Autism in patients with eosinophilic gastrointestinal disease: A systematic review with meta-analysis.

PURPOSE: Neurodevelopmental disorders, such as autism spectrum disorder (ASD), have been increasingly associated with eosinophilic gastrointestinal disorders (EGID). However, the relationship between these diseases remains unclear. We performed a systematic review with meta-analysis to address this issue. METHODS: The search was performed according to the PRISMA guidelines using descriptors for ASD and EGIDs from the MEDLINE, Embase, PsycInfo, LILACS, and Web of Science databases. Observational studies with the prevalence of ASD in any EGID were included. The study protocol was registered on the PROSPERO platform under the number CRD42023455177. RESULTS: The total dataset comprised 766,082 participants. The result of the single-arm meta-analysis showed an overall prevalence of ASD in the population with EGID of 21.59% (95% CI: 10.73-38.67). There was an association between EGID and ASD (OR: 3.44; 95% CI: 1.25-2.21), also significant when restricted only to EoE (OR: 3.70; 95% CI: 2.71-5.70). DISCUSSION: Recent studies have implicated the influence of an inadequate epithelial barrier integrity in the pathogenesis of several diseases. The role of this mechanism can be extended to situations beyond allergic reactions, including other conditions with underlying immunological mechanisms. Several diseases are potentially related to the systemic effect of bacterial translocation in tissues with defective epithelial barriers. CONCLUSION: Our meta-analysis provides evidence that supports the consideration of EGID in patients with ASD and ASD in patients with EGID. Despite its limitations, the results should also be validated by future studies, preferably using multicenter prospective designs in populations with low referral bias.

Eosinophilic bronchiectasis increases length and cost of hospitalization: a retrospective analysis in a hospital of southern China from 2012 to 2020.

BACKGROUND: The concept of eosinophilic bronchiectasis has received clinical attention recently, but the association between blood eosinophil count (BEC) and hospital characteristics has rarely been reported yet. We aim to investigate the clinical impact of BEC on patients with acute bronchiectasis exacerbation. METHODS: A total of 1332 adult patients diagnosed with acute exacerbation of bronchiectasis from January 2012 to December 2020 were included in this retrospective study. A propensity-matched analysis was performed by matching age, sex and comorbidities in patients with high eosinophil count (≥ 300 cell/µL) and low eosinophil count (< 300 cell/µL). Clinical characteristics, length of hospital stay (LOS), hospitalization cost and inflammatory markers were compared between the two groups. RESULTS: Eosinophilic bronchiectasis occurred in approximately 11.7% of all patients. 156 propensity score-matched pairs were identified with and without high eosinophil count. Eosinophilic bronchiectasis presented with a longer LOS [9.0 (6.0-12.5) vs. 5.0 (4.0-6.0) days, p < 0.0001] and more hospitalization cost [15,011(9,753-27,404) vs. 9,109(6,402-12,287) RMB, p < 0.0001] compared to those in non-eosinophilic bronchiectasis. The median white blood cell (WBC), lymphocyte, platelet (PLT) and C-reactive protein (CRP) levels in eosinophilic bronchiectasis were significantly increased. Multivariate logistic regression analysis confirmed that the high levels of eosinophil count (OR = 13.95, p < 0.0001), worse FEV1% predicted (OR = 7.80, p = 0.0003) and PLT (OR = 1.01, p = 0.035) were independent prognostic factors for length of hospital (LOS) greater than 7 days. CONCLUSION: Eosinophilic bronchiectasis patients had longer length of hospital stay and more hospitalization cost compared to those in non-eosinophilic bronchiectasis group, which might be associated with the stronger inflammatory reaction.

Blood Eosinophil Count and Its Determinants in a Chinese Population-Based Cohort.

