gene expression. Am J Pathol 1999; 155: 493-503
• 12 Fernández-Bañares F, de Sousa MR, Salas A. et al. Impact of current smoking on the clinical course of microscopic colitis. Inflammatory Bowel Dis 2013; 19: 1470-1476
• 13 Burke KE, Ananthakrishnan AN, Lochhead P. et al. Identification of menopausal and reproductive risk factors for microscopic colitis – Results from the Nursesʼ Health Study. Gastroenterology 2018; 155: 1764-1775.e1762
• 14 Bonderup OK, Nielsen GL, Dall M. et al. Significant association between the use of different proton pump inhibitors and microscopic colitis: a nationwide Danish case-control study. Aliment Pharmacol Ther 2018; 48: 618-625
• 15 Masclee GM, Coloma PM, Kuipers EJ. et al. Increased risk of microscopic colitis with use of proton pump inhibitors and non-steroidal anti-inflammatory drugs. Am J Gastroenterol 2015; 110: 749-759
• 16 Verhaegh BP, de Vries F, Masclee AA. et al. High risk of drug-induced microscopic colitis with concomitant use of NSAIDs and proton pump inhibitors. Aliment Pharmacol Ther 2016; 43: 1004-1013
• 17 Fernández-Bañares F, de Sousa MR, Salas A. et al. Epidemiological risk factors in microscopic colitis: a prospective case-control study. Inflammatory Bowel Dis 2013; 19: 411-417
• 18 Nimri FM, Muhanna A, Almomani Z. et al. The association between microscopic colitis and celiac disease: a systematic review and meta-analysis. Ann Gastroenterol 2022; 35: 281-289
• 19 Bjørnbak C, Engel PJ, Nielsen PL. et al. Microscopic colitis: clinical findings, topography and persistence of histopathological subgroups. Aliment Pharmacol Ther 2011; 34: 1225-1234
• 20 Madisch A, Miehlke S, Bartosch F. et al. [Microscopic colitis: clinical presentation, treatment and outcome of 494 patients]. Z Gastroenterol 2014; 52: 1062-1065
• 21 Kane JS, Irvine AJ, Derwa Y. et al. Fatigue and its associated factors in microscopic colitis. Therap Adv Gastroenterol 2018; 11: 1756284818799599
• 22 Cotter TG, Binder M, Loftus jr. EV. et al. Development of a microscopic colitis disease activity index: a prospective cohort study. Gut 2018; 67: 441-446
• 23 Kane JS, Rotimi O, Everett SM. et al. Development and validation of a scoring system to identify patients with microscopic colitis. Clin Gastroenterol Hepatol 2015; 13: 1125-1131
• 24 Larsson JK, Sonestedt E, Ohlsson B. et al. The association between the intake of specific dietary components and lifestyle factors and microscopic colitis. Eur J Clin Nutr 2016; 70: 1309-1317
• 25 Calabrese C, Fabbri A, Areni A. et al. Mesalazine with or without cholestyramine in the treatment of microscopic colitis: randomized controlled trial. J Gastroenterol Hepatol 2007; 22: 809-814
• 26 Fine KD, Lee EL. Efficacy of open-label bismuth subsalicylate for the treatment of microscopic colitis. Gastroenterology 1998; 114: 29-36
• 27 Madisch A, Miehlke S, Eichele O. et al. Boswellia serrata extract for the treatment of collagenous colitis. A double-blind, randomized, placebo-controlled, multicenter trial. Int J Colorectal Dis 2007; 22: 1445-1451
• 28 Baert F, Schmit A, DʼHaens G. et al. Budesonide in collagenous colitis: a double-blind placebo-controlled trial with histologic follow-up. Gastroenterology 2002; 122: 20-25
• 29 Miehlke S, Heymer P, Bethke B. et al. Budesonide treatment for collagenous colitis: a randomized, double-blind, placebo-controlled, multicenter trial. Gastroenterology 2002; 123: 978-984
• 30 Miehlke S, Aust D, Mihaly E. et al. Efficacy and safety of budesonide, vs. mesalazine or placebo, as induction therapy for lymphocytic colitis. Gastroenterology 2018; 155: 1795-1804.e3
