Population-level retrospective study associating lichen sclerosus with autoimmune dermatologic and rheumatologic conditions

To the Editor:

Lichen sclerosus (LS) is a chronic inflammatory dermatosis that commonly involves the anogenital region in women and is speculated to have an autoimmune pathogenesis.^1–3 Previous studies have reported an association with human leukocyte antigen constellations, and LS has been linked to several other autoimmune diseases, including thyroid disease, morphea, psoriasis, and primary biliary cirrhosis.^1–5 Herein, we performed a population-level retrospective study to evaluate the association between LS and other autoimmune conditions.

We retrospectively identified our cohort using TriNetX, a global health research network. Within TriNetX, the United States Collaborative Network incorporates data from 60 health care organizations with over 104 million patients. Data were extracted in December 2023. International Classification of Diseases-10 (ICD-10) code L90.0, lichen sclerosus et atrophicus, was used to identify cases. Though ICD-10 codes cannot differentiate between genital and extragenital LS, LS most frequently affects the vulva. Therefore, ICD-10 code N95, postmenopausal atrophic vaginitis, was used to identify the control cohort, as this is a common vulvar diagnosis without a known autoimmune disease association. Diagnoses prior to the use of ICD-10 codes were mapped using General Equivalence Mappings. Only female patients were included. Patients with a diagnosis of LS were excluded from the control cohort. Cohorts were matched by age and race/ethnicity, resulting in a 1:1 propensity score. Patients diagnosed with an autoimmune condition following LS diagnosis were then identified. Odds ratios and 95% confidence intervals were used to identify associations.

The LS cohort consisted of 83,103 patients with an equal number of matched controls (Table I). Patients with LS had increased odds of the following autoimmune conditions: morphea, systemic sclerosis, lichen planus, vitiligo, other local lupus erythematosus, alopecia areata, primary biliary cirrhosis, systemic lupus erythematosus, discoid lupus erythematosus, psoriasis, autoimmune thyroiditis, psoriatic arthritis, type 1 diabetes, Sjogren’s syndrome, celiac disease, Crohn’s disease, and other rheumatoid arthritis. Patients with LS were found to have a decreased odds of myasthenia gravis (MG) and multiple sclerosis (MS) compared to controls (Table II).

Table I.

Patient demographics for lichen sclerosus and control cohorts after propensity score matching

Characteristic	No. (%) Lichen sclerosus (n = 83,103)	No. (%) Control (n = 83,103)
Age, mean (SD)	66.0 (15.9)	66.3 (15.3)
Not Hispanic or Latino	61,605 (74.130)	62,177 (74.819)
Unknown ethnicity	17,149 (20.636)	17,124 (20.606)
Hispanic or Latino	4350 (5.234)	3802 (4.575)
White	66,121 (79.565)	66,982 (80.601)
Unknown race	7719 (9.288)	7431 (8.942)
Black or African American	4865 (5.854)	4490 (5.403)
Asian	1335 (1.606)	1178 (1.418)
American Indian or Alaska Native	227 (0.273)	210 (0.253)
Native Hawaiian or Other Pacific Islander	89 (0.107)	81 (0.097)

Table II.

Odds ratios for diagnosis of select autoimmune conditions in lichen sclerosus compared to control cohort, following lichen sclerosus diagnosis (index event)

	ICD-10 code	Odds ratio	95% confidence interval	P value
Conditions with increased odds
Morphea	L94.0	395.988	307.912–509.259	<.0001
Systemic sclerosis	M34	10.371	9.142–11.765	<.0001
Lichen planus	L43	4.112	3.776–4.479	<.0001
Vitiligo	L80	3.391	2.993–3.842	<.0001
Other local lupus erythematosus	L93.2	2.403	1.966–2.935	<.0001
Alopecia areata	L63	2.136	1.799–2.536	<.0001
Primary biliary cirrhosis	K74.3	1.891	1.533–2.332	<.0001
Systemic lupus erythematosus	M32	1.628	1.497–1.770	<.0001
Discoid lupus erythematosus	L93.0	1.623	1.438–1.831	<.0001
Psoriasis	L40	1.525	1.442–1.612	<.0001
Autoimmune thyroiditis	E06.3	1.273	1.191–1.362	<.0001
Psoriatic arthritis	L40.5	1.262	1.117–1.426	.0002
Type 1 diabetes	E10.9	1.159	1.057–1.271	.0017
Sjogren's syndrome	M35.0	1.139	1.069–1.213	<.0001
Celiac disease	K90.0	1.133	1.022–1.255	.0174
Crohn's disease	K50	1.111	1.006–1.227	.0378
Other rheumatoid arthritis	M06	1.072	1.018–1.128	.0080
Conditions with decreased odds
Multiple sclerosis	G35	0.776	0.694–0.863	<.0001
Myasthenia gravis	G70	0.813	0.727–0.909	.0003
Conditions with no association
Reactive arthritis	M02.9	1.500	0.674–3.339	.3173
Subacute cutaneous lupus erythematosus	L93.1	1.441	0.931–2.233	.0996
Rheumatoid arthritis	M06.9	1.039	0.982–1.099	.1871
Vitamin D deficiency	E55	0.995	0.972–1.019	.6867
Ulcerative colitis	K51	0.974	0.888–1.069	.5850

ICD-10, International Classification of Diseases-10.

These findings support the association between LS and other autoimmune diseases, confirming previously known disease associations and identifying additional associations. We therefore encourage clinicians to consider assessing for other autoimmune conditions in individuals with LS who have other inflammatory cutaneous, gastrointestinal, or joint symptoms. Interestingly, LS had a negative association with MG and MS. Though the rationale for this is unclear, both MG and MS are autoimmune neurologic conditions without specific connective tissue disease manifestations.

Limitations of this study include the retrospective nature of data collection, the utilization of ICD-10 codes, resulting in possible diagnosis misclassification, and inclusion of both anogenital and extragenital LS which may have different disease comorbidities. Additionally, patients with conditions such as morphea, lichen planus, or vitiligo could have been misdiagnosed with LS initially, since these conditions have overlapping clinical features.

Overall, our study found LS is associated with multiple autoimmune diseases, both systemic and cutaneous. This suggests LS may be part of a more systemic/complex autoimmune process or other linking factors such as genetics could put these patients at an increased risk.