Waleed Alazmi

Collagenous colitis associated with Clostridium difficile: A cause effect?

To the Editor: A widely accepted hypothesis on the etiology of collagenous colitis is that a noxious luminal stimulant leads to an inflammatory reaction that is perpetuated by an immun response to the injury (1). We report a patient with diarrhea who was found to have collagenous colitis and also to be Clostridium difficile toxin positive. His symptoms persisted after treatment of C. difficile. We propose that C. difficile may be a noxious stimulant that could catalyze a chain of events resulting in collagenous colitis. This is the third documented case of an association between C. difficile and collagenous colitis (2, 3). A 73-year-old man presented with a 6-week history of diarrhea. It was of insidious onset, intermittent in course, having 8–10, large-volume, watery bowel movements per day with a nocturnal component. This was associated with increased flatus and with one incidence of fecal incontinence, as well as weight loss of 5 lb over the last 6 months. He had no passage of mucus or blood per rectum, abdominal pain, or tenesmus. He denied recent travel, antibiotic use, or hospitalization in the last year. The patient’s medical history was significant for coronary artery disease, vitiligo, dyslipidemia, gastroespophageal reflux disease, chronic obstructive pulmonary disease, posttraumatic stress disorder, and Alzheimer’s disease. His medications included aspirin, somatostatin, lisinopril, rabeprazol, multivitamin tablets, and amitryptiline. Family history was negative for diarrhea, irritable bowel disease, and cancer. His physical examination and laboratory tests were within normal limits. Stool examinations for ova, parasites and white blood cells were negative. Fecal occult blood tests were negative. A qualitative fecal fat estimation was within normal limits and the fecal osmolal gap was <50 mosm/kg. A stool study for C. difficile toxin using the enzyme immunoassay (EIA) technique was positive. The patient was treated as an outpatient for C. difficile colitis with metronidazole 250 mg, three times a day for one week with very little improvement in his diarrhea. A second course of metronidazole at a dose of 250 mg four times a day for 2 weeks was then initiated and his stool was tested for C. difficile. The follow up C. difficile assay was negative, as were tests for stool ova and parasites, WBCs, and occult blood. A CT of the abdomen and a small bowel follow through were both unremarkable. Colonoscopy was performed and revealed left-sided diverticulosis and normal colonic mucosa to the hepatic flexure. There were no signs of ischemia and/or pseudomembranous colitis. Multiple random biopsies revealed diffuse thickening of the subepithelial collagen layer beneath the basement membrane. There was crypt fission seen in one of the biopsy samples; however, there were no other histopathological changes suggesting inflammatory bowel disease. Double-contrast barium enema was within normal limits. An EGD revealed antritis, and small bowel biopsies revealed normal duodenal mucosa. He was treated with Lomotil, loperamide, and Pepto-Bismol with minimal relief of symptoms. Subsequently he was begun on Asacol 3.6 g/day with clinical improvement. At threemonth follow-up, he was completely free of symptoms and had gained 4 lb. He continues to take Asacol 3.6 g/day. There is strong evidence supporting the contribution of a noxious luminal stimulant to the disease process. Jarnerot et al found that fecal stream diversion via an ostomy induced clinical and histopathologic remission of collagenous colitis (4). Conversely, the disease returned after closure of the ostomy with return of the luminal stream in contact with the colon (4). Recently, bacterial toxins have been implicated as being responsible for collagenous colitis (2, 3, 5, 6). Two separate centers have recently demonstrated the occurrence of collagenous colitis in the presence of C. difficile infection (2, 3). In a retrospective study of six patients diagnosed with collagenous colitis, Makinen et al found that three had had a previous Yersinia enterocolitica infection (6). In another study, an unidentified bacterial toxin found in the stool of a patient with collagenous colitis was shown to have a potent cytotoxic effect on McCoy cells (5). This patient responded favorably to treatment with cholestyramine, a bile-binding resin that can also bind C. difficile toxins. In addition, treatment with cholestyramine significantly decreased stool frequency in 21/27 (78%) of patients with collagenous colitis (7). Patients with collagenous colitis have also been successfully treated with antibiotics, including metronidazole, erythromycin, penicillin G, and sulfhasalazine (5, 8). There are several clues that support the theory of infection as the cause of collagenous colitis. First, there is the sudden onset of symptoms in 43% of patients with collagenous colitis in the Swedish registry (9), which is similar to that seen in an infectious disease. Second, there is the efficacy of antibacterials and a bacterial toxin binding agent, ie, cholestyramine. Third, and the strongest evidence for an association with a luminal irritant, there is the effect of fecal stream diversion on the disease. It is probable that

