Haemorrhagic ulcerative duodenitis in a patient with COVID-19 infection: clinical improvement following treatment with budesonide.

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.

Immune checkpoint inhibitor-associated celiac disease.

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.

Iron pill-induced duodenitis: A distinct pattern of duodenal mucosal injury in a patient with a duodenal mass.

Ferrous sulfate is an oral iron supplement commonly used to treat iron deficiency anemia. Upper gastrointestinal (GI) tract mucosal damage with associated tissue iron accumulation can sometimes occur with therapeutic dosages of oral iron-containing medications. A distinct histologic pattern of iron deposition with associated inflammatory and reactive changes caused by mucosal injury from oral iron-containing medications has been most commonly described within gastric biopsies and has been referred to as "iron-pill gastritis". There have only been very rare reports of duodenal mucosa biopsies demonstrating predominantly extracellular crystalline iron deposits with surrounding tissue inflammation and injury analogous to the "iron-pill gastritis" pattern. Here we report a case of "iron pill-induced duodenitis", an uncommon histologic pattern of duodenal iron deposition and mucosal injury seen in a female in her 50 s with clinical findings of a duodenal mass.

Nod2 Protects the Gut From Experimental Colitis Spreading to Small Intestine.

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.

Taurine regulates mucosal barrier function to alleviate lipopolysaccharide-induced duodenal inflammation in chicken.

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.

[Enteropathy due to olmesartan]. / Entéropathie due à l'olmesartan.

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.

Catastrophic gastrointestinal complication of systemic immunosuppression.

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.

Results of drug correction of structural and functional changes in the gingiva in experimental gastroduodenitis.

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.

Non-steroidal anti-inflammatory drugs use and risk of upper gastrointestinal adverse events in cirrhotic patients.

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.

[The role of E2 and F2alpha prostaglandins in development of erosive-ulcerative lesions of the gastroduodenal region].

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.

Prevalence of gastroduodenal mucosal injury in asymptomatic patients taking antiplatelet agents in Japan.

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.

Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis.

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.

Acute NSAID-related transmural duodenitis and extensive duodenal ulceration.

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.

Targeted inhibition of glucuronidation markedly improves drug efficacy in mice - a model.

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.