© Borgis - Postępy Nauk Medycznych 1/2014, s. 36-40
*Edyta Zagórowicz, Marek Bugajski
Ciężki rzut wrzodziejącego zapalenia jelita grubego
Severe ulcerative colitis
Department of Gastroenterology and Hepatology, Medical Center of Postgraduate Education and Department of Gastroenterological Oncology, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa
Head of Department: prof. Jarosław Reguła, MD, PhD
Wrzodziejące zapalenie jelita grubego jest przewlekłą nieswoistą chorobą zapalną jelit, która zwykle zajmuje odbytnicę, a u większości pacjentów także proksymalne odcinki jelita grubego. Lewostronne i rozległe wrzodziejące zapalenie jelita grubego może przebiegać w postaci ciężkiego rzutu z licznymi krwistymi wypróżnieniami, objawami układowymi, takimi jak tachykardia i gorączka, oraz laboratoryjnymi wykładnikami stanu zapalnego. Ciężki rzut wrzodziejącego zapalenia jelita grubego jest stanem zagrożenia życia i wskazaniem do hospitalizacji. Multidyscyplinarna opieka nad pacjentem z udziałem gastroenterologa, chirurga i radiologa, od chwili przyjęcia do szpitala, jest niezbędna do prawidłowego postępowania w tym stanie. Po wykluczeniu czynników zaostrzających zapalenie jelita, przede wszystkim infekcyjnych, w leczeniu pierwszego rzutu podaje się kortykosteroidy. Inne niezbędne elementy postępowania to suplementacja płynów i elektrolitów oraz leczenie przeciwzakrzepowe. Brak odpowiedzi na kortykosteroidy jest wskazaniem do leczenia immunosupresyjnego drugiego wyboru (infliksymabem lub cyklosporyną) lub leczenia operacyjnego. Przeciwwskazania do leczenia immunosupresyjnego należy rozważyć już w chwili przyjęcia pacjenta do szpitala. Oprócz braku odpowiedzi na leczenie farmakologiczne, wskazaniem do proktokolektomii jest nieopanowane krwawienie z jelita grubego oraz toksyczne rozszerzenie okrężnicy.
Ulcerative colitis is a chronic, intermittent inflammatory bowel disease usually involving the rectum and, in majority of patients, proximal bowel segments. Left-sided and extensive colitis may present as severe colitis, with numerous bloody stools, systemic inflammation symptoms including tachycardia and pyrexia, anemia and laboratory markers of inflammation. Severe colitis is a life-threatening condition and indication for hospital treatment. Multidisciplinary care by gastroenterologist, surgeon and radiologist, begun at the admission, is necessary to achieve uncomplicated recovery. Following exclusion of exacerbating factors, and infections in particular, systemic corticosteroids are given as the first line therapy. Fluids and electrolytes supplementation and anti-thrombotic therapy are the other essential measures. Lack of response to steroids is an indication to second line of immunosuppressive drugs (infliximab or cyclosporine) or surgical treatment. Possible contraindications to these drugs should be revised immediately at the admission. In addition to lack of response to first or second line of pharmacologic treatment, indications to proctocolectomy include uncontrolled bleeding and toxic megacolon.
Ulcerative colitis (UC) is an inflammatory bowel disease affecting large bowel’s mucosa. It usually affects the rectum and in continuity, differing in length, proximal parts of large bowel.
The extent of disease is usually described using Montreal classification, presented in table 1 (1). This classification takes into account a maximum extent of inflammatory altered mucosa, as seen in colonoscopy.
Table 1. Montreal classification for UC distribution.
|E1||Proctitis||Involvement limited to the rectum|
|E2||Left-sided||Involvement limited to the colon distal to the splenic flexure|
|E3||Extensive||Involvement extends proximal to the splenic flexure, including pancolitis|
Disease activity, or otherwise exacerbation severity, is defined by Truelove and Witts scale (tab. 2) (2), based on several clinical and laboratory parameters, however it is advisable to endoscopically confirm the presence of active inflammation in large bowel.
