Diana Bolotin

Dermatitis herpetiformis: Part I. Epidemiology, pathogenesis, and clinical presentation

Dermatitis herpetiformis (DH) is an autoimmune disease that is linked to gluten sensitivity and has a clear relationship to celiac disease. Both conditions are mediated by the IgA class of autoantibodies and the diagnosis of DH is dependent on detection of granular deposits of IgA in the skin. There is an underlying genetic predisposition to the development of DH but environmental factors are also important. Typically, young adults present with excoriations only, as the severe pruritus effectively destroys any primary lesions. Based upon our experience with DH and a comprehensive literature review, we provide an update of DH epidemiology, pathophysiology, and clinical presentation.

AP-2α: 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-2α is essential for governing the balance between growth and differentiation in epidermis. In vivo, epidermis lacking AP-2α 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-2α repression, and, in the absence of AP-2α, this is manifested primarily in excessive EGF-dependent phosphoinositol-3 kinase/Akt activity. Together, our findings unveil a hitherto unrecognized repressive role for AP-2α 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-2α levels are often associated with terminal differentiation and why tumor cells often display reduced AP-2α and elevated EGFR proteins.

Dermatitis herpetiformis: Part II. Diagnosis, management, and prognosis

The prompt recognition of the clinical features of dermatitis herpetiformis (DH) is important, but securing a definitive diagnosis requires further work-up. Recent advances in understanding of the immunologic basis for DH have led to the development and wider availability of serologic testing, which is rapidly becoming an essential part of the diagnosis and management of DH. Part II of this series will detail the diagnosis, treatment, and follow-up for patients with DH, and will particularly focus on recent advances in the field.

Dissection of a complex enhancer element: maintenance of keratinocyte specificity but loss of differentiation specificity.

ABSTRACT In this report, we explored the mechanisms underlying keratinocyte-specific and differentiation-specific gene expression in the skin. We have identified five keratinocyte-specific, open chromatin regions that exist within the 6 kb of 5′ upstream regulatory sequence known to faithfully recapitulate the strong endogenous keratin 5 (K5) promoter and/or enhancer activity. One of these, DNase I-hypersensitive site (HSs) 4, was unique in that it acted independently to drive abundant and keratinocyte-specific reporter gene activity in culture and in transgenic mice, despite the fact that it was not essential for K5 enhancer activity. We have identified evolutionarily conserved regulatory elements and a number of their associated proteins that bind to this compact and complex enhancer element. The 125-bp 3′ half of this element (referred to as 4.2) is by far the smallest known strong enhancer element possessing keratinocyte-specific activity in vivo. Interestingly, its activity is restricted to a subset of progeny of K5-expressing cells located within the sebaceous gland. The other half of HSs 4 (termed 4.1) possesses activity to suppress sebocyte-specific expression and induce expression in the channel (inner root sheath) cells surrounding the hair shaft. Our findings lead us to a view of keratinocyte gene expression which is determined by multiple regulatory modules, many of which contain AP-2 and/or Sp1/Sp3 binding sites for enhancing expression in skin epithelium, but which also harbor one or more unique sites for the binding of factors which determine specificity. Through mixing and matching of these modules, additional levels of specificity are obtained, indicating that both transcriptional repressors and activators govern the specificity.

Adverse Events Associated With Mohs Micrographic Surgery Multicenter Prospective Cohort Study of 20 821 Cases at 23 Centers

IMPORTANCE Detailed information regarding perioperative risk and adverse events associated with Mohs micrographic surgery (MMS) can guide clinical management. Much of the data regarding complications of MMS are anecdotal or report findings from single centers or single events. OBJECTIVES To quantify adverse events associated with MMS and detect differences relevant to safety. DESIGN, SETTING, AND PARTICIPANTS Multicenter prospective inception cohort study of 21 private and 2 institutional US ambulatory referral centers for MMS. Participants were a consecutive sample of patients presenting with MMS for 35 weeks at each center, with staggered start times. EXPOSURE Mohs micrographic surgery. MAIN OUTCOMES AND MEASURES Intraoperative and postoperative minor and serious adverse events. RESULTS Among 20 821 MMS procedures, 149 adverse events (0.72%), including 4 serious events (0.02%), and no deaths were reported. Common adverse events reported were infections (61.1%), dehiscence and partial or full necrosis (20.1%), and bleeding and hematoma (15.4%). Most bleeding and wound-healing complications occurred in patients receiving anticoagulation therapy. Use of some antiseptics and antibiotics and sterile gloves during MMS were associated with modest reduction of risk for adverse events. CONCLUSIONS AND RELEVANCE Mohs micrographic surgery is safe, with a very low rate of adverse events, an exceedingly low rate of serious adverse events, and an undetectable mortality rate. Common complications include infections, followed by impaired wound healing and bleeding. Bleeding and wound-healing issues are often associated with preexisting anticoagulation therapy, which is nonetheless managed safely during MMS. We are not certain whether the small effects seen with the use of sterile gloves and antiseptics and antibiotics are clinically significant and whether wide-scale practice changes would be cost-effective given the small risk reductions.

Treatment of forehead/glabellar rhytide complex with combination botulinum toxin a and hyaluronic acid versus botulinum toxin a injection alone: a split‐face, rater‐blinded, randomized control trial

Forehead and glabella rhytides are treated mostly with neurotoxins, although some practitioners prefer the concurrent use of fillers. It has been suggested that combination treatments can result in a better overall improvement.

The comparative effectiveness of suction-curettage and onabotulinumtoxin-A injections for the treatment of primary focal axillary hyperhidrosis: a randomized control trial.

