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We present a case of a male patient in his mid-30s with COVID-19-induced lung failure requiring extracorporeal membrane oxygenation, who needed an emergency oesophagogastroduodenoscopy due to major upper gastrointestinal bleeding. Endoscopy exposed severe ulcerative duodenitis with diffuse mucosal bleeding. While CT angiography did not show any signs of ischaemia, histopathology revealed duodenitis with substantial inflammatory cell infiltrates consisting of neutrophils and CD3 + T lymphocytes with equal CD4 + /CD8 + distribution. Since the composition of cell infiltrates coincides with changes in inflammatory patterns of the respiratory mucosa from patients with COVID-19 and in COVID-19-associated enterocolitis, and systemic dexamethasone treatment became standard of care in ventilated intensive care unit patients with COVID-19 infection, we initiated an individualised therapeutic attempt to treat the duodenitis with topical enteral budesonide. Follow-up oesophagogastroduodenoscopies within 4 weeks of enteral budesonide administration revealed a full clinical and histological healing of the duodenal mucosa with marked reduction of neutrophilic and lymphocytic infiltrates.To our knowledge, the current report is the first description of enteral budesonide treatment of duodenitis in a patient with COVID-19 infection and warrants further investigation, whether budesonide might constitute a novel therapeutic strategy for the management of COVID-19-related intestinal mucosal damage., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Nucleotide oligomerization domain 2 [NOD2] mutations are key risk factors for Crohn's disease [CD]. NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the exact roles of NOD2 in CD and other NOD2-associated disorders remain poorly known., Methods: We initially observed that NOD2 expression was increased in epithelial cells away from inflamed areas in CD patients. To explore this finding, Nod2 mRNA expression, inflammation, and cytokines expression were examined in the small bowel of wild-type [WT], Nod2 knockout and Nod2 mutant mice after rectal instillation of 2,4,6-trinitrobenzene sulphonic acid [TNBS]., Results: In WT mice, Nod2 upregulation upstream to rectal injury was associated with pro-inflammatory cytokine expression but no overt histological inflammatory lesions. Conversely, in Nod2-deficient mice the inflammation spread from colitis to ileum and duodenum., Conclusions: Nod2 protects the gut from colitis spreading to small intestine., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Rare cases of immune checkpoint inhibitor (ICI)-associated celiac disease (ICI-CeD) have been reported, suggesting that disruption of tolerance mechanisms by ICIs can unmask celiac disease (CeD). This study aims to characterize the clinicopathological and immunophenotypic features of ICI-CeD in comparison to ICI-associated duodenitis (ICI-Duo) and usual CeD., Methods: A medical and pathological records search between 2015 and 2019 identified eight cases of ICI-CeD, confirmed by tTG-IgA. Nine cases of ICI-Duo, 28 cases of moderate CeD, as well as 5 normal controls were used as comparison groups. Clinical information was collected from the electronic medical records. Immunohistochemistry for CD3, CD8, T-cell receptor gamma/delta (γδ), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) were performed, with quantification of intraepithelial lymphocyte (IEL) subsets in three well-oriented villi. CD68, PD-L1, and PD-1 were assessed as a percentage of lamina propria surface area infiltrated by positive cells. Statistical significance was calculated by the Student's t-test and Fisher's exact test., Results: The eight patients with ICI-CeD (F:M=1:3) and nine patients with ICI-Duo (F:M=5:4) presented similarly with diarrhea (13/17) and abdominal pain (11/17) after a median of 1.6 months on ICI therapy. In patients with ICI-CeD, tTG-IgA ranged from 104 to >300 IU/mL. Histological findings in ICI-CeD and ICI-Duo were similar and included expansion of the lamina propria, active neutrophilic duodenitis, variably increased IELs, and villous blunting. Immunohistochemistry showed that the average number of IELs per 100 enterocytes is comparable between ICI-CeD and ICI-Duo, with increased CD3 + CD8 + T cells compared with normal duodenum but decreased γδ T cells compared with CeD. Average PD-L1 percentage was 9% in ICI-CeD and 18% in ICI-Duo, in comparison to <1% in CeD and normal duodenum; average PD-1 percentage was very low to absent in all cases (<3%). On follow-up, five patients with ICI-CeD improved on a gluten-free diet (GFD) as the sole therapeutic intervention (with down-trending tTG-IgA) while the other three required immunosuppression. All patients who developed ICI-Duo received immunosuppression with variable improvement in symptoms., Conclusions: ICI-CeD resembles ICI-Duo clinically and histologically but shares the serological features and response to gluten withdrawal with classic CeD. Immunophenotyping of IELs in ICI-CeD and ICI-Duo also shows similar CD3, CD8, γδ T cell subsets, and PD-L1 populations, all of which differed quantitatively from usual CeD. We conclude that ICI-CeD is biologically similar to ICI-Duo and is likely a variant of ICI-Duo, but treatment strategies differ, with ICI-CeD often improving with GFD alone, whereas ICI-Duo requires systemic immunosuppression., Competing Interests: Competing interests: MD is a consultant for Genentech-Roche, Tillotts Pharma, and Partner Therapeutics. He received research funding from Novartis. He is on the scientific advisory board for Neoleukin Therapeutics., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

