Saudi Journal of Gastroenterology
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Year : 2005  |  Volume : 11  |  Issue : 3  |  Page : 157-163
Crohn's disease among Saudis in Al-Gassim region


1 Department of Medicine, King Fahad Specialist Hospital, Buraidah, Saudi Arabia
2 Department of Surgery, King Fahad Specialist Hospital, Buraidah, Saudi Arabia
3 Department of Laboratory Medicine, King Fahad Specialist Hospital, Buraidah, Saudi Arabia

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Date of Submission23-Oct-2004
Date of Acceptance02-Jul-2005
 

   Abstract 

Background: Crohn's disease is being increasingly reported from Saudi Arabia and information about its pattern is still accumulating.
Aim of the study: To describe and classify the disease and assess the response to therapy in patients referred to a tertiary care centre in Gassim region, Kingdom of Saudi Arabia (KSA).
Patients and Methods: Fifteen Saudi patients found to have Crohn's disease over an eight-year period were studied. The presenting symptoms, area of involvement and the response to therapy were assessed.
Results: There were five males and ten females. The age of 14 patients was less than 40 years. Symptoms had existed for more than one year before diagnosis in 14 patients. Common symptoms were diarrhea, pain during defecation, blood in stool and weight loss. The ileum was involved in three patients, the colon in four and the involvement was ileocolonic in eight patients. The behavior of the disease was non-stricturing nonpenetrating in eight, stricturing in two, penetrating in one and stricturing as well as penetrating in four patients. Three patients presented as acute appendicitis, four as intestinal obstruction and five with perianal disease. Histological diagnosis was possible in 12 patients. Thrombocytosis was present in seven patients and three had episodes of deep vein thrombosis. Eight patients responded to medical therapy. Surgical intervention was necessary in seven patients and three had multiple operations. One patient died during a median follow-up period of 18 months (range: 6 months to 8 years).
Conclusion: Crohn's disease occurs more commonly in young Saudi females. Patients are symptomatic for almost a year prior to diagnosis. The presentation is variable and response to therapy is satisfactory. Surgery is necessary in a high number of patients

Keywords: Crohn′s disease, inflammatory bowel disease, regional enteritis

How to cite this article:
Contractor QQ, Contractor TQ, Ul Haque I, El Mahdi EE. Crohn's disease among Saudis in Al-Gassim region. Saudi J Gastroenterol 2005;11:157-63

How to cite this URL:
Contractor QQ, Contractor TQ, Ul Haque I, El Mahdi EE. Crohn's disease among Saudis in Al-Gassim region. Saudi J Gastroenterol [serial online] 2005 [cited 2020 Oct 29];11:157-63. Available from: https://www.saudijgastro.com/text.asp?2005/11/3/157/33319


Inflammatory bowel disease (IBD) consistent with Crohn's disease (CD) was described three hundred years ago. [1] During the 19th as well as early in the 20th century similar cases were reported prior to the pivotal paper by Crohn, Ginzburg and Oppenheimer in 1932 (2) . Subsequent epidemiologic surveys documented the worldwide distribution of IBD. The rising incidence of CD was noted in Brazil and South Korea [1] . Among the bedouin Arabs in Israel, the incidence has been reported to be 32/100,000 [3] . This was much higher than the hospital based incidence of 1.66/100,000 reported recently from Riyadh [4] . This could be due to racial differences.

Two decades ago IBD was believed to be rare or nonexistent in Saudi Arabia [5] . Two cases of CD were first reported in 1982 from Saudi Arabia [6] . Since then the diagnosis has been made more frequently in Saudis [4],[7],[8],[9] The annual incidence has increased five folds over the past twenty years in a teaching hospital in Riyadh [4] . The disease has been reported from various parts of the country. Crohn's disease has also been reported with increasing frequency from other Arab countries [10],[11] Experience with CD over an eight-year period from a tertiary care centre in Gassim (KSA) is described in this study.


