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Autoimmune and dermatologic conditions associated with lichen sclerosus

Published:August 07, 2020DOI:https://doi.org/10.1016/j.jaad.2020.08.011
      To the Editor: Lichen sclerosus (LS) is a chronic, inflammatory disorder that may lead to anogenital malignancy and scarring.
      • 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.
      ,
      • Kreuter A.
      • Kryvosheyeva Y.
      • Terras S.
      • et al.
      Association of autoimmune diseases with lichen sclerosus in 532 male and female patients.
      The pathophysiology is poorly understood; although autoantibodies targeting extracellular matrix 1 protein and the basement membrane zone have been identified, experts favor a T-cell–mediated pathogenesis.
      • 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.
      ,
      • Kreuter A.
      • Kryvosheyeva Y.
      • Terras S.
      • et al.
      Association of autoimmune diseases with lichen sclerosus in 532 male and female patients.
      Small studies show an association with thyroid disorders, vitiligo, and psoriasis.
      • 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.
      • Kreuter A.
      • Kryvosheyeva Y.
      • Terras S.
      • et al.
      Association of autoimmune diseases with lichen sclerosus in 532 male and female patients.
      • Meyrick Thomas R.H.
      • Ridley C.M.
      • McGibbon D.H.
      • Black M.M.
      Lichen sclerosus et atrophicus and autoimmunity—a study of 350 women.
      Increased risk of vulvar squamous cell carcinoma is also reported, with a lifetime incidence of 0.4% to 6% in women with LS.
      • Meani R.
      • Howard A.
      • Veysey E.
      Incidence of vulval squamous cell carcinoma in women with vulval lichen sclerosus in an Australian tertiary referral centre.
      We sought to determine the prevalence of these commonly cited comorbidities in the largest cohort of women with LS to date.
      The study population included patients in the IBM MarketScan Databases from 2015 to 2017 with 2 or more independent diagnoses of LS (International Classification of Diseases, 10th Revision–Clinical Modification L90.0). This database comprises more than 21.7 million commercially insured women in the United States. The study population was compared to a control group of women without LS. Stata statistical analysis software version 15.0 (StataCorp, College Station, TX) was used to examine the prevalences of Hashimoto disease/chronic lymphocytic thyroiditis/autoimmune thyroiditis, Graves disease/thyrotoxicosis, vitiligo, psoriasis, and vulvar carcinoma. Odds ratios and 95% confidence intervals were calculated. A P value of <.05 was considered significant.
      We identified 10,004 women with LS and 21,672,016 female control individuals without LS from 2015 to 2017 in the United States. The mean age was 50.8 years; 79% were between 45 and 65 years old. The rates of comorbid conditions are shown in Table I. In the LS population, the prevalences were as follows: autoimmune thyroid diseases, 6.11%; vitiligo, 1.95%; psoriasis, 5.12%; and vulvar carcinoma, 1.9%. All comorbidities were more likely to occur in patients with LS compared to control individuals (Table II). The most commonly associated autoimmune disease was hypothyroidism, with a prevalence of 4.26%. Notably, vulvar carcinoma was 26 times more likely and vitiligo was 12 times more likely to occur in patients with LS.
      Table IPrevalence of comorbid diseases in the LS and control populations
      Comorbid diseaseControl individuals, % (n)

      (n = 21,672,016)
      Patients with LS, % (n)