INTRODUCTION: Blood eosinophil count has been shown markedly variable across different populations. However, its distribution in Chinese general population remains unclear. We aimed to investigate blood eosinophil count and its determinants in a Chinese general population. METHODS: In this population-based study, general citizens of Sichuan province in China were extracted from the China Pulmonary Health study. Data on demographics, personal and family history, living condition, lifestyle, spirometry, and complete blood count test were obtained and analyzed. A stepwise multivariate binary logistic regression analysis was performed to identify determinants of high blood eosinophils (>75th percentile). RESULTS: A total of 3,310 participants were included, with a mean age (standard deviation) of 47.0 (15.6) years. In total population, the median blood eosinophil count was 110.0 (interquartile range [IQR]: 67.2-192.9) cells/µL, lower than that in smokers (133.4 cells/µL, IQR: 79.3-228.4) and patients with asthma (140.7 cells/µL, IQR: 79.6-218.2) or post-bronchodilator airflow limitation (141.5 cells/µL, IQR: 82.6-230.1), with a right-skewed distribution. Multivariate analyses revealed that oldness (aged ≥60 years) (odds ratio [OR]: 1.66, 95% confidence interval [CI]: 1.11-2.48), smoking ≥20 pack-years (OR: 1.90, 95% CI: 1.20-3.00), raising a dog/cat (OR: 1.72, 95% CI: 1.17-2.52), and occupational exposure to dust, allergen, and harmful gas (OR: 1.58, 95% CI: 1.15-2.15) were significantly associated with high blood eosinophils. CONCLUSION: This study identifies a median blood eosinophil count of 110.0 cells/µL and determinants of high blood eosinophils in a Chinese general population, including oldness (aged ≥60 years), smoking ≥20 pack-years, raising a dog/cat, and occupational exposure to dust, allergen, and harmful gas.

Characterization of drug-induced liver injury associated with drug reaction with eosinophilia and systemic symptoms in two prospective DILI registries.

Idiosyncratic drug-induced liver injury (DILI) associated with drug reactions with eosinophilia and systemic symptoms (DRESS) is poorly characterized among patients of Western countries. We aimed to comprehensively assess the clinical characteristics, outcomes, and causative agents in a prospective, well-vetted cohort of DILI patients with DRESS (DILI-DRESS). We identified 53 DILI-DRESS cases from the Spanish DILI Registry and the Latin American DILI Network. For comparison purposes, we defined a group of DILI patients (n = 881). DILI-DRESS cases were younger (47 vs. 53 years, respectively; p = 0.042) and presented more frequently with cholestatic/mixed damage (p = 0.018). Most DILI-DRESS patients showed moderate liver injury, 13% developed severe damage, and only one patient (with hepatocellular injury due to anti-tuberculosis drugs) progressed to acute liver failure and died. DILI-DRESS cases showed a distinctive causative drug pattern compared to DILI cases. The most frequent drugs were carbamazepine (13%), anti-tuberculosis drugs (13%), amoxicillin-clavulanate (11%), and allopurinol and lamotrigine (7.6% each). Among all cases of DILI due to allopurinol and lamotrigine, 67% presented with a DILI-DRESS phenotype, respectively. Higher total bilirubin (TBL) levels at DILI recognition (odds ratio [OR] 1.23; 95% confidence interval [CI] 1.04-1.45) and absence of eosinophilia (OR 8.77; 95% CI 1.11-69.20) increased the risk for developing a severe-fatal injury in DILI-DRESS patients. DILI-DRESS patients have a more frequent cholestasis/mixed pattern of injury at presentation, with antiepileptics as distinctive causative drug class. Most of the lamotrigine and allopurinol cases present with this phenotype. Higher TBL levels and absence of eosinophilia at DILI recognition are markers of poor outcomes.

Characteristics of DRESS Syndrome in the Elderly: A Comparative Study of 55 Patients.

