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Background:
Systematic Review

The Association between Cardiovascular Risk Factors and Lichen Sclerosus: A Systematic Review and Meta-Analysis

by
Suvijak Untaaveesup
1,
Piyawat Kantagowit
2,
Nattawut Leelakanok
3,
Petcharpa Chansate
4,
Wongsathorn Eiumtrakul
5,
Walaiorn Pratchyapruit
6 and
Chutintorn Sriphrapradang
5,*
1
Phaholpolpayuhasena Hospital, Kanchanaburi 71000, Thailand
2
Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
3
Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand
4
Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand
5
Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
6
Institute of Dermatology, Ministry of Public Health, Bangkok 10400, Thailand
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2024, 13(16), 4668; https://doi.org/10.3390/jcm13164668
Submission received: 3 July 2024 / Revised: 29 July 2024 / Accepted: 30 July 2024 / Published: 9 August 2024
(This article belongs to the Section Dermatology)
Browse Figures
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Abstract

:
Background/Objective: Lichen sclerosus is a chronic inflammatory skin disease that affects people of all ages and sexes. Evidence of cardiovascular risk factors in lichen sclerosus has been continuously reported; however, the definitive association remains inconclusive. This meta-analysis aimed to summarize the association between cardiovascular risk factors and lichen sclerosus. Methods: Electronic databases, including MEDLINE and EMBASE, were systematically searched from inception to May 2024 to identify the literature reporting the association between cardiovascular risk factors and lichen sclerosus. A random-effects model was used for the meta-analysis. Results: We included 16 eligible studies: nine case–control studies, six retrospective cohort studies, and one cross-sectional study. A total of 432,457 participants were included. Lichen sclerosus was significantly associated with type 2 diabetes mellitus with an odds ratio of 2.07 (95% CI: 1.21–3.52). Although not statistically significant, a trend of increasing risk in hypertension, dyslipidemia, obesity, and metabolic syndrome was observed among lichen sclerosus patients, with odds ratios of 1.56 (95% CI: 0.90–2.70), 1.44 (95% CI: 0.94–2.23), 5.84 (95% CI: 0.37–92.27), and 1.36 (95% CI: 0.52–3.54), respectively. Conclusions: Lichen sclerosus was associated with diabetes mellitus and potentially correlated with hypertension, dyslipidemia, obesity, and metabolic syndrome. Population-based prospective observational studies are required to further elucidate these findings and assess the impact of these associations.

1. Introduction

Lichen sclerosus (LS) is a chronic, benign, inflammatory skin disease characterized by inflammation, epithelial thinning, and distinctive dermal changes. LS typically occurs in the genital area, predominantly in females, with two onset peaks: prepubertal and postmenopausal age groups. In young individuals, LS involves prepubertal children and can manifest as hypoestrogenism [1,2]. Lesions in extragenital areas are mostly asymptomatic, while those in genital areas can present as glittering, whitish, patchy, and hyperkeratotic lesions. Clinical symptoms or signs may include pruritus, pain, balanoposthitis, phimosis, scarring, and stricture in affected organs [3]. In male patients, the lesions can involve the penis glans, urethra, and foreskin. Symptoms include phimosis, urethral stricture, and paraphimosis [4,5]. In female patients with LS, lesions occur in the inner areas of the labia minora, labia majora, clitoral hood, and perianal area. This anogenital involvement can lead to stenosis of the introitus, adherence of the labia minora, phimosis of the clitoris, and difficulties with defecation [1].
Although the exact prevalence of LS remains unknown [6], it was estimated to be 3% to 13% of older adult females in specialist clinics [7,8] and was likely underreported since one-third of the cases were asymptomatic [8]. The incidence of LS is increasing, as can be seen by the age-standardized incidence rate among Dutch women, which increased from 5 per 100,000 person–years in 1997–1998 to 35.7 per 100,000 person–years in 2021–2022 [9]. The etiology of LS is not fully understood [3], but probable mechanisms include hereditary factors, an autoimmune phenotype, and genetic alterations. LS is associated with microvessel injury, characterized by endothelial necrosis and basement membrane thickening. The link between inflammatory change and microvascular injury remains unclear, although the presence of C5b-9 in vessels of LS patients suggests a potential role in vessel injury [10].
The association between LS and cardiovascular risk factors may be explained by the aforementioned mechanisms, similar to other chronic inflammatory skin diseases. For instance, inflammation and the autoimmune nature of LS may lead to diabetes mellitus, whereas microvascular damage from LS may lead to hypertension. Uncontrolled diabetes mellitus and hypertension can cause further microvascular injury [11,12]. Nonetheless, the association between LS and cardiovascular risk factors remains inconclusive. Previous relevant studies showed an increasing risk of cardiovascular risk factors in individuals with LS [13,14,15,16]. Gulin et al. showed a significant correlation between LS and the risk of type 1 diabetes mellitus (OR = 1.9; 95% CI 1.6–2.1) [17]. In addition, Hieta et al. demonstrated a significant risk of cardiovascular risk factors, including type 2 diabetes mellitus, hypertension, and dyslipidemia among LS patients [17]. However, certain studies demonstrated a decreased risk of these comorbidities in LS [18,19,20]. Furthermore, Liu et al. reported no bidirectional association between diabetes mellitus or body mass index (BMI) and LS [21]. Given the inconsistency in existing results, this systematic review and meta-analysis were performed to summarize the association between cardiovascular risk factors and influencing factors of the association to provide comprehensive evidence.

2. Materials and Methods

This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement (Table S1) [22] and the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) checklists (Table S2) [23]. The protocol was registered before the initiation of this study (INPLASY202460045) [24].

2.1. Search Strategy

Four investigators (SU, PK, PC, and EC) independently constructed the search strategy to include relevant published articles. The search was conducted in the MEDLINE and EMBASE databases from inception to May 2024. The search strategy was based on terms related to LS and cardiovascular risk factors (diabetes mellitus, hypertension, dyslipidemia, obesity, and metabolic syndrome) (Table S3). To ensure comprehensiveness, we also manually searched each reference of potentially included articles.

