Crown Vessels of Desmoplastic Trichilemmoma: Use of Dermoscopy with Pathological Correlation.

Desmoplastic trichilemmoma is a rare histological variant of a benign tumor of the pilosebaceous hair follicle that often clinically appears as similar in appearance to other cutaneous lesions. Here, an 81-year-old male patient with desmoplastic trichilemmoma found on the left zygoma is presented. During the dermatoscopic evaluation of the neoplasm, crown vessels with radial distribution in the periphery were displayed. Histopathologic evaluation revealed peripheral palisading lobules of tumor cells surrounded by sclerotic hyalinized stroma displacing the vessels of the tumor. This case highlights the value of using dermoscopy for improving the clinical diagnosis of desmoplastic trichilemmoma. These findings highlight a need to further investigate the diagnosis of desmoplastic trichilemmoma when crown vessels are displayed during the clinical evaluation.

Factors contributing to burnout in dermatologists.

Physician burnout is associated with increased medical errors, lower patient satisfaction, and decreased professional work effort. Although rates of burnout are lower in dermatology than in other specialties, the prevalence is still high and increasing. Burnout affects both personal and patient care. It is important to consider factors and ways to combat this phenomenon to prevent deterioration. To achieve this, a comprehensive understanding of the causes contributing to burnout in dermatology is crucial. To date, a limited number of publications have specifically addressed burnout in dermatology. In this contribution, burnout in dermatology, burnout prevention, and promotion of dermatologist wellness through the systemic approach of the Stanford model for professional fulfillment, which includes creating a culture of wellness, workplace efficiency, and resilience, are reviewed.

Neutrophilic Urticarial Dermatosis Without Underlying Systemic Disease.

Neutrophilic urticarial dermatosis (NUD) is rare and poorly understood. First described in 2009, NUD has been reported in association with systemic and autoinflammatory disorders. Here, we describe an example of NUD occurring in the absence of underlying systemic findings that showed an excellent response to low-dose dapsone.

Repigmentation in vitiligo universalis after starting dialysis-could they be related?

Vitiligo is an acquired disorder of pigmentation characterized by the development of white macules and patches on the skin. Although multiple theories have been proposed to understand the underlying pathophysiology behind the pigment loss, the exact etiology remains unknown. Vitiligo universalis is an extremely rare variant that causes nearly complete depigmentation of the entire body surface. Treatment is challenging, especially when pigment loss is generalized and diffuse. We present a unique case of a patient with vitiligo universalis that had remained untreated and stable for >20 years until she developed repigmentation shortly after initiation of dialysis.

Successful treatment of recalcitrant molluscum contagiosum in a stem cell transplant patient with Candida immunotherapy.

Solid organ and stem cell transplant recipients have an increased risk of developing cutaneous infections, which often are refractory to conventional treatment (Euvrard et al., Journal of the American Academy of Dermatology, 2001, 44, 932-939). Molluscum contagiosum, a common self-limited disease primarily affecting children, can be more severe and unresponsive to therapy in transplant patients (Gardner & Ormond, Clinical and Experimental Dermatology, 2006, 31, 452-453). Candida immunotherapy has been widely used for the treatment of warts, and recently its application has been expanded to include treatment of symptomatic molluscum in pediatric patients (Enns & Evans, Pediatric Dermatology, 2011, 28, 254-258; Maronn et al., Pediatric Dermatology, 2008, 25, 189-192). However, to our knowledge there have been no reports in the literature of its utility in the setting of adult transplant or immunocompromised patients. Herein, we report a case of successful treatment of refractory molluscum contagiosum in a stem cell transplant patient with Candida immunotherapy.

Dietary phosphate restriction suppresses phosphaturia but does not prevent FGF23 elevation in a mouse model of chronic kidney disease.

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that in end-stage renal disease is markedly increased in serum; however, the mechanisms responsible for this increase are unclear. Here, we tested whether phosphate retention in chronic kidney disease (CKD) is responsible for the elevation of FGF23 in serum using Col4α3 knockout mice, a murine model of Alport disease exhibiting CKD. We found a significant elevation in serum FGF23 in progressively azotemic 8- and 12-week-old CKD mice along with an increased fractional excretion of phosphorus. Both moderate and severe phosphate restriction reduced fractional excretion of phosphorus by 8 weeks, yet serum FGF23 levels remained strikingly elevated. By 12 weeks, FGF23 levels were further increased with moderate phosphate restriction, while severe phosphate restriction led to severe bone mineralization defects and decreased FGF23 production in bone. CKD mice on a control diet had low serum 1,25-dihydroxyvitamin D (1,25(OH)(2)D) levels and 3-fold higher renal Cyp24α1 gene expression compared to wild-type mice. Severe phosphate restriction increased 1,25(OH)(2)D levels in CKD mice by 8 weeks and lowered renal Cyp24α1 gene expression despite persistently elevated serum FGF23. Renal klotho gene expression declined in CKD mice on a control diet, but improved with severe phosphate restriction. Thus, dietary phosphate restriction reduces the fractional excretion of phosphorus independent of serum FGF23 levels in mice with CKD.

