Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2025;15(1):4969 1 Evaluation of the Effects of systemic Therapy on Inflammatory Markers and Disease Severity in Patients with Pemphigus Mehmet Enes Güner1, Perihan Öztürk1, Mine Müjde Kuş1 1 Sutcu Imam University Hospital of Health, Practice and Research, Kahramanmaras Sutcu Imam University, Department Of Dermatology, Kahramanmaras, Turkey Key words: Inflammatory Markers, IVIG, Remission, Pemphigus Citation: Güner ME, Öztürk P, Kuş MM. Evaluation of the Effects Of systemic Therapy on Inflammatory Markers and Disease Severity in Patients With Pemphigus. Dermatol Pract Concept. 2025;15(1):4969. DOI: https://doi.org/10.5826/dpc.1501a4969 Accepted: November 11, 2024; Published: January 2025 Copyright: ©2024 Güner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Mehmet Enes Güner, MD, Department of Dermatology, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey. E-mail: mehmetenesguner171@hotmail.com Introduction: In recent years, various inflammatory markers that can change in inflammatory states have been investigated. On the basis of these, we thought that inflammatory markers could also be used in the follow-up of pemphigus disease and monitoring its activity. Objectives: In this study, our objective was to investigate changes in the inflammatory markers neu- trophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), lymphocyte to monocyte ratio (LMR), C-reactive protein (CRP) erythrocyte sedimentation rate (ESR), which are inflammatory markers, before treatment and during follow-up, and the correlation of dis- ease severity with these markers in patients with pemphigus receiving intravenous immunoglobulin (IVIG) and/or systemic immunosuppressant agents. Methods: Seventy-six pemphigus patients (69 had pemphigus vulgaris, 5 had pemphigus foliaceus, 2 had paraneoplastic pemphigus) who received IVIG and/or systemic immunosuppressant agents such as corticosteroids and azathioprine and used these treatments for at least 6 months were included. Changes in NLR, PLR, LMR, MPV, CRP and sedimentation values were examined in patients who received systemic treatment for at least 6 months, before the start of treatment and 3 and 6 months after the start of treatment. Results: Significant changes in inflammatory markers and correlation values were found in all patients. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2025;15(1):4969 Introduction Pemphigus is a group of chronic autoimmune diseases char- acterized by bullae. The pemphigus group can be divided into four main subtypes: pemphigus vulgaris, pemphigus folia- ceous, paraneoplastic pemphigus and IgA pemphigus. Pem- phigus herpetiformis and drug-induced pemphigus are rarer forms that show some clinical, histological and immuno- pathological features that differ from the classical types [1,2]. The inflammatory response, also known as inflammation, is a process in which the immune system responds to tissue damage, infection, or other types of stress, and is a dynamic process involving a variety of different cell types, signaling pathways, and mediators. Its primary purpose is to remove any harmful stimuli, such as pathogens or damaged tissue and to promote healing and repair of the affected area [3]. In recent years, various inflammatory markers that can change in inflammatory states have been investigated. Neutrophils constitute 50%-70% of circulating leuko- cytes and are the most abundant innate immune cell type in circulation. Its amount can be measured with simple blood count examinations. During the inflammatory reac- tion, neutrophils are stimulated and activated by inflamma- tory cytokines to increase their phagocytic and bactericidal effects. They also play an important role in the resolution and healing of inflammation [4]. Since neutrophils have long been focused only on their lethal function by research- ers, their importance in diseases has not been adequately understood. Studies conducted in recent years shed light on the role of neutrophils in inflammatory diseases and malignancies. Statistically significant elevation of neutro- phils has been detected in patients with breast cancer and lung cancer [4-6]. Recently, it has been understood that platelets play an important role in immunological and in- flammatory processes [7-8]. Since platelets increase in number in systemic