Association between Helicobacter pylori genotypes and severity of chronic gastritis, peptic ulcer disease and gastric mucosal interleukin-8 levels: evidence from a study in the Middle East

BackgroundThe varied clinical presentations of Helicobacter pylori (H. pylori) infection are most likely due to differences in the virulence of individual strains, which determines its ability to induce production of interleukin-8 (IL-8) in the gastric mucosa. The aim of this study was to examine association between cagA, vacA- s1 and vacA- s2 genotypes of H. pylori and severity of chronic gastritis and presence of peptic ulcer disease (PUD), and to correlate these with IL-8 levels in the gastric mucosa.MethodsGastric mucosal biopsies were obtained from patients during esophagogastroduodenoscopy. The severity of chronic gastritis was documented using the updated Sydney system. H. pylori cagA and vacA genotypes were detected by PCR. The IL-8 levels in the gastric mucosa were measured by ELISA.ResultsH. pylori cagA and/or vacA genotypes were detected in 99 patients (mean age 38.4-12.9; 72 males), of whom 52.5% were positive for cagA, 44.4% for vacA-s1 and 39.4% for vacA-s2; and 70.7% patients had PUD. The severity of inflammation in gastric mucosa was increased with vacA-s1 (p=0.017) and decreased with vacA-s2 (p=0.025), while cagA had no association. The degree of neutrophil activity was not associated with either cagA or vacA-s1, while vacA-s2 was significantly associated with decreased neutrophil activity (p=0.027). PUD was significantly increased in patients with cagA (p=0.002) and vacA-s1 (p=0.031), and decreased in those with vacA-s2 (p=0.011). The level of IL-8 was significantly increased in patients with cagA (p=0.011) and vacA-s1 (p=0.024), and lower with vacA-s2 (p=0.004). Higher levels of IL-8 were also found in patients with a more severe chronic inflammation (p=0.001), neutrophil activity (p=0.007) and those with PUD (p=0.001).ConclusionsPresence of vacA-s1 genotype of H. pylori is associated with more severe chronic inflammation and higher levels of IL-8 in the gastric mucosa, as well as higher frequency of PUD. Patients with vacA-s2 have less severe gastritis, lower levels of IL-8, and lower rates of PUD. The presence of cagA genotype is not associated with the severity of gastritis or IL-8 induction in the gastric mucosa. The association of cagA with PUD may be a reflection of its presence with vacA-s1 genotype.

Clinical epidemiology of Crohn's disease in Arabs based on the Montreal classification

Background: There has been a remarkable increase in the incidence of Crohns disease (CD) among Arabs in recent years. We conducted this study to determine the clinical epidemiology of CD in Kuwait. Methods: Sociodemographic and clinical information was collected for a continuous series of 206 Arab patients with CD and age at diagnosis and location and behavior of disease was determined according to the Montreal Classification. Results: Among the 206 patients, 100 (48.5%) were males and 106 (51.5%) females. The mean age at diagnosis (±SD) was 21.9 ± 10 years. Family history of CD was reported by 39 (18.9%) patients. The disease was limited to the ileum in 115 (55.8%) patients, whereas in 28 (13.6%) it involved the colon and in 63 (30.6%) it involved both the ileum and colon. The behavior of the disease was nonstricturing, nonpenetrating in 146 (70.9%) patients, whereas 49 (23.8%) had stricturing and 11 (5.3%) penetrating disease. Perianal disease was present in 41 (19.9%) patients. In the multivariate analysis, the use of biologic therapy and duration of the disease for ≥6 years were significantly associated with the presence of perianal disease, and the need for surgery was significantly associated with stricturing and penetrating disease behavior. Conclusions: CD among Arabs is equally common in males and females, presents at a relatively younger age, and in about half of the patients is limited to the small bowel. These features may indicate an underlying genetic predisposition for the disease in this population, which needs further investigation. (Inflamm Bowel Dis 2012;)

Rheumatic complications of inflammatory bowel disease among Arabs: a hospital-based study in Kuwait

To investigate the rheumatic complications of inflammatory bowel disease (IBD) Arab patients in relation to the clinical manifestations of IBD using the Montréal classification system in a hospital‐based population in Kuwait.

Antibodies to mutated citrullinated vimentin and anti-cyclic citrullinated peptide antibodies in inflammatory bowel disease and related arthritis.

