en Allergy & Clinical Immunology Original Research Original Research <span style="font-size:13pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="text-autospace:none"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-style:italic"><b><span style="font-size:9.0pt"><span style="font-style:normal">Background: </span></span></b><span style="font-size:9.0pt"><span style="font-style:normal">Refractory chronic spontaneous urticaria (R-CSU) is characterized by systemic mast-cell-driven inflammation, which may present with extra-cutaneous conditions such as gastroesophageal reflux disease (GERD). The utility of simple blood-derived inflammatory ratios that characterize this systemic inflammation is currently limited. We investigated the neutrophil-to-lymphocyte ratio (NLR), eosinophil-to-lymphocyte ratio (ELR), and platelet-to-lymphocyte ratio (PLR) as potential inflammatory markers in patients with R-CSU, both with and without GERD.</span></span></span></span></span></span></span></span><br> <span style="font-size:13pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="text-autospace:none"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-style:italic"><span style="font-size:9.0pt"><span style="font-style:normal">&nbsp;&nbsp; <b>Methods:</b> A retrospective case-control study was conducted involving 116 patients with recurrent chronic spontaneous urticaria (R-CSU) between 2023 and 2024 at Ali ibn Abi Talib Hospital in Zahedan. Among these patients, 58 were diagnosed with GERD, while the remaining 58 were not. Initially, GERD was clinically confirmed, after which complete blood count (CBC) parameters were utilized to calculate the neutrophil-to-lymphocyte ratio (NLR), eosinophil-to-lymphocyte ratio (ELR), and platelet-to-lymphocyte ratio (PLR). Group differences were analyzed using Mann&ndash;Whitney U tests and multivariate regression, adjusted for potential confounders. Receiver operating characteristic (ROC) analysis was employed to assess diagnostic accuracy.</span></span></span></span></span></span></span></span><br> <span style="font-size:13pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="text-autospace:none"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-style:italic"><span style="font-size:9.0pt"><span style="font-style:normal">&nbsp;&nbsp; <b>Results:</b> NLR was significantly higher in R-CSU patients with GERD compared to those without GERD (NLR: 2.05 &plusmn; 1.7 vs 1.05 &plusmn; 0.91, </span></span><span style="font-size:9.0pt">P</span><span style="font-size:9.0pt"><span style="font-style:normal"> = 0.041; ELR: 0.26 &plusmn; 0.18 vs 0.21 &plusmn; 0.11, </span></span><span style="font-size:9.0pt">P</span><span style="font-size:9.0pt"><span style="font-style:normal"> = 0.084). In contrast, PLR did not differ significantly (</span></span><span style="font-size:9.0pt">P</span><span style="font-size:9.0pt"><span style="font-style:normal"> = 0.500). In the multivariate analysis, NLR remained an independent predictor of GERD comorbidity after adjustment (&beta; = 0.41, </span></span><span style="font-size:9.0pt">P</span><span style="font-size:9.0pt"><span style="font-style:normal"> < 0.001). ROC analysis identified an NLR cut-off of 1.24, demonstrating 81% sensitivity and 64% specificity for distinguishing R-CSU with GERD.</span></span></span></span></span></span></span></span><br> <span style="font-size:13pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="text-autospace:none"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-style:italic"><span style="font-size:9.0pt"><span style="font-style:normal">&nbsp;&nbsp; <b>Conclusion:</b> Elevated NLR and ELR indicate systemic inflammation in patients with refractory CSU and GERD. These findings support the hypothesis that systemic inflammation contributes to extracutaneous symptoms in this population. Routine, readily available CBC-derived ratios may serve as cost-effective markers for identifying systemic inflammatory activity in R-CSU.</span></span></span></span></span></span></span></span><br> &nbsp; Chronic spontaneous urticaria, Refractory urticaria, Gastroesophageal reflux disease, Systemic inflammation, Neutrophil-to-lymphocyte ratio, Eosinophil-to-lymphocyte ratio, Platelet-to-lymphocyte ratio, Mast cell activation 683 688 http://mjiri.iums.ac.ir/browse.php?a_code=A-10-10059-1&slc_lang=en&sid=1 Mohammad Sina Bamedi Mohammadbamedi@yahoo.com 200319475328460099057 0009-0004-9798-8701 No School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran Hossein Ansari Ansarih88@gmail.com 200319475328460099058 0009-0007-7293-563X No Department of Biostatistics and Epidemiology, School of Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran Ebrahim Alijani alijani@zaums.ac.ir 200319475328460099059 200319475328460099059 No Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran Hossein Shahriari hosseinshahriari@yahoo.com 200319475328460099060 200319475328460099060 No Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran Hossein Ali Khazaei h_khazaei118@yahoo.com 200319475328460099061 200319475328460099061 No Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran Seyed Ghader Azizi sg.azizi@zaums.ac.ir 200319475328460099062 200319475328460099062 Yes Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran