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Teledermoscopy referrals surpass paper for managing skin cancer patients
Smartphone teledermoscopy referrals were faster and allowed for more efficient management of patients with skin cancer, compared with paper referrals, according to Dr. Alexander Börve of the University of Gothenburg, Sweden, and his associates.
The waiting time was significantly shorter using teledermoscopy for patients with various melanomas and carcinomas when surgical treatment was necessary. “Triage decisions were also more reliable with teledermoscopy, and over 40% of the teledermoscopy patients could potentially have avoided face-to-face visits,” the researchers noted (Acta. Derm. Venereol. 2015;95:186-90).
Less than 1% of teledermoscopy referrals were excluded because of poor image quality, they said.
Read the full article at Acta Dermato-Venereologica (doi:10.2340/00015555-1906).
Smartphone teledermoscopy referrals were faster and allowed for more efficient management of patients with skin cancer, compared with paper referrals, according to Dr. Alexander Börve of the University of Gothenburg, Sweden, and his associates.
The waiting time was significantly shorter using teledermoscopy for patients with various melanomas and carcinomas when surgical treatment was necessary. “Triage decisions were also more reliable with teledermoscopy, and over 40% of the teledermoscopy patients could potentially have avoided face-to-face visits,” the researchers noted (Acta. Derm. Venereol. 2015;95:186-90).
Less than 1% of teledermoscopy referrals were excluded because of poor image quality, they said.
Read the full article at Acta Dermato-Venereologica (doi:10.2340/00015555-1906).
Smartphone teledermoscopy referrals were faster and allowed for more efficient management of patients with skin cancer, compared with paper referrals, according to Dr. Alexander Börve of the University of Gothenburg, Sweden, and his associates.
The waiting time was significantly shorter using teledermoscopy for patients with various melanomas and carcinomas when surgical treatment was necessary. “Triage decisions were also more reliable with teledermoscopy, and over 40% of the teledermoscopy patients could potentially have avoided face-to-face visits,” the researchers noted (Acta. Derm. Venereol. 2015;95:186-90).
Less than 1% of teledermoscopy referrals were excluded because of poor image quality, they said.
Read the full article at Acta Dermato-Venereologica (doi:10.2340/00015555-1906).
Vitiligo indicates effective melanoma treatment, predicts survival benefit
The development of vitiligo in melanoma patients on immunotherapy may predict improved survival, according to findings from a systematic review and meta-analysis.
In 137 studies reported between 1995 and 2013 and including 5,737 patients with stage III to IV melanoma who were treated with immunotherapy, the pooled cumulative incidence of vitiligo was 3.4%. In those with vitiligo for whom individual patient data were available, both progression-free and overall survival were significantly improved, compared with those without vitiligo after researchers adjusted for age and sex (hazard ratio, 0.51 and 0.25, respectively), Dr. Hansje-Eva Teulings of the University of Amsterdam and her colleagues reported online Jan. 19 in the Journal of Clinical Oncology.
Immune-related effects after melanoma immunotherapy have been linked to increased clinical efficacy. Vitiligo, which results from “strong antimelanoma immunity that also targets healthy melanocytes as a result of shared expression melanocyte differentiation antigens,” is no exception, but it was unclear whether data from individual studies showing tumor regression and improved survival in those with vitiligo could be extrapolated to all immunotherapy studies, the investigators explained (J. Clin. Oncol. 2015 Jan. 19 [doi:10.1200/JCO.2014.57.4756]).
The current findings highlight the significance of vitiligo as a clinical marker for effective antimelanoma immunity and for improved clinical outcome, they said, concluding that “more awareness of vitiligo induction in patients with melanoma by oncologists may contribute to better recognition of patients with effective antimelanoma immunity and may influence their treatment options and prognosis.”
The development of vitiligo in melanoma patients on immunotherapy may predict improved survival, according to findings from a systematic review and meta-analysis.
In 137 studies reported between 1995 and 2013 and including 5,737 patients with stage III to IV melanoma who were treated with immunotherapy, the pooled cumulative incidence of vitiligo was 3.4%. In those with vitiligo for whom individual patient data were available, both progression-free and overall survival were significantly improved, compared with those without vitiligo after researchers adjusted for age and sex (hazard ratio, 0.51 and 0.25, respectively), Dr. Hansje-Eva Teulings of the University of Amsterdam and her colleagues reported online Jan. 19 in the Journal of Clinical Oncology.
Immune-related effects after melanoma immunotherapy have been linked to increased clinical efficacy. Vitiligo, which results from “strong antimelanoma immunity that also targets healthy melanocytes as a result of shared expression melanocyte differentiation antigens,” is no exception, but it was unclear whether data from individual studies showing tumor regression and improved survival in those with vitiligo could be extrapolated to all immunotherapy studies, the investigators explained (J. Clin. Oncol. 2015 Jan. 19 [doi:10.1200/JCO.2014.57.4756]).
The current findings highlight the significance of vitiligo as a clinical marker for effective antimelanoma immunity and for improved clinical outcome, they said, concluding that “more awareness of vitiligo induction in patients with melanoma by oncologists may contribute to better recognition of patients with effective antimelanoma immunity and may influence their treatment options and prognosis.”
The development of vitiligo in melanoma patients on immunotherapy may predict improved survival, according to findings from a systematic review and meta-analysis.
In 137 studies reported between 1995 and 2013 and including 5,737 patients with stage III to IV melanoma who were treated with immunotherapy, the pooled cumulative incidence of vitiligo was 3.4%. In those with vitiligo for whom individual patient data were available, both progression-free and overall survival were significantly improved, compared with those without vitiligo after researchers adjusted for age and sex (hazard ratio, 0.51 and 0.25, respectively), Dr. Hansje-Eva Teulings of the University of Amsterdam and her colleagues reported online Jan. 19 in the Journal of Clinical Oncology.
Immune-related effects after melanoma immunotherapy have been linked to increased clinical efficacy. Vitiligo, which results from “strong antimelanoma immunity that also targets healthy melanocytes as a result of shared expression melanocyte differentiation antigens,” is no exception, but it was unclear whether data from individual studies showing tumor regression and improved survival in those with vitiligo could be extrapolated to all immunotherapy studies, the investigators explained (J. Clin. Oncol. 2015 Jan. 19 [doi:10.1200/JCO.2014.57.4756]).
The current findings highlight the significance of vitiligo as a clinical marker for effective antimelanoma immunity and for improved clinical outcome, they said, concluding that “more awareness of vitiligo induction in patients with melanoma by oncologists may contribute to better recognition of patients with effective antimelanoma immunity and may influence their treatment options and prognosis.”
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Vitiligo appears to serve as a clinical marker for effective antimelanoma immunity and improved clinical outcome.
Major finding: Progression-free and overall survival were improved in patients who developed vitiligo (HR, 0.51 and 0.25, respectively).
Data source: A systematic review and meta-analysis of 139 studies including 5,737 patients.
Disclosures: Dr. Teulings reported having no disclosures.
Handheld device illuminates possible routes of melanoma metastases
Investigators using a handheld dermoscopy device that allows visualization of colors, structures, and patterns in skin lesions not evident to the naked eye were able to visualize nonblanching blue and red lines in a branched pattern in two patients with in-transit cutaneous melanoma metastases.
Dr. Michael A. Marchetti and his associates at Memorial Sloan Kettering Cancer Center, New York, reported the “intriguing” visualization of dissemination for cutaneous melanoma metastases in a letter to JAMA Dermatology.
In-transit cutaneous melanoma metastases are those located more than 2 cm from the primary melanoma, but not beyond the regional nodal basin.
The first patient had wide local excision of a primary cutaneous melanoma on the forehead, and a year later, received localized irradiation for satellite skin metastases. A year after that, skin examination revealed six blue macules on the scalp more than 2 cm from the excision scar. Dermoscopy revealed nonblanching bluish lines in a branched pattern. Histopathologic examination of a skin biopsy confirmed in-transit metastatic melanoma with atypical melanocytes present in superficial dermal lymphatics, Dr. Marchetti and his associates reported (JAMA Dermatology 2015;103-5)
The second patient had a history of multiple primary melanomas, the most recent being one on the chest treated with wide local excision. At a follow-up visit 5 years later, skin examination revealed eight blue-gray macules on the chest, all more than 2 cm from the excision scar. Dermoscopy revealed nonblanching, red-bluish, fuzzy, branching lines. Histopathologic examination of a skin biopsy confirmed in-transit metastatic melanoma with atypical melanocytes present in superficial dermal blood vessels, the investigators wrote.
Typical dermoscopic features of cutaneous melanoma metastases include peripheral gray spots, atypical vessels, and a blue nevus-like pattern. The histopathologic findings in these two cases suggest that the dermoscopic color differences correspond to unique microanatomic routes of melanoma dissemination, with blue and red-blue lines corresponding to lymphatic and hematogenous dissemination of tumors, respectively, they said.
“While the factors driving lymphatic vs. hematogenous in-transit dissemination of melanoma remain unknown, as do any differences in their biologic significance, our finding is an intriguing clinical/dermoscopic/histopathologic observation,” the investigators concluded.
On Twitter @nikolaideslaura
Investigators using a handheld dermoscopy device that allows visualization of colors, structures, and patterns in skin lesions not evident to the naked eye were able to visualize nonblanching blue and red lines in a branched pattern in two patients with in-transit cutaneous melanoma metastases.
Dr. Michael A. Marchetti and his associates at Memorial Sloan Kettering Cancer Center, New York, reported the “intriguing” visualization of dissemination for cutaneous melanoma metastases in a letter to JAMA Dermatology.
In-transit cutaneous melanoma metastases are those located more than 2 cm from the primary melanoma, but not beyond the regional nodal basin.
The first patient had wide local excision of a primary cutaneous melanoma on the forehead, and a year later, received localized irradiation for satellite skin metastases. A year after that, skin examination revealed six blue macules on the scalp more than 2 cm from the excision scar. Dermoscopy revealed nonblanching bluish lines in a branched pattern. Histopathologic examination of a skin biopsy confirmed in-transit metastatic melanoma with atypical melanocytes present in superficial dermal lymphatics, Dr. Marchetti and his associates reported (JAMA Dermatology 2015;103-5)
The second patient had a history of multiple primary melanomas, the most recent being one on the chest treated with wide local excision. At a follow-up visit 5 years later, skin examination revealed eight blue-gray macules on the chest, all more than 2 cm from the excision scar. Dermoscopy revealed nonblanching, red-bluish, fuzzy, branching lines. Histopathologic examination of a skin biopsy confirmed in-transit metastatic melanoma with atypical melanocytes present in superficial dermal blood vessels, the investigators wrote.
Typical dermoscopic features of cutaneous melanoma metastases include peripheral gray spots, atypical vessels, and a blue nevus-like pattern. The histopathologic findings in these two cases suggest that the dermoscopic color differences correspond to unique microanatomic routes of melanoma dissemination, with blue and red-blue lines corresponding to lymphatic and hematogenous dissemination of tumors, respectively, they said.
“While the factors driving lymphatic vs. hematogenous in-transit dissemination of melanoma remain unknown, as do any differences in their biologic significance, our finding is an intriguing clinical/dermoscopic/histopathologic observation,” the investigators concluded.
On Twitter @nikolaideslaura
Investigators using a handheld dermoscopy device that allows visualization of colors, structures, and patterns in skin lesions not evident to the naked eye were able to visualize nonblanching blue and red lines in a branched pattern in two patients with in-transit cutaneous melanoma metastases.
