Nisan 2013

15-18

Atakan YEŞİL ¹ , Ebubekir ŞENATEŞ ² , Kadir KAYATAŞ ³ , Koray KOÇHAN ¹, Emrullah Düzgün ERDEM ¹ , Banu ERKALMA ŞENATEŞ ⁴ , Can GÖNEN ¹

Departments of ¹ Gastroenterology and ³ 3rd Internal Medicine Clinic Haydarpaşa Numune Education and Research Hospital, İstanbul
Department of ² Gastroenterology Dicle University Medical School, Diyarbakır
Department of ⁴ Internal Medicine, Diyarbakır Education and Research Hospital, Diyarbakır

Amaç: İnflamatuvar barsak hastalıkları; ülseratif kolit ve Crohn hastalığı olarak iki önemli hastalığı içerir. Barsak hastalıkları olarak nitelendirilmelerine rağmen sistemik tutulumları da mevcuttur. Bu çalışmadaki amacımız kliniğimizde yatırarak takip ettiğimiz inflamatuvar barsak hastalarındaki ekstraintestinal tutulum tiplerini ve sıklığını belirlemek, hastalık aktivitesiyle ilişkisini araştırmaktır. Gereç ve Yöntem:Çalışma gastroenteroloji kliniğimizde takip ettiğimiz inflamatuvar barsak hastalıkları tanısı olan 85 hasta üzerinde yapıldı. Hastalar 39 Chron hastası ve 46 ülseratif kolit hastasından oluşmaktaydı. Bulgular:Crohn hastalığı grubu ve ülseratif kolit grubu arasında yaş, cinsiyet, boy, vücut ağırlığı, beden kitle indeksi, eritrosit sedimentasyon hızı, C-reaktif protein, hemoglobin, hastalık süresi, ekstraintestinal tutulum sıklığı açısından istatistiksel anlamlı farklılık bulunmadı (p>0.05). Lökosit sayısı ortalaması Crohn hastalığı grubunda ülseratif kolit grubuna göre anlamlı dü-şük bulundu (p:0.003). Hastalar ekstraintestinal tutulum olup olmamasına göre ikiye ayrıldığında gruplar arasında yaş, cinsiyet, vücut ağırlığı, beden kitle indeksi, C-reaktif protein, eritrosit sedimentasyon hızı, hemoglobin, lökosit sayısı, hastalık süresi açısından anlamlı farklılık bulunmadı (p>0.05). Ekstraintestinal tutulum tipleri sıklık sırasına göre: sakroileit (%40.7), artralji (%11.1), psöriazis (%11.1) artrit (%7.4), ankilozan spondilit (%7.4), iridosiklit (%7.4), primer sklerozan kolanjit (%3.7) ve üveit (%3.7) şeklindeydi. Hastalarda ekstraintestinal tutulum varlığı ile hastalık aktivitesi, tipi ve endoskopik tutulum bölgeleri arasında anlamlı ilişki saptanmadı. Sonuç: Sonuç olarak inflamatuvar barsak hastalarımızda ekstraintestinal tutulum oranı Crohn hastalığı grubunda %38.46, ülseratif kolit grubunda %26.08 olmak üzere, literatürle uyumlu olarak sıktır. Hastaların tanı aldıkları andan itibaren ekstraintestinal bulgular açısından düzenli muayene ve takiplerinin yapılması önemlidir.

Ülseratif kolit, Crohn hastalığı, ekstraintestinal tutulum

Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases in genetically predisposed individuals characterized by an unknown etiology and mechanism and chronic periods of remission and exacerbation. It includes two important diseases - ulcerative colitis (UC) and Crohn’s disease (CD) (1-3). Although they are described as bowel diseases, they also have systemic involvement. This clinical condition, also called extraintestinal involvement, includes a broad spectrum of involvement that ranges from mild to severe. The relationship between the severity of extraintestinal involvement and the severity of the underlying bowel disease shows differences according to the type of involvement. Joint (excluding axial), mouth, eye and skin involvement is associated with disease activity and they are referred to as inflammatory diseases (4). Areas of involvement other than these are generally not associated with disease activity; the underlying mechanism is attributed to autoimmune, nutritional and metabolic causes(4). While the most important variables related to extraintestinal involvement in UC are extent of colonic involvement and disease activity, the variables in CD are multifactorial (5). Our aim in this study was to determine the types and frequencies of extraintestinal involvement in IBD cases followed after admission to our clinic and to investigate the relationship between extraintestinal involvement and disease activity.

