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.

Perceptions and impact of patient reviews: a survey of academic dermatologists.

BACKGROUND: Patient reviews (PRs) have emerged as a method to assess patient experiences with healthcare in order to improve the quality of care. Both institutional and third-party organizations collect quantitative data and comments from these patient surveys, usually accessible to the public for review. Our study examined dermatologists' perceptions of PRs and assessed their impact on dermatologists. METHODS: A survey was sent to the Association of Professors of Dermatology listserv (response rate 30%). RESULTS: Most respondents disagreed with the statements that PRs are good for doctors (63%), good for patients (58%), helpful for doctors (58%), or that high PRs indicate being a good doctor (65%). The majority disagreed that PRs should be available publicly (60%). Respondents agreed that PRs contribute to depersonalization (60%), energy depletion or exhaustion (55%), added stress at work (70%), negativism/cynicism about work (60%), and diminished professional efficacy (29%). Self-identified female respondents were more likely to agree that PRs added stress to work compared to self-identified males (66% vs. 42%, P < 0.05). CONCLUSIONS: Overall, these findings suggest that PRs may negatively impact dermatologists' well-being and perceived stress levels.

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.

Low dose oral minoxidil and the conundrum of cardiovascular complications.

In recent months, the general public has become more cognizant of the potential of oral minoxidil to promote hair growth; this was promulgated, in part, by an article published in the New York Times entitled, "An Old Medicine Grows New Hair for Pennies a Day, Doctors Say." Minoxidil was added to the pharmacologic armamentarium as an antihypertensive nearly 60 years ago and was found to trigger hypertrichosis in many patients, but its use dropped sharply as cardiologists observed a number of adverse cardiovascular events including ischemic heart disease, left ventricular hypertrophy, pleural effusions, and pericardial effusions. Studies in the realm of dermatology have explored the utility and safety of low dose oral minoxidil (LDOM) for management of alopecia. This article highlights potential clinical conundrums posed by these rare but severe cardiovascular complications and the importance of collaboration between cardiologists and dermatologists when employing this agent in patients with cardiorenal or cardiovascular risk factors.

Eosinophils in Traditionally Noneosinophil-Rich Dermatoses.

ABSTRACT: The presence or absence of tissue eosinophilia has previously aided in the diagnosis of inflammatory skin conditions. However, recent studies have elucidated the presence of eosinophils in traditionally eosinophil-poor inflammatory skin diseases, such as dermatomyositis (DM), psoriasis, and lichen sclerosus (LS). This systematic review of the literature explores previous studies of tissue eosinophilia in skin biopsies of dermatoses that are believed to be classically poor in eosinophil. We identified 26 studies, the majority of which were retrospective reviews. The percent of specimens with increased eosinophils in psoriasis ranged from 18%-73%, pityriasis rubra pilaris (PRP) 22%-63%, LS 29%-53%, DM 15%-44%, morphea 8%-45%, hypertrophic lichen planus (LP) 0%-21%, and oral LP 0%-4%. These reports of tissue eosinophilia in reputed eosinophil-poor dermatologic conditions present a diagnostic pitfall and suggest that tissue eosinophilia itself should not be used to rule out a diagnosis of one of these conditions.

Expanding the Histologic Spectrum of Sudden Conjunctivitis, Lymphopenia, and Rash Combined With Hemodynamic Changes.

ABSTRACT: Sudden conjunctivitis, lymphopenia, and rash combined with hemodynamic changes (SCoRCH) is a recently described hypersensitivity reaction to trimethoprim-sulfamethoxazole. To date, only 1 case of histologic findings in SCoRCH has been reported, revealing a superficial perivascular dermatitis. In this article, we present a 53-year-old woman with a four-day history of a widespread, confluent, erythematous, and dusky rash after exposure to trimethoprim-sulfamethoxazole. Histologic examination revealed a vacuolar interface dermatitis with several apoptotic keratinocytes at multiple levels of the epidermis, similar to an erythema multiforme-like presentation. As described in SCoRCH, our patient's clinical findings rapidly improved within 48 hours of presentation without treatment. This case adds to the current literature by identifying a newly described histopathological presentation of SCoRCH.

Microblading-Induced Granulomatous Reaction: Case Report and Review of the Literature.

ABSTRACT: Microblading is a common cosmetic procedure that can modify the appearance of one's eyebrows. Although generally well-tolerated, the procedure can cause a number of dermatologic issues; on rare occasions, granulomatous reactions can manifest. We use this case to highlight a presentation of a nonsarcoidal granulomatous dermatitis and review the literature on granulomatous reactions secondary to microblading. Of the 21 cases included in our review, approximately half (10/21) were diagnosed with foreign-body granulomas and the other half with sarcoidosis (7 of 21 with systemic sarcoidosis and 4 of 21 with cutaneous sarcoidosis). Although microblading remains a commonplace cosmetic technique, it is not without risk. Much like other types of tattoos, microblading can cause granulomatous reactions for which we must be vigilant, and further workup for sarcoidosis might be considered in select patients.

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.