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare drug reaction characterized by a skin rash, eosinophilia, and organ involvement. Objective: Our purpose is to focus on the clinical and epidemiological characteristics of DRESS in the elderly and to identify the incriminated drugs. Methods: This is a retrospective study including patients, hospitalized for DRESS with a RegiSCAR ≥4. The population was divided into 2 groups according to age: 65 years or older (G1) and <65 years (G2). The statistical study was performed using the comparative and multivariate analysis. Results: We included 55 patients (30.9% G1 and 69.1% G2). Skin manifestations were comparable in both groups. Lymphadenopathy was less common in G1 with a statistically significant difference (P = 0.012). Renal impairment was more frequent in the elderly with a statistically significant result (P = 0.005). DRESS in the elderly group was significantly associated with the occurrence of sepsis (P = 0.008). Allopurinol was the most common culprit associated with DRESS in G1 (P = 0.001). Relapses and recurrences were comparable in both groups (P = 0.71). Conclusions: DRESS in the elderly is associated with a high risk of complications, mainly kidney involvement and sepsis. Allopurinol is the most incriminated drug.

[Health implications of the finding of Angiostrongylus cantonensis, the main cause of eosinophilic meningoencephalitis, in continental Europe (Valencia, Spain)]. / Implicaciones sanitarias del hallazgo de Angiostrongylus cantonensis, causa principal de la meningoencefalitis eosinofílica, en Europa continental (València, España).

The rat pulmonary artery nematode, Angiostrongylus cantonensis (discovered in rats from the province of Canton, southern China, in 1933 ) is the main cause in humans of what is known as eosinophilic meningoencephalitis (EEM), with around of 3,000 confirmed cases in various parts of the world.

El nematodo de las arterias pulmonares de las ratas, Angiostrongylus cantonensis (descubierto en ratas de la provincia de Cantón, en el sur de China, en 1933  es el principal responsable en el ser humano de la conocida como meningoencefalitis eosinofílica (MEE), con alrededor de 3.000 casos confirmados en diversas partes del mundo.

Clinical Characteristics and Treatment Outcome of Eosinophilic Meningoencephalitis in South Indian Children: Experience From a Prospective Registry.

BACKGROUND: To describe the clinical features and therapeutic outcomes of a prospective cohort of children with eosinophilic meningoencephalitis. METHODS: Children admitted with clinical features suggestive of meningitis along with cerebrospinal fluid (CSF) eosinophilia during the period of 14 years (2008 to 2021) were included. Their baseline characteristics, epidemiologic associations, and treatment outcomes were analyzed and compared with the previous studies. RESULTS: We identified 25 children (13 males) satisfying the inclusion criteria. The median age at presentation was 3.9 years (range 0.8 to 17 years); 68% were aged less than two years. Fourteen (56%) children had a history of exposure to snails. Most of them presented with fever, headache, irritability, lateral rectus palsy, and early papilledema. Symptoms started three to 42 days (median duration: 14 days) before admission to our center. All children had peripheral eosinophilia, which ranged from 9% to 41%. The mean CSF white blood cell count was 416/mm3 (range 50 to 1245 cells/mm3) with CSF eosinophilia ranging from 11% to 80%. Brain magnetic resonance imaging was done in 24 children and was normal in 15 (62.5%). Leptomeningeal enhancement was seen in two (8.3%) children, and other nonspecific changes were noted in seven (29.1%) children. All children recovered without any neurological deficits with a standard treatment regimen of albendazole and oral steroids. All were asymptomatic at the last follow-up. None of them had any recurrence during the follow-up period. CONCLUSION: We report one of the largest clinical series of children with eosinophilic meningoencephalitis from an endemic area of South India.