• 31 Miehlke S, Madisch A, Karimi D. et al. Budesonide is effective in treating lymphocytic colitis: a randomized double-blind placebo-controlled study. Gastroenterology 2009; 136: 2092-2100
• 32 Hjortswang H, Tysk C, Bohr J. et al. Defining clinical criteria for clinical remission and disease activity in collagenous colitis. Inflammatory Bowel Dis 2009; 15: 1875-1881
• 33 Miehlke S, Guagnozzi D, Zabana Y. et al. European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations. United Eur Gastroenterol J 2021; 9: 13-37
• 34 Münch A, Mihaly E, Nagy F. et al. Budesonide as induction therapy for incomplete microscopic colitis: A randomised, placebo-controlled multicentre trial. United Eur Gastroenterol J 2021; 9: 837-847
• 35 Sebastian S, Wilhelm A, Jessica L. et al. Budesonide treatment for microscopic colitis: systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2019; 31: 919-927
• 36 Bonderup OK, Hansen JB, Teglbjaerg PS. et al. Long-term budesonide treatment of collagenous colitis: a randomised, double-blind, placebo-controlled trial. Gut 2009; 58: 68-72
• 37 Miehlke S, Madisch A, Bethke B. et al. Oral budesonide for maintenance treatment of collagenous colitis: a randomized, double-blind, placebo-controlled trial. Gastroenterology 2008; 135: 1510-1516
• 38 Miehlke S, Madisch A, Voss C. et al. Long-term follow-up of collagenous colitis after induction of clinical remission with budesonide. Aliment Pharmacol Ther 2005; 22: 1115-1119
• 39 Cotter TG, Kamboj AK, Hicks SB. et al. Immune modulator therapy for microscopic colitis in a case series of 73 patients. Aliment Pharmacol Ther 2017; 46: 169-174
• 40 Münch A, Bohr J, Vigren L. et al. Lack of effect of methotrexate in budesonide-refractory collagenous colitis. Clin Exp Gastroenterol 2013; 6: 149-152
• 41 Riddell J, Hillman L, Chiragakis L. et al. Collagenous colitis: oral low-dose methotrexate for patients with difficult symptoms: long-term outcomes. J Gastroenterol Hepatol 2007; 22: 1589-1593
• 42 Esteve M, Mahadevan U, Sainz E. et al. Efficacy of anti-TNF therapies in refractory severe microscopic colitis. J Crohns Colitis 2011; 5: 612-618
• 43 Pola S, Fahmy M, Evans E. et al. Successful use of infliximab in the treatment of corticosteroid dependent collagenous colitis. Am J Gastroenterol 2013; 108: 857-858
• 44 Rivière P, Münch A, Michetti P. et al. Vedolizumab in refractory microscopic colitis: An international case series. J Crohns Colitis 2019; 13: 337-340
• 45 Järnerot G, Tysk C, Bohr J. et al. Collagenous colitis and fecal stream diversion. Gastroenterology 1995; 109: 449-455
• 46 Bjarnason I, Hayllar J, MacPherson AJ. et al. Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 1993; 104: 1832-1847
• 47 Allison MC, Howatson AG, Torrance CJ. et al. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. N Engl J Med 1992; 327: 749-754
• 48 Laine L, Curtis SP, Langman M. et al. Lower gastrointestinal events in a double-blind trial of the cyclo-oxygenase-2 selective inhibitor etoricoxib and the traditional nonsteroidal anti-inflammatory drug diclofenac. Gastroenterology 2008; 135: 1517-1525
• 49 Goldstein JL, Eisen GM, Lewis B. et al. Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo. Clin Gastroenterol Hepatol 2005; 3: 133-141
• 50 Hawkey CJ, Ell C, Simon B. et al. Less small-bowel injury with lumiracoxib compared with naproxen plus omeprazole. Clin Gastroenterol Hepatol 2008; 6: 536-544
