Increased Neutrophil-to-LymphocyteRatio as a Marker of Systemic Immunity in Lichen Sclerosus
Keywords:
NLR, neutrophil-to-lymphocyte ratio, lichen sclerosus, autoimmunity, chronic inflammatory skin diseasesAbstract
Introduction: Lichen sclerosus (LS) is a chronic inflammatory dermatosis traditionally considered a localized condition, yet associations with autoimmune comorbidities and circulating autoantibodies suggest possible systemic immune involvement. The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive biomarker of systemic inflammation and frailty, but its role in LS has not been investigated.
Aims: To evaluate NLR values in patients with LS and assess whether LS is associated with systemic inflammatory changes.
Methods: This single-center retrospective observational study analyzed anonymized laboratory data from patients diagnosed with LS at IDI-IRCCS (Rome, Italy) between January 2020 and January 2025. Full blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), age, and sex were collected. Patients were subdivided into three age groups (<65, 65–74, ≥75 years). Welch’s ANOVA and t-tests assessed group differences; chi-square tests examined NLR frailty-range distribution; Pearson correlations evaluated associations with CRP and ESR.
Results: A total of 631 samples were included. Mean NLR was 2.34 ±1.36, increasing significantly with age (P=0.02). Approximately one third of patients fell within frailty-associated NLR ranges. Among adults <65 years, mean NLR (2.17 ±1.00) was significantly higher than in two healthy control cohorts (1.85 ± 0.64 and 1.65 ± 1.96; both P<0.01). NLR correlated moderately with ESR (r=0.47) and modestly with CRP (r=0.36).
Conclusions: LS is associated with higher NLR values than those observed in healthy controls, indicating mild systemic inflammation. These findings support the concept that LS may not be exclusively localized but may involve broader immune dysregulation. NLR may help identify LS patients with potential systemic involvement, although prospective validation is required.
References
Jerkovic Gulin S, Liljeberg L, Seifert O. The Impact of Genital Lichen Sclerosus in Men and Women on Quality of Life: A Prospective Cohort Study. Int J Womens Dermatol 2024, 10, e131, DOI:10.1097/JW9.0000000000000131.
Kirtschig G, Becker K, Günthert A, et al. Evidence-Based (S3) Guideline on (Anogenital) Lichen Sclerosus. J Eur Acad Dermatol Venereol 2015, 29, e1-43, DOI:10.1111/jdv.13136.
Fistarol SK, Itin PH. Diagnosis and Treatment of Lichen Sclerosus: An Update. Am J Clin Dermatol 2013, 14, 27–47, DOI:10.1007/s40257-012-0006-4.
Kirtschig G. Lichen Sclerosus-Presentation, Diagnosis and Management. Dtsch Arztebl Int 2016, 113, 337–343, DOI:10.3238/arztebl.2016.0337.
Halonen P, Jakobsson M, Heikinheimo O, Gissler M, Pukkala E. Incidence of Lichen Sclerosus and Subsequent Causes of Death: A Nationwide Finnish Register Study. BJOG 2020, 127, 814–819, DOI:10.1111/1471-0528.16175.
Veerabagu SA, Li Y, Grinsfelder M, Little AJ, Srivastava D, Wehner MR. Lichen Sclerosus Prevalence and Squamous Cell Carcinoma Development in Female Medicare Beneficiaries. JAMA Dermatol 2025, 161, 978–980, DOI:10.1001/jamadermatol.2025.2257.
Paganelli A, Fabbri PV, Ghidini F, Bigi L, Lasagni C, Ceccarelli PL. Treatment and Follow-up of Genital Lichen Sclerosus in Male Children: Multidisciplinary Management at a Tertiary Care Center. Dermatol Reports 2023, DOI:10.4081/dr.2023.9774.
Gambichler T, Belz D, Terras S, Kreuter A. Humoral and Cell-Mediated Autoimmunity in Lichen Sclerosus. Br J Dermatol 2013, 169, 183–184, DOI:10.1111/bjd.12220.
Paganelli A, Didona D, Scala E. Cytokine Networks in Lichen Sclerosus: A Roadmap for Diagnosis and Treatment? Int J Mol Sci 2025, 26, 4315, DOI:10.3390/ijms26094315.
Corazza M, Schettini N, Zedde P, Borghi A. Vulvar Lichen Sclerosus from Pathophysiology to Therapeutic Approaches: Evidence and Prospects. Biomedicines 2021, 9, 950, DOI:10.3390/biomedicines9080950.
