Gillian Watermeyer

World Gastroenterology Organization Practice Guidelines for the Diagnosis and Management of IBD in 2010

Inflammatory bowel disease (IBD) represents a group of idiopathic, chronic, inflammatory intestinal conditions. Its two main disease categories are: Crohns disease (CD) and ulcerative colitis (UC), which feature both overlapping and distinct clinical and pathological features. While these diseases have, in the past, been most evident in the developed world, their prevalence in the developing world has been gradually increasing in recent decades. This poses unique issues in diagnosis and management which have been scarcely addressed in the literature or in extant guidelines. Depending on the nature of the complaints, investigations to diagnose either form of IBD or to assess disease activity will vary and will also be influenced by geographic variations in other conditions that might mimic IBD. Similarly, therapy varies depending on the phenotype of the disease being treated and available resources. The World Gastroenterology Organization has, accordingly, developed guidelines for diagnosing and treating IBD using a cascade approach to account for variability in resources in countries around the world.

Use of thiopurines in the treatment of inflammatory bowel disease is associated with an increased risk of non-melanoma skin cancer in an at-risk population: A cohort study

Background and Aim:  The thiopurines azathioprine and 6‐mercaptopurine are effective in the management of patients with inflammatory bowel disease (IBD) in whom aminosalicylates, antibiotics and corticosteroids have failed to induce or maintain remission. Long‐term use of these agents has been linked to a greatly increased risk of non‐melanoma skin cancer and lymphatic cancer in organ transplant recipients. There is some evidence to suggest that IBD patients receiving thiopurines might be at increased risk of cancer. Our aim was to determine the incidence of cancer in a cohort of patients with IBD managed in our clinic, and to relate this to thiopurine exposure.

Childhood helminth exposure is protective against inflammatory bowel disease: A case control study in South Africa

Background:Inflammatory bowel disease (IBD) is more common in countries with improved hygiene, suggesting that environmental exposures may be associated with its development. The primary objective of this study was to examine the association between self-reported childhood helminth infection and the development of IBD in South Africa. Methods:Unmatched case–control study. Logistic regression was used to model associations with IBD. Results:There were 88 patients with Crohn’s disease (CD), 63 with ulcerative colitis (UC), and 219 control subjects. Of the 151, 93 (61.6%) IBD subjects (35 of 63 [55.6%] had UC and 58 of 88 [65.9%] had CD) reported childhood helminth exposure compared with 200 of 219 (91.3%) non-IBD subjects (P < 0.001). Helminth infection (adjusted odds ratio [AOR] = 0.2; 95% confidence interval [CI], 0.1–0.4), shared housing (AOR = 0.1; 95% CI, 0.04–0.4), and raw beef consumption (AOR = 0.2; 95% CI, 0.1–0.6) were protective, whereas urban dwelling (AOR = 4.2; 95% CI, 2.0–8.8) and parental tertiary education (AOR = 18.2; 95% CI, 3.2–103.7) were associated with CD. Helminth infection (AOR = 0.2; 95% CI, 0.1–0.6), mixed race (AOR = 0.1; 95% CI, 0.03–0.5), smoking (AOR = 0.2; 95% CI, 0.07–0.5), shared housing (AOR = 0.1; 95% CI, 0.01–0.4), and raw beef consumption (AOR = 0.1; 95% CI 0.04–0.5) were protective against UC, whereas parental tertiary education (AOR = 12.7; 95% CI, 1.0–157.4) was associated with UC. Conclusion:This study demonstrates a protective association of childhood helminth infection against the development of IBD and supports the “hygiene hypothesis” that improved living conditions may increase the incidence of IBD. Our epidemiologic conclusions provide support that helminths may have immunomodulatory effects which provides protection against the development of IBD later in life.

