Ulcerative Colitis: Experience at a Tertiary Care Center
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1 Original Article Ulcerative Colitis: Experience at a Tertiary Care Center Nasir Khokhar From Division of gastroenterology, Department of Medicine, Shifa International Hospital and Shifa College of Medicine, Islamabad, Pakistan. Correspondence: Dr. Nasir Khokhar Shifa International Hospital Islamabad Pakistan drnkhokhar@yahoo.com Received: January 1, 2005 Accepted: March 22, 2005 ABSTRACT Objective: Ulcerative colitis has a world-wide distribution but its prevalence and clinical patterns in Pakistan are not known. This study was performed to ascertain the clinical patterns of ulcerative colitis in patients referred to a tertiary care center. Methods: All patients presenting with diarrhea, blood in stools and biopsy proven for ulcerative colitis were prospectively followed for clinical features, laboratory findings, endoscopic features and treatment response over the study period. Results: A total of 85 patients were seen and followed for up to 8 years. All had diarrhea with blood in stools. All had numerous white blood cells in stool. Erythrocyte sedimentation rate was elevated in 94 % of patients. More than half had mild disease and distal colitis. All patients responded well to standard treatment with anti-inflammatory drugs.
2 Conclusion: Most patients of ulcerative colitis were mild in severity and had distal involvement. Clinical features in this cohort were similar to patients in most other parts of world. All responded to standard treatment. (Rawal Med J 2005; 30: ) Key Words: Ulcerative colitis, Inflammatory Bowel Disease, Flexible Sigmoidoscopy, Colonoscopy, Mesalazine, 5 ASA INTRODUCTION Inflammatory bowel disease is a common disorder of unknown etiology with worldwide distribution. Ulcerative colitis and inflammatory bowel disease has been noted in the sub continent for past many years. 1,2 In Pakistan, ulcerative colitis has been noted in various parts of the country including Karachi, Multan, Lahore and Peshawar. 3-6 The disease typically presents with loose motions associated with blood and mucus. There are often systemic features of inflammation consisting of fever, malaise and weight loss. With disease progression and longer duration, patients become anemic and develop proteinlosing enteropathy. The studies from Pakistan have shown presence of ulcerative colitis in several parts of the country. However, not much has been known about this condition in this region of Pakistan. This study was therefore aimed to evaluate patients with ulcerative colitis who were referred to a tertiary care center in Islamabad/Rawalpindi area, and were followed for many years. Their clinical features and other patterns and management were reviewed with the course over the years. MATERIAL AND METHODS All patients who presented with abdominal pain, diarrhea, blood in the stool, and were diagnosed on colon biopsy to have ulcerative colitis were included in this study. These patients had complete blood count (CBC), erythrocyte sedimentation rate (ESR), stool routine examination, and either flexible sigmoidoscopy or colonoscopy performed. A 2
3 colon biopsy was standard protocol in these patients. Only those patients who were diagnosed to have ulcerative colitis on histopathology were included in the study. Clinical features, age of onset, extent of involvement of the colon, and extra-intestinal features were noted. Smoking and socio-economic class were also noted. Patients were followed every month or sooner if required and later every 3 months when condition was considered stable. Follow up colonoscopies were performed every 6 months after the initial diagnosis, or whenever necessary according to patients condition. Compliance was monitored closely. All patients were followed up to period of six months to eight years. Clinical severity was classified according to the Truelove and Witts classification. 7 It takes into account the number of motions per day, amount of weight loss, pulse, temperature, hemoglobin concentration and ESR. Endoscopic classification was performed according to the Baron definition. 