The objective of the study was to investigate how taurine alleviates mucosal injury. Young chickens were fed with taurine for 1 week and then challenged with lipopolysaccharide. We found that, under lipopolysaccharide challenge, taurine could attenuate diarrhea and mucosal inflammation. Additionally, under LPS challenge, taurine could enhance epithelial proliferation and goblet cell function, could also decrease epithelial apoptosis by improving the mitochondrial membrane permeability. The high-performance liquid chromatography assay showed that taurine feeding could elevate taurine concentration in duodenum obviously. The antioxidant assay showed that taurine could reverse lipopolysaccharide-induced low GSH level, GSH/GSSG ratio, GSH-Px activity and SOD activity, high GSSG and MDA content. In summary, we suggested that taurine could enhance duodenal antioxidant status locally and further ameliorated lipopolysaccharide-induced chicken duodenal inflammation by improving mitochondrial membrane permeability and goblet cell function.

The olmesartan is a selective antagonist of angiotensin II indicated for the treatment of essential hypertension. We report the case of a gastrointestinal involvement with duodenal villous atrophy and lymphocytic infiltrate duodenal epithelial and colonic secondary to the olmesartan taking with test of positive reintroduction. The patient had chronic diarrhea with weight loss of 10kg occurred 1 month after the passage of 20 to 40mg/day olmesartan took 3 years. A rectosigmoidoscopy highlighted some puncture slightly erythematous areas. The responsibility of olmesartan was suspected and the drug was stopped. The evolution was rapidly favorable with disappearance of diarrhea 4 8hours later. Two days after the patient took the drug on its own initiative. Sigmoid biopsies showed an inflammatory infiltrate rich in lymphocytes. Gastroscopy showed erosive esophagitis and duodenal biopsies showed chronic duodenitis with epithelial lymphocytosis and subtotal villous atrophy. The reintroduction has led to the immediate resumption of diarrhea. olmetec was finalized. Diarrhea has not returned since. A colonoscopy performed 6 weeks after discharge was normal. Knowledge of the bowel olmesartan is recent and based almost solely on the description of 22 cases observed at the Mayo Clinic with patients, as in our case, have similar symptoms and lesions. We stress about a publication an isolated case the possibility of less severe cases with histological abnormalities without clinical translation., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

We present a case of acute upper gastrointestinal haemorrhage in a patient with systemic vasculitis immunosuppressed on cyclophosphamide and prednisolone. The patient presented with a diffuse haemorrhagic oesophagitis and a non-specific duodenitis. Biopsies taken from the oesophagus and duodenum demonstrated infection with herpes simplex virus (HSV) and cytomegalovirus (CMV) respectively. Viral infection of the upper gastrointestinal tract is a recognised complication of immunosuppression and HSV is one of the most common pathogens. CMV on the other hand most commonly causes a colitis or less commonly oesophagitis. CMV enteritis is rare as is the synchronous infection with two viral agents in an immunocompromised patient having being described in a few case series only. Viral infection of the gastrointestinal tract in immunocompromised patients should be treated with systemic anti-viral medication and consideration to withdrawal of the immunosuppressive therapy if possible and appropriate. The authors highlight the need for a high suspicion of viral infection in immunosuppressed patients presenting with upper gastrointestinal bleeding.

Morphological changes in the gingiva under the effect of drugs improving microcirculation were studied in pubertal Wistar rats with experimental gastroduodenitis. Chronic gastroduodenitis was induced by intragastric administration of 50% medical bile (1 ml/100 g body weight daily) for 40 days. The best medical correction was attained with altan and citrarginine. Morphologic studies showed signs of regeneration plastic activity of the epithelium, restructuring of the gingival lamina propria, and enlargement of the vascular bed area. Calcium-D3 Nycomed disordered the regeneration processes in the rat epithelium, because of calcium ion capacity to increase oxygen demand in tissues and cause destructive processes. Hence, pathogenetic drug correction of degenerative processes in the gingiva under conditions of chronic gastroduodenitis should include drugs promoting recovery of the microcirculatory bed, altan and citrarginine.