Guideline for the diagnosis and treatment of chronic pancreatitis

BACKGROUND Chronic pancreatitis (CP) is defined as a continuing inflammatory disease of the pancreas characterised by irreversible morphological changes, often associated with pain and with the loss of exocrine and/or endocrine function that may be clinically relevant. Alcohol is the predominant cause of CP in the western world and is particularly prevalent in South Africa, especially in the indigent patient. CP ranks high among intractable diseases of the gastrointestinal tract. The tendency for substance abuse in the alcohol-induced group poses major psychological and socio-economic problems. OBJECTIVE CP is a disease with significant clinical and pathological heterogeneity. Level 1 evidence to support definitive guidelines for diagnosis, medical management and interventional therapy is lacking. Despite this paucity of robust scientific evidence, it is important to provide some assistance based on the best available evidence as to the current standard of care for CP in the South African context; this will aid all involved in the management of the disease, and includes clinicians, health care managers and funders. SCOPE The guidelines were developed as recommendations addressing the diagnosis, medical management and interventions, both endoscopic and surgical, for the management of a very complex and heterogeneous disease of the pancreas. The recommendations are particularly relevant in the South African context where the predominant patho-aetiological agents are alcohol-associated with smoking. RECOMMENDATIONS The guidelines provide clear recommendations regarding the diagnostic modalities available, both imaging (which includes MRI and endoscopic ultrasound (EUS)) and pancreatic function tests. The section on medical management makes recommendations on the use of analgesics, enzyme replacement and other therapeutic options in the non-interventional management of the majority of patients with CP. The section on interventional procedures identifies the indications and options available for the interventional management of both uncomplicated and complicated CP. The role of endoscopic and surgical modalities is defined, but it is in this context especially that the best available evidence, combined with the experience of the group, influenced the recommendations put forward. Owing to the lack of evidence and the complexity of the disease, it is recommended that, where possible, CP is managed in the context of a multidisciplinary team. VALIDATION The guidelines are based on best practice principles determined by the available evidence and the opinions of the group, which comprised 7 medical and surgical gastroenterologists with significant experience in dealing with patients with chronic pancreatitis in the South African context. The group convened between May 2009 and August 2010 under the auspices of the Hepato-Pancreatico-Biliary Association of South Africa (HPBASA) and the South African Gastroenterology Society (SAGES), and the guidelines are the result of broad consensus within this group. The draft was presented to other experts in this field of endeavour to ensure broader participation and consensus. PLANS FOR GUIDELINE REVISION: HPBASA and SAGES will publish a revised modification of the recommendations when new levels 1 and 2 evidence data are published.

World Gastroenterology Organisation Global Guidelines Inflammatory Bowel Disease: Update August 2015.

Review Team: Charles N. Bernstein, MD (Chair, Canada), Abraham Eliakim, MD (Israel), Suliman Fedail, MD (Sudan), Michael Fried, MD (Switzerland), Richard Gearry, MD (New Zealand), Khean-Lee Goh, MD (Malaysia), Saeed Hamid, MD (Pakistan), Aamir G. Khan, MD (Pakistan), Igor Khalif, MD (Russia), Siew C. Ng, MD (Hong Kong, China), Qin Ouyang, MD (China), Jean-Francois Rey, MD (France), Ajit Sood, MD (India), Flavio Steinwurz, MD (Brazil), Gillian Watermeyer, MD (South Africa), and Anton LeMair, MD (The Netherlands)

The Association between Race and Crohn's Disease Phenotype in the Western Cape Population of South Africa, Defined by the Montreal Classification System

Background Inter-racial differences in disease characteristics and in the management of Crohns disease (CD) have been described in African American and Asian subjects, however for the racial groups in South Africa, no such recent literature exists. Methods A cross sectional study of all consecutive CD patients seen at 2 large inflammatory bowel disease (IBD) referral centers in the Western Cape, South Africa between September 2011 and January 2013 was performed. Numerous demographic and clinical variables at diagnosis and date of study enrolment were identified using an investigator administered questionnaire as well as clinical examination and patient case notes. Using predefined definitions, disease behavior was stratified as ‘complicated’ or ‘uncomplicated’. Results One hundred and ninety four CD subjects were identified; 35 (18%) were white, 152 (78%) were Cape Coloured and 7(4%) were black. On multiple logistic regression analysis Cape Coloureds were significantly more likely to develop ‘complicated’ CD (60% vs. 9%, p = 0.023) during the disease course when compared to white subjects. In addition, significantly more white subjects had successfully discontinued cigarette smoking at study enrolment (31% vs. 7% reduction, p = 0.02). No additional inter-racial differences were found. A low proportion of IBD family history was observed among the non-white subjects. Conclusions Cape Coloured patients were significantly more likely to develop ‘complicated’ CD over time when compared to whites.