Dr. Michael A. Marchetti and his associates at Memorial Sloan Kettering Cancer Center, New York, reported the “intriguing” visualization of dissemination for cutaneous melanoma metastases in a letter to JAMA Dermatology.
In-transit cutaneous melanoma metastases are those located more than 2 cm from the primary melanoma, but not beyond the regional nodal basin.
The first patient had wide local excision of a primary cutaneous melanoma on the forehead, and a year later, received localized irradiation for satellite skin metastases. A year after that, skin examination revealed six blue macules on the scalp more than 2 cm from the excision scar. Dermoscopy revealed nonblanching bluish lines in a branched pattern. Histopathologic examination of a skin biopsy confirmed in-transit metastatic melanoma with atypical melanocytes present in superficial dermal lymphatics, Dr. Marchetti and his associates reported (JAMA Dermatology 2015;103-5)
The second patient had a history of multiple primary melanomas, the most recent being one on the chest treated with wide local excision. At a follow-up visit 5 years later, skin examination revealed eight blue-gray macules on the chest, all more than 2 cm from the excision scar. Dermoscopy revealed nonblanching, red-bluish, fuzzy, branching lines. Histopathologic examination of a skin biopsy confirmed in-transit metastatic melanoma with atypical melanocytes present in superficial dermal blood vessels, the investigators wrote.
Typical dermoscopic features of cutaneous melanoma metastases include peripheral gray spots, atypical vessels, and a blue nevus-like pattern. The histopathologic findings in these two cases suggest that the dermoscopic color differences correspond to unique microanatomic routes of melanoma dissemination, with blue and red-blue lines corresponding to lymphatic and hematogenous dissemination of tumors, respectively, they said.
“While the factors driving lymphatic vs. hematogenous in-transit dissemination of melanoma remain unknown, as do any differences in their biologic significance, our finding is an intriguing clinical/dermoscopic/histopathologic observation,” the investigators concluded.
On Twitter @nikolaideslaura
FROM JAMA DERMATOLOGY
MEK inhibitors can induce skin eruptions with distinctive duskiness
Case reports of unusual drug hypersensitivity to MEK inhibitors, involving skin eruptions with distinctive central duskiness, have been described online in JAMA Dermatology.
Three patients who were receiving different MEK inhibitors (selumetinib, cobimetinib, and trametinib) developed grade 2 or 3 eruptions, all associated with unique duskiness, reported Dr. Urvi Patel and associates at Washington University, St. Louis.
A 60-year-old man with pancreatic cancer who was receiving selumetinib as part of a clinical trial presented with a grade 2 generalized eruption and pruritus 12 days after initiating therapy. He had diffuse targetoid patches with central duskiness. Selumetinib and other study drugs were withheld, the patient was given topical corticosteroid treatment, and the eruption completely resolved after 4 weeks. The patient did not restart the study drugs because of an elevated alkaline phosphatase level and fatigue.
A woman in her 40s who was receiving cobimetinib and other medication for metastatic melanoma developed grade 2 coalescing urticarial patches with surrounding duskiness on day 28 of treatment. Histopathologic examination showed a superficial perivascular lymphocytic infiltrate with rare eosinophils. After treatment was halted for 7 days and a regimen of oral prednisone was started, cobimetinib therapy was reinstituted at a lower dose. There was no recurrence of the eruption 1 year after cobimetinib therapy was restarted, Dr. Patel and associates reported (JAMA Dermatol. 2015 Jan. 14 [doi:10.1001/jamadermatol.2014.3207]).
The third patient, a woman in her 50s with metastatic melanoma, developed a grade 3 eruption 7 weeks into trametinib treatment together with another drug. The worsening urticarial patches and plaques had surrounding diffuse duskiness. After trametinib treatment was withheld for a week, and a regimen of oral prednisone was begun, trametinib therapy was restarted and the eruption did not return.
“As shown in our patients, successful treatment of this MEK inhibitor–associated cutaneous eruption can include a drug holiday and oral corticosteroid therapy, with reinstitution of the drug at a lower dose without recurrence,” Dr. Patel and his associates wrote.
MEK inhibitors target the mitogen-activated protein kinase pathway. Trametinib has been approved for treating advanced melanoma, and more than a dozen other MEK inhibitors are in clinical trials (including selumetinib and cobimetinib) for treatment of melanoma and other solid-organ malignant neoplasms, including pancreatic, hepatocellular, colorectal, and non–small cell lung cancer, the authors noted.
On Twitter @nikolaideslaura
Case reports of unusual drug hypersensitivity to MEK inhibitors, involving skin eruptions with distinctive central duskiness, have been described online in JAMA Dermatology.
Three patients who were receiving different MEK inhibitors (selumetinib, cobimetinib, and trametinib) developed grade 2 or 3 eruptions, all associated with unique duskiness, reported Dr. Urvi Patel and associates at Washington University, St. Louis.
A 60-year-old man with pancreatic cancer who was receiving selumetinib as part of a clinical trial presented with a grade 2 generalized eruption and pruritus 12 days after initiating therapy. He had diffuse targetoid patches with central duskiness. Selumetinib and other study drugs were withheld, the patient was given topical corticosteroid treatment, and the eruption completely resolved after 4 weeks. The patient did not restart the study drugs because of an elevated alkaline phosphatase level and fatigue.
A woman in her 40s who was receiving cobimetinib and other medication for metastatic melanoma developed grade 2 coalescing urticarial patches with surrounding duskiness on day 28 of treatment. Histopathologic examination showed a superficial perivascular lymphocytic infiltrate with rare eosinophils. After treatment was halted for 7 days and a regimen of oral prednisone was started, cobimetinib therapy was reinstituted at a lower dose. There was no recurrence of the eruption 1 year after cobimetinib therapy was restarted, Dr. Patel and associates reported (JAMA Dermatol. 2015 Jan. 14 [doi:10.1001/jamadermatol.2014.3207]).
The third patient, a woman in her 50s with metastatic melanoma, developed a grade 3 eruption 7 weeks into trametinib treatment together with another drug. The worsening urticarial patches and plaques had surrounding diffuse duskiness. After trametinib treatment was withheld for a week, and a regimen of oral prednisone was begun, trametinib therapy was restarted and the eruption did not return.
“As shown in our patients, successful treatment of this MEK inhibitor–associated cutaneous eruption can include a drug holiday and oral corticosteroid therapy, with reinstitution of the drug at a lower dose without recurrence,” Dr. Patel and his associates wrote.
MEK inhibitors target the mitogen-activated protein kinase pathway. Trametinib has been approved for treating advanced melanoma, and more than a dozen other MEK inhibitors are in clinical trials (including selumetinib and cobimetinib) for treatment of melanoma and other solid-organ malignant neoplasms, including pancreatic, hepatocellular, colorectal, and non–small cell lung cancer, the authors noted.
On Twitter @nikolaideslaura
Case reports of unusual drug hypersensitivity to MEK inhibitors, involving skin eruptions with distinctive central duskiness, have been described online in JAMA Dermatology.
Three patients who were receiving different MEK inhibitors (selumetinib, cobimetinib, and trametinib) developed grade 2 or 3 eruptions, all associated with unique duskiness, reported Dr. Urvi Patel and associates at Washington University, St. Louis.
A 60-year-old man with pancreatic cancer who was receiving selumetinib as part of a clinical trial presented with a grade 2 generalized eruption and pruritus 12 days after initiating therapy. He had diffuse targetoid patches with central duskiness. Selumetinib and other study drugs were withheld, the patient was given topical corticosteroid treatment, and the eruption completely resolved after 4 weeks. The patient did not restart the study drugs because of an elevated alkaline phosphatase level and fatigue.
A woman in her 40s who was receiving cobimetinib and other medication for metastatic melanoma developed grade 2 coalescing urticarial patches with surrounding duskiness on day 28 of treatment. Histopathologic examination showed a superficial perivascular lymphocytic infiltrate with rare eosinophils. After treatment was halted for 7 days and a regimen of oral prednisone was started, cobimetinib therapy was reinstituted at a lower dose. There was no recurrence of the eruption 1 year after cobimetinib therapy was restarted, Dr. Patel and associates reported (JAMA Dermatol. 2015 Jan. 14 [doi:10.1001/jamadermatol.2014.3207]).
The third patient, a woman in her 50s with metastatic melanoma, developed a grade 3 eruption 7 weeks into trametinib treatment together with another drug. The worsening urticarial patches and plaques had surrounding diffuse duskiness. After trametinib treatment was withheld for a week, and a regimen of oral prednisone was begun, trametinib therapy was restarted and the eruption did not return.
“As shown in our patients, successful treatment of this MEK inhibitor–associated cutaneous eruption can include a drug holiday and oral corticosteroid therapy, with reinstitution of the drug at a lower dose without recurrence,” Dr. Patel and his associates wrote.
MEK inhibitors target the mitogen-activated protein kinase pathway. Trametinib has been approved for treating advanced melanoma, and more than a dozen other MEK inhibitors are in clinical trials (including selumetinib and cobimetinib) for treatment of melanoma and other solid-organ malignant neoplasms, including pancreatic, hepatocellular, colorectal, and non–small cell lung cancer, the authors noted.
On Twitter @nikolaideslaura
FROM JAMA DERMATOLOGY
Key clinical point: This MEK inhibitor–associated cutaneous eruption can be treated with a drug holiday and oral corticosteroid treatment, restarting the drug at a lower dose without recurrence.
Major finding: Three patients who were receiving different MEK inhibitors (selumetinib, cobimetinib, and trametinib) developed grade 2 or 3 eruptions, all associated with unique duskiness.
Data source: Three case studies of patients receiving different MEK inhibitors.
Disclosures: Dr. Lynn Cornelius has received a research grant from Genentech and is a clinical subinvestigator for GlaxoSmithKline. Dr. Milan J. Anadkat has received honoraria as a speaker and/or consultant from AstraZeneca, Bristol-Myers Squibb, Eisai, ImClone, and Therakos. No other disclosures were reported.
Sunscreens Causing Cancer? The Facts
Skin cancer is the most common form of cancer in the United States and continues to rise in incidence and mortality each year.1 It is common knowledge that UV light plays a major role in the development of skin cancer.2,3 Studies have long demonstrated that using sunscreen on a daily basis can help prevent the development of skin cancer, premature aging, and exacerbation of photodermatoses.4-7 Although there are several photoprotective measures available, sunscreen remains the most popular and widely used among patients.8 Sunscreens that are on the market today contain either organic or inorganic UV filters or a combination of both based on their chemical composition and photoprotection mechanisms.9 Concerns about these ingredients causing cancer have created confusion among consumers. I will attempt to clarify these concerns by critically analyzing available evidence-based data on sunscreen use so that as dermatology residents we will be more knowledgeable about sunscreen safety topics and will be able to provide accurate and up-to-date information to our patients.
Organic UV Filters
Organic UV filters are classified as aromatic compounds that provide photoprotection by absorbing UV light.10 Aside from the photoallergic potential of organic UV filters, controversy has arisen in response to studies reporting their possible hormone disruptive effects.11-18 Although there are several US Food and Drug Administration (FDA)–approved organic UV filters in use today, one of the most commonly manufactured and controversial agents is oxybenzone.10 Claims regarding the estrogenic and antiandrogenic effects of oxybenzone have been investigated with results refuting the claims or concluding that more sensitive studies are needed to determine if these organic ingredients pose such risks.10,19,20 One study demonstrated that nearly 300 years of daily sunscreen application would be needed to reach similar exposure levels of oxybenzone used and described in prior animal studies.21 Additionally, most of the studied adverse effects of UV filters have been evaluated based on oral exposure rather than actual dermal application.11 Although these compounds are absorbed systemically, studies have reported that the amounts are insignificant and noncumulative in the body.10,22-24 Furthermore, the binding affinity of oxybenzone for estrogen receptors has been shown to be much weaker and near insignificant compared to estrogen and estradiol.24,25 Although numerous important studies examining systemic absorption have not shown a clinically significant disruption of hormonal homeostasis or acute toxicity in humans by organic UV filters, further studies are needed.
