Test For Inflammatory Bowel Disease Research Articles

Current status and prospects of laboratory tests for inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic inflammatory disease affecting the gastrointestinal tract, with a global incidence increasing year by year, and the incidence of IBD in developing countries has been increasing since the end of the last century. The pathogenesis of IBD remains unclear, which is the combined result of genetic, immune, diet, environmental and other factors. There is no gold standard for the diagnosis of IBD. Colonoscopy and mucosal biopsy are the preferred clinical tests, but these invasive and time-consuming methods are not conducive to early screening and frequent monitoring. Therefore, convenient, fast, non-invasive and reliable methods are urgently needed to assist the clinical diagnosis and evaluation of IBD. This paper aims to elaborate the laboratory diagnosis and monitoring methods of IBD based on fecal and blood indicators, which can provide ideas for the prevention, screening, diagnosis and monitoring of IBD, and help reduce its burden on people's living standards, public health and society.

Machine Learning in Antibody Diagnostics for Inflammatory Bowel Disease Subtype Classification.

Antibody testing in inflammatory bowel disease (IBD) can add to diagnostic accuracy of the main subtypes Crohn's disease (CD) and ulcerative colitis (UC). Whether modern modeling techniques such as supervised and unsupervised machine learning are of value for finer distinction of subtypes such as IBD-unclassified (IBD-U) is not known. We determined the antibody profile of 100 adult IBD patients from the Swiss IBD cohort study with known subtype (50 CD, 50 UC) as well as of 76 IBD-U patients. We included ASCA IgG and IgA, p-ANCA, MPO- and PR3-ANCA, and xANCA measurements for computing different antibody panels as well as machine learning models. The AUC of an optimized antibody panel was 85% (95%CI, 78-92%) to distinguish CD from UC patients. The antibody profile of IBD-U patients was closely related to UC. No specific antibody profile was predictive for IBD-U nor for re-classification. The panel diagnostic was in favor of UC reclassification prediction with a correct assignment rate of 69.2-73.1% depending on the cut-off applied. Supervised machine learning could not distinguish between CD, UC, and IBD-U. More so, unsupervised machine learning suggested only two distinct clusters as a likely number of IBD subtypes. Antibodies in IBD are supportive in confirming clinical determined subtypes CD and UC but have limited capacity to predict IBD-U and reclassification during follow-up. In terms of antibody profiles, IBD-U is not a distinct subtype of IBD.

Comparing outcomes from tailored meta-analysis with outcomes from a setting specific test accuracy study using routine data of faecal calprotectin testing for inflammatory bowel disease

BackgroundMeta-analyses of test accuracy studies may provide estimates that are highly improbable in clinical practice. Tailored meta-analysis produces plausible estimates for the accuracy of a test within a specific setting by tailoring the selection of included studies compatible with a specific setting using information from the target setting. The aim of this study was to validate the tailored meta-analysis approach by comparing outcomes from tailored meta-analysis with outcomes from a setting specific test accuracy study.MethodsA retrospective cohort study of primary care electronic health records provided setting-specific data on the test positive rate and disease prevalence. This was used to tailor the study selection from a review of faecal calprotectin testing for inflammatory bowel disease for meta-analysis using the binomial method and the Mahalanobis distance method. Tailored estimates were compared to estimates from a study of test accuracy in primary care using the same routine dataset.ResultsTailoring resulted in the inclusion of 3/14 (binomial method) and 9/14 (Mahalanobis distance method) studies in meta-analysis. Sensitivity and specificity from tailored meta-analysis using the binomial method were 0.87 (95% CI 0.77 to 0.94) and 0.65 (95% CI 0.60 to 0.69) and 0.98 (95% CI 0.83 to 0.999) and 0.68 (95% CI 0.65 to 0.71), respectively using the Mahalanobis distance method. The corresponding estimates for the conventional meta-analysis were 0.94 (95% CI 0.90 to 0.97) and 0.67 (95% CI 0.57 to 0.76) and for the FC test accuracy study of primary care data 0.93 (95%CI 0.89 to 0.96) and 0.61 (95% CI 0.6 to 0.63) to detect IBD at a threshold of 50 μg/g. Although the binomial method produced a plausible estimate, the tailored estimates of sensitivity and specificity were not closer to the primary study estimates than the estimates from conventional meta-analysis including all 14 studies.ConclusionsTailored meta-analysis does not always produce estimates of sensitivity and specificity that lie closer to the estimates derived from a primary study in the setting in question. Potentially, tailored meta-analysis may be improved using a constrained model approach and this requires further investigation.