Incidence and Risk Factors for Eosinophilia and Lung Disease in Biologic-Exposed Children With Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: Although interleukin-1 (IL-1)/IL-6 inhibitors are effective therapies for systemic juvenile idiopathic arthritis (JIA), some patients develop eosinophilia and lung disease during treatment. This study was undertaken to retrospectively evaluate incidence and risk factors for eosinophilia and describe lung disease outcomes in IL-1/IL-6 inhibitor-exposed patients with systemic JIA. METHODS: Among JIA patients at our institution exposed to interleukin-1 (IL-1)/IL-6 inhibitors (1995-2022), we compared incidence rate of eosinophilia in systemic JIA compared to other JIA, stratified by medication class (IL-1/IL-6 inhibitors, other cytokine inhibitors, methotrexate). We used Cox models to identify predictors of eosinophilia during IL-1/IL-6 inhibitor use and summarized treatment changes and outcomes after eosinophilia, including lung disease. HLA typing was performed on a clinical or research basis. RESULTS: There were 264 new medication exposures in 75 patients with systemic JIA and 41 patients with other JIA. A total of 49% of patients with systemic JIA with HLA typing (n = 45) were positive for HLA-DRB1*15 alleles. Eosinophilia was common during IL-1/IL-6 inhibitor use and did not differ by systemic JIA compared to other JIA (0.08 and 0.07 per person-year, respectively; P = 0.30). Among systemic JIA patients, pretreatment macrophage activation syndrome (MAS) was associated with a higher rate of subsequent eosinophilia on biologic therapy (unadjusted hazard ratio 3.2 [95% confidence interval 1.2-8.3]). A total of 4 of 5 patients who switched therapy within 10 weeks of eosinophilia experienced disease flare compared to none of the patients who continued the original therapy. A total of 8 of 25 patients with pulmonary evaluations had lung disease, and all had severe manifestations of systemic JIA (MAS, intensive care unit stay). One death was attributed to systemic JIA-lung disease. CONCLUSION: Eosinophilia is common in JIA patients using IL-1/IL-6 inhibitors. Severe disease may be associated with eosinophilia and lung disease in systemic JIA.

HLA-DRB1*15 and Eosinophilia Are Common Among Patients With Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: Concern exists that medications used to treat patients with systemic juvenile idiopathic arthritis (JIA), particularly interleukin (IL)-1 and IL-6 blocking agents, might be causing adverse drug reactions and lung disease (systemic JIA-LD). Carriage of HLA-DRB1*15 has been reported as a risk factor for adverse drug reactions among patients with systemic JIA. We performed a retrospective chart review to evaluate these factors at our center. METHODS: We reviewed the records of 86 subjects with systemic JIA followed for at least 6 months between 1996 and 2022. HLA typing was performed in 23 of the subjects. We compared characteristics of patients with or without eosinophilia. Among patients with HLA typing, we compared clinical characteristics of subjects with or without DRB1*15 and with or without systemic JIA-LD. RESULTS: Among the 23 patients with HLA typing, 74% carried DRB1*15, and 63% of patients without systemic JIA-LD carried DRB1*15. Seven subjects had systemic JIA-LD, all of whom carried DRB1*15. Patients with systemic JIA-LD were younger at the time of diagnosis and more likely to have had macrophage activation syndrome. Exposure to IL-1 and IL-6 blockers was common, occurring in 95% of patients. Eosinophilia occurred in 39% of patients with systemic JIA, often before IL-1 or IL-6 blockade. Eosinophilia was associated with adverse drug reactions and macrophage activation syndrome. There was 1 death, unrelated to active systemic JIA disease. CONCLUSION: Carriage of DRB1*15 was more common in this cohort of patients with systemic JIA than in the general population. Eosinophilia and systemic JIA-LD were more common among patients with severe systemic JIA complicated by macrophage activation syndrome.

Epidemiology, clinical presentation, and outcomes of 620 patients with eosinophilia in the intensive care unit.

