Single-cell and spatial transcriptomics of vulvar lichen sclerosus reveal multi-compartmental alterations in gene expression and signaling cross-talk.

Vulvar diseases are a critical yet often neglected area of women's health, profoundly affecting patients' quality of life and frequently resulting in long-term physical and psychological challenges. Lichen sclerosus (LS) is a chronic inflammatory skin disorder that predominantly affects the vulva, leading to severe itching, pain, scarring, and an increased risk of malignancy. Despite its profound impact on affected individuals, the molecular pathogenesis of vulvar LS (VLS) is not well understood, hindering the development of FDA-approved therapies. Here, we utilize single-cell and spatial transcriptomics to analyze lesional and non-lesional skin from VLS patients, as well as healthy control vulvar skin. Our findings demonstrate histologic, cellular, and molecular heterogeneities within VLS, yet highlight unifying molecular changes across keratinocytes, fibroblasts, immune cells, and melanocytes in lesional skin. They reveal cellular stress and damage in fibroblasts and keratinocytes, enhanced T cell activation and cytotoxicity, aberrant cell-cell signaling, and increased activation of the IFN, JAK/STAT, and p53 pathways in specific cell types. Using both monolayer and organotypic culture models, we also demonstrate that knockdown of select genes, which are downregulated in VLS lesional keratinocytes, partially recapitulates VLS-like stress-associated changes. Collectively, these data provide novel insights into the pathogenesis of VLS, identifying potential biomarkers and therapeutic targets for future research.

Dermatomyositis with Eosinophils.

Dermatomyositis is an idiopathic inflammatory myopathy that often presents with symmetric proximal skeletal muscle weakness and characteristic skin findings. Typical skin biopsy findings include vacuolar changes of the basal layer, increased dermal mucin, and a predominantly lymphocytic infiltrate. We report a case of dermatomyositis presenting as intensely pruritic papules and plaques, with initial histopathology being atypical of dermatomyositis due to the presence of eosinophils. The initial biopsy demonstrated a superficial dermatitis with eosinophils, initially thought to represent a drug eruption. A second biopsy of the same cutaneous manifestation was performed at a later time given high clinical suspicion for dermatomyositis and demonstrated a more classic vacuolar interface dermatitis with increased mucin and an absence of eosinophils. Notably, increased pruritus was specifically associated with the lesion that demonstrated tissue eosinophilia. The case illustrates the importance of considering tissue eosinophilia in the histologic presentation of dermatomyositis.

Acquired vulvar lymphangioma: risk factors, disease associations, and management considerations: a systematic review.

Acquired vulvar lymphangioma (AVL) is not well-characterized. Diagnosis is delayed and the condition is often refractory to therapy. Objective: The objective of this study was to provide a systematic review of AVL including risk factors, disease associations, and management options. Methods: A primary literature search was conducted using 3 databases: PubMed, CINAHL, and OVID, from all years to 2022. Results: In total, 78 publications with 133 patients (48 ± 17 years) were included. Most studies were case reports/series. The most common disease association was prior malignancy (70 patients, 53% of cases) and inflammatory bowel disease (6 patients, 5% of cases). The most common malignancy was cervical cancer (57 patients, 43% of cases). Most patients had prior radiation or surgery, with 36% (n = 48) treated with radiation, 30% (n = 40) with lymph node dissection, and 27% (n = 36) with surgical resection. Common presenting symptoms included discharge/oozing, pain, and pruritus. Most patients underwent surgical treatment for AVL with 39% treated with excision, 12% with laser therapy (the majority used CO2), and 11% with medical therapies. Most patients had failed prior therapies and there was a diagnostic delay. Limitations: Retrospective nature. Most studies were limited to case reports and case series, with interstudy variability and result heterogeneity. Conclusion: AVL is an underrecognized entity and should be considered in patients with a history of malignancy or radiation to the urogenital area. Treatment should include multidisciplinary care and address underlying lymphatic changes, manage any existing inflammatory conditions, and utilize skin-directed therapies and barrier agents while addressing symptoms of pruritus and pain. Prospective studies are needed to further characterize AVL and develop treatment guidelines.

Epithelioma Cuniculatum (Plantar Verrucous Carcinoma): A Systematic Review of Treatment Options.