Background/aims: The upper gastrointestinal (GI) toxicity associated with non-steroidal anti-inflammatory drugs (NSAID) use among cirrhotic patients remains unclear. The objective of this study was to evaluate the risk of upper GI adverse events associated with celecoxib and oral and parenteral non-selective NSAIDs in cirrhotic patients., Methods: All the patients aged ≥ 20 years with a diagnosis of cirrhosis hospitalized for variceal bleeding and non-variceal upper GI adverse events (oesophageal, gastric, duodenal ulcer, bleeding; gastritis and duodenitis) in 2006 were identified using ICD-9-CM diagnosis codes from inpatient claims from the Taiwan National Health Insurance Database. In the case-crossover study design, the case period was defined as 1-30 days and the control period as 31-60 days before the date of hospitalization. The information for individual NSAID use was obtained from the outpatient pharmacy prescription database. Adjusted self-matched odds ratios (OR) and their 95% confidence intervals (CI) were estimated with a conditional logistic regression model., Results: A total of 4876 cirrhotic patients were included. The adjusted OR (95% CI) was 1.44 (0.89-2.31) for celecoxib, 1.87 (1.66-2.11) for oral non-selective NSAIDs and 1.90 (1.55-2.32) for parenteral NSAIDs overall. Risks were similar for variceal and non-variceal events. Concomitant use of proton pump inhibitors and histamine-2 receptor antagonists tended to decrease the upper GI toxicity associated with non-selective NSAIDs and celecoxib., Conclusion: The use of nsNSAIDs but not celecoxib was associated with a two-fold increased risk of variceal and non-variceal upper GI events among cirrhotic patients., (© 2012 John Wiley & Sons A/S.)

Purpose: There is little knowledge regarding the prevalence of mucosal injury (MI) in Japanese patients receiving antiplatelet therapy. This study estimated the prevalence of gastroduodenal MI in asymptomatic Japanese patients taking antiplatelet agents and nonsteroidal anti-inflammatory drugs (NSAIDs)., Methods: Among patients who underwent an upper gastrointestinal endoscopy at Teikyo University Hospital (Tokyo, Japan), 382 asymptomatic patients taking either low-dose aspirin, ticlopidine, cilostazol, or other NSAIDs and 119 people not taking any of these agents were included. Endoscopic records were evaluated for the presence of MI., Results: Aspirin and NSAIDs users showed a higher prevalence of MI than controls (Aspirin, OR = 2.6 (95% CI = 1.4 - 4.9), NSAIDs, 2.9 (1.4 - 4.4)). Concomitant use of aspirin and NSAIDs increased the prevalence of MI (11.2 (2.8 - 44.8)). Ticlopidine and cilostazol were less likely to cause injury than aspirin and other NSAIDs, the difference remained insignificant due to small sample number (ticlopidine, 0.8 (0.2 - 4.0), cilostazol, 1.3 (0.3 - 4.8))., Conclusions: In asymptomatic Japanese patients receiving low-dose aspirin, the prevalence of the gastroduodenal MI was the same as that in patients taking NSAIDs and higher than that in controls.

The Purpose of the Study: To study role of E2 and F2alpha prostaglandins in development of erosive-ulcerative lesions of gastrointestinal tract., Materials and Methods: were examined patients with mucosal erosive-ulcerative and inflammatory lesions of gastrointestinal tract, as well as patients with osteoarthritis who received selective and non selective NSAIDs. Determination of E2 and F2alpha endogenous PG group was investigated with help of immunefuoration method with help of R&D Systems, Inc. Control group was 15 healthy patients., Results: in presented work you can find that there is relationship between degree of reduction of PG level and severity of gastrointestinal mucosal lesion area. The lowest values of PGE2 and PG F2alpha observed in patients with gastric ulcer disease, especially during exacerbation. Patients with low PG synthesis in body increases likelihood of gastropathy as to reception of non-selective COX inhibitors, and at receiving selective COX-2 inhibitors.

The inhibitory receptor CTLA4 has a key role in peripheral tolerance of T cells for both normal and tumor-associated antigens. Murine experiments suggested that blockade of CTLA4 might have antitumor activity and a clinical experience with the blocking antibody ipilimumab in patients with metastatic melanoma did show durable tumor regressions in some patients. Therefore, a phase II study of ipilimumab was conducted in patients with metastatic renal cell cancer with a primary end point of response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Two sequential cohorts received either 3 mg/kg followed by 1 mg/kg or all doses at 3 mg/kg every 3 weeks (with no intention of comparing cohort response rates). Major toxicities were enteritis and endocrine deficiencies of presumed autoimmune origin. One of 21 patients receiving the lower dose had a partial response. Five of 40 patients at the higher dose had partial responses (95% confidence interval for cohort response rate 4% to 27%) and responses were seen in patients who had previously not responded to IL-2. Thirty-three percent of patients experienced a grade III or IV immune-mediated toxicity. There was a highly significant association between autoimmune events (AEs) and tumor regression (response rate=30% with AE, 0% without AE). CTLA4 blockade with ipilimumab induces cancer regression in some patients with metastatic clear cell renal cancer, even if they have not responded to other immunotherapies. These regressions are highly associated with other immune-mediated events of presumed autoimmune origin by mechanisms as yet undefined.

