A prospective pilot study to assess for histologic changes on vulvar biopsies in postmenopausal women with lichen sclerosus treated with fractionated CO2 laser therapy.

OBJECTIVES: To investigate the histologic characteristics of vulvar tissues before and after completion of fractionated carbon dioxide (CO2 ) laser therapy (FxCO2) for vulvar lichen sclerosus (LS). The secondary objective was to assess subjective improvement in symptoms via the Skindex-16 questionnaire. METHODS: This prospective single-arm study was conducted from April 2021 to August 2022 at one academic medical center. Ten postmenopausal women with biopsy-proven LS planning FxCO2 laser treatment were enrolled. Exclusion criteria included prior transvaginal mesh for prolapse, topical corticosteroid use within 8 weeks, prior pelvic radiation, malignancy, active genital infection, or pregnancy. The vulvovaginal SmartXide2-V2-LR laser system fractionated CO2 laser (DEKA) was utilized to treat visually affected areas of vulvar and perianal LS with a single pass. Subjects underwent three treatments 4-6 weeks apart. Subjects completed the Skindex-16 questionnaire and had vulvar biopsy at baseline and at 4 weeks after completion of fractionated CO2 laser therapy. Blinded histologic slides were scored by one dermatopathologist (Michael A. Cardis) rating from 1 to 5 the degree of dermal sclerosis, inflammation, and epidermal atrophy. Change scores were calculated as the difference between pre- and post-treatment scores for each subject. RESULTS: The 10 subjects enrolled had a mean age of 61 and most were white, privately insured, and had a college/graduate-level education. Post-fractionated CO2 laser treatment vulvar biopsies showed significant improvement in sclerosis and epidermal atrophy compared with pretreatment baseline biopsy specimens (p < 0.05) with no statistically significant change found in inflammation score. Skindex-16 and FSFI scores showed a trend towards improvement (p > 0.05 for both). A statistically significant correlation was found between change in sclerosis and Skindex-16 symptoms scores with an average change of 21.4 units in Skindex-16 symptoms score for every one-point change in histologic sclerosis score (p = 0.03). CONCLUSIONS: In postmenopausal women with vulvar LS undergoing fractionated CO2 laser, symptomatic improvements correlated with histologic change in degree of sclerosis on vulvar biopsy. These results demonstrate FxCO2 laser therapy as a promising option for the treatment of LS and suggest that further studies should assess degree of sclerosis on histopathology.

A widespread blistering eruption: diffuse cutaneous mastocytosis.

Diffuse cutaneous mastocytosis with bullous formation is a rare childhood disease. We report a 5-month-old male who presented with a 3-week history of cutaneous bullae and pruritus. On examination, he had erythema of the cheeks bilaterally and diffuse slightly hyperpigmented, indurated skin on his trunk and abdomen. There were tense vesicles, bullae, and erosions linearly arranged on his trunk and extremities. Both the laboratory and imaging workup were normal. Subsequently, a punch biopsy of a vesicle on the abdomen was obtained and findings confirmed a diagnosis of diffuse cutaneous mastocytosis. An EpiPen(r) was prescribed due to the slightly increased anaphylaxis risk compared to other forms of mastocytosis. There are many purported triggers of diffuse cutaneous mastocytosis and there is currently no known cure which makes management of this disease challenging. This case highlights a rare condition for which official treatment guidelines do not exist. A prompt dermatologic diagnosis is necessary to ensure proper workup and regulation is in place.

"Knife-cut" intertriginous ulcers related to herpes simplex virus in three patients.

Linear intertriginous erosions and ulcerations related to herpes simplex virus (HSV) infection have been reported in patients with underlying immunosuppression. This rare presentation of HSV seems to occur predominantly in patients undergoing treatment of hematologic malignancies and rheumatologic conditions. Herein, we report three cases of linear "knife-cut" ulcerations in patients who were not undergoing active pharmacologic immunosuppressive therapy and lacked coexisting malignancy or autoimmune disease. Close examination of the skin folds for HSV infection is warranted to rule out disseminated infection as early intervention can be lifesaving.

Vulvovaginal manifestations in Stevens-Johnson syndrome and toxic epidermal necrolysis: Prevention and treatment.

