Neelam A. Vashi

De-N-acetyl GM3 Promotes Melanoma Cell Migration and Invasion through Urokinase Plasminogen Activator Receptor Signaling–Dependent MMP-2 Activation

We have recently discovered that de-N-acetyl GM3 [NeuNH(2)LacCer, d-GM3], a derivative of ganglioside GM3, is specifically expressed in metastatic tumor cells and that its expression correlates with an enhanced metastatic phenotype. Although the classic N-acetylated form of GM3 (NeuAcLacCer, c-GM3) is found in both normal and tumor cells, metastatic tumor cells (but not other cells) predominantly express d-GM3 (82-95% of total GM3). d-GM3 expression is mainly found in metastatic melanomas, but not in benign nevi or the majority of primary melanomas. Using metastatic (d-GM3-positive) and poorly invasive (d-GM3-negative) human melanoma cell lines, we found that d-GM3 stimulates cell migration and invasion by increasing the expression and activation of urokinase-like plasminogen activator (uPA). Further studies showed that d-GM3 activates matrix metalloproteinase-2 (MMP-2), but not MMP-9, when uPA receptor signaling is activated. These results implicate d-GM3 as a specific marker for metastatic melanoma and a novel therapeutic target for neoplastic diseases.

Facial hyperpigmentation: causes and treatment

By midcentury, the U.S.A. will be more ethnically and racially diverse. Skin of colour will soon constitute nearly one‐half of the U.S. population, and a full understanding of skin conditions that affect this group is of great importance. Structural and functional differences in the skin, as well as the influence of cultural practices, produce variances in skin disease and presentation based on skin type. In the skin of colour population, dyschromia is a growing concern, and a top chief complaint when patients present to the physician. A thorough understanding of the aetiology and management strategies of facial hyperpigmentation is of importance in caring for those afflicted and also in the development of new therapies.

Bat-Associated Leptospirosis

ABSTRACTLeptospirosis is a globally prevalent disease that affects humans, causing systemic illness that may lead to multi-organ involvement. Clinical signs include sudden fever, general malaise, muscular pain, conjunctival suffusion, and jaundice. Disease is caused by pathogenic bacteria including over 200 serologic variants. Most serologic variants have primary reservoirs in wild mammals, which continually infect and colonize domesticated animals. The organism has been recovered from rats, swine, dogs, cattle, and other animals, notably bats. Most studies have focused on domestic animals as reservoir hosts; however, because of their abundance, spatial distribution, and interrelationship with domestic animals, bats are becoming an epidemiologically significant source of leptospires. We present a case of serologically confirmed leptospirosis after bat exposure to add to the growing literature of bats as a possible source of transmission. Recognition of the common presentation of leptospirosis and Weil’s disease, and identification of animal vectors, including bats, allows for the selection of appropriate antibiotic management to aid in resolution of symptomotology.

Guidelines for the use of local anesthesia in office-based dermatologic surgery

There are an increasing number and variety of dermatologic surgical procedures performed safely in the office setting. This evidence-based guideline addresses important clinical questions that arise regarding the use and safety of local anesthesia for dermatologic office-based procedures. In addition to recommendations for dermatologists, this guideline also takes into account patient preferences while optimizing their safety and quality of care. The clinical recommendations presented here are based on the best evidence available as well as expert opinion.

Allergic contact dermatitis caused by methylphenidate

The transdermal route of drug administration has the ability to provide steady drug delivery, permit less frequent dosing, and achieve reduced peak plasma drug concentrations for small, highly potent, and lipid-soluble drugs (1–3). Irritant and allergic reactions to components of a transdermal formulation for methylphenidate (MPH), a first-line psychostimulant for attention-deficit/hyperactivity disorder, are exceedingly rare, and we present the first case of allergic contact dermatitis caused by the active ingredient of MPH (4, 5).

The ethics of the medical-pharmaceutical relationship

Physician interaction with the pharmaceutical industry raises many ethical concerns. This relationship is complex, owing to a pluralism of beliefs held by physicians, patients, and third parties. As a result, determining whether physicians fulfill their responsibilities to both the professional and public communities is an arduous endeavor. In an effort to clarify the situation and provide transparency to this complex relationship, medical and pharmaceutical organizations have enacted their own respective codes and guidelines. Even with adherence to these guidelines, questions remain regarding the codependent relationship that interweaves the pharmaceutical industry with the medical community. Owing to the ever-changing landscape enmeshing product development, scientific advancement, corporate realities and patient care, the proper choice for physicians is rarely obvious; however, to operate to the highest standards, those in the medical community must be candid about relations with the pharmaceutical industry and transparent in their financial interests. Further undertakings should focus not on the eradication of physician-pharmaceutical interaction, but instead on the education of physicians about industry marketing strategies and the delineation of boundaries of these interactions to benefit not the individual physician, but our patients.

