Sex-related Variations in Comorbidities in Lichen Sclerosus: A Systematic Review and Meta-Analysis
DOI:
https://doi.org/10.2340/actadv.v104.39982Keywords:
comorbidities, lichen, sclerosus, sex, systematic review, meta-analysisAbstract
The comorbidities of lichen sclerosus (LS) are presumed but have not been analysed in detail. The purpose of this review was to identify evidence-based associated diseases in patients with LS and explore the potential need for sex-dependent screening protocols. A comprehensive search of the MEDLINE, Embase, and PsycINFO databases from inception to 29 February 2024 was conducted using the key search terms LS and all its synonyms. Pooled odds ratios and 95% confidence intervals of comorbidities were generated using the DerSimonian and Laird random-effects model. A total of 21 case-control studies met the inclusion criteria. Of the 75 comorbidities analysed, only 16 (21.3%) were studied in both sexes, revealing no contrasting associations based on sex. Both female and male LS patients showed significantly increased odds of common dermatological conditions (i.e., lichen planus, vitiligo, alopecia areata, atopic dermatitis, and psoriasis), various cardiovascular risk factors (i.e., essential hypertension, obesity, dyslipidaemia, diabetes mellitus, and diabetes mellitus type 2), genital warts, and hypothyroidism compared with controls. Overall, the scarcity of data currently does not support the implementation of sex-dependent screening strategies. The findings do, however, present significant associations with a range of potentially serious comorbidities, which warrants further elucidation and clinical vigilance.
Downloads
References
Kirtschig G, Kinberger M, Kreuter A, Simpson R, Günthert A, van Hees C, et al. EuroGuiDerm guideline on lichen sclerosus [Internet]. 2023 [cited 2024 May 19]. Available from: https://www.guidelines.edf.one//uploads/attachments/clmub3q4l0an5uhjrluc4r0yq-lichen-sclerosus-gl.pdf.
Harrington CI, Dunsmore IR. An investigation into the incidence of auto-immune disorders in patients with lichen sclerosus and atrophicus. Br J Dermatol 1981; 104: 563-566.
https://doi.org/10.1111/j.1365-2133.1981.tb08172.x DOI: https://doi.org/10.1111/j.1365-2133.1981.tb08172.x
Sideri M, Parazzini F, Rognoni MT, La Vecchia C, Negri E, Garsia S, et al. Risk factors for vulvar lichen sclerosus. Am J Obstet Gynecol 1989; 161: 38-42.
https://doi.org/10.1016/0002-9378(89)90228-7 DOI: https://doi.org/10.1016/0002-9378(89)90228-7
Meeks J, Qi T, Cashy J, Yang X, Gonzalez C. 849 Role of testosterone in the pathogenesis and treatment of lichen sclerosus. J Urol 2010; 183: e331.
https://doi.org/10.1016/j.juro.2010.02.2351 DOI: https://doi.org/10.1016/j.juro.2010.02.2351
Bjekić M, Šipetić S, Marinković J. Risk factors for genital lichen sclerosus in men. Br J Dermatol 2011; 164: 325-329.
https://doi.org/10.1111/j.1365-2133.2010.10091.x DOI: https://doi.org/10.1111/j.1365-2133.2010.10091.x
Higgins CA, Cruickshank ME. A population-based case-control study of aetiological factors associated with vulval lichen sclerosus. J Obstet Gynaecol 2012; 32: 271-275.
https://doi.org/10.3109/01443615.2011.649320 DOI: https://doi.org/10.3109/01443615.2011.649320
Becker K, Meissner V, Farwick W, Bauer R, Gaiser MR. Lichen sclerosus and atopy in boys: coincidence or correlation? Br J Dermatol 2013; 168: 362-366.
https://doi.org/10.1111/j.1365-2133.2012.11201.x DOI: https://doi.org/10.1111/j.1365-2133.2012.11201.x
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.