PURPOSE: Although eosinophil-induced manifestations can be life-threatening, studies focusing on the epidemiology and clinical manifestations of eosinophilia in the intensive care unit (ICU) are lacking. METHODS: A retrospective, national, multicenter (14 centers) cohort study over 6 years of adult patients who presented with eosinophilia ≥ 1 × 109/L on two blood samples performed from the day before admission to the last day of an ICU stay. RESULTS: 620 patients (0.9% of all ICU hospitalizations) were included: 40% with early eosinophilia (within the first 24 h of ICU admission, ICU-Eo1 group) and 56% with delayed (> 24 h after ICU admission, ICU-Eo2 group) eosinophilia. In ICU-Eo1, eosinophilia was mostly due to respiratory (14.9%) and hematological (25.8%) conditions, frequently symptomatic (58.1%, mainly respiratory and cardiovascular manifestations) requiring systemic corticosteroids in 32.2% of cases. In ICU-Eo2, eosinophil-related organ involvement was rare (25%), and eosinophilia was mostly drug-induced (46.8%). Survival rates at day 60 (D60) after ICU admission were 21.4% and 17.2% (p = 0.219) in ICU-Eo1 and ICU-Eo2 patients, respectively. For ICU-Eo1 patients, in multivariate analysis, risk factors for death at D60 were current immunosuppressant therapy at ICU admission, eosinophilia of onco-hematological origin and the use of vasopressors at ICU admission, whereas older age and the use of vasopressors or mechanical ventilation at the onset of eosinophilia were associated with a poorer prognosis for ICU-Eo2 patients. CONCLUSION: Eosinophilia ≥ 1 × 109/L is not uncommon in the ICU. According to the timing of eosinophilia, two subsets of patients requiring different etiological workups and management can be distinguished.

Clinical Implications of Low-grade Duodenal Eosinophilia in Functional Dyspepsia: A Prospective Real-life Study.

BACKGROUND: Functional dyspepsia (FD) is a multifactorial disorder with no targeted therapy. Duodenal eosinophilia and low-grade inflammation are potential pathogenic mechanisms. However, the impact of duodenal eosinophils (D-EO) histologic evaluation in real-life clinical practice was not explored. AIM: To evaluate the clinical utility of D-EO and low-grade inflammation in FD in real-life practice. MATERIALS AND METHODS: A multicenter prospective study was conducted. A total of 636 patients who meet Rome-III criteria were selected before upper endoscopy and 516 patients were included after normal endoscopy were assessed. Clinical parameters, Helicobacter pylori ( H. pylori), and duodenal histology were evaluated. RESULTS: FD subtypes were 231 (45%) patients who had epigastric pain syndrome (EPS), 168 (33%) postprandial distress syndrome (PDS), and 117 (22%) EPS/PDS overlap. Two hundred fifty-nine (50.3%) patients were H. pylori+ . Histologic duodenal grading of chronic inflammation and intraepithelial lymphocytes showed no difference between FD subtypes. Increased in D-EO densities (>10 per high power field) was significant in PDS compared with EPS and EPS/PDS overlap subtypes. The odds ratio of PDS in subjects with duodenal eosinophilia densities was 2.28 (95% CI, 1.66-3.14; P <0.0001), adjusting for age, gender, H. pylori and nonsteroidal anti-inflammatory drug the odds ratio was 3.6 (95% CI, 2.45-5.28; P <0.0001). receiver operating characteristic curve analysis further demonstrated that low-grade duodenal eosinophilia, in particular H. pylori- , was highly accurate for PDS with the area under the curve 0.731 compared with H. pylori+ area under the curve 0.598. Furthermore, low-grade duodenal eosinophilia was significantly correlated with treatment response under 4 to 6 weeks of proton pump inhibitor therapy. CONCLUSION: Our findings suggest that low-grade duodenal eosinophilia is associated with PDS subtype non- H. pylori FD patients and could be a useful marker of treatment response.

Seroprevalence and microscopy detection rates of strongyloidiasis in Croatian patients with eosinophilia.

Infection with the parasitic nematode Strongyloides stercoralis is characteristic for tropical and subtropical regions of the world, but autochthonous cases have been reported in European countries as well. Here we present the first nation-wide survey of S. stercoralis seroprevalence in Croatian individuals presenting with eosinophilia, and evaluate the fraction of positive microscopy rates in stool specimens of seropositive individuals. In our sample of 1407 patients tested between 2018 and 2021, the overall prevalence of strongyloidiasis was 9.31%, with significantly higher rates in those older than 60 years of age (P = 0.005). Of those, one-quarter (25.95%) were also positive following microscopy examination of faeces after using the merthiolate-iodine-formaldehyde concentration method. Our findings reinforce the notion of endemic strongyloidiasis transmission in Croatia, particularly in older individuals, and highlight the need to consider the presence of S. stercoralis in patients with eosinophilia.