The prevalence of acute vulvovaginal involvement in toxic epidermal necrolysis can be as high as 70%; up to 28% of female patients will also develop chronic vulvovaginal sequelae. There is little consensus regarding prevention and treatment of the gynecologic sequelae of both Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). We review acute and chronic sequelae, including erosions, scar formation, chronic skin changes, urethral complications, adenosis, malignant transformation, vulvodynia, and dyspareunia. We provide comprehensive recommendations for acute and long-term vulvovaginal care in adult and pediatric SJS/TEN patients. Treatment should include an ultrapotent topical steroid, followed by a nonirritating barrier cream applied to vulvar and perineal lesions. A steroid should be used intravaginally along with vaginal dilation in all adults (but should be avoided in prepubertal adolescents) with vaginal involvement. Menstrual suppression should be considered in all reproductive age patients until vulvovaginal lesions have healed. Last, referrals for pelvic floor physical therapy and to surgical subspecialties should be offered on a case-by-case basis. This guide summarizes the current available literature combined with expert opinion of both dermatologists and gynecologists who treat a high volume of SJS/TEN patients.

Hydrogen Peroxide 40% for the Treatment of Seborrheic Keratoses.

OBJECTIVE: Hydrogen peroxide 40% (HP40) was approved by the US Food and Drug Administration for topical treatment of seborrheic keratosis (SK) in December 2017. This article will review phase II and III clinical trials to assess the drug's efficacy, safety, and clinical application. DATA SOURCES: A systematic literature review was performed using the terms "Eskata AND seborrheic keratosis," and "hydrogen peroxide AND seborrheic keratosis" in the OVID MEDLINE, PubMed, Cochrane Library, EMBASE, and Web of Science databases. ClinicalTrials.gov was searched to identify ongoing or nonpublished studies. STUDY SELECTION AND DATA ABSTRACTION: Articles written in English between January 2000 and mid-June 2020 discussing phase II and phase III clinical trials were evaluated. DATA SYNTHESIS: In 2 phase III clinical trials, 4% and 8% of patients treated with HP40 had a Physician Lesion Assessment score of zero for all 4 SKs, respectively, compared with 0% in both vehicle groups at the primary end point of day 106 (P < 0.01; P < 0.0001). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: HP40, although less effective, has a better safety profile than other treatment options. It should be especially considered for treatment of facial SKs, where it is most efficacious and where other treatment modalities, such as cryotherapy, are more challenging. CONCLUSIONS: HP40 is a new, safe alternative treatment for SKs, although it is expensive and only modestly effective, both of which somewhat limit its overall utility. HP40 is a promising topical alternative, particularly for cosmetically sensitive locations, such as the face.

Scalp metastasis as initial presentation of neuroendocrine carcinoma.

Neuroendocrine carcinomas are a rare, heterogenous group of malignancies that arise from neuroendocrine cells throughout the body. Cutaneous metastasis of neuroendocrine carcinoma is uncommon and they can be easily misdiagnosed as benign epidermal cysts or Merkel cell carcinoma. Collectively, histopathology, immunochemical profile, biochemical markers, and nuclear imaging can guide the diagnosis of neuroendocrine metastasis and localization of primary tumors.

The effect of gluten on skin and hair: a systematic review.

Non-celiac gluten sensitivity is often clinically indistinguishable from celiac disease, and patients show improvement or resolution of their symptoms with a gluten-free diet. In contrast to celiac disease, the effects of gluten on the skin and hair in the context of non-celiac gluten sensitivity are not as clear. This review aims to describe the impact of gluten on the skin and hair in patients with non-celiac gluten sensitivity and those without a definitive celiac disease diagnosis. A literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guidelines for systematic reviews. Forty-two publications met inclusion criteria with five studies describing the skin manifestations of non-celiac gluten sensitivity. Trials identifying the impact of a gluten-free diet on skin disease, as well as dermatologic conditions and their associations with antigliadin antibodies were also identified. Dermatologic manifestations in patients with non-celiac gluten sensitivity vary and may be non-specific. It may be appropriate for some of these patients with skin manifestations to trial a gluten-free diet. Dermatologic conditions that may respond positively to a gluten-free diet include psoriasis, atopic dermatitis, vitiligo, and palmoplantar pustulosis, while linear IgA disease does not appear to improve with this dietary change.