https://doi.org/10.1007/s00345-013-1090-7 DOI: https://doi.org/10.1007/s00345-013-1090-7
Blaschko SD, Gaither TW, Alwaal A, Harris CR, McCulloch CE, McAninch JW, et al. Lichen sclerosus comorbidities and complications from a national sample of patients treated with urethroplasty. Urol Pract 2015; 2: 329-334.
https://doi.org/10.1016/j.urpr.2015.02.006 DOI: https://doi.org/10.1016/j.urpr.2015.02.006
Erickson BA, Elliott SP, Myers JB, Voelzke BB, Smith TG 3rd, McClung CD, et al. Understanding the Relationship between chronic systemic disease and lichen sclerosus urethral strictures. J Urol 2016; 195: 363-368.
https://doi.org/10.1016/j.juro.2015.08.096 DOI: https://doi.org/10.1016/j.juro.2015.08.096
Fuchs ME, Beecroft N, Dajusta DG, McLeod DJ. The association between BXO and obesity in boys undergoing circumcision. Glob Pediatr Health 2017; 4: 2333794X17742749.
https://doi.org/10.1177/2333794X17742749 DOI: https://doi.org/10.1177/2333794X17742749
Basile S, Pinelli S, Benedetti Panici P, Angioli R, Plotti F, Giannarelli D, et al. Association between Helicobacter pylori infection and vulvar lichen sclerosus: a clinical comparative study. Eur J Dermatol 2018; 28: 226-227.
https://doi.org/10.1684/ejd.2017.3207 DOI: https://doi.org/10.1684/ejd.2017.3207
Hu J, Hesson A, Haefner HK, Rominski S. The prevalence of self-reported medical comorbidities in patients with vulvar lichen sclerosus: a single-center retrospective study. Int J Gynaecol Obstet 2021; 153: 340-343.
https://doi.org/10.1002/ijgo.13480 DOI: https://doi.org/10.1002/ijgo.13480
Bieber AK, Steuer AB, Melnick LE, Wong PW, Pomeranz MK. Autoimmune and dermatologic conditions associated with lichen sclerosus. J Am Acad Dermatol 2021; 85: 228-229.
https://doi.org/10.1016/j.jaad.2020.08.011 DOI: https://doi.org/10.1016/j.jaad.2020.08.011
Hieta N, Rintala M, Söderlund JM, Samu K, Orte K, Hietanen S. Comorbidity of dermal and cardiovascular disorders with lichen sclerosus: a case-control study. Acta Derm Venereol 2021; 101: adv00594.
https://doi.org/10.2340/actadv.v101.433 DOI: https://doi.org/10.2340/actadv.v101.433
Nizinski K, Orszulak D, Janik M, Skowronek K, Stojko R, Drosdzol-Cop A. The analysis of coexistence of celiac disease and vulvar lichen sclerosus in girls. Ginekol Pol 2022; 93: 793-798.
https://doi.org/10.5603/GP.a2022.0102 DOI: https://doi.org/10.5603/GP.a2022.0102
Fan R, Leasure AC, Maisha FI, Little AJ, Cohen JM. Depression and anxiety in patients with lichen sclerosus. JAMA Dermatol 2022; 158: 953-954.
https://doi.org/10.1001/jamadermatol.2022.1964 DOI: https://doi.org/10.1001/jamadermatol.2022.1964
Fan R, Leasure AC, Maisha FI, Cohen JM, Little AJ. Thyroid disorders associated with lichen sclerosus: a case-control study in the All of Us Research Program. Br J Dermatol 2022; 187: 797-799.
https://doi.org/10.1111/bjd.21702 DOI: https://doi.org/10.1111/bjd.21702
Hieta NK, Haataja MAM, Tapana L. Comorbidities in male patients with lichen sclerosus: a case-control study. J Low Genit Tract Dis 2023; 27: 378-383.
https://doi.org/10.1097/LGT.0000000000000769 DOI: https://doi.org/10.1097/LGT.0000000000000769
El Khoury J, Andraos J, Kanbar A, Halabi R, Assaf S, Mina A, et al. A potential protective effect of alcohol consumption in male genital lichen sclerosus: a case-control study. Adv Urol 2023; 2023: 7208312.