Inorganic UV Filters
Used as the main active ingredients in sunscreen for decades, titanium dioxide (TiO2) and zinc oxide (ZnO) compounds generally are more photostable and less photoallergic than their organic counterparts.10 In recent years, the safety of these long-used photoprotectors has been questioned because of the development of nanoparticle (<100 nm) formulas that are less opaque on application. Although this formula provides a thin, transparent, and cosmetically appealing medium, there is concern that the metal oxides penetrate the skin and cause local and systemic toxicities.26-28 Several recent scientific studies have shown no percutaneous permeation of these particles in normal adult human skin and reported no causal damage to mammalian cells.10,29-31 Although skin penetration of TiO2 and ZnO has been described as insignificant, focus has shifted to health risks associated with inhaling TiO2 through the use of spray or powder products following statements made by the International Agency for Research on Cancer in 2006.32 Several studies investigating increased health risks, specifically lung cancer, in factory workers who were subjected to TiO2 and ZnO inhalation concluded that exposure was unlikely to pose substantial health risks or subchronic toxicity.33,34 Despite a relatively strong safety profile, a major concern of using these metal oxides as UV filters has been potential free radical formation.35-39 For this reason, the Scientific Committee on Emerging and Newly Identified Health Risks extensively researched and delivered opinions on the use of TiO2 and ZnO in cosmetics, concluding that topical application of either compound does not result in toxicity or other adverse effects.30,40-42 Additionally, an effort has been made by manufacturers to encapsulate nanoparticles with magnesium and other materials to quench the reactive oxygen species along with the human body’s own antioxidant defense system.10 In summary, it appears that the current weight of scientific evidence suggests that percutaneous absorption and toxicity by UV filters in humans may be overestimated and that the use of nanoparticles in sunscreens poses no or negligible potential risks to human health.43,44
Concerns Beyond Organic and Inorganic UV Filters
Beyond these concerns with organic and inorganic UV filters, there are several other claims regarding sunscreen safety that have stirred up controversy, including the side-effect profile of retinyl palmitate, vitamin D deficiency, phototoxicity, environmental effects, futility of sun protection factor levels greater than 50, and increased health risks in children. Although some studies report mixed results, the majority of scientific investigations have addressed and refuted several of these claims, again confirming the relative safety of sunscreen use. It is beyond the scope of this article to further discuss these topics specifically. However, it is worth mentioning that consumer studies report that the actual use of sunscreens is 0.5 mg/cm2 or less compared to the ideal application of 2 mg/cm2, thereby confounding many of the claims made about sunscreen use, such as vitamin D deficiency.45 Sunscreens often contain a combination of several UV filters. To date, only a few existing studies have shown that mixtures of the photoprotective agents discussed might interact and exhibit toxic activity when combined, even when there is no observed adverse toxic effect when used individually in products.46-48
The current FDA ruling on sunscreen labeling does not require manufacturers to state if inorganic UV filters have been formulated into nanoparticles; however, manufacturers are now required to include a statement on all sunscreen labels warning consumers to avoid using sunscreen on damaged or broken skin49 in an effort to prevent the active ingredients from getting under the skin, potentially causing inflammation and/or health risks, because available data do not provide conclusive evidence on increased penetration of open skin.50 Additional information regarding the 2011 FDA sunscreen ruling can be found in a prior Cutis Resident Corner column.51
Final Thoughts
As health care providers, we should take advantage of opportunities to educate our patients about other sun safety practices, such as avoiding excessive sun exposure during peak hours (10 am to 2 pm), seeking shade, and wearing photoprotective clothing (eg, wide-brimmed hats, sunglasses).
The research is quite clear: Using broadband sunscreens that absorb and/or block UV radiation results in reduced damage to the skin’s DNA, a fact that should be considered when taking into account the risks and benefits of sunscreen use.2,3 Although sunscreen use is highly recommended in addition to the other sun protection methods, it is ultimately the patient’s choice. If a patient is still concerned about the active ingredients of UV filters, even given the high probability of safety, there are products available on the market that do not include organic filters or nanoparticles. Given the established benefits of UV protection, the use of sunscreens remain one of the most important photoprotective methods, and with increased usage by the public, continuous monitoring of the overall safety and benefit profile of future products is prudent.
1. Skin cancer statistics. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/cancer/skin/statistics/index.htm. Updated September 2, 2014. Accessed December 30, 2014.
2. World Health Organization, International Agency for Research on Cancer. Solar and ultraviolet radiation. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 55. Lyon, France: International Agency for Research on Cancer; 1992.
3. Green AC, Williams GM, Logan V, et al. Reduced melanoma after regular sunscreen use: randomized trial follow-up. J Clin Oncol. 2011;29:257-263.
4. Darlington S, Williams G, Neale R, et al. A randomized controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses. Arch Dermatol. 2003;139:451-455.
5. Van der Pols JC, Williams GM, Pandeya N, et al. Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. Cancer Epidemiol Biomarkers Prev. 2006;15:2546-2548.
6. Hughes MC, Williams GM, Baker P, et al. Sunscreen and prevention of skin aging: a randomized trial. Ann Intern Med. 2013;158:781-790.
7. Bissonnette R, Nigen S, Bolduc C. Influence of the quantity of sunscreen applied on the ability to protect against ultraviolet-induced polymorphous light eruption. Photodermatol Photoimmunol Photomed. 2012;28:240-243.
8. Cancer trends progress report 2011/2012 update: sun protection. National Cancer Institute Web site. http://progressreport.cancer.gov/doc_detail.asp?pid¡1&did¡2009&chid¡91&coid¡911. Accessed December 30, 2014.
9. Sunscreen Drug Products for Over-the-counter Human Use, 21 CFR §352.10. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=352.10. Updated September 1, 2014. Accessed December 30, 2014.
10. Burnett ME, Wang SQ. Current sunscreen controversies: a critical review. Photodermatol Photoimmunol Photomed. 2011;27:58-67.
11. Krause M, Klit A, Blomberg Jensen M, et al. Sunscreens: are they beneficial for health? an overview of endocrine disrupting properties of UV-filters. Int J Androl. 2012;35:424-436.
12. Schlumpf M, Cotton B, Conscience M, et al. In vitro and in vivo estrogenicity of UV screens. Environ Health Perspect. 2001;109:239-244.
13. Schlumpf M, Schmid P, Durrer S, et al. Endocrine activity and developmental toxicity of cosmetic UV filters–an update. Toxicol. 2004;205:113-122.
14. Schlumpf M, Kypke K, Vökt C, et al. Endocrine active UV filters: developmental toxicity and exposure through breast milk. Chimia. 2008;62:345-351.
15. Nakagawa Y, Suzuki T. Metabolism of 2-hydroxy-4-methoxybenzophenone in isolated rat hepatocytes and xenoestrogenic effects of its metabolites on MCF-7 human breast cancer cells. Chem Biol Interact. 2002;139:115-128.
16. Ma R, Cotton B, Lichtensteiger W, et al. UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay. Toxicol Sci. 2003;74:43-50.
17. Heneweer M, Muusse M, van den Berg M, et al. Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells. Toxicol Appl Pharmacol. 2005;208:170-177.
18. Knobler E, Almeida L, Ruzkowski AM, et al. Photoallergy to benzophenone. Arch Dermatol. 1989;125:801-804.
19. Draelos ZD. Are sunscreens safe? J Cosmet Dermatol. 2010;9:1-2.
20. Gilbert E, Pirot F, Bertholle V. Commonly used UV filter toxicity on biological functions: review of last decade studies. Int J of Cosmet Sci. 2013;35:208-219.
21. Wang SQ, Burnett ME, Lim HW. Safety of oxybenzone: putting numbers into perspective. Arch Dermatol. 2011;147:865-866.
22. Mancebo SE, Hu JY, Wang SQ. Sunscreens: a review of health benefits, regulations, and controversies. Dermatol Clin. 2014;32:427-438.
23. Jansen R, Osterwalder U, Wang SQ, et al. Photoprotection: part II. sunscreen: development, efficacy, and controversies. J Am Acad Dermatol. 2013;69:867.e1-867.e14.
24. Janjua NR, Mogensen B, Andersson AM, et al. Systemic absorption of the sunscreens benzo- phenone-3, octyl-methoxycinnamate, and 3-(4-methyl-benzy-lidene) camphor after whole-body topical application and reproductive hormone levels in humans. J Invest Dermatol. 2004;123:57-61.
25. Kadry AM, Chukwuemeka SO, Mohamed S, et al. Pharmacokinetics of benzophenone-3 after oral exposure in male rats. J Appl Toxicol. 1995;15:97-102.
26. Gulson B, McCall M, Korsch M, et al. Small amounts of zinc from zinc oxide particles in sunscreens applied outdoors are absorbed through human skin. Toxicol Sci. 2010;118:140-149.
27. Gulson B, Wong H, Korsch M, et al. Comparison of dermal absorption of zinc from different sunscreen formulations and differing UV exposure based on stable isotope tracing. Sci Total Environ. 2012:420:313-318.
28. Benech-Kieffer F, Meuling WJ, Leclerc C, et al. Percutaneous absorption of Mexoryl SX in human volunteers: comparison with in vitro data. Skin Pharmacol Appl Skin Physiol. 2003;16:343-355.
29. Nash JF. Human safety and efficacy of ultraviolet filters and sunscreen products. Dermatol Clin. 2006;24:35-51.
30. Nohynek GJ, Lademann J, Ribaud C, et al. Grey goo on the skin? nanotechnology, cosmetic and sunscreen safety. Crit Rev Toxicol. 2007;37:251-277.
31. Sadrieh N, Wokovich AM, Gopee NV, et al. Lack of significant dermal penetration of titanium dioxide from sunscreen formulations containing nano- and submicron-size TiO2 particles. Toxicol Sci. 2010;115:156-166.
32. International Agency for Research on Cancer. Carbon black, titanium dioxide, and talc. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 93. Lyon, France: International Agency for Research on Cancer; 2006.
33. Liao CM, Chiang YH, Chio CP. Model-based assessment for human inhalation exposure risk to airborne nano/fine titanium dioxide particles. Sci Total Environ. 2008:15;407:165-177.
34. Adamcakova-Dodd A, Stebounova LV, Kim JS, et al. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models. Part Fibre Toxicol. 2014;11:15.
35. Wamer WG, Yin JJ, Wei RR. Oxidative damage to nucleic acids photosensitized by titanium dioxide. Free Radic Biol Med. 1997;23:851-858.
36. Nakagawa Y, Wakuri S, Sakamoto K, et al. The photogenotoxicity of titanium dioxide particles. Mutat Res. 1997;394:125-132.
37. Dunford R, Salinaro A, Cai L, et al. Chemical oxidation and DNA damage catalysed by inorganic sunscreen ingredients. FEBS Lett. 1997;418:87-90, 99.
38. Hidaka H, Kobayashi H, Koike T, et al. DNA damage photoinduced by cosmetic pigments and sunscreen agents under solar exposure and artificial UV illumination. J Oleo Sci. 2006;55:249-261.
