Prevalence and incidence of comorbid diseases and mortality risk associated with lichen planopilaris: a Korean nationwide population-based study.

BACKGROUND: Various comorbid diseases have been reported in patients with lichen planopilaris (LPP); however, data regarding the risks of incident diseases and mortality are lacking. OBJECTIVES: To investigate the risks of incident diseases and mortality associated with LPP. METHODS: This was a retrospective nationwide population-based study, using data from the National Health Insurance Service Database of Korea from 2002 to 2019. Patients aged ≥ 18 years with three or more documented medical visits for LPP were included. The adjusted hazard ratios (aHRs) for incident disease outcomes and mortality were compared with 1 : 20 age-, sex-, insurance type- and income-level-matched controls. RESULTS: In total, 2026 patients with LPP and 40 520 controls were analysed. The risks of incident systemic lupus erythematosus [aHR 1.91, 95% confidence interval (CI) 1.21-3.03], psoriasis (aHR 3.42, 95% CI 2.83-4.14), rheumatoid arthritis (aHR 1.39, 95% CI 1.19-1.63), lichen planus (aHR, 10.07, 95% CI 7.17-14.15), atopic dermatitis (aHR 2.15, 95% CI 1.90-2.44), allergic rhinitis (aHR 1.29, 95% CI 1.13-1.49), thyroid diseases (hyperthyroidism: aHR 1.42, 95% CI 1.14-1.77, hypothyroidism aHR 1.19 95% CI 1.01-1.41, and thyroiditis: aHR, 1.35, 95% CI 1.08-1.69), nonmelanoma skin cancer (aHR 2.33, 95% CI 1.00-5.44) and vitamin D deficiency (aHR 1.23, 95% CI 1.03-1.47) were higher in patients with LPP. Patients with LPP had a higher mortality rate than controls (aHR 1.30, 95% CI 1.04-1.61), although the risk was not significant after adjusting for comorbidities (aHR 1.08, 95% CI 0.87-1.34). CONCLUSIONS: Patients with LPP had a higher risk of various diseases following LPP diagnosis. Close follow-up is needed to optimize comprehensive patient care.

Oral lichen planus in children: An Italian case series.

Oral lichen planus usually occurs in adults; there are no clear data regarding the incidence and the clinical features of oral lichen planus in children. This paper reports clinical findings, treatments, and outcomes of 13 Italian patients with oral lichen planus in childhood diagnosed between 2001 and 2021. The most common finding was keratotic lesions with reticular or papular/plaque-like patterns, confined to the tongue in seven patients. Although oral lichen planus in childhood is rare and the malignant transformation index is unknown, specialists must be aware of its characteristics and oral mucosal lesions must be correctly diagnosed and managed.

Lichen planus in Germany - epidemiology, treatment, and comorbidity. A retrospective claims data analysis.

BACKGROUND AND OBJECTIVES: Lichen planus (LP) is a chronic inflammatory skin disease and is a major burden for affected patients. However, data on this condition are scarce. This study aims to expand the knowledge on the epidemiology and treatment patterns of LP using German health claims data. PATIENTS AND METHODS: This retrospective observational study was based on the InGef research database. Prevalent and incident LP patients were identified in the years 2015 and 2018. Descriptive statistics were calculated for demographic characteristics, treatment patterns, and comorbidity. RESULTS: The prevalence of LP was 95.9 and the incidence was 20.1 per 100,000 individuals in 2018, corresponding to 79,605 prevalent LP cases in Germany. The first LP diagnosis was generally documented by a dermatologist or a primary care physician. Three-quarters of the incident and half of the prevalent patients received topical therapy, mostly without further systemic therapy. Comorbidity in LP patients was consistent with previously known associations. CONCLUSIONS: Available treatment options remain limited, underscoring the unmet need for safe and efficacious systemic treatment modalities. Lichen planus is frequently accompanied by clinically relevant systemic comorbidity. Taken together, these observations may improve our understanding of the burden of this disease and increase diagnostic awareness among clinicians.

Long-term impact of certain coexisting extrahepatic unisystem and multisystem manifestations on trends in incidence of liver cirrhosis in treatment-naïve patients with chronic hepatitis C: A nested case-control study.