inflammation, their role has been inves- tigated in various malignancies and inflammatory diseases such as Crohn disease and vasculitis, and platelet elevation has been found to be associated with disease severity and poor prognosis [9-13]. Platelets have also been studied in various dermatological diseases. The condition shown to be most clearly related to its pathogenesis is atopic dermatitis [7]. Many studies have been conducted on inflammatory diseases and lymphocyte-related malignancies, which are important components of the immune system. It has been suggested that the number of lymphocytes in peripheral blood decreases with bexarotene treatment in mycosis fun- goides and may be a prognostic factor in the follow-up of mycosis fungoides [14]. The role of platelets in various inflammatory disorders is understood, and the activation and function of platelets can be seen with the mean platelet volume (MPV), one of the pa- rameters included in the whole blood analysis. Neutrophil- lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), C reactive protein (CRP) and erythrocyte sedimentation values (ESR), which can be measured by simple blood tests, increase in cases of systemic inflammation and can be easily detected. Their place in the diagnosis and prognosis of malignancies and inflammatory diseases has been investigated. These markers have been in- vestigated in response to psoriasis treatment and in correla- tion with disease severity, and significant results have been found. On the basis of these, we thought that inflammatory markers could also be used in the follow-up of pemphigus disease and monitoring its activity. Objectives In this study, our objective was to investigate the changes in the values of the inflammatory markers NLR, PLR, MPV, LMR, CRP and ESR values, which are inflammatory mark- ers, before treatment and during follow-up, and the correla- tion of disease severity with these markers in pemphigus patients who received IVIG and/or systemic immunosup- pressant agents such as corticosteroids, azathioprine and/or mycophenolate mofetil (Figure 1). Methods The approval for the study was received from Clinical Re- search Ethics Committee of Kahramanmaras Sutcu Imam University. (Date: 11.01.2022 Session: 2022/02 Decision no: 03). It was planned to compare the efficacy of these drugs with changes in inflammatory markers and Pemphigus Dis- ease Area Index (PDAI) in different groups. Additionally, Conclusions: We think that neutrophil, platelet, NLR and PLR values can be used to monitor the response to treatment in pemphigus, since they show a significant decrease with treatment and are significantly positively correlated with Pemphigus Disease Area Index, which indicates the severity of the disease. LMR values were indicators of a poor prognosis. We found that the duration of remission was longer in the group receiving IVIG. Although there was no difference between the treatments in terms of disease recovery, only IVIG prolonged the duration of remission. Original Article | Dermatol Pract Concept. 2025;15(1):4969 3 Figure 1. Flowchart of materials and methods. Abbreviations. CRP: C-reactive protein; LMR: lymphocyte-to-monocyte ratio; MPV: mean platelet volume; NLR: neutrophil-to-lymphocyte ratio; PDAI: pemphigus disease area index; PLR: platelet-to-lymphocyte ratio; PLT: platelet. the duration of patients staying in remission from the time they entered their first remission was recorded according to the remission criteria determined by the International Pemphigus Committee [15]. We diagnosed all of our pa- tients based on the results of the direct immunofluores- cence method applied by the pathology department on the biopsies we took from our patients, in addition to the clinical findings. We use the guideline by the European Dermatology Forum (EDF) in cooperation with the Euro- pean Academy of Dermatology and Venereology (EADV) for the management and treatment of pemphigus patients in our clinic [16]. The analyzes were evaluated in IBM BM SPSS (Statistical Package for Social Sciences; SPSS Inc.) Statistics 22, statis- tic software. In the study, descriptive data are shown with n and % values when using categorical data, while they are shown with mean ± standard deviation (Mean±SD) values when using continuous data. The suitability of continuous variables for normal distribution was evaluated with the Kolmogorov-Smirnov test. The Mann Whitney U test was applied to compare paired groups. Friedman analysis was applied to compare the measurement parameters over time. In the analyses the level of statistical significance was ac- cepted as P less than 0.05. 