Background: A 40-year-old previously healthy white man presented to the emergency department at American University of Beirut Medical Center, Beirut, Lebanon, with severe upper abdominal pain of 36-hour duration. The pain started a few hours after the intake of a single tablet of tiaprofenic acid and became more intense after the intake of another tablet 24 hours later. He had no other symptoms. He had no prior upper gastrointestinal (GI) symptoms, ulcer disease, steroidal or nonsteroidal anti-inflammatory drug use, or ethanol intake. Physical examination revealed mild upper abdominal tenderness. Complete blood count, amylase, lipase, and liver function tests were unremarkable. Computed tomography of the abdomen showed marked thickening of the duodenal wall with surrounding mesenteric streaking. Upper GI endoscopy revealed extensive ulceration involving the duodenal bulb, apex, and proximal D2, as well as a few gastric erosions. Histopathologic examination of duodenal biopsy samples showed extensive epithelial cell necrosis and infiltration of the lamina propria with neutrophils and eosinophils. The patient responded well to rabeprazole 20 mg BID and remains well 5 months later., Methods: We performed a literature search of PubMed for all English-language articles published between January 1970 and present (June 2007) using the key words tiaprofenic acid, nonsteroidal anti-inflammatory drugs, NSAID, duodenitis, duodenal erosion, duodenal ulcer, gastritis, gastric erosion, gastric ulcer, or peptic ulcer. We reviewed all randomized controlled trials involving NSAIDs found using PubMed, with a focus on their GI adverse effects., Results: Based on the PubMed search, there were no published reports of acute transmural duodenitis and complicated duodenal ulcers associated with short-term exposure to tiaprofenic acid or other NSAIDs. The Naranjo adverse drug reaction (ADR) probability scale was used and a score of 6 was obtained, indicating a probable ADR from tiaprofenic acid use., Conclusion: We report a patient who developed symptomatic severe transmural duodenitis and periduodenal mesenteric streaking, consistent with a complicated ulcer, probably associated with very short-term exposure to tiaprofenic acid.

Finding UDP-glucuronosyltransferases (UGT) require protein kinase C-mediated phosphorylation is important information that allows manipulation of this critical system. UGTs glucuronidate numerous aromatic-like chemicals derived from metabolites, diet, environment and, inadvertently, therapeutics to reduce toxicities. As UGTs are inactivated by downregulating PKCs with reversibly-acting dietary curcumin, we determined the impact of gastro-intestinal glucuronidation on free-drug uptake and efficacy using immunosuppressant, mycophenolic acid (MPA), in mice. Expressed in COS-1 cells, mouse GI-distributed Ugt1a1 glucuronidates curcumin and MPA and undergoes irreversibly and reversibly dephosphorylation by PKC-specific inhibitor calphostin-C and general-kinase inhibitor curcumin, respectively, with parallel effects on activity. Moreover, oral curcumin-administration to mice reversibly inhibited glucuronidation in GI-tissues. Finally, successive oral administration of curcumin and MPA to antigen-treated mice increased serum free MPA and immunosuppression up to 9-fold. Results indicate targeted inhibition of GI glucuronidation in mice markedly improved free-chemical uptake and efficacy using MPA as a model.

Studies in 45 cryolite production workers (facing chronic gastritis and gastroduodenitis) demonstrated that the diseases in them have moderate inflammatory activity, atrophy of gastric lining contaminated with Helicobacter pylori, hypergastrine mia, hypopancreozymine mia and hyposecretine mia in half of the examinees.

Objective: To evaluate the gastrointestinal safety of cyclo-oxygenase-2 inhibitors under their real conditions of use. DESIGN. Case/non-case study., Setting: Adverse drug reactions (ADRs) in adults recorded in the French Pharmacovigilance Database between 25 May 2000 and 31 December 2002., Materials: Cases were all reports of "serious" oeso-gastro-duodenal ADRs (oeso-gastro-duodenal ulcers, oesophagitis, gastritis, duodenitis). Five non-cases were randomly selected for one case from all other non oeso-gastro-duodenal reports in the database after matching them for age, gender and period of occurrence., Analysis: Coxib exposure was compared among cases and non-cases, with adjustment for matching factors: French Regional Pharmacovigilance Centres that collected ADRs, reporter health professional's characteristics and exposures to non-selective non-steroidal anti-inflammatory, aspirin, anticoagulant, antiplatelet and gastroprotective drugs., Results: Included in the study were 505 cases and 2,525 non-cases. A positive association was found between occurrence of oeso-gastro-duodenal ADRs and coxib (adjusted odds ratio 14.9 [95% CI 9.3-23.7]), diclofenac (9.2 [3.8-22.2]), ibuprofen (7.3 [3.2-16.6]) or oxicam (25.3 [11.9-53.6]) use., Conclusion: Despite the compulsory limits of the case/non-case methodology, the present study shows that coxibs did induce "serious" gastrointestinal ADRs in real clinical practice. These results underline the need for pharmacoepidemiological studies under real conditions of use in order to verify (or not) the conclusions of clinical trials.