39. Dufour EK, Kumaravel T, Nohynek GJ, et al. Clastogenicity, photo-clastogenicity or pseudo-photo-clastogenicity: genotoxic effects of zinc oxide in the dark, in pre-irradiated or simultaneously irradiated Chinese hamster ovary cells [published online ahead of print June 21, 2006]. Mutat Res. 2006;607:215-224.
40. Opinion of the Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers concerning titanium dioxide. http://ec.europa.eu/health/archive/ph_risk/committees/sccp/documents/out135_en.pdf. Published October 24, 2000. Accessed December 30, 2014.
41. The Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers opinion concerning zinc oxide. http://ec.europa.eu/health/archive/ph_risk/committees/sccp/documents/out222_en.pdf. Published June 24-25, 2003. Accessed December 30, 2014.
42. Hackenberg S, Friehs G, Kessler M, et al. Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes. Environ Mol Mutagen. 2010;52:264-268.
43. Bach-Thomsen M, Wulf HC. Sunbather’s application of sunscreen is probably inadequate to obtain the sun protection factor assigned to the preparation. Photodermatol Photoimmunol Photomed. 1993:9;242-244.
44. Nohynek GJ, Antignac E, Re T, et al. Safety assessment of personal care products/cosmetics and their ingredients. Toxicol Appl Pharmacol. 2010:1;243:239-259.
45. Diffey BL. Sunscreens: use and misuse. In: Giacomoni PU, ed. Sun Protection in Man. Vol 3. Amsterdam, the Netherlands: Elsevier Science BV; 2001:521-534.
46. Heneweer M, Muusse M, Van den BM, et al. Additive estrogenic effects of mixtures of frequently used UV-filters on pS2-gene transcription in MCF-7 cells. Toxicol Appl Pharmacol. 2005;208:170-177.
47. Kunz PY, Galicia HF, Fent K. Comparison of in vitro and in vivo estrogenic activity of UV-filters in fish. Toxicol Sci. 2006;90:349-361.
48. Kortenkamp A, Faust M, Scholze M, et al. Low-level exposure to multiple chemicals: reason for human health concerns? Environ Health Perspect. 2007;115(suppl 1):106-114.
49. Labeling and effectiveness testing: sunscreen drug products for over-the-counter human use—small entity compliance guide. US Food and Drug Administration Web site. http://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm330694.htm. Published December 2012. Updated May 13, 2014. Accessed December 30, 2014.
50. Schafer-Korting M, Korting HC, Ponce-Poschl E. Liposomal tretinoin for uncomplicated acne vulgaris. Clin Investig. 1994;72:1086-1091.
51. Bronfenbrener R. Simplifying sun safety: a guide to the new FDA sunscreen monograph. Cutis. 2014;93:e17-e19.
Skin cancer is the most common form of cancer in the United States and continues to rise in incidence and mortality each year.1 It is common knowledge that UV light plays a major role in the development of skin cancer.2,3 Studies have long demonstrated that using sunscreen on a daily basis can help prevent the development of skin cancer, premature aging, and exacerbation of photodermatoses.4-7 Although there are several photoprotective measures available, sunscreen remains the most popular and widely used among patients.8 Sunscreens that are on the market today contain either organic or inorganic UV filters or a combination of both based on their chemical composition and photoprotection mechanisms.9 Concerns about these ingredients causing cancer have created confusion among consumers. I will attempt to clarify these concerns by critically analyzing available evidence-based data on sunscreen use so that as dermatology residents we will be more knowledgeable about sunscreen safety topics and will be able to provide accurate and up-to-date information to our patients.
Organic UV Filters
Organic UV filters are classified as aromatic compounds that provide photoprotection by absorbing UV light.10 Aside from the photoallergic potential of organic UV filters, controversy has arisen in response to studies reporting their possible hormone disruptive effects.11-18 Although there are several US Food and Drug Administration (FDA)–approved organic UV filters in use today, one of the most commonly manufactured and controversial agents is oxybenzone.10 Claims regarding the estrogenic and antiandrogenic effects of oxybenzone have been investigated with results refuting the claims or concluding that more sensitive studies are needed to determine if these organic ingredients pose such risks.10,19,20 One study demonstrated that nearly 300 years of daily sunscreen application would be needed to reach similar exposure levels of oxybenzone used and described in prior animal studies.21 Additionally, most of the studied adverse effects of UV filters have been evaluated based on oral exposure rather than actual dermal application.11 Although these compounds are absorbed systemically, studies have reported that the amounts are insignificant and noncumulative in the body.10,22-24 Furthermore, the binding affinity of oxybenzone for estrogen receptors has been shown to be much weaker and near insignificant compared to estrogen and estradiol.24,25 Although numerous important studies examining systemic absorption have not shown a clinically significant disruption of hormonal homeostasis or acute toxicity in humans by organic UV filters, further studies are needed.
Inorganic UV Filters
Used as the main active ingredients in sunscreen for decades, titanium dioxide (TiO2) and zinc oxide (ZnO) compounds generally are more photostable and less photoallergic than their organic counterparts.10 In recent years, the safety of these long-used photoprotectors has been questioned because of the development of nanoparticle (<100 nm) formulas that are less opaque on application. Although this formula provides a thin, transparent, and cosmetically appealing medium, there is concern that the metal oxides penetrate the skin and cause local and systemic toxicities.26-28 Several recent scientific studies have shown no percutaneous permeation of these particles in normal adult human skin and reported no causal damage to mammalian cells.10,29-31 Although skin penetration of TiO2 and ZnO has been described as insignificant, focus has shifted to health risks associated with inhaling TiO2 through the use of spray or powder products following statements made by the International Agency for Research on Cancer in 2006.32 Several studies investigating increased health risks, specifically lung cancer, in factory workers who were subjected to TiO2 and ZnO inhalation concluded that exposure was unlikely to pose substantial health risks or subchronic toxicity.33,34 Despite a relatively strong safety profile, a major concern of using these metal oxides as UV filters has been potential free radical formation.35-39 For this reason, the Scientific Committee on Emerging and Newly Identified Health Risks extensively researched and delivered opinions on the use of TiO2 and ZnO in cosmetics, concluding that topical application of either compound does not result in toxicity or other adverse effects.30,40-42 Additionally, an effort has been made by manufacturers to encapsulate nanoparticles with magnesium and other materials to quench the reactive oxygen species along with the human body’s own antioxidant defense system.10 In summary, it appears that the current weight of scientific evidence suggests that percutaneous absorption and toxicity by UV filters in humans may be overestimated and that the use of nanoparticles in sunscreens poses no or negligible potential risks to human health.43,44
Concerns Beyond Organic and Inorganic UV Filters
Beyond these concerns with organic and inorganic UV filters, there are several other claims regarding sunscreen safety that have stirred up controversy, including the side-effect profile of retinyl palmitate, vitamin D deficiency, phototoxicity, environmental effects, futility of sun protection factor levels greater than 50, and increased health risks in children. Although some studies report mixed results, the majority of scientific investigations have addressed and refuted several of these claims, again confirming the relative safety of sunscreen use. It is beyond the scope of this article to further discuss these topics specifically. However, it is worth mentioning that consumer studies report that the actual use of sunscreens is 0.5 mg/cm2 or less compared to the ideal application of 2 mg/cm2, thereby confounding many of the claims made about sunscreen use, such as vitamin D deficiency.45 Sunscreens often contain a combination of several UV filters. To date, only a few existing studies have shown that mixtures of the photoprotective agents discussed might interact and exhibit toxic activity when combined, even when there is no observed adverse toxic effect when used individually in products.46-48
The current FDA ruling on sunscreen labeling does not require manufacturers to state if inorganic UV filters have been formulated into nanoparticles; however, manufacturers are now required to include a statement on all sunscreen labels warning consumers to avoid using sunscreen on damaged or broken skin49 in an effort to prevent the active ingredients from getting under the skin, potentially causing inflammation and/or health risks, because available data do not provide conclusive evidence on increased penetration of open skin.50 Additional information regarding the 2011 FDA sunscreen ruling can be found in a prior Cutis Resident Corner column.51
Final Thoughts
As health care providers, we should take advantage of opportunities to educate our patients about other sun safety practices, such as avoiding excessive sun exposure during peak hours (10 am to 2 pm), seeking shade, and wearing photoprotective clothing (eg, wide-brimmed hats, sunglasses).
The research is quite clear: Using broadband sunscreens that absorb and/or block UV radiation results in reduced damage to the skin’s DNA, a fact that should be considered when taking into account the risks and benefits of sunscreen use.2,3 Although sunscreen use is highly recommended in addition to the other sun protection methods, it is ultimately the patient’s choice. If a patient is still concerned about the active ingredients of UV filters, even given the high probability of safety, there are products available on the market that do not include organic filters or nanoparticles. Given the established benefits of UV protection, the use of sunscreens remain one of the most important photoprotective methods, and with increased usage by the public, continuous monitoring of the overall safety and benefit profile of future products is prudent.
Skin cancer is the most common form of cancer in the United States and continues to rise in incidence and mortality each year.1 It is common knowledge that UV light plays a major role in the development of skin cancer.2,3 Studies have long demonstrated that using sunscreen on a daily basis can help prevent the development of skin cancer, premature aging, and exacerbation of photodermatoses.4-7 Although there are several photoprotective measures available, sunscreen remains the most popular and widely used among patients.8 Sunscreens that are on the market today contain either organic or inorganic UV filters or a combination of both based on their chemical composition and photoprotection mechanisms.9 Concerns about these ingredients causing cancer have created confusion among consumers. I will attempt to clarify these concerns by critically analyzing available evidence-based data on sunscreen use so that as dermatology residents we will be more knowledgeable about sunscreen safety topics and will be able to provide accurate and up-to-date information to our patients.
Organic UV Filters
Organic UV filters are classified as aromatic compounds that provide photoprotection by absorbing UV light.10 Aside from the photoallergic potential of organic UV filters, controversy has arisen in response to studies reporting their possible hormone disruptive effects.11-18 Although there are several US Food and Drug Administration (FDA)–approved organic UV filters in use today, one of the most commonly manufactured and controversial agents is oxybenzone.10 Claims regarding the estrogenic and antiandrogenic effects of oxybenzone have been investigated with results refuting the claims or concluding that more sensitive studies are needed to determine if these organic ingredients pose such risks.10,19,20 One study demonstrated that nearly 300 years of daily sunscreen application would be needed to reach similar exposure levels of oxybenzone used and described in prior animal studies.21 Additionally, most of the studied adverse effects of UV filters have been evaluated based on oral exposure rather than actual dermal application.11 Although these compounds are absorbed systemically, studies have reported that the amounts are insignificant and noncumulative in the body.10,22-24 Furthermore, the binding affinity of oxybenzone for estrogen receptors has been shown to be much weaker and near insignificant compared to estrogen and estradiol.24,25 Although numerous important studies examining systemic absorption have not shown a clinically significant disruption of hormonal homeostasis or acute toxicity in humans by organic UV filters, further studies are needed.