2.2. Inclusion Criteria

We included eligible studies, including cross-sectional, cohort, or case–control studies, that reported the risk of diabetes mellitus, metabolic syndrome, hypertension, dyslipidemia, or obesity in patients with LS. These studies needed to use patients without LS as their controls. Eligible studies were limited to those published in the English language.
The articles were screened in two rounds. The first round was for title and abstract screening, and the second was for full-text review. Four investigators (SU, PK, PC, and EC) independently screened the articles. Any discrepancies were resolved through discussions with the senior investigators (NL and CS).

2.3. Data Extraction

Four investigators (SU, PK, PC, and EC) independently extracted the following topics to the standardized data extraction form: (1) baseline characteristics, including the last name of the first author, publication year, country, type of study design, study period, number of total participants, locations of LS, diagnostic criteria for LS, percentage of males, mean age of participants, and mean BMI of participants; (2) outcomes of interest, including the risk of diabetes mellitus, metabolic syndrome, hypertension, dyslipidemia, or obesity in patients with LS compared with patients without LS, reported as an adjusted and unadjusted odd ratio (OR), relative risk (RR), or hazard risk ratio (HR), with their 95% confidence interval (CI); and (3) adjusted factors for statistical analysis. Corresponding authors of articles potentially included were contacted to retrieve missing information for comprehensiveness.

2.4. Quality Assessment

Two researchers (SU and PK) used the Newcastle–Ottawa quality assessment scale for case–control, cohort, and cross-sectional studies to assess the quality of the included articles [25]. Any conflicts were resolved through consultation with NL.

2.5. Risk of Bias Assessment

Three investigators (SU, PK, and PC) independently assessed the risk of bias in the included studies using the Quality In Prognosis Studies (QUIPS) tool. This tool includes six domains (study participants, study attrition, prognostic factor measurements, outcome measurement, confounding, and statistical analysis and reporting). The risk of bias was reported as high, moderate, and low. Any of the conflicts were resolved by consulting NL.

2.6. Certainty of Evidence

Three investigators (SU, PK, and PC) independently evaluated the certainty of evidence in the included studies using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. This tool includes five domains (risk of bias, inconsistency, indirectness, imprecision, and publication bias). The certainty was categorized as high, moderate, low, and very low. Any conflicts were resolved by consulting NL.

2.7. Statistical Analysis

The association between cardiovascular risk factors and LS was meta-analyzed using Review Manager 5.3 software (clicktime.com, Inc., San Francisco, CA, USA) from the Cochrane Collaboration. A random-effect model was used due to variations in study methodologies and settings. Overall effect sizes were estimated using the Mantel–Haenszel method. Heterogeneity among included studies was examined using the I2 statistic. A value of I2 between 0 and 25% indicated insignificant heterogeneity, 51–75% represented moderate heterogeneity, and I2 greater than 75% signified high heterogeneity [26]. Meta-regression by age, sex, study design, quality of studies, study country region, and the use of pathology for diagnosis was planned a priori. Heterogeneity was further examined through sensitivity analyses by removing one study with different methodologies at a time. Publication bias was assessed through visual inspection of the funnel plot without performing a statistical test for asymmetry. Significant asymmetry indicated potential publication bias or heterogeneity [27]. If studies reported both numbers for patients with type 1 and type 2 diabetes mellitus, only those with type 2 were included in the analysis.

3. Results

3.1. Search Results

The systematic search retrieved 1123 potential articles (791 from EMBASE and 332 from MEDLINE), of which 247 were duplicates and removed. Subsequently, the titles and abstracts of 876 articles were screened. After reviewing 81 full-text articles, 65 were excluded due to their irrelevant outcomes, unrelated study designs, or the unavailability of articles in English. As a result, 16 articles were included in the analysis (Figure 1) [13,14,15,16,17,18,19,20,28,29,30,31,32,33,34,35].

3.2. Baseline Characteristics of Eligibility Studies

A total of 432,457 participants from 16 articles were included. The included studies comprised nine case–control studies [15,16,17,18,19,29,30,31,32], six retrospective cohort studies [13,14,20,28,33,34], and one cross-sectional study [35]. Of these, eight studies [14,15,19,20,28,31,33,34] were from the Americas, seven [13,16,17,18,29,32,35] from Europe, and one [30] from the Eastern Mediterranean Region. Table 1 demonstrates the baseline characteristics with quality assessment of the eligibility articles. The diagnostic criteria for LS in each study are detailed in Table S4.

3.3. Risk of Bias Assessment

The risk of bias assessment classified four studies [14,29,31,33] as low risk and twelve studies [13,16,17,18,19,20,28,30,32,33,34,35] as moderate risk (Table S6). The overall risk of bias assessment in each study is demonstrated in Figure S1. A high risk of bias assessments was found in only bias due to confounding domain. Figure S2 depicts the summarized proportion of the risk of bias assessment for each domain.

3.4. Certainty of Evidence Assessment

Table S7 describes the certainty of evidence assessment from the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Evidence supporting the outcomes of diabetes mellitus and hypertension was graded as low certainty. The other comorbidities were supported by very low certainty of evidence.

3.5. Associated Outcomes in Lichen Sclerosus Patients

3.5.1. Diabetes Mellitus

Thirteen studies with 18,192 LS patients were included in the meta-analysis of the risk of diabetes mellitus [13,14,15,16,17,18,19,20,29,30,32,34,35]. The pooled unadjusted odds ratio (OR) was 2.07 (95% CI: 1.21–3.52, I2 = 96%), which was statistically significant (p = 0.008, Figure 2). Meyrick Thomas et al. [35] were excluded from the analysis due to the absence of event numbers. Of the included studies, only Halonen et al. [18] reported a decreased risk of diabetes mellitus.

3.5.2. Hypertension

Nine studies [14,15,17,18,19,20,28,30,33] (13,412 LS individuals) reported their unadjusted OR with hypertension outcome (Figure 3). The pooled OR was 1.56 (95% CI: 0.90–2.70, I2 = 98%), which was not statistically significant (p = 0.12). Of these, six [14,17,20,28,30,33] reported a significantly increased risk of hypertension, whereas Halonen et al. [18] reported a decreased risk.