Diabetes mellitus (DM) was found to be more common in hepatitis C virus (HCV)-related cirrhotic males. However, the association between DM, or other extrahepatic manifestations (EHMs), and liver cirrhosis is still undetermined. We used a large-scale long-term study to analyze the cirrhosis risk of treatment-naïve HCV patients with EHMs as compared to those without. In this retrospective nested case-control study, we identified 11 872 treatment-naïve patients with chronic HCV between 2001 and 2013 from Taiwan National Health Insurance Research Database and divided them into patients with (cases) and without cirrhosis (controls). All patients were followed up from the index month (exact month of diagnosis) to the end of 2013, death, or study outcome, whichever occurred first. The cases and controls were 1:6 propensity score matched for age, sex, and exact month of diagnosis; finally, 8078 patients (1154 with and 6924 without cirrhosis) were included in the analysis. The presence of coexisting EHMs and a new diagnosis of cirrhosis was analyzed. Adjusted hazard ratios (HRs) and cumulative incidence for cirrhosis were calculated in conditional Cox regression models after propensity score matching. Patients with high-cirrhosis-risk EHMs, such as DM (HR: 1.72, 95% CI: 1.51-1.96, P < .001), HCD (HR: 1.45, 95% CI: 1.27-1.67, P < .007), CKD (HR: 1.21, 95% CI: 1.05-1.38, P < .001), hyperlipidemia (HR: 0.53, 95% CI: 0.46-0.60, P < .001), lichen planus (HR: 2.71, 95% CI: 1.56-4.72, P < .001), and palpable purpura (HR: 2.67, 95% CI: 2.13-3.35, P < .001) exhibited significantly higher risk of liver cirrhosis than those without. Cumulative incidence (P < .001) of liver cirrhosis by pairwise comparisons of multiple high-cirrhosis-risk EHMs, and that of lichen planus was the highest. Our study provided direct estimates of specific HCV-associated EHM time trends of cirrhosis risk, with an upward trend in incidence. Lichen planus was at the top of the list of single-EHM comparisons, and the maximum combination of certain EHMs was the greatest risk factor across a different array of multi-EHM comparisons for liver cirrhosis development.

Comorbidities in lichen planus by phenome-wide association study in two biobank population cohorts.

BACKGROUND: Lichen planus (LP) is a relatively frequent mucocutaneous inflammatory disease affecting the skin, skin appendages and mucosae, including oral mucosae, and less frequently the anogenital area, conjunctivae, oesophagus or larynx. OBJECTIVES: To estimate the association of LP, with emphasis on dermatological and gastrointestinal conditions, in two large independent population cohorts. MATERIALS AND METHODS: We performed a phenome-wide association study (PheWAS) and examined conditions associated with LP in two unrelated cohorts, i.e. the multicentre, community-based UK Biobank (UKB: 501 381 controls; 1130 LP subjects) and the healthcare-associated Penn Medicine BioBank (PMBB; 42 702 controls; 764 LP subjects). The data were analysed in 2021. The 'PheWAS' R package was used to perform the PheWAS analyses and Bonferroni correction was used to adjust for multiple testing. Odds ratios (ORs) were adjusted for age, sex and body mass index. RESULTS: In the UKB, PheWAS revealed 133 phenome codes (PheCodes) significantly associated with LP and most of them were confirmed in PMBB. Dermatological and digestive PheCodes were the most abundant: 29 and 34 of these disorders, respectively, were significantly overrepresented in LP individuals from both cohorts. The 29 dermatological and 12 oral disorders were often highly enriched, whereas hepatic, gastric, oesophageal and intestinal PheCodes displayed ORs in the range of 1·6-4·5. Several autoimmune disorders also exhibited OR > 5 in both cohorts. CONCLUSIONS: PheWAS in two large unrelated cohorts identified previously unknown comorbidities and may support clinical counselling of patients with LP. What is already known about this topic? Lichen planus (LP) is known to affect the skin, skin appendages and mucosae, including oral mucosae, and less frequently the anogenital area, conjunctivae, oesophagus or larynx. What does this study add? Our data provide the most comprehensive collection of associated dermatological, digestive and autoimmune disorders to date. Our findings are expected to be useful for the evaluation and management of patients with LP.

High Incidence of Metabolic Syndrome Components in Lichen Planus Patients: A Prospective Cross-Sectional Study.

Background: Lichen planus (LP) is a chronic inflammatory dermatosis, involving the skin, appendages, and mucous membranes. There is a growing body of evidence about higher risk of metabolic syndrome and dyslipidemia in some dermatoses including LP. Aim: To evaluate lipid profile, leptin, and CRP status among Iranian LP patients, compared to healthy controls, and peruse the relationship between abnormal values of these parameters with the disease duration and physical characteristics of patients. Methods: 40 LP patients and 40 age- and sex-matched healthy controls were enrolled in the study. Data on weight, height, lipid profile, leptin, and CRP values were recorded and compared. Results: The mean values for leptin, CRP, and lipid profile parameters (except for HDL) were higher in patients, compared to controls. Total cholesterol level was negatively associated with disease duration in patients (P value: 0.039, r: -0.33). Serum leptin level was positively correlated with BMI both in patients and controls (P value: 0.037 and 0.003, respectively). In the patient group, LDL level, although insignificant, was higher in men, but HDL and leptin levels were significantly higher in women in comparison with men (P value: 0.018). Conclusion: Screening of LP patients in regard to their lipid profile might be more reasonable in men or those who have other cardiovascular risk factors to prevent morbidity and mortality in result of developing cardiovascular events.