   Patients and Methods Top


Over an eight-year period (1995-2003), 15 patients were diagnosed to have CD based on symptoms, radiological, endoscopic, histological and operative findings. This was a cohort study of patients seen in the Department of Gastroenterology at King Fahad Specialist Hospital (KFSH), Al Gassim. The population of Gassim Region is 1,016,756 (Saudis- 817,492) as per the National Census for Population and Housing, 1425H (2004), and KFSH is a 585-bedded tertiary care centre serving this region. Detailed history and physical examination were obtained from all patients. Complete hemogram, ESR, stool microscopic examination and culture, complete serum chemistry and C-reactive protein (CRP) were requested at the time of presentation. Plain chest and abdomen x-ray were also obtained. Colonoscopic examination was recommended after sigmoidoscopic assessment and endoscopic biopsies were taken. Patients who refused endoscopic biopsies, had an air double-contrast barium enema. Air double-contrast barium study of the stomach, duodenum and small bowel, and tuberculin test were performed in all patients.

Colonic biopsies were evaluated by the criteria established by Jenkins et al for the diagnosis of IBD [12] . Several morphological features that characterize CD were assessed. Variation in inflammatory intensity within and between biopsy specimens, deep active chronic inflammation despite normal surface epithelium, isolated crypt inflammation amidst otherwise normal looking crypts and epitheloid cell granuloma, especially between crypts and abutting the muscularis mucosae were noted.

Treatment was started after the diagnosis of CD was made on the basis of total assessment. Features suggestive were: a) recurrent symptoms, b) radiographic evidence of isolated small bowel or associated small and large bowel disease, c) endoscopic evidence of aphthous or linear ulcerations or cobblestoning with skip lesions and d) the presence of histological findings suggestive of CD, especially noncaseating granulomas with the exclusion of tuberculosis as a possibility. Fat wrapping or creeping fat on laparoscopy or laparotomy was also suggestive of CD. Patients were classified according to Vienna classification of CD [13] . Therapy was initiated with steroids, Salazopyrin and metronidazole and patients were regularly followed up in the clinic.


   Results Top


All the patients were Saudis and their clinical characteristics of the patients at the time of presentation are shown in [Table - 1]. There was only one instance of two sisters being affected from one family. Categorization of the patients as per the Vienna Classification of CD is shown in [Table - 2]; 33% (5 patients) were clustered as A1 B 1 L3 and this was the most frequently encountered subgroup. Colonoscopy was performed in all patients except two patients, who had emergency surgery for intestinal obstruction.

The resected specimens revealed ileocolonic involvement and they have subsequently refused lower GI. endoscopy. Colonoscopy was normal in three patients. Abnormalities noted were aphthous ulcers, linear and oval ulcers, polypoid mucosa, patches of granular and easily friable mucosa, luminal narrowing and mucosal bridges. The rectosigmoid region was involved in eight patients, the descending colon in six, the transverse colon in six, the ascending in seven, the caecum in nine and the entire colon in six patients. Seven patients had barium enema and it was abnormal in all. Abnormalities included cicatrization of the caecum, ileocolonic fistula, cobblestone appearance, luminal narrowing and segmental involvement. Barium meal with small bowel follow through was performed in twelve patients and it was abnormal in 11, and terminal ileum was involved in all of them. Irregularity, narrowing of the lumen with the typical string sign and pseudosacculation were the abnormalities noted.

Biopsy samples included 13 sets of endoscopic colonic biopsies from multiple sites generated in ten patients and from the anal fistula in three and two surgically-resected ileocolectomy specimens. Tissue diagnosis was not possible in three patients with only ileal involvement. In the ten sets of biopsies studied the number of mucosal fragments ranged from 2 to 7 with an average of 4.5. One had only a single tissue and two were represented by only inflammatory granulation tissue. The first three features were most consistently seen, in 8/10 sets of biopsies, whereas granuloma was found in 5/10 biopsy sets [Table - 3]. Other features noted were focal mild distortion of the crypts and mucodepletion in inflamed crypts. The ileocolectomy specimens revealed cobblestoning and thickening of the mucosa in terminal ileum with all the bonafide features of CD.

Thrombocytosis (platelets > 400,000/cu mm) was present in seven patients, three of them had episodes of deep vein thrombosis. The mean Hb level of the patients with and without Thrombocytosis was 10 and 11.5 g/dl respectively.

Eleven patients were treated with prednisone to induce remission. Four patients received 30 mg/day and seven received 40. Thirteen patients received Salazopyrin 1.5 to 4 gm/day and two received 5-aminosalicylic acid 800 mg/day. Metronidazole 0.5 to 1 gm/day was given to eight patients who had perianal and rectal involvement. Treatment discontinued in three patients for an average period of eight months. Metronidazole was always discontinued during pregnancy. Eight patients had exacerbations needing steroid therapy.