Ultra-proactive Therapeutic Drug Monitoring of Infliximab Based on Point of Care Testing in Inflammatory Bowel Disease: Results of a Pragmatic Trial.

With point of care testing [POCT] for infliximab [IFX], ultraproactive therapeutic drug monitoring [TDM] with ad-hoc dose optimisation is possible in patients with inflammatory bowel disease [IBD]. To compare the clinical outcomes of an ultraproactive TDM algorithm of IFX based on POCT with reactive TDM in patients with IBD, in a pragmatic clinical trial. All patients with IBD and maintenance IFX treatment were included between June and August 2018 in two centres. Centre A applied an ultra-proactive TDM algorithm incorporating POCT, and centre B applied reactive TDM. Primary endpoint was failure of IFX therapy after 1 year. Secondary endpoints included sustained clinical remission and mucosal remission. In total 187 patients [n = 115/72 cohort A/B] were included. Cohort A had more trough level [TL] measurements compared with cohort B [8.8 vs 1/patient/year; p <0.0001], leading to a significant higher number of dose optimisations. POCT testing was required in 27% after the first round of ultra-proactive TDM and in a mean of 6.3% (standard deviation [SD] 1.9) in the subsequent rounds. Ad-hoc extra dosing was needed in 13% of the POCT. After 1 year, no difference was seen between cohort A and cohort B in IFX failure [19% vs 10%; p = 0.08], nor in sustained clinical remission [75% vs 83%; p = 0.17]. Mucosal remission was evaluated in 71 patients [38%], and was more frequent in the reactive TDM cohort [p = 0.02]. Ultra-proactive TDM in patients with IBD and maintenance IFX treatment leads to equal clinical outcomes as reactive TDM after 1 year of follow-up.

P684 Multiplex Gastrointestinal Pathogen Panel Testing is Associated with Higher Rates of Inflammatory Bowel Disease Therapy Escalation in Patients Hospitalised with Flare

Abstract Background Although the role of Clostridioides difficile infection (CDI) testing in inflammatory bowel disease (IBD) flare is well established, the function of additionally testing for non-CDI enteric infections (EI) via multiplex gastrointestinal pathogen polymerase chain reaction (GI panel) stool tests remains unclear. Patients with PCR-confirmed EI are less likely to have IBD therapy escalated; however, it is unknown whether performing testing itself affects IBD-related decision-making and outcomes. This is vital given the similar clinical presentations of flare and EI. We examined differences in IBD outcomes among patients who – in addition to testing for CDI – were and were not co-tested for EI during hospitalisation for flare. Methods We conducted a retrospective cohort study of IBD patients hospitalised with flare and tested for CDI at an urban academic medical centre. We collected data on demographics, IBD disease severity, IBD therapy, and antibiotic therapy. Patients were cohorted by co-testing for EI using a GI panel. The primary outcome was escalation of IBD therapy within 24 hours of emergency department presentation. Each IBD therapy was also studied separately. Secondary outcomes were antibiotic therapy, length of stay, and colectomy. Results Of 134 patients, 66 (49.3%) were co-tested and 7 (10.6%) had an EI detected. Disease severity and CDI rates were comparable between groups (Table 1). Co-tested patients were more likely to receive a new IBD therapy (92.4% vs. 75.0%, p=0.006), specifically intravenous (IV) steroids (89.4% vs. 36.8%, p=&amp;lt;0.001; Table 2). Patients who were not co-tested were more likely to have their existing IBD therapy continued on admission. Co-tested patients were less likely to undergo colonoscopy during admission and had lower rates of prolonged antibiotic therapy (&amp;gt;10 days; 4.5% vs. 14.7%, p=0.047), although prolonged antibiotic use was comparable between groups after excluding patients treated for CDI (5.1% co-tested vs. 1.8% not co-tested, p=0.276). Colectomy rates and length of stay were comparable between groups. Conclusion Co-testing for non-CDI enteric pathogens by GI panel was associated with a greater degree of inpatient IBD flare management – especially IV steroids. Patients not co-tested were more likely to stay on their existing IBD therapy regimen despite similar flare severities at presentation. Given the low pathogen detection rates, early negative testing for EI may promote provider confidence in intensifying IBD therapy. Early clinical improvement after therapy escalation may obviate the need for colonoscopy in these patients. Use of the GI panel may affect IBD decision-making during relapse, and should be considered in all IBD patients hospitalised with flare.