Risk of Development of Vulvar Cancer in Women With Lichen Sclerosus or Lichen Planus: A Systematic Review.

OBJECTIVE: Vulvar lichen sclerosus (VLS) and possibly vulvar lichen planus (VLP) are associated with an increased vulvar cancer (VC) risk. We analyzed the risk of VC and its precursors after a diagnosis of VLS or VLP. MATERIALS AND METHODS: A search was performed to identify articles describing the development of vulvar neoplasia in women with VLS or VLP. This systematic review was registered with the PROSPERO database. RESULTS: Fourteen studies on VLS included 14,030 women without a history of vulvar neoplasia. Vulvar cancer, differentiated vulvar intraepithelial neoplasia (dVIN), and vulvar high-grade squamous intraepithelial lesion occurred in 2.2% (314/14,030), 1.2% (50/4,175), and 0.4% (2/460), respectively. Considering women with previous or current VC, the rate was 4.0% (580/14,372). In one study, dVIN preceded VC in 52.0% of the cases. Progression of dVIN to VC was 18.1% (2/11).The risk was significantly higher in the first 1-3 years after a biopsy of VLS and with advancing age; it significantly decreased with ultrapotent topical steroid use.For the 14,268 women with VLP (8 studies), the rates of VC, dVIN, and vulvar high-grade squamous intraepithelial lesion were 0.3% (38/14,268), 2.5% (17/689), and 1.4% (10/711), respectively. CONCLUSIONS: Vulvar lichen sclerosus is associated with an increased risk of VC, especially in the presence of dVIN and with advancing age. Ultrapotent topical steroids seem to reduce this risk. An increased risk of developing VC has been suggested for VLP. Hence, treatment and regular life-long follow-up should be offered to women with VLS or VLP.

Risk of anxiety and depression in patients with lichen planus: A nationwide population-based study.

BACKGROUND: This study aims to determine the risk of developing anxiety and/or depression among patients with lichen planus. METHODS: Based on the Longitudinal Health Insurance Database of Taiwan National Health Insurance Research Database, a total of 4012 patients with lichen planus and 16,048 matched controls (1:4) were enrolled between January 1, 2000, and December 31, 2015. After controlling for the risk variables, multivariate Cox proportional hazard regression and the log-rank test with Kaplan-Meier method were performed to assess the influence of anxiety/depression among individuals with lichen planus under a maximum follow-up period of 16 years. RESULTS: The subsequent anxiety or depression incidence of the lichen planus group and the comparisons was 19.67% (1962.70 per 105 person-years) and 10.11% (982.23 per 105person-years), respectively. Additionally, after adjustment of the risk variables, the hazard ratios for anxiety, depression, anxiety without depression, depression without anxiety, anxiety or depression, and both anxiety and depression combined were 1.779 (95%CI: 1.289-2.477, p < 0.001), 2.010 (95%CI: 1.454-2.790, p < 0.001), 2.015 (95%CI: 1.463-2.799, p < 0.001), 2.356 (95%CI: 1.705-3.286, p < 0.001), 2.011 (95%CI: 1.457-2.793, p < 0.001), and 1.515 (95%CI: 1.100-2.134, p < 0.001), respectively. LIMITATIONS: Individuals with lichen planus were unable to be classified into oral subtype and cutaneous subtype based on the ICD-9-CM. Moreover, the results of our study could not demonstrate the mechanism between lichen planus and anxiety and/or depression. CONCLUSION: Patients with lichen planus was positively associated with developing anxiety or depression. Physicians should to be aware of the signs of anxiety and/or depression while facing the patients with lichen planus during the clinical practices.