Background: Antibodies that react with citrullinated proteins (anti‐mutated citrullinated vimentin [anti‐MCV] and second‐generation anti‐cyclic citrullinated peptide antibodies [anti‐CCP2]) are markers for rheumatoid arthritis. Recent studies have demonstrated that these antibodies are present in other arthropathies including the spondyloarthritis, psoriatic arthritis, and juvenile idiopathic arthritis. Arthritis associated with inflammatory bowel disease (IBD) takes various forms, with some shared similarities with classic spondylarthropathies. Our objective was to investigate the role of anti‐MCV and anti‐CCP2 as potential biomarkers in IBD and related arthritis. Methods: In all, 125 IBD patients (71 males, 54 females) were compared to 81 age‐ and sex‐matched healthy controls. Anti‐MCV and Anti‐CCP2 IgG were measured using an enzyme linked immunosorbent assay. Results: In the 125 IBD patients (mean age 32.6 ± 12.3 years), 44 (35.2%) had ulcerative colitis and 81 (64.8%) had Crohns disease. Forty‐four (35.2%) IBD patients developed arthritic manifestations. Antibody positivity was observed in 24/125 (19.2%) IBD patients and in 18/81 (22.2%) healthy subjects. The proportion of anti‐MCV positivity among IBD patients and healthy individuals were similar: 16.8% vs. 16.0%, P = 0.887. Anti‐CCP2 positivity among IBD patients and healthy individuals was also comparable: 6.4% vs. 6.2%, P = 0.948. Similarly, the presence of anti‐MCV and anti‐CCP2 antibodies was not different among IBD patients with and without arthritis. The mean titers of antibodies were low: anti‐MCV (29.6 ± 7.5 U/mL) and anti‐CCP2 (27.6 ± 4.0 U/mL) in IBD patients with arthritis. Conclusions: Autoantibodies to citrullinated proteins were low in IBD‐related arthritis. These findings suggest that these antibodies are not useful biomarkers in IBD to predict who may develop IBD‐related arthropathy. (Inflamm Bowel Dis 2012)

Demography and clinical course of ulcerative colitis in Arabs – a study based on the Montreal classification

Abstract Objective. Ulcerative colitis (UC) is generally considered a disease of the Caucasian populations in developed countries, but its incidence is increasing rapidly in many developing countries, including the Middle East. The objective of this study was to determine the clinical epidemiology of UC in Arabs. Material and methods. This cross-sectional medical record-based descriptive study collected sociodemographic and clinical information on 182 Arab patients with UC in Kuwait. Age at diagnosis, extent and severity of disease were determined according to the Montreal classification. Results. Among the 182 patients, 91 (50.0%) were males. The median age at diagnosis was 28.5 years. Family history of UC was reported by 26 (14.3%) patients. The extent of the disease was limited to the rectum in 34 (18.7%) patients, left sided in 67 (36.8%) and pan colitis in 81 (44.5%). At the time of inclusion in the study, 127 (69.8%) patients were in clinical remission, 53 (29.1%) had mild-to-moderate disease and 2 (1.1%) had severe colitis. Younger age at diagnosis and non-smoking were associated with more extensive colitis. The majority of patients were treated with mesalamine, steroids and immunomodulators, while biologic therapy and surgery were needed in 5% and 4% of the patients, respectively. Conclusions. UC presents more commonly at younger age among Arabs in Kuwait. Extensive disease at presentation is associated with younger age at diagnosis and absence of tobacco smoking. There also appears to be less need for surgery and biologic therapy for the disease in this population.

CASE REPORT: Vascular Pancreatic Gastric Fistula: A Complication of Colloidal 32P Injection for Nonresectable Pancreatic Cancer

Major advances in cancer therapy have occurred during the last several years, with many new and efficacious medications against neoplastic diseases becoming available. Information of these therapies is available on the Internet, and patients with terminal disease seek these therapies as a last effort to preserve their life. Access to these modalities through the experimental protocols occurs prior to our understanding and knowledge of unusual and unpredictable adverse reactions. Recognition of these adverse reactions leads to modifications in the recommendations and precautions regarding the use of these therapeutic agents. A novel treatment option for nonmetastatic locally unresectable pancreatic cancer involving injection of the radioactive isotope of phosphorus has recently been under study (1–4). We report a hitherto underscribed effect of colloidal 32P injection with creation of a vascular pancreatic gastric fistula secondary to presumed tissue necrosis. This tissue effect may have wide implications for prescribers and the recipients of such therapy.