Mild to Moderate Dysphagia Following Very Low-dose Abobotulinumtoxin A for Platysmal Bands.

Onabotulinumtoxin A (Botox) can be a safe and successful off-label treatment of vertical platysma bands of various severities. Due to risk of the botulinum toxin diffusing to the underlying anatomic structures such as the deglutition muscles, the larynx, and the neck flexors, a maximal dose of 100 units has been suggested and there have been no known reports of untoward effects with doses less than 60 units. We present a case of mild to moderate dysphagia in a patient after very low doses of Abobutulinumtoxin (60 units, equivalent to 20 units of Onabotulinumtoxin using a 3:1 conversion ratio). We speculate that the adverse effects noted may be due to several possibilities, such as diffusion, injection technique, or intravascular injection. Thus, although botulinum toxin-A is generally considered a safe off-label treatment for vertical platysma bands, readers should still be aware of the possible side-effects even with low dose use, as supported by our case report of mild to moderate dysphagia with relatively conservative doses of Abobotulinumtoxin A.

J Drugs Dermatol. 2017;16(9):929-930.

Computer-aided classification of melanocytic lesions using dermoscopic images.

BACKGROUND: Computer-assisted diagnosis of dermoscopic images of skin lesions has the potential to improve melanoma early detection. OBJECTIVE: We sought to evaluate the performance of a novel classifier that uses decision forest classification of dermoscopic images to generate a lesion severity score. METHODS: Severity scores were calculated for 173 dermoscopic images of skin lesions with known histologic diagnosis (39 melanomas, 14 nonmelanoma skin cancers, and 120 benign lesions). A threshold score was used to measure classifier sensitivity and specificity. A reader study was conducted to compare the sensitivity and specificity of the classifier with those of 30 dermatology clinicians. RESULTS: The classifier sensitivity for melanoma was 97.4%; specificity was 44.2% in a test set of images. In the reader study, the classifier's sensitivity to melanoma was higher (P < .001) and specificity was lower (P < .001) than that of clinicians. LIMITATIONS: This is a retrospective study using existing images primarily chosen for biopsy by a dermatologist. The size of the test set is small. CONCLUSIONS: Our classifier may aid clinicians in deciding if a skin lesion should be biopsied and can easily be incorporated into a portable tool (that uses no proprietary equipment) that could aid clinicians in noninvasively evaluating cutaneous lesions.

The contribution of Langerhans cells to cutaneous malignancy.

The skin is at the forefront of environmental exposures, such as ultraviolet radiation and a myriad of chemicals, and is at risk for malignant transformation. The skin is a highly responsive immunological organ that contains a unique population of immature intraepidermal dendritic cells (DCs) called Langerhans cells (LCs). Although LCs show morphological and migratory changes in response to epidermal perturbation, and can function as antigen-presenting cells to activate T cells, their role in carcinogenesis is unknown. Here we review recent studies that have provided clues to the potential roles that LCs might play in the pathogenesis of skin cancer, beyond their stimulation or regulation of adaptive immunity. Understanding this role of LCs might provide new perspectives on the relevance of DC populations that are resident within other epithelial tissues for cancer.

EBI3 deficiency leads to diminished T helper type 1 and increased T helper type 2 mediated airway inflammation.