Table 2. Truelove and Witts’ criteria of UC exacerbation severity with ECCO modification.
|Bloody stools per day||< 4||≥ 4||≥ 6|
|Pulse||< 90/min||≤ 90/min||> 90/min|
|Temperature||< 37.5°C||< 37.8°C||< 37.8°C|
|Hemoglobin||< 11.5 g%||≥ 10.5 g%||< 10.5 g%|
|ESR||< 20 mm/h||≤ 30 mm/h||> 30 mm/h|
|CRP||normal||≤ 30 mg/l||> 30 mg/l|
A severe exacerbation is defined as 6 or more bloody stools per 24 hours and at least one systemic symptom (tachycardia, fever, anemia, high level of CRP or increased ESR). Severe colitis is a life-threatening condition and an indication for urgent hospitalization in order to perform necessary diagnostic procedures and to initiate intensive treatment.
Patient assessment at hospital admission
It is crucial to take a medical history of present exacerbation symptoms, including extraintestinal manifestations, probable causative factors, current medical treatment (including medications for other conditions) and the course of previous exacerbations. During physical evaluation it is necessary to assess vital signs, hydration, bloating, peristalsis, pain and presence of peritoneal signs. Conditions other than inflammatory bowel disease are necessary to be considered in differential diagnosis of any abdominal symptoms.
Laboratory work-up, which is includes: blood count, basic biochemical tests, albumin ratio, CRP level and ESR. Moreover it is crucial to assess microbiological status, as infections may be a cause of UC exacerbation or may occur simultaneously. This includes Clostridium difficile toxin in stool sample, basic stool culture and cytomegalovirus (CMV) status (either IgG and IgM antibodies, or blood sample PCR for CMV DNA).
Abdominal x-ray should be performed immediately after admission in order to exclude large bowel perforation or toxic megacolon. It is advised to perform an abdominal computed tomography or magnetic resonance, preferably with oral contrast intake (enterography) in patients without prior diagnosis of inflammatory bowel disease to look for Crohn’s disease as a possible cause.
Sigmoidoscopy without prior preparation should be performed shortly after admission in order to assess the endoscopic activity and extent of disease and to perform a forceps biopsy for CMV infection evaluation. Findings typical for pseudomembranous colitis are an indication to start C. difficile infection treatment, however lack of typical findings does not exclude this infection. When deep ulcerations are present, a full colonoscopy should be avoided due to increased risk of perforation and toxic megacolon. Suspicion of the latter, based on radiological findings, is a contraindication to endoscopy.
Approximately 30% of the patients with severe exacerbation of UC do not respond to conventional treatment (intravenous corticosteroids), therefore preparation for second line treatment should start at the admission, so that when first choice treatment fails, the second choice treatment could be started immediately (3, 4). Contraindications to any considered drugs should be excluded. Hypomagnesaemia and hypocholesterolemia are contraindications to cyclosporine treatment, because of increased convulsions risk. Exclusion of tuberculosis (either overt or latent) by chest x-ray and IGRA (interferon-gamma reactivity assay) is necessary prior to infliximab treatment. It is crucial to assess cardiologic status.
Gastrointestinal surgeon’s consultation should be obtained on admission and immediately after performing all examinations necessary to assess the exacerbation severity, as surgeon should be aware of the patient and take part in therapeutical decisions in case of deterioration.
First choice pharmacological therapy
UC prognosis significantly improved in 1950’s, when corticosteroids were introduced to pharmacotherapy (2). Mortality due to severe exacerbation was reduced from 75% in 1933 to 7% in 1950’s, whereas nowadays it has been reduced to 2.9%, or even less than 1% in referral centers. Colectomy risk during hospitalization due to severe exacerbation is 9%, however the total colectomy risk reaches 27% (3-6).
The patient admitted to the hospital due to severe exacerbation should receive intravenous methylprednisolone (40 to 60 mg daily, however no more than 1 mg per 1 kg of body mass), even if oral corticosteroids were administered prior to admission. A response to such treatment occurs in approximately 60% of patients and clinical improvement is very fast – usually remission occurs in 5 to 7 days (7). Intravenous corticotherapy usually lasts 7 to 10 days and the following treatment is based on oral corticosteroid intake, either 40 mg of prednisolone or 32 mg of methylprednisolone daily. After next 10 to 14 days the daily dose is reduced by 5 mg or 4 mg respectively per week, and gradually discontinued.
Intravenous hydration and electrolyte supplementation is of crucial importance. It should be noted that hypokalemia and hypomagnesaemia rise susceptibility to toxic megacolon.
Patients malnourished and those not able to ingest orally should receive nutritional treatment, preferably enteral. Parenteral nutrition should be restricted to patients with lack of tolerance to the former approach. A nil per os diet does not improve the outcome.
