Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism.

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are lymphocytic scarring alopecias affecting primarily the scalp. Although both diseases may share some clinical and histopathological features, in the last decade, FFA has become an "epidemic" particularly in Europe, North and South America with unique clinical manifestations compared to LPP, thus, raising the idea that this disease may have a different pathogenesis. Symptoms such as scalp burning, pruritus or pain are usually present in both diseases, suggesting a possible role for nerves and neuropeptides in the pathogenesis of both diseases. Based on some previous studies, neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), have been associated with lipid metabolism and many chronic inflammatory disorders. In this study, we asked if these neuropeptides are associated with LPP and FFA scalp lesions. Alteration in the expression of SP and CGRP in affected and unaffected scalp skin from patients with both diseases was found with examination of sections using immunohistochemical techniques and confocal microscopy. We then quantitatively assessed and compared SP and CGRP expression from control, LPP and FFA scalp biopsies. Although LPP and FFA share similar histopathologic findings, opposite results were found in affected and unaffected scalp in the ELISA tests, suggesting that these diseases may have different pathogenic mechanisms. We also found presence of histopathological inflammation irrespective of evident clinical lesions, which raises the possibility that both diseases may be more generalized processes affecting the scalp.

PPAR-γ signalling as a key mediator of human hair follicle physiology and pathology.

Peroxisome proliferator-activated receptors (PPARs) are abundantly expressed in human skin, with PPAR-γ being the most intensively investigated isoform. In various ex vivo and in vivo models, PPAR-γ-mediated signalling has recently surfaced as an essential element of hair follicle (HF) development, growth and stem cell biology. Moreover, the availability of novel, topically applicable PPAR-γ modulators with a favourable toxicological profile has extended the range of potential applications in clinical dermatology. In this review, we synthesize where this field currently stands and sketch promising future research avenues, focussing on the role of PPAR-γ-mediated signalling in the biology and pathology of human scalp HFs, with special emphasis on scarring alopecias such as lichen planopilaris and frontal fibrosing alopecia as model human epithelial stem cell diseases. In particular, we discuss whether and how pharmacological modulation of PPAR-γ signalling may be employed for the management of hair growth disorders, for example, in scarring alopecia (by reducing HF inflammation as well as by promoting the survival and suppressing pathological epithelial-mesenchymal transition of keratin 15 + epithelial stem cells in the bulge) and in hirsutism/hypertrichosis (by promoting catagen development). Moreover, we explore the potential role of PPAR-γ in androgenetic alopecia, HF energy metabolism and HF ageing, and consider clinical perspectives that emanate from the limited data available on this so far. As this field of translational human hair research is still in its infancy, many open questions exist, for which we briefly delineate selected experimental approaches that promise to generate instructive answers in the near future.

Intraoperative onychoscopy and histopathological correlation of red lunula in nail lichen planus: a case series.

The lunula is the white half-moon-shaped area located at the base of the fingernails and toenails, and is the only visible part of nail matrix. Red lunula can present as a complete form (the whole lunula is red), incomplete form (only the proximal lunula is red) or mottled form. Red lunula has been associated with a number of dermatological and systemic conditions. It is one of the less common manifestations of nail lichen planus (LP). However, the pathogenesis of the red lunula is not yet clear. We present a series of six patients with nail LP presenting with red lunula, and describe the findings of intraoperative onychoscopy and histopathology in an attempt to understand the pathogenesis underlying the condition.

The importance of topical steroids after adhesiolysis in erosive lichen planus and graft versus host disease.

The aim of this study was to assess the efficacy of a postoperative steroid regimen in maintaining vulvovaginal architecture and vaginal patency following surgical adhesiolysis in severe erosive lichen planus (ELP) and genital graft versus host disease (GVHD). Sixteen women applied potent topical steroids to the vulva and vagina from 48 hours after surgery. Sexual and urinary function and vulvovaginal anatomy were assessed at 6 weeks, 6, 12 and 24 months. All of the patients had failed sexual function due to vaginal stenosis. Eleven patients were unable to have cervical smears and three had associated haematocolpos. Vaginal adhesiolysis achieving complete patency occurred in all patients with stenosis. Fifteen (93.7%) patients were compliant with the regimen. After two years, 12 (75%) patients had maintained complete vaginal patency. Four patients (25%) developed vaginal restenosis. This study demonstrates that the potent topical steroids used post-operatively are very effective in maintaining vaginal patency and function. Impact statement What is already known on this subject? Potent topical steroids are the first line treatment for ELP and GVHD and have been reported to be helpful after surgery to release adhesions. What do the results of this study add? Topical steroids used immediately after surgical adhesiolysis in patients with vulvo-vaginal lichen planus and graft-versus-host disease improves the outcomes and maintains function, which can give a prolonged benefit. What are the implications of these findings for clinical practice and/or further research? The use of potent topical steroids should be considered as routine practice after surgery in erosive inflammatory disease to control inflammation and improve the long term outcomes for these patients.