(1) We investigated the effect of the cannabinoid CB1 receptor antagonist, SR 141716, on indomethacin-induced small intestine inflammation and Escherichia coli lipopolysaccharide (LPS)-induced plasma TNF-alpha (TNF) release in comparison to the cannabinoid CB2 receptor antagonist, SR 144528, in rodents. (2) In rats, indomethacin induced significant ulcer formation in the small intestine; this was accompanied by an increase in tissue TNF levels and myeloperoxidase (MPO) activity. SR 141716 prevented the ulcers and the rise in TNF levels (ID50 3.3, 0.4 mg kg-1, respectively) and MPO activity. SR 144528 prevented intestinal ulcers only. (3) The effect of SR 141716 against indomethacin-induced ulcers and increase of plasma TNF levels after LPS was also studied in wild-type and CB1 receptor knockout mice. Indomethacin induced intestinal ulcers in mice, but not tissue TNF production and MPO activity. SR 141716 reduced the ulcers to a similar extent in wild-type and CB1 receptor knockout mice. In rats and wild-type mice, but not in CB1 receptor knockout mice, SR 141716 inhibited the LPS-induced increase in plasma TNF levels. (4) These findings provide evidence that the indomethacin model of intestinal lesions differs in rat and mouse and support the existence of several mechanisms for the antiulcer activity of SR141716, the most important involving the inhibition of TNF production. The potent anti-inflammatory activity of SR141716 in rodents indicated its potential therapeutic interest in chronic immune-inflammatory diseases.

Background: This study was aimed at evaluating the role of Helicobacter pylori in erosive gastroduodenitis and the necessity for its eradication., Material/methods: A total of forty-nine consecutive patients who presented with hematemesis and or melena and proved to have erosive gastroduodenitis on endoscopy were included in the study. H. pylori status was determined by urease, histology and serology. The presence of at least two positive tests was considered as positive H. pylori status. The erosion sites were noted and classified according to predominance. Correlation of H. pylori status was done between NSAID users and non-users., Results: 28 males and 21 females comprised the study group. H. pylori positivity was 43% in men and 52% in women (p=0.51); the overall H. pylori positivity rate was 47%. 39 patients had taken NSAIDs and three had taken indigenous drugs, which did not belong to the group of NSAIDs. The H. pylori status of drug users and non-users was 48% and 43% respectively (p=0.57) Erosions were most common in the body of the stomach (61%) compared to the antrum (23%), fundus (10%) and duodenum (6%)., Conclusions: Erosive gastroduodenitis is commonly associated with NSAID intake. The body of the stomach is the most common site of erosions. Only 47% of patients with erosive gastritis have a positive H. pylori status. The H. pylori status between drug users and non-users was not significantly different. Eradication of H. pylori is not indicated in patients with erosive gastroduodenitis.

The paper considers the principles of classification of chronic duodenitis. The current classification of chronic duodenitis may be divided into three parts: endoscopic, histological, and etiological. The characterizing terms of the endoscopic part are as follows: erythema, hemorrhages, atrophy, erosions, follicles. The endoscopic localization of duodenitis is as follows: proximal and distal portions (panduodenitis, including bulbitis in the proximal portion and postbulbitis in the distal portion, palpilitis). The nonspecific terms of the histological part are as follows: activity, inflammation, and atrophy. Its specific terms are: ventricular metaplasia, ventricular heterotopia, Helicobacter pylori, granulomas, lymphatic follicles, eosinophilic infiltration, lymphocytic infiltration. The following morphological categories of duodenitis are: nonatrophic, nodular, granulomatous, eosinophilic, and lymphocytic. The morphological localization of duodenitis is as follows: proximal and distal portions (panduodenitis, including bulbitis in the proximal portion and postbulbitis in the distal portion). The following degrees of its severity are: none changes, mild, moderate, and sever. The types (etiological factors) of duodenitis are as follows: acid-associated, drug-dependent, toxic (eliminating), and isolated nonspecific (idiopathic). Its special forms are: H. pylori-induced, granulomatous (Crohn's disease, sarcoidosis), nodal (Crohn's disease, sarcoidosis, acid-associated diseases), eosinophilic (unspecified allergens), lymphocytic (gluten-induced).

We report two cases of mortality associated with the recent winter influenza outbreak. Both cases were associated with self-medication. In one case an elderly lady died from haemorrhagic duodenitis induced by over the counter ibuprofen. In the second case the lady died from the consequences of exceeding the recommended doses of paracetamol by combining doses of the generic product with proprietary flu-remedies and Tylex (paracetamol and codeine).