4 Original Article | Dermatol Pract Concept. 2025;15(1):4969 Table 1. Evaluation of parameters according to time. Beginning Mean±SD 3rd month Mean±SD 6th month Mean±SD P Neutrophil 6.81±3.08a 5.92±2.58a.b 5.84±2.66b 0.039 Lymphocyte 2.03±1.00a.b 2.22±1.01a 1.97±.89b 0.029 PLT 306.42±111.05a 296.79±108.11a.b 275.96±106.26b 0.049 MPV 9.71±1.65 9.90±1.21 10.06±1.49 0.204 CRP 11.78±23.91 9.14±14.51 6.02±4.72 0.083 NLR 4.51±4.53a 3.30±2.62b 3.54±2.31a.b 0.019 LMR 3.66±1.70 3.99±1.79 3.77±1.51 0.196 PLR 184.03±121.34a 161.94±103.86b 162.06±83.28a.b 0.014 PDAI 13.01±11.91a 7.74±8.33b 7.07±9.37b <0.001 Sedimantation 20.26±16.38 22.29±17.98 19.83±16.61 0.370 Friedman analysis was applied. a.b.c. The groups from which the statistical significance found in the analysis originates. Abbreviations. CRP: C-reactive protein; LMR: lymphocyte-to-monocyte ratio; MPV: mean platelet volume; NLR: neutrophil-to-lymphocyte ratio; PDAI: pemphi- gus disease area index; PLR: platelet-to-lymphocyte ratio; PLT: platelet; SD: standart deviation. Results Seventy-six patients with pemphigus with an average age of 49.59±16.03 (min=18-max=99) were included in the study. 34 (44.7%) of the patients are male and 42 (55.3%) are female. It was observed that 45 (59.2%) of the patients received intravenous immunoglobulin (IVIG), systemic steroid and azathioprine treatment, and 31 (40.8%) received azathio- prine and systemic steroid treatment without IVIG. In all pa- tients, the value of neutrophil count at 6 months was found to be significantly decreased (P = 0.039) compared to the baseline value. Additionally, neutrophil counts showed a sig- nificant positive correlation (baseline P = 0.037; 6th month P = 0.030) with simultaneously measured PDAI scores at the beginning of treatment and at 6 months of treatment. There was a significant decrease (P = 0.049) in platelet values at 6 months from baseline in all patients, but there was no sig- nificant correlation between platelet values and PDAI at any time. In all patients, both NLR and PLR values were found to decrease significantly in the third month of treatment (P = 0.019 for NLR; P = 0.014 for PLR) compared to the baseline value, and also showed a significant positive cor- relation with PDAI at 3 and 6 months. LMR values in all patients showed a negative and significant correlation with PDAI scores at 3 months and 6 months (3 months r = -0.318 P = 0.005; 6 months r = -0.353 P = 0.002). MPV and CRP values in all patients showed a significant positive correlation with PDAI (P = 0.027; P = 0.005, respectively). There was no significant change in sedimentation at any time of treatment and no correlation with PDAI was found. The change in PDAI did not differ significantly in the group of patients who received IVIG compared to the group of patients who did not receive IVIG. Furthermore, when the 6-month change in inflammatory markers was examined in the treatment groups, no significant differences were found between the two groups in the change of any parameter other than LMR (P > 0.05). LMR change was found to be significantly higher in the group that received IVIG than in the group that did not. While the mean 6-month LMR change in the IVIG group was 0.54 in the positive direction, the mean LMR change in the group that did not receive IVIG was 0.51 in the nega- tive direction, and these findings were statistically significant (P = 0.002). Taking into account the duration of the first remission after treatment, the duration of the first remission in the group receiving IVIG was found to be significantly higher in the IVIG group (30.95±20.17 months) than in the group that did not receive IVIG (11.87±10.53 months) (P < 0.001). LMR values measured at all times in IVIG pa- tients were found to be significantly positively correlated with the duration of the first remission of the disease (baseline P = 0.007; 3rd month p=0.005; 6th month pP 0.02). A significant decrease in neutrophil (p=0.039) and PLT (p=0.049) values was observed between the baseline and the 6th month. In all patients, there was a significant