3.5.3. Dyslipidemia

Five studies [14,15,16,17,18] with 11,398 LS subjects were included in the analysis (Figure S3). Of these, only one [18] indicated a decreased risk of dyslipidemia in LS patients, while three [14,16,17] noted an increased risk of dyslipidemia among LS patients. The meta-analysis showed that LS was not associated with the risk of dyslipidemia (pooled unadjusted OR = 1.44, 95% CI: 0.94–2.23, I2 = 85%, p = 0.10).

3.5.4. Obesity

The outcomes regarding obesity in 11,255 LS participants were investigated in three studies [18,28,31], as depicted in Figure S4. The meta-analysis showed that LS did not significantly increase the risk of obesity (pooled unadjusted OR = 5.84, 95% CI: 0.37–92.27, I2 = 89%, p = 0.21). Blaschko et al. [28] and Fuchs et al. [31] reported an enhanced risk of obesity in LS patients, while Halonen et al. [18] presented an insignificant risk of obesity.

3.5.5. Metabolic Syndrome

Two studies [18,20] revealed the OR of metabolic syndrome in LS, as shown in Figure S5. The pooled unadjusted OR was 1.36 (95% CI: 0.52–3.54, I2 = 92%), without statistical significance (p = 0.53). Only one [20] showed a positive association between metabolic syndrome and LS.

3.6. Publication Bias

Table S7 provides an overall biases assessment for each outcome. The publication bias in this systematic review was investigated using the funnel plot from data on diabetes mellitus in LS patients since diabetes mellitus was the only outcome with sufficient publications (Figure S6). The funnel plot was not symmetrical; therefore, publication bias was probable.

3.7. Meta-Regression

Because of the high heterogeneity, meta-regression was conducted. In diabetes mellitus studies, the study location (p = 0.003) and the study quality score (p = 0.009) were identified as the causes of heterogeneity. In hypertension studies, the study location, as classified by the World Health Organization (WHO) (p = 0.020), percentage of male participants (p = 0.030), average age of participants (p = 0.016), and study design (p = 0.024) were causes of heterogeneity. Table 2 summarizes the meta-regression analysis based on the baseline characteristics of eligible studies. We did not perform meta-regress for other outcomes due to the limited number of included articles.

3.8. Sensitivity Analysis

In the sensitivity analyses, by removing Halonen et al. [18], significant ORs with I2 reduction in diabetes mellitus and hypertension in LS were demonstrated as follows: 2.04 (95% CI: 1.68–2.48, I2 = 31%, p < 0.001) and 1.78 (95% CI: 1.35–2.35, I2 = 83%, p < 0.001), respectively (Figure 4 and Figure 5).

4. Discussion

This meta-analysis demonstrated a significant association between diabetes mellitus and LS, with a 2.04-fold increasing risk, along with observed rising trends for hypertension, dyslipidemia, obesity, and metabolic syndrome in patients with LS. Sensitivity analyses revealed a 2.04-fold and 1.78-fold significantly elevated risk for diabetes mellitus and hypertension in LS patients, respectively. Halonen et al. [18] was the only study showing a significant decrease in the risk of diabetes mellitus and hypertension in our meta-analysis of LS patients.
Our results depicted the significantly enhanced risk of diabetes mellitus in LS patients, which can be explained by inflammatory processes and microvascular diseases. The pathogenesis of LS is superficial vessel damage, which represents necrosis of the endothelium or microvessel walls and a decrease in size and density in dermal papillae under microscopic findings. The C5b-9 mediators play a significant role in endothelial injury due to their deposition in superficial vessels. The concurrence of diabetes mellitus in LS is linked to microvascular impairment through vascular dropout, which diminishes vessel density through C5b-9 mediators in some studies [10,11,36]. Furthermore, the deregulatory of inflammatory molecules, including cytokines and adipocytokines, may be involved in the development of diabetes mellitus in LS patients [37].
This study revealed a significant association between hypertension and LS. Hypertensive diseases cause microvascular injury and endothelial dysfunction through glycosylation of the other molecules of C5b-9 (CD59). C5b-9 accumulates in endothelial tissues, which causes the basement membrane layer enlargement. The other mechanism is to diminish the capillary density (rarefaction), which is caused by the resistance of vessels. However, the pathogenesis of rarefaction has not been elucidated [10,11,12,38,39].
The pathogenesis of LS is the genetic alteration that involves reactive oxygen species (ROS), causing changes in macromolecules (DNA, proteins, and lipids). The alteration leads to conditions such as cancer, autoimmune, and sclerosis. A previous study revealed a correlation between oxidative stress and LS pathogenesis [40]. Genetic alteration is also linked to oxidative stress in LS. High activation and production of wild-type p53 can induce oxidation reactions, which can lead to the development of cancerous lesions. Conversely, loss of p53 and genetic alteration of CDKN2A can precipitate cancer [41]. These ROS and oxidative stress could be linked to elevated cardiovascular risk factors in our study.
Increased cardiovascular risk factors observed in other chronic inflammatory skin diseases in adults, such as psoriasis [42,43] and atopic dermatitis [44,45,46], are similar in LS. While the specific inflammatory pathways differed among these conditions, these diseases shared a common aspect of chronic inflammation [42,47,48], which possibly led to increased risks. Nonetheless, evidence elucidating the mechanisms by which these comorbidities exacerbated LS or precipitated cardiovascular events remains limited in LS.
Management of cardiovascular risk factors in LS has not been emphasized. Recent guidelines mentioned an observed link between diabetes mellitus and BMI in LS patients [49,50]. Despite this, only obese male patients with LS and a buried penis are recommended to lose weight through multidisciplinary approaches [49]. In contrast, multidisciplinary approaches to all cardiovascular risk factors in patients with psoriasis are widely suggested [51,52]. Given the potential for elevated cardiovascular risk factors, healthcare providers should consider adopting a multidisciplinary approach for monitoring and managing cardiovascular health in selected patients with LS, similar to strategies for psoriasis. In addition, prompt and frequent evaluation and monitoring of cardiovascular risk factors may benefit certain selected LS patients [53]. Current diabetes guidelines emphasize reducing cardiovascular and renal complications and recommend glucose-lowering drugs with cardiorenal benefits. With the increasing use of sodium–glucose cotransporter receptor-2 (SGLT2) inhibitors, clinicians should be aware that these medications can cause vulvar pruritus, rash, and candidiasis, which may be mistaken for LS. It is important for clinicians to differentiate between these conditions to ensure the appropriate treatment for each [54,55].
Our findings robustly highlight the necessity for vigilant cardiovascular screening and monitoring in LS patients. However, the study was limited by the retrospective nature and the heterogeneity of the included studies, potential publication bias, and the lack of studies from certain geographic regions, including Africa, the Western Pacific, and Asia, which could affect the generalizability of the findings. The search terms may not include incorrect spelling, such as ‘lichen sclerosis’, and synonyms of LS, such as ‘balanitis xerotica obliterans’. However, we manually screened the keywords ‘lichen sclerosis’ and ‘balanitis xerotica obliterans’ to ensure comprehensiveness, resulting in no additional references. Prospective observational studies are needed to address these limitations and confirm our findings.
Based on our findings, further studies are needed to establish more evidence on the risk of each type of diabetes mellitus and the interaction between sex, locations of involvement (genital/extragenital involvement), and cardiovascular risk factors in LS patients. Crucially, there is a lack of evidence supporting the correlation between LS and cardiovascular diseases such as cerebrovascular disease, acute coronary syndrome, and atherosclerosis. Therefore, future research should investigate the risk of cardiovascular diseases and mortality in LS patients.