https://doi.org/10.1155/2023/7208312 DOI: https://doi.org/10.1155/2023/7208312
Söderlund JM, Hieta NK, Kurki SH, Orte KJ, Polo-Kantola P, Hietanen SH, et al. Comorbidity of urogynecological and gastrointestinal disorders in female patients with lichen sclerosus. J Low Genit Tract Dis 2023; 27: 156-160.
https://doi.org/10.1097/LGT.0000000000000727 DOI: https://doi.org/10.1097/LGT.0000000000000727
Luu Y, Cheng AL, Reisz C. Elevated body mass index, statin use, and cholecystectomy are associated with vulvar lichen sclerosus: a retrospective, case-control study. J Am Acad Dermatol 2023; 88: 1376-1378.
https://doi.org/10.1016/j.jaad.2023.01.023 DOI: https://doi.org/10.1016/j.jaad.2023.01.023
Chan I. The role of extracellular matrix protein 1 in human skin. Clin Exp Dermatol 2004; 29: 52-56.
https://doi.org/10.1111/j.1365-2230.2004.01440.x DOI: https://doi.org/10.1111/j.1365-2230.2004.01440.x
Chan I, Oyama N, Neill SM, Wojnarowska F, Black MM, McGrath JA. Characterization of IgG autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Clin Exp Dermatol 2004; 29: 499-504.
https://doi.org/10.1111/j.1365-2230.2004.01573.x DOI: https://doi.org/10.1111/j.1365-2230.2004.01573.x
Sander CS, Ali I, Dean D, Thiele JJ, Wojnarowska F. Oxidative stress is implicated in the pathogenesis of lichen sclerosus. Br J Dermatol 2004; 151: 627-635.
https://doi.org/10.1111/j.1365-2133.2004.06142.x DOI: https://doi.org/10.1111/j.1365-2133.2004.06142.x
Gambichler T, Belz D, Terras S, Kreuter A. Humoral and cell-mediated autoimmunity in lichen sclerosus. Br J Dermatol 2013; 169: 183-184.
https://doi.org/10.1111/bjd.12220 DOI: https://doi.org/10.1111/bjd.12220
Wang L, Yi JL, Chen HY, Wang PL, Shen YL. Level of Foxp3, DNMTs, methylation of Foxp3 promoter region, and CD4 + CD25 + CD127low regulatory T cells in vulvar lichen sclerosus. Kaohsiung J Med Sci 2021; 37: 520-527.
https://doi.org/10.1002/kjm2.12356 DOI: https://doi.org/10.1002/kjm2.12356
Li YZ, Wu Y, Zhang QH, Wang Y, Zhen JH, Li SL. Hypoxia-ischaemia is involved in the pathogenesis of vulvar lichen sclerosus. Clin Exp Dermatol 2009; 34: e531-536.
https://doi.org/10.1111/j.1365-2230.2009.03571.x DOI: https://doi.org/10.1111/j.1365-2230.2009.03571.x
Saravanamuthu J, Reid WM, George DS, Crow JC, Rolfe KJ, MacLean AB, et al. The role of angiogenesis in vulvar cancer, vulvar intraepithelial neoplasia, and vulvar lichen sclerosus as determined by microvessel density analysis. Gynecol Oncol 2003; 89: 251-258.
https://doi.org/10.1016/S0090-8258(03)00055-6 DOI: https://doi.org/10.1016/S0090-8258(03)00055-6
Additional Files
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2024 Špela Šuler Baglama, Gregor B. E. Jemec, Jan Zmazek, Katarina Trčko
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All digitalized ActaDV contents is available freely online. The Society for Publication of Acta Dermato-Venereologica owns the copyright for all material published until volume 88 (2008) and as from volume 89 (2009) the journal has been published fully Open Access, meaning the authors retain copyright to their work.
Unless otherwise specified, all Open Access articles are published under CC-BY-NC licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.