Inorganic UV Filters
Used as the main active ingredients in sunscreen for decades, titanium dioxide (TiO2) and zinc oxide (ZnO) compounds generally are more photostable and less photoallergic than their organic counterparts.10 In recent years, the safety of these long-used photoprotectors has been questioned because of the development of nanoparticle (<100 nm) formulas that are less opaque on application. Although this formula provides a thin, transparent, and cosmetically appealing medium, there is concern that the metal oxides penetrate the skin and cause local and systemic toxicities.26-28 Several recent scientific studies have shown no percutaneous permeation of these particles in normal adult human skin and reported no causal damage to mammalian cells.10,29-31 Although skin penetration of TiO2 and ZnO has been described as insignificant, focus has shifted to health risks associated with inhaling TiO2 through the use of spray or powder products following statements made by the International Agency for Research on Cancer in 2006.32 Several studies investigating increased health risks, specifically lung cancer, in factory workers who were subjected to TiO2 and ZnO inhalation concluded that exposure was unlikely to pose substantial health risks or subchronic toxicity.33,34 Despite a relatively strong safety profile, a major concern of using these metal oxides as UV filters has been potential free radical formation.35-39 For this reason, the Scientific Committee on Emerging and Newly Identified Health Risks extensively researched and delivered opinions on the use of TiO2 and ZnO in cosmetics, concluding that topical application of either compound does not result in toxicity or other adverse effects.30,40-42 Additionally, an effort has been made by manufacturers to encapsulate nanoparticles with magnesium and other materials to quench the reactive oxygen species along with the human body’s own antioxidant defense system.10 In summary, it appears that the current weight of scientific evidence suggests that percutaneous absorption and toxicity by UV filters in humans may be overestimated and that the use of nanoparticles in sunscreens poses no or negligible potential risks to human health.43,44
Concerns Beyond Organic and Inorganic UV Filters
Beyond these concerns with organic and inorganic UV filters, there are several other claims regarding sunscreen safety that have stirred up controversy, including the side-effect profile of retinyl palmitate, vitamin D deficiency, phototoxicity, environmental effects, futility of sun protection factor levels greater than 50, and increased health risks in children. Although some studies report mixed results, the majority of scientific investigations have addressed and refuted several of these claims, again confirming the relative safety of sunscreen use. It is beyond the scope of this article to further discuss these topics specifically. However, it is worth mentioning that consumer studies report that the actual use of sunscreens is 0.5 mg/cm2 or less compared to the ideal application of 2 mg/cm2, thereby confounding many of the claims made about sunscreen use, such as vitamin D deficiency.45 Sunscreens often contain a combination of several UV filters. To date, only a few existing studies have shown that mixtures of the photoprotective agents discussed might interact and exhibit toxic activity when combined, even when there is no observed adverse toxic effect when used individually in products.46-48
The current FDA ruling on sunscreen labeling does not require manufacturers to state if inorganic UV filters have been formulated into nanoparticles; however, manufacturers are now required to include a statement on all sunscreen labels warning consumers to avoid using sunscreen on damaged or broken skin49 in an effort to prevent the active ingredients from getting under the skin, potentially causing inflammation and/or health risks, because available data do not provide conclusive evidence on increased penetration of open skin.50 Additional information regarding the 2011 FDA sunscreen ruling can be found in a prior Cutis Resident Corner column.51
Final Thoughts
As health care providers, we should take advantage of opportunities to educate our patients about other sun safety practices, such as avoiding excessive sun exposure during peak hours (10 am to 2 pm), seeking shade, and wearing photoprotective clothing (eg, wide-brimmed hats, sunglasses).
The research is quite clear: Using broadband sunscreens that absorb and/or block UV radiation results in reduced damage to the skin’s DNA, a fact that should be considered when taking into account the risks and benefits of sunscreen use.2,3 Although sunscreen use is highly recommended in addition to the other sun protection methods, it is ultimately the patient’s choice. If a patient is still concerned about the active ingredients of UV filters, even given the high probability of safety, there are products available on the market that do not include organic filters or nanoparticles. Given the established benefits of UV protection, the use of sunscreens remain one of the most important photoprotective methods, and with increased usage by the public, continuous monitoring of the overall safety and benefit profile of future products is prudent.
1. Skin cancer statistics. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/cancer/skin/statistics/index.htm. Updated September 2, 2014. Accessed December 30, 2014.
2. World Health Organization, International Agency for Research on Cancer. Solar and ultraviolet radiation. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 55. Lyon, France: International Agency for Research on Cancer; 1992.
3. Green AC, Williams GM, Logan V, et al. Reduced melanoma after regular sunscreen use: randomized trial follow-up. J Clin Oncol. 2011;29:257-263.
4. Darlington S, Williams G, Neale R, et al. A randomized controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses. Arch Dermatol. 2003;139:451-455.
5. Van der Pols JC, Williams GM, Pandeya N, et al. Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. Cancer Epidemiol Biomarkers Prev. 2006;15:2546-2548.
6. Hughes MC, Williams GM, Baker P, et al. Sunscreen and prevention of skin aging: a randomized trial. Ann Intern Med. 2013;158:781-790.
7. Bissonnette R, Nigen S, Bolduc C. Influence of the quantity of sunscreen applied on the ability to protect against ultraviolet-induced polymorphous light eruption. Photodermatol Photoimmunol Photomed. 2012;28:240-243.
8. Cancer trends progress report 2011/2012 update: sun protection. National Cancer Institute Web site. http://progressreport.cancer.gov/doc_detail.asp?pid¡1&did¡2009&chid¡91&coid¡911. Accessed December 30, 2014.
9. Sunscreen Drug Products for Over-the-counter Human Use, 21 CFR §352.10. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=352.10. Updated September 1, 2014. Accessed December 30, 2014.
10. Burnett ME, Wang SQ. Current sunscreen controversies: a critical review. Photodermatol Photoimmunol Photomed. 2011;27:58-67.
11. Krause M, Klit A, Blomberg Jensen M, et al. Sunscreens: are they beneficial for health? an overview of endocrine disrupting properties of UV-filters. Int J Androl. 2012;35:424-436.
12. Schlumpf M, Cotton B, Conscience M, et al. In vitro and in vivo estrogenicity of UV screens. Environ Health Perspect. 2001;109:239-244.
13. Schlumpf M, Schmid P, Durrer S, et al. Endocrine activity and developmental toxicity of cosmetic UV filters–an update. Toxicol. 2004;205:113-122.
14. Schlumpf M, Kypke K, Vökt C, et al. Endocrine active UV filters: developmental toxicity and exposure through breast milk. Chimia. 2008;62:345-351.
15. Nakagawa Y, Suzuki T. Metabolism of 2-hydroxy-4-methoxybenzophenone in isolated rat hepatocytes and xenoestrogenic effects of its metabolites on MCF-7 human breast cancer cells. Chem Biol Interact. 2002;139:115-128.
16. Ma R, Cotton B, Lichtensteiger W, et al. UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay. Toxicol Sci. 2003;74:43-50.
17. Heneweer M, Muusse M, van den Berg M, et al. Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells. Toxicol Appl Pharmacol. 2005;208:170-177.
18. Knobler E, Almeida L, Ruzkowski AM, et al. Photoallergy to benzophenone. Arch Dermatol. 1989;125:801-804.
19. Draelos ZD. Are sunscreens safe? J Cosmet Dermatol. 2010;9:1-2.
20. Gilbert E, Pirot F, Bertholle V. Commonly used UV filter toxicity on biological functions: review of last decade studies. Int J of Cosmet Sci. 2013;35:208-219.
21. Wang SQ, Burnett ME, Lim HW. Safety of oxybenzone: putting numbers into perspective. Arch Dermatol. 2011;147:865-866.
22. Mancebo SE, Hu JY, Wang SQ. Sunscreens: a review of health benefits, regulations, and controversies. Dermatol Clin. 2014;32:427-438.
23. Jansen R, Osterwalder U, Wang SQ, et al. Photoprotection: part II. sunscreen: development, efficacy, and controversies. J Am Acad Dermatol. 2013;69:867.e1-867.e14.
24. Janjua NR, Mogensen B, Andersson AM, et al. Systemic absorption of the sunscreens benzo- phenone-3, octyl-methoxycinnamate, and 3-(4-methyl-benzy-lidene) camphor after whole-body topical application and reproductive hormone levels in humans. J Invest Dermatol. 2004;123:57-61.
25. Kadry AM, Chukwuemeka SO, Mohamed S, et al. Pharmacokinetics of benzophenone-3 after oral exposure in male rats. J Appl Toxicol. 1995;15:97-102.
26. Gulson B, McCall M, Korsch M, et al. Small amounts of zinc from zinc oxide particles in sunscreens applied outdoors are absorbed through human skin. Toxicol Sci. 2010;118:140-149.
27. Gulson B, Wong H, Korsch M, et al. Comparison of dermal absorption of zinc from different sunscreen formulations and differing UV exposure based on stable isotope tracing. Sci Total Environ. 2012:420:313-318.
28. Benech-Kieffer F, Meuling WJ, Leclerc C, et al. Percutaneous absorption of Mexoryl SX in human volunteers: comparison with in vitro data. Skin Pharmacol Appl Skin Physiol. 2003;16:343-355.
29. Nash JF. Human safety and efficacy of ultraviolet filters and sunscreen products. Dermatol Clin. 2006;24:35-51.
30. Nohynek GJ, Lademann J, Ribaud C, et al. Grey goo on the skin? nanotechnology, cosmetic and sunscreen safety. Crit Rev Toxicol. 2007;37:251-277.
31. Sadrieh N, Wokovich AM, Gopee NV, et al. Lack of significant dermal penetration of titanium dioxide from sunscreen formulations containing nano- and submicron-size TiO2 particles. Toxicol Sci. 2010;115:156-166.
32. International Agency for Research on Cancer. Carbon black, titanium dioxide, and talc. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 93. Lyon, France: International Agency for Research on Cancer; 2006.
33. Liao CM, Chiang YH, Chio CP. Model-based assessment for human inhalation exposure risk to airborne nano/fine titanium dioxide particles. Sci Total Environ. 2008:15;407:165-177.
34. Adamcakova-Dodd A, Stebounova LV, Kim JS, et al. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models. Part Fibre Toxicol. 2014;11:15.
35. Wamer WG, Yin JJ, Wei RR. Oxidative damage to nucleic acids photosensitized by titanium dioxide. Free Radic Biol Med. 1997;23:851-858.
36. Nakagawa Y, Wakuri S, Sakamoto K, et al. The photogenotoxicity of titanium dioxide particles. Mutat Res. 1997;394:125-132.
37. Dunford R, Salinaro A, Cai L, et al. Chemical oxidation and DNA damage catalysed by inorganic sunscreen ingredients. FEBS Lett. 1997;418:87-90, 99.
38. Hidaka H, Kobayashi H, Koike T, et al. DNA damage photoinduced by cosmetic pigments and sunscreen agents under solar exposure and artificial UV illumination. J Oleo Sci. 2006;55:249-261.
39. Dufour EK, Kumaravel T, Nohynek GJ, et al. Clastogenicity, photo-clastogenicity or pseudo-photo-clastogenicity: genotoxic effects of zinc oxide in the dark, in pre-irradiated or simultaneously irradiated Chinese hamster ovary cells [published online ahead of print June 21, 2006]. Mutat Res. 2006;607:215-224.
40. Opinion of the Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers concerning titanium dioxide. http://ec.europa.eu/health/archive/ph_risk/committees/sccp/documents/out135_en.pdf. Published October 24, 2000. Accessed December 30, 2014.
41. The Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers opinion concerning zinc oxide. http://ec.europa.eu/health/archive/ph_risk/committees/sccp/documents/out222_en.pdf. Published June 24-25, 2003. Accessed December 30, 2014.
42. Hackenberg S, Friehs G, Kessler M, et al. Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes. Environ Mol Mutagen. 2010;52:264-268.
43. Bach-Thomsen M, Wulf HC. Sunbather’s application of sunscreen is probably inadequate to obtain the sun protection factor assigned to the preparation. Photodermatol Photoimmunol Photomed. 1993:9;242-244.
