Differential proteomic expression profiles in vulvar lichen planus as compared to normal vulvar tissue, vulvar lichen sclerosus, or oral lichen planus: An exploratory study.

Vulvar lichen planus (VLP) is a chronic inflammatory disease which adversely affects patients' quality of life. The pathogenesis of VLP is unknown although Th1 immune response has been implicated. We aimed to discover specific tissue-based protein biomarkers in VLP compared to normal vulvar tissue (NVT), vulvar lichen sclerosus (VLS) and oral lichen planus (OLP). We used laser capture microdissection-liquid chromatography- tandem mass spectrometry to assess protein expression in fixed lesional mucosal specimens from patients with VLP (n = 5). We then compared proteomic profiles against those of NVT (n = 4), VLS (n = 5), OLP (n = 6) and normal oral mucosa (n = 5), previously published by our group. IL16, PTPRC, PTPRCAP, TAP1 and ITGB2 and were significantly overexpressed in VLP compared to NVT. Ingenuity pathway analysis identified antigen presentation and integrin signalling pathways. Proteins overexpressed in both VLP versus NVT and OLP versus NOM included IL16, PTPRC, PTPRCAP, TAP1, HLA-DPB1, HLA-B and HLA-DRA. This proteomic analysis revealed several overexpressed proteins in VLP that relate to Th1 autoimmunity, including IL16. Overlapping pathways, including those involving IFNγ and Th1 signalling, were observed between VLP, VLS, and OLP.

Differential proteomic expression in indolent vulvar lichen sclerosus, transforming vulvar lichen sclerosus and normal vulvar tissue.

Vulvar lichen sclerosus (VLS) confers approximately 3% risk of malignant transformation to vulvar squamous cell carcinoma (VSCC). We used unbiased proteomic methods to identify differentially expressed proteins in tissue of patients with VLS who developed VSCC compared to those who did not. We used laser capture microdissection- and nanoLC-tandem mass spectrometry to assess protein expression in individuals in normal vulvar tissue (NVT, n = 4), indolent VLS (no VSCC after at least 5 years follow-up, n = 5) or transforming VSCC (preceding VSCC, n = 5). Interferon-γ and antigen-presenting pathways are overexpressed in indolent and transforming VLS compared to NVT. There was differential expression of malignancy-related proteins in transforming VLS compared to indolent VLS (CAV1 overexpression, AKAP12 underexpression), particularly in the EIF2 translation pathway, which has been previously implicated in carcinogenesis. Results of this study provide additional molecular evidence supporting the concept that VLS is a risk factor for VSCC and highlights possible future biomarkers and/or therapeutic targets.

Autoimmune progesterone dermatitis: a retrospective case series.

Autoimmune progesterone dermatitis (APD) is a rare hypersensitivity disorder characterized by recurring dermatologic manifestations during the luteal phase of the menstrual cycle in women. Well-defined clinical and diagnostic criteria, outcomes measurements, and standard treatments are lacking. Methods: We performed a single-institution retrospective review of adult patients (older than 20 years at the time of diagnosis) with APD. Results: Fourteen patients were included with mean age of clinical onset of 34.3 ± 7.7 (range 24-54) years. There was a delay of 3.9 ± 5.5 (range 0.4-20) years between the onset of disease symptoms and diagnosis. The onset of APD was after exposure to exogenous progesterone in 9 of 14 patients. Progesterone skin test was performed in 9 patients and 6 were positive. Patients frequently presented with urticaria (9/14, 64.3%) and dermatitis (4/14, 28.6%). Continuous combined oral contraceptives (4/14, 28.6%), gonadotropin-releasing hormone agonist (3/14, 21.4%), and hysterectomy with bilateral salpingo-oophorectomy (2/14, 14.3%) were the most common attempted treatments with reliable outcomes. Conclusions: APD is a rare disorder which lacks universal diagnostic measures and criteria, contributing to a significant delay in diagnosis. Large-scale multicenter studies are needed to develop accurate tests, establish diagnostic criteria, and define treatment outcomes.

Candida Infection Associated with Anti-IL-17 Medication: A Systematic Analysis and Review of the Literature.