decrease in the lymphocyte values in the sixth month compared to the values of the third month (P = 0.029). There was a significant decrease in NLR (P = 0.019) and PLR (P = 0.014) in all pa- tients at the third month. There was a significant decrease in the PDAI value between all times (Table 1). When the initial parameters were examined, a signifi- cant positive correlation was observed between PDAI and neutrophils. When the 3rd month parameters are examined, there is a positive relationship between 3rd month PDAI and NLR and PLR; a significant negative correlation was observed between PDAI and lymphocyte and LMR. When Original Article | Dermatol Pract Concept. 2025;15(1):4969 5 the parameters of the 6th month were examined, there was a positive correlation between the PDAI of the 6th month and neutrophils, MPV, CRP, NLR and PLR; A significant nega- tive correlation was observed between PDAI and lympho- cytes and LMR (Table 2). The mean follow-up period of the patients was found to be 57 months (min = 18, max 123). The duration of remission in the IVIG-treated group was significantly longer than the duration of the group not receiving IVIG (P < 0.001). The change in LMR in the group that received IVIG was significantly higher than the change in the group that did not receive IVIG (P = 0.002). There was no sig- nificant difference between those who received IVIG and those who did not (P > 0.05) in terms of changes in other parameters (Table 3). A significant positive correlation was observed between the duration of remission and the LMR value at baseline. 3rd and 6th months in patients receiving IVIG (Table 4). Table 2. Correlation of PDAI values with other parameters over time. PDAI at the beginning PDAI at 3 months PDAI at 6 months r P r P r P Neutrophil .237 .039 .142 .222 .249 .030 Lymphocyte -.110 .346 -.238 .039 -.226 .049 Monocyte -.016 .891 .023 .841 .152 .189 PLT -.026 .822 .072 .538 -.004 .975 MPV .002 .989 .148 .203 .254 .027 CRP -.082 .482 .195 .091 .322 .005 Sedimantation .001 .990 .109 .350 .089 .445 NLR .213 .065 .282 .014 .386 .001 LMR -.064 .582 -.318 .005 -.353 .002 PLR .073 .531 .240 .037 .236 .041 Abbreviations. CRP: C-reactive protein; LMR: lymphocyte-to-monocyte ratio; MPV: mean platelet volume; NLR: neutrophil-to-lymphocyte ratio; PDAI: pemphigus disease area index; PLR: platelet-to-lymphocyte ratio; PLT: platelet. Table 3. Comparison of changes in parameters according to treatment status. Receiving IVIG Not receiving IVIG PMean±SD Mean±SD Duration of remission 30.95±20.17 11.87±10.53 <0.001 Change of MPV value .50±1.97 .15±1.30 0.330 Change of CRP value 5.02±18.59 6.84±28.61 0.232 Change of sedimantation -.60±16.69 1.94±19.32 0.582 Change of NLR 1.50±5.55 .22±3.74 0.234 Change of LMR .54±1.38 -.51±1.49 0.002 Change of PLR 31.76±109.30 7.75±102.87 0.456 Change of PDAI 6.62±7.13 4.97±6.03 0.186 *Mann Whitney U analysis was applied. Abbreviations. CRP: C-reactive protein; IVIG: Intravenous immunoglobulin; LMR: lympho- cyte-to-monocyte ratio; MPV: mean platelet volume; NLR: neutrophil-to-lymphocyte ratio; PDAI: pemphigus disease area index; PLR: platelet-to-lymphocyte ratio; PLT: platelet; SD: standart deviation. Table 4. Correlation of the duration of remission and the LMR value in patients receiving IVIG. Duration of remission r P LMR at the beginning 0.398 0.007 LMR at 3 months 0.414 0.005 LMR at 6 months 0.350 0.020 Change of LMR -0.077 0.617 Abbreviations. LMR: lymphocyte-to-monocyte ratio Conclusions Currently, there is no biomarker that shows the efficacy of pemphigus treatment and the duration of disease remission. We think that neutrophil, platelet, NLR and PLR values can be used to monitor the response to treatment in pemphigus, 6 Original Article | Dermatol Pract Concept. 