      (n = 10,004)
      All autoimmune thyroid1.93 (433,239)6.11 (767)
       Hashimoto/chronic lymphocytic thyroiditis/autoimmune thyroiditis1.13 (245,710)4.26 (426)
       Graves/thyrotoxicosis0.8 (173,183)1.85 (185)
      Vitiligo0.2 (34,539)1.95 (195)
      Psoriasis1.2 (255,270)5.12 (512)
      Vulvar carcinoma0.05 (16,055)1.89 (189)
      LS, Lichen sclerosus.
      Table IILikelihood of autoimmune comorbidities in LS compared to control populations
      Comorbid diseaseOR (95% CI), P value
      All autoimmune thyroid3.23 (2.98-3.5), <.00001
       Hashimoto/chronic lymphocytic thyroiditis/autoimmune thyroiditis3.88 (3.52-4.27), <.00001
       Graves disease/thyrotoxicosis2.34 (2.02-2.71), <.00001
      Vitiligo12.45 (10.8-14.36), <.00001
      Psoriasis4.53 (4.14-4.95), <.00001
      Vulvar carcinoma25.97 (22.47-30.02), <.00001
      CI, Confidence interval; LS, lichen sclerosus; OR, odds ratio.
      We identified only 4 studies that examined the rates of similar comorbidities in LS.
      • 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.
      • Kreuter A.
      • Kryvosheyeva Y.
      • Terras S.
      • et al.
      Association of autoimmune diseases with lichen sclerosus in 532 male and female patients.
      • Meyrick Thomas R.H.
      • Ridley C.M.
      • McGibbon D.H.
      • Black M.M.
      Lichen sclerosus et atrophicus and autoimmunity—a study of 350 women.
      ,
      • Harrington C.I.
      • Dunsmore I.R.
      An investigation into the incidence of auto-immune disorders in patients with lichen sclerosus and atrophicus.
      One comparing 50 patients with LS to 50 control individuals cited an autoimmune disease prevalence of 34% among patients with LS, significantly higher than in control individuals.
      • Harrington C.I.
      • Dunsmore I.R.
      An investigation into the incidence of auto-immune disorders in patients with lichen sclerosus and atrophicus.
      Three smaller studies similarly reported high prevalences of autoimmune disorders comorbid with LS (21%, 28%, and 15.4%, respectively).
      • 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.
      • Kreuter A.
      • Kryvosheyeva Y.
      • Terras S.
      • et al.
      Association of autoimmune diseases with lichen sclerosus in 532 male and female patients.
      • Meyrick Thomas R.H.
      • Ridley C.M.
      • McGibbon D.H.
      • Black M.M.
      Lichen sclerosus et atrophicus and autoimmunity—a study of 350 women.
      The most commonly associated autoimmune diseases across all studies were thyroid diseases.
      • 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.
      • Kreuter A.
      • Kryvosheyeva Y.
      • Terras S.
      • et al.
      Association of autoimmune diseases with lichen sclerosus in 532 male and female patients.
      • Meyrick Thomas R.H.
      • Ridley C.M.
      • McGibbon D.H.
      • Black M.M.
      Lichen sclerosus et atrophicus and autoimmunity—a study of 350 women.
      Although our study found lower comorbid disease prevalences than previous studies, our data support their findings that these conditions affect patients with LS more frequently than control individuals. The reasons for these differences may include our focus on only 3 autoimmune conditions and the fact that women older than 65 years were not represented. Diagnostic coding errors may also pose limitations, given that confirmatory biopsy was performed in only 22.7% of cases.
      Compared to our control population, women with LS were significantly more likely to have all related conditions. Dermatologists should remain aware that patients with LS are more likely to have psoriasis and vitiligo, both of which commonly affect genital skin. This study also highlights evidence for continued screening for vulvar carcinoma in women with LS and suggests that screening for autoimmune thyroid diseases may be indicated as well.
      This project was accomplished through a generous gift from The Louis and Rachel Rudin Foundation, Inc , which supports the research education of residents at New York University Langone Health’s Ronald O. Perelman Department of Dermatology .

      References

        • 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
        • Kreuter A.
        • Kryvosheyeva Y.
        • Terras S.
        • et al.
        Association of autoimmune diseases with lichen sclerosus in 532 male and female patients.
        Acta Derm Venereol. 2013; 93: 238-241
        • Meyrick Thomas R.H.
        • Ridley C.M.
        • McGibbon D.H.
        • Black M.M.
        Lichen sclerosus et atrophicus and autoimmunity—a study of 350 women.
        Br J Dermatol. 1988; 118: 41-46
        • Meani R.
        • Howard A.
        • Veysey E.
        Incidence of vulval squamous cell carcinoma in women with vulval lichen sclerosus in an Australian tertiary referral centre.
        Australas J Dermatol. 2019; 60: 76-77
        • Harrington C.I.
        • Dunsmore I.R.
        An investigation into the incidence of auto-immune disorders in patients with lichen sclerosus and atrophicus.
        Br J Dermatol. 1981; 104: 563-566