Longitudinal evaluation of FGF23 changes and mineral metabolism abnormalities in a mouse model of chronic kidney disease.

Fibroblast growth factor 23 (FGF23) is a phosphaturic and vitamin D-regulatory hormone of putative bone origin that is elevated in patients with chronic kidney disease (CKD). The mechanisms responsible for elevations of FGF23 and its role in the pathogenesis of chronic kidney disease-mineral bone disorder (CKD-MBD) remain uncertain. We investigated the association between FGF23 serum levels and kidney disease progression, as well as the phenotypic features of CKD-MBD in a Col4a3 null mouse model of human autosomal-recessive Alport syndrome. These mice exhibited progressive renal failure, declining 1,25(OH)(2)D levels, increments in parathyroid hormone (PTH) and FGF23, late-onset hypocalcemia and hyperphosphatemia, high-turnover bone disease, and increased mortality. Serum levels of FGF23 increased in the earliest stages of renal damage, before elevations in blood urea nitrogen (BUN) and creatinine. FGF23 gene transcription in bone, however, did not increase until late-stage kidney disease, when serum FGF23 levels were exponentially elevated. Further evaluation of bone revealed trabecular osteocytes to be the primary cell source for FGF23 production in late-stage disease. Changes in FGF23 mirrored the rise in serum PTH and the decline in circulating 1,25(OH)(2)D. The rise in PTH and FGF23 in Col4a3 null mice coincided with an increase in the urinary fractional excretion of phosphorus and a progressive decline in sodium-phosphate cotransporter gene expression in the kidney. Our findings suggest elevations of FGF23 in CKD to be an early marker of renal injury that increases before BUN and serum creatinine. An increased production of FGF23 by bone may not be responsible for early increments in FGF23 in CKD but does appear to contribute to FGF23 levels in late-stage disease. Elevations in FGF23 and PTH coincide with an increase in urinary phosphate excretion that likely prevents the early onset of hyperphosphatemia in the face of increased bone turnover and a progressive decline in functional renal mass.

Different mechanisms for resistance to trastuzumab versus lapatinib in HER2-positive breast cancers--role of estrogen receptor and HER2 reactivation.

INTRODUCTION: The human epidermal growth factor receptor 2 (HER2)-targeted therapies trastuzumab (T) and lapatinib (L) show high efficacy in patients with HER2-positive breast cancer, but resistance is prevalent. Here we investigate resistance mechanisms to each drug alone, or to their combination using a large panel of HER2-positive cell lines made resistant to these drugs. METHODS: Response to L + T treatment was characterized in a panel of 13 HER2-positive cell lines to identify lines that were de novo resistant. Acquired resistant lines were then established by long-term exposure to increasing drug concentrations. Levels and activity of HER2 and estrogen receptor (ER) pathways were determined by qRT-PCR, immunohistochemistry, and immunoblotting assays. Cell growth, proliferation, and apoptosis in parental cells and resistant derivatives were assessed in response to inhibition of HER or ER pathways, either pharmacologically (L, T, L + T, or fulvestrant) or by using siRNAs. Efficacy of combined endocrine and anti-HER2 therapies was studied in vivo using UACC-812 xenografts. RESULTS: ER or its downstream products increased in four out of the five ER+/HER2+ lines, and was evident in one of the two intrinsically resistant lines. In UACC-812 and BT474 parental and resistant derivatives, HER2 inhibition by T reactivated HER network activity to promote resistance. T-resistant lines remained sensitive to HER2 inhibition by either L or HER2 siRNA. With more complete HER2 blockade, resistance to L-containing regimens required the activation of a redundant survival pathway, ER, which was up-regulated and promoted survival via various Bcl2 family members. These L- and L + T-resistant lines were responsive to fulvestrant and to ER siRNA. However, after prolonged treatment with L, but not L + T, BT474 cells switched from depending on ER as a survival pathway, to relying again on the HER network (increased HER2, HER3, and receptor ligands) to overcome L's effects. The combination of endocrine and L + T HER2-targeted therapies achieved complete tumor regression and prevented development of resistance in UACC-812 xenografts. CONCLUSIONS: Combined L + T treatment provides a more complete and stable inhibition of the HER network. With sustained HER2 inhibition, ER functions as a key escape/survival pathway in ER-positive/HER2-positive cells. Complete blockade of the HER network, together with ER inhibition, may provide optimal therapy in selected patients.