Are calprotectin and lactoferrin equivalent screening tests for inflammatory bowel disease?

BackgroundLactoferrin and calprotectin are frequently ordered stool tests used to screen patients for inflammatory bowel disease versus functional bowel disease. Current guidelines recommend using either one to screen for inflammation in the GI tract; however, little information is available on how these 2 assays compare and their use in different clinical specialties. MethodsWe compared order patterns for lactoferrin and calprotectin using data from a large reference laboratory over a 10-y period (2009–2019). We also studied the concordance of lactoferrin and calprotectin in cases where both tests were ordered concurrently. Finally, we reviewed the records at a university hospital to determine which clinicians ordered each test and the indications associated with orders. ResultsOrders for calprotectin are increasing relative to lactoferrin. The relative proportion of calprotectin orders have increased from 60% to nearly 90% over the past decade. Results for lactoferrin and calprotectin show concordance (90%). Calprotectin and lactoferrin are ordered by different clinical specialties for different indications. Calprotectin is most often ordered by gastroenterologists in the context of abdominal pain. Lactoferrin is most often ordered by primary care providers in the context of acute diarrhea. ConclusionLactoferrin and calprotectin are not treated as equivalent tests by clinicians.

Patients’ perceptions of faecal calprotectin testing in inflammatory bowel disease: results from a prospective multicentre patient-based survey*

Introduction: Despite its success, there appears to be practical issues with Faecal Calprotectin (FC) testing in Inflammatory Bowel Diseases (IBD), including sample collection, delivery and processing delays. Patients’ perception and barriers to FC testing are yet to be explored in clinical practice.Method: A prospective patient survey was undertaken at IBD units in UK, Europe and Australia. A 9-point patient-based questionnaire was completed in clinic and included demographics, previous FC testing and FC sample difficulty rating score. Predictors of testing difficulty were derived using multivariable logistic regression analysis.Results: A total of 585 patients with IBD completed the survey; 306 males with a median age of 43 years (IQR: 31–54). There were 446 patients (76%) who had prior FC testing experience. Of these, 37% (n = 165) rated FC testing difficult; ‘sample collection’ (n = 106; 67%) being the most common reason reported. Multivariable regression analysis identified age <49 years (odds ratio (OR): 2.5, CI:1.6-4.0), disease duration <35 months (OR 1.4, CI:0.9–2.1) and testing location (UK centre: OR 1.9, CI:1.2-3.1) as predictors of a difficult FC rating score.Conclusions: A total of 37% of patients find FC testing challenging, in particular those aged <49 years, disease duration <35 months. Further studies understanding and addressing these practical issues may aid higher FC uptake in clinic.

Thiopurine metabolite testing in inflammatory bowel disease.