Plasmacytoid Dendritic Cells and Type I Interferon Signature in Lichen Striatus.

BACKGROUND/OBJECTIVES: In addition to several infectious and neoplastic cutaneous entities, plasmacytoid dendritic cells (pDCs) have been shown to be involved in the pathogenesis of multiple cutaneous inflammatory and autoimmune disorders, including those characterized histologically by an "interface dermatitis" pattern such as lupus or lichen planus (LP), but their role in lichen striatus (LS), which is also known to have this histologic inflammatory pattern, has never been studied. The objective of the study was to investigate the role of pDCs in LS. METHODS: Fifteen LS patients were found in our database and were immunohistochemically tested for pDC occurrence and activity using anti-blood-derived dendritic cell antigen-2 and anti-myxovirus resistance protein A (MxA) antibodies, respectively. These individuals were also compared with 15 individuals with LP. RESULTS: pDCs were present in all individuals with LS and LP, but they were less abundant in those with LS, although MxA (surrogate marker of local type I interferon production and thus an indirect assessment of pDC activity) was similarly intense and diffuse in all individuals with LS and LP. In addition to being part of the upper dermal inflammatory bandlike infiltrate as in LP, LS cases, unlike LP, also showed perieccrine pDCs. CONCLUSIONS: pDCs constitute a central component of the inflammatory infiltrate in LS, suggesting a significant role in its pathogenesis. pDC distribution (perieccrine distribution) could also help in microscopically differentiating LS from LP.

Facial lesions in frontal fibrosing alopecia (FFA): Clinicopathological features in a series of 12 cases.

BACKGROUND: Facial lesions in frontal fibrosing alopecia (FFA) have been poorly described in published series. OBJECTIVE: We sought to describe facial lesions in FFA. METHODS: We reviewed our series of 55 cases of FFA, selecting 12 cases with clinically significant facial lesions. We performed a histologic study of these lesions. RESULTS: In addition to the observations already described in the literature such as facial papules or follicular red dots, we observed perifollicular and diffuse erythema, sometimes with a reticular pattern, and the gradual appearance of pigmented macules on facial skin. Biopsy specimens from the areas with facial erythema showed perifollicular and interfollicular lymphocytic infiltrate and fibrosis around vellus hair follicles. Histologic evaluation of pigmented macules sometimes exhibited an increased epidermal pigmentation and on occasions, pigmentary incontinence. LIMITATIONS: More patients are needed to determine the prevalence of these lesions in FFA. CONCLUSION: On facial skin of patients with FFA, we can observe papules or perifollicular erythema secondary to vellus hair follicle involvement. We describe diffuse erythema, owing to follicular and interfollicular lichenoid infiltrate, and the gradual appearance of pigmented macules, which could be secondary to an increased epidermal pigmentation or to pigmentary incontinence.

[Not Available]. / Síndrome de Graham-Little-Piccardi-Lassueur: variante disseminada de líquen plano folicular.

Graham-Little-Piccardi-Lassueur syndrome is a rare lichenoid dermatosis. It is characterized by the triad of scarring alopecia of the scalp, alopecia of the axilla and or groin, and keratotic follicular papules of the body. The present paper reports on two cases affecting young women. Histopathological findings suggest the disorder represents a generalized form of lichen planus follicularis.

Vulvar Dermatoses: A Review and Update.

The purpose of this article is to review six important inflammatory dermatoses of the vulva and to update readers on the new advancements in treatment of these mucosal conditions. Psoriasis, lichen sclerosis, lichen simplex chronicus and lichen planus are common vulvar conditions that cause pruritis and/or pain. PIasma cell vulvitis and desquamative inflammatory vaginitis are rare and challenging to be recognized, which often remain undiagnosed.

Absence of catagen/telogen phase and loss of cytokeratin 15 expression in hair follicles in lichen planopilaris.

