Permanent Alopecia in Breast Cancer Patients: Role of Taxanes and Endocrine Therapies.

Permanent chemotherapy-induced alopecia (PCIA) has been described following high-dose chemotherapy regimens for allogeneic bone marrow transplants; however, reports of PCIA in breast cancer patients are increasing. Many prior reports involve treatment with taxanes, but the role of endocrine therapies has not been well defined. Permanent alopecia in breast cancer patients appears to be a potential adverse effect of taxanes and endocrine therapies. Although the cytotoxic effects of taxanes may lead to permanent hair loss, the influence of endocrine therapies on the remaining follicles may affect the pattern of hair loss. Further characterization of these cases may elucidate risk factors for developing permanent alopecia, allowing for more appropriate risk stratification and counseling. We describe 3 patients with breast cancer who experienced PCIA following chemotherapy with taxanes.

Anetoderma in a patient with a history of primary syphilis.

Anetoderma is a rare cutaneous disorder presenting with atrophic skin lesions. It can be associated with several autoimmune and infectious diseases. With the current resurgence of syphilis, clinicians must be aware of its association with anetoderma.

COX-2 inhibition prevents the appearance of cutaneous squamous cell carcinomas accelerated by BRAF inhibitors.

Keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cuSCCs) develop in 15-30% of patients with BRAF(V600E) metastatic melanoma treated with BRAF inhibitors (BRAFi). These lesions resemble mouse skin tumors induced by the two-stage DMBA/TPA skin carcinogenesis protocol; in this protocol BRAFi accelerates tumor induction. Since prior studies demonstrated cyclooxygenase 2 (COX-2) is necessary for DMBA/TPA tumor induction, we hypothesized that COX-2 inhibition might prevent BRAFi-accelerated skin tumors. Celecoxib, a COX-2 inhibitor, significantly delayed tumor acceleration by the BRAFi inhibitor PLX7420 and decreased tumor number by 90%. Tumor gene expression profiling demonstrated that celecoxib partially reversed the PLX4720-induced gene signature. In PDV cuSCC cells, vemurafenib (a clinically approved BRAFi) increased ERK phosphorylation and soft agar colony formation; both responses were greatly decreased by celecoxib. In clinical trials trametinib, a MEK inhibitor (MEKi) increases BRAFi therapy efficacy in BRAF(V600E) melanomas and reduces BRAFi-induced KA and cuSCC frequency. Trametinib also reduced vemurafenib-induced PDV soft agar colonies, but less efficiently than celecoxib. The trametinb/celecoxib combination was more effective than either inhibitor alone. In conclusion, celecoxib suppressed both BRAFi-accelerated skin tumors and soft-agar colonies, warranting its testing as a chemopreventive agent for non-melanoma skin lesions in patients treated with BRAFi alone or in combination with MEKi.

An unusual presentation and distribution of generalized eruptive syringomas.

A 19-year-old Caucasian man presented with numerous erythematous to flesh-colored papules that appeared in crops on his neck, axillae, buttocks, and lower back. The lesions started on his anterior neck at age 12. At 18 years, new crops of papules appeared on his axillae, back, and buttocks over several months. He reported pruritus in the lesions following exercise and perspiration. He denied any family history of similar lesions. His primary care physician treated him with topical triamcinolone 0.1% cream, which made the lesions smaller, less erythematous, and less pruritic; however, the papules never fully resolved. After discontinuation of the steroids, these erythematous pruritic papules gradually recurred in the same areas of his body. The patient denied any other medical complaints.

Acute graft-versus-host disease after pediatric solid organ transplant.

Acute graft-versus-host disease (GVHD) is a rare and life threatening complication after solid organ transplantation. The diagnosis can be made with clinical and laboratory evidence of skin, liver, or intestinal involvement. The role of skin biopsy in confirming acute GVHD is debatable. However, it is proposed that the skin biopsy is a valuable tool in confirming the diagnosis in low prior probability settings. An atypical case of acute GVHD following orthotopic liver and small bowel transplantation in a 2-year-old male is presented. Seven weeks posttransplantation, the patient developed a bullous eruption limited to the buttocks and upper thighs. A skin biopsy was performed which showed interface dermatitis and epidermal necrosis consistent with acute GVHD. Prompt treatment with daclizumab and intravenous corticosteroids was given and the patient survived without evidence of systemic GVHD. This case highlights the importance of skin biopsy in establishing the prompt diagnosis of GVHD in low prior probability settings.

Cutaneous side effects of epidermal growth factor receptor inhibitors: clinical presentation, pathogenesis, and management.

The growing investigation and use of epidermal growth factor receptor (EGFR) inhibitors in anticancer therapy has been motivated by their specificity for EGFR, which improves their ability to target cancer cells and enhances their safety profile compared with many other conventional chemotherapeutic agents. However, their growing use has been accompanied by an increasing incidence of cutaneous toxicities, which can cause serious discomfort and be disabling. This review illustrates the common cutaneous side effects seen in patients receiving EGFR inhibitors and discusses various options for management. With effective management of these side effects, dermatologists can play an integral role in facilitating compliance with anti-EGFR therapy and aid with effective oncologic management.

Inhibitory and excitatory responses of single neurons in the human medial temporal lobe during recognition of faces and objects.

The medial temporal lobe (MTL) plays a critical role in transforming complex stimuli into permanent memory traces, yet little is known on how the activity of neurons in the human brain mediates this process. Recording from single neurons in the human MTL during visual encoding and retrieval of faces and objects, we found that in the hippocampus faces evoked predominantly suppression of neuronal firing below prestimulus baseline ('inhibitory responses'). These responses were also prevalent in the entorhinal cortex but were absent in the amygdala during the first second of stimulus encoding when all responses to faces were 'excitatory' (neuronal firing increased above the prestimulus baseline). Inhibitory responses were more prevalent during recognition than encoding and were also present during processing of objects, albeit less frequently than during processing of faces. Despite the prevalence in the hippocampus of cells with inhibitory responses and their relative specificity to faces, it was mainly the activity of the cells with excitatory responses that was selective for stimulus features such as gender and emotional expression of faces. These findings suggest that a large population of cells with inhibitory responses is engaged in the hippocampal memory network, but primarily cells with excitatory responses process feature-specific information.