8 This consists of grade-i (mild activity) which means loss of vascularity with no spontaneous bleeding, grade-ii (moderate activity) showing bleeding on light touch and grade-iii (severe activity) showing spontaneous bleeding on initial inspection. Patients treatment modalities and response for inflammation and exacerbation during this period were noted. Histological diagnosis was made with standard colon biopsies showing crypt abscesses, crypt distortion, acute inflammatory cell infiltrates and other histopathological features 9 by an experienced pathologist. RESULTS A total of 85 patients were diagnosed histologically and followed for a mean period of 5 years. The follow up period ranged from 6 months to 8 years. The demographic and clinical features are summarized in table-1. 3
4 Table-1. Features of Ulcerative Colitis N = 85 Age Range (years) Males 55 Females 30 Duration of symptoms at presentation 3 months - 6 years Smokers (%) 5 (6 %) Hemoglobin (< 10.5) 18 (21 %) High ESR 80 (94 %) Stool WBC 85 (100 %) Increased Eiosinophils 5 (6 %) Increased Platelets 10 (12 %) Distal colitis 55 (65 %) Extra Intestinal Features 40 (47 %) Fifty five patients (65%) showed involvement of the left colon only. Thirty patients (35%) showed pancolitis. Forty-eight patients (56 %) had mild disease, 23 patients (27%) had moderate disease and 14 patients (17 %) had severe disease endoscopically (Table- 2). Although all patients showed histological criteria of diagnosis, clinically several patients were not as sick as the endoscopic appearance of their colons. Sixty patients (70%) were treated with mesalamine, mainly as Asacol, and the dose ranged from mg per day which was eventually tapered down to mg per day for maintenance. Twenty-five patients (30%) were treated with sulfasalazine with the dose ranging from 2-6 g per day. Fifteen patients (18%) were also given steroids with 8 patients (10%) given oral and intravenous steroids and 7 patients (8%) given as steroid enemas in the form of Colifoam. Two patients (2%) were given azathioprin in dose of 100 mg per day. Twenty-eight patients (33%) received Asacol enemas for 2-3 weeks time, and after that were maintained on oral mesalamine. No refractory cases were found. Two patients died of complications. One was a 78 years old female who died of toxic megacolon and other was an 84 years old male who succumbed to sepsis. 4
5 Table-2. Severity Classes of Ulcerative Colitis N = 85 Mild (%) 48 (56 %) Moderate 23 (27 %) Severe 14 (17 %) Extra-intestinal features consisted mainly of stomatitis, which was noted in 31 patients (36%). Arthralgias were noted in 10 patients (12%). Cirrhosis was found in one patient. None of the patient was diagnosed as colon cancer during the follow up period. Exacerbation was noted in 3 patients, which was related to stress in the form of job and marital disharmony. None of the patients in this series was noted to be on non-steroidal anti-inflammatory drugs. DISCUSSION These patients showed high ESR and presence of numerous WBCs, which are commonly found in acute ulcerative colitis. 10 Few patients showed eiosinophilia, which has been noted, to be present in patients of Asian origin. 11 This returned to normal levels after the treatment. Extra intestinal manifestation of ulcerative colitis are known widely 12 but most commonly found in our series were stomatitis and mucocutaneous features, as was found in studies from Lahore and Multan. 4,5 Stress can exacerbate ulcerative colitis, and it can be acute or chronic. 13 In our case, the stress was found to be acute and related to job or marital problems. Non-steroidal anti-inflammatory drugs have been reported to either exacerbate or cause complications in ulcerative colitis 14 but in our patients, none was on these medications. The majority of our patients had distal colitis, as seen in earlier studies from Pakistan. 3,4 Our patients responded well to the aminosalicylic acid, as has been reported. 19 We did not encounter any refractory cases, although in those cases, there are recent additions of anti tumor necrosis factor, Balsalazide and Cyclosporin 16,17 among others. During our follow up, we did not notice any extension of these cases with distal colitis; however, that has 5
