Data have emerged from a recent Austrian study suggesting that marathon runners have a heightened risk of contracting skin cancer. This link is believed to be a result of either increased sun exposure, immunosuppression caused by intensive long-term exercise or a combination of the two.
Christina Ambros-Rudolph and fellow researchers at the University of Graz (Austria) compared observations from 210 athletes with a sex- and age-matched control group. They observed anamnestic, phenotypic, sun-related and clinical variables in all study participants. Of the 210 athletes, 166 were men and 44 were women. All were 19–71 years of age.
From this research, they observed that non-runners were more likely to have a higher sensitivity to sun and present with more common melanocytic nevi. However, athletes, such as marathon runners, were more likely to present with more atypical melanocytic nevi, solar lentigines and nonmelanoma skin cancer suggestive lesions.
The study authors also recorded that the majority of marathon runners they observed wore shorts (96.7%) and a t-shirt (98.6%). This clothing left the runner’s backs and extremities either fully or partially exposed. Only 56.2% of the athletic participants in the study reported regular sunscreen use and 1.9% admitted that they did not use it at all.
The data are important, especially in view of the fact that, as the study notes, ‘marathon running has surged in popularity’.
In conclusion, the researchers advise that ‘in short, until further sport–physiologic studies elucidate in detail the potential association between exercise-induced immunosuppression and malignant melanoma, runners should be alerted to the crucial role of UV radiation in the development of malignant melanoma and nonmelanoma skin cancer. In particular, they should be advised to reduce UV exposure during exercising by choosing training and competition schedules with low sun exposure, wearing adequate clothing and regularly using water-resistant sunscreens.’
Source: Ambros-Rudolph CM, Hofmann-Wellenhof R, Richtig E, Muller-Furstner M, Soyer HP, Kerl H Malignant melanoma in marathon runners. Arch. Dermatol. 142(11), 1471–1474 (2006).
What is the best way to prevent fetal exposure to isotretinoin?
Isotretinoin is an effective treatment for severe acne. With over 1.4 million prescriptions dispensed annually in the USA, the drug provides a great benefit to patients with this physically, emotionally and socially disabling condition. However, isotretinoin is also highly teratogenic, associated with a risk of birth defects if taken by pregnant women.
Since the introduction of the drug in 1982, several risk management programs have been implemented in an attempt to reduce fetal exposure but with suboptimal levels of success. The latest program, iPLEDGE, was introduced by the manufacturers of isotretinoin in March 2006 at the request of the US FDA, but concerns remain over its utility.
In a paper published in the November 2006 issue of PLoS Medicine, Lorien Abroms and colleagues discuss the advantages and disadvantages of the iPLEDGE system.
iPLEDGE is the most rigorous risk management program to date. All patients and all parties involved in isotretinoin distribution, including wholesalers, pharmacies and healthcare professionals, are required to register a single online database at www.ipledgeprogram.com.
Previous interventions have failed to sufficiently reduce the number of pregnancies exposed to isotretinoin, perhaps owing to a lack of motivation or education on the part of patients and a lack of compliance by providers of the drug.
To try to improve compliance and motivation, under the iPLEDGE program, pharmacists may now dispense isotretinoin only when the iPLEDGE database indicates that the following requirements have been met:
| • | Physicians must provide results of two negative pregnancy tests and two agreed forms of contraception to be used throughout treatment; | ||||
| • | Each month, physicians must provide negative results of additional pregnancy tests, re-identify the patient’s contraceptive choices and provide pregnancy prevention counseling; | ||||
| • | Patients must sign a consent form, identify their two chosen forms of contraception and answer questions demonstrating their understanding of the risks of isotretinoin. | ||||
iPLEDGE has the advantages of being able to prevent pregnant patients from beginning treatment, identify unplanned pregnancies earlier and increase awareness of the risks.