5. Conclusions

LS is likely correlated with diabetes mellitus and possibly associated with hypertension, dyslipidemia, obesity, and metabolic syndrome. Population-based prospective observational studies are required to further elucidate the findings and assess the impact of these associations.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jcm13164668/s1, Figure S1: The overall risk of bias assessment using the QUIPS tool in each study. Figure S2: The summarized proportion of the risk of bias assessment for each domain by the QUIPS tool. Figure S3: The forest plot for the pooled odds ratio of dyslipidemia in patients with lichen sclerosus. Figure S4: The forest plot for the pooled odds ratio of obesity in patients with lichen sclerosus. Figure S5: The forest plot for the pooled odds ratio of metabolic syndrome in patients with lichen sclerosus. Figure S6: The funnel plot for included articles. Table S1: PRISMA checklist 2020. Table S2: MOOSE checklist. Table S3: Search strategy. Table S4: Diagnostic criteria of patients with lichen sclerosus in each of the included studies. Table S5: Severity of lichen sclerosus and criteria for diagnosis of diabetes mellitus, hypertension, dyslipidemia, obesity, and metabolic syndrome among included studies. Table S6: The risk of bias using the QUIPS tool for included articles. Table S7: GRADE assessment of the eligible studies.

Author Contributions

Conceptualization, S.U., P.K., N.L., P.C., W.E., W.P. and C.S.; Methodology, S.U., P.K., N.L., P.C., W.E., W.P. and C.S.; Validation, S.U., P.K., N.L., P.C., W.E., W.P. and C.S.; Formal Analysis, N.L.; Investigation, N.L.; Resources, S.U., P.K. and C.S.; Data Curation, S.U. and P.K.; Writing—Original Draft Preparation, S.U. and P.K.; Writing—Review and Editing, N.L., W.P. and C.S.; Visualization, S.U., P.K., N.L., W.P. and C.S.; Supervision, N.L., W.P. and C.S.; Project Administration, S.U. and C.S. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Ethical review and approval were waived for this study due to the type of research (systematic review and meta-analysis).

Informed Consent Statement

Patient consent was waived due to the type of research (systematic review and meta-analysis).

Data Availability Statement

The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding authors.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

BMIBody mass index
CIConfidence interval
GRADEGrading of Recommendations, Assessment, Development, and Evaluations
HRHazard risk ratio
LSLichen sclerosus
OROdds ratio
PRISMAPreferred Reporting Items for Systematic Reviews and Meta-Analyses
QUIPSQuality In Prognosis Studies
RRRelative risk

