Letters

Figure. Clinical and Histopathologic Images Illustrating the Present Case A

B

sis, but several secondary effects on the molecular and cellular level may also be explained.1-3 In the present case, we found a discrepancy between the clinical picture of hypertrophic actinic keratosis and the histopathologic findings of mycosis fungoides. We believe that the topical application of imiquimod, 5%, in cream may have induced the histologic picture observed and then promoted the resolution of what was originally an actinic keratosis. Our hypothesis was supported by the clinical features of the skin lesion treated with imiquimod, the patient’s history of severe actinic skin damage, and the absence of monoclonal T-cell receptor expansion found by PCR analysis. In conclusion, we hypothesize that imiquimod, 5%, for treatment of actinic keratoses or epithelial skin neoplasms could induce histopathologic changes mimicking mycosis fungoides, and this phenomenon may represent a potential diagnostic pitfall for the dermatopathologist. Davide Altamura, MD Francesco Simonacci, MD Torkan Hirbod, MD Evdokia Arkoumani, MD Roberto Verdolini, MD, FRCP Author Affiliations: Department of Dermatology, The Princess Alexandra Hospital Trust, Harlow, Essex, England (Altamura, Simonacci, Hirbod, Verdolini); Department of Pathology, The Princess Alexandra Hospital Trust, Harlow, Essex, England (Arkoumani). Corresponding Author: Davide Altamura, MD, Department of Dermatology, The Princess Alexandra Hospital Trust, Hamstel Road, Harlow, Essex CM20 1QX, England ([email protected]). Published Online: August 13, 2014. doi:10.1001/jamadermatol.2014.929. Conflict of Interest Disclosures: None reported. 1. Torres A, Storey L, Anders M, et al. Immune-mediated changes in actinic keratosis following topical treatment with imiquimod 5% cream. J Transl Med. 2007;5:7. 2. Schön MP, Schön M. Imiquimod: mode of action. Br J Dermatol. 2007;157(157) (suppl 2):8-13. 3. Wagstaff AJ, Perry CM. Topical imiquimod: a review of its use in the management of anogenital warts, actinic keratoses, basal cell carcinoma and other skin lesions. Drugs. 2007;67(15):2187-2210. 4. Buettiker UV, Yawalkar NY, Braathen LR, Hunger RE. Imiquimod treatment of lentigo maligna: an open-label study of 34 primary lesions in 32 patients. Arch Dermatol. 2008;144(7):943-945.

A, Growing and eroded skin lesion on the scalp of a man in his 80s; the photograph shows an erythematous, eroded, and partially keratotic plaque on a background of actinic changes of the skin. B, Histopathologic findings of a punch biopsy specimen taken from the excoriated plaque on the scalp (hematoxylin-eosin, original magnification ×20). The image shows the presence of a dense infiltrate of atypical lymphocytes in the upper dermis; collections of lymphocytes resembling Pautrier microabscesses are seen in the epidermis.

Discussion | Topical imiquimod is an active imidazoquinoline immunomodulator agent currently indicated as nonablative treatment for superficial basal cell carcinomas, actinic keratoses, and genital warts.3 Imiquimod, 5%, in cream has also shown efficacy against many other tumor entities and primary cutaneous lymphomas such as mycoses fungoides.4-6 The basic mechanism of its action is explained by the production and release of proinflammatory cytokines leading to the activation of antigen-presenting cells and induction of apopto-

5. Adams S, Kozhaya L, Martiniuk F, et al. Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer. Clin Cancer Res. 2012;18(24):6748-6757. 6. Coors EA, Schuler G, Von Den Driesch P. Topical imiquimod as treatment for different kinds of cutaneous lymphoma. Eur J Dermatol. 2006;16(4):391-393.

COMMENT & RESPONSE

The Good, the Bad, and the Ugly of Free Drug Samples To the Editor I read with interest the article by Hurley et al1 that sets out to describe the relationship between free drug samples and dermatologists’ prescribing patterns. The authors duly note their study limitations, including its restriction to a single academic medical center, its representation of the nonacademic pool by the National Disease and Therapeutic Index (NDTI), and its inability to control for other factors such as pharmaceutical mar-

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keting or even differences in patient demographics in such a small pool of patients at only 1 academic medical center. As a former participant in the NDTI database—who stopped participating because it was too cumbersome to effectively provide data—I am skeptical of the validity of the study data. However, the authors did a fine job at presenting the data with balance and ultimately suggesting that free drug samples may lead to a higher cost in acne vulgaris treatment. This was thought provoking even if limited in its ability to answer the ultimate question. However, I write this letter because of the unbalanced editorial by Katz et al.2 The title of the editorial alone makes it clear that the authors believe free samples belong in the dustbin. This was not my conclusion after reading the study by Hurley et al.1 When Katz and colleagues chose to modify the word “opposed” with “starkly” but not modify the word “favorable,” it felt like demagoguery. The editorial compelled me to write this counterpoint. It is evidence, and not editorials, that drives physicians’ dayto-day practice of medicine. I know a dermatologist at an academic center that allows free drug samples. This physician sees as many patients per week as a dermatologist in private practice and dispenses free drug samples. Despite this practice of dispensing free drug samples, this dermatologist has been commended by a national insurer for adopting a cost-saving approach to care and for being among the top 5% of physicians who prescribe generic medications in the state. Clearly, therefore, dispensing free samples can live in harmony with good, cost-saving medicine. It is wrong for Katz et al to recommend a “strong, united stance discouraging physicians from dispensing free drug samples in any form,”2(p484) at least with our present knowledge. Moreover, the American Academy of Dermatology, as our representative body, should not be encouraged to put anything in the dustbin just because we do not know at the moment if the component in hand is a vital piece of the running machine or useless trash.

it comes to drug samples. Indeed, a substantial and growing body of evidence 1, 2 (including the study on which we commented3) has shown that physicians who give patients drug samples are more likely than other physicians to prescribe medicines that are more expensive and less appropriate as firstline treatments. Moreover, drug samples are more likely to be newer and therefore more likely to have emerging safety concerns, including concerns that lead to black-box warnings.4 Concerns about the negative effects of drug sampling have prompted many organizations, including the Association of American Medical Colleges, the American Society of HealthSystem Pharmacists, the Institute of Medicine, and the Joint Commission, to advocate banning or much more stringently limiting drug sampling. The list of institutions already banning or sharply restricting drug sampling includes large managed care organizations, government-run health care institutions, and many universities, including the University of Rochester Medical Center.5 As the study by Hurley et al3 showed, dermatologists’ use of samples increased by 50% during the 2001-2010 period, while other physicians’ use of samples decