Lilani P. Perera

QuantiFERON TB gold testing for tuberculosis screening in an inflammatory bowel disease cohort in the United States.

Background: Reactivation of latent Mycobacterium tuberculosis (TB) is a rare, yet devastating infectious complication associated with anti‐tumor necrosis factor alpha (TNF‐&agr;) therapy. We evaluated the performance of the QuantiFERON TB Gold test (QFT‐G) for TB screening in a cohort of inflammatory bowel disease (IBD) patients in the United States. Methods: We performed a retrospective, observational study of patients initiated and/or maintained on an anti‐TNF‐&agr; agent in a single IBD referral center and recorded the frequency and the test results of QFT‐G testing and the rate of TB reactivation. Results: 512 QFT‐G tests were done in 340 patients. Five patients (1.5%) had a positive, nine (2.7%) indeterminate, and 326 patients (95.8%) had a negative QFT‐G. After a mean follow‐up of 17 months there was one case of TB reactivation (0.3%). The use of immunosuppressive therapy or anti‐TNF therapy at the time of testing did not affect the results of the QFT‐G testing. Test–retest had substantial concordance (&kgr; = 0.72). 25% of patients (n = 85) had TST testing. Concordance between the TST and QFT‐G was found to be moderate (&kgr; = 0.4152, P = 0.0041). Conclusions: Most patients with negative QFT‐G tolerated anti‐TNF therapy with no evidence of TB reactivation. Concomitant use of immunosuppressive therapy or anti‐TNF did not seem to affect QFT‐G results. One patient had an indeterminate QFT‐G while on infliximab and later developed miliary TB. Concordance with TST is moderate. (Inflamm Bowel Dis 2011;)

Upper Esophageal Sphincter and Gastroesophageal Junction Pressure Changes Act to Prevent Gastroesophageal and Esophagopharyngeal Reflux During Apneic Episodes in Patients With Obstructive Sleep Apnea

BACKGROUND Gastroesophageal reflux (GER) is thought to be induced by decreasing intraesophageal pressure during obstructive sleep apnea (OSA). However, pressure changes in the upper esophageal sphincter (UES) and gastroesophageal junction (GEJ) pressure during OSA events have not been measured. The aim of this study was to determine UES and GEJ pressure change during OSA and characterize the GER and esophagopharyngeal reflux (EPR) events during sleep. METHODS We studied 15 controls, nine patients with GER disease (GERD) and without OSA, six patients with OSA and without GERD, and 11 patients with both OSA and GERD for 6 to 8 h postprandially during sleep. We concurrently recorded the following: (1) UES, GEJ, esophageal body (ESO), and gastric pressures by high-resolution manometry; (2) pharyngeal and esophageal reflux events by impedance and pH recordings; and (3) sleep stages and respiratory events using polysomnography. End-inspiration UES, GEJ, ESO, and gastric pressures over intervals of OSA were averaged in patients with OSA and compared with average values for randomly selected 10-s intervals during sleep in controls and patients with GERD. RESULTS ESO pressures decreased during OSA events. However, end-inspiratory UES and GEJ pressures progressively increased during OSA, and at the end of OSA events were significantly higher than at the beginning (P < .01). The prevalence of GER and EPR events during sleep in patients with OSA and GERD did not differ from those in controls, patients with GERD and without OSA, and patients with OSA and without GERD. CONCLUSIONS Despite a decrease in ESO pressure during OSA events, compensatory changes in UES and GEJ pressures prevent reflux.

Terminating motor events for TLESR are influenced by the presence and distribution of refluxate

Transient lower esophageal sphincter relaxation (TLESR) is frequently associated with reflux events and terminates with a primary or secondary peristaltic wave. However, it is unclear whether the presence and properties of the refluxate affect TLESR-termination events. The aims of this study were to determine the pattern of terminating esophageal motor activity after TLESR in healthy subjects and factors affecting the type of terminating motor event. Fifteen healthy subjects (7 men, age 18-56) were studied. High-resolution manometry and impedance/pH monitoring were performed simultaneously in supine position for 2 h after subjects took a 1,000-kcal meal (Awake Study). This procedure was repeated during the night under polysomnographic recording for 6-8 h after consuming a 1,000-kcal meal (Sleep Study). We categorized three types of TLESR-terminating motor events, primary peristalsis (PP), full secondary contraction (FSC), which propagated the entire esophagus, and partial secondary contractions (PSC), which started distal to the upper esophageal sphincter. Overall, 289 TLESR events were found. The percentages of TLESR events terminated by PP, FSC, and PSC were 22%, 14%, and 64%, respectively. TLESR events terminated by PP were less likely to be accompanied by reflux events. TLESR events terminated by FSC were significantly more likely to have evidence for proximal esophageal reflux and esophago-pharyngeal reflux. Findings were similar in awake and sleep states. We concluded that, in healthy recumbent subjects, the most common TLESR-termination event is a secondary contraction, rather than PP. Presence and distribution of the refluxate is a major influence on the type of terminating contraction.

