Yevgeniy Balagula

Photoprotection: A review of the current and future technologies

Exposure to ultraviolet (UV) radiation is associated with a variety of harmful effects ranging from photoaging to skin cancer. UVB (290 to 320 nm) directly damages the cellular DNA leading to the formation of the 6‐4 cyclobutane pyrimidine dimmers, and UVA (320 to 400 nm) indirectly damages the DNA via the production of oxygen radical species. In this review, we focused on the technological and scientific aspects of photoprotection using sunglasses and clothing while attempting to dispel some of the misconceptions. In addition to the basic knowledge relating to sunscreens, we reviewed the current guidelines for testing and labeling UVA protection around the world, controversies associated with nanoparticles, and future sunscreens actives waiting for the Food and Drug Administration approval. Lastly, we reviewed alternative agents, such as antioxidants, that can be used to supplement and augment photoprotection provided by sunscreens.

The significance of crystalline/chrysalis structures in the diagnosis of melanocytic and nonmelanocytic lesions

BACKGROUND Crystalline/chrysalis structures (CS) are white shiny streaks that can only be seen with polarized dermatoscopy. OBJECTIVES We sought to estimate the prevalence and assess the clinical significance of CS in melanocytic and nonmelanocytic lesions. METHODS This was a prospective observational study in which dermatoscopic assessment of lesions was recorded in consecutive patients examined during a 6-month period. In addition, a data set of biopsy-proven melanomas was retrospectively analyzed. RESULTS In all, 11,225 lesions in 881 patients were prospectively examined. Retrospectively, 229 melanomas imaged with polarized dermatoscopy were analyzed. In the prospective data set, a median of 12.7 lesions (range, 1-54) were evaluated per patient. None of clinically diagnosed Clark nevi (n = 9750, 86.8%) demonstrated CS. Overall, CS were observed in 206 (1.8%) lesions, most commonly dermatofibromas and scars among nonbiopsied lesions. A total of 265 (2.4%) lesions were biopsied, including 20 melanomas and 36 nevi. Among biopsied malignant lesions, CS were most commonly observed in basal cell carcinoma (47.6%) and invasive melanomas (84.6%). Melanomas were more likely to have CS than biopsied nevi (odds ratio = 9.7, 95% confidence interval 2.7-34.1). In the retrospective data set, CS were more commonly observed among invasive melanomas (41%) compared with in situ melanomas (17%) (odds ratio = 3.4, 95% confidence interval 1.9-6.3, P < .001). The prevalence of CS correlated with increased melanoma thickness (P = .001). LIMITATIONS Biopsied lesions represent a small percentage of the total number of lesions evaluated. CONCLUSION Among biopsied malignant lesions, CS are most commonly observed in basal cell carcinoma and invasive melanomas and rarely seen in nevi. In melanoma, CS may reflect increased tumor thickness and progression.

The emergence of supportive oncodermatology: The study of dermatologic adverse events to cancer therapies

Cancer therapies have led to remarkable results due to improved toxicity profiles and effects on survival. While these medical, surgical, and radiation protocols are chiefly responsible for these noteworthy contributions, an unexpected constellation of toxicities has emerged. Most notably, dermatologic adverse events have gained considerable attention, due to their high frequency, visibility, and impact on physical and psychosocial health, all of which affect dose intensity and possibly clinical outcome. Consequently, increased attention to cutaneous health in oncology has resulted in supportive oncodermatology clinical programs and toxicity-driven investigations, aiming to mitigate these untoward events and permit the continued optimization of cancer treatments.

Clinical presentation and management of dermatological toxicities of epidermal growth factor receptor inhibitors

The last decade in oncology has been highlighted by the emergence of novel, highly specific anti‐cancer agents, targeting a variety of molecular structures and able to inhibit aberrantly activated oncogenic pathways. Epidermal growth factor receptor inhibitors (EGFRIs) represent one type of such “targeted” agents. Their use made treatment more tolerable and resulted in significant reduction of systemic adverse effects. However, EGFRIs are associated with toxicities affecting the skin and adnexal structures, and mucosal surfaces that affect the majority of treated patients. Significant dermatologic toxicities have changed the role and involvement of dermatologists in their care. It is essential to be familiar with these adverse effects, potential complications, long‐term sequelae, and available effective treatment strategies in order to appropriately manage these patients. This review will describe the clinical presentation, histopathology, underlying mechanisms, and management options, emphasizing evidence‐based approaches.