References

  1. Perez-Lopez, F.R.; Vieira-Baptista, P. Lichen sclerosus in women: A review. Climacteric 2017, 20, 339–347. [Google Scholar] [CrossRef] [PubMed]
  2. Taylor, A.H.; Guzail, M.; Al-Azzawi, F. Differential expression of oestrogen receptor isoforms and androgen receptor in the normal vulva and vagina compared with vulval lichen sclerosus and chronic vaginitis. Br. J. Dermatol. 2008, 158, 319–328. [Google Scholar] [CrossRef] [PubMed]
  3. Kirtschig, G. Lichen Sclerosus-Presentation, Diagnosis and Management. Dtsch. Arztebl. Int. 2016, 113, 337–343. [Google Scholar] [CrossRef] [PubMed]
  4. Bunker, C.B.; Shim, T.N. Male genital lichen sclerosus. Indian J. Dermatol. 2015, 60, 111–117. [Google Scholar] [CrossRef] [PubMed]
  5. Hieta, N.K.; Haataja, M.A.M.; Tapana, L. Comorbidities in Male Patients With Lichen Sclerosus: A Case-Control Study. J. Low. Genit. Tract. Dis. 2023, 27, 378–383. [Google Scholar] [CrossRef] [PubMed]
  6. Singh, N.; Ghatage, P. Etiology, Clinical Features, and Diagnosis of Vulvar Lichen Sclerosus: A Scoping Review. Obstet. Gynecol. Int. 2020, 2020, 7480754. [Google Scholar] [CrossRef] [PubMed]
  7. Fischer, G.O. The commonest causes of symptomatic vulvar disease: A dermatologist’s perspective. Australas. J. Dermatol. 1996, 37, 12–18. [Google Scholar] [CrossRef] [PubMed]
  8. Goldstein, A.T.; Marinoff, S.C.; Christopher, K.; Srodon, M. Prevalence of vulvar lichen sclerosus in a general gynecology practice. J. Reprod. Med. 2005, 50, 477–480. [Google Scholar] [PubMed]
  9. Baandrup, L.; Hannibal, C.G.; Hertzum-Larsen, R.; Kjaer, S.K. Biopsy-verified vulvar lichen sclerosus: Incidence trends 1997–2022 and increased risk of vulvar squamous precancer and squamous cell carcinoma. Int. J. Cancer 2024, 155, 501–507. [Google Scholar] [CrossRef]
  10. Magro, C.M.; Kalomeris, T.A.; Mo, J.H.; Rice, M.; Nuovo, G. Lichen sclerosus: A C5B-9 mediated chronic microvascular injury syndrome potentially reflective of common adult comorbidities. Ann. Diagn. Pathol. 2023, 63, 152098. [Google Scholar] [CrossRef]
  11. Behrouz, N.; Defossez, A.; Delacourte, A.; Mazzuca, M. The immunohistochemical evidence of amyloid diffuse deposits as a pathological hallmark in Alzheimer’s disease. J. Gerontol. 1991, 46, B209–B212. [Google Scholar] [CrossRef] [PubMed]
  12. Yu, B.B.; Zhi, H.; Zhang, X.Y.; Liang, J.W.; He, J.; Su, C.; Xia, W.H.; Zhang, G.X.; Tao, J. Mitochondrial dysfunction-mediated decline in angiogenic capacity of endothelial progenitor cells is associated with capillary rarefaction in patients with hypertension via downregulation of CXCR4/JAK2/SIRT5 signaling. EBioMedicine 2019, 42, 64–75. [Google Scholar] [CrossRef] [PubMed]
  13. Gulin, S.J.; Lundin, F.; Seifert, O. Comorbidity in patients with Lichen sclerosus: A retrospective cohort study. Eur. J. Med. Res. 2023, 28, 338. [Google Scholar] [CrossRef] [PubMed]
  14. Erickson, B.A.; Elliott, S.P.; Myers, J.B.; Voelzke, B.B.; Smith, T.G.; McClung, C.D.; Alsikafi, N.F.; Vanni, A.J.; Brant, W.O.; Broghammer, J.A.; et al. Understanding the Relationship between Chronic Systemic Disease and Lichen Sclerosus Urethral Strictures. J. Urol. 2016, 195, 363–368. [Google Scholar] [CrossRef]
  15. Hofer, M.D.; Meeks, J.J.; Mehdiratta, N.; Granieri, M.A.; Cashy, J.; Gonzalez, C.M. 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. [Google Scholar] [CrossRef] [PubMed]
  16. Bjekić, M.; Šipetić, S.; Marinković, J. Risk factors for genital lichen sclerosus in men. Br. J. Dermatol. 2011, 164, 325–329. [Google Scholar] [CrossRef] [PubMed]
  17. Hieta, N.; Rintala, M.; Soderlund, J.M.; 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. [Google Scholar] [CrossRef]
  18. Halonen, P.; Heikinheimo, O.; Hadkhale, K.; Gissler, M.; Pukkala, E.; Jakobsson, M. Risk Factors for Lichen Sclerosus: A Case-Control Study of 43,000 Finnish Women. J. Low. Genit. Tract. Dis. 2024, 28, 164–168. [Google Scholar] [CrossRef] [PubMed]
  19. Luu, Y.; Cheng, A.L.; 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. [Google Scholar] [CrossRef]
  20. Ranum, A.; Freese, R.; Ramesh, V.; Pearson, D.R. Lichen sclerosus in female patients is associated with an increased risk of metabolic syndrome and cardiovascular comorbidities: A retrospective cohort review. Br. J. Dermatol. 2022, 187, 1030–1032. [Google Scholar] [CrossRef]
  21. Liu, L.; Zhang, Q.; Chang, J.; Yang, K. Causal Association Between Diabetes, Body Mass Index and Lichen Sclerosus: A Bidirectional Two-Sample Mendelian Randomization Analysis. Clin. Cosmet. Investig. Dermatol. 2024, 17, 931–940. [Google Scholar] [CrossRef] [PubMed]
  22. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, n71. [Google Scholar] [CrossRef] [PubMed]
  23. Brooke, B.S.; Schwartz, T.A.; Pawlik, T.M. MOOSE Reporting Guidelines for Meta-analyses of Observational Studies. JAMA Surg. 2021, 156, 787–788. [Google Scholar] [CrossRef] [PubMed]
  24. Untaaveesup, S.; Kantagowit, P.; Leelakanok, N.; Chansate, P.; Eiumtrakul, W.; Pratchyapruit, W.; Sriphrapradang, C. The association between cardiovascular risk factors and lichen sclerosus patients: A systematic review and meta-analysis. INPLASY 2024. [Google Scholar] [CrossRef]
