Roflumilast foam 0.3% for adolescent and adult patients with seborrheic dermatitis: A randomized, double-blinded, vehicle-controlled, phase 3 trial.

BACKGROUND: The topical phosphodiesterase 4 inhibitor roflumilast has been studied in several dermatologic conditions. OBJECTIVE: Roflumilast foam 0.3% is being investigated as a topical treatment for seborrheic dermatitis (SD). METHODS: In this phase 3, double-blinded trial, patients with SD were randomly assigned (2:1 ratio) to once-daily roflumilast foam 0.3% or vehicle foam for 8 weeks. The primary efficacy outcome was Investigator Global Assessment (IGA) Success at week 8, defined as IGA of 0 (Clear) or 1 (Almost Clear) plus ≥2-point improvement from baseline. Safety was also assessed. RESULTS: 79.5% of roflumilast-treated and 58.0% of vehicle-treated patients met the primary endpoint (P < .001); statistically significant differences in IGA Success also favored roflumilast at week 2 (roflumilast: 43.0%; vehicle: 25.7%; P < .001) and week 4 (roflumilast: 73.1%; vehicle: 47.1%; P < .001). Roflumilast was well-tolerated with a low rate of treatment-emergent adverse events. LIMITATIONS: Study limitations include the 8-week treatment period for this chronic condition. CONCLUSIONS: Once-daily roflumilast foam was superior to vehicle in leading to IGA of Clear or Almost Clear plus ≥2-point improvement from baseline at 8 weeks in patients with SD. Longer trials are needed to determine durability and safety of roflumilast foam in SD.

AP-2alpha: a regulator of EGF receptor signaling and proliferation in skin epidermis.

AP-2 transcription factors have been implicated in epidermal biology, but their functional significance has remained elusive. Using conditional knockout technology, we show that AP-2alpha is essential for governing the balance between growth and differentiation in epidermis. In vivo, epidermis lacking AP-2alpha exhibits elevated expression of the epidermal growth factor receptor (EGFR) in the differentiating layers, resulting in hyperproliferation when the receptors are activated. Chromatin immunoprecipitation and promoter activity assays identify EGFR as a direct target gene for AP-2alpha repression, and, in the absence of AP-2alpha, this is manifested primarily in excessive EGF-dependent phosphoinositol-3 kinase/Akt activity. Together, our findings unveil a hitherto unrecognized repressive role for AP-2alpha in governing EGFR gene transcription as cells exit the basal layer and withdraw from the cell cycle. These results provide insights into why elevated AP-2alpha levels are often associated with terminal differentiation and why tumor cells often display reduced AP-2alpha and elevated EGFR proteins.

Detecting early functional damage in glaucoma suspect and ocular hypertensive patients with the multifocal VEP technique.

PURPOSE: To determine whether the multifocal visual evoked potential (mfVEP) technique can detect early functional damage in ocular hypertensive (OHT) and glaucoma suspect (GS) patients with normal standard achromatic automated perimetry (SAP) results. PATIENTS AND METHODS: Twenty-five GS patients (25 eyes), 25 patients with OHT (25 eyes), and 50 normal controls (50 eyes) were enrolled in this study. All GS, OHT and normal control eyes had normal SAP as defined by a pattern standard deviation and mean deviation within the 95% confidence interval and a glaucoma hemifield test within normal limits on the Humphrey visual field 24-2 program. Eyes with GS had optic disc changes consistent with glaucoma with or without raised intraocular pressure (IOP), and eyes with OHT showed no evidence of glaucomatous optic neuropathy and IOPs >or=22 mm Hg. Monocular mfVEPs were obtained from both eyes of each subject using a pattern-reversal dartboard array with 60 sectors. The entire display had a radius of 22.3 degrees. The mfVEPs, for each eye, were defined as abnormal when either the monocular or interocular probability plot had a cluster of 3 or more contiguous points with P<0.05 and at least 2 of these points with P<0.01. RESULTS: The mfVEP results were abnormal in 4% of the eyes from normal subjects. Abnormal mfVEPs were detected in 20% of the eyes of GS patients and 16% of the eyes of OHT patients. Significantly more mfVEP abnormalities were detected in GS patients than in normal controls. However, there was no significant difference in mfVEP results between OHT patients and normal controls. CONCLUSIONS: The mfVEP technique can detect visual field deficits in a minority of eyes with glaucomatous optic disks and normal SAP results.

Generalized eruptive keratoacanthoma of Grzybowski.

We describe the case of a 71-year-old woman with a six-year history of generalized eruptive keratoacanthomas on the extremities. We review the diagnostic clinical and histologic features of the rare Grzybowski variant of generalized eruptive keratoacanthoma. The course of this disease is chronic and often demonstrates a poor response to therapy.

Steatocystoma multiplex.

A 25-year-old man with a 20-year history of asymptomatic nodules on his arms and trunk, which histopathological analysis showed to be consistent with steatocystoma multiplex, is presented. Steatocystoma multiplex is a disorder characterized by multiple, asymptomatic, dermal cysts that usually occur on the trunk and proximal aspects of the extremities. Steatocystoma multiplex with acral predominance has only recently been described. Development of steatocystomas has been hypothesized to be due to alterations in the structure of keratin 17. Treatment for lesions has included surgical excision or drainage, oral retinoids, and liquid nitrogen cryotherapy.

Progressive and symmetric erythrokeratoderma.

A case of progressive and symmetric erythrokeratoderma in a 9-year-old boy is presented. The evidence for loricrin as a candidate gene for this disorder as well as the clinical features of this disease are reviewed.

Generalized eruptive keratoacanthomas.

We describe the case of a 71-year-old-woman with a 6-year history of generalized eruptive keratoacanthomas on the extremities. We review the diagnostic clinical and histologic features of the rare Grzybowski variant of generalized eruptive keratoacanthoma. The course of this disease is chronic and often demonstrates a poor response to therapy.

Verrucous plaque on the foot.

Amelanotic melanoma can present clinically in multiple ways, often mimicking benign processes. This makes diagnosis more difficult and often delays proper medical attention. This case report highlights the importance of having a high suspicion of melanoma in cases that do not behave clinically as expected.