Background: During screening for latent tuberculosis infection (LTBI), before anti-TNF-alpha treatment, most patients are already receiving immunosuppressive therapy. Objective was to evaluate the performance of the QuantiFERON In-Tube (QFT-IT) and the Tuberculin Skin Test (TST) in these groups Methods: We included 248 patients with Ulcerative Colitis, Crohns disease, rheumatoid arthritis, and spondylo-arthropathy. Results: QFT-IT was positive in 7/248 (3%), negative in 229 (92%), and indeterminate in 12 (5%). TST was positive in 54/238 (23%) patients. Chest X-ray was suspect in 5/236 (2%), and 35/167 (21%) had risk-factors. We found a pronounced negative effect on QFT-IT and TST performance associated with prednisolone treatment; the IFN- response to mitogen stimulation was impaired (median IFN- response 4.9IU/ml (IQR0.8-10.0)) compared to patients a) not receiving corticosteroids (median 10.0 (IQR 5.0-10.0) (p=0.0015) or b) receiving long-acting corticosteroids (median 10.0 (IQR 9.7-10.0) (p=0.0058). Prednisolone treatment was strongly associated with negative TST, AOR 0.22 (0.1-0.8 (p= 0.018), and with an increased risk of indeterminate QFT-IT results AOR (16.1-69.0) p=0.001). No negative effect was found for long-acting corticosteroids. Prednisolon doses above 10 mgresulted in 27% indeterminate results. Conclusion: Oral prednisolone severely suppressed QFT-IT and TST performance whereas long-acting corticosteoroids, Metotrexate, Azathioprin and 5-ASA did not have similar detrimental effect. Patients should be screened for LTBI with QFT-IT or TST prior to initiation of prednisolone.
During screening for latent tuberculosis infection (LTBI), before anti-tumor-necrosis-factor-α treatment, most patients are already receiving immunosuppressive therapy. The objective was to evaluate the performance of the QuantiFERON Gold In-Tube (QFT-IT) and the Tuberculin Skin Test (TST).A prospective multicenter study included 248 patients with ulcerative colitis (39), Crohn's disease (54), rheumatoid arthritis (111), and spondylo-arthropathy (44).QFT-IT was positive in 7/248 (3%), negative in 229 (92%), and indeterminate in 12 (5%). TST was positive in 54/238 (23%) patients. Chest x-ray was suspect for tuberculosis in 5/236 (2%), and 35/167 (21%) had ≥1 risk-factors for infection with Mycobacterium tuberculosis. The main finding was a pronounced negative effect on QFT-IT and TST performance associated with prednisolone treatment. During prednisolone treatment interferon gamma (IFN-γ) response to mitogen stimulation was impaired (median IFN-γ response 4.9 IU/mL; interquartile range [IQR] 0.8 to ≥10.0) compared to patients 1) not receiving corticosteroids (median ≥10.0; IQR 5.0 to ≥10.0; P = 0.0015) or 2) receiving long-acting corticosteroids (median >10.0; IQR 9.7 to >10.0; P = 0.0058). Prednisolone treatment was strongly associated with negative TST, adjusted odds ratio (AOR) 0.22 (0.1-0.8; P = 0.018), and with an increased risk of indeterminate QFT-IT results AOR 16.1 (4.1-63.2; P < 0.001), whereas no negative effect was found for long-acting corticosteroids. Doses of ≥10 mg prednisolone were associated with a 27% risk of indeterminate results. Single use of azathioprine, methotrexate, or 5-aminosalicylate (5-ASA) did not affect the test results.Oral prednisolone severely suppressed QFT-IT and TST performance, whereas the long-acting corticosteroids methotrexate, azathioprine, and 5-ASA did not have a similar detrimental effect. Patients should be screened for LTBI with QFT-IT or TST prior to initiation of prednisolone therapy and negative QFT-IT or TST results interpreted with caution in patients treated with any corticosteroid until further data are available.
e n t r e v i e w i s t o s u m m a r i z e the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials.Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against Post Endoscopic retrograde cholangiopancreatography Pancreatitis (PEP).The protease inhibitor Gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice.Nitroglycerin (NGL) is a nitrogen oxide (NO) donor, which relaxes the sphincter of Oddi.Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted.Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials.The non-steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP.Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results.Antibodies against tumor necrosis factor-alpha (TNF-α) have a potential as rescue therapy but no clinical trials are currently being conducted.The antibiotics betalactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis.Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.
