Granulomatous hepatitis associated with glyburide

Summary A wide variety of diseases and injuries can cause granulomatous hepatitis, and drug-induced granulomatous hepatitis is a well-described entity. Sulfonylurea derivatives, which are commonly used oral hypoglycemic agents in the treatment of non-insulin-dependent diabetes mellitus, have been implicated in liver disease. However, glyburide, a second-generation sulfonylurea and a potent hypoglycemic drug, is considered to have less hepatic side effects than chlorpropamide. It has been reportedly associated with cholestatic jaundice and hepatitis and with hypersensitivity angiitis. A case of necrotizing granuloma has been reported. We present a second case of granulomatous hepatitis occurring in a patient who had been taking glyburide for approximately three years, and we review the literature for glyburide-associated hepatitis.     

Molecular basis and cellular mechanisms of eosinophilic esophagitis for the clinical practice

Introduction: Eosinophilic esophagitis (EoE) is a chronic, allergen-driven inflammatory esophageal disease characterized by predominantly eosinophilic inflammation leading to esophageal dysfunction. Recent efforts to understand EoE have increased our knowledge of the disease.

Areas covered: Multiple cells, molecules, and genes interplay with early life environmental factors in the pathophysiology of EoE to converge in the esophageal epithelium at the center of disease pathogenesis. Epithelial cells constitute a mayor cytokine source for TSLP and Calpain-14; an impaired epithelial barrier function allowing penetration of food and microbiota-derived antigens is involved in triggering and maintaining inflammation. Eosinophil and mast cell-derived products, including TGFβ, together with IL-1β and TNFα, promote epithelial mesenchymal transition in EoE, contributing to tissue remodeling by synthetizing and depositing extracellular matrix in subepithelial layers. This article aims to provide a state-of-the-art update on the pathophysiology of EoE applied to clinical practice, and latest research and developments with potential interest to improve the diagnosis and treatment of patients with EoE are revised.

Expert commentary: Preliminary approaches have provided promising results toward incorporating minimally invasive methods for patient diagnosis and monitoring in clinical practice. Early diagnosis and optimized therapies will allow for personalized medicine in EoE.     

Granulomatous disease in selective IgA deficiency

Although common variable immunodeficiency (CVID) is sometimes associated with sarcoidosis/granulomatous disease, there have only been isolated reports of selective immunoglobulin A (IgA) deficiency and granulomatous disease. We present a patient with IgA deficiency who developed Heerfordt syndrome, a variant of neurosarcoidosis. This specific entity has not been previously reported to occur in IgA deficiency. Our case expands the reported associations of IgA deficiency and provides another example to the paucity of reported cases of sarcoidosis occurring in patients with IgA deficiency. As CVID and IgA deficiency have common underlying genetic factors, such an association is biologically plausible.     

Pleural tuberculosis in Harare, Zimbabwe: the relationship between human immunodeficiency virus, CD4 lymphocyte count, granuloma formation and disseminated disease

objective   To elucidate the relationship between HIV, CD4¹ count and pleural TB. method   In a prospective study, 94 patients presenting at two large Harare hospitals with clinically suspected pleural TB were enrolled over a 10-month period. All underwent standardized evaluation, closed pleural aspiration and biopsy. Patients receiving directly observed anti-TB therapy were followed-up. results   Pleural TB was diagnosed in 90 individuals (median age 33 years; range 18-65; 64 males); the seroprevalence of HIV was 85%. HIV-positive patients were older than HIV-negative individuals (median age 33 vs 23 years, P = 0.013) and had a significantly lower median CD4¹ count (191 vs 1106 × 10⁶/l respectively, P = 0.004). A CD4¹ count of <200 × 10⁶/l was associated with a length of illness >30 days (65% vs 37%; P = 0.05), a positive pleural fluid smear (37% vs 0%; P = 0.0006) and a positive pleural biopsy Ziehl-Neelsen stain (35% vs 7%; P = 0.021). However, a relationship between CD4¹ count and either pleural granuloma formation or radiological evidence of disseminated disease was not observed. conclusion   In sub-Saharan Africa, TB pleural effusions have become associated with older age, a chronic onset, and an increased mycobacterial load. These data emphasize the complex relationship between pleural TB, HIV infection and a low CD4¹ count.     

Pulmonary TCR γδ T cells induce the early inflammation of granuloma formation by a glycolipid trehalose 6,6′-dimycolate (TDM) isolated from Mycobacterium tuberculosis

We previously showed that formation of pulmonary granulomas in mice in response to a mycobacterial glycolipid, trehalose 6,6′-dimycolate (TDM) is due to the action of TNF-α and not of IFN-γ. However, the mechanisms of formation and maintenance of pulmonary granulomas are not yet clear. The purpose of the present study is to evaluate the mechanisms of granuloma formation by TDM at the early phase. Histological analysis showed that inflammatory cells infiltrated the murine pulmonary interstitium on day 2 after an intravenous injection with TDM as a w/o/w emulsion. Clear granuloma formation was observed on day 7 after the injection. The mRNA expression of IL-17, IFN-γ and macrophage inflammatory protein 2 was found in lung mononuclear cells at the day after TDM injection. The major IL-17-producing cells were T-cell receptor (TCR) γδ T cells expressing Vγ6. In mice depleted of γδ T cells by treatment with anti-TCR γδ monoclonal antibody, the number of TDM-induced granuloma was decreased, but the size of granuloma was not affected. Our results suggest that the mycobacterial glycolipid TDM causes activation of IL-17-producing TCR γδ T cells and stimulates chemotaxis of inflammatory cells including neutrophils in to lung.     