Surgical intervention was necessary in seven patients who presented with either acute appendicitis, intestinal obstruction or perianal fistula. Three of them had multiple operations. A resection of the terminal ileum, caecum and ascending colon was performed in two patients who had presented with intestinal obstruction. Left hemicolectomy with drainage of rectus sheath abscess were performed in two stages in a patient with inflammatory mass involving the ascending colon and extending to the rectus sheath; that patient had presented with acute appendicitis. Three other patients who presented with acute appendicitis and one patient with perianal fistula also had surgery. Two patients with an established diagnosis of Crohn's disease and intestinal obstruction, were admitted to the medical side, responded to conservative therapy. Median follow up was 1.5 years (range: 3 months to 8 yrs).


   Discussion Top


The present study confirms that the diagnosis of CD is being made more frequently in KSA. Can this be due to improving economy and progress in the last few decades? Socioeconomic factors describe a collection of demographic variables including education, income and occupation, contributing to the epidemiologic analysis of many diseases. Two studies of CD in Scotland and England have shown a higher proportion of white-collar occupations being affected more than the control groups [14],[15] The rising incidence of CD over many decades is highly suggestive of an environmental contribution to the expression of disease.

Several risk factors have been implicated in epidemiological studies. Breast feeding has been found to be protective for IBD. Smoking, use of oral contraceptives, NSAIDs and increased intake of refined sugars have been associated with the development of CD [16],[17] . These factors will have to be studied to understand the increasing incidence of CD in KSA. In this study five out of the ten females had breast fed and the other five were single at the time of presentation. There was only one smoker and none of them were regularly consuming NSAIDs. The use of oral contraceptives was denied by the female patients. Excess risk of CD among women has been documented at different times all over the world. The recent report from Riyadh as well as our data shows that young Saudi females are more frequently affected. The implications of sex differences in the etiology of CD is not known but could be related to hormonal and life-style factors.

The median age of the patients was 21 years and 14/15 were < 40 years old. These figures are similar to those reported from Riyadh. Population-based studies have shown that the median age at diagnosis was approximately 30 year [18] . Some studies have showed a smaller second peak in incidence later in life, generally in the seventh decade [19] . This second peak could be due to more frequent medical evaluation of older patients. However, the age at diagnosis may range from early childhood through the entire life span. Recently, CD was reported in a newborn from Gassim region [20]

Genetic predisposition in IBD is based on the observation that the relative risk among first-degree relatives is 14-15 times higher than that of the general population [21] . It is believed that 1 of 5 patients with CD will report having at least one affected relative. With progress in genome-wide scans for regions of IBD linkage, specific IBD genes have been identified. The presence of a locus on chromosome 16 has been linked to CD [22] . A recent report supports the hypothesis that NOD2/CARD 15 mutations are associated with a phenotype of CD including a younger age at diagnosis, ileal involvement, ileocecal resections and a high risk of postoperative relapse and reoperation [23] In the present report there was only one family in which two sisters were affected and both had terminal ileal disease. Previous reports from Saudi Arabia have made no mention of familial incidence.

In the clinical investigation of CD it is important to define subgroups with distinct characteristics. Subgroups with distinct prognoses could add tremendous power to the investigation of new therapies and to genetic studies. The Vienna classification of CD incorporates the patient's age at onset, disease location and disease behavior into a schema with 24 potential subgroups. Significant associations between age at diagnosis and location and between disease behavior and location are observed, along with a trend towards an association between age at diagnosis and disease behavior. The result is a clustering of patients in some subgroups and virtually none in others. Distribution and behavior of the disease process as per Vienna classification in our patients indicates that 33% (five patients) were clustered as A 1 B 1 L3.

The presenting symptoms and distribution of the lesions in this study are similar to those from other parts of KSA. More than half of the patients had presented initially to the surgeon with either acute appendicitis, intestinal obstruction or bleeding per rectum.