• 51 Bjarnason I, Fehilly B, Smethurst P. et al. Importance of local versus systemic effects of non-steroidal anti-inflammatory drugs in increasing small intestinal permeability in man. Gut 1991; 32: 275-277
• 52 Reuter BK, Davies NM, Wallace JL. Nonsteroidal anti-inflammatory drug enteropathy in rats: role of permeability, bacteria, and enterohepatic circulation. Gastroenterology 1997; 112: 109-117
• 53 Wallace JL, Syer S, Denou E. et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology 2011; 141: 1314-1322.e5
• 54 Matsuhashi N, Yamada A, Hiraishi M. et al. Multiple strictures of the small intestine after long-term nonsteroidal anti-inflammatory drug therapy. Am J Gastroenterol 1992; 87: 1183-1186
• 55 Ona MA, Patil R, Etienne D. et al. Through-the-scope endoscopic balloon dilatation of a nonsteroidal anti-inflammatory drug-induced diaphragm-like colonic stricture. Ann Gastroenterol 2016; 29: 229
• 56 Bundrick C, Ayyagari R, Tharian B. NSAID-induced colitis and colonic stricture: 1597. ACG 2018; 113: S918
• 57 Slesser AA, Wharton R, Smith GV. et al. Systematic review of small bowel diaphragm disease requiring surgery. Colorectal Dis 2012; 14: 804-813
• 58 Nielsen DL, Juhl CB, Chen IM. et al. Immune checkpoint Inhibitor-Induced diarrhea and Colitis: Incidence and Management. A systematic review and Meta-analysis. Cancer Treat Rev 2022; 109: 102440
• 59 Garg M, Wahid M, Khan FD. Regulation of peripheral and central immunity: Understanding the role of Src homology 2 domain-containing tyrosine phosphatases, SHP-1 & SHP-2. Immunobiology 2020; 225: 151847
• 60 Li K, Yuan Z, Lyu J. et al. PD-1 suppresses TCR-CD8 cooperativity during T-cell antigen recognition. Nat commun 2021; 12: 2746
• 61 Qin S, Xu L, Yi M. et al. Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4. Mol Cancer 2019; 18: 155
• 62 Dougan M, Luoma AM, Dougan SK. et al. Understanding and treating the inflammatory adverse events of cancer immunotherapy. Cell 2021; 184: 1575-1588
• 63 Cohen JV, Dougan M, Zubiri L. et al. Liver biopsy findings in patients on immune checkpoint inhibitors. Modern Pathology 2021; 34: 426-437
• 64 Marthey L, Mateus C, Mussini C. et al. Cancer immunotherapy with anti-CTLA-4 monoclonal antibodies induces an inflammatory bowel disease. J Crohns Colitis 2016; 10: 395-401
• 65 Luoma AM, Suo S, Williams HL. et al. Molecular pathways of colon inflammation induced by cancer immunotherapy. Cell 2020; 182: 655-671.e22
• 66 Sasson SC, Slevin SM, Cheung VTF. et al. Interferon-gamma-producing CD8(+) tissue resident memory T cells are a targetable hallmark of immune checkpoint inhibitor-colitis. Gastroenterology 2021; 161: 1229-1244.e9
• 67 Messmer M, Upreti S, Tarabishy Y. et al. Ipilimumab-induced enteritis without colitis: A new challenge. Case Rep Oncol 2016; 9: 705-713
• 68 Isidro RA, Ruan AB, Gannarapu S. et al. Medication-specific variations in morphological patterns of injury in immune check-point inhibitor-associated colitis. Histopathology 2021; 78: 532-541
• 69 Pai RK, Pai RK, Brown I. et al. The significance of histological activity measurements in immune checkpoint inhibitor colitis. Aliment Pharmacol Ther 2021; 53: 150-159
• 70 Cheung VTF, Gupta T, Olsson-Brown A. et al. Immune checkpoint inhibitor-related colitis assessment and prognosis: can IBD scoring point the way?. Br J Cancer 2020; 123: 207-215
• 71 Mooradian MJ, Wang DY, Coromilas A. et al. Mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitis. J Immunother Cancer 2020; 8
• 72 Abu-Sbeih H, Ali FS, Luo W. et al. Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis. J Immunother Cancer 2018; 6: 95