In the studies investigating the frequency of extraintestinal involvement in IBD patients, it was reported that systemic involvement was present in approximately one-third of the patients (6,7). Depending upon the areas of reporting, this rate ranges between 20% and 40% (6). We determined this rate as 32% in this study conducted on the patients followed up after admission in our clinic. Although the extraintestinal involvement rate in the patients with CD (38.46%) was higher than in the UC group (26.08%), the difference between them was not statistically significant. In the studies performed, joint involvement was reported to be the most frequent involvement encountered in IBD, with a rate of 10-30% (8). Joint involvement in IBD can be axial, peripheral or combined. Peripheral arthritis is generally nonerosive, oligoarticular and shows a parallelism with disease activity. Axial arthritis can be grouped as inflammatory back pain, sacroiliitis and ankylosing spondylitis (9). In our patient group, extraintestinal involvement was seen in 27 of 85 patients, and in 11 of those 27 (40%), the involvement was sacroiliitis. The frequency of sacroiliitis in different published studies ranges from 10-32% (8-12). The reason for this wide range may be due to some of the studies being population-based and others hospital-based, variability of activity status of the patients and geographical differences. In this study, we determined the prevalence of sacroiliitis as 11/85, namely 12%. However, no prominent extraintestinal involvement other than sacroiliitis was observed. The prevalences of arthralgia and psoriasis were determined to be approximately 3.5%. We determined the frequency of erythema nodosum as 2.3%, and the frequencies of uveitis and primary sclerosing cholangitis as 1.2%, similar to each other. These rates showed similarity with many studies in the literature (8-15). In this study, there was no significant difference between the CD patients with and without extraintestinal involvement regarding disease activity, type of disease, CDAI, CDES index and areas of involvement on endoscopy. There was no significant difference between the UC patients with and without extraintestinal involvement regarding disease activity (according to Truelove and Witts’ criteria), Mayo index, and areas of involvement on endoscopy. These findings show us that there is no correlation between the presence of extraintestinal involvement and the disease activity, type of the disease and mucosal healing in the IBD cases followed up in our clinic. The major limitation in our study is the small sample size and the nonhomogeneity of the patient population due to their selection from the patients admitted to our clinic. Despite the present limitations, this study shows that frequencies of extraintestinal involvement are high in IBD patients independent of the parameters of disease activity, type of the disease and areas of involvement on endoscopy. Our results call attention to the importance of regular examination and follow-up of the patients, from the time of diagnosis, regarding extraintestinal symptoms

