Lichen Sclerosus et Atrophicus With Histopathologic Features Mimicking Mycosis Fungoides: A Large Series of Cases Comparing Genital With Extragenital Lichen Sclerosus.

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory dermatosis of unknown etiology involving the genital and/or extragenital area, showing histopathologically a characteristic homogeneization and sclerosis of the superficial collagen with variably dense lymphoid infiltrates. Intraepidermal lymphocytes may be observed, and in some cases may pose differential diagnostic problems with mycosis fungoides (MF). We studied the histopathologic features of 121 cases of LSA with dense lymphoid infiltrates (genital: 94; male:female: 93:1; age range: 2 to 87 y; median age: 11 y; extragenital: 27; male:female: 0.1:1; age range: 11 to 79 y; median age: 59 y), to better characterize the intraepidermal lymphoid infiltrate and to compare genital with extragenital cases. Epidermotropic lymphocytes mimicking the histopathologic features of MF were present in 93.6% of the genital specimens but none of the extragenital cases. Interestingly, typical features of LSA were mssing in 39.4% of genital LSA, and in a further 25.5% were present only focally. Immunohistochemical analyses showed a predominance of CD8+ T-lymphocytes within the epidermis. Molecular studies of the T-cell receptor genes revealed a monoclonal population of T-lymphocytes in nearly half of the cases. Our study shows that MF-like histopathologic features are extremely common in genital LSA but are never encountered in extragenital cases. A diagnosis of MF in the genital area should be made only upon compelling features, keeping in mind the frequent pseudolymphomatous aspects of LSA.

Lymphocyte-Peppered Sclerotic Collagen: An Additional Histological Clue in Lichen Sclerosus, Morphea, and Systemic Sclerosis.

BACKGROUND: "Line sign," "cookie cutter sign," "square biopsy sign," "high eccrine glands sign" have been previously described in morphoea and lichen sclerosus. We found focal areas of thickened collagen bundles with lymphocytes interspersed between them in several biopsies of these conditions. MATERIALS AND METHODS: We reviewed slides of sclerosing disorders obtained from the archives of the pathology department in our hospital for the period 2013-2019. RESULTS: A total of 73 slides including 40 of lichen sclerosus, 24 of morphea, 2 of lichen sclerosus-morphea overlap, and 7 of systemic sclerosis were evaluated. Lymphocytes were noted between sclerotic collagen bundles in 46 (63%) slides, being most common in lichen sclerosus (80%, 32/40) followed by morphea (50%, 12/24), whereas it was seen in one case each of lichen sclerosus with morphea overlap (50%, 1/2) and systemic sclerosis (14.3%, 1/7). The finding was noted in the upper dermis in 20 of 32 (62.5%) slides of lichen sclerosus and in both the superficial and deep dermis in 11 (91.7%) of 12 slides of morphea. CONCLUSION: Lymphocyte-peppered sclerotic collagen may be a useful histological clue to the diagnosis of lichen sclerosus, morphea, and systemic sclerosis.

One-Stage Buccal Mucosal Graft Urethroplasty for Lichen Sclerosus-Related Urethral Stricture Disease: A Systematic Review and Pooled Proportional Meta-Analysis.

PURPOSE: Performing 1-stage urethroplasty in patients with urethral strictures caused by lichen sclerosus (LS) is hotly debated among reconstructive urologists due to conflicting reports of success. Therefore, the objective of this study was to determine the pooled incidence of stricture recurrence following 1-stage buccal mucosal graft (BMG) urethroplasty in patients with LS, to determine the impact of surgical technique on recurrence and to compare recurrence risk between patients with and without LS after 1-stage repairs. MATERIALS AND METHODS: A systematic review was conducted in accordance with PRISMA criteria. The primary outcome was pooled incidence of recurrence, which was calculated using a Der-Simonian-Laird binary random effects model with a Freeman-Tukey arcsine transformation. A total of 21 studies were included, of which 15 provided data for comparative analyses. RESULTS: Pooled data from 625 LS patients revealed a stricture recurrence rate of 10% (95% CI 6-14). Among studies with longer followup (≥24 months), this increased to 18%. Among patients with penile urethral involvement, studies utilizing a penile skin incision had significantly higher pooled recurrence rates than those utilizing penile invagination (p=0.004). Across all studies, there was no evidence to suggest a difference in pooled recurrence rate between patients with and without LS (p=0.36). However, across only long-term studies, recurrence risk was significantly higher for patients with LS (OR 1.83, p=0.05). CONCLUSIONS: One-stage BMG urethroplasty is likely a viable surgical option for patients with LS-related strictures; however, high-quality data are limited. Future multi-institutional, long-term prospective studies are needed to assess durability of 1-stage repair.