Objective: To report a possible case of leukocytoclastic vasculitis associated with clarithromycin therapy., Case Summary: An 83-year-old white woman was prescribed clarithromycin for pneumonia. Six days after her initial presentation, she developed lesions on her palms. Clarithromycin was discontinued at that time. The following day she developed purpuric eccymotic nonblanching lesions that primarily appeared on the lower extremities, buttocks, and abdomen. Colonoscopy revealed generalized erythema and edema of the bowel mucosa. Gastroscopy revealed duodenitis and gastritis, but no bleeding or ulceration. Skin biopsy of the lesions was compatible with leukocytoclastic vasculitis. Renal function was not affected, although hematuria was noted. All symptoms resolved after drug withdrawal and a short course of corticosteroids., Data Sources: Searches were performed on MEDLINE, Embase, International Pharmaceutical Abstracts, and major adverse drug reaction databases to identify reports and articles discussing clarithromycin- and macrolide-induced leukocytoclastic vasculitis., Discussion: Leukocytoclastic vasculitis is one category of drug hypersensitivity reactions characterized by distinctive patterns of perivascular inflammation. The case described here is consistent with the diagnosis of leukocytoclastic vasculitis, and is similar to the other single published case report associated with clarithromycin., Conclusions: Leukocytoclastic vasculitis induced by clarithromycin is a rare but serious potential adverse effect.

Epinephrine (adrenaline) is an important drug in the treatment of severe anaphylactic reactions. Along with other drugs such as H1-antihistamines and glucocorticosteroids, it is found in every first aid kit for at-risk individuals, such as those who are allergic to insect stings. Subcutaneous or intramuscular injections if carried out by an untrained individual or the patient himself might give rise to potential problems. Therefore, it is common to prescribe epinephrine pressure aerosol as a safer alternative. If epinephrine aerosol is overused, it can cause serious problems. A patient developed by self-medication following a wasp sting lung edema as well as an erosive gastroduodenitis. She consumed two aerosol vials each of which contained about 73 mg of adrenaline. In order to avoid such incidents it is crucial that every doctor provides his or her patient with sufficient oral and written information regarding the correct use fo epinephrine inhalers.

As the majority of patients with chronic arthritis are treated, for many years, with non-steroidal anti-inflammatory drugs (NSAID), it is only natural to expect the long-term use of these agents to be associated with a range of oesophago-gastro-duodenal histopathological changes. We have demonstrated that oesophagitis (defined as basis of papillary length, basal cell hyperplasia and inflammatory cell infiltration) is less prevalent in patients taking NSAID. This phenomenon can be utilised in the treatment of certain conditions such as post-irradiation oesophagitis and Barrett's oesophagitis. It also implies that NSAID-related oesophageal ulceration is due to lodging of tablets in the oesophagus and is, in turn, preventable by swallowing of some fluids or solids after taking NSAID. In the stomach, long-term use of NSAID is associated with a specific entity known as chemical or reactive gastritis in about 25% of cases. This is frequently associated with ulceration. Chronic active superficial gastritis, in the presence of Helicobacter pylori, can be found in about 70% of cases. Not unlike oesophagitis, the prevalence of active duodenitis is low in chronic NSAID users. Local ulceration still takes place. This implies that duodenitis is not required in at least some cases of NSAID-related duodenal ulcers, and demonstrates the multi-factorial nature of the pathogenesis of mucosal damage in long-term users of a NSAID.

A prospective case-controlled study was performed to evaluate the gastrointestinal symptoms and mucosal abnormalities occurring in patients with osteofluorosis. Ten patients with documented osteofluorosis and ten age- and sex-matched healthy volunteers were included in the study. Clinical evaluation, real-time ultrasound, and upper gastrointestinal endoscopy and biopsy from the gastric antrum and duodenum were performed in all subjects. The biopsies were subjected to a rapid urease test and light and electron microscopic examinations. Ionic fluoride levels were estimated in the drinking water, serum, and urine using an ION 85 ion analyzer. All patients with osteofluorosis had gastrointestinal symptoms, the most common being abdominal pain. Endoscopic abnormalities were found in seven patients with osteofluorosis. In all 7 of these patients, chronic atrophic gastritis was seen on histology. Electron microscopic abnormalities were observed in all 10 patients with osteofluorosis. These included loss of microvilli, cracked-clay appearance, and the presence of surface abrasions on the mucosal cells. None of the control subjects had any clinical symptoms or mucosal abnormalities. It was concluded that gastrointestinal symptoms as well as mucosal abnormalities are common in patients with osteofluorosis.