Radiological features of central giant cell granuloma: comparative study of 7 cases and literature review

Objective:To review and analyze the clinical and imaging features of central giant cell granuloma patients and to review the relevant literatures for the diagnosis and clinical manifestation of central giant cell granuloma.Methods:Seven cases of central giant cell granuloma were retrospectively selected for the study, all of which were confirmed by pathology and had relevant imaging investigations. All seven cases had undergone CT scan, three cases had undergone MRI scan. Detailed clinical features were compared along with the imaging findings and analysis was done on the basis of their presentation and imaging features.Results:The clinical features, radiologic features were varied according to the site of the lesion. CT features include unevenly dense expansile mass causing bone destruction and cortical thinning. While MRI features with low to iso-intensity in T₁- and T₂ weighted images. There may be presence of cystic degeneration, hemorrhage or hemosiderin deposits or osteoid formation, which can cause T1 and T2 signal changes. On contrast study, the lesion doesn’t enhance but periphery may enhance mildly.Conclusion:Unevenly dense expansile mass with bone destruction and cortical thinning with low to iso-intensity in T₁ weighted and T₂ weighted images and mildly enhance peripherally, Central giant cell granuloma should be considered.     

The influence of individual characteristics and non‐respiratory diseases on blood eosinophil count

BackgroundBlood eosinophil (B‐Eos) count is an emerging biomarker in the management of respiratory disease but determinants of B‐Eos count besides respiratory disease are poorly described. Therefore, we aimed to evaluate the influence of non‐respiratory diseases on B‐Eos count, in comparison to the effect on two other biomarkers: fraction of exhaled nitric oxide (FeNO) and C‐reactive protein (CRP), and to identify individual characteristics associated with B‐Eos count in healthy controls.MethodsChildren/adolescents (<18 years) and adults with complete B‐Eos data from the US National Health and Nutritional Examination Surveys 2005–2016 were included, and they were divided into having respiratory diseases (n = 3333 and n = 7,894, respectively) or not having respiratory disease (n = 8944 and n = 15,010, respectively). After excluding any respiratory disease, the association between B‐Eos count, FeNO or CRP, and non‐respiratory diseases was analyzed in multivariate models and multicollinearity was tested. After excluding also non‐respiratory diseases independently associated with B‐Eos count (giving healthy controls; 8944 children/adolescents and 5667 adults), the independent association between individual characteristics and B‐Eos count was analyzed.ResultsIn adults, metabolic syndrome, heart disease or stroke was independently associated with higher B‐Eos count (12%, 13%, and 15%, respectively), whereas no associations were found with FeNO or CRP. In healthy controls, male sex or being obese was associated with higher B‐Eos counts, both in children/adolescents (15% and 3% higher, respectively) and adults (14% and 19% higher, respectively) (p < 0.01 all). A significant influence of race/ethnicity was also noted, and current smokers had 17% higher B‐Eos count than never smokers (p < 0.001).ConclusionsNon‐respiratory diseases influence B‐Eos count but not FeNO or CRP. Male sex, obesity, certain races/ethnicities, and current smoking are individual characteristics or exposures that are associated with higher B‐Eos counts. All these factors should be considered when using B‐Eos count in the management of respiratory disease.     

A Retrospective Brazilian Multicenter Study of Biopsies at the Periapical Area: Identification of Cases of Nonendodontic Periapical Lesions

IntroductionThe purpose of this study was to analyze the features of lesions obtained from biopsies at the periapical area of teeth with a radiographic or clinical initial diagnosis of apical periodontitis.MethodsA retrospective study was conducted on biopsies obtained from 1953–2018 at 3 Brazilian oral and maxillofacial pathology centers. Cases of endodontic and nonendodontic periapical lesions (NPLs) with a clinical diagnosis of endodontic pathoses were retrieved. Data regarding patient age, sex, and anatomic location were obtained from patients’ records. The frequency and percentage of cases with clinical diagnoses of a periapical cyst, periapical granuloma, or dentoalveolar abscess were recorded, and the final histopathologic diagnosis was documented.ResultsAmong 66,179 oral biopsies, 7246 (10.94%) were clinically diagnosed as periapical disease, 306 (4.22%) of which were histopathologically diagnosed as NPLs. The most frequent NPLs were odontogenic keratocysts (n = 107, 34.96%) followed by dentigerous cysts (n = 48, 15.68%). The mean age at diagnosis was 39.68 years with a range of 6–80 years. A total of 159 (51.96%) cases occurred in females and 147 (48.03%) in males (female to male ratio = 1.08:1). Most lesions (137, 44.77%) were located in the posterior mandible.ConclusionsA wide variety of histopathologic diagnoses, including benign odontogenic and nonodontogenic cystic and tumorous lesions, infectious diseases, and malignant neoplasms, was reported in the present survey. The features presented in this study were consistent with previous findings reported in the literature.