2025;15(1):4969 think that the number of lymphocytes measured in periph- eral blood can be used in pemphigus diseases after the be- ginning of treatment, both in estimating the severity of the disease and in the follow-up of the treatment. NLR levels, obtained by dividing the number of neutro- phils measured in peripheral blood by the number of lympho- cytes, have been investigated for use in the follow-up of many different diseases such as malignant, inflammatory and psychi- atric diseases [22-28]. NLR was also investigated in dermato- logical diseases such as bullous pemphigoid [29], psoriasis [30] and lichen planus, and significantly higher values were found in the patient group compared to healthy controls [31]. In the study by Ucmak et al, it was determined that the value of NLR was higher in patients with PV than in healthy controls, but was not correlated with the severity of the disease [32]. In the study by Lyakhovitsky et al, a significant positive cor- relation was observed between disease activity and the value of NLR in pemphigus. NLR was found to be high at diagno- sis, showed a significant decrease in remission, and increased again in relapse [33]. In our study, consistent with the study by Lyakhovitsky et al, it was found that the NLR value showed a significant difference (P = 0.019) and decreased significantly in the third month of treatment compared to the beginning of treatment, and there was also a significant positive correlation with PDAI, which indicates disease activity, at 3 and 6 months (3 months P = 0.014; 6th month P = 0.001). These findings demonstrate the potential utility of NLR to monitor treatment response early and predict disease severity at follow-up. PLR, obtained by dividing the number of platelets mea- sured in peripheral blood by the number of lymphocytes, is a marker that reveals changes in platelet and lymphocyte numbers due to acute inflammatory and prothrombotic con- ditions [34]. In the study by Hayta et al, the PLR value was found in pemphigus patients to be higher than in healthy controls, but no relationship was found between the PLR value and the course of the disease [35]. On the contrary, in the study conducted by Lyakhovitsky et al, it was revealed that there was a significant decrease in PLR in remission compared to baseline [33]. In our study, a significant de- crease in PLR values was observed in the third month, con- sistent with the study by Lyakhovitsky et al Additionally, a significant positive correlation was detected between the PDAI score and the PLR value at 3 and 6 months. In these respects, it can be said that PLR and NLR show similar fea- tures in our study, consistent with the study by Lyakhovitsky et al. Therefore, both the PLR and NLR values may play a role in monitoring the response to treatment in pemphigus disease in the early stages and predicting the severity of the disease during follow-up. LMR is a marker obtained by dividing the number of lymphocytes in peripheral blood by the number of mono- cytes. Low LMR values have been thought to be an indicator since they show a significant decrease with treatment and are significantly positively correlated with PDAI, which indi- cates the severity of the disease. LMR values were indicators of a poor prognosis. We found that the duration of remission was longer in the group receiving IVIG, and although there was no difference between the treatments in terms of disease recovery, it should be noted that IVIG treatment prolonged the duration of remission. Neutrophils have also been studied in dermatological diseases. Park et al reported that neutrophil counts were positively correlated with disease severity in bullous pem- phigoid patients [17]. Ameglio et al reported that there was a significant correlation between antibody titers and the number of lesions in patients with PV and the number of neutrophils in peripheral blood [18]. In our study, similar to the studies above, neutrophil count and disease severity were positively correlated, and although all patients received systemic steroid treatment, which is known to increase the number of neutrophils, there was a significant decrease in the number of neutrophils in the sixth month. We thought that the change in neutrophil values in PV patients could be used in disease treatment and follow-up. There are no studies in the literature on the role of plate- let counts in pemphigus disease. From this perspective, our work has gained importance. In our study, platelet counts decreased significantly at 6 months compared to baseline. However, it did not correlate significantly with PDAI at any time point. Consequently, we think platelet count may be a parameter that can be measured at the beginning and sixth month of treatment to evaluate the response to treatment in pemphigus, but more studies are needed to investigate the role of platelets in the follow-up of the severity and treat- ment of pemphigus disease. The