Objective: The objective of this endoscopic, double-blind study was to evaluate the gastric tolerability of nabumetone, a novel nonsteroidal anti-inflammatory drug, compared with naproxen in patients with rheumatoid arthritis., Methods: Patients with definite or classic rheumatoid arthritis as defined by ACR criteria were eligible for entry into the study if an initial endoscopy was normal or showed the presence of only one erosion or one or two submucosal hemorrhages. After a 7-day washout period, the patients were randomized to receive either nabumetone, 1 g, or naproxen, 500 mg, b.i.d. Blinding was achieved by the use of double dummies. Endoscopy was repeated after 4 wk of treatment. The primary efficacy parameters were Ritchie articular index, duration of morning stiffness, and global assessments., Results: Gastric mucosal lesions of different degrees were observed in 9% (2/22) of nabumetone-treated patients and in 40% (12/30) of those who received naproxen (p = 0.01). One duodenal ulcer was found in a patient treated with nabumetone, and this patient had a history of duodenal ulcer. In the naproxen group, six patients were found to have an ulcer. Clinical evaluation of rheumatological symptomatology showed no statistical difference in relieving symptoms between the two drugs in the primary efficacy assessments. However, six nabumetone-treated patients dropped out because of lack of efficacy, compared with one in the naproxen group. Side effects were noted in three patients treated with nabumetone and in 14 treated with naproxen (p = 0.004)., Conclusion: This study showed that nabumetone, 1 g daily, results in significantly less deterioration of gastric mucosa than naproxen, 500 mg daily, but the efficacy of naproxen, 1 g, appears to be more than that achieved with nabumetone, 1 g.

In a cohort of children with juvenile rheumatoid arthritis treated with nonsteroidal antiinflammatory drugs and referred for gastrointestinal complaints, more than 75% had gastritis, antral erosions, or ulcers. Epigastric pain strongly correlated with documented gastroduodenal injury. Therapy with ranitidine or misoprostol led to clinical improvement. Nonsteroidal antiinflammatory drugs are associated with significant gastrointestinal abnormalities in children.

Forty-five patients taking long-term indomethacin and with endoscopic erosions or superficial ulcers in the oesophagus, stomach or duodenal bulb were randomized in a double-blind study to continue with standard indomethacin or receive a 'delayed-release' formulation. This consisted of microgranules of indomethacin coated with an acrylic resin, Eudragit L, which releases drug in the small intestine. Endoscopy was repeated after 8 weeks and biopsies taken on both occasions. Changes in endoscopic lesions and histological appearances were similar in both groups, although mucosal erythema was less in those given Eudragit L indomethacin. Systemic, rather than topical, effects of indomethacin may therefore be responsible for persistence of gastro-duodenal mucosal lesions in these patients. There is reason to question the clinical practice of using expensive, delayed-release preparations.

A prospective double-blind randomized placebo-controlled study was conducted to compare the injurious effects of aspirin and naproxen on the gastroduodenal mucosa. Patients with rheumatoid arthritis attending the immunology clinic of a tertiary care center were included in the study. Ninety consecutive patients were randomized to receive aspirin, naproxen, or placebo. Clinical evaluation was done every 2 wk. Upper gastrointestinal endoscopy, biopsies from the gastric antrum and duodenum for histological examination, and Helicobacter pylori studies were done at entry and after 2 months. The number of patients with dyspeptic symptoms was similar in the aspirin (12) and naproxen (9) groups. In both cases, however, it was higher (p less than 0.01) than in the placebo group (none). Naproxen was associated with a higher score of endoscopic abnormalities in the gastric body (0.6 +/- 1.3) than aspirin (0.2 +/- 0.6) or placebo (0.03 +/- 0.18). H. pylori was present in a similar proportion of patients in the three groups (33-43%). A greater fall in hemoglobin was observed with aspirin (0.35 +/- 0.48 g%) and naproxen (0.44 +/- 0.53 g%) than with placebo (0.09 +/- 0.4 g%). The present study suggests that aspirin and naproxen produce a similar degree of injury to the gastroduodenal mucosa.

The authors describe two patients who suffered gastrointestinal toxicity after receiving chemotherapy for unresectable lesions in the liver that metastasized from colonic carcinoma. One patient had severe ileitis caused by intravenous administration of 5-fluorouracil; the other had severe duodenitis caused by infusion of 5-floxuridine into the hepatic artery by an implanted pump. The type of toxicity that occurred was directly related to the route of administration of these chemotherapeutic agents. Cessation of the chemotherapy led to a dramatic clinical response in these patients.