Diffuse lichen planus-like keratoses and clinical pseudo-progression associated with avelumab treatment for Merkel cell carcinoma, a case report.

BACKGROUND: Avelumab is an anti-programmed cell death ligand 1 (PD-L1) antibody approved for treatment of Merkel cell carcinoma (MCC) and locally advanced or metastatic urothelial carcinoma. It shares a similar side effect profile to other immune checkpoint inhibitors, including immune-related adverse reactions in the skin. These adverse skin reactions can present as a morbilliform exanthem, lichenoid dermatitis, vitiligo, autoimmune bullous disorder, among others. CASE PRESENTATION: We describe a patient with advanced MCC successfully treated with avelumab who developed acute onset diffuse lichen planus-like keratoses (LPLK) at sites of existing seborrheic keratoses (SK) and lentigines. Histopathology of an affected SK revealed papillomatous epidermal hyperplasia with lichenoid interface changes, numerous dyskeratotic keratinocytes and intermittent hypergranulosis. The findings resembled lichen planus (LP) arising in an SK. Onset of the skin symptoms corresponded with an inflammatory cancer response (clinical pseudo-progression), and the eruption improved as overall tumor burden decreased. The patient's pruritus was treated with topical steroids and cyrotherapy for individual symptomatic lesions. CONCLUSION: Diffuse LPLK is a distinct immune-related reaction pattern associated with PD-L1/PD-1 checkpoint blockade. This is an important side effect to be aware of as LPLK frequently mimic keratinocytic neoplasms. Further observation is needed to assess the prevalence and significance of this immune therapy-associated adverse reaction.

Recurrent fevers, progressive lipodystrophy, and annular plaques in a child.

KEY TEACHING POINTS.

Topical sirolimus for treatment of a venolymphatic malformation in an adolescent girl.

Sirolimus has emerged as a promising treatment for complex congenital vascular malformations but is limited because of systemic side effects. Topically compounded formulations, which have been found to be successful in the treatment of several other conditions, are a preferred drug delivery system to provide local therapy. We report a case of a venolymphatic malformation in an adolescent girl treated with topical 1% sirolimus cream leading to improvement in appearance and associated symptoms.

Rapidly growing subcutaneous mass in an infant.

Fibrous hamartoma of infancy (FHI) is a benign mesenchymal tumor of young children. It has a broad clinical differential diagnosis and is often clinically confused for vascular and malignant soft tissue neoplasms. Recognition of the unique histologic features of FHI, a triphasic population of mature adipose tissue, mature fibrous tissue, and immature mesenchymal tissue, will ensure the correct diagnosis. In this report we present a case of this rare entity, including the associated clinical, radiologic, and histologic findings.

HIV-associated erythema elevatum diutinum: a case report and review of a clinically distinct variant.

A 24-year-old man with untreated human immunodeficiency virus (HIV) infection consulted our outreach clinic owing to the development of numerous asymptomatic nodules on his palms and fingers. Histopathologic evaluation revealed leukocytoclastic vasculitis and prominent fibrosis with a neutrophilic infiltrate consistent with erythema elevatum diutinum (EED). We referred the patient for initiation of antiretroviral therapy and started him on dapsone. The pathogenesis of EED is not completely understood, but it has been associated with numerous systemic conditions that may be infectious, inflammatory, or neoplastic. Only recently has EED been recognized as a defined reactive dermatosis of HIV. We present an exemplary case of HIV-associated EED and review the differential diagnosis, highlighting clinical features of EED that appear to be more frequently encountered in the HIV-infected population.

Giant Cutaneous Horn Arising in an Epidermal Nevus.

Cutaneous horns, which rarely occur in children, can overlie a large array of pathologic lesions that range from benign to malignant. When a cutaneous horn is encountered, it is not the horn itself that is of relevance, it is the nature of the underlying disease that dictates overall prognosis and management. In this report we present a case of a cutaneous horn arising within a linear verrucous epidermal nevus and briefly review cutaneous horns, with an emphasis on their clinical implications and differential diagnosis.