  25. Herzog, R.; Álvarez-Pasquin, M.J.; Díaz, C.; Del Barrio, J.L.; Estrada, J.M.; Gil, Á. Are healthcare workers’ intentions to vaccinate related to their knowledge, beliefs and attitudes? a systematic review. BMC Public Health 2013, 13, 154. [Google Scholar] [CrossRef] [PubMed]
  26. Higgins, J.P.; Thompson, S.G.; Deeks, J.J.; Altman, D.G. Measuring inconsistency in meta-analyses. BMJ 2003, 327, 557–560. [Google Scholar] [CrossRef]
  27. Egger, M.; Davey Smith, G.; Schneider, M.; Minder, C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997, 315, 629–634. [Google Scholar] [CrossRef] [PubMed]
  28. Blaschko, S.D.; Gaither, T.W.; Alwaal, A.; Harris, C.R.; McCulloch, C.E.; McAninch, J.W.; Breyer, B.N. Lichen Sclerosus Comorbidities and Complications from a National Sample of Patients Treated with Urethroplasty. Urol. Pract. 2015, 2, 329–334. [Google Scholar] [CrossRef] [PubMed]
  29. Cooper, S.M.; Ali, I.; Baldo, M.; Wojnarowska, F. The Association of Lichen Sclerosus and Erosive Lichen Planus of the Vulva With Autoimmune Disease: A Case-Control Study. Arch. Dermatol. 2008, 144, 1432–1435. [Google Scholar] [CrossRef]
  30. El Khoury, J.; Andraos, J.; Kanbar, A.; Halabi, R.; Assaf, S.; Mina, A.; El Breidi, S.; Dabal, C.; El Hachem, C.; Saad, R.; et al. A Potential Protective Effect of Alcohol Consumption in Male Genital Lichen Sclerosus: A Case-Control Study. Adv. Urol. 2023, 2023, 7208312. [Google Scholar] [CrossRef]
  31. Fuchs, M.E.; Beecroft, N.; Dajusta, D.G.; McLeod, D.J. The Association Between BXO and Obesity in Boys Undergoing Circumcision. Glob. Pediatr. Health 2017, 4, 2333794X17742749. [Google Scholar] [CrossRef] [PubMed]
  32. Higgins, C.A.; Cruickshank, M.E. A population-based case-control study of aetiological factors associated with vulval lichen sclerosus. J. Obstet. Gynaecol. 2012, 32, 271–275. [Google Scholar] [CrossRef] [PubMed]
  33. Hu, J.; Hesson, A.; Haefner, H.K.; 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. [Google Scholar] [CrossRef] [PubMed]
  34. Meeks, J.; Mehdiratta, N.; Granieri, M.; Cashy, J.; Gonzalez, C. Lichen sclerosus in men is associated with diabetes and coronary artery disease and smoking. J. Urol. 2011, 185, e240. [Google Scholar] [CrossRef]
  35. Meyrick Thomas, R.H.; Ridley, C.M.; Black, M.M. The association of lichen sclerosus et atrophicus and autoimmune-related disease in males. Br. J. Dermatol. 1983, 109, 661–664. [Google Scholar] [CrossRef] [PubMed]
  36. Kowalewski, C.; Kozłowska, A.; Górska, M.; Woźniak, K.; Krajewski, M.; Błaszczyk, M.; Jabłońska, S. Alterations of basement membrane zone and cutaneous microvasculature in morphea and extragenital lichen sclerosus. Am. J. Dermatopathol. 2005, 27, 489–496. [Google Scholar] [CrossRef] [PubMed]
  37. Davidovici, B.B.; Sattar, N.; Prinz, J.; Puig, L.; Emery, P.; Barker, J.N.; van de Kerkhof, P.; Stahle, M.; Nestle, F.O.; Girolomoni, G.; et al. Psoriasis and systemic inflammatory diseases: Potential mechanistic links between skin disease and co-morbid conditions. J. Investig. Dermatol. 2010, 130, 1785–1796. [Google Scholar] [CrossRef]
  38. Gallo, G.; Volpe, M.; Savoia, C. Endothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications. Front. Med. 2021, 8, 798958. [Google Scholar] [CrossRef] [PubMed]
  39. Serne, E.H.; Gans, R.O.; ter Maaten, J.C.; Tangelder, G.J.; Donker, A.J.; Stehouwer, C.D. Impaired skin capillary recruitment in essential hypertension is caused by both functional and structural capillary rarefaction. Hypertension 2001, 38, 238–242. [Google Scholar] [CrossRef]
  40. Sander, C.S.; Ali, I.; Dean, D.; Thiele, J.J.; Wojnarowska, F. Oxidative stress is implicated in the pathogenesis of lichen sclerosus. Br. J. Dermatol. 2004, 151, 627–635. [Google Scholar] [CrossRef]
  41. Tran, D.A.; Tan, X.; Macri, C.J.; Goldstein, A.T.; Fu, S.W. Lichen Sclerosus: An autoimmunopathogenic and genomic enigma with emerging genetic and immune targets. Int. J. Biol. Sci. 2019, 15, 1429–1439. [Google Scholar] [CrossRef] [PubMed]
  42. Miller, I.M.; Ellervik, C.; Yazdanyar, S.; Jemec, G.B.E. Meta-analysis of psoriasis, cardiovascular disease, and associated risk factors. J. Am. Acad. Dermatol. 2013, 69, 1014–1024. [Google Scholar] [CrossRef] [PubMed]
  43. Liu, L.; Cui, S.; Liu, M.; Huo, X.; Zhang, G.; Wang, N. Psoriasis Increased the Risk of Adverse Cardiovascular Outcomes: A New Systematic Review and Meta-Analysis of Cohort Study. Front. Cardiovasc. Med. 2022, 9, 829709. [Google Scholar] [CrossRef]
  44. Ascott, A.; Mulick, A.; Yu, A.M.; Prieto-Merino, D.; Schmidt, M.; Abuabara, K.; Smeeth, L.; Roberts, A.; Langan, S.M. Atopic eczema and major cardiovascular outcomes: A systematic review and meta-analysis of population-based studies. J. Allergy Clin. Immunol. 2019, 143, 1821–1829. [Google Scholar] [CrossRef] [PubMed]
  45. Silverberg, J.I. Association between adult atopic dermatitis, cardiovascular disease, and increased heart attacks in three population-based studies. Allergy 2015, 70, 1300–1308. [Google Scholar] [CrossRef]
  46. Yousaf, M.; Ayasse, M.; Ahmed, A.; Gwillim, E.C.; Janmohamed, S.R.; Yousaf, A.; Patel, K.R.; Thyssen, J.P.; Silverberg, J.I. Association between atopic dermatitis and hypertension: A systematic review and meta-analysis. Br. J. Dermatol. 2022, 186, 227–235. [Google Scholar] [CrossRef] [PubMed]