The mean age of the patients with CD (Group 1) was 36.67±12.07 (min: 19, max: 63) years, and the mean age of the patients with UC (Group 2) was 36.61±13.06 (min: 16, max: 74) years. There was no statistically significant difference between the groups regarding age and gender (p: 0.983, 0.235, respectively). There was no statistically significant difference between Group 1 and Group 2 regarding height, body weight, body mass index (BMI), ESR, CRP, hemoglobin (Hb), disease duration, and the frequency of extraintestinal involvement (p>0.05). Average white blood cell (WBC) count was 7.28±2.07/mm3 in Group 1 and 8.78±2.33/mm3 in Group 2, and the difference between them was found to be statistically significant (p=0.003). Demographic and clinical characteristics and laboratory data of Group 1 and Group 2 are seen in Table 1. Patients were divided into two groups regarding the presence or not of extraintestinal involvement. Group A (with extraintestinal involvement) comprised 27 patients (16 females, 11 males), and Group B (without extraintestinal involvement) comprised 58 patients (26 females, 32 males). The mean age of Group A was 37.41±13.52 (min: 19, max: 70) years, and the mean age of Group B was 36.28±13.16 (min: 16, max: 74) years. There was no statistically significant difference between groups regarding age and gender (p: 0.701, 0.215, respectively). There was no statistically significant difference between Group A and Group B regarding body weight, BMI, ESR, CRP, Hb, WBC, or disease duration (p>0.05). Mean height was 164.81±7.05 cm in Group A and 168.34±6.70 cm in Group B, and the difference between them was found to be statistically significant (p=0.029). Demographic and clinical characteristics and laboratory data of the groups with and without extraintestinal involvement are seen in Table 2. The types of extraintestinal involvement were investigated, and were determined as follows, in decreasing order of frequency: sacroiliitis 40.7% (11 patients: 7 CD, 4 UC), arthralgia 11.1% and psoriasis (11.1%). The other types of extraintestinal involvement included arthritis (7.4%), ankylosing spondylitis (7.4%), iridocyclitis (7.4%), primary sclerosing cholangitis (3.7%), and uveitis (3,7%). Types and frequencies of extraintestinal involvement seen in our study group are shown in Table 3. When the disease activity of the patients with UC was evaluated according to Truelove and Witts’ criteria, mild, moderate and severe disease activity was determined in 12 (26.1%), 23 (27.1%) and 11 (12.9%) patients, respectively. When the disease activity of the patients was evaluated according to the Mayo scoring system, the numbers of patients with a score of 0, 1, 2, and 3 were 5 (10.9%), 4 (8.7%), 24 (52.2%), and 13 (28.3%), respectively. Areas of involvement on endoscopy were as follows: rectum in 4 patients, distal colon in 10 patients, left colon in 15 patients, and entire large intestine in 17 patients. There was no significant difference between the UC patients with and without extraintestinal involvement regarding disease activity, Mayo index and areas of involvement on endoscopy (p: 0.902, 0.632, and 0.645, respectively). When the disease activity of the patients with CD was investigated, inactive, mild and moderate disease activity was determined in 22 (56.4%), 9 (23.1%) and 8 (20.5%) patients, respectively. The types of CD were as follows: inflammatory in 18 patients (47.4%), obstructive in 10 patients (26.3%), fistulizing in 9 patients (23.7%), fibrotic in 1 patient (2.6%), and unknown 1 patient (2.6%). Areas of involvement on endoscopy were as follows: normal in 4 patients, colonic in 6 patients, ileal in 13 patients, and ileocolonic in 14 patients. There was no significant difference between the CD patients with and without extraintestinal involvement regarding disease activity, type of disease, Crohn’s Disease Activity Index (CDAI), Crohn’s Disease Endoscopic Index of Severity (CDEIS) and areas of involvement on endoscopy (p=0.352, 0.427, 0.522, 0.959, and 0.988, respectively).