Does primary sclerosing cholangitis impact quality of life in patients with inflammatory bowel disease

Background: Impairment of health‐related quality of life (HRQoL) is an important concern in inflammatory bowel disease (IBD; ulcerative colitis [UC], Crohns disease [CD]). Between 2%–10% of patients with IBD have primary sclerosing cholangitis (PSC). There has been limited examination of the disease‐specific HRQoL in this population compared to non‐PSC IBD controls. Methods: This was a retrospective, case–control study performed at a tertiary referral center. Cases comprised 26 patients with a known diagnosis of PSC and IBD (17 UC, 9 CD). Three random controls were selected for each case after matching for IBD type, gender, age, and duration of disease. Disease‐specific HRQoL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Disease activity for CD was measured using the Harvey–Bradshaw index (HB) and using the UC activity index for UC. Independent predictors of HRQoL were identified. Results: There was no significant difference in the age, gender distribution, or disease duration between PSC‐IBD and controls. There was no difference in use of immunomodulators or biologics between the 2 groups. Mean SIBDQ score was comparable between PSC‐IBD patients (54.5) and controls (54.1), both for UC and CD. Likewise, the disease activity scores were also similar (2.8 versus 3.1, P = 0.35). On multivariate analysis, higher disease activity score (−1.33, 95% confidence interval [CI] 95% CI −1.85 to −0.82) and shorter disease duration were predictive of lower HRQoL. Coexisting PSC did not influence IBD‐related HRQoL. There was a higher proportion of permanent work disability in PSC‐IBD (7.7%) compared to controls (0%). Conclusions: PSC does not seem to influence disease‐specific HRQoL in our patients with IBD but is associated with a higher rate of work disability. (Inflamm Bowel Dis 2010)

Initial Vancomycin Monotherapy is Associated With Higher Rates of Subsequent Clostridium difficile Infection in Inflammatory Bowel Disease Population

BACKGROUND: Screening and treatment for latent tuberculosis (TB) before the use of antiTNF therapy has decreased the risk of active TB. In Spain, which has a high prevalence of TB, the recommended TB screening according to national guidelines includes 2-step tuberculin skin test (TST) and chest X-ray. No data are available on the risk of developing a positive response in serial TST in inflammatory bowel disease (IBD) patients receiving long-term infliximab therapy whose initial 2-step TST was negative. The aim of this study was to determine the likelihood of detecting latent TB by the positive conversion of serial TST in a cohort of IBD patients treated with infliximab. The outcome of patients with positive conversion in the TST was also investigated. METHODS: This prospective single-center study included all consecutive IBD patients with negative 2-step TST before starting infliximab treatment. TST was positive if induration was ≥5 mm in first test or the induration was ≥5 mm in the second test (if the first TST was <5mm but provided a booster effect). We performed annual serial TST in all patients. Patients with a positive result in any serial TST were treatedwith a complete therapeutic regimen for latent TBwhile continuing on infliximab. These patients were followed to assess clinical outcomes. RESULTS: Sixty two patients (mean age 41 years, 39% male) with either Crohns disease (n=33) or ulcerative colitis (n=29) were enrolled. Eight patients had a positive TST during follow-up (mean TST induration 13 mm, range 9-20 mm). At one year, positive conversion had occurred in 5/62 (8.1%; 95% CI: 2.7-17.8) patients. At two and three years, 2/27 (7.4%; 95% CI: 0.9-24.2) patients and 1/ 11 (9.1%; 95% CI: 0.2-41.2) patients had a positive TST, respectively. The cumulative two year risk of positive conversion of TST was 7/32 (21.8%; 95% CI: 6-37.8) patients. The patients with positive conversion of TST received a 9month course of isoniazid and continued with infliximab therapy. An occupational exposure to TB was identified in only 1/8 patients. After a median of 16 months (range 3-30 months) follow-up, none of the patients with positive conversion of TST had clinical or radiological signs of active TB. CONCLUSION: Patients with IBD treated with infliximab were at high risk of conversion in the serial TST, even when the initial 2-step TST was negative. Although the exact significance of these positive conversions is not well known, annual TST is advisable as false negative responses to latent TB or new TB contacts are possible in IBD patients receiving long-term infliximab therapy, especially in countries with a high prevalence of TB.

Impact of pregnancy on health-related quality of life of patients with inflammatory bowel disease

To examine the impact of pregnancy on health‐related quality of life (HRQoL) of women with inflammatory bowel disease (IBD).

Long-Term Use of Purine Analogues in Inflammatory Bowel Disease: A Single Referral Center Experience

for more than three months, 272 (53%) patients had peripheral joint pain and/or swelling and 105 (21%) had both back pain and peripheral joint pain and/or swelling. Ninety-four IBD patients were thus far examined (table 1). Axial involvement occurred in 8 (9%) patients, peripheral involvement in 45 (48%) patients and 41 (44%) patients had axial, as well as, peripheral involvement. No differences in manifestations were observed between CD and UC. AS was found in 2 (2%) IBD patients with IBP. HLA-B27 was positive in 5 (5%) of patients and was more frequently seen in IBD patients with IBP than in IBD patients without IBP (26 vs. 1%). Three (3%) patients could be classified as axial SpA and 4 (4%) as peripheral SpA. Conclusion: Joint complaints are reported by themajority of IBD patients, more frequent in CD patients and in female patients. Arthralgia is the most often seen joint manifestation in IBD patients and mainly affects the knees and small joints of the hands. Joint manifestations did not differ between CD and UC. A positive HLA-B27 was more frequently observed in IBD patients with IBP. Table 1: Characteristics of 94 IBD patients with joint manifestations