Eosinophilic infiltration of oesophagus following carbamazepine-induced drug reaction with eosinophilia and systemic symptoms: an under-reported sequel?

We report a patient with carbamazepine-induced drug reaction with eosinophilia and systemic symptoms (DRESS), who developed painful dysphagia in the follow-up period. Gastrointestinal, including oesophageal, complications are rarely reported following DRESS, and we wish to highlight this possibly under-reported phenomenon.

Disorders of gut-brain interaction and the long-term risks of opioids.

Prescription opioid abuse has become a public health crisis. It is often challenging to manage affected patients as their symptoms are often viewed through a prism of complex psychosocial issues. Clinicians are often unaware of the lack of evidence regarding opioid prescribing for non-cancer pain, and these trends in prescribing have been significantly escalated by pharmaceutical companies and prescribing culture in recent years. Opioid prescribing in the context of disorders of gut-brain interaction (formerly known as functional gastrointestinal disorders) can worsen conditions such as centrally-mediated abdominal pain syndrome and narcotic bowel syndrome. Opioids should not be prescribed to these patients as the harm is significantly greater than the benefit. However, in certain patients, such as those being investigated for organic abdominal pain, a trial of opioids may be indicated. In these groups, an opioid contract should be used, in addition to risk tools to identify those most vulnerable to the negative effects of these drugs. Prevention and treatment of the long-term effects of opioids requires a multidisciplinary approach and health-care professionals should all become 'opioid aware'.

The management of low-risk primary upper gastrointestinal haemorrhage in the community: a 5-year observational study.

BACKGROUND: Acute upper gastrointestinal haemorrhage is a common medical emergency, initially managed with inpatient care. Bleeding stops spontaneously in over 80% of cases, indicating that patients with low-risk upper gastrointestinal haemorrhage may be more optimally managed in the community, without the need for admission to hospital. AIM: To assess the safety of managing patients with low-risk upper gastrointestinal haemorrhage without admission to hospital. METHODS: Prospective/retrospective study of all patients presenting to a UK teaching hospital with low-risk upper gastrointestinal haemorrhage who were managed without admission to hospital over 5 years. Low risk was defined as Glasgow Blatchford Score of 2 or less, age below 70 years, no other active medical problems, not taking warfarin and suspected nonvariceal bleed. Outcome measures were the need for intervention (blood transfusion, endoscopic therapy or surgery) and death. RESULTS: One hundred and forty-two patients fulfilled the inclusion criteria, and were managed without admission to hospital. No patients required endoscopic intervention, blood transfusion or surgery. The 28-day mortality was nil. Forty-one patients had normal endoscopic examination and 11 had significant endoscopic findings (peptic ulceration=10, oozing Mallory-Weiss tear=1) but did not require intervention. CONCLUSION: Patients presenting with a primary upper gastrointestinal haemorrhage aged below 70 years with a Glasgow Blatchford Score of 2 or less are at a low risk, and can be safely managed in the community.

Comparison of high-resolution magnification narrow-band imaging and white-light endoscopy in the prediction of histology in Barrett's oesophagus.

OBJECTIVE: To evaluate whether there is any appreciable difference in imaging characteristics between high-resolution magnification white-light endoscopy (WLE-Z) and narrow-band imaging (NBI-Z) in Barrett's oesophagus (BE) and if this translates into superior prediction of histology. MATERIAL AND METHODS: This was a prospective single-centre study involving 21 patients (75 areas, corresponding NBI-Z and WLE-Z images) with BE. Mucosal patterns (pit pattern and microvascular morphology) were evaluated for their image quality on a visual analogue scale (VAS) of 1-10 by five expert endoscopists. The endoscopists then predicted mucosal morphology based on four subtypes which can be visualized in BE. Type A: round pits, regular microvasculature; type B: villous/ridge pits, regular microvasculature; type C: absent pits, regular microvasculature; type D: distorted pits, irregular microvasculature. The sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Acc) were then compared with the final histopathological analysis and the interobserver variability calculated. RESULTS: The overall pit and microvasculature quality was significantly higher for NBI-Z, pit: NBI-Z=6, WLE-Z=4.5, p < 0.001; microvasculature: NBI-Z=7.3, WLE-Z=4.9, p < 0.001. This translated into a superior prediction of histology (Sn: NBI-Z: 88.9, WLE-Z: 71.9, p < 0.001). For the prediction of dysplasia, NBI-Z was superior to WLE-Z (chi(2)=10.3, p < 0.05). The overall kappa agreement among the five endoscopists for NBI-Z and WLE-Z, respectively, was 0.59 and 0.31 (p < 0.001). CONCLUSIONS: NBI-Z is superior to WLE-Z in the prediction of histology in BE, with good reproducibility. This novel imaging modality could be an important tool for surveillance of patients with BE.