Sun-protective behaviors in patients with cutaneous hyperpigmentation: A cross-sectional study

Background: Disorders of hyperpigmentation are seen commonly in clinical practice. Despite numerous studies investigating sun‐protective habits among healthy persons, little is known about these behaviors within patient populations with hyperpigmentation disorders. Objective: We sought to examine photo‐protective behaviors and their associations in individuals with disorders of hyperpigmentation. Methods: This cross‐sectional study was conducted with 404 adults who complained of cutaneous hyperpigmentation. Results: About 67.5% reported using a product containing sunscreen, and 91% endorsed using one with a sun protection factor of 21 or higher. Among the participants, 48.5% were not sure if their sunscreen provided broad‐spectrum protection, and only 7.6% reapplied every 2 hours. The odds of a patient with melasma using sunscreen were 6.7 times the odds of a patient with postinflammatory hyperpigmentation using sunscreen (P < .001). Additional predictors for sunscreen use were female sex (OR = 3.8, P = .0004) and disease duration of ≥1 year (OR = 2.1, P = .003). In a multivariate analysis, the odds ratio of sunscreen use among African Americans compared to whites was 0.31 (P = .008). Limitations: Limitations included recall bias, question misinterpretation, and reporter bias. Conclusion: Patients diagnosed with postinflammatory hyperpigmentation, men, and those with disease duration <1 year reported lower sunscreen usage. These groups might benefit from increased counseling on sun‐protective behaviors.

Reading between the layers: early histopathological findings in exogenous ochronosis.

Exogenous ochronosis (EO), although rare, is a well-known pigmentary disorder. Being extremely difficult to treat, early identification is very important, with histopathology remaining the gold standard in diagnosis. A 66-year-old woman presented with periocular and lateral neck blue-gray pigmentation, who after workup including history, physical examination, and skin biopsy was diagnosed with EO based on early histopathologic findings. Classically, banana-shaped collagen fibers are considered the pathognomonic histopathologic sign; however, we present this unique case to illustrate the early findings of EO including basophilia of the collagen fibers in the upper dermis, homogenization and swelling of the collagen bundles, and altered texture and arrangement of elastic fibers in the dermis resembling solar elastosis.

Facial Hyperpigmentation in Skin of Color: Special Considerations and Treatment.

Differences in cutaneous diseases in people of color call for nuanced evaluation and management. One of the most common dermatological complaints from patients with skin of color is dyspigmentation, particularly hyperpigmentation. The challenge for clinicians is to establish correct diagnoses along with consistently successful treatments to meet the needs of the increasingly diverse population served. This review focuses on facial hyperpigmentation and outlines the most common skin disorders and treatment options.

Assessing the safety of superficial chemical peels in darker skin: A retrospective study

Background: Chemical peels have shown efficacy in the treatment of acne, photoaging, and pigmentary dyschromias; however, studies evaluating side effects, particularly in patients with skin of color, are limited. Objective: We sought to determine the frequency of side effects and complications associated with superficial chemical peels in patients with skin types III‐VI. Methods: A 5‐year single center retrospective analysis was performed. Results: Of 473 chemical peel treatments included in this study, 18 (3.8%) were associated with short‐term (≤2 weeks) or long‐term (>2 weeks) complications. The most frequent complications were crusting (2.3%), postinflammatory hyperpigmentation (1.9%), and erythema (1.9%). All side effects resolved within 8 months of treatment and were located on the face. When stratified by season, side effects were noted to be less common during the winter. In the adjusted model, Fitzpatrick skin type VI was associated with a higher odds of side effects (odds ratio 5.14, 95% confidence interval 1.21–21.8; P = .0118). Limitations: Single center retrospective design. Conclusion: In this study, superficial chemical peels performed on patients with skin types III‐VI had a relatively low complication rate, and skin type VI had higher odds of experiencing an adverse event. Side effects were noted to be less frequent during the winter months.