Clinical features of pediatric eosinophilic gastroenteritis.

BACKGROUND: No study has analyzed more than100 cases of eosinophilic gastroenteritis (EGE) in children in a single center. We aimed to describe the clinical features of pediatric EGE. METHODS: This retrospective study was conducted at a single center. Between April 2007 and December 2017, 860 children between the ages of 1 year and 15 years underwent endoscopy for gastrointestinal symptoms of unknown cause. Among them, 109 (12.7%) were diagnosed with EGE according to the diagnostic criteria for EGE developed by the research group of the Ministry of Health, Labour and Welfare of Japan for eosinophilic gastrointestinal disorder in 2015. We investigated their symptoms, comorbidities, endoscopic findings, pathological findings, treatments, and outcomes. RESULTS: Seventy-one boys (65.1%) and 38 girls (34.9%) were diagnosed with EGE. The median age at diagnosis was 11 years (range, 1-15 years). The chief complaints were abdominal pain in 83 (76.1%) and diarrhea in 26 (23.9%). Upper and lower gastrointestinal endoscopies showed normal findings in 32 patients (29.4%). The most common treatment was a combination of elimination of foods suspected of causing EGE and anti-allergic agents in 50 cases (45.9%). The outcomes were symptom disappearance in 43 patients (39.4%) and symptom improvement in 53 patients (48.6%). CONCLUSIONS: For gastrointestinal symptoms of unknown cause in children, EGE should be considered as a differential diagnosis. Although the symptoms and endoscopic findings are nonspecific, cracked mucosa may be a specific endoscopic finding for pediatric EGE. An elimination diet and/or anti-allergic drugs were effective in most patients with pediatric EGE.

Laboratory Features of Trichinellosis and Eosinophilia Threshold for Testing, Nunavik, Quebec, Canada, 2009-2019.

Prolonged eosinophilia is characteristic of trichinellosis. To determine the optimal eosinophil threshold for reflex Trichinella testing, we examined all 43 cases in Nunavik, Quebec, Canada, during 2009-2019. Using receiver operating characteristic analysis, we determined that eosinophil counts >0.8 × 109 cells/L should prompt consideration of trichinellosis and testing to rapidly identify potential outbreaks.

Duodenal eosinophilia is associated with symptomatic erosive gastro-oesophageal reflux disease, presence of co-morbidities, and ethnicity but not undifferentiated functional dyspepsia: A retrospective Malaysian study.

BACKGROUND: Duodenal eosinophilia is postulated to play a key role in the pathogenesis of functional dyspepsia, a common condition responsible for considerable impairment of quality of life. Our objective was to evaluate the relative strength of the associations between duodenal eosinophilia, functional dyspepsia, symptomatic erosive gastroesophageal reflux disease (GERD), the presence of co-morbidities, and a number of other variables. METHODS: Eosinophil counts of archived endoscopic duodenal biopsies of 289 subjects were determined by a pathologist blinded to the clinical data. Duodenal eosinophilia was defined by a count of more than 15 per 5 high power fields. Clinical charts were reviewed by a gastroenterologist blinded to the histology review. RESULTS: In the study sample, the primary diagnosis was functional dyspepsia (undifferentiated by subtypes) in 45, symptomatic erosive GERD in 29, gall stone disease in 17, irritable bowel syndrome in 23, and an alternative or undetermined diagnosis in 175 subjects, respectively. On logistic regression analyses, eosinophil counts were positively associated with symptomatic erosive GERD (Odds Ratio, OR 1.03, 95% Confidence Interval, 95%CI: 1.00, 1.05; p=0.035) but not functional dyspepsia. Pre-defined duodenal eosinophilia was associated with symptomatic erosive gastro-oesophageal reflux disease (OR 3.36, 95%CI 1.18,-9.60; p=0.023), the presence of co-morbidities (OR 2.00, 95%CI 1.10, 3.62; p=0.022), and Chinese (as compared to Malay and Indian) ethnicity but not with either functional dyspepsia, irritable bowel syndrome, gallstone disease, Helicobacter pylori infection, or gender. CONCLUSION: Duodenal eosinophilia was associated with symptomatic erosive GERD, the presence of co-morbidities, and Chinese ethnicity but not with undifferentiated functional dyspepsia.