Epithelioma cuniculatum (EC) is a subtype of verrucous carcinoma (VC) that affects the feet. Treatment involves complete tumor removal by wide local excision (WLE) or Mohs micrographic surgery (MMS). Extensive local destruction may require amputation. We sought to compare reported treatment methods for EC and determine their efficacy by assessing for tumor recurrence and treatment-associated complications. A systematic review of the literature spanning multiple databases was performed. To date, surgical excision is recommended as the standard of care for treatment of EC, with amputation considered in more advanced cases. Mohs micrographic surgery appears to be a promising treatment modality for EC and may have lower recurrence rates than WLE but requires further investigation.

Enfortumab Vedotin-Associated Toxic Epidermal Necrolysis-like Toxic Erythema of Chemotherapy.

ABSTRACT: Enfortumab vedotin is an antibody-drug conjugate used for treatment of urothelial cancer. It has recently been associated with several reports of Stevens Johnson syndrome/toxic epidermal necrolysis (TEN). In this report, we describe the case of a 63-year-old man who developed widespread, near full-thickness desquamation, clinically mimicking TEN but with histologic features of toxic erythema of chemotherapy. This distinction is significant because it may have implications for prognosis and treatment. Further investigation is needed to ascertain the incidence of true TEN versus clinical imitators in patients with enfortumab vedotin-related cutaneous toxicity.

Inflammatory Vulvar Dermatoses (Part I).

Vulvar disease is common, and urologists are often the first providers to see patients with a vulvar skin condition. Primary vulvar dermatoses can be localized to the anogenital area or a manifestation of more diffuse cutaneous disease. Additionally, secondary dermatoses can develop from exogenous agents and inflammatory vaginitis. Vulvar conditions are challenging to diagnose due to location and different types of skin and mucosal epithelium involved. Herein, we provide an overview of noninfectious inflammatory vulvar dermatoses (part I) and benign and malignant vulvar neoplasms (part II), grouped by morphologic findings. We include diagnostic evaluation, workup, and management of these conditions.

Vulvar Neoplasms (Part II).

Vulvar disease is common, and urologists are often the first providers to see patients with a vulvar skin condition. Primary vulvar dermatoses can be localized to the anogenital area or a manifestation of more diffuse cutaneous disease. Additionally, secondary dermatoses can develop from exogenous agents and inflammatory vaginitis. Vulvar conditions are challenging to diagnose due to location and different types of skin and mucosal epithelium involved. Herein, we provide an overview of noninfectious inflammatory vulvar dermatoses (Part I) and benign and malignant vulvar neoplasms (Part II), grouped by morphologic findings. We include diagnostic evaluation, workup, and management of these conditions.

Plasma cell vulvitis: A systematic review.

BACKGROUND: Plasma cell vulvitis (PCV) is an inflammatory vulvar dermatosis that is not well characterized. Diagnosis is often delayed, and the condition can be refractory to treatment. To date, there are no systematic reviews on this topic. OBJECTIVE: This study aimed to provide a systematic review of PCV, including epidemiologic, clinical, and histopathologic findings, as well as associated comorbidities and treatment options. METHODS: A primary literature search was conducted using the PubMed, Ovid Medline, Cochrane, and CINAHL databases. RESULTS: Fifty-three publications with 196 patients (mean age: 55.3 ± 14.5 years) were included. The majority of studies were case reports and case series. Common symptoms included burning/stinging (52%), dyspareunia (44%), and pruritus (41%). Common findings included erythema (84%), glistening/shiny appearance (29%), well-demarcated lesions (25%), and erosions (22%). Common anatomic sites were the labia minora (45%), introitus (31%), and periurethral (19%). Fifty-three percent of patients had a solitary lesion. Common histologic findings were a predominant plasma cell infiltrate (88%), presence of other inflammatory cells (55%), hemosiderin/siderophages (46%), and epidermal atrophy (43%). Topical corticosteroids (64%) and tacrolimus ointment (13%) were the most frequent treatment modalities. In most reports, previous treatments were tried, and there was a diagnostic delay. CONCLUSION: PCV is likely underrecognized and should be considered in patients with erythema of the mucous and modified mucous membranes, symptoms of burning or stinging, and a predominant plasma cell infiltrate on histopathology. First-line therapy should begin with high-potency topical corticosteroids, with the most evidence for clobetasol 0.05% or tacrolimus 0.1% ointment. Prospective studies are needed to further characterize this condition and to develop treatment guidelines.