Cell renewal in the duodenal mucosa of Mastomys was studied by autoradiography 1 and 24 h after intraperitoneal injection of tritiated thymidine. Non-specific duodenitis and duodenal ulceration were produced with a continuous infusion of histamine. Mucosal renewal in the duodenum of 30 control Mastomys was compared with 30 which received histamine dihydrochloride for 5 days. No abnormality developed in the controls, but 11 of the experimental group developed non-specific duodenitis and 12 duodenal ulcers. The size of the proliferative zone was increased in the Mastomys sacrificed 1 h after injection of tritiated thymidine which received histamine, compared with controls (p = 0.004). The number of labelled nuclei (p = 0.0003) and the size of the columns of labelled nuclei (p = 0.001) were increased in the Mastomys receiving histamine and sacrificed 24 h after injection of tritiated thymidine, compared with controls. The number of labelled nuclei (p = 0.004) and the size of the columns of labelled nuclei (p = 0.01) were increased in the Mastomys with ulcers compared with the other Mastomys which had received histamine. Cimetidine prevented duodenitis and ulceration, normalising the pattern of cell renewal. There was correlation between the severity of non-specific and ulcer-related duodenitis as judged by Lance's system and the number of labelled nuclei (Spearman rank correlation coefficient 0.771, p less than 0.002). Cell renewal increased as duodenitis became more severe and duodenal ulcers were found in duodenal mucosa where cell renewal was fastest.

The effect of ketoprofen, a nonsteroidal anti-inflammatory drug, was tested on the upper gastrointestinal tract (UGIT) in patients with osteoarthritis. The drug was given in two forms; as simple ketoprofen (Orudis) and as a slow release preparation (Oruvail), when the drug was not released into the stomach, but into the small intestine. These formulations were compared with indomethacin for endoscopically proven damage to the UGIT. Orudis and Oruvail produced similar damage to previously normal UGITs over 56 days; each formulation produced about a 50% incidence of ulceration and inflammation. Indomethacin, by comparison produced less damage. The results suggested that the direct action of ketoprofen (barrier breaking effect) adds little to the mechanism of gastric cytotoxicity of this drug, which may be assumed to be predominantly caused by a systemic effect of ketoprofen on gastric cytoprotective mechanisms.

The purpose of this study was to record the frequency of invasive candidiasis of duodenal ulcer and to determine whether or not it is enhanced by cimetidine treatment. Our multicenter prospective trial involved 99 patients with endoscopically proven duodenal ulcer who were undergoing a 4- or 8-week cimetidine (800 mg/day) treatment program. At the endoscopic examination, performed before and after the 4- or 8-week treatment, three biopsy samples were taken from the ulcer edge or from the healed tissue. Ulcer infiltration by Candida was presumed by the presence of mycetes in stained tissue samples. Healing rate was 76% at 4 weeks and 89.9% at 8 weeks. Candida infiltration was not seen in any biopsy specimen. Short-term treatment with cimetidine does not promote invasion of mycetes into the duodenal ulcer lesion.

Forty-eight normal men participated in a 14-day, single blind, single center, multiple dose study of gastric irritation using endoscopy. Subjects were randomly assigned to one of 4 treatment groups after a one week lead-in period, as follows: etodolac 200 mg BID, 400 mg BID, 600 mg BID, or aspirin 975 mg QID. Etodolac at all dose levels produced significantly (p less than or equal to 0.0001) less gastrointestinal irritation than aspirin as assessed by endoscopic examination of the gastric and duodenal sites. There were no significant differences among the 3 etodolac groups.

In a randomized, double-blind, placebo-controlled, prospective trial, the activity of rioprostil, a new prostaglandin E1 alcohol analogue, on non-steroidal anti-inflammatory drug-induced gastroduodenal mucosal lesions is studied in 30 patients with rheumatic diseases. Both treatment regimens, rioprostil, 150 micrograms t.i.d., and rioprostil, 200 micrograms b.i.d., for a period of 12 weeks, significantly reduce the rate of mucosal lesions in all patients when compared to placebo. Furthermore, rioprostil achieves a reduction in gastrointestinal symptoms without enhancement of joint disease activity, and significantly reduces antacid intake. Therapy is safe and well tolerated by all patients. It can be concluded from this study that prostaglandins could play an important part in the prevention and treatment of gastrointestinal damage due to NSAIDs.

The effect of nonsteroidal antiinflammatory drugs (NSAIDs) on duodenal mucosa was assessed both retrospectively and prospectively. In 444 patients with duodenal ulcer, the incidence of upper gastrointestinal bleeding was five times higher in 56 patients who were treated with NSAIDs than in those who did not receive NSAIDs. Indomethacin and naproxen had the most potent damaging effects. In a control group of patients with gastric ulcer, nine out of 134 had taken NSAIDs. The incidence of bleeding in these patients was three times higher than in those who were not on NSAIDs. The effect of indomethacin, 150 mg/day, on the upper gastrointestinal tract was examined in a prospective study of 75 patients with acute musculoskeletal disorders. Endoscopy after 1 week of therapy showed that 45% had mucosal damage in the duodenum, and this was as frequent and as severe as the gastric mucosal damage. In most instances, the duodenal damage was erosive duodenitis.