6 been reported. 6 Over 80% of our patients had mild to moderate disease. This is about the same severity as found else where in Pakistan. 3,6 Patient with ulcerative colitis can develop multiple organ dysfunction, and two of our cases developed this complication and died. None of our cases developed carcinoma of the colon. Although this is common in these patients, 18 and occurs late in the course of disease, our follow up has not been long enough in this study. Patients with ulcerative colitis have problem with compliance 19 and in our case, there were people who did not follow the instructions well but were still able to keep the disease under control. Some patients with diarrhea and intermittent bleeding have ulcerative colitis but are treated empirically as infectious diarrheas with antimicrobials and other drugs. Patients with these symptoms must be worked up appropriately with stool examination and other appropriate tests. It is considered essential that any diarrhea with bleeding, with or without systemic symptoms, lasting six weeks or longer, should be investigated with a flexible sigmoidoscopy and colon biopsy to rule out inflammatory bowel disease. In conclusion, the experience with ulcerative colitis at our tertiary care center revealed that the disease was mainly located to the left colon and mild in severity. The condition could be adequately controlled with standard therapeutic regimens. The clinical features, endoscopic extent and severity of illness does not significantly differ from other parts of Pakistan and elsewhere in the world. REFERENCES 1. Montgomery SM, Morris DL, Pounder RE, Wakefield AJ. Asian ethnic orgin and risk of inflammatory bowel disease. Eur J. Gastroenterol Hepatol 1999; 11: Probert CS, Mayberry JF, Mann R. Inflammatory bowel disease in the rural Indian subcontinent: a survey of patients attending mission hospitals. Digestion 1990; 47:
7 3. Qureshi H, Zuberi SJ, Banatwala N, Anwar A, Shamsi Z, Khan MN. Ulcerative colitis in Karachi. J. Gastroenterol Hepatol 1989; 4: Naqvi AB, Inayatullah M, Arshad M, Nasir SA, Anjum AH. Features of ulcerative colitis: A study of 30 cases from Multan Region. Pak. J. Gastroenterol 1994; 8: Malik MN, Masaud G, Raana K. Ulcerative colitis: An experience in a medical unit of a teaching hospital at Lahore. Pak J. Gastroenterol 1995; 9: Hameed K, Khan I, Farooqi JI, Shah S. Correlation of endoscopic extent and severity with the clinical presentation of ulcerative colitis. JCPSP 2001; 11: Truelove SC, Witts LJ. Cortisone in ulcerative colitis: final report on a therapeutic trial. BMJ 1955; 2: Baron JH, Connel AM, Lennard jones JE. Variation between describing mucosal appearance in proctocolitis. BMJ 1964; 1: Kumar V, Cotran RS, Robbins SL. Eds. Basic Pathology. PP W.B. Saunders Co Nielsen OH, Vainer B, Madsen SM, Seidelin JB, Heegaard NHH. Established and emerging biological activity markers of inflammatory bowel disease. Am J. Gastroenterol 2000; 95: Benfield GF, Asquith P. Blood eosinophilia and ulcerative colitis - influence of ethnic orgin. Postgrad Med J. 1986; 62:
8 12. Bernstein CN, Blanchard JF, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: A population - Based study. Am J Gastroenterol 2001; 96: Levenstein S, Prantera C, Varvo V, Scribano ML, Andreoli A, Luzi C, et al. Stress and exacerbation in ulcerative colitis: A prospective study of patients enrolled in Remission. Am J. Gastroenterol 2000; 95: O Brien J. Non steroidal anti-inflammatory drugs in patients with inflammatory bowel disease. Am J Gastroenterol 2000; 95: Cohen RD, Woseth DM, Thisted RA, Hanauer S. A meta-analysis and overview of the literature on treatment options for left sided ulcerative colitis and ulcerative proctitis. Am J Gastroenterol 2000; 95: Blam ME, Stein RB, Lichtenstein GR. Integrating anti tumor necrosis factor therapy in inflammatory bowel disease: current and future perspectives. Am J Gastroenterol 2001; 96: Rowe FA, Walker JH, Karp LC, Vasilauskas EA, Plevy SE, Targan SR. Factors predictive of response to cyclosporin treatment for severe, steroid - Resistant ulcerative colitis. Am J Gastroenterol 2000; 95: Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. GUT 2001; 48: Kane SV, Cohen RD, Aikens JE, Hanauer SB. Prevalence of nonadherence with maintenance mesalamine in quiescent ulcerative colitis. Am J Gastroenterol 2001; 96:
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