44. Nohynek GJ, Antignac E, Re T, et al. Safety assessment of personal care products/cosmetics and their ingredients. Toxicol Appl Pharmacol. 2010:1;243:239-259.
45. Diffey BL. Sunscreens: use and misuse. In: Giacomoni PU, ed. Sun Protection in Man. Vol 3. Amsterdam, the Netherlands: Elsevier Science BV; 2001:521-534.
46. Heneweer M, Muusse M, Van den BM, et al. Additive estrogenic effects of mixtures of frequently used UV-filters on pS2-gene transcription in MCF-7 cells. Toxicol Appl Pharmacol. 2005;208:170-177.
47. Kunz PY, Galicia HF, Fent K. Comparison of in vitro and in vivo estrogenic activity of UV-filters in fish. Toxicol Sci. 2006;90:349-361.
48. Kortenkamp A, Faust M, Scholze M, et al. Low-level exposure to multiple chemicals: reason for human health concerns? Environ Health Perspect. 2007;115(suppl 1):106-114.
49. Labeling and effectiveness testing: sunscreen drug products for over-the-counter human use—small entity compliance guide. US Food and Drug Administration Web site. http://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm330694.htm. Published December 2012. Updated May 13, 2014. Accessed December 30, 2014.
50. Schafer-Korting M, Korting HC, Ponce-Poschl E. Liposomal tretinoin for uncomplicated acne vulgaris. Clin Investig. 1994;72:1086-1091.
51. Bronfenbrener R. Simplifying sun safety: a guide to the new FDA sunscreen monograph. Cutis. 2014;93:e17-e19.
1. Skin cancer statistics. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/cancer/skin/statistics/index.htm. Updated September 2, 2014. Accessed December 30, 2014.
2. World Health Organization, International Agency for Research on Cancer. Solar and ultraviolet radiation. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 55. Lyon, France: International Agency for Research on Cancer; 1992.
3. Green AC, Williams GM, Logan V, et al. Reduced melanoma after regular sunscreen use: randomized trial follow-up. J Clin Oncol. 2011;29:257-263.
4. Darlington S, Williams G, Neale R, et al. A randomized controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses. Arch Dermatol. 2003;139:451-455.
5. Van der Pols JC, Williams GM, Pandeya N, et al. Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. Cancer Epidemiol Biomarkers Prev. 2006;15:2546-2548.
6. Hughes MC, Williams GM, Baker P, et al. Sunscreen and prevention of skin aging: a randomized trial. Ann Intern Med. 2013;158:781-790.
7. Bissonnette R, Nigen S, Bolduc C. Influence of the quantity of sunscreen applied on the ability to protect against ultraviolet-induced polymorphous light eruption. Photodermatol Photoimmunol Photomed. 2012;28:240-243.
8. Cancer trends progress report 2011/2012 update: sun protection. National Cancer Institute Web site. http://progressreport.cancer.gov/doc_detail.asp?pid¡1&did¡2009&chid¡91&coid¡911. Accessed December 30, 2014.
9. Sunscreen Drug Products for Over-the-counter Human Use, 21 CFR §352.10. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=352.10. Updated September 1, 2014. Accessed December 30, 2014.
10. Burnett ME, Wang SQ. Current sunscreen controversies: a critical review. Photodermatol Photoimmunol Photomed. 2011;27:58-67.
11. Krause M, Klit A, Blomberg Jensen M, et al. Sunscreens: are they beneficial for health? an overview of endocrine disrupting properties of UV-filters. Int J Androl. 2012;35:424-436.
12. Schlumpf M, Cotton B, Conscience M, et al. In vitro and in vivo estrogenicity of UV screens. Environ Health Perspect. 2001;109:239-244.
13. Schlumpf M, Schmid P, Durrer S, et al. Endocrine activity and developmental toxicity of cosmetic UV filters–an update. Toxicol. 2004;205:113-122.
14. Schlumpf M, Kypke K, Vökt C, et al. Endocrine active UV filters: developmental toxicity and exposure through breast milk. Chimia. 2008;62:345-351.
15. Nakagawa Y, Suzuki T. Metabolism of 2-hydroxy-4-methoxybenzophenone in isolated rat hepatocytes and xenoestrogenic effects of its metabolites on MCF-7 human breast cancer cells. Chem Biol Interact. 2002;139:115-128.
16. Ma R, Cotton B, Lichtensteiger W, et al. UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay. Toxicol Sci. 2003;74:43-50.
17. Heneweer M, Muusse M, van den Berg M, et al. Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells. Toxicol Appl Pharmacol. 2005;208:170-177.
18. Knobler E, Almeida L, Ruzkowski AM, et al. Photoallergy to benzophenone. Arch Dermatol. 1989;125:801-804.
19. Draelos ZD. Are sunscreens safe? J Cosmet Dermatol. 2010;9:1-2.
20. Gilbert E, Pirot F, Bertholle V. Commonly used UV filter toxicity on biological functions: review of last decade studies. Int J of Cosmet Sci. 2013;35:208-219.
21. Wang SQ, Burnett ME, Lim HW. Safety of oxybenzone: putting numbers into perspective. Arch Dermatol. 2011;147:865-866.
22. Mancebo SE, Hu JY, Wang SQ. Sunscreens: a review of health benefits, regulations, and controversies. Dermatol Clin. 2014;32:427-438.
23. Jansen R, Osterwalder U, Wang SQ, et al. Photoprotection: part II. sunscreen: development, efficacy, and controversies. J Am Acad Dermatol. 2013;69:867.e1-867.e14.
24. Janjua NR, Mogensen B, Andersson AM, et al. Systemic absorption of the sunscreens benzo- phenone-3, octyl-methoxycinnamate, and 3-(4-methyl-benzy-lidene) camphor after whole-body topical application and reproductive hormone levels in humans. J Invest Dermatol. 2004;123:57-61.
25. Kadry AM, Chukwuemeka SO, Mohamed S, et al. Pharmacokinetics of benzophenone-3 after oral exposure in male rats. J Appl Toxicol. 1995;15:97-102.
26. Gulson B, McCall M, Korsch M, et al. Small amounts of zinc from zinc oxide particles in sunscreens applied outdoors are absorbed through human skin. Toxicol Sci. 2010;118:140-149.
27. Gulson B, Wong H, Korsch M, et al. Comparison of dermal absorption of zinc from different sunscreen formulations and differing UV exposure based on stable isotope tracing. Sci Total Environ. 2012:420:313-318.
28. Benech-Kieffer F, Meuling WJ, Leclerc C, et al. Percutaneous absorption of Mexoryl SX in human volunteers: comparison with in vitro data. Skin Pharmacol Appl Skin Physiol. 2003;16:343-355.
29. Nash JF. Human safety and efficacy of ultraviolet filters and sunscreen products. Dermatol Clin. 2006;24:35-51.
30. Nohynek GJ, Lademann J, Ribaud C, et al. Grey goo on the skin? nanotechnology, cosmetic and sunscreen safety. Crit Rev Toxicol. 2007;37:251-277.
31. Sadrieh N, Wokovich AM, Gopee NV, et al. Lack of significant dermal penetration of titanium dioxide from sunscreen formulations containing nano- and submicron-size TiO2 particles. Toxicol Sci. 2010;115:156-166.
32. International Agency for Research on Cancer. Carbon black, titanium dioxide, and talc. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 93. Lyon, France: International Agency for Research on Cancer; 2006.
33. Liao CM, Chiang YH, Chio CP. Model-based assessment for human inhalation exposure risk to airborne nano/fine titanium dioxide particles. Sci Total Environ. 2008:15;407:165-177.
34. Adamcakova-Dodd A, Stebounova LV, Kim JS, et al. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models. Part Fibre Toxicol. 2014;11:15.
35. Wamer WG, Yin JJ, Wei RR. Oxidative damage to nucleic acids photosensitized by titanium dioxide. Free Radic Biol Med. 1997;23:851-858.
36. Nakagawa Y, Wakuri S, Sakamoto K, et al. The photogenotoxicity of titanium dioxide particles. Mutat Res. 1997;394:125-132.
37. Dunford R, Salinaro A, Cai L, et al. Chemical oxidation and DNA damage catalysed by inorganic sunscreen ingredients. FEBS Lett. 1997;418:87-90, 99.
38. Hidaka H, Kobayashi H, Koike T, et al. DNA damage photoinduced by cosmetic pigments and sunscreen agents under solar exposure and artificial UV illumination. J Oleo Sci. 2006;55:249-261.
39. Dufour EK, Kumaravel T, Nohynek GJ, et al. Clastogenicity, photo-clastogenicity or pseudo-photo-clastogenicity: genotoxic effects of zinc oxide in the dark, in pre-irradiated or simultaneously irradiated Chinese hamster ovary cells [published online ahead of print June 21, 2006]. Mutat Res. 2006;607:215-224.
40. Opinion of the Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers concerning titanium dioxide. http://ec.europa.eu/health/archive/ph_risk/committees/sccp/documents/out135_en.pdf. Published October 24, 2000. Accessed December 30, 2014.
41. The Scientific Committee on Cosmetic Products and Non-Food Products intended for Consumers opinion concerning zinc oxide. http://ec.europa.eu/health/archive/ph_risk/committees/sccp/documents/out222_en.pdf. Published June 24-25, 2003. Accessed December 30, 2014.
42. Hackenberg S, Friehs G, Kessler M, et al. Nanosized titanium dioxide particles do not induce DNA damage in human peripheral blood lymphocytes. Environ Mol Mutagen. 2010;52:264-268.
43. Bach-Thomsen M, Wulf HC. Sunbather’s application of sunscreen is probably inadequate to obtain the sun protection factor assigned to the preparation. Photodermatol Photoimmunol Photomed. 1993:9;242-244.
44. Nohynek GJ, Antignac E, Re T, et al. Safety assessment of personal care products/cosmetics and their ingredients. Toxicol Appl Pharmacol. 2010:1;243:239-259.
45. Diffey BL. Sunscreens: use and misuse. In: Giacomoni PU, ed. Sun Protection in Man. Vol 3. Amsterdam, the Netherlands: Elsevier Science BV; 2001:521-534.
46. Heneweer M, Muusse M, Van den BM, et al. Additive estrogenic effects of mixtures of frequently used UV-filters on pS2-gene transcription in MCF-7 cells. Toxicol Appl Pharmacol. 2005;208:170-177.
47. Kunz PY, Galicia HF, Fent K. Comparison of in vitro and in vivo estrogenic activity of UV-filters in fish. Toxicol Sci. 2006;90:349-361.
48. Kortenkamp A, Faust M, Scholze M, et al. Low-level exposure to multiple chemicals: reason for human health concerns? Environ Health Perspect. 2007;115(suppl 1):106-114.
49. Labeling and effectiveness testing: sunscreen drug products for over-the-counter human use—small entity compliance guide. US Food and Drug Administration Web site. http://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm330694.htm. Published December 2012. Updated May 13, 2014. Accessed December 30, 2014.
50. Schafer-Korting M, Korting HC, Ponce-Poschl E. Liposomal tretinoin for uncomplicated acne vulgaris. Clin Investig. 1994;72:1086-1091.
51. Bronfenbrener R. Simplifying sun safety: a guide to the new FDA sunscreen monograph. Cutis. 2014;93:e17-e19.
Does Your Dermatology Center Need a Dermatoscenter?