role of lymphocytes in pemphigus has been inves- tigated in various studies. When lesional biopsies in pem- phigus were examined, a large number of lymphocytes were detected in the infiltrates of the lesions, and it was suggested that they played an important role in the pathogenesis of pemphigus [19]. El-Naby et al found that the number of T lymphocytes in the lesional infiltrate was correlated with the severity of the disease in 40 PV patients [20]. In a study conducted by Kowalska-Kępczyńska et al, it was determined that the lymphocyte count of 32 patients with pemphigus was correlated with the PDAI score [21]. However, no stud- ies were found in the literature on the use of the absolute lymphocyte value in peripheral blood, which we evaluated in our study, in pemphigus disease. In our study, the absolute lymphocyte value measured in peripheral blood decreased in the sixth month. Furthermore, a significant negative cor- relation was found between the absolute lymphocyte value measured in peripheral blood at 3 and 6 months and the PDAI values measured at the same time. In this regard, we Original Article | Dermatol Pract Concept. 2025;15(1):4969 7 of a poor prognosis in several types of tumor [36-38]. In the study by Sirin et al with patients with psoriasis vulgaris, it was found that LMR levels did not differ significantly be- tween healthy controls and the group of patients, but LMR was negatively correlated with the psoriasis area severity index (PASI), which expresses the severity of the disease in psoriasis [39]. In the literature, no study investigating the re- lationship between pemphigus disease and LMR was found. In our study, LMR values showed a significant negative cor- relation with PDAI scores at 3 and 6 months. In this case, it can be thought that LMR values may be an indicator of a poor prognosis for the disease. Again, we think that LMR values can be used to predict the severity of the disease in the third and sixth months of treatment in Pemphigus. Another issue that draws attention in our study is a significant differ- ence in LMR was observed between the treatment groups. The LMR change in the group receiving IVIG was signifi- cantly higher than the LMR change in the group not receiv- ing IVIG. To investigate whether the significant difference in LMR change in those receiving IVIG compared to those not receiving IVIG was related to the difference in the dura- tion of remission between treatment groups, the duration of remission in the group receiving IVIG was found to be sig- nificantly higher than the duration in the group not receiv- ing IVIG. In patients receiving IVIG, a significant positive correlation was observed between the duration of remission and the LMR values measured at baseline, 3 months and 6 months. We propose that LMR levels can be used to predict the length of time the disease remains in remission. In our study, no significant differences were found in changes in inflammatory markers and disease severity in the group receiving IVIG, except for the LMR value. In our study, the mean follow-up period of the patients was deter- mined to be 57 months (min = 18, max 123). According to the consensus determined by the International Pemphigus Committee, the criteria for complete remission under mini- mal treatment or without treatment were taken into account, and when the duration of the first remission after treatment was considered, the duration of remission in the group re- ceiving IVIG was found to be significantly longer. In the study by Svecova et al, 10 PV patients receiving IVIG were followed for 12 months, and long remission periods were observed and a significant decrease in PDAI was observed [40]. More studies are needed to investigate the duration of remission of treatments in pemphigus. Pemphigus is a serious disease that can lead to mortal- ity. A treatment modality that provides complete remission is not yet available. The existence of markers that can be used in daily practice, which can evaluate the effectiveness of existing treatments and provide guidance for remission peri- ods, will facilitate the follow-up and treatment of the disease for the physician. References 1. Schmidt E, Kasperkiewicz M, Joly P. Pemphigus. Lancet. 2019;394(10201):882-894. DOI: 10.1016/S0140-6736(19) 31778-7. PMID: 31498102. 