Clinical features and three-year prognosis of AECOPD patients with different levels of blood eosinophils.

BACKGROUND: Eosinophils are thought to be associated with the frequency and severity of acute exacerbations of chronic obstructive pulmonary disease (AECOPD); however, the role of eosinophilic inflammation in AECOPD is still incompletely understood. OBJECTIVES: To investigate the relationship between different levels of blood eosinophils and clinical features, including comorbidities, therapy, and prognosis, and to further explore the optimal eosinophilic cutoff. METHODS: We retrospectively collected and analyzed medical data, laboratory findings, chest CT images, treatment, and three-year follow-up data from 984 AECOPD patients with different blood eosinophil (EOS) levels: EOS%<2%, ≥2%; EOS%<3%, ≥3%; eosinophil counts<100 cells/L, ≥100 cells/L. RESULTS: The prevalence of eosinophilia was 36.48% of EOS≥2% (359 cases), 22.87% of EOS≥3% (225 cases), and 48.48% with eosinophil counts≥100 cells/µl (477 cases). EOS was associated with comorbidities, including pulmonary heart disease, arrhythmia (atrial fibrillation), laboratory testing and clinical treatment, including respiratory failure, airway limitation, infectious inflammation, rate of antibiotic use, systemic glucocorticoids, and three mortality rates. The ROC curve showed that the indicators of AUC≥0.5 included chest CT imaging (emphysema 1.8% or ≥100/µl, bronchitis, 1.7% or ≥100/µl), osteoporosis (2.4% or ≥140/µl), mental illness 6.1% (or ≥400/µl), dust exposure (2.2% or ≥240/µl) and ex-smoker (1.3% or ≥100/µl). CONCLUSIONS: The relatively higher EOS group (≥2% or ≥100/µl) was associated with fewer complications, mild airflow limitation, a tendency of noninfectious inflammation, and lower 3-year mortality. Eosinophils can not only guide clinical treatment but also be an indicator of predicting clinical outcome and prognosis in AECOPD patients.

Potential Biomarker Identification by RNA-Seq Analysis in Antibiotic-Related Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Pilot Study.

One of the most severe forms of cutaneous adverse drug reactions is "drug reaction with eosinophilia and systemic symptoms" (DRESS), hence subsequent avoidance of the causal drug is imperative. However, attribution of drug culpability in DRESS is challenging and standard skin allergy tests are not recommended due to patient safety reasons. Whilst incidence of DRESS is relatively low, between 1:1000 and 1:10 000 drug exposures, antibiotics are a commoner cause of DRESS and absence of confirmatory diagnostic test can result in unnecessary avoidance of efficacious treatment. We therefore sought to identify potential biomarkers for development of a diagnostic test in antibiotic-associated DRESS. Peripheral blood mononuclear cells from a "discovery" cohort (n = 5) challenged to causative antibiotic or control were analyzed for transcriptomic profile. A panel of genes was then tested in a validation cohort (n = 6) and compared with tolerant controls and other inflammatory conditions which can clinically mimic DRESS. A scoring system to identify presence of drug hypersensitivity was developed based on gene expression alterations of this panel. The DRESS transcriptomic panel identified antibiotic-DRESS cases in a validation cohort but was not altered in other inflammatory conditions. Machine learning or differential expression selection of a biomarker panel consisting of 6 genes (STAC, GPR183, CD40, CISH, CD4, and CCL8) showed high sensitivity and specificity (100% and 85.7%-100%, respectively) for identification of the culprit drug in these cohorts of antibiotic-associated DRESS. Further work is required to determine whether the same panel can be repeated for larger cohorts, different medications, and other T-cell-mediated drug hypersensitivity reactions.