Dermoscopic Features of Basal Cell Carcinomas: Differences in Appearance Under Non‐Polarized and Polarized Light

Background Basal cell carcinomas (BCCs) can be diagnosed using different dermoscopic modalities. Objective To evaluate dermoscopic features of BCCs using nonpolarized and polarized dermoscopy to highlight similarities and differences between dermoscopic modalities. Materials and Methods Retrospective study of 149 BCCs under nonpolarized dermoscopy (NPD), polarized contact dermoscopy (PCD), and polarized noncontact dermoscopy (PNCD). Images were evaluated for a range of dermoscopic colors, structures, and vessels. Features were compared according to histopathologic subtype. Results The most common dermoscopic structures in BCCs across all modalities included globules (50.3–51.0%), dots (49.7–50.3%), white structureless areas (63.1–74.5%), structureless gray–brown areas (24.2–24.8%), and ulcerations (28.2%). The most frequently observed vasculature included arborizing vessels (18.8–38.3%), short fine telangiectasias (SFTs) (73.8–82.6%), and vascular blush (41.6–83.2%). Structures with higher levels of agreement across modalities included pigmented structures and ulcerations. Lower levels of agreement existed between contact and noncontact modalities for certain vascular features. White shiny structures, which include shiny white lines (chrysalis and crystalline structures) (0–69.1%), shiny white areas (0–25.5%), and rosettes (0–11.4%), exhibited no agreement between NPD and polarized modalities. Conclusions This study highlights differences in dermoscopic features of BCCs under three dermoscopic modalities. Shiny white lines (chrysalis and crystalline structures) and shiny white areas may be used as additional criteria to diagnose BCCs.

Clinical and histopathologic characteristics of rash in cancer patients treated with mammalian target of rapamycin inhibitors

Dermatologic adverse events stemming from anticancer therapies have become an increasingly frequent clinical problem. Inhibitors of mammalian target of rapamycin (mTOR), such as temsirolimus and everolimus, have been associated with a high rate of skin eruptions, but their clinical and histopathologic characteristics have not been explored.

The effect of cytotoxic chemotherapy on the risk of high-grade acneiform rash to cetuximab in cancer patients: a meta-analysis

BACKGROUND The effect of chemotherapy on the risk of cetuximab-induced acneiform rash is unknown. We carried out a systematic review and meta-analysis of published studies to quantify the incidence and risk of high-grade acneiform rash with combination therapy. METHODS Relevant studies were identified from PubMed database, abstracts presented at the American Society of Clinical Oncology conferences, and Web of Science. Incidence of acneiform rash to cetuximab monotherapy was estimated based on updated data from our previously published meta-analysis. Incidence, relative risk (RR), and 95% confidence intervals (CIs) were calculated based on the heterogeneity of included studies. RESULTS A total of 5333 patients from nine trials were included in the analysis. The incidence of high-grade acneiform rash was significantly increased in patients receiving combination treatment (12.8%, 95% CI 9.1% to 17.7%) as compared with cetuximab monotherapy (6.3%, 95% CI 3.7% to 10.5%), with a risk ratio of 2.03 (95% CI 1.52-2.71, P < 0.01). Cetuximab significantly increased the risk of high-grade rash in patients receiving combination therapy (RR = 37.7, 95% CI 17.8-80.0, P < 0.001). CONCLUSIONS Addition of cytotoxic chemotherapy to cetuximab significantly increases the risk of high-grade acneiform rash compared with cetuximab monotherapy. This emphasizes the need for effective management strategies.

Life-threatening dermatologic adverse events in oncology.

