Citations

AbstractBackgroundAcute generalized exanthematous pustulosis (AGEP) is a rare skin condition typically caused by medications. The objective of this study was to examine the clinical features, causes, and outcomes of AGEP at a sole tertiary care center.MethodsA retrospective review of patients with AGEP (European Study of Severe Cutaneous Adverse Reactions score of ≥ 5) seen at Mayo Clinic (Rochester, MN, USA) between January 1, 1996, and December 31, 2013, was conducted.ResultsOf 28 patients (mean age at onset: 56 years), 17 (61%) were women. The development of AGEP was attributed to medications in 25 patients (89%), with clindamycin the most common culprit (six patients). Three patients (11%) had mucous membrane involvement, and 21 (75%) showed systemic involvement. Ten patients (36%) received systemic corticosteroids for treatment of AGEP. Skin findings resolved within 15 days in 26 patients (93%) (mean time to resolution: 7.6 days). In three patients (11%), generalized skin eruptions or dermatitis developed weeks to months after the resolution of AGEP. Twenty‐four patients (86%) had a personal history of drug reactions before the development of AGEP.ConclusionsA previous history of drug reactions and clindamycin causation were more common in the present cohort than in prior reports. A small subset of patients experienced new‐onset non‐AGEP skin eruptions within a few months of the resolution of AGEP.

AbstractBackgroundThe prevalence of chronic opioid use among non‐cancer patients presenting with acute abdominal pain (AAP) is unknown. The aim was to characterize opioid use, constipation, diagnoses, and risk factors for surgical diagnoses among non‐cancer patients presenting with AAP to an emergency department (ED).MethodsWe performed a retrospective, observational cohort study of all (n=16,121) adult patients (88% from MN, IA and WI) presenting during 2014 with AAP. We used electronic medical records, and focused on 2352 adults with AAP who underwent abdominal CT scan within 24 hours of presentation. We determined odds ratios of association with constipation and features predicting conditions that may require surgery (surgical diagnosis).Key ResultsThere were 2352 eligible patients; 18.8% were opioid users. Constipation was more frequent in opioid (35.1%) compared to non‐opioid users [OR 2.88 (95% CI 2.28, 3.62)]. Prevalence of surgical diagnosis in the opioid and non‐opioid users was 35.3% and 41.7% respectively (P=.019). By univariate analysis, age and neutrophil count independently predicted increased risk, and chronic opioid use decreased risk of surgical diagnosis. Internal validation of logistic models using a randomly selected validation subset (25% of entire cohort, 587/2352) showed receiver operating characteristic (ROC) curves for the validation and full cohorts were similar.Conclusions and InferencesApproximately 19% of adults presenting with AAP were opioid users; constipation is almost three times as likely in opioid users compared to non‐opioid users presenting with AAP. Factors significantly associated with altered risk of surgical diagnoses were age, opioid use, and neutrophil count.

Amicrobial pustulosis of the folds (APF) is a rare disease characterized by aseptic pustular lesions involving cutaneous folds, typically occurring in the context of an autoimmune disorder. We present 4 patients with APF, focusing on clinical and histopathologic characteristics to improve the recognition of this entity. All 4 patients had intertriginous and extra‐intertriginous involvement. Common histopathologic features of skin biopsies in these patients were intracorneal, subcorneal, intraepidermal, perivascular, perifollicular and interstitial neutrophilic inflammation. Pustules overlying adnexal ostium and papillary dermal edema were consistently observed. The pustules were negative for microorganisms on stain testing. In these cases, associated conditions were undifferentiated connective tissue disease, systemic lupus erythematosus, antiphospholipid syndrome, Crohn disease and Hashimoto thyroiditis. The aforementioned clinical and histopathologic characteristics of patients with suspected or diagnosed connective tissue disorders should lead to suspicion for APF.

SummaryBackgroundAlthough eosinophilic oesophagitis (EoE) is putatively mediated by an abnormal response to food antigen, the oesophagus is considered relatively impermeable to large molecules.AimTo assess whether food antigens penetrate the oesophageal mucosa in patients with EoE.MethodsAnti‐gliadin staining was performed in three groups: active EoE, inactive EoE and EoE patients on a low or gluten free diet. To appraise the specificity of our results, we also performed gliadin staining on six patients without oesophageal disease who were consuming gluten. The groups with EoE on gluten also underwent endoscopic infusion with gluten containing soy sauce and repeat biopsies during the endoscopy. We measured eosinophil density, dilated intercellular spaces (on a 0–4+ scale) and gliadin in oesophageal mucosa by immunofluorescence.ResultsPatients with active EoE had significantly greater epithelial density of anti‐gliadin staining when compared to inactive EoE (P < 0.0065) and gluten‐free patients (P < 0.0008) at baseline and after soy infusion. Gliadin was not detected in non‐EoE control patients. The distribution of gliadin was both cytoplasmic and nuclear. There was good correlation of dilated intercellular spaces grade and total gliadin staining intensity (r = 0.577, P = 0.0077). Acute oesophageal perfusion of a commercial gliadin‐rich soy sauce did not lead to an increase in gliadin staining in active or inactive EoE.ConclusionThese findings suggest, although do not prove, that antigen penetration in active eosinophilic oesophagitis might be facilitated by impairment of epithelial integrity.

Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase–isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase–isomaltase ( SI ) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case–control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.

Several chemical and molecular factors in the intestine are reported to be altered and to have a potentially significant role in irritable bowel syndrome (IBS), particularly in IBS with diarrhea. These include bile acids; short-chain fatty acids; mucosal barrier proteins; mast cell products such as histamine, proteases, and tryptase; enteroendocrine cell products; and mucosal mRNAs, proteins, and microRNAs. This article reviews the current knowledge and unanswered questions in the pathobiology of the chemical and molecular factors in IBS. Evidence continues to point to significant roles in pathogenesis of these chemical and molecular mechanisms, which may therefore constitute potential targets for future research and therapy. However, it is still necessary to address the interaction between these factors in the gut and to appraise how they may influence hypervigilance in the central nervous system in patients with IBS.