Peripheral blood eosinophilia in dogs: Prevalence and associated diseases.

BACKGROUND: Canine eosinophilia has not been evaluated over the last two decades. As in human local differences, changes in the prevalence and associated diseases over time can be expected. OBJECTIVE: This study aims to determine the prevalence and causes of marked blood eosinophilia in dogs. METHODS: Retrospective study. A total of 317 clinical histories of dogs with an eosinophil concentration > 1.5 × 109 /L (marked eosinophilia) between 2013 and 2017 were evaluated. Patients were allocated to 10 groups according to their major clinical findings. RESULTS: Eosinophilia was present in 1,592 of 10,829 dogs (14.7%); it was mild (0.8-1.49 × 109 /L) in 78.4%, moderate (1.5 - 4.9 × 109 /L) in 20.5% and severe (> 5 × 109 /L) in 1.1% of cases. Rottweilers were overrepresented (16.1%). Of 317 cases with marked eosinophilia, 19.6% had neoplasia, 19.1% gastrointestinal disorders, 13.6% health check, 10.4% endoparasites, 6% respiratory, 5.4% neurologic, 5.4% dermatologic, 4.8% urogenital, 3.2% endocrine disorders and 12.6% miscellaneous. Lymphomas (29%) and mast cell tumours (12.9%) were the most frequent tumours in the neoplasia group. A total of 72.6% of tumour-bearing dogs were older than 8 years, while 63.6% of dogs had endoparasites, and 86% of apparently healthy dogs were younger than 5 years. Eosinophilia was significantly higher in patients with respiratory disorders (p < 0.0146). Leukocytosis was found in 50.2% of cases. CONCLUSION: Malignancy was the most common cause of marked blood eosinophilia in older dogs and endoparasitism in younger dogs. Eosinophilia was common in apparently healthy young dogs and may be related to undiagnosed parasitic infestations.

Screening the European pharmacovigilance database for reports of clozapine-related DRESS syndrome: 47 novel cases.

Clozapine-related drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare adverse reaction. We aimed to screen a large pharmacovigilance database to identify clozapine-related DRESS cases, even if otherwise reported and provide a clinical overview. We screened spontaneous reports of clozapine-related DRESS syndrome in EudraVigilance database applying the European Registry on Severe Cutaneous Adverse Drug Reactions (RegiSCAR) criteria and scores to identify probable/definite DRESS syndrome cases. Clinical and demographic characteristics of included cases were provided and associations between RegiSCAR scores, and time to develop/recover DRESS were assessed. In a total of 262,146 adverse drug reactions reports for 75,190 clozapine-treated patients, 596 cases fulfilled RegiSCAR criteria; ultimately, 51 cases were rated as probable/definite DRESS according to RegiSCAR scores, of which 4 were previously published as case reports. The mean age of patients was 41.06 years (43.1% females), with 13 patients (25.5%) receiving reported co-medication with other DRESS culprit drugs. Median time between clozapine initiation and DRESS symptoms was 25 days. Clozapine dose was associated with days to develop symptoms (Spearman's ρ 0.40, p = 0.03). Organ involvement was reported in all cases followed by fever (n = 49; 96.1%) and eosinophilia (n = 47; 92.2%). Treatment involved clozapine discontinuation for 37 patients (72.5%), while 3.9% (n = 2) of cases ended fatally. Clozapine rechallenge was undertaken in 25 patients (49.0%). The screening of the EudraVigilance database revealed 47 novel clozapine-related DRESS cases, and only one was originally reported as DRESS. Clozapine-related DRESS may occur with clozapine monotherapy not only during dose titration, but also during maintenance treatment.