  47. Armstrong, A.W.; Read, C. Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review. JAMA 2020, 323, 1945–1960. [Google Scholar] [CrossRef] [PubMed]
  48. Langan, S.M.; Irvine, A.D.; Weidinger, S. Atopic dermatitis. Lancet 2020, 396, 345–360. [Google Scholar] [CrossRef] [PubMed]
  49. Lewis, F.M.; Tatnall, F.M.; Velangi, S.S.; Bunker, C.B.; Kumar, A.; Brackenbury, F.; Mohd Mustapa, M.F.; Exton, L.S. British Association of Dermatologists guidelines for the management of lichen sclerosus, 2018. Br. J. Dermatol. 2018, 178, 839–853. [Google Scholar] [CrossRef]
  50. Kirtschig, G.; Kinberger, M.; Kreuter, A.; Simpson, R.; Gunthert, A.; van Hees, C.; Becker, K.; Ramakers, M.J.; Corazza, M.; Muller, S.; et al. EuroGuiderm guideline on lichen sclerosus-Treatment of lichen sclerosus. J. Eur. Acad. Dermatol. Venereol. 2024. [Google Scholar] [CrossRef]
  51. Daudén, E.; Castañeda, S.; Suárez, C.; García-Campayo, J.; Blasco, A.J.; Aguilar, M.D.; Ferrándiz, C.; Puig, L.; Sánchez-Carazo, J.L. Clinical practice guideline for an integrated approach to comorbidity in patients with psoriasis. J. Eur. Acad. Dermatol. Venereol. 2013, 27, 1387–1404. [Google Scholar] [CrossRef] [PubMed]
  52. Dauden, E.; Blasco, A.J.; Bonanad, C.; Botella, R.; Carrascosa, J.M.; González-Parra, E.; Jodar, E.; Joven, B.; Lázaro, P.; Olveira, A.; et al. Position statement for the management of comorbidities in psoriasis. J. Eur. Acad. Dermatol. Venereol. 2018, 32, 2058–2073. [Google Scholar] [CrossRef] [PubMed]
  53. Takeshita, J.; Grewal, S.; Langan, S.M.; Mehta, N.N.; Ogdie, A.; Van Voorhees, A.S.; Gelfand, J.M. Psoriasis and comorbid diseases: Implications for management. J. Am. Acad. Dermatol. 2017, 76, 393–403. [Google Scholar] [CrossRef] [PubMed]
  54. Forman, J.L.; Mercurio, M.G. Vulvar Pruritus in Postmenopausal Diabetic Women With Candidiasis Secondary to Sodium-Glucose Cotransporter Receptor-2 Inhibitors. J. Low. Genit. Tract. Dis. 2023, 27, 68–70. [Google Scholar] [CrossRef]
  55. American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2024. Diabetes Care 2024, 47, S158–S178. [Google Scholar] [CrossRef]
Jcm 13 04668 g001
Figure 1. Flow diagram according to the PRISMA guideline.
Figure 1. Flow diagram according to the PRISMA guideline.
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Figure 2. The forest plot for the pooled unadjusted odds ratio of diabetes mellitus in patients with lichen sclerosus [13,14,15,16,17,18,19,20,29,30,32,34,35].
Figure 2. The forest plot for the pooled unadjusted odds ratio of diabetes mellitus in patients with lichen sclerosus [13,14,15,16,17,18,19,20,29,30,32,34,35].
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Figure 3. The forest plot for the unadjusted pooled odds ratio of hypertension in patients with lichen sclerosus [14,15,17,18,19,20,28,30,33].
Figure 3. The forest plot for the unadjusted pooled odds ratio of hypertension in patients with lichen sclerosus [14,15,17,18,19,20,28,30,33].
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Figure 4. The sensitivity analysis of the forest plot for the pooled unadjusted odds ratio of diabetes mellitus in patients with lichen sclerosus [13,14,15,16,17,19,20,29,30,32,34,35].
Figure 4. The sensitivity analysis of the forest plot for the pooled unadjusted odds ratio of diabetes mellitus in patients with lichen sclerosus [13,14,15,16,17,19,20,29,30,32,34,35].
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Figure 5. The sensitivity analysis of the forest plot for the pooled unadjusted odds ratio of hypertension in patients with lichen sclerosus [14,15,17,19,20,28,30,33].
Figure 5. The sensitivity analysis of the forest plot for the pooled unadjusted odds ratio of hypertension in patients with lichen sclerosus [14,15,17,19,20,28,30,33].
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Table 1. The baseline characteristics and quality assessment of the eligible studies.
Table 1. The baseline characteristics and quality assessment of the eligible studies.
ReferenceCountryStudy DesignStudy Period/DurationTotal Participants, nMale Sex, n (%)Mean Age, Years (SD)Mean BMI (SD)Location of LSConfoundersNewcastle-Ottawa Scale
Bjekić 2011 [16] SerbiaCC2007 to 2008292292 (100)All participants < 25 years: 26 (8.9%), 25–34 years: 54 (18.5%), 35–44 years: 40 (13.7%), 45–54 years: 48 (16.4%), 55+ years: 124 (42.5%) *NRGenital areaNASelection: 3, Comparabilit-y: 1,
Outcome: 3
Blaschko 2015 [28]USRC2000 to 201013,70013,700 (100)LS group: 50.4
non-LS group: 45.3		NRUrethra, specifically related to urethral stricture diseaseageSelection: 4, Comparabilit-y: 0,
Outcome: 2
Cooper 2008 [29]UKCC2 years12380 (0)LS group: 63
non-LS group: 62 		NRVulvaNASelection: 3, Comparabilit-y: 1,
Outcome: 2
Elkhoury 2023 [30]LebanonCC2010 to 20209494
(100)		LS group:
49.8 (22.9)
non-LS group: 45.7 (20.3)		LS group:
26.00 (2.72)
non-LS group: 25.55 (3.57)		Genital areaNASelection: 2, Comparabilit-y: 1,
Outcome: 3
Erickson 2015 [14]USRCNR11511151 (100)LS group:
51.3 (13.8)
non-LS group: 45.7 (16.6)		LS group:
34.6 (7.9)
non-LS group: 29.6 (6.7)		Urethra, specifically related to urethral stricture diseaseageSelection: 3, Comparabilit-y: 1,
Outcome: 3
Fuchs 2017 [31]USCC2008 to 2015300300 (100)LS group: 10.3
non-LS group: 10.1		LS group: 70.7
non-LS group: 52.4		Penile skinNASelection: 4, Comparabilit-y: 0,
Outcome: 3