Despite extensive investigation of the signals required for development of T helper type 1 (Th1) and type 2 (Th2) immune responses, the mechanisms involved are still not well-defined. A critical role for Epstein-Barr virus-induced gene 3 (EBI3) in these responses has been proposed. EBI3, initially discovered as a transcriptionally activated gene in Epstein-Barr virus-infected B lymphocytes, codes for a subunit of the cytokine interleukin-27 (IL-27). While initial studies suggested that it had an important role in promoting Th1 responses, subsequent studies have revealed that EBI3 receptor signalling influences a variety of immune cell types and can inhibit both Th1 and Th2 responses. In the present study, we evaluated EBI3(-/-) mice for their ability to mount both Th1-mediated and Th2-mediated airway inflammatory responses. The EBI3(-/-) mice sensitized by exposure to inhaled ovalbumin plus a high dose of lipopolysaccharide, which normally results in Th1 responses in wild-type (WT) mice, instead developed Th2 type airway inflammation, with increased numbers of eosinophils. The EBI3(-/-) mice that were exposed to inhaled ovalbumin with a low dose of lipopolysaccharide, which induces Th2 responses in WT mice, showed a marked enhancement of these responses, with increased airway eosinophils, increased serum IgE levels and increased levels of Th2 cytokines (IL-4, IL-5 and IL-13) in culture supernatants of mediastinal lymph node cells. Increased production of Th2 cytokines was also seen when naive CD4(+) T cells from EBI3(-/-) mice were stimulated in vitro compared with cells from WT mice. These results provide the first evidence that EBI3 may play an inhibitory role in allergic asthma development.

Linear porokeratosis associated with multiple squamous cell carcinomas.

Linear porokeratosis is a rare subtype of porokeratosis with a higher rate of malignant transformation than other subtypes of porokeratosis. Identification of cornoid lamellae on histology allows for definitive diagnosis, which makes high clinical suspicion and appropriate biopsy essential in establishing the correct diagnosis and developing an effective management plan. We present a case report of linear porokeratosis and discuss aspects of etiology, diagnosis, and management.

Langerhans Cells Facilitate UVB-Induced Epidermal Carcinogenesis.

UVB light is considered the major environmental inducer of human keratinocyte (KC) DNA mutations, including within the tumor-suppressor gene p53, and chronic exposure is associated with cutaneous squamous cell carcinoma formation. Langerhans cells (LCs) comprise a dendritic network within the suprabasilar epidermis, yet the role of LCs in UVB-induced carcinogenesis is largely unknown. Herein we show that LC-intact epidermis develops UVB-induced tumors more readily than LC-deficient epidermis. Although levels of epidermal cyclopyrimidine dimers following acute UVB exposure are equivalent in the presence or absence of LCs, chronic UVB-induced p53 mutant clonal islands expand more readily in association with LCs, which remain largely intact and are preferentially found in proximity to the expanding mutant KC populations. The observed LC facilitation of mutant p53 clonal expansion is completely αß and γδ T-cell independent and is associated with increased intraepidermal expression of IL-22 and the presence of group 3 innate lymphoid cells. These data demonstrate that LCs have a key role in UVB-induced cutaneous carcinogenesis and suggest that LCs locally stimulate KC proliferation and innate immune cells that provoke tumor outgrowth.

Mechanisms of chemical cooperative carcinogenesis by epidermal Langerhans cells.

Cutaneous squamous cell carcinoma (SCC) is the most prevalent invasive malignancy with metastatic potential. The epidermis is exposed to a variety of environmental DNA-damaging chemicals, principal among which are polyaromatic hydrocarbons (PAHs) ubiquitous in the environment, tobacco smoke, and broiled meats. Langerhans cells (LCs) comprise a network of dendritic cells situated adjacent to basal, suprabasal, and follicular infundibular keratinocytes that when mutated can give rise to SCC, and LC-intact mice are markedly more susceptible than LC-deficient mice to chemical carcinogenesis provoked by initiation with the model PAH, 7,12-dimethylbenz[a]anthracene (DMBA). LCs rapidly internalize and accumulate DMBA as numerous membrane-independent cytoplasmic foci. Repopulation of LC-deficient mice using fetal liver LC-precursors restores DMBA-induced tumor susceptibility. LC expression of p450 enzyme CYP1B1 is required for maximal rapid induction of DNA-damage within adjacent keratinocytes and their efficient neoplastic transformation; however, effects of tumor progression also attributable to the presence of LC were revealed as CYP1B1 independent. Thus, LCs make multifaceted contributions to cutaneous carcinogenesis, including via the handling and metabolism of chemical mutagens. Such findings suggest a cooperative carcinogenesis role for myeloid-derived cells resident within cancer susceptible epithelial tissues principally by influencing early events in malignant transformation.