Paganelli A, Contu L, Ficarelli E, Garbarino F, Motolese A. Management of Lichen Sclerosus and Related Comorbidities at a Tertiary Referral Center: Beyond Topical Steroids. Dermatol Pract Concept 2024, 14, e2024262, DOI:10.5826/dpc.1404a262.
De Luca DA, Papara C, Vorobyev A, et al. Lichen Sclerosus: The 2023 Update. Front Med (Lausanne) 2023, 10, 1106318, DOI:10.3389/fmed.2023.1106318.
Farrell AM, Dean D, Millard PR, Charnock FM, Wojnarowska F. Cytokine Alterations in Lichen Sclerosus: An Immunohistochemical Study. Br J Dermatol 2006, 155, 931–940, DOI:10.1111/j.1365-2133.2006.07414.x.
Tchórzewski H, Rotsztejn H, Banasik M, Lewkowicz P, Głowacka E. The Involvement of Immunoregulatory T Cells in the Pathogenesis of Lichen Sclerosus. Med Sci Monit 2005, 11, CR39-43.
Peterson DM, Damsky WE, Vesely MD. Treatment of Lichen Sclerosus and Hypertrophic Scars with Dupilumab. JAAD Case Rep 2022, 23, 76–78, DOI:10.1016/j.jdcr.2022.03.002.
Moreau JM, Velegraki M, Bolyard C, Rosenblum MD, Li Z. Transforming Growth Factor-Β1 in Regulatory T Cell Biology. Sci Immunol 2022, 7, eabi4613, DOI:10.1126/sciimmunol.abi4613.
Iyer SS, Cheng G. Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease. Crit Rev Immunol 2012, 32, 23–63, DOI:10.1615/critrevimmunol.v32.i1.30.
Terlou A, Santegoets LAM, van der Meijden, et al. An Autoimmune Phenotype in Vulvar Lichen Sclerosus and Lichen Planus: A Th1 Response and High Levels of microRNA-155. J Invest Dermatol 2012, 132, 658–666, DOI:10.1038/jid.2011.369.
Soltanzadeh-Yamchi M, Shahbazi M, Aslani S, Mohammadnia-Afrouzi M. MicroRNA Signature of Regulatory T Cells in Health and Autoimmunity. Biomed Pharmacother 2018, 100, 316–323, DOI:10.1016/j.biopha.2018.02.030.
Divekar AA, Dubey S, Gangalum PR, Singh RR. Dicer Insufficiency and microRNA-155 Overexpression in Lupus Regulatory T Cells: An Apparent Paradox in the Setting of an Inflammatory Milieu. J Immunol 2011, 186, 924–930, DOI:10.4049/jimmunol.1002218.
Stahl HF, Fauti T, Ullrich N, et al. miR-155 Inhibition Sensitizes CD4+ Th Cells for TREG Mediated Suppression. PLoS One 2009, 4, e7158, DOI:10.1371/journal.pone.0007158.
Oyama N, Chan I, Neill SM, et al. Autoantibodies to Extracellular Matrix Protein 1 in Lichen Sclerosus. Lancet 2003, 362, 118–123, DOI:10.1016/S0140-6736(03)13863-9.
Edmonds EVJ, Oyama N, Chan I, Francis N, McGrath JA, Bunker CB. Extracellular Matrix Protein 1 Autoantibodies in Male Genital Lichen Sclerosus: Correspondence. British Journal of Dermatology 2011, 165, 218–219, DOI:10.1111/j.1365-2133.2011.10326.x.
Forget P, Khalifa C, Defour JP, Latinne D, Van Pel MC, De Kock M. What Is the Normal Value of the Neutrophil-to-Lymphocyte Ratio? BMC Res Notes 2017, 10, 12, DOI:10.1186/s13104-016-2335-5.
Accardi G, Calabrò A, Caldarella R, et al. Immune-Inflammatory Response in Lifespan—What Role Does It Play in Extreme Longevity? A Sicilian Semi- and Supercentenarians Study. Biology 2024, 13, 1010, DOI:10.3390/biology13121010.
Pellegrino R, Paganelli R, Di Iorio A, et al. Temporal Trends, Sex Differences, and Age-Related Disease Influence in Neutrophil, Lymphocyte Count and Neutrophil to Lymphocyte-Ratio: Results from InCHIANTI Follow-up Study. Immun Ageing 2023, 20, 46, DOI:10.1186/s12979-023-00370-8.