Vitamin D Deficiency Increases the Risk for Moderate to Severe Disease Activity in Crohn's Disease Patients in South Africa, Measured by the Harvey Bradshaw Index

Objective: Vitamin D has immunoregulatory properties and appears to influence disease outcomes in patients with Crohns disease (CD). The primary aim of this study was to evaluate the association between vitamin D status and CD activity in South Africa. Methods: In a cross-sectional study performed between September 2011 and January 2013, serum 25-hydroxyvitamin D (25(OH)D) was measured in 186 consecutive patients with CD seen at 2 inflammatory bowel disease (IBD) centers and 199 healthy controls in the Western Cape, South Africa. Lifestyle and clinical variables were identified using an investigator-administered questionnaire, as well as clinical examination and patient case notes. Vitamin D status was evaluated in 2 ways: ≤20 ng/mL vs ≥21 ng/mL and ≤29 ng/mL vs ≥30 ng/mL. Disease activity was measured by the Harvey Bradshaw Index (HBI). Various 25(OH)D threshold concentrations for predicting a higher HBI score were also investigated. Results: On multiple log-binomial regression analysis, higher HBI scores and not having taken vitamin D supplementation in the 6 months prior to enrollment were identified as risk factors for vitamin D deficiency in patients with CD, defined either as ≤20 ng/mL or as ≤29 ng/mL (p < 0.03). Compared to patients with HBI < 5, those with HBI ≥ 8 were 2.5 times more likely to have 25(OH)D concentrations ≤21 ng/mL (prevalence risk [PR] = 2.5; 95% confidence interval [CI], 1.21–6.30). The risk was similar, though not as high, when defined as ≤29 ng/mL (PR = 2.0; 95% CI, 1.13–3.51). When vitamin D deficiency was defined as <20, <30, <40, and <50 ng/mL, the sensitivity and specificity obtained were 44.9% and 78.8%; 75.5% and 62.4%; 86.7% and 44.7%; and 92.9% and 23.5%, respectively (area under the curve = 0.71; p < 0.0001). Conclusion: Low serum 25(OH)D was associated with increased CD activity in a South African cohort.

Evaluation of a locally produced rapid urease test for the diagnosis of Helicobacter pylori infection

BACKGROUND The rapid urease test (RUT) is used at Groote Schuur Hospital for diagnosing Helicobacter pylori infection. This is an in-house method, which has not been validated. OBJECTIVE To validate our practice of reading the RUT immediately after endoscopy (RUT(0)), by comparing this with a reading at 24 hours (RUT(24)) and with histological analysis. DESIGN Ninety consecutive patients undergoing upper endoscopy over a 6-week period from October 2005 to November 2005, and in whom rapid urease testing was indicated, were included in the study. Patients with recent exposure (within 2 weeks of endoscopy) to proton pump inhibitors (PPIs), histamine receptor antagonists (H2RAs) and antibiotics (confounders) were noted and included in the cohort. Two antral and two body biopsies were taken for histological examination and a third antral biopsy was placed in the RUT bottle. Both haematoxylin and eosin and modified Giemsa staining methods were used to identify H. pylori. The RUT was read immediately (within 5 minutes of upper endoscopy) (RUT(0)), as per our current practice, and each specimen was re-read at 24 hours (RUT(24)). Sensitivity, specificity, positive and negative predictive values and the impact of confounders were calculated. RESULTS Of the 90 patients undergoing rapid urease testing, 39% were male and 61% were female, with a mean age of 55 years (range 22-79 years). Histological examination revealed H. pylori in 67.8% (N=61) of the biopsy specimens. In the 65 patients without confounders, the sensitivity and specificity of the RUT(0) were 65.9% and 100% respectively, and 90.9% and 100% for RUT(24). After including the 25 patients with confounders, the sensitivity and specificity were 68.8% and 100% for RUT(0), and 90.1% and 100% for RUT(24) respectively. Thirteen RUT(0) specimens (30.9%) that were initially negative became positive at the RUT(24) reading. There were 6 (9.8%) RUT(0)- and RUT(24)-negative but histology-positive specimens. Four of these 6 false-negative RUT(24) results could be accounted for by a low H. pylori density on histological analysis (2 patients were taking PPIs). Confounders did not alter the sensitivity and specificity outcomes or impact on the number of false-negative RUTs. CONCLUSIONS Our locally prepared RUT is a specific test for the detection of H. pylori infection. The sensitivity is greatly enhanced by reading the test at 24 hours. The use of PPIs, H(2)RAs and antibiotics preceding endoscopy did not impact significantly on the results.