Gene silencing of extracellular matrix protein 1 (ECM1) results in phenotypic alterations of dermal fibroblasts reminiscent of clinical features of lichen sclerosus.

BACKGROUND: Lichen sclerosus (LS) is an acquired inflammatory mucocutaneous disease affecting the anogenital area, characterized histologically by hyalinosis and thickened vessel walls in the dermis. The presence of serum autoantibodies against extracellular matrix protein 1 (ECM1) in LS patients may suggest its involvement in disease pathogenesis. OBJECTIVE: To examine if reduced ECM1 production by dermal fibroblasts contributes to the pathogenic features of LS. METHODS: Gene expression in ECM1 knockdown human dermal fibroblasts was analyzed by cDNA microarray. Functional enrichment for genes involved in cellular functions was conducted. Protein expression was analyzed by ELISA and confocal laser scanning microscopy using LS skin. RESULTS: Microarray analysis identified 3035 differentially expressed genes in ECM1 knockdown cells, wherein 1471 were upregulated genes related exclusively to cell adhesion, proliferation, apoptosis, intracellular signaling, and extracellular matrix organization. Further narrowing with criteria specific for localization and function of ECM1 identified 48 upregulated genes identified to have structural, fibrogenic, and carcinogenic properties. Of these, laminin-332 and collagen-IV displayed altered immunolabeling within the basement membrane zone (BMZ) and dermal vessels in LS skin, similar to that of collagen-VII, which exhibited unchanged transcription levels in ECM1-knockdown fibroblasts. Collagen-VII bound to recombinant ECM1 in a solid-phase immunoassay and colocalized with ECM1 in the skin BMZ. Further, ECM1-knockdown fibroblasts exhibited a marked delay in cell migration and gel contraction. CONCLUSION: In the absence of ECM1 expression in fibroblasts there is selective dysregulation and disassembly of structural and extracellular matrix molecules, which may result in microstructural abnormalities reminiscent of LS.

Lichen Sclerosus: An autoimmunopathogenic and genomic enigma with emerging genetic and immune targets.

Lichen sclerosus (LS) is an inflammatory dermatosis with a predilection for anogenital skin. Developing lesions lead to vulvar pain and sexual dysfunction, with a significant loss of structural anatomical architecture, sclerosis, and increased risk of malignancy. Onset may occur at any age in both sexes, but typically affects more females than males, presenting in a bimodal fashion among pre-pubertal children and middle-aged adults. A definitive cure remains elusive as the exact pathogenesis of LS remains unknown. A general review of LS, histologic challenges, along with amounting support for LS as an autoimmune disease with preference for a Th1 immune response against a genetic background is summarized. In addition to the classically referenced ECM1 (extracellular matrix protein 1), a following discussion of other immune and genetic targets more recently implicated as causative or accelerant agents of disease, particularly miR-155, downstream targets of ECM1, galectin-7, p53, and epigenetic modifications to CDKN2A, are addressed from the viewpoint of their involvement in three different, but interconnected aspects of LS pathology. Collectively, these emerging targets serve not only as inherently potential therapeutic targets for treatment, but may also provide further insight into this debilitating and cryptic disease.

ALA-Photodynamic treatment in Lichen sclerosus-clinical and immunological outcome focusing on the assesment of antinuclear antibodies.