2. Porro AM, Caetano Lde V, Maehara Lde S, Enokihara MM. Non-classical forms of pemphigus: pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pem- phigus.  An Bras Dermatol.  2014;89(1):96-106. DOI: 10.1590 /abd1806-4841.20142459 PMID:24626654  3. Chen L, Deng H, Cui H, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018;9(6): 7204-18. DOI: 10.18632/oncotarget.23208 PMID:29467962  4. Bartneck M, Wang J. Therapeutic Targeting of Neutrophil Granulo- cytes in Inflammatory Liver Disease. Front Immunol. 2019;10:2257. DOI:10.3389/fimmu.2019.02257 PMID:31616430  5. Yoon CI, Park S, Cha YJ, et al. Associations between absolute neutrophil count and lymphocyte-predominant breast cancer. Breast. 2020;50:141-8. DOI: 10.1016/j.breast.2019.09.013 PMID: 31607527  6. Zhu X, Chen Y, Cui Y. Absolute Neutrophil Count and Mean Platelet Volume in the Blood as Biomarkers to Detect Lung Cancer. Dis Markers. 2020;2020:1371964. DOI: 10.1155/2020/ 1371964 PMID:32377267 7. Katoh N. Platelets as versatile regulators of cutaneous inflammation. J Dermatol Sci. 2009;53(2):89-95. DOI: 10.1016 /j.jdermsci.2008.08.019 PMID:18922681 8. Dan K, Gomi S, Inokuchi K, et al. Effects of interleukin-1 and tumor necrosis factor on megakaryocytopoiesis: mechanism of reactive thrombocytosis. Acta Haematol. 1995;93(2-4):67-72. DOI: 10.1159/000204114 PMID:7639054 9. Leblanc R, Peyruchaud O. Metastasis: new functional impli- cations of platelets and megakaryocytes.  Blood.  2016;128(1): 24-31. DOI: 10.1182/blood-2016-01-636399 PMID:27154188 10. Bednarz-Knoll N, Popęda M, Kryczka T, et al. Higher platelet counts correlate to tumour progression and can be induced by intratumoural stroma in non-metastatic breast carcinomas. Br J Cancer.  2022;126(3):464-71. DOI: 10.1038/s41416-021 -01647-9 PMID:34857895 11. Kim KH, Park TY, Lee JY, et al. Prognostic significance of ini- tial platelet counts and fibrinogen level in advanced non-small cell lung cancer.  J Korean Med Sci.  2014;29(4):507-11. DOI: 10.3346/jkms.2014.29.4.507 PMID:24753697 12. Shen H, Xu C, Chen C. [Platelet count predicts therapeutic re- sponse of infliximab for active Crohn’s disease].  Zhejiang Da Xue Xue Bao Yi Xue Ban. 2016;45(1):81-5. DOI: 10.3785/j.issn .1008-9292.2016.01.13  PMID:27045246 13. Willeke P, Kümpers P, Schlüter B, Limani A, Becker H, Schotte H. Platelet counts as a biomarker in ANCA-associated vasculi- tis. Scand J Rheumatol. 2015;44(4):302-8. DOI: 10.3109/03009 742.2015.1006247  PMID:25744854 14. Tamer F, Gulekon A. Novel Inflammatory Biomarkers in Patients with Mycosis Fungoides Treated with Bexarotene. J Coll Physi- cians Surg Pak. 2021;31(6):716-8. DOI: 10.29271/jcpsp.2021.0 6.716  PMID:34102787 15. Murrell DF, Dick S, Ahmed AR, et al. Consensus statement on defi- nitions of disease, end points, and therapeutic response for pem- phigus. J Am Acad Dermatol. 2008;58(6):1043-6. DOI: 10.1016 /j.jaad.2008.01.012 PMID:18339444 16. Hertl M, Jedlickova H, Karpati S, et al. Pemphigus. S2 Guide- line for diagnosis and treatment--guided by the European 8 Original Article | Dermatol Pract Concept. 2025;15(1):4969 Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV).  J Eur Acad Dermatol Venereol.  2015;29(3):405-14. DOI: 10.1111/ jdv.12772 PMID:25338479 17. Park SH, Lee SH, Kim JH, Kim SC. Circulating Eosinophil and Neutrophil Counts Correlate with Disease Severity in Bullous Pemphigoid.  Ann Dermatol.  2018;30(5):544-9. DOI: 10.5021 /ad.2018.30.5.544 PMID:33911476 18. Ameglio F, D’Auria L, Cordiali-Fei P, et al. Anti-intercellular sub- stance antibody log titres are correlated with serum concentrations of interleukin-6, interleukin-15 and tumor necrosis factor-alpha in patients with Pemphigus vulgaris relationships with periph- eral blood neutrophil counts, disease severity and duration and patients’ age. J Biol Regul Homeost Agents. 1999;13(4): 220-4. PMID:10703946 19. Yuan H, Zhou S, Liu Z, et al. Pivotal Role of Lesional and Perile- sional T/B Lymphocytes in Pemphigus Pathogenesis. J Invest Der- matol. 2017;137(11):2362-70. DOI: 10.1016/j.jid.2017.05.032 PMID:28647348 20. El-Naby SM, Amin MM, Ali MA, Gaballah MA. Evaluation of the relation between T-Lymphocytes (CD4 + ve and CD8 + ve) and pemphigus vulgaris pathogenesis and severity. Indian J Der- matopathol Diagn Dermatol 2019;6:30-5 DOI: 10.4103/ijdpdd. ijdpdd_70_18 21. Kowalska-Kępczyńska A, Mleczko M, Domerecka W, Krasowska D, Donica H. Assessment of Immune Cell Activation in Pem- phigus. Cells. 