Risk of Lichen Sclerosus and Lichen Planus in Patients Receiving Immune Checkpoint Inhibitors.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are recommended for various types of cancer. On the other hand, these ICIs may cause immune-related adverse events (irAEs). Lichen sclerosus (LS) and lichen planus (LP) are two distinct phenotypes of irAEs that occur in a subset of patients treated with ICIs. These adverse effects have a detrimental effect on the patient's quality of life and treatment phases; however, the clinical evaluation and assessment of LS and LP remain uncertain. This study aims to assess and evaluate the risk of LS and LP associated with the use of ICIs via a systematic review of the literature and the USA FDA Adverse Events FAERS database. METHOD: The study searched electronic databases such as PubMed, Medline, Cochrane, and Google Scholar for case reports on immune-checkpoint-inhibitor-associated lichen sclerosus and lichen planus published in English between inception and 31 December 2021. The FDA's adverse event reporting system (FAERS) database was also analyzed. RESULTS: Thirty-eight case reports and two retrospective studies with a total of 101 patients, in addition to the FAERS data, were evaluated. More cases involved lichen planus (78.9%) than lichen sclerosis (21%). Nivolumab and pembrolizumab were most frequently reported with LS and LP, among other ICIs. Thirty-six out of thirty-eight patients with LS or LP experienced complete remission, while two patients experienced partial remission. Most of the cases had an excellent response to corticosteroids (92.1%), while the remainder had moderate (5.2%) and poor (2.6%) responses. Additionally, the reporting odds ratio (ROR) of the FAERS database indicated a favorable association for ICIs, the risk of LP, and LS. A stronger association was uniquely found between nivolumab and pembrolizumab. CONCLUSION: There have been published case reports for these adverse events. Healthcare providers should be aware of the possibility of lichen sclerosis and lichen planus developing in patients receiving ICIs which could necessitate hospitalization or discontinuation. Regulatory agencies are advised to monitor the risks as a potential safety signal.

Risk of Vulvar Squamous Cell Carcinoma in Lichen Sclerosus and Lichen Planus: A Systematic Review.

OBJECTIVES: The objectives of this study were to determine: 1) the prevalence of lichen sclerosus (LS) and lichen planus (LP) present in association with vulvar squamous cell carcinoma (VSCC), and 2) the incidence and absolute risk of developing VSCC in LS and LP. METHODS: A search was performed of MEDLINE, EMBASE and CINAHL databases. Three independent reviewers screened articles published before September 1, 2020, first on title/abstract and then on the full text. Women with a history of VSCC, human papillomavirus, smoking, or autoimmune disease were excluded. Newcastle-Ottawa observational study scales were used to assess the risk of bias and methodological quality of the included studies. Of the 3132 studies assessed, 31 were selected for analysis. Due to study heterogeneity, a qualitative synthesis was conducted. RESULTS: The prevalence of LS and LP in association with VSCC ranged from 0% (95% CI 0-5) to 83% (95% CI 36-100) and 1% (95% CI 0-7) to 33% (95% CI 4-78), respectively. The incidence of VSCC ranged from 1.16 (95% CI 0.03-6.44) to 13.67 (95% CI 5.50-28.17) per 1000 person-years for LS. The absolute risk of developing VSCC in patients ranged from 0.0% (95% CI 0.0-5.52) to 21.88% (95% CI 9.28-39.97) with LS and was 1.16% (95% CI 0.1-4.1) with LP. Incidence was not calculable for LP owing to study characteristics. CONCLUSIONS: This review provides evidence that there is an increased risk of developing VSCC in women with LS, while associations with LP are less clear. Early identification, treatment, and long-term follow-up are essential to prevent potential malignant progression of these vulvar dermatoses.

Distinctive age distribution and hair loss pattern putatively highlighting uniqueness of Japanese cases of fibrosing alopecia in a pattern distribution.

Fibrosing alopecia in a pattern distribution (FAPD) is a unique entity which presents clinicopathological characteristics of both male/female pattern androgenetic alopecia (AGA) and lichen planopilaris (LPP). This entity was first reported in 2000 and its criteria was recently proposed. Etiopathogenesis of FAPD has been speculated to be immunological destruction involving miniaturized hair follicles but still remains elusive. To date, few Asian FAPD cases have been reported in the literature. In this study, Japanese FAPD cases were identified based on the aforementioned criteria and analyzed to delineate clinicopathological characteristics. By retrospectively revisiting medical records and clinical photographs, 24 Japanese cases comprising 17 women and seven men were diagnosed as FAPD. All male patients had disease onset by their early 30s, whereas most female patients had developed the condition in middle age or later. Their initial diagnoses prior to the diagnostic confirmation of FAPD were mostly LPP. Based on the clinical phenotypes, the cases were categorized into AGA and LPP types. These subtypes were characterized by foremost trichoscopic and histopathological findings of AGA or LPP, respectively. Unlike previously reported cases, our patients tended to manifest hair loss in both vertex and frontal to mid-scalp with minimal regression of anterior hairline, manifesting unique "parachute" pattern, which has been reported as a representative characteristic of East Asian AGA in the literature. Anti-inflammatory therapies seemed to be effective to deter hair loss but insufficient to achieve improvement. Further accumulation of the cases is necessary; however, these findings may provide additional pathophysiological insights into FAPD and highlight uniqueness of the etiology and clinical phenotype of Japanese FAPD putatively influenced by racial predispositions.