The incidences of life-threatening toxicities such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are inconsistently reported. The potential association of anticancer agents with SJS or TEN has not been systematically investigated. We searched the literature (Ovid: 1950 to June 2013 and PubMed: 1948 to June 2013) using terms for SJS/TEN and anticancer therapies. Primary case reports, case series, and clinical trials were included. In addition, MedWatch, the Food and Drug Administration Adverse Event Reporting System (FAERS), was searched (1968 to August 2012) for SJS/TEN reports associated with anticancer therapies. Proportional reporting ratios (PRR>2, N>3), empirical Bayes geometric mean (EBGM>2, N>3), and lower 95% confidence interval (EBGM0.05>2) were used as thresholds to constitute a signal of association between SJS/TEN and anticancer drugs. There were 46 SJS and 37 TEN cases associated with 18 and 22 anticancer drugs in the literature, respectively. Among cases in the FAERS, significant signals were associated with SJS for bendamustine and with TEN for bendamustine, busulfan, chlorambucil, fludarabine, lomustine, and procarbazine. Several drugs reported in the published literature to be associated with SJS/TEN were not found to have significant signals in FAERS. Proactive pharmacovigilance to detect and define safety signals serves to aid oncology practitioners in the recognition of possible, yet uncommon, serious, and/or life-threatening skin reactions.

Characteristics of Oral Mucosal Events Related to Bevacizumab Treatment

BACKGROUND Bevacizumab, a monoclonal antibody targeting a vascular endothelial growth factor (VEGF) protein, has been reported to induce mucosal toxicities. However, the clinical characteristics of these particular toxicities have not been well characterized. We aimed at providing a detailed clinical description of signs and symptoms limited to the tongue mucosa in patients treated with bevacizumab. METHODS A retrospective review of medical records and clinical photographs was performed with specific attention to clinical presentation, evolution, associated symptoms, concomitant medications, and treatment methods. RESULTS In total, four patients presented to the dermatology service with clinical findings characterized by multifocal, erythematous circinate and serpiginous erosions on the dorsal tongue surrounded by white hyperkeratotic rims that were temporally related to bevacizumab therapy. Associated increased sensitivity to spicy foods was frequently observed. CONCLUSION These characteristic clinical findings are consistent with geographic tongue. However, large prospective evaluations are necessary to confirm this potential relationship. If bevacizumab is indeed associated with geographic tongue, increased awareness may result in improved reporting and characterization of this particular adverse event.

White Shiny Structures in Melanoma and BCC

W HITE SHINY STRUCTURES SEEN UNDER polarized dermoscopy take on 3 distinct morphological appearances. One category includes white shiny lines, which are often orthogonally oriented. This structure also has a metaphoric name known as chrysalis, although some authors believe that chrysalis is a misnomer and prefer that it be replaced with the term crystalline. (We are in agreement with this opinion.) White shiny areas, also known as white shiny clods, appear as larger structureless areas of shiny white color. Finally, rosettes (also a metaphoric term) appear as 4 shiny white points arranged in a pattern reminiscent of a 4-leaf clover. Although both white shiny lines and white shiny areas have been observed in basal cell carcinoma (BCC) and melanoma, the prevalence of these structures seems to differ between these 2 malignant neoplasms. In BCC, we have noticed that it is common to see both white shiny lines (112 of 162 cases [69.1%]) and white shiny areas (39 of 162 cases [24.1%]). In contrast, although we have observed that crystalline structures are prevalent in melanoma (71 of 249 cases [28.5%]), white shiny areas are seen only rarely (8 of 249 cases [3.2%]) (unpublished observation, October 2010). Herein, we show intensely white, widespread, haphazard white shiny lines (Figure, A and C, white arrows) and white shiny areas (Figure, A and C, black arrows) in a superficial BCC (Figure, A and B) and a nodular BCC (Figure, C) under polarized dermoscopy. These structures cannot be seen in the nonpolarized dermoscopic image (Figure, B). We also show white shiny lines in an in situ and invasive melanoma (Figure, D, arrows) and a melanoma metastasis (Figure, E, arrows).