There are anecdotal reports of dogs detecting melanoma and studies of canines being able to not only detect but also distinguish cancer from noncancer. Analysis of volatile compounds or metabolites from exhaled human breath and excreted urine also has been shown to differentiate between patients with certain cancers and healthy individuals. In addition, investigators have demonstrated that melanoma tissue has a volatile profile that is distinct from healthy nonneoplastic skin and nevi.
Abaffy et al (Metabolomics. 2013;9:998-1008) conducted a study that gives further support to the potential for analyzing volatile organic compounds as biomarkers of melanoma. They used the headspace solid phase microextraction method followed by gas chromatography and mass spectrometry to compare the volatile metabolic profiles of melanoma and nonneoplastic healthy-appearing adjacent skin from the same patient. They discovered increased levels of lauric acid (C12:0) and palmitic acid (C16:0) in melanoma and they postulated that the increased levels of these fatty acids were due to cancer-associated upregulation of de novo lipid synthesis.
What’s the issue?
In the 1980s, nail fold capillary microscopy using an ophthalmoscope was occasionally performed to evaluate for disease-associated vascular changes in patients who were being evaluated for connective tissue disorders. Within 2 decades, a dermoscope to assist in the evaluation of not only nail folds but also pigmented and other lesions replaced the ophthalmoscope. The US Food and Drug Administration recently approved a software-driven optical imaging and data analysis device that can be used to obtain additional information to assist the clinician in making a decision whether to biopsy a pigmented lesion.
As our ability to develop more sensitive and specific methods to diagnose melanoma and differentiate it from benign lesions advances, our approach to the evaluation of patients with pigmented lesions shall continue to be modified. Based on the detection of melanoma-associated volatile organic compounds coupled with their potential use as readily accessible tumor-related biomarkers, it is reasonable to speculate: (1) that a handheld office-based device, a dermatoscenter, that can identify melanoma-induced volatile tumor markers shall be developed to evaluate whether pigmented lesions are malignant or benign, and (2) that this device will eventually become an integral component of the dermatologist’s diagnostic armamentarium. Does your dermatology center need a dermatoscenter?
There are anecdotal reports of dogs detecting melanoma and studies of canines being able to not only detect but also distinguish cancer from noncancer. Analysis of volatile compounds or metabolites from exhaled human breath and excreted urine also has been shown to differentiate between patients with certain cancers and healthy individuals. In addition, investigators have demonstrated that melanoma tissue has a volatile profile that is distinct from healthy nonneoplastic skin and nevi.
Abaffy et al (Metabolomics. 2013;9:998-1008) conducted a study that gives further support to the potential for analyzing volatile organic compounds as biomarkers of melanoma. They used the headspace solid phase microextraction method followed by gas chromatography and mass spectrometry to compare the volatile metabolic profiles of melanoma and nonneoplastic healthy-appearing adjacent skin from the same patient. They discovered increased levels of lauric acid (C12:0) and palmitic acid (C16:0) in melanoma and they postulated that the increased levels of these fatty acids were due to cancer-associated upregulation of de novo lipid synthesis.
What’s the issue?
In the 1980s, nail fold capillary microscopy using an ophthalmoscope was occasionally performed to evaluate for disease-associated vascular changes in patients who were being evaluated for connective tissue disorders. Within 2 decades, a dermoscope to assist in the evaluation of not only nail folds but also pigmented and other lesions replaced the ophthalmoscope. The US Food and Drug Administration recently approved a software-driven optical imaging and data analysis device that can be used to obtain additional information to assist the clinician in making a decision whether to biopsy a pigmented lesion.
As our ability to develop more sensitive and specific methods to diagnose melanoma and differentiate it from benign lesions advances, our approach to the evaluation of patients with pigmented lesions shall continue to be modified. Based on the detection of melanoma-associated volatile organic compounds coupled with their potential use as readily accessible tumor-related biomarkers, it is reasonable to speculate: (1) that a handheld office-based device, a dermatoscenter, that can identify melanoma-induced volatile tumor markers shall be developed to evaluate whether pigmented lesions are malignant or benign, and (2) that this device will eventually become an integral component of the dermatologist’s diagnostic armamentarium. Does your dermatology center need a dermatoscenter?
There are anecdotal reports of dogs detecting melanoma and studies of canines being able to not only detect but also distinguish cancer from noncancer. Analysis of volatile compounds or metabolites from exhaled human breath and excreted urine also has been shown to differentiate between patients with certain cancers and healthy individuals. In addition, investigators have demonstrated that melanoma tissue has a volatile profile that is distinct from healthy nonneoplastic skin and nevi.
Abaffy et al (Metabolomics. 2013;9:998-1008) conducted a study that gives further support to the potential for analyzing volatile organic compounds as biomarkers of melanoma. They used the headspace solid phase microextraction method followed by gas chromatography and mass spectrometry to compare the volatile metabolic profiles of melanoma and nonneoplastic healthy-appearing adjacent skin from the same patient. They discovered increased levels of lauric acid (C12:0) and palmitic acid (C16:0) in melanoma and they postulated that the increased levels of these fatty acids were due to cancer-associated upregulation of de novo lipid synthesis.
What’s the issue?
In the 1980s, nail fold capillary microscopy using an ophthalmoscope was occasionally performed to evaluate for disease-associated vascular changes in patients who were being evaluated for connective tissue disorders. Within 2 decades, a dermoscope to assist in the evaluation of not only nail folds but also pigmented and other lesions replaced the ophthalmoscope. The US Food and Drug Administration recently approved a software-driven optical imaging and data analysis device that can be used to obtain additional information to assist the clinician in making a decision whether to biopsy a pigmented lesion.
As our ability to develop more sensitive and specific methods to diagnose melanoma and differentiate it from benign lesions advances, our approach to the evaluation of patients with pigmented lesions shall continue to be modified. Based on the detection of melanoma-associated volatile organic compounds coupled with their potential use as readily accessible tumor-related biomarkers, it is reasonable to speculate: (1) that a handheld office-based device, a dermatoscenter, that can identify melanoma-induced volatile tumor markers shall be developed to evaluate whether pigmented lesions are malignant or benign, and (2) that this device will eventually become an integral component of the dermatologist’s diagnostic armamentarium. Does your dermatology center need a dermatoscenter?
RNA sequencing characterized high-risk squamous cell carcinomas
SAN DIEGO – Cutaneous squamous cell carcinomas from organ transplant recipients had a more aggressive molecular profile than did tumor samples from immunocompetent patients, according to an RNA sequencing study presented at the annual meeting of the American Society for Dermatologic Surgery.
Specimens from organ transplant recipients showed greater induction of biologic pathways related to cancer signaling, fibrosis, and extracellular matrix remodeling, said Dr. Cameron Chesnut, a dermatologist in private practice in Spokane, Wash., who carried out the research while he was a dermatologic surgery resident at the University of California, Los Angeles.
Furthermore, the TP53 tumor suppressor gene was inhibited at least five times more in samples from organ transplant recipients, compared with those from immunocompetent patients, Dr. Chesnut said in an interview.
Squamous cell carcinoma (SCC) is the most common cancer to occur after organ transplantation, Dr. Chesnut and his associates noted. The malignancy is 65-250 times more common, is more than 4 times more likely to metastasize, and has a mortality rate of 5% compared with a rate of less than 1% in immunocompetent patients, based on data published online in the journal F1000 Prime Reports, they said.
To characterize these high-risk SCCs and compare them with lower-risk SCCs, the researchers performed RNA sequencing of three normal skin samples and SCC specimens from 15 patients – 7 organ transplant recipients and 8 otherwise healthy individuals. The researchers used an Illumina GAIIx RNA Seq instrument to generate RNA sequencing libraries of the specimens. They also used the web-based Ingenuity Pathway Analysis technique to identify the major biological pathways regulated within the tumors.
In all, 690 highly expressed genes were induced at least fivefold in SCCs from organ transplant recipients compared with those from otherwise healthy patients. These genes encoded pathways related to fibrosis, extracellular remodeling, the cell cycle, and tumor signaling, the investigators said. The COX-2 pathway for prostaglandin synthesis also was induced fivefold or more in the high-risk SCCs compared with those from immunocompetent patients, Dr. Chesnut added.
The researchers also identified 1,290 highly expressed genes that were inhibited at least fivefold in SCCs from organ transplant recipients compared with specimens from immunocompetent patients. The most strongly inhibited pathways were related to sterol biosynthesis and epithelial differentiation, followed by nucleotide excision repair, interleukin-6 and IL-17, and apoptosis, they said.
Based on these findings, novel therapeutics might someday be able to target specific biologic pathways that are highly induced in SCCs from organ transplant recipients, Dr. Chesnut said. “It’s hard to say what the most likely candidates are,” but based on the study findings, “regulating inflammation may be a target,” he added. Dr. Chesnut and his associates reported no external funding sources or conflicts of interest.
SAN DIEGO – Cutaneous squamous cell carcinomas from organ transplant recipients had a more aggressive molecular profile than did tumor samples from immunocompetent patients, according to an RNA sequencing study presented at the annual meeting of the American Society for Dermatologic Surgery.
Specimens from organ transplant recipients showed greater induction of biologic pathways related to cancer signaling, fibrosis, and extracellular matrix remodeling, said Dr. Cameron Chesnut, a dermatologist in private practice in Spokane, Wash., who carried out the research while he was a dermatologic surgery resident at the University of California, Los Angeles.
Furthermore, the TP53 tumor suppressor gene was inhibited at least five times more in samples from organ transplant recipients, compared with those from immunocompetent patients, Dr. Chesnut said in an interview.
Squamous cell carcinoma (SCC) is the most common cancer to occur after organ transplantation, Dr. Chesnut and his associates noted. The malignancy is 65-250 times more common, is more than 4 times more likely to metastasize, and has a mortality rate of 5% compared with a rate of less than 1% in immunocompetent patients, based on data published online in the journal F1000 Prime Reports, they said.
To characterize these high-risk SCCs and compare them with lower-risk SCCs, the researchers performed RNA sequencing of three normal skin samples and SCC specimens from 15 patients – 7 organ transplant recipients and 8 otherwise healthy individuals. The researchers used an Illumina GAIIx RNA Seq instrument to generate RNA sequencing libraries of the specimens. They also used the web-based Ingenuity Pathway Analysis technique to identify the major biological pathways regulated within the tumors.
In all, 690 highly expressed genes were induced at least fivefold in SCCs from organ transplant recipients compared with those from otherwise healthy patients. These genes encoded pathways related to fibrosis, extracellular remodeling, the cell cycle, and tumor signaling, the investigators said. The COX-2 pathway for prostaglandin synthesis also was induced fivefold or more in the high-risk SCCs compared with those from immunocompetent patients, Dr. Chesnut added.
The researchers also identified 1,290 highly expressed genes that were inhibited at least fivefold in SCCs from organ transplant recipients compared with specimens from immunocompetent patients. The most strongly inhibited pathways were related to sterol biosynthesis and epithelial differentiation, followed by nucleotide excision repair, interleukin-6 and IL-17, and apoptosis, they said.
Based on these findings, novel therapeutics might someday be able to target specific biologic pathways that are highly induced in SCCs from organ transplant recipients, Dr. Chesnut said. “It’s hard to say what the most likely candidates are,” but based on the study findings, “regulating inflammation may be a target,” he added. Dr. Chesnut and his associates reported no external funding sources or conflicts of interest.
SAN DIEGO – Cutaneous squamous cell carcinomas from organ transplant recipients had a more aggressive molecular profile than did tumor samples from immunocompetent patients, according to an RNA sequencing study presented at the annual meeting of the American Society for Dermatologic Surgery.