BACKGROUND: Lichen planopilaris (LPP) is a lymphocyte-mediated cicatricial alopecia mostly involving the bulge region of the hair follicle. The origin of LPP is unknown. Therapy for LPP often does not prevent disease progression. We describe histologic and immunohistologic features that aid in diagnosis and provide an explanation for disease progression in LPP. OBJECTIVE: We sought to demonstrate a decrease in the number of catagen-/telogen-phase follicles and to confirm the loss of cytokeratin 15 (CK15) expression in the stem cells of LPP-affected follicles. METHODS: In all, 144 LPP cases were retrieved; 55 cases were stained immunohistochemically, targeting the CK15 antigen with 40 cases ultimately analyzed for CK15 expression. RESULTS: Catagen/telogen phase was significantly decreased or absent in all cases of LPP, a novel clue useful in histologic diagnostics. The loss of CK15+ stem cells in most affected follicles in LPP was also confirmed, with unaffected follicles retaining CK15+ stem cells. LIMITATIONS: Limited tissue for analysis remained in the clinical sample tissue blocks. CONCLUSION: Damaged follicles that have lost their CK15+ stem cells disappear when they enter catagen phase. CK15+ stem cell loss explains the clinical observation that LPP progresses despite immunosuppressive therapies. Finally, the absence of catagen/telogen hair follicles is a helpful diagnostic clue for LPP.

Choroidal thickness and retinal vascular changes in patients with lichen planus: an inflammatory disease beyond the skin.

BACKGROUND: Lichen planus (LP) is a common inflammatory condition of unknown etiology that commonly affects the skin and mucous membranes. Optical coherence tomography angiography (OCTA) is a noninvasive technique for identifying early retinal vascular impairment in systemic disease without clinical damage by imaging deep and superficial capillary networks. AIMS: To assess the impacts of LP on the choroid and assess vascular changes in retinal capillary density using OCTA. METHODS: This single-center prospective case-control study included 30 therapeutic-naïve LP patients and 30 age and sex-matched healthy individuals. All study subjects underwent a complete ophthalmological examination, including best-corrected visual acuity (BCVA) measurement using a Snellen chart, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, and fundus examination. They were then examined using spectral domain OCT and choroidal thickness was measured. The vessel density of the superficial and deep capillary networks was measured and assessed using OCTA. RESULTS: Patients had significantly thicker choroidal and retinal thickness than controls, with subfoveal, nasal, and temporal areas showing a significant difference. A significantly higher vascular density in the superficial capillary plexus, particularly in the nasal perifoveal area, was found compared to the control group. Significantly, higher vascular density in the deep capillary plexus in the parafoveal area compared to controls was reported. Significant correlations were found between visual acuity and IOP, and age, duration of disease, and severity of disease. CONCLUSIONS: This study is the first to reveal that LP patients exhibit choroidal changes and retinal vascular alterations compared to healthy controls.

Systemic treatment of cutaneous lichen planus: an update.

Lichen planus (LP) is a chronic and remitting dermatosis that may be idiopathic or associated with underlying systemic diseases, such as hepatitis C virus. Although numerous cases of LP resolve spontaneously, many cases require systemic treatment. Several therapeutic advances have occurred in the last 10 years: acitretin (30 mg daily for 8 weeks) remains a first-line therapy (level B, controlled clinical trial >20 participants); systemic corticosteroids are second-line therapies (level C, clinical trial <20 participants, or larger trial without appropriate controls); and new data recommend against the use of tetracycline (level C). This article reviews the current status of systemic therapies for cutaneous LP.

Identification and management of vulval problems of the postmenopausal woman - Tips and tricks.

Vulval irritation and discomfort can be a common presentation to both primary and secondary care. These symptoms can become increasingly prevalent due to physiological changes, which occur to the female genitalia following menopausal transition or due to inflammatory conditions. The correct diagnosis and management can have a huge impact on the patients' quality of life. However, due to the nature of the symptoms, there can be delayed presentation to healthcare professionals. This article gives an overview of the most common benign vulval conditions in the post-menopausal woman, their clinical features and the diagnosis and initial management.

Impairment of myocardial functions and arterial stiffness in patients with lichen planus.

BACKGROUND: Lichen planus is a chronic inflammatory mucocutaneous disease. Recent studies have suggested that it is associated with an increased risk of cardiovascular comorbidities. OBJECTIVE: The purpose of this study was to assess and compare arterial stiffness and cardiovascular hemodynamics in patients with lichen planus and a healthy control group. METHODS: Fifty-five patients with lichen planus and 42 healthy controls were enrolled. All patients underwent echocardiographic examination, and arterial stiffness was measured using applanation tonometry. RESULTS: No statistically significant difference was determined between the patient and control groups in terms of arterial stiffness, but stiffness was markedly higher in patients with erosive lichen planus compared to the control group and other patients (p=0.006, and p=0.023, respectively). Moderate positive correlation was determined between duration of disease and arterial stiffness. Impairment of systolic and diastolic functions was also determined in patients with lichen planus compared to the control group (p<0.001, and p=0.005, respectively). STUDY LIMITATIONS: Relatively low number of patients. CONCLUSION: The positive correlation observed between duration of disease and arterial stiffness in patients with lichen planus suggests that these patients should be followed-up in terms of cardiovascular risk in the presence of resistant and long-term disease, particularly in case of erosive lichen planus.