Anti-interleukin (IL)-17 agents have shown excellent therapeutic efficacy in patients with psoriasis and are expected to be expanded to other chronic inflammatory diseases. However, patients receiving anti-IL-17 agents are at an increased risk of developing Candida infection, with some agents reported to increase the incidence in a dose-dependent manner. Interleukin-17 is secreted by the Th17 subset of CD4+ lymphocytes, CD8+ T cells, and innate cells, including natural killer T cells, lymphoid tissue inducer cells, innate lymphoid cells, and γδ-T cells, and plays an important role in antifungal defense. Genetic defects in the IL-17-signaling pathway in both humans and animal models render susceptibility to candidiasis caused by Candida albicans. The purpose of this narrative review is to evaluate the literature on the role of IL-17 in protection against candidiasis, the prevalence of candidiasis in anti-IL-17 agent use, and to offer clinical recommendations on the diagnosis and management of anti-IL-17 medication-associated candidiasis.

The spectrum of pediatric scarring alopecia: A retrospective review of 27 patients seen at Mayo Clinic.

BACKGROUND/OBJECTIVE: There are few studies examining pediatric scarring alopecia. The objective of this study is to characterize the clinicopathologic findings, comorbidities, and treatment outcomes of pediatric patients with scarring alopecia. METHODS: Retrospective review of patients under age 18 diagnosed with scarring alopecia at Mayo Clinic from 01/01/1992 through 02/05/2019. RESULTS: 27 patients met inclusion criteria with a mean age of 11.2 years and a racial breakdown of 85.2% (23) White, 11.1% (3) Black, and 3.7% (1) Multiracial. Clinical scarring was noted in most (23, 85.2%). Biopsy confirmed the diagnosis in most (24, 88.9%). The most common diagnoses were folliculitis decalvans (6, 22.2%), lichen planopilaris (6, 22.2%), aplasia cutis congenita (4, 14.8%), tinea capitis (4, 14.8%), and morphea (3, 11.1%). Comorbid depression (6, 22.2%) and anxiety (6, 22.2%) were prevalent. Of the patients who received follow-up, most who pursued treatment achieved stabilization (55.5%) or slowing of progression (27.8%), with 44.4% of those treated experiencing regrowth. Mean time to stabilization in the treated population was 19.6 months. Two patients did not pursue treatment, but received follow-up and these untreated patients did not experience hair regrowth. CONCLUSIONS: Most patients presented with clinically evident primary scarring alopecia. Biopsy may confirm the diagnosis. Active treatment should be pursued, and successful treatment often requires combination therapies. Time to stabilization often takes years. Screening for depression and anxiety should be pursued.

Lichen planopilaris in men: a retrospective clinicopathologic study of 19 patients.

BACKGROUND: Lichen planopilaris (LPP) is a scarring alopecia rarely described in men. OBJECTIVE: To investigate the clinical and histopathologic features of LPP in men. METHODS: We performed a retrospective cohort study of male patients with LPP seen at Mayo Clinic between 1992 and 2016. RESULTS: Nineteen men with biopsy-confirmed LPP were included. The disease most commonly presented with diffuse (42.1%) or vertex scalp (42.1%) involvement. None of the patients had eyebrow or body hair involvement. Perifollicular erythema (94.7%) and pruritus (57.9%) were the most frequent clinical findings. Androgenetic alopecia (AGA) co-occurred in 26.3% of patients. Mucosal lichen planus was found in four patients (21.1%). Thyroid disease occurred in three patients (15.8%). Disease improvement (47.3%) occurred with combination topical and systemic therapy, topical clobetasol monotherapy, and minocycline monotherapy. CONCLUSIONS: LPP in men has similar clinical and histologic presentations as reported in women. Nonscalp hair loss appears less likely in men with classic LPP than reported in men with frontal fibrosing alopecia, while mucosal lichen planus and thyroid disease appear to be more common in classic LPP. Men with AGA can present with new-onset concomitant LPP. Limitations included small study size, variable follow-up, and lack of standardized clinical assessment due the study's retrospective nature.

Lichen Planopilaris in Women: A Retrospective Review of 232 Women Seen at Mayo Clinic From 1992 to 2016.