An increased risk of thromboembolism (both arterial and venous) in patients with IBD is known. It has been suggested that IBD causes functional changes in the blood rheology, which predispose the patient to thromboembolic events. Contributing factors include thrombocytosis, increased levels of fibrinogen, fibrinopeptide A, factor V, and factor VIII, antithrombin III deficiency, and free protein S deficiency. Solem et al reported 98 patients with IBD in whom thromboembolic events occurred [24] . Thrombophilia was present in 33% of the 40 patients tested. The most common of these disorders was factor V Leiden mutation, followed by hyperhomocysteinemia, antiphospholipid antibodies, protein S deficiency, dysfibrinogenemia, and prothrombin 20210 gene mutation. However, most of their patients (87%) also had other risk factors. It was concluded that venous thromboembolism is a serious complication of IBD that may lead to death. Thrombocytosis was present in 47% of our patients but tests for other clotting factors were not available to us. Three patients had thromboembolic phenomenon and one died, possibly of pulmonary embolism. Prophylaxis should be considered for patients hospitalized for active disease who have significantly decreased mobility.

Although surgical intervention was necessary in seven patients all the others responded to medical therapy. Steroids were necessary to induce remission in 11 patients and none of them required immunosuppressants except one who was referred to another centre for placement of an IVC filter and possibly received immunosuppression there. Infliximab, a monoclonal antibody against tumor necrosis factor, has been shown to be effective in treating Crohn's disease with and without fistulas [25]

In conclusion, Crohn's disease occurs more frequently in young Saudi females in Gassim Region. Response to medical therapy is satisfactory although a high number needed surgical intervention.

 
   References Top

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2.Crohn BB, Ginzburg L, Oppenheimer GD. Landmark article of October1932. Regional Ileitis. A pathological and clinical entity. By Burril B. Crohn, Leon Ginzburg and Gordon D. Oppenheimer. JAMA 1984; 251: 73-9.  Back to cited text no. 2    
3.Odes HS, Fraser D, Krugliak P, Fenyves D, Fraser GM, Sperber AD. Inflammatory bowel disease in Bedouin Arabs of Southern Israel: Rarity of diagnosis and clinical features. Gut 1991; 32: 1024-6.  Back to cited text no. 3    
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5.Kirsner JB, Shorter RG. Recent development in inflammatory bowel disease N Engl J Med 1982; 306: 837-48.  Back to cited text no. 5    
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12.Jenkins D, Balsitis M, Gallivan S, et al. Guidelines for the initial biopsy diagnosis of suspected chronic idiopathic inflammatory bowel disease. The British Society of Gastroenterology Initiative. J Clin Pathol 1997; 50: 93-105.  Back to cited text no. 12    
13.Gasche C, Scholmerich J, Brynskov J, et al. A simple classification of Crohn's disease: report of the working Party for the World Congress of Gastroenterology, Vienna 1998. Inflam Bowel Dis 2000; 6: 8-11.  Back to cited text no. 13    
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15.Keighley A, Miller DS, Hughes AD, Langman MJS. The demographic and social characteristics of patients with Crohn's disease in the Nottingham area. Scand J Gastroenterol 1976; 11: 293-6.  Back to cited text no. 15    
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20.Mushaikih A. Colonic Crohn's disease - is it? Saudi J Gastroenterol 2003; 9: 109.  Back to cited text no. 20    
21.21 Sands BE. Crohn's Disease. In: Feldman M, Friedman LS, Sleisenger MH, (Eds). Sleisenger & Fordtran's Gastrointestinal and Liver Disease. Pathophysiology/Diagnosis/Management. Seventh edition. Philadelphia: Saunders, 2002: 2009.  Back to cited text no. 21    
22.Hugot JP, Laurent-Puig P, Gower-Rousseau C, et al. Mapping of a susceptible locus for Crohn's disease on chromosome 16. Nature 1996; 379: 821-3.  Back to cited text no. 22    
23.Buning C, Genschel J, Buhner S, et al. Mutations in the NOD2/CARD 15 Gene in Crohn's Disease are associated with ileocecal resection and are a risk factor for reoperation. Aliment Pharmacol Ther 2004; 19: 1073-8.  Back to cited text no. 23    
24.Solem CA, Lofts EV, Tremaine WJ, Sandborn WJ. Venous thromboembolism in inflammatory bowel disease. Am J Gastroenterol 2004; 99: 97-101  Back to cited text no. 24    
25.Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med 2004; 350: 876-85.  Back to cited text no. 25    

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Correspondence Address:
Qais Qutub Contractor
King Fahad Specialist Hospital, P 0 Box 2290, Buraidah, Al-Gassim
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-3767.33319

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