A comparison of Clostridium difficile diagnostic methods for identification of local strains in a South African centre.

Accurate diagnosis of Clostridium difficile infection is essential for disease management. A clinical and molecular analysis of C. difficile isolated from symptomatic patients at Groote Schuur Hospital, South Africa, was conducted to establish the most suitable clinical test for the diagnosis and characterization of locally prevalent strains. C. difficile was detected in stool samples using enzyme-based immunoassays (EIA) and nucleic acid amplification methods, and their performance was compared with that of C. difficile isolation using direct selective culture combined with specific PCR to detect the C. difficile tpi gene, toxin A and B genes and binary toxin genes. Toxigenic isolates were characterized further by ribotyping. Selective culture isolated 32 C. difficile strains from 145 patients (22 %). Of these, the most prevalent (50 %) were of ribotype 017 (toxin A- B+) while 15.6 % were ribotype 001 (toxin A+B+). No ribotype 027 strains or binary toxin genes (cdtA and cdtB) were detected. The test sensitivities and specificities, respectively, of four commercial clinical diagnostic methods were as follows: ImmunoCard Toxins A & B (40 % and 99.1 %), VIDAS C. difficile Toxin A & B (50 % and 99.1 %), GenoType CDiff (86.7 % and 88.3 %) and Xpert C. difficile (90 % and 97.3 %). Ribotype 001 and 017 strains had a 100 % detection rate by Xpert C. difficile, 100 % and 93.3 % by GenoType CDiff, 75 % and 53.3 % by ImmunoCard and 75 % and 60 % by VIDAS, respectively. The overall poor performance of EIA suggests that a change to PCR-based testing would assist diagnosis and ensure reliable detection of locally prevalent C. difficile 017 strains.

The efficacy of endoscopic therapy in bleeding peptic ulcer patients

BACKGROUND Endotherapy is the primary modality for the control of bleeding from peptic ulceration. OBJECTIVE To assess the efficacy of endoscopic intervention for high-risk bleeding peptic ulcer disease and to benchmark our surgical and mortality rates. METHODS Two hundred and twenty-seven patients with peptic ulcers stratified by Rockall and Forrest scores as at high risk for re-bleeding underwent therapeutic intervention (adrenalin injection) between January 2004 and December 2009. The median age of the patients was 57 years (range 19 - 87 years); 60% were males. Results. Primary endoscopic haemostasis failed in 51/227 patients (22.5%); 18 patients (7.9%) required surgery for bleeding not controlled at initial or second endoscopy; and 29 patients (12.8%) died, 12 by day 3 and 17 by day 30. Fifteen patients, all with significant medical co-morbidity, died after successful primary endotherapy, and 4 died after surgery. Surgical patients required more blood (odds ratio (OR) 1.45, p=0.0001) than those not undergoing surgery, but had similar mortality. Rebleeding was the only predictor of death in patients who died by day 3 (OR 18.77). A high Rockall score was the only predictor of death by day 30 (OR 1.98). CONCLUSION The overall surgical and mortality rates were 7.9% and 12.8%, respectively. Over half the deaths resulted from medical co-morbidity, despite successful primary endotherapy. This finding is supported by the use of the Rockall score as a predictor of mortality at day 30. Improving the technical success of primary endoscopic haemostasis, currently 77.5%, has the potential to reduce rebleeding after primary endotherapy, a predictor of death at day 3 in this study.