The surgical first choice treatment for patients with ulcerative colitis (UC) involves total proctocolectomy with ileal pouch-anal anastomosis (IPAA). Postoperative development of pouch-related fistula is a rare complication, but it is associated with significant morbidity, a high recurrence rate and is a major cause of pouch failure. We report the use of infliximab, a monoclonal antibody to tumour necrosis factor-alpha, in three patients who developed pouch-related fistula after undergoing IPAA surgery for UC.
Background: IGRAs are recommended tests in the screening for latent tuberculosis infection in patients with autoimmune diseases before anti-TNF-α treatment. The aim of this study was to evaluate the performance of IP-10 as an alternative biomarker to IFN-γ.
Method: Blood samples from 79 patients with Rheumatoid Arthritis and 63 patients with Inflammatory Bowel Diseases were stimulated using the QFT-IT tubes. IFN-γ and IP-10 were measured in the supernatant with ELISA.
Results: Overall the performance of IP-10 was comparable to IFN-γ (agreement 138/142, (96.5%) kappa 0.80) with high levels of IP-10. QFT-IT and IP-10 test results were positive in 3(2.3%) and 4 (3.2%) patients respectively reflecting the low TB incidence in Denmark. Prednisolone treated patients had significantly more indeterminate QFT and IP-10 test results: 28%(10/36) and 22% (8/36) compared to patients receiving other DMARDs 2%(2/106) and 0% (0/106) respectively.
This effect was dose dependent for both tests (p=0.0001 test for trend)
Similarly, the median IFN-γ and IP-10 responses to mitogen were reduced in prednisolone treated patients (2.81 (IQR 0.05->10) and 7.8ng/ml (IQR 2.2-16.7) respectively) compared to patients receiving other DMARDs (>10.0IU/ml (IQR 8.43->10.0) and 20.9 (14.5-25.8ng/ml) (p<0.0001))respectively.
Conclusion: This is the first study to investigate the influence of prednisolone treatment on IP-10 responses; IP-10 was equally affected by prednisolone and the study was too small to determine the value of a combined biomarker approach. IP-10 can be stored on filter paper bypassing centrifugation, freezer and cold chain which gives an IP-10 based test an advantage to the current IFN-γ based test.
Objective. Spontaneous bacterial peritonitis is a common infection in cirrhosis, associated with a high mortality. Third-generation cephalosporins are recommended as first-line treatment. The aim was to evaluate the epidemiology of microbiological ascitic fluid findings and antimicrobial resistance in Denmark. Material and Methods. All patients with cirrhosis and a positive ascitic fluid culture, at three university hospitals in the Copenhagen area during a 7-year period, were retrospectively evaluated. Patients with apparent secondary peritonitis were excluded from the study. Results. One hundred and forty cases with 187 microbiological isolates were identified. The findings were: Gram-positive cocci, n = 86 (45.9%); Enterobacteriaceae, n = 59 (31.7%), with Escherichia coli identified in 31 cases; anaerobes, n = 14 (7.5%); yeast, n = 12 (6.4%); and cutaneous flora, n = 15 (8.0%). One case of Listeria monocytogenes was identified (0.5%). Overall antibiotic coverage was 57% for cephalosporins, 73% for piperacillin–tazobactam, and 72% for meropenem. Mortality rates in patients with isolates susceptible or resistant to the initial antibiotic treatment at 30 days follow-up were 35% and 55%, respectively (p = 0.017, Log-rank test). Conclusion. Almost half of the isolates were Gram-positive cocci, and as the overall antibiotic coverage with a cephalosporin was only 57%, and survival significantly dependent on whether the microbial etiology was susceptible to initial antibiotic treatment or not, a change of standard empiric antibiotic regime should be considered. Piperacillin–tazobactam could be a favorable choice.
Herbal medicinal products can cause toxic hepatitis. This case report presents a patient who developed severe toxic hepatitis with beginning liver failure following four weeks of consumption of the herbal medicinal product Cascara Sagrada. A similar case was reported from the United States. Cascara Sagrada is found in 30-40 herbal medicinal products in Denmark. We recommend that herbal medicinal products containing Cascara Sagrada be withdrawn from the market.
