Pathophysiology of Autoimmune Bullous Diseases: Nature Versus Nurture.

Pemphigus and pemphigoid are the prototypical immunobullous diseases. Although it has been well established that they are caused by deposition of autoreactive antibodies directed against adherence proteins within the skin, the specific genetic and environmental factors leading to development of these diseases continue to be an area of investigation. Herein, we discuss several of the potential environmental triggers that may induce patients to develop immunobullous diseases including medications, viral infections, UV exposure or other radiation injury and dietary factors. In addition, the potential genetic and immunologic mechanisms contributing to the pathogenesis of pemphigus and pemphigoid will be reviewed. The multifactorial nature of these diseases contributes to their complexity and highlights the importance of a detailed personal and family history when caring for these patients.

Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic Studies.

BACKGROUND: Pyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood. OBJECTIVE: Use data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology. METHODS: Ten PG patients participated and answered questions about new ulcer formation. Skin biopsies of healed prior ulcers and adjacent normal skin were obtained from four patients for immunohistochemistry. Scars from healthy patients and patients with discoid lupus were used as additional controls. New onset PG papules were analyzed using immunohistochemistry and gene expression analysis via quantitative real-time PCR. RESULTS: All PG patients reported that healed sites of previous ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and uninvolved skin triggered ulceration only in the latter. On immunohistochemistry, healed PG scars showed complete loss of pilosebaceous units, which were present in normal skin, and to a lesser extent in control scars, and discoid scars. Early PG papules showed perivascular and peripilosebaceous T cell infiltrates, rather than neutrophils. These early inflammatory events were dominated by increased gene expression of CXCL9, CXCL10, CXCL11, IL-8, IL-17, IFNG, and IL-36G and transcription factors consistent with Th1 phenotype. LIMITATIONS: Small sample size was the main limitation. CONCLUSION: We put forth the hypothesis that PG is a T cell response resulting in the destruction of pilosebaceous units.

Trends in National Institutes of Health Funding of Principal Investigators in Dermatology Research by Academic Degree and Sex.

IMPORTANCE: National Institutes of Health (NIH) grants are becoming increasingly competitive in the academic research arena. Identifying NIH funding disparities is an important step in improving academic diversity. OBJECTIVE: To examine recent NIH funding trends in dermatology. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study with linear regression analysis and repeated-measures analysis of variance of all NIH grants awarded to departments of dermatology from fiscal year 2009 to 2014. Funding data were exported from the NIH Research Portfolio Online Reporting Tools Expenditures and Results. Publication data were drawn from Scopus. All NIH-funded principal investigators in dermatology were categorized by their academic degree and sex. MAIN OUTCOMES AND MEASURES: The NIH funding trends were compared by investigator degree (MD, PhD, or MD/PhD) and sex. RESULTS: A total of 1292 NIH-funded grants were awarded to dermatology research from fiscal year 2009 through 2014. Adjusted NIH funding for dermatologic research diminished by 4.6% from $67.3 million in 2009 to $64.2 million in 2014, with a nadir of $58.6 million in 2013. Funding for the NIH's Research Project Grant Program (R01) decreased by 21.0% from $43.9 million to $34.7 million during this period. The dollar amount of NIH funding significantly trended down for investigators with an MD degree by $1.35 million per year from $23.6 million in 2009 to $18.4 million in 2014 (P = .02) while there was no significant change in NIH funding for MD/PhD (from $17.6 million in 2009 to $19.8 million in 2014; P = .44) and PhD investigators (from $26.1 million in 2009 to $25.9 million in 2014; P = .74). Similarly, the total dollar amount of R01 grants awarded to principal investigators with only an MD degree trended down by $1.4 million per year from $13.2 million in 2009 to $6.0 million in 2014 (P < .001). The number of female investigators with NIH grants in dermatology trended down significantly compared with the trend of their male counterparts (from 49 women in 2009 to 43 women in 2014 vs from 84 men in 2009 to 97 men in 2014; P = .04). CONCLUSIONS AND RELEVANCE: There is a downward trend in NIH funding for female and MD-only dermatology investigators. Departmental support and junior faculty mentorship for women and MD investigators is crucial for maintaining their presence in NIH-funded dermatology research.

Cyclosporine-induced sebaceous hyperplasia in a hematopoetic stem cell transplant patient: delayed onset of a common adverse event.

Cyclosporine-induced sebaceous hyperplasia (SH) is a well-documented entity, occurring in up to 30% of renal transplant patients treated with cyclosporine and has also been reported to occur following heart or hematopoetic stem cell transplantation (HCST). Cyclosporine has a stimulatory effect on undifferentiated sebocytes, resulting in the clinical and histologic findings in these patients. Sebaceous hyperplasia most commonly presents as asymptomatic papules over the face, chest, or groin. Herein we describe a case of a 27-year-old man who developed facial sebaceous hyperplasia five months after completing cyclosporine therapy for cutaneous graft versus host disease (GVHD) following HSCT.

Metastatic melanoma - a review of current and future treatment options.

Despite advances in treatment and surveillance, melanoma continues to claim approximately 9,000 lives in the US annually (SEER 2013). The National Comprehensive Cancer Network currently recommends ipilumumab, vemurafenib, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma. Little data exists to guide management of cutaneous and subcutaneous metastases despite the fact that they are relatively common. Existing options include intralesional Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod, cryotherapy, radiation therapy, interferon therapy, and intratumoral interleukin-2 injections. Newly emerging treatments include the anti-programmed cell death 1 receptor agents (nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec). Available treatments for select sites include adoptive T cell therapies and dendritic cell vaccines. In addition to reviewing the above agents and their mechanisms of action, this review will also focus on combination therapy as these strategies have shown promising results in clinical trials for metastatic melanoma treatment.