However, although adopted widely, many dermatologists complain that the system is inflexible and confusing and that there are too many requirements. Moreover, it is still unknown whether the program actually reduces the number of exposed pregnancies, since there has been no formal evaluation of the system to date. Writing in the PLoS Medicine article, Steven Feldman, MD, comments, “A lesson from the history of past programs is that new programs should be tested before implementation. Until then, physicians must continue to use isotretinoin with great caution. Isotretinoin should be a last-line acne treatment for women of child-bearing potential.”
Sources: Abroms L, Maibach E, Lyon-Daniel K, Feldman SR. What is the best approach to reducing birth defects associated with isotretinoin? PLoS Med. 3(11), e483 (2006).
www.ipledgeprogram.com
Possible link between gadolinium and rare skin disease
Nephrogenic systemic fibrosis (NSF), a rare skin disease affecting patients with kidney failure, may be associated with exposure to gadolinium-containing contrast agents.
Approximately 200 cases of this rare condition have been diagnosed since its identification in 1997. Also known as nephrogenic fibrosing dermopathy (NFD), symptoms include discoloration, tightening and thickening of the skin, which can lead to pain, muscle weakness and difficulties in bending the joints. In some cases, fibrosis of the internal organs may lead to organ failure and death.
The cause of the disease is unknown but increasing evidence has suggested a link to gadolinium-containing contrast agents, which are used in magnetic resonance imaging (MRI).
In a study published in the November 11 issue of the Journal of the American Academy of Dermatology, researchers found traces of gadolinium in four out of 13 tissue samples from NSF patients who had been exposed to the substance previously during MRI. No gadolinium was found in a tissue sample from a negative control.
The research was led by Whitney High from the University of Colorado Health Sciences Center (Denver, CO, USA). “Although gadolinium-based contrast agents have a long history of safe and effective use in MRI, the dose of the agent administered to kidney failure patients undergoing magnetic resonance angiography to examine blood vessels is up to three times higher than the amount used in a typical MRI test,” explained Dr High. “Recent publications have suggested an association between exposure to gadolinium and the development of NSF/NFD and our pilot study was designed to determine whether gadolinium was detected within the skin and soft tissue of patients with the disease who were exposed to this contrast agent.”
“While clearly more research needs to be done, we are encouraged by our findings and hope that it provides an important first step in understanding the cause of this elusive disease. Until more data becomes available, we urge patients with end-stage kidney disease and their healthcare providers to be aware of this potentially fatal association between gadolinium and NSF/NFD and make every effort to avoid any unnecessary, excessive dosage of this contrast agent.”
The US FDA are gathering additional data currently to assess the link between NSF/NFD and gadolinium-containing contrast agents and recommend that the substance is avoided in at-risk patients unless absolutely necessary.
Sources: High WA, Ayers RA, Chandler J, Zito G, Cowper SE. Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis. J. Am. Acad. Dermatol. (2006) (Epub ahead of print)
US Food and Drug Administration: www.fda.gov/cder/drug/advisory/ gadolinium_agents.htm
Medical news today: www.medicalnew stoday.com/medicalnews.php?newsid=56897
Red hair genes associated with increased risk of skin cancer
New research has confirmed association of ‘red hair color’ genes with increased risk of skin cancer.
Scientists assessed associations of common variants of the skin color gene melanocortin 1 receptor (MC1R) with risks of three different types of skin cancer. Three particular polymorphisms (151Cys, 160Trp and 294His) were linked to red hair, fair skin and tendency to tan in childhood. These variants were particularly associated with a risk of contracting the three melanoma types, in particular 151Cys which conferred a 56–67% increase in risk for the three cancer types.
Although ‘red hair’ gene variants do seem to confer increased risk, women with medium or olive skin who were heterozygous for the red hair and nonred hair alleles had the highest melanoma risk of the group. This indicated that the influence of MC1R variants on skin cancer risk seems to be independent of phenotypic pigmentation.
This study provides further information on predicting a person’s risk of skin cancer by determining their MC1R genotype. However, these findings need to be confirmed through future research into MC1R variants.
Sources: Han J, Kraft P, Colditz GA, Wong J, Hunter DJ. Melanocortin 1 receptor variants and skin cancer risk. Int. J. Cancer 119(8), 1976–1984 (2006).