Specimens from organ transplant recipients showed greater induction of biologic pathways related to cancer signaling, fibrosis, and extracellular matrix remodeling, said Dr. Cameron Chesnut, a dermatologist in private practice in Spokane, Wash., who carried out the research while he was a dermatologic surgery resident at the University of California, Los Angeles.
Furthermore, the TP53 tumor suppressor gene was inhibited at least five times more in samples from organ transplant recipients, compared with those from immunocompetent patients, Dr. Chesnut said in an interview.
Squamous cell carcinoma (SCC) is the most common cancer to occur after organ transplantation, Dr. Chesnut and his associates noted. The malignancy is 65-250 times more common, is more than 4 times more likely to metastasize, and has a mortality rate of 5% compared with a rate of less than 1% in immunocompetent patients, based on data published online in the journal F1000 Prime Reports, they said.
To characterize these high-risk SCCs and compare them with lower-risk SCCs, the researchers performed RNA sequencing of three normal skin samples and SCC specimens from 15 patients – 7 organ transplant recipients and 8 otherwise healthy individuals. The researchers used an Illumina GAIIx RNA Seq instrument to generate RNA sequencing libraries of the specimens. They also used the web-based Ingenuity Pathway Analysis technique to identify the major biological pathways regulated within the tumors.
In all, 690 highly expressed genes were induced at least fivefold in SCCs from organ transplant recipients compared with those from otherwise healthy patients. These genes encoded pathways related to fibrosis, extracellular remodeling, the cell cycle, and tumor signaling, the investigators said. The COX-2 pathway for prostaglandin synthesis also was induced fivefold or more in the high-risk SCCs compared with those from immunocompetent patients, Dr. Chesnut added.
The researchers also identified 1,290 highly expressed genes that were inhibited at least fivefold in SCCs from organ transplant recipients compared with specimens from immunocompetent patients. The most strongly inhibited pathways were related to sterol biosynthesis and epithelial differentiation, followed by nucleotide excision repair, interleukin-6 and IL-17, and apoptosis, they said.
Based on these findings, novel therapeutics might someday be able to target specific biologic pathways that are highly induced in SCCs from organ transplant recipients, Dr. Chesnut said. “It’s hard to say what the most likely candidates are,” but based on the study findings, “regulating inflammation may be a target,” he added. Dr. Chesnut and his associates reported no external funding sources or conflicts of interest.
Key clinical point: Squamous cell carcinomas from organ transplant recipients showed a more aggressive molecular profile than did those from immunocompetent individuals.
Major finding: The high-risk tumors showed greater induction of biologic pathways related to cancer signaling, fibrosis, and extracellular matrix remodeling, and inhibition of the tp53 tumor suppressor gene.
Data source: RNA sequencing of 15 squamous cell carcinomas, including seven from organ transplant recipients.
Disclosures: The investigators reported no external funding sources or conflicts of interest.
Indoor tanning rates down for high school students in 2013
Indoor tanning by high school girls decreased from 2009 to 2013, according to a recent study from the Centers for Disease Control and Prevention.
The overall indoor tanning rate for all high school girls dropped to about 20% in 2013, down from just over 25% in 2009. There was a significant drop in indoor tanning for non-Hispanic white girls and a slight decrease for Hispanic girls. The rate of indoor tanning for non-Hispanic black girls remained steady.
Decreases in indoor tanning “may be partly attributable to increased awareness of its harms,” with new or strengthened laws in 40 states having an impact as well, according to Gery P. Guy Jr., Ph.D., of the Division of Cancer Prevention and Control at the CDC in Atlanta.
Non-Hispanic white girls were by far the most likely to indoor tan in 2013, with nearly 31% tanning at least once in the previous year and almost 17% tanning at least 10 times in the same period. No other measured ethnic group had such high rate of usage, with only 2.5% of non-Hispanic blacks, about 8% of Hispanics, and just under 10% of non-Hispanic others engaging in indoor tanning at least once, the investigators reported (JAMA Dermatol. 2014 Dec. 23 [doi:10.1001/jamadermatol.2014.4677]).
Indoor tanning by high school boys was much lower than for girls, with about 5% of all boys tanning at least once in 2013. White boys had the highest rate of measured ethnicities, but this was only at about 6%, the researchers said.
The study is based on data collected for the 2009, 2011, and 2013 Youth Risk Behavior Surveys.
Indoor tanning by high school girls decreased from 2009 to 2013, according to a recent study from the Centers for Disease Control and Prevention.
The overall indoor tanning rate for all high school girls dropped to about 20% in 2013, down from just over 25% in 2009. There was a significant drop in indoor tanning for non-Hispanic white girls and a slight decrease for Hispanic girls. The rate of indoor tanning for non-Hispanic black girls remained steady.
Decreases in indoor tanning “may be partly attributable to increased awareness of its harms,” with new or strengthened laws in 40 states having an impact as well, according to Gery P. Guy Jr., Ph.D., of the Division of Cancer Prevention and Control at the CDC in Atlanta.
Non-Hispanic white girls were by far the most likely to indoor tan in 2013, with nearly 31% tanning at least once in the previous year and almost 17% tanning at least 10 times in the same period. No other measured ethnic group had such high rate of usage, with only 2.5% of non-Hispanic blacks, about 8% of Hispanics, and just under 10% of non-Hispanic others engaging in indoor tanning at least once, the investigators reported (JAMA Dermatol. 2014 Dec. 23 [doi:10.1001/jamadermatol.2014.4677]).
Indoor tanning by high school boys was much lower than for girls, with about 5% of all boys tanning at least once in 2013. White boys had the highest rate of measured ethnicities, but this was only at about 6%, the researchers said.
The study is based on data collected for the 2009, 2011, and 2013 Youth Risk Behavior Surveys.
Indoor tanning by high school girls decreased from 2009 to 2013, according to a recent study from the Centers for Disease Control and Prevention.
The overall indoor tanning rate for all high school girls dropped to about 20% in 2013, down from just over 25% in 2009. There was a significant drop in indoor tanning for non-Hispanic white girls and a slight decrease for Hispanic girls. The rate of indoor tanning for non-Hispanic black girls remained steady.
Decreases in indoor tanning “may be partly attributable to increased awareness of its harms,” with new or strengthened laws in 40 states having an impact as well, according to Gery P. Guy Jr., Ph.D., of the Division of Cancer Prevention and Control at the CDC in Atlanta.
Non-Hispanic white girls were by far the most likely to indoor tan in 2013, with nearly 31% tanning at least once in the previous year and almost 17% tanning at least 10 times in the same period. No other measured ethnic group had such high rate of usage, with only 2.5% of non-Hispanic blacks, about 8% of Hispanics, and just under 10% of non-Hispanic others engaging in indoor tanning at least once, the investigators reported (JAMA Dermatol. 2014 Dec. 23 [doi:10.1001/jamadermatol.2014.4677]).
Indoor tanning by high school boys was much lower than for girls, with about 5% of all boys tanning at least once in 2013. White boys had the highest rate of measured ethnicities, but this was only at about 6%, the researchers said.
The study is based on data collected for the 2009, 2011, and 2013 Youth Risk Behavior Surveys.
FROM JAMA DERMATOLOGY
FDA approves nivolumab for patients with advanced melanoma
The Food and Drug Administration has approved the PD-1 inhibitor nivolumab for patients with unresectable or metastatic melanoma who no longer respond to other drugs.
Nivolumab, marketed as Opdivo, is intended for patients who have been previously treated with ipilimumab and, for patients whose tumors express a BRAF V600 mutation, for use after treatment with ipilimumab and a BRAF inhibitor, according to the FDA statement.
“Opdivo is the seventh new melanoma drug approved by the FDA since 2011,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research, said in the statement. “The continued development and approval of novel therapies based on our increasing understanding of tumor immunology and molecular pathways are changing the treatment paradigm for serious and life-threatening diseases.”
The FDA granted nivolumab breakthrough therapy designation and it was approved under the agency’s accelerated approval program.
Approval was based on CheckMate-037, a trial that demonstrated a 32% objective response rate with nivolumab vs. 11% with investigator’s choice chemotherapy among 120 patients with unresectable metastatic melanoma that progressed despite prior ipilimumab or a BRAF inhibitor, if BRAF mutation-positive.
The most common side effects of the drug were rash, itching, cough, upper respiratory tract infections, and edema. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands, according to the FDA statement
Opdivo is marketed by Bristol-Myers Squibb.
The most common side effects of the drug were rash, itching, cough, upper respiratory tract infections, and edema. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands, according to the FDA statement
On Twitter @NikolaidesLaura
The Food and Drug Administration has approved the PD-1 inhibitor nivolumab for patients with unresectable or metastatic melanoma who no longer respond to other drugs.
Nivolumab, marketed as Opdivo, is intended for patients who have been previously treated with ipilimumab and, for patients whose tumors express a BRAF V600 mutation, for use after treatment with ipilimumab and a BRAF inhibitor, according to the FDA statement.
“Opdivo is the seventh new melanoma drug approved by the FDA since 2011,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research, said in the statement. “The continued development and approval of novel therapies based on our increasing understanding of tumor immunology and molecular pathways are changing the treatment paradigm for serious and life-threatening diseases.”
The FDA granted nivolumab breakthrough therapy designation and it was approved under the agency’s accelerated approval program.
Approval was based on CheckMate-037, a trial that demonstrated a 32% objective response rate with nivolumab vs. 11% with investigator’s choice chemotherapy among 120 patients with unresectable metastatic melanoma that progressed despite prior ipilimumab or a BRAF inhibitor, if BRAF mutation-positive.
The most common side effects of the drug were rash, itching, cough, upper respiratory tract infections, and edema. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands, according to the FDA statement
Opdivo is marketed by Bristol-Myers Squibb.
The most common side effects of the drug were rash, itching, cough, upper respiratory tract infections, and edema. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands, according to the FDA statement
On Twitter @NikolaidesLaura
The Food and Drug Administration has approved the PD-1 inhibitor nivolumab for patients with unresectable or metastatic melanoma who no longer respond to other drugs.
Nivolumab, marketed as Opdivo, is intended for patients who have been previously treated with ipilimumab and, for patients whose tumors express a BRAF V600 mutation, for use after treatment with ipilimumab and a BRAF inhibitor, according to the FDA statement.
“Opdivo is the seventh new melanoma drug approved by the FDA since 2011,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research, said in the statement. “The continued development and approval of novel therapies based on our increasing understanding of tumor immunology and molecular pathways are changing the treatment paradigm for serious and life-threatening diseases.”
The FDA granted nivolumab breakthrough therapy designation and it was approved under the agency’s accelerated approval program.
Approval was based on CheckMate-037, a trial that demonstrated a 32% objective response rate with nivolumab vs. 11% with investigator’s choice chemotherapy among 120 patients with unresectable metastatic melanoma that progressed despite prior ipilimumab or a BRAF inhibitor, if BRAF mutation-positive.
The most common side effects of the drug were rash, itching, cough, upper respiratory tract infections, and edema. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands, according to the FDA statement
Opdivo is marketed by Bristol-Myers Squibb.
The most common side effects of the drug were rash, itching, cough, upper respiratory tract infections, and edema. The most serious side effects are severe immune-mediated side effects involving healthy organs, including the lung, colon, liver, kidneys and hormone-producing glands, according to the FDA statement
On Twitter @NikolaidesLaura
Small victories add up to paradigm shifts for hard-to-treat tumors
Click on the PDF icon at the top of this introduction to read the full article.
Click on the PDF icon at the top of this introduction to read the full article.
Click on the PDF icon at the top of this introduction to read the full article.