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Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction generally accompanied by skin manifestations as the first and most frequent symptoms. However, skin manifestations and associated clinical features of DRESS have not been fully explored and evaluated.This study aimed to describe the skin manifestations of DRESS in detail and analyse their association with demographic characteristics and extra-cutaneous clinical features.We conducted this retrospective study on patients with DRESS diagnosed between September 2009 and August 2021 at three medical institutes and validated using the RegiSCAR score. Data regarding demographics, skin manifestations and clinical characteristics were retrieved through thorough chart reviews.Among 182 potential cases of DRESS, the validated 125 cases were analysed. A widespread rash extending over more than 50% of the body surface area was observed in 122 patients (97.6%) and typical facial oedema was experienced by 67 patients (53.6%). Polymorphous maculopapules were the most common rash morphology (106, 84.8%): specifically, exfoliative (59, 47.2%), urticarial (57, 45.6%) and purpuric forms (39, 31.2%) were common. Mucosal involvement was observed in 41 patients (32.8%). Patients with carboxamide antiepileptics (carbamazepine and oxcarbazepine) experienced more oedema (P = 0.014) and typical facial oedema than those with allopurinol (P = 0.021). The RegiSCAR score was higher in patients with purpura (P 0.01).Skin manifestations of DRESS exhibit a wide range of skin lesions and can vary according to the culprit drugs. Early suspicion and prompt intervention are needed to improve prognosis.

Olfactory receptors are ectopically expressed in extra-nasal tissues. The gut is constantly exposed to high levels of odorants where ectopic olfactory receptors may play critical roles. Activation of ectopic olfactory receptor 544 (Olfr544) by azelaic acid (AzA), an Olfr544 ligand, reduces adiposity in mice fed a high-fat diet (HFD) by regulating fuel preference to fats. Herein, we investigated the novel function of Olfr544 in the gut. In GLUTag cells, AzA induces the cAMP-PKA-CREB signaling axis and increases the secretion of GLP-1, an enteroendocrine hormone with anti-obesity effects. In mice fed a HFD and orally administered AzA, GLP-1 plasma levels were elevated in mice. The induction of GLP-1 secretion was negated in cells with Olfr544 gene knockdown and in Olfr544-deficient mice. Gut microbiome analysis revealed that AzA increased the levels of Bacteroides acidifaciens and microbiota associated with antioxidant pathways. In fecal metabolomics analysis, the levels of succinate and trehalose, metabolites correlated with a lean phenotype, were elevated by AzA. The function of Olfr544 in gut inflammation, a key feature in obesity, was further investigated. In RNA sequencing analysis, AzA suppressed LPS-induced activation of inflammatory pathways and reduced TNF-α and IL-6 expression, thereby improving intestinal permeability. The effects of AzA on the gut metabolome, microbiome, and colon inflammation were abrogated in Olfr544-KO mice. These results collectively demonstrated that activation of Olfr544 by AzA in the gut exerts multiple effects by regulating GLP-1 secretion, gut microbiome and metabolites, and colonic inflammation in anti-obesogenic phenotypes and, thus, may be applied for obesity therapeutics.

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in non-obese individuals. Gut microbiome profiles of 171 Asians with biopsy-proven NAFLD and 31 non-NAFLD controls are analyzed using 16S rRNA sequencing; an independent Western cohort is used for external validation. Subjects are classified into three subgroups according to histological spectra of NAFLD or fibrosis severity. Significant alterations in microbiome diversity are observed according to fibrosis severity in non-obese, but not obese, subjects. Ruminococcaceae and Veillonellaceae are the main microbiota associated with fibrosis severity in non-obese subjects. Furthermore, stool bile acids and propionate are elevated, especially in non-obese subjects with significant fibrosis. Fibrosis-related Ruminococcaceae and Veillonellaceae species undergo metagenome sequencing, and four representative species are administered in three mouse NAFLD models to evaluate their effects on liver damage. This study provides the evidence for the role of the microbiome in the liver fibrosis pathogenesis, especially in non-obese subjects., Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in individuals without obesity. Here, gut microbiome analysis using a biopsy-proven NAFLD cohort reveal distinct signatures of microbiome-metabolites associated with significant fibrosis in patients with NAFLD without obesity.