Dermatoscopic features of Koebner phenomenon in lichen planus on light and dark skin.

The Koebner phenomenon is well described and well known in clinical practice. Sometimes it can take on a linear appearance, the diagnosis of which can be facilitated by the use of dermatoscopy. In this case, we present a comparison between a linear Koebner phenomenon on light and dark skin, reporting the salient dermatoscopic characteristics and relating them to histopathology.

Adult-onset lichen striatus versus adult blaschkitis: a clinicopathological review of 40 cases of acquired blaschkolinear inflammatory dermatosis.

BACKGROUND: Since the first description of adult blaschkitis (AB), the existence of this entity has been a matter of great debate. OBJECTIVES: To compare clinicopathological features of lichen striatus (LS) and AB cases. MATERIALS AND METHODS: We retrospectively reviewed the clinicopathological features of patients who clinically showed linear inflammatory dermatosis along Blaschko's lines based on a skin biopsy registry. RESULTS: Through a process of clinicopathological differential diagnosis, 27 cases of LS, three of AB, eight of linear lichen planus, and two of linear psoriasis were identified. Clinicopathological differences between LS and AB were mostly insignificant except for age at onset and multiple site involvement. In these cases, females were affected more frequently than males. The mean age at onset was 31.6 years, and the most common involved site was the leg. The lesions lasted approximately 8.3 months with few relapses. The most common histopathological finding was perivascular infiltration followed by peri-appendageal infiltration. CONCLUSION: Distinction between LS and AB appears to be unnecessary given their overlapping features.

The measurement of serum TNF-α levels in patients with lichen planus.

BACKGROUND: Lichen planus is a common mucocutaneous inflammatory skin disease with a multifactorial etiology. Cytokines play a key role in lichen planus pathogenesis. This study investigates the relationship between disease severity and levels of tumor necrosis factor-α (TNF-α), which is considered a primary cytokine that initiates cytotoxicity. MATERIAL AND METHODS: Serum TNF-α levels were compared between a patient group (n = 34) and a control group (n = 20). TNF-α serum levels were measured using human TNF-α Enzyme-Linked Immunosorbent Assay (ELISA) test kits, and the two groups were statistically compared to each other. RESULTS: Mean serum TNF-α levels were found to be significantly higher in the patient group than in the control group (p < 0.005). However, no significant association was observed between TNF-α levels and oral mucosal involvement (p > 0.005). No relationship was detected between TNF-α levels and patients' sex. CONCLUSION: It is thought that TNF-α, a proinflammatory cytokine, may play an important role in the pathogenesis of lichen planus. TNF-α may be a simple and effective predictor to illustrate the inflammatory status in patients with lichen planus.

Does Lichen Planus Cause Increased Carotid Intima-Media Thickness and Impaired Endothelial Function?

BACKGROUND: Lichen planus (LP) has been associated with cardiovascular disease (CVD) risk factors, but there are no studies on the association between LP and subclinical atherosclerosis. We investigated the presence of subclinical atherosclerosis in patients with LP not known to have CVD using carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD). METHODS: The study included 30 patients with LP and 30 controls. High-resolution ultrasonography was used to assess CIMT and FMD. Participants' biochemical parameters, body mass index (BMI), and waist circumference were recorded in both groups. RESULTS: FMD was significantly lower (7.45% ± 3.63% vs 11.01% ± 5.34%; P = 0.004) and CIMT was higher (0.8 mm [range, 0.7-0.9 mm] vs 0.6 mm [0.4-0.6 mm]; P < 0.001) in the LP group compared with the control group. After adjustment for age, sex, BMI, high-density lipoprotein cholesterol levels, and C-reactive protein levels, the presence of LP was associated with impairment of FMD (ß = -0.441; 95% CI, -9.336 to -0.321; P = 0.037) and an increase in CIMT (ß = 0.459; 95% CI, 0.057 to -0.351; P = 0.008). CONCLUSIONS: Reduced FMD and increased CIMT levels are sensitive indicators of target-organ damage and display increased risk for cardiovascular morbidity and mortality. Our study found that patients with LP showed a tendency toward impaired levels of FMD and increased CIMT. LP may be a novel predictor of early vascular dysfunction and structural changes.