BACKGROUND Botulinum toxin injections and suction-curettage have been separately shown to be effective in treating axillary hyperhidrosis but have not been compared in the same patients. OBJECTIVE We sought to compare effectiveness of suction-curettage versus neurotoxin for the treatment of axillary hyperhidrosis. METHODS Each of 20 patients was randomized to receive toxin injections to one axilla and suction-curettage to the contralateral axilla. The primary outcome measure was reduction of sweat rate measured by gravimetry, and the secondary measure was quality of life as measured by a patient-directed questionnaire. RESULTS At 3 months posttreatment, toxin injections decreased baseline resting sweat production by 72.1% versus 60.4% (P = .29) for suction-curettage, and baseline exercise-induced sweat production by 73.8% versus 58.8% (P = .10). When patients were stratified into the categories of light and heavy sweaters, there was a difference among heavy sweaters, with exercise-induced sweat production lower by 10.48 mg/min or 34.3% (P = .0025) at toxin-treated sites. Compared with suction-curettage, toxin also resulted in greater improvements in quality of life by 0.80 points (P = .0002) and 0.90 points (P = .0017) at 3 and 6 months posttreatment, respectively, as measured by the patient questionnaire. LIMITATIONS The follow-up period was limited to 6 months. CONCLUSIONS By objective measures 3 months after treatment, neurotoxin injections are nominally more effective than suction-curettage in all cases, and markedly more effective in heavy sweaters. Patients have a very significant preference for neurotoxin injections at 3 months, and this is maintained at 6 months.

Objective Structured Assessment of Technical Skills in Elliptical Excision Repair of Senior Dermatology Residents: A Multirater, Blinded Study of Operating Room Video Recordings

IMPORTANCE Surgical training in dermatology residencies has increased, and there is growing interest in measuring resident competence more precisely. This study applies the use of the objective structured assessment of technical skills (OSATS) to measure competence in dermatologic surgery. OBJECTIVE To evaluate the utility of OSATS as a tool for measuring surgery skills during dermatology residency training. DESIGN, SETTING, AND PARTICIPANTS Multirater, blinded review and ratings of taped video recordings of elliptical excisions performed by senior dermatology residents applying for procedural or Mohs surgery fellowships. MAIN OUTCOMES AND MEASURES Ratings on a specific OSATS measure, including global rating scale and task checklist. RESULTS Twelve videos, representing approximately 20% of fellowship applicants during 2009-2010, were rated. Raters agreed on 272 of 288 subscore ratings (94.4%). Mean global ratings were 4 or 5 for all categories, except time and motion, which had a rating of 3. Task checklist ratings had a mean of 14.5 and a mode of 16 (perfect score), with eversion least often performed successfully. No association was found between a residents scores and the number of surgical rotation months or between scores and the number of Mohs surgeons at the home institution. CONCLUSIONS AND RELEVANCE Senior dermatology residents preparing for surgery fellowships are highly skilled in performing elliptical excisions and bilayered repairs. The OSATS appears useful and reliable for the evaluation of dermatologic surgery skills.

Multicenter prospective cohort study of the incidence of adverse events associated with cosmetic dermatologic procedures: Lasers, energy devices, and injectable neurotoxins and fillers

IMPORTANCE Common noninvasive to minimally invasive cosmetic dermatologic procedures are widely believed to be safe given the low incidence of reported adverse events, but reliable incidence data regarding adverse event rates are unavailable to date. OBJECTIVE To assess the incidence of adverse events associated with noninvasive to minimally invasive cosmetic dermatologic procedures, including those involving laser and energy devices, as well as injectable neurotoxins and fillers. DESIGN, SETTING, AND PARTICIPANTS A multicenter prospective cohort study (March 28, 2011, to December 30, 2011) of procedures performed using laser and energy devices, as well as injectable neurotoxins and soft-tissue augmentation materials, among 8 geographically dispersed US private and institutional dermatology outpatient clinical practices focused on cosmetic dermatology, with a total of 23 dermatologists. Participants represented a consecutive sample of 20 399 cosmetic procedures. Data acquisition was for 3 months (13 weeks) per center, with staggered start dates to account for seasonal variation. EXPOSURES Web-based data collection daily at each center to record relevant procedures, by category type and subtype. Adverse events were detected by (1) initial observation by participating physicians or staff; (2) active ascertainment from patients, who were encouraged to self-report after their procedure; and (3) follow-up postprocedural phone calls to patients by staff, if appropriate. When adverse events were not observed by physicians but were suspected, follow-up visits were scheduled within 24 hours to characterize these events. Detailed information regarding each adverse event was entered into an online form. MAIN OUTCOMES AND MEASURES The main outcome was the total incidence of procedure-related adverse events (total adverse events divided by total procedures performed), as verified by clinical examination. RESULTS Forty-eight adverse events were reported, for a rate of 0.24% (95% CI, 0.18%-0.31%). Overall, 36 procedures resulted in at least 1 adverse event, for a rate of 0.18% (95% CI, 0.13%-0.25%). No serious adverse events were reported. Adverse events were infrequently associated with known risk factors. CONCLUSIONS AND RELEVANCE Noninvasive to minimally invasive cosmetic dermatologic procedures, including energy, neurotoxin, and filler procedures, are safe when performed by experienced board-certified dermatologists. Adverse events occur in less than 1% of patients, and most of these are minor and transient.

Cancer: More than skin deep.

Activation of the nuclear factor NF-κB has been linked with many human cancers. But in tumours of some tissues this molecule is inactive. New work examines how turning off NF-κB promotes cancer in one tissue, the skin.