Thiopurine use in inflammatory bowel disease (IBD) is limited by drug toxicity and lack of therapeutic efficacy. We assessed the utility of thiopurine metabolite testing and the relationship between disease activity, dose, and metabolite levels in a real world setting. Patients identified from pathology databases (2007-2012) at two tertiary IBD centers were included if they had thiopurines for at least four weeks. Demographics, dose, test indication, clinical status, action taken, and outcome were obtained by retrospective medical record review. A total of 169 patients were included. 6-Thioguanine (TGN) levels were sub-therapeutic in 52%, therapeutic in 34%, and supratherapeutic in 14%. Test indication was active disease (79%), adverse effect (11%), or adherence assessment (7%). TGN trended lower in the active disease group compared to those with adverse effects (273 (+/- 23.2) versus 447 (+/- 117.7) pmol/8 × 10(8) RBC, P = 0.05). Weight-based dosing did not improve rates of therapeutic TGN levels (under-dosed 31.5% vs standard dose 35.4%), but was significantly associated with shunting toward 6-MMP (23.1% vs 6.8%, P = 0.008, OR = 4.1). Testing resulted in a change in patient treatment in 86% of patients with active disease and subtherapeutic levels and in 68% of tested patients overall. Metabolite testing resulted in a change in management in most patients not responding to thiopurines or experiencing adverse events. Weight-based dosing did not increase rates of therapeutic levels but was associated with increased 6MMP shunting.

Sa1192 Predictors of Indeterminate QuantiFERON-TB Gold Testing in Inflammatory Bowel Disease and Impact on Clinical Outcomes

Sa1192 Predictors of Indeterminate QuantiFERON-TB Gold Testing in Inflammatory Bowel Disease and Impact on Clinical Outcomes

Changes in Physiology and Pathophysiology of Calprotectin Excretion from Neonate to Adult

Background: Measurement of faecal calprotectin (FCP) concentrations is a theoretically justified laboratory test used in lieu of quantitative evaluation of neutrophils penetrating into the intestinal lumen. This parameter is organspecific and identifies intestinal inflammation. Aim: Search for individual interpretation of the cut-off values for the FCP test, taking into consideration different age groups of patients and causes of intestinal inflammation. Methods: Review of the literature data about the calprotectin concentrations in the meconium and faeces of neonates, infants, older children and adults. Results: FCP levels in meconium and faeces of infants are significantly higher than the concentration in older children and adults. In adults FCP is a simple and sensitive screening test for inflammatory bowel disease, also used in monitoring of disease activity and treatment efficacy. However, the diagnostic significance of high FCP levels in healthy infants and young children remains unclear. Conclusions: FCP levels in the first year of life are higher than in adults and probably reflect ‘physiological’ intestinal inflammation associated with the adaptation of the neonate’s intestine to life outside the uterus. On the other hand, high CP levels in meconium may indicate the important role played by neutrophils in the fetal intestine during its development.

P-034: Diagnostic non-invasive tests for inflammatory bowel disease in children, a systematic review and meta-analysis

P-034: Diagnostic non-invasive tests for inflammatory bowel disease in children, a systematic review and meta-analysis

P312 Thiopurine metabolite testing in inflammatory bowel disease

P312 Thiopurine metabolite testing in inflammatory bowel disease

P-106 Laboratory Testing in Patients with Inflammatory Bowel Disease Increases After the Initial Diagnostic Period