Less small-bowel injury with lumiracoxib compared with naproxen plus omeprazole.

BACKGROUND & AIMS: The selective cyclooxygenase-2 inhibitor lumiracoxib has been shown to reduce endoscopically detected ulcers and ulcer complications in the upper gastrointestinal tract compared with nonselective nonsteroidal anti-inflammatory drugs. We investigated whether lumiracoxib would reduce small-bowel injury compared with naproxen plus omeprazole. METHODS: Healthy volunteers were randomized to receive lumiracoxib 100 mg once daily, naproxen 500 mg twice daily plus omeprazole 20 mg once daily, or placebo in a 16-day double-blind, parallel-group study. Small-bowel mucosal injury and inflammation were assessed by video capsule endoscopy, the lactulose:L-rhamnose permeability assessment, and the fecal calprotectin test. RESULTS: Of 152 randomized subjects, 139 completed the study with valid video capsule endoscopies (lumiracoxib, n = 47; naproxen plus omeprazole, n = 45; placebo, n = 47). Compared with placebo, an increased number of subjects on naproxen plus omeprazole had small-bowel mucosal breaks (77.8% vs 40.4%, P < .001), with increased permeability (P = .023) and increased fecal calprotectin (increase, 96.8 vs 14.5 mg/kg for placebo; P < .001). With lumiracoxib, 27.7% of subjects had small-bowel mucosal breaks (P = .196 vs placebo; P < .001 vs naproxen), there was no increase in permeability (P = .157 vs placebo; P = .364 vs naproxen), and no increase in fecal calprotectin (-5.7 mg/kg; P = .377 vs placebo; P < .001 vs naproxen). CONCLUSIONS: As assessed by 3 different measures, acute small-bowel injury on lumiracoxib treatment is less frequent than with naproxen plus omeprazole and similar to placebo.

Nonsteroidal antiinflammatory drugs and the small intestine.

PURPOSE OF REVIEW: The small intestine may be a more common site for nonsteroidal antiinflammatory drug toxicity than the gastroduodenal mucosa. Two-thirds of regular nonsteroidal antiinflammatory drug users develop subclinical small bowel enteropathy. This review highlights this emerging issue in patients requiring antiinflammatory drugs. RECENT FINDINGS: Nonsteroidal antiinflammatory drug enteropathy is a stepwise process involving direct mucosal toxicity, mitochondrial damage, breakdown of intercellular integrity, enterohepatic recirculation and neutrophil activation by luminal contents including bacteria. Unlike upper gastrointestinal toxicity, cyclooxygenase-mediated mechanisms are probably less important. Newer imaging modalities such as capsule endoscopy studies demonstrate nonsteroidal antiinflammatory drug-induced small bowel erosions, but the clinical implications are unclear. SUMMARY: Nonsteroidal antiinflammatory drug toxicity to the small intestine is common. Useful research tools have been developed to indirectly measure intestinal inflammation and permeability, but these are not generally available to the clinician, although enteroscopy and capsule endoscopy can be illuminating. Anaemia or hypoalbuminaemia are useful indications of nonsteroidal antiinflammatory drug enteropathy. Cessation of the drug would be the preferred option, alternatively there are experimental data to support the use of sulphasalazine and metronidazole. Animal models are unravelling new mechanisms for mucosal toxicity beyond the cyclooxygenase model, including mucosal oxidative injury and nitric oxide mediated pathways.

Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli.

BACKGROUND: Broccoli consumption is associated with a reduction in the risk of cancer, particularly in persons with a functional glutathione S-transferase M1 allele, as opposed rotrose whose GSTM1 gene has been deleted. Sulforaphane, the major isothiocyanate derived from 4-methylsulfinylbutyl glucosinolate, is thought to be the main agent conferring protection. OBJECTIVE: We compared sulforaphane metabolism in GSTM1-null and GSTM1-positive subjects after they consumed standard broccoli and high-glucosinolate broccoli (super broccoli). DESIGN: Sixteen subjects were recruited into a randomized, 3-phase crossover dietary trial of standard broccoli, super broccoli, and water. Liquid chromatography linked to tandem mass spectrometry was used to quantify sulforaphane and its thiol conjugates in plasma and urine. RESULTS: GSTM1-null subjects had slightly higher, but statistically significant, areas under the curve for sulforaphane metabolite concentrations in plasma, a greater rate of urinary excretion of sulforaphane metabolites during the first 6 h after broccoli consumption, and a higher percentage of sulforaphane excretion 24 h after ingestion than did GSTM1-positive subjects. Consumption of high-glucosinolate broccoli led to a 3-fold greater increase in the areas under the curve and maximum concentrations of sulforaphane metabolites in plasma, a greater rate of urinary excretion of sulforaphane metabolites during the first 6 h after consumption, and a lower percentage of sulforaphane excretion after its ingestion than did the consumption of standard broccoli. CONCLUSIONS: GSTM1 genotypes have a significant effect on the metabolism of sulforaphane derived from standard or high-glucosinolate broccoli. It is possible that the difference in metabolism may explain the greater protection that GSTM1-positive persons gain from consuming broccoli. The potential consequences of consuming glucosinolate-enriched broccoli for GSTM1-null and -positive persons are discussed.