BACKGROUND: Lichen sclerosus (LS) is a difficult to treat, often relapsing disease with unknown background. Autoimmune diseases also coexist with LS. Over recent years photodynamic therapy (PDT) has been shown to be a noninvasive and successful therapeutic approach for the effective treatment of many conditions. However, the change of immune status of the patients based on ANA antibodies has not been yet reported. Our aim was to observe the clinical response followed by possible changes in autoimmune antibodies levels before and after PDT for LS. MATERIAL AND METHODS: We enrolled 100 women with Lichen sclerosus with or without a concomitant autoimmune disease. All patients received 10 cycles of PDT (65 treated with DIOMED Light, 35 with PhotoDYN Light). We assessed autoimmune antibodies before and after PDT in addition to the clinical response evaluation.Two-year prospective controlled before-and-after study. RESULTS: Following PDT, patients showed a significant attenuation in symptoms' intensity (itching, pruritus, vulvar discomfort). After therapy 41% of patients had partial response, 51% of patients had no symptoms and 8% had persistent or worsened symptoms. The most frequent autoimmune disease were thyroid disorders, followed by vitiligo and arthritis. 57% patients with an additional autoimmune disease before PDT had ANA antibodies. The mean level of ANA in this group diminished significantly after PDT treatment (261.74 IU/ml before vs. 123.20 IU/ml after treatment). CONCLUSION: Based on our results, we assume that PDT may influence the immune status of patients with Lichen sclerosus.

Eosinophils in lichen sclerosus et atrophicus.

BACKGROUND: The classic histopathologic features of lichen sclerosus et atrophicus (LS) include lymphoplasmacytic inflammation below a zone of dermal edema and sclerosis. The presence of eosinophils in LS has received little attention, but the finding of tissue eosinophils, particularly eosinophilic spongiosis in LS, has been suggested as a marker for the coexistence of autoimmune bullous disease or allergic contact dermatitis (or both). We sought to determine whether the histopathologic presence of dermal eosinophils or eosinophilic spongiosis (or both) in biopsies from patients with LS is associated with autoimmune bullous disease, autoimmune connective tissue disease or allergic contact dermatitis. METHODS: A retrospective review of the histopathology and medical records of 235 patients with LS who were evaluated from June 1992 to June 2012 was performed. RESULTS: Sixty-nine patients (29%) had eosinophils on histopathology. Among patients with associated diseases, a statistically significant association between the eosinophil cohort and the cohort without eosinophils was not detected. CONCLUSIONS: The importance of eosinophils is uncertain, but our data suggest that the finding of tissue eosinophils alone is not sufficient to prompt an extensive workup for additional diagnoses.

L1 gene sequence of a putative novel type human papillomavirus in an immunocompetent patient with glans lichen sclerosus.

The identification of a putative novel type human papillomaviruses (HPV) strain related to HPV-RTRX3 in a subject with penile skin warts and glans lichen sclerosus is reported. A beta-HPV-RTRX3-like strain was detected in a immunocompetent patient with glans lichen sclerosus. HPV screening was performed by PCR in L1 gene. The MY fragment showed 99% nt identity with HPV-RTRX3 and 64.5% nt identity with HPV-37. The remaining part of the L1 gene showed similarity with HPV 80, 15, 17, and 37. Based on the presence of penile lichen sclerosus and the HPV-RTRX3-like strain found in our patient, a potential correlation was hypothesized.

[Lichen sclerosus--clinical and therapeutic aspects].

Lichen sclerosus (LS) is a lymphocyte-mediated inflammatory dermatosis with a characteristic location (85-98%) in the anogenital region. The authors point out the main features in the epidemiology and clinical presentation of the disease and the possible approach to neoplastic development. Expanded differential diagnosis of LS sparked not only dermatologists but also gynecologists, urologists and GPs. Points are the chronic course of the disease and resistance to therapy. Discuss the results of the treatment of LS with less potent topical corticosteroids, calcineurin inhibitors, phototherapy and photodynamic therapy, surgery.

Bacterial vaginosis in the context of lichen sclerosus in a prepubertal girl.