Laboratory testing is an important component of diagnosis and management of chronic diseases. Similar to other medical interventions, laboratory studies contribute to rising healthcare costs. There is increased focus on laboratory expenditures and suggestions that over-utilization may reflect suboptimal chronic disease management. Individuals with inflammatory bowel disease require periodic, and occasionally frequent, laboratory testing. There is limited data assessing the amount of labs performed during the course inflammatory bowel disease. This study evaluated the amount of laboratory testing by gastroenterologists in individuals with inflammatory bowel disease at the time of diagnosis compared to later in the course of the disease. A medical record review of inflammatory bowel disease patients at a university medical center during an 18-month period was performed. Patients in whom the date of diagnosis was unknown were excluded. Patient age, gender, disease type, date of diagnosis, and outpatient labs by gastroenterologists were obtained. The amount of labs ordered during the study period in individuals diagnosed within 0–6 months and in those with a diagnosis >6 months, in individuals diagnosed within 0–18 months and in those with a diagnosis >18 months, and in individuals diagnosed within 0–30 months and in those with a diagnosis >30 months were compared. A database, maintaining patient confidentiality, was created. Statistical analysis was performed using unpaired T testing, with statistical significance set at P < 0.05. The study was approved by the university institutional review board. Two hundred ninety-five medical records (174 women, 121 men; mean age of 41.1 years) were reviewed. One hundred sixty patients had Crohn’s disease, 133 ulcerative colitis and 2 with indeterminate colitis. The average disease duration was 12.37 years. During the study period, the number of labs performed 0–6 months following diagnosis were significantly less than the number of labs performed in individuals with a diagnosis >6 months (3.84 versus 8.91, P = 0.019). There was no significant difference in the number of labs performed in individuals 0–18 months following diagnosis compared to individuals with a diagnosis >18 months (7.24 versus 8.75, P = 0.39). Additionally, there was no significant difference in the number of labs performed in individuals 0–30 months following diagnosis compared to individuals with a diagnosis >30 months (8.83 versus 8.39, P = 0.83). Individuals with chronic diseases, including inflammatory bowel disease, have more health care encounters and laboratory testing than others. Few studies have compared the amount of laboratory testing in inflammatory bowel disease at the time of diagnosis and later in the course of the disease. This study revealed that during an 18-month period, there were less labs obtained in individuals who were diagnosed within 0–6 months compared to individuals who had been diagnosed for >6 months. Increased labs later in the course of disease likely reflect the monitoring necessary for health maintenance, during exacerbations and for medication stabilization. As the focus on health care costs continues, it is important that there is recognition that laboratory testing in inflammatory bowel disease may not be a reflection of excess health care expenditure, but necessary to ensure optimal management.

Fecal Calprotectin to Screen for IBD?

Van de Vijver E, Schreuder AB, Cnossen WR, et al. Safely ruling out inflammatory bowel disease in children and teenagers without referral for endoscopy. Arch Dis Child. 2012; 97 (12): 1014– 1018; doi: 10.1136/archdischild-2011-301206[OpenUrl][1][Abstract/FREE Full Text][2] Researchers in Belgium and the Netherlands conducted a diagnostic accuracy study to determine if the use of fecal calprotectin as a screening test for inflammatory bowel disease (IBD) could reduce the number of children undergoing endoscopy. Participants included children and teens 6 to 18 years of age with abdominal complaints suggesting IBD who were evaluated in pediatric clinics of 6 general hospitals and 1 tertiary care hospital in northern Holland. Inclusion criteria included persistent diarrhea for >4 weeks or recurrent (>2 episodes in 6 months) abdominal pain and diarrhea, and at least 1 of the following: rectal bleeding, unintended weight loss, linear growth retardation, perianal symptoms (skin tag, fistula, fissure, or abscess), anemia, other extraintestinal manifestations (erythema nodosum, arthritis, uveitis), or increased inflammatory markers (ESR or CRP). At entry, a stool sample was … [1]: {openurl}?query=rft.jtitle%253DArch%2BDis%2BChild%26rft_id%253Dinfo%253Adoi%252F10.1136%252Farchdischild-2011-301206%26rft_id%253Dinfo%253Apmid%252F23019289%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=archdischild&resid=97/12/1014&atom=%2Faapgrand%2F29%2F4%2F38.atom

The Utility of Thiopurine Methyltransferase Enzyme Testing in Inflammatory Bowel Disease

To assess the levels of red blood cell thiopurine methyltransferase (TPMT) in subjects with inflammatory bowel disease (IBD) and to determine how these levels impacted thiopurine dosing and leukopenia over the first six months of therapy. A retrospective chart review was performed on all adult IBD patients (n=423, 88.2% Caucasian) who had TPMT levels measured by 11 participating gastroenterologists in Manitoba between 2008 and 2010. In addition to descriptive data, white blood cell count, dose and reason for discontinuation were analyzed for the first six months of therapy. Patients receiving ≥2.0 mg/kg of azathioprine (AZA) or ≥1.0 mg/kg of 6-mercapatopurine were considered to be 'substantially' dosed. Of the 423 patients, 8.3% had intermediate levels and 93.4% had normal levels of TPMT. Only one subject had a low level. A total of 216 patients had sufficient data to be included for full analysis. Patients with intermediate TPMT levels were generally started at lower doses of thiopurine than patients with normal TPMT levels (mean [± SD] 1.0±0.6 mg/kg versus 1.8±0.5 mg/kg). Of the subjects with normal TPMT levels, only 37.8% were dosed with ≥2.0 mg/kg of AZA. Each month, approximately 5% of subjects were leukopenic. These subjects received a mean overall AZA dose of 1.9±0.3 mg/kg and had a mean white blood cell count of 3.8±0.4×10(9)/L. Normal TPMT levels did not prevent the development of leukopenia, although life-threatening leukopenia was rare. Physicians are not using TPMT levels to substantially dose thiopurines at the outset, which may limit the speed at which adequate doses are reached to facilitate remission.