Cyclooxygenase-2 inhibitors.

PURPOSE OF REVIEW: The purpose of this review is to summarize new information regarding the use of selective inhibitors of the cyclooxygenase-2 enzyme, emphasizing recent developments regarding cardiovascular risk. RECENT FINDINGS: Selective cyclooxygenase-2 inhibitors are as effective as nonselective nonsteroidal antiinflammatory drugs in relieving pain and inflammation but are associated with significantly fewer gastric, duodenal, and intestinal ulcers and ulcer complications. Cyclooxygenase-2 inhibitors may also reduce colorectal polyp development or recurrence as well as reduce the risk of colorectal and esophageal cancer. Some, but not all, studies have suggested increased myocardial infarction with certain cyclooxygenase-2 inhibitors, in particular rofecoxib. It is unclear whether this is a class effect because there are inconclusive data to incriminate celecoxib despite a relatively large number of clinical trials enrolling a large number of patients. Rofecoxib was voluntarily withdrawn by the manufacturer. The European Medicines Agency concluded that cyclooxygenase-2 inhibitors are contraindicated in patients with established cardiovascular disease, should be used with caution in patients with risk factors, and were justified in patients at risk for serious gastrointestinal adverse events. SUMMARY: Rofecoxib, but perhaps not all cyclooxygenase-2 inhibitors, may be associated with increased risk for myocardial infarction. It is unclear whether nonselective nonsteroidal antiinflammatory drugs increase or decrease the rate of myocardial infarction. The final truth awaits further studies.

Suture material as a nidus for common bile duct stones: taking a closer look.

A 72-year-old female with recurrent biliary colic and abnormal liver function 27 years after open cholecystectomy, was investigated by abdominal ultrasound, magnetic resonance pancreatocholangiogram (MRCP), and endoscopic retrograde cholangiopancreatography (ERCP). The ultrasound scan demonstrated a polypoid filling defect in the common bile duct (confirmed at ERCP), thus raising the possibility of a common bile duct tumour. The MRCP was normal. Visual examination of the duct with a choledochoscope revealed two stones attached to the wall by black suture material. The role of suture material in the formation of common bile duct stones, and direct choledochoscopy, is reviewed.

Nonsteroidal antiinflammatory drugs and the small intestine.

PURPOSE OF REVIEW: The small intestine is a more common site for nonsteroidal antiinflammatory drug (NSAID) toxicity than the well-recognized effects on the stomach and duodenum. Although NSAID strictures and perforation are rare, two thirds of regular NSAID users may be prone to small bowel enteropathy. This review highlights this emerging issue in patients requiring antiinflammatory drugs. RECENT FINDINGS: NSAID enteropathy is a stepwise process involving direct mucosal toxicity, mitochondrial damage, breakdown of intercellular integrity, enterohepatic recirculation, and neutrophil activation by luminal contents, including bacteria. Unlike upper gastrointestinal toxicity, cyclooxygenase-mediated mechanisms are probably less important. Newer imaging modalities such as capsule endoscopy studies suggest that small bowel erosions may be common in nonselective NSAID users. Sulfasalazine and metronidazole may prove to be useful, therapeutic options for patients who cannot cease their NSAIDs. SUMMARY: NSAID toxicity to the small intestine is common. Useful research tools have been developed to measure intestinal inflammation and permeability indirectly, but these are not generally available to the clinician, although enteroscopy and capsule endoscopy may be helpful. Anemia or hypoalbuminemia are useful clues to NSAID enteropathy. Cessation of the drug is ideal; otherwise, there is experimental data to support the use of sulfasalazine and metronidazole. Animal models are unraveling new mechanisms for mucosal toxicity beyond the cyclooxygenase model.