Group A beta-hemolytic streptococcus cause most vulvovaginal infections seen in prepubertal girls. Bacterial vaginosis is a common cause of abnormal vaginal discharge in women of childbearing age but is rare in children. Data are insufficient to suggest that bacterial vaginosis is an exclusively sexually transmitted disease. We report a 10-year-old girl with no history or suspicion of sexual abuse who developed bacterial vaginosis in the context of a lichen sclerosus being treated with tacrolimus ointment. Secondary bacterial infection in lichen sclerosus is uncommon. We speculate that the immunosuppressive effect of topical tacrolimus could have triggered the infection.

Association of autoimmune diseases with lichen sclerosus in 532 male and female patients.

Lichen sclerosus is a relatively common chronic inflammatory skin disease that predominantly affects the anogenital area. Accumulating evidence indicates that lichen sclerosus in women may be associated with other autoimmune disease, whereas this association seems to lack in male patients. We retrospectively evaluated the prevalence of autoimmune diseases and serological parameters indicative for autoimmunity in male and female patients with lichen sclerosus. Of the 532 patients (396 women, 136 men; 500 adults, 32 children; mean age: 49 years; range 1-89 years; female:male ratio 3:1), 452 (85%) had genital and 80 (15%) had extragenital disease. In women, lichen sclerosus was significantly more often associated with at least one autoimmune disease as compared to men (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.9-9.6; p<0.0001). Moreover, female patients with lichen sclerosus had sinificantly more often associated autoimmune thyroid diseases (OR 4.7, 95% CI 1.8-11.9; p<0.0002), antithyroid-antibodies (OR 2.7, 95% CI 1.1-6.5; p=0.023), and elevated autoantibodies (OR 4.1, 95% CI 1.9-9.3; p<0.0001) as compared to male patients. This observation is suggestive for a different pathogenetic background in male and female patients.

Lichen sclerosus: a review of literature and a case of an atypic surgical treatment.

Lichen sclerosus is a chronic immuno-mediated skin disease of the genital region in men and women. The treatment may be pharmacological or surgical, the choice depending on the extension of the involved area, the histological pattern and the level of functional disease complained by the patient. If the biopsy is negative for neoplastic degeneration the treatment may be pharmacological only. In our paper, we describe the case of a patient with vulvar disease and labial fusion, burial of the clitoris and severe introital stenosis. In this case, the treatment was surgical.

Folliculocentric lichen sclerosus et atrophicus.

A 71-year-old black woman presented to the dermatology clinic with a several-year history of increasing numbers of itchy white spots spreading over the chest, back, elbows, and legs. In 2004, the patient developed clusters of mildly pruritic hypopigmented and depigmented macules on her back and left shoulder along with depigmented flat papules on the lower extremities. The patient's condition was unresponsive to topical triamcinolone and tacrolimus, after which she was lost to follow-up for 3 years until her entire chest became involved. Her medical history was significant for hypertension and diabetes mellitus and her medications included amlodipine, aspirin, atorvastatin, hydrochlorothiazide, irbesartan, and metformin. Family history, social history, and review of systems were unremarkable. Physical examination revealed multiple shiny white perifollicular macules, some with slight scale, on the trunk (Figure 1) and extremities (Figure 2). On the left shoulder and back were 2 shiny plaques with hypopigmented macules and follicular scale within. Punch biopsies from the abdomen and back showed atrophy of the epidermis, edema and sclerosis of the papillary dermis, and a patchy lichenoid lymphocytic infiltrate (Figure 3). Despite inspecting multiple step sections, we were unable to histopathologically confirm the clinically apparent folliculocentric distribution. Based on the clinical and histological findings, extragenital lichen sclerosus et atrophicus (LSA) was diagnosed and the patient was treated with clobetasol proprionate 0.05% ointment. While being prepared for narrowband UV-B therapy, a serologic screen revealed antinuclear antibodies at 1:640 with a homogeneous pattern. A subsequent rheumatologic evaluation was negative for autoimmune disorders; pertinent negative serologies included anti-double-stranded DNA, smooth muscle, mitochondrial, thyroid, and parietal cell antibodies.