Peripheral blood MicroRNAs distinguish active ulcerative colitis and Crohnʼs disease

Crohn's disease (CD) and ulcerative colitis (UC) result from pathophysiologically distinct dysregulated immune responses, as evidenced by the preponderance of differing immune cell mediators and circulating cytokine expression profiles. MicroRNAs (miRNAs) are small, noncoding RNAs that act as negative regulators of gene expression and have an increasingly recognized role in immune regulation. We hypothesized that differences in circulating immune cells in CD and UC patients are reflected by altered miRNA expression and that miRNA expression patterns can distinguish CD and UC from normal healthy individuals. Peripheral blood was obtained from patients with active CD, inactive CD, active UC, inactive UC, and normal healthy adults. Total RNA was isolated and miRNA expression assessed using miRNA microarray and validated by mature miRNA quantitative reverse-transcription polymerase chain reaction. Five miRNAs were significantly increased and two miRNAs (149* and miRplus-F1065) were significantly decreased in the blood of active CD patients as compared to healthy controls. Twelve miRNAs were significantly increased and miRNA-505* was significantly decreased in the blood of active UC patients as compared to healthy controls. Ten miRNAs were significantly increased and one miRNA was significantly decreased in the blood of active UC patients as compared to active CD patients. Peripheral blood miRNAs can be used to distinguish active CD and UC from healthy controls. The data support the evidence that CD and UC are associated with different circulating immune cells types and that the differential expression of peripheral blood miRNAs may form the basis of future diagnostic tests for inflammatory bowel disease.

Genetic Testing for Inflammatory Bowel Disease: Focus Group Analysis of Patients and Family Members

Inflammatory bowel disease (IBD) is a chronic gastrointestinal illness with complex genetic underpinnings. Genetic testing for IBD, in particular, for high-risk alleles, is not currently used in clinical practice. Further, preferences and concerns of patients and their family members regarding a genetic test for this condition are not well studied. Thirty IBD patients and eighteen unaffected first-degree family members or spouses listened to a general educational session about IBD and then participated in one of eight focus groups in order to identify themes of concern and interest regarding a genetic test for IBD. Participants also completed demographic, attitude, and knowledge surveys prior to the focus group sessions. Qualitative analysis of transcripts was performed, and simple comparative statistics of survey data were calculated. There were few differences between the responses of patients and unaffected family members. Participants were interested in undergoing genetic testing for IBD despite the fact that information at this time cannot be clinically applied in the diagnosis, prognosis, or treatment of the disease. Advantages of genetic testing commonly identified included benefit to themselves and family members through the possibility of earlier diagnosis and targeted therapies. Disadvantages commonly cited were discrimination by insurance companies and employers and concerns about protection of information. In general, participants were interested in receiving both pre- and posttest information from an informed gastroenterologist, which included a clear basis for testing and the implications of the results for themselves and for family members. The results of the first focus group assessment about genetic testing for IBD reveal themes that are similar in interests and concerns to other genetic diseases. These findings will aid in the construction of patient-centered models of genetic testing that emphasize patient education and interpretation of results.