Pellegrino R, Paganelli R, Di Iorio A, et al. Lack of Immune Resilience Negatively Affects Physical Resilience: Results From the InCHIANTI Follow-Up Study. J Gerontol A Biol Sci Med Sci 2024, 79, glae076, DOI:10.1093/gerona/glae076.
Solak B, Dikicier BS, Cosansu NC, Erdem T. Neutrophil to Lymphocyte Ratio in Patients with Vitiligo. Postepy Dermatol Alergol 2017, 34, 468–470, DOI:10.5114/ada.2017.71114.
Chen X, Yang X, Zhang M, Zhao Y, Guo S. Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios as Systemic Inflammatory Biomarkers for Atopic Dermatitis in US Adults: A Cross-Sectional NHANES Study Revealing Subgroup Heterogeneity. Front Immunol 2025, 16, 1585451, DOI:10.3389/fimmu.2025.1585451.
Oyama N, Chan I, Neill et al. Autoantibodies to Extracellular Matrix Protein 1 in Lichen Sclerosus. Lancet 2003, 362, 118–123, DOI:10.1016/S0140-6736(03)13863-9.
Goolamali SK, Barnes EW, Irvine WJ, Shuster S. Organ-Specific Antibodies in Patients with Lichen Sclerosus. Br Med J 1974, 4, 78–79, DOI:10.1136/bmj.4.5936.78.
Howard A, Dean D, Cooper S, Kirtshig G, Wojnarowska F. Circulating Basement Membrane Zone Antibodies Are Found in Lichen Sclerosus of the Vulva. Australas J Dermatol 2004, 45, 12–15, DOI:10.1111/j.1440-0960.2004.00026.x.
Paganelli R, Di Iorio A. The Neutrophil-to-Lymphocyte Ratio in Aging and Immunosenescence. Explor Immunol 2025, 5, 1003200, DOI:10.37349/ei.2025.1003200.
Pellegrino R, Paganelli R, Di Iorio A, et al. Neutrophil, Lymphocyte Count, and Neutrophil to Lymphocyte Ratio Predict Multimorbidity and Mortality-Results from the Baltimore Longitudinal Study on Aging Follow-up Study. Geroscience 2024, 46, 3047–3059, DOI:10.1007/s11357-023-01034-7.
Tap L, Corsonello A, Di Rosa M, et al. Inflammaging and Blood Pressure Profiles in Late Life: The Screening for CKD among Older People across Europe (SCOPE) Study. J Clin Med 2022, 11, 7311, DOI:10.3390/jcm11247311.
Ye JH, Zhang Y, Naidoo K, Ye S. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Psoriasis: A Systematic Review and Meta-Analysis. Arch Dermatol Res 2024, 316, 85, DOI:10.1007/s00403-024-02823-6.
Ma L, Zeng A, Chen B, Chen Y, Zhou R. Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Patients with Systemic Lupus Erythematosus and Their Correlation with Activity: A Meta-Analysis. Int Immunopharmacol 2019, 76, 105949, DOI:10.1016/j.intimp.2019.105949.
Hofer MD, Meeks JJ, Mehdiratta N, Granieri MA, Cashy J, Gonzalez CM. Lichen Sclerosus in Men Is Associated with Elevated Body Mass Index, Diabetes Mellitus, Coronary Artery Disease and Smoking. World J Urol 2014, 32, 105–108, DOI:10.1007/s00345-013-1090-7.
Zheng Z, Liu J, He T, Liu C. The Predictive Value of NLR, SII, and Complement 3 in Treatment Response for Systemic Lupus Erythematosus with Immune Thrombocytopenia. Front Immunol 2025, 16, 1606510, DOI:10.3389/fimmu.2025.1606510.
Ali NT, Ali GS, Mohsen Ali H. NLR Outperforms PLR in SLE Diagnosis and Prognosis: An AI-Enhanced Meta-Analysis of 12 850 Patients with Ethnicity-Specific Cut-Offs. Lupus Sci Med 2025, 12, e001696, DOI:10.1136/lupus-2025-001696.
Yoon D, Yun C, Beerman I, Beydoun MA, Launer LJ, Song M. Elevated Neutrophil-to-Lymphocyte Ratio and the Incidence of Autoimmune Diseases: Evidence from a Large Prospective Cohort Study. Sci Rep 2026, 16, 667, DOI:10.1038/s41598-025-21188-y.
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