In the studies investigating the frequency of extraintestinal involvement in IBD patients, it was reported that systemic involvement was present in approximately one-third of the patients (6,7). Depending upon the areas of reporting, this rate ranges between 20% and 40% (6). We determined this rate as 32% in this study conducted on the patients followed up after admission in our clinic. Although the extraintestinal involvement rate in the patients with CD (38.46%) was higher than in the UC group (26.08%), the difference between them was not statistically significant. In the studies performed, joint involvement was reported to be the most frequent involvement encountered in IBD, with a rate of 10-30% (8). Joint involvement in IBD can be axial, peripheral or combined. Peripheral arthritis is generally nonerosive, oligoarticular and shows a parallelism with disease activity. Axial arthritis can be grouped as inflammatory back pain, sacroiliitis and ankylosing spondylitis (9). In our patient group, extraintestinal involvement was seen in 27 of 85 patients, and in 11 of those 27 (40%), the involvement was sacroiliitis. The frequency of sacroiliitis in different published studies ranges from 10-32% (8-12). The reason for this wide range may be due to some of the studies being population-based and others hospital-based, variability of activity status of the patients and geographical differences. In this study, we determined the prevalence of sacroiliitis as 11/85, namely 12%. However, no prominent extraintestinal involvement other than sacroiliitis was observed. The prevalences of arthralgia and psoriasis were determined to be approximately 3.5%. We determined the frequency of erythema nodosum as 2.3%, and the frequencies of uveitis and primary sclerosing cholangitis as 1.2%, similar to each other. These rates showed similarity with many studies in the literature (8-15). In this study, there was no significant difference between the CD patients with and without extraintestinal involvement regarding disease activity, type of disease, CDAI, CDES index and areas of involvement on endoscopy. There was no significant difference between the UC patients with and without extraintestinal involvement regarding disease activity (according to Truelove and Witts’ criteria), Mayo index, and areas of involvement on endoscopy. These findings show us that there is no correlation between the presence of extraintestinal involvement and the disease activity, type of the disease and mucosal healing in the IBD cases followed up in our clinic. The major limitation in our study is the small sample size and the nonhomogeneity of the patient population due to their selection from the patients admitted to our clinic. Despite the present limitations, this study shows that frequencies of extraintestinal involvement are high in IBD patients independent of the parameters of disease activity, type of the disease and areas of involvement on endoscopy. Our results call attention to the importance of regular examination and follow-up of the patients, from the time of diagnosis, regarding extraintestinal symptoms

1. Scaldaferri F, Fiocchi C. Inflammatory bowel disease: progress and current concepts of etiopathogenesis. J Dig Dis 2007;8:171-8. 2. Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 2006;12(Suppl 1):S3-9. 3. Xia B, Crusius J, Meuwissen S, Pena A. Inflammatory bowel disease definition, epidemiology, etiologic aspects, and immunogenetic studies. World J Gastroenterol 1998;4:446-58. 4. Veloso FT. Extraintestinal manifestations of inflammatory bowel disease: do they influence treatment and outcome? World J Gastroenterol 2011;17:2702-7. 5. Vilela EG, Torres HO, Martins FP, Ferrari Mde L, Andrade MM, Cunha AS. Evaluation of inflammatory activity in Crohn’s disease and ulcerative colitis. World J Gastroenterol 2012;18:872-81. 6. Larsen S, Bendtzen K, Nielsen OH. Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management. Ann Med 2010;42:97-114. 7. Beslek A, Onen F, Birlik M, et al. Prevalence of spondyloarthritis in Turkish patients with inflammatory bowel disease. Rheumatol Int 2009;29:955-7. 8. Brakenhoff LK, van der Heijde DM, Hommes DW, Huizinga TW, Fidder HH. The joint-gut axis in inflammatory bowel diseases. J Crohns Colitis 2010;4:257-68. 9. Hwangbo Y, Kim HJ, Park JS, et al. Sacroiliitis is common in Crohn’s disease patients with perianal or upper gastrointestinal involvement. Gut Liver 2010;4:338-44. 10. Marques MR, Oliveira S, Gorjão Clara JP. [Ulcerative colitis initial presentation with multiple extra-intestinal manifestations]. Acta Med Port 2010;23:705-8. 11. Queiro R, Maiz O, Intxausti J, et al. Subclinical sacroiliitis in inflammatory bowel disease: a clinical and follow-up study. Clin Rheumatol 2000;19:445-9. 12. Orchard TR, Holt H, Bradbury L, et al. The prevalence, clinical features and association of HLA-B27 in sacroiliitis associated with established Crohn’s disease. Aliment Pharmacol Ther 2009;29:193-7. 13. Denadai R, Teixeira FV, Saad-Hossne R. The onset of psoriasis during the treatment of inflammatory bowel diseases with infliximab: should biological therapy be suspended? Arq Gastroenterol 2012;49:172-6. 14. Tozun N, Atug O, Imeryuz N, et al. Clinical characteristics of inflammatory bowel disease in Turkey: a multicenter epidemiologic survey. J Clin Gastroenterol 2009;43:51-7. 15. Schwartz RA, Nervi SJ. Erythema nodosum: a sign of systemic disease. Am Fam Physician 2007;75:695-700.