Attitudes toward genetic testing in patients with inflammatory bowel disease

Significant progress has been observed in our understanding of the role of genetics in inflammatory bowel disease susceptibility and phenotype. The clinical role of genetic testing for inflammatory bowel disease is not well developed, but may become important as more susceptibility genes are found. The aim of this study was to evaluate the attitudes of patients with inflammatory bowel disease toward genetic testing. Two hundred and fifty patients (108 ulcerative colitis, 142 Crohn's disease) attending the outpatient clinic completed a questionnaire regarding clinical and family history data, as well as their attitudes toward genetic testing for inflammatory bowel disease. Ninety percent (225/250) of all patients expressed an interest in undergoing genetic testing themselves, with 87.6% (219/250) also expressing a desire for their children to be tested. Although the proportion of ulcerative colitis and Crohn's disease patients interested in testing was similar, levels of interest decreased as the predictive value of a putative genetic test decreased. A comparable proportion of those with [80/86 (93.0%)] and those without [145/164 (88.4%)] a family history of inflammatory bowel disease expressed an interest in genetic testing. More patients who had received immunomodulating or biologic therapies [123/128 (96.1%)], however, wished to undergo testing than those who had not received these medications [78/93 (83.9%; P<0.01)]. Patients with inflammatory bowel disease have a high level of interest in genetic testing, both for themselves and for their children, and this will have an impact upon the provision of genetic services as progress is made toward defining a clinical role for inflammatory bowel disease susceptibility genes.

Use of Serologic Markers as a Screening Tool in Inflammatory Bowel Disease Compared With Elevated Erythrocyte Sedimentation Rate and Anemia

The purpose of this work was to evaluate the use of serologic testing as a screening test for inflammatory bowel disease compared with erythrocyte sedimentation rate and hemoglobin in a referred patient population with suspected inflammatory bowel disease. A retrospective study was performed, reviewing medical charts of patients who had inflammatory bowel disease serology performed at Prometheus Laboratories from September 2002 to September 2004. Patients were divided into 4 categories: ulcerative colitis, Crohn disease, indeterminate colitis, and noninflammatory bowel disease groups. Patients were categorized based on clinical evaluation by board-certified pediatric gastroenterologists. A total of 227 patients seen at the Lucile Packard Children's Hospital Gastroenterology Clinic had inflammatory bowel disease serology performed at or before the time of diagnosis. Seventeen charts were excluded secondary to inadequate information. Forty children were found to have inflammatory bowel disease, a prevalence of 19%. Overall, serologic testing for inflammatory bowel disease had 60% sensitivity and 92% specificity. A positive laboratory test for anemia or an elevated erythrocyte sedimentation rate had 83% sensitivity, whereas the combination of anemia and elevated erythrocyte sedimentation rate had 96% specificity. The positive predictive value of serologic testing was 60% compared with 79% in patients with anemia and elevated erythrocyte sedimentation rate. The positive predictive value of serologic testing in the subgroup of subjects without rectal bleeding (139 subjects) was only 35% compared with 60% using routine tests. Almost one third of all positive serologic tests were in patients with no demonstrable inflammatory bowel disease. As a pediatric inflammatory bowel disease screening strategy for the general pediatrician or gastroenterologist, the measurement of the combination of erythrocyte sedimentation rate and hemoglobin has a higher positive predictive value and is more sensitive, more specific, and less costly than commercial serologic testing.

The Complexity and Challenges of Genetic Counseling and Testing for Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is an umbrella term referring to two chronic idiopathic intestinal diseases: ulcerative colitis (UC) and Crohn's disease (CD). Both UC and CD are characterized by immune activation that leads to symptoms, but the location, severity and behavior of the inflammation varies among individuals and in characteristic ways between UC and CD. A majority of patients with IBD are diagnosed in young adulthood, but the response to therapy is variable and difficult to predict, with some patients demonstrating a prompt and effective remission while others have continuous symptoms that do not respond to existing medical options. Surgery remains a frequent and necessary occurrence among patients with IBD, but in UC it is considered curative, while in CD only temporizing. Clinical observations, epidemiological studies, and molecular genetics have provided strong evidence that both genetic and environmental factors are important determinants for disease susceptibility. In recent years, a number of genes have been identified that associate with CD and UC, although the clinical utility of these discoveries in patients or in susceptible family members has not been determined. Nonetheless, it is hoped that these fundamental advances in our understanding of IBD will lead to better therapies for patients and prevention strategies for those who are susceptible. Effective incorporation of clinical genetic testing for IBD into practice will require appropriate education and counseling.