Gulin 2023 [13]SwedenRC2001 to 2021368,248LS: 1802 (31.7)
non-LS: 184,848 (50.9)		LS group: 57 +
non-LS group: 40 +		NRAnogenital regionage, sexSelection: 3, Comparabilit-y: 0,
Outcome: 3
Halonen 2024 [18]FinlandCC1998 to 201642,7680 (0)LS group: 60.8
non-LS group: 60.8		NRVulvaNASelection: 4, Comparabilit-y: 1,
Outcome: 3
Hieta 2021 [17]FinlandCC2004 to 2012NA0 (0)LS group: 64.4
non-LS group: NR		NRGenital and perianal areasNASelection: 3, Comparabilit-y: 1,
Outcome: 2
Higgins 2012 [32]UKCCNR1580 (0)LS group: 65.0 (58.5, 71.5) +
non-LS group: 46.0 (37.5, 53.0) +		NRAnogenital regionNASelection: 4, Comparabilit-y: 1,
Outcome: 2
Hofer 2014 [15]USCC1986 to 2009582582 (100)LS group: 46.6
non-LS group: 48.3		LS group: 31.0
non-LS group: 28.1		Urethra, penis, prepuce, and scrotumNASelection: 3, Comparabilit-y: 1,
Outcome: 2
Hu 2020 [33]USRC1996 to 201919830 (0)LS group: 54.4 (15.7)
non-LS group: 42.9 (16.0)		NRVulvaNASelection: 3, Comparabilit-y: 2,
Outcome: 3
Meeks 2011 [34]USRC1986 to 2009588588 (100)NR, but LS group age was matched within 3 years with non-LS group.LS group: 31.0
non-LS group: 28.1		Urethra, penile skin, prepuce, and scrotumNASelection: 3, Comparabilit-y: 2,
Outcome: 3
Meyrick thomas 1983 [35]UKCSNR5050 (100)LS group: 43
non-LS group: 44		NRPenis, trunk, and limbsNASelection: 3, Comparabilit-y: 1,
Outcome: 3
Ranum 2022 [20]USRC2015 to 201911700 (0)Total participants: 57.3 *LS group: 29.8 (7.1)
non-LS group: 29.3 (7.6)		Genital and body areasNASelection: 3, Comparabilit-y: 1,
Outcome: 3
Yen Luu 2023 [19]USCC2019 to 20211350 (0)LS group: 71
non-LS group: 54		LS group: 29.8 (8.4)
non-LS group: 24.9 (5.5)		VulvaNASelection: 4, Comparabilit-y: 1,
Outcome: 3
Abbreviations: BMI, body mass index; CC, case–control study; CS, cross-sectional study; LS, lichen sclerosus; NA, not available; NR, not reported; RC, retrospective cohort study; SD, standard deviation; UK, United Kingdom; US, United States. * The data are presented in the form available from the study. + median (IQR) is shown instead of mean (SD).
Table 2. Meta-regression for the association between lichen sclerosus and the risk of diabetes mellitus and hypertension.
Table 2. Meta-regression for the association between lichen sclerosus and the risk of diabetes mellitus and hypertension.
Possible Source of HeterogeneityNumber of Included StudiesCoefficient
[95% CI]		p-Value
Diabetes Mellitus
Male (%)130.004 [−0.002 to 0.011]0.165
Age (mean)13−0.012 [−0.075 to 0.052]0.718
Study design13 0.866
     Case–control study80.532 [0.098 to 0.966]0.016
     Retrospective cohort study40.148 [−0.494 to 0.790]0.651
     Cross-sectional study1−0.532 [−4.602 to 3.538]0.798
Quality of study by NOS stars13−0.399 [−0.699 to −0.099]0.009
Study country13 0.003
     Serbia10.700 [−0.251 to 1.651]0.149
     England21.324 [−0.547 to 3.195]0.166
     Finland2−0.800 [−1.815 to 0.215]0.122
     Lebanon10.571 [−0.964 to 2.105]0.466
     Scotland10.949 [−2.211 to 4.109]0.556
     Sweden10.532 [0.098 to 0.966]0.745
     United States5−0.074 [−1.084 to 0.936]0.886
WHO regions13 0.515
     EUR70.467 [0.038 to 0.897]0.033
     AMR50.193 [−0.450 to 0.836]0.556
     EMR10.803 [−0.645 to 2.251]0.277
Pathology for diagnosis 0.289
     Yes8−0.427 [−1.217 to 0.362]0.289
     No21.036 [0.283 to 1.788]0.007
Hypertension
Male (%)90.007 [0.001 to 0.013]0.030
Age (mean)9−0.052 [−0.095 to −0.010]0.016
Study design9 0.024
     Case–control study5−0.642 [−1.201 to −0.084]0.024
     Retrospective cohort study40.737 [0.342 to 1.131]<0.001
Quality of study by NOS stars9−0.308 [−0.685 to 0.069]0.110
Study country9 0.020
     United States 60.567 [0.242 to 0.891]<0.001
     Finland2−0.696 [−1.296 to −0.097]0.023
     Lebanon10.804 [−0.419 to 2.027]0.198
WHO regions9 0.020
     EUR2−0.696 [−1.296 to −0.097]0.023
     AMR60.567 [0.242 to 0.891]<0.001
     EMR10.804 [−0.419 to 2.027]0.198
Abbreviations: AMR, Region of the Americas; EMR, Eastern Mediterranean Region; EUR, European Region; NOS, Newcastle–Ottawa Scale; WHO, World Health Organization. The WHO regions’ classification was derived from the World Health Organization. (2023). World Health Statistics 2023 (ISBN-13: 9789240074323). World Health Organization.
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Untaaveesup, S.; Kantagowit, P.; Leelakanok, N.; Chansate, P.; Eiumtrakul, W.; Pratchyapruit, W.; Sriphrapradang, C. The Association between Cardiovascular Risk Factors and Lichen Sclerosus: A Systematic Review and Meta-Analysis. J. Clin. Med. 2024, 13, 4668. https://doi.org/10.3390/jcm13164668

AMA Style

Untaaveesup S, Kantagowit P, Leelakanok N, Chansate P, Eiumtrakul W, Pratchyapruit W, Sriphrapradang C. The Association between Cardiovascular Risk Factors and Lichen Sclerosus: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2024; 13(16):4668. https://doi.org/10.3390/jcm13164668

Chicago/Turabian Style

Untaaveesup, Suvijak, Piyawat Kantagowit, Nattawut Leelakanok, Petcharpa Chansate, Wongsathorn Eiumtrakul, Walaiorn Pratchyapruit, and Chutintorn Sriphrapradang. 2024. "The Association between Cardiovascular Risk Factors and Lichen Sclerosus: A Systematic Review and Meta-Analysis" Journal of Clinical Medicine 13, no. 16: 4668. https://doi.org/10.3390/jcm13164668

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