There is an increased risk of venous and arterial thrombosis in patients with inflammatory bowel disease. The risk rises when disease is active, therefore during severe exacerbation the antithrombotic prophylaxis is necessary. Subcutaneous low-molecular-weight heparin is most commonly used, despite intestinal bleeding, which is a common symptom of severe exacerbation (8).
The hemoglobin concentration should be maintained over 8-10 g/dl.
Antibiotic therapy does not improve the outcome and should be employed only on suspicion or confirmation of infective cause of exacerbation or perioperatively.
Mesalazine, sulfasalazine and other agents containing 5-aminosalicylic acid do not belong to severe UC exacerbation treatment and they can be withdrawn until clinical improvement is achieved with other agents.
Monitoring the response to treatment
Powyżej zamieściliśmy fragment artykułu, do którego możesz uzyskać pełny dostęp.
Płatny dostęp do wszystkich zasobów Czytelni Medycznej
1. Silverberg MS, Satsangi J, Ahmad T et al.: Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a working party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005; 19 (suppl. A): 5-36.
2. Truelove SC, Witts LJ: Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J 1955; 2: 1041-1048.
3. Edwards FC, Truelove SC: The course and prognosis of ulcerative colitis. Gut 1963; 4: 299-315.
4. Truelove SC, Jewell DP: Intensive intravenous regimen for severe attacks of ulcerative colitis. Lancet 1974; 1: 1067-1070.
5. Jakobovits SL, Travis SP: Management of acute severe colitis. Br Med Bull 2005; 75-76: 131-144.
6. Dinesen LC, Walsh AJ, Protic MN et al.: The pattern and outcome of acute severe colitis. J Crohns Colitis 2010; 4: 431-437.
7. Turner D, Walsh CM, Steinhart AH et al.: Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression. Clin Gastroenterol Hepatol 2007; 5: 103-110.
8. Grainge MJ, West J, Card TR: Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet 2010; 375: 657-663.
9. Travis SP, Farrant JM, Ricketts C et al.: Predicting outcome in severe ulcerative colitis. Gut 1996; 38: 905-910.
10. Dignass A, Lindsay JO, Sturm A et al.: Second European evidence-based consensus on the diagnosis and management of ulcerative colitis. Part 2. Current management. J Crohns Colitis 2012 Dec; 6(10): 991-1030.
11. Gustavsson A, Halfvarson J, Magnuson A et al.: Long-term colectomy rate after intensive intravenous corticosteroid therapy for ulcerative colitis prior to the immunosuppressive treatment era. Am J Gastroenterol 2007; 102: 2513-2519.
12. Maser EA, Deconda D, Lichtiger S et al.: Cyclosporine and infliximab as rescue therapy for each other in patients with steroid-refractory ulcerative colitis. Clin Gastroenterol Hepatol 2008; 6: 1112-1116.
13. Leblanc S, Allez M, Seksik P et al.: Successive treatment with cyclosporine and infliximab in steroid-refractory ulcerative colitis. Am J Gastroenterol 2011; 106: 771-777.
14. Lichtiger S, Present DH, Kornbluth A et al.: Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med 1994; 330: 1841-1845.
15. D’Haens G, Lemmens L, Geboes K et al.: Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology 2001; 120: 1323-1329.
16. Van Assche G, D’Haens G, Noman M et al.: Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Gastroenterology 2003; 125: 1025-1031.
17. Moskovitz DN, Van Assche G, Maenhout B et al.: Incidence of colectomy during long-term follow-up after cyclosporine-induced remission of severe ulcerative colitis. Clin Gastroenterol Hepatol 2006; 4: 760-765.
18. Ogata H, Matsui T, Nakamura M et al.: A randomised dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis. Gut 2006; 55: 1255-1262.
19. Järnerot G, Hertervig E, Friis-Liby I et al.: Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology 2005; 128: 1805-1811.
20. Rutgeerts P, Sandborn WJ, Feagan BG et al.: Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005; 353: 2462-2476.
21. Laharie D, Bourreille A, Branche J et al.: Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label trial. Lancet 2012 Dec 1; 9857: 1909-1915.
22. Sands BE: Fulminant colitis. J Gastrointest Surg 2008; 12: 2157-2159.
23. Pola S, Patel D, Ramamoorthy S et al.: Strategies for the care of adults hospitalized for active ulcerative colitis. Clin Gastroenterol Hepatol 2012 Dec; 10(12): 1315-1325.