2022;11(12):1912. DOI: 10.3390/cells11121912 PMID:35741041 22. Yang Z, Zhang Z, Lin F, et al. Comparisons of neutrophil-, monocyte-, eosinophil-, and basophil- lymphocyte ratios among various systemic autoimmune rheumatic diseases. APMIS. 2017; 125(10):863-71. DOI: 10.1111/apm.12722 PMID:28766758 23. Al-Osami MH, Awadh NI, Khalid KB, Awadh AI. Neutrophil/ lymphocyte and platelet/lymphocyte ratios as potential mark- ers of disease activity in patients with Ankylosing spondylitis: a case-control study. Adv Rheumatol. 2020;60(1):13. DOI: 10.1186/s42358-020-0113-5 PMID:32000859 24. Mercan R, Bitik B, Tufan A, et al. The Association Between Neutrophil/Lymphocyte Ratio and Disease Activity in Rheu- matoid Arthritis and Ankylosing Spondylitis. J Clin Lab Anal. 2016;30(5):597-601. DOI: 10.1002/jcla.21908 PMID:26666737 25. Langley BO, Guedry SE, Goldenberg JZ, Hanes DA, Beards- ley JA, Ryan JJ. Inflammatory Bowel Disease and Neutrophil- Lymphocyte Ratio: A Systematic Scoping Review. J Clin Med. 2021;10(18):4219. DOI: 10.3390/jcm10184219 PMID:34575330 26. Najjar M, Agrawal S, Emond JC, Halazun KJ. Pretreatment neutrophil-lymphocyte ratio: useful prognostic biomarker in he- patocellular carcinoma. J Hepatocell Carcinoma. 2018;5:17-28. DOI: 10.2147/JHC.S86792 PMID:29404284 27. Tang H, Lu W, Li B, Li C, Xu Y, Dong J. Prognostic significance of neutrophil-to-lymphocyte ratio in biliary tract cancers: a system- atic review and meta-analysis. Oncotarget. 2017;8(22):36857-68. 28. Marazziti D, Torrigiani S, Carbone MG, et al. Neutrophil/ Lymphocyte, Platelet/Lymphocyte, and Monocyte/Lymphocyte Ratios in Mood Disorders. Curr Med Chem. 2022;29(36):5758-81. DOI: 10.2174/0929867328666210922160116 PMID:34551689 29. Şereflican B, Parlak AH. Clinical, Demographical Features, Accompanying Diseases and Neutrophil to Lymphocyte Ratio- Platelet to Lymphocyte Ratio in Patients with Bullous Pemphi- goid in Bolu. Cumhur Med J. 2019; 41(1):88-93. https://doi. org/10.7197/223.vi.475189 30. Wang WM, Jin HZ. Role of Neutrophils in Psoriasis. J Immu- nol Res. 2020;2020:3709749. DOI: 10.1155/2020/3709749 PMID:32587871 31. Ataş H, Cemil BÇ, Kurmuş GI, Gönül M. Assessment of systemic inflammation with neutrophil-lymphocyte ratio in lichen planus. Postepy Dermatol Alergol. 2016;33(3):188-92. DOI: 10.5114/ pdia.2016.56930 PMID:27512353 32. UÇMAK D, AKKURT M, UÇAK H, ARICA M Nötrofil/ lenfosit Oranının Pemfigus Vulgaris ile İlişkisi. KONURALP TIP DERGİSİ. 2015;7(2):88-92. 33. Lyakhovitsky A, Dascalu J, Drousiotis T, Barzilai A, Baum S. Hematological Inflammatory Markers in Patients with Pemphi- gus Vulgaris. Dermatology. 2021;237(6):912-20. DOI: 10.1159 /000512916 PMID:33472194 34. Gasparyan AY, Ayvazyan L, Mukanova U, Yessirkepov M, Kitas GD. The Platelet-to-Lymphocyte Ratio as an Inflamma- tory Marker in Rheumatic Diseases. Ann Lab Med. 2019;39(4): 345-57. DOI: 10.3343/alm.2019.39.4.345 PMID:30809980 35. Hayta S, Güner R, Akyol M. Blood mean platelet volume may be predictive for disease course in the cases with pemphigus vul- garis. Biomed Res (Aligarh). 2017;9(28):4223–7.36) 36. Rajwa P, Życzkowski M, Paradysz A, Bujak K, Bryniarski P. Eval- uation of the prognostic value of LMR, PLR, NLR, and dNLR in urothelial bladder cancer patients treated with radical cystec- tomy. Eur Rev Med Pharmacol Sci. 2018;22(10):3027-37. DOI: 10.26355/eurrev_201805_15060 PMID:29863247 37. Ma Y, Zhang J, Chen X. Lymphocyte-to-Monocyte Ratio is Asso- ciated with the Poor Prognosis of Breast Cancer Patients Receiv- ing Neoadjuvant Chemotherapy. Cancer Manag Res. 2021;13: 1571-80. DOI: 10.2147/CMAR.S292048 PMID:33623436 38. Liu X, Li M, Zhao F, et al. The lymphocyte-monocyte ratio predicts tumor response and survival in patients with locally advanced esophageal cancer who received definitive chemora- diotherapy. Onco Targets Ther. 2017;10:871-7. DOI: 10.2147 /OTT.S124915 PMID:28243122 39. Sirin MC, Korkmaz S, Erturan I, et al. Evaluation of monocyte to HDL cholesterol ratio and other inflammatory markers in patients with psoriasis. An Bras Dermatol. 2020;95(5):575-82. DOI: 10.1016/j.abd.2020.02.008 PMID:32711928 40. Svecova D. IVIG therapy in pemphigus vulgaris has corticosteroid-sparing and immunomodulatory effects. Australas J Dermatol. 2016;57(2):141-4. DOI:10.1111/ajd.12422 PMID: 26581165