OBJECTIVE: To characterize the clinicopathologic findings, comorbidities, and treatment outcomes of women with lichen planopilaris (LPP). METHOD: In this retrospective review of women with LPP at Mayo Clinic from 1992 to 2016, we searched for scarring alopecia in all female patients aged 1 to 100 years from January 1, 1992, through December 31, 2016. Men were excluded from this study to more accurately determine the association of hormonal factors in LPP pathogenesis. Two hundred thirty-two patients were included as they met diagnostic criteria for LPP based on clinicopathologic correlation, with 217 having confirmatory biopsies. RESULTS: We identified 232 women with LPP (mean age, 59.8 years). Of those, 92.7% (215) presented with hair loss; 23.7% (55) had preceding inflammation; 30.6% (71) had thyroid disease, including hypothyroidism (23.2%; 54); and 9.4% (22) had vitamin D deficiency. Incidence of depression and anxiety was 45.7% (106) and 41.8% (97), respectively. History of total abdominal hysterectomy/bilateral salpingo-oophorectomies and hormone replacement therapy was found in 16.8% (39) and 16.4% (38), respectively. Lichen planus at other body sites occurred in 16.4% (38) of patients; and 53.2% (123) had slowing of disease progression or disease stabilization, often requiring combination therapies. In those who achieved slowing or stabilization of disease, mean time to recurrence was 1.8 year. The mean time to remission was 1.1 year. CONCLUSION: The typical LPP patient is a 60-year-old female with vertex scarring alopecia who presents with burning, erythema, inflammation, and scale. Almost half of patients will have comorbid autoimmunity. As previously reported, LPP is associated with thyroid disease. We also found higher rates of depression, anxiety, nutritional deficiencies, and skin cancer than reported in the general population.

Lichen planopilaris in women: A survey-based study examining baseline hair characteristics and product use in 129 patients seen at Mayo Clinic.

BACKGROUND: Cicatricial alopecia is a type of permanent hair loss in which the hair follicle is replaced by scar tissue. Given its relatively low incidence, limited information is available regarding baseline hair characteristics, onset, and other disease-associated factors. OBJECTIVE: We sought to further elucidate this information in our lichen planopilaris (LPP) patients. METHODS: Between 1993 and 2016, 505 patients were diagnosed with biopsy-proven LPP. Of these patients, we mailed a 20-question survey to 420 patients with updated mailing address and contact information. Responses were received from 129 of 420 patients for a response rate of 30.7%. A total of 108 patients completed the survey and 21 patients declined participation. Descriptive analysis was performed using JMP software. RESULTS: Median age at time of pathologic diagnosis was 58 years, with self-reported average age of onset accordingly from 50 to 60 years. Approximately 15% of patients were diagnosed with frontal fibrosing alopecia (FFA), a subtype of LPP. Median follow-up from date of pathologic diagnosis was 72 months. At baseline, 46 out of 108 patients (42.6%) endorsed having thicker hair than peers in childhood. No trend was identified in the rate of traction hairstyle use in childhood, current use of cosmetics, sunscreen, or facial cleanser. CONCLUSIONS: Within our LPP cohort, FFA subtype pathology comprised approximately 15% of cases. There was no trend toward sunscreen use and FFA subtype. Our findings support previously published studies in terms of average age at disease onset, location of hair loss, and median follow-up at 72 months (range: 29-273) from date of pathologic diagnosis.

Incidence of squamous cell carcinoma in oral lichen planus: a 25-year population-based study.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory condition of the oral mucosa. Multiple studies have shown that approximately 1% of patients with OLP will develop oral squamous cell carcinoma (OSCC), however, no study has taken a population-based multicenter approach to demonstrate this association. Our main objective was to determine the incidence of OSCC in OLP in a specific population and secondarily to assist physicians regarding appropriate long-term monitoring of patients with OLP. METHODS: We conducted a population-based retrospective cohort study. Patients with OLP from 1986 through 2010 were identified using the Rochester Epidemiology Project (REP) for Olmsted County, Minnesota. For each OLP case (n = 303), we randomly selected two age- and gender-matched referents (n = 606). OLP diagnosis was established based on the World Health Organization (WHO) criteria. Medical records were reviewed for development of OSCCafter the OLP diagnosis (index date). The association between OLP and development of OSCC was assessed. RESULTS: In total, 303 patients with incident OLP were identified; the overall incidence of OLP per 100,000 person-years was 11.4 (95% CI, 10.1-12.7). Among the OLP cohort, 7 had OSCC (incidence of OSCC, 3.1%; 95% CI, 0.6-6.4%) at 20 years after OLP diagnosis. Three OSCC cases were identified among the referents. Patients with OLP were 4.8 times more likely to have OSCC than the matched referents. The median time to OSCC development was 14.7 years earlier for the OLP cohort. CONCLUSIONS: Patients with OLP, particularly the erosive type, have an increased incidence of OSCC development and should be monitored closely.

Frontal Fibrosing Alopecia in Women: The Mayo Clinic Experience With 148 Patients, 1992-2016.

OBJECTIVE: To characterize the clinicopathologic findings, comorbidities, and treatment outcomes of women with frontal fibrosing alopecia. PATIENTS AND METHODS: Retrospective review of women with frontal fibrosing alopecia at Mayo Clinic from January 1, 1992, to February 22, 2016. The terms "scarring alopecia," "lichen," "planopilaris," "fibrosing," and "alopecia" were used for the search of female patients aged 1 to 100 years. A total of 686 patients were reviewed to confirm the diagnosis of frontal fibrosing alopecia. Patients were included if they met diagnostic criteria. RESULTS: A total of 148 women with frontal fibrosing alopecia were identified, with a mean age of 62 years; 60.1% presented with eyebrow loss; 67.6% and 27.7% described preceding or concurrent pruritus and trichodynia, respectively; 44.6% had a history of hypothyroidism; 13% had a history of surgical menopause; and 63.3% had a history of hormone replacement therapy. A total of 18.2% had lichen planus at other body sites, and 26.3% achieved disease stabilization, often requiring combination therapies. The mean time to remission was 1.8 years. CONCLUSION: Patients with frontal fibrosing alopecia typically present with frontotemporal and eyebrow alopecia with preceding symptoms. Hypothyroidism and a history of hysterectomy may be more common than previously reported. Time to presentation, diagnosis, and stabilization is often months to years. Patients who lack treatment response may present with eyebrow loss, eyelash loss, and facial papules. Combination therapy is helpful in achieving slowing of disease progression or disease stabilization, although recurrence is common. Additional studies on treatment and efficacy are needed. Limitations to this study include the retrospective design and varied follow-up.

Lichen planus affecting the female genitalia: A retrospective review of patients at Mayo Clinic.

BACKGROUND: Genital or vulval lichen planus (VLP) may have a disabling effect on a patient's quality of life. Evidence-based management guidelines are lacking for VLP. OBJECTIVE: We sought to review clinical presentation and treatment of patients who received a diagnosis of VLP. METHODS: The 100 consecutive patients who received a diagnosis of VLP at Mayo Clinic between January 1, 1997, and December 31, 2015, were reviewed retrospectively. Descriptive statistics were used for data analysis. Fisher's exact test and the Wilcoxon rank sum test were used for analysis of categorical and continuous variables, respectively. All statistical tests were 2 sided, with the α level set at .05 for statistical significance. RESULTS: The time to diagnosis for 49% of patients was more than 1 year. Three patients (3%) had vulval dysplasia, including invasive squamous cell carcinoma. Sixty-eight patients (68%) had multisite lichen planus disease. Eleven patients (11%) had disease remission. Dermatology was the lead specialty for 9 of these cases of remission. LIMITATIONS: This was a retrospective, small-cohort study. CONCLUSION: A low frequency of disease remission was seen in patients with VLP. Patients with lichen planus benefit considerably from dermatology consultation. Further research is warranted to establish high-quality, evidence-based guidelines for multidisciplinary management of this challenging disease.

Final Diagnosis of 112 Girls Presenting With Genital Mucocutaneous Symptoms and Signs: The Mayo Clinic Experience.

Pediatric genital mucocutaneous diseases are rare. A retrospective review was performed of children presenting with symptomatology of genital dermatoses to a hospital-based dermatology service. This study highlights that the range of genital diseases in children is not as broad as in adults. The diagnosis of genital mucocutaneous disease in children is usually genital lichen sclerosus, but other diagnoses should be considered.

Frontal fibrosing alopecia among men: A clinicopathologic study of 7 cases.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a lichen planopilaris-variant scarring alopecia that has rarely been described in men. OBJECTIVE: To characterize the clinicopathologic findings of FFA in men by studying a series of 7 male patients. METHODS: We conducted a retrospective review of all cases of male patients with FFA at the Mayo Clinic from 1992 to 2016. RESULTS: Seven male patients with FFA were identified. The frontal scalp (in 6 of 7 patients), sideburns (in 4 of 7), and temporal scalp (in 4 of 7) were most frequently involved. Three patients had involvement of the eyebrows. One patient had hair loss of the upper cutaneous lip. All patients had biopsy evidence of lichen planopilaris. None of the patients had associated autoimmune or thyroid disease. Two patients had hypogonadism upon testosterone studies. LIMITATIONS: Limitations include small sample size and varied follow-up. CONCLUSIONS: Although most often reported among postmenopausal women, FFA also occurs among men. The clinical and histopathologic characteristics of FFA in men parallel those described in women with FFA. Unique areas of involvement in men include sideburns and facial hair. Concomitant mucocutaneous lichen planus, autoimmune disease, and thyroid disease are infrequent among men with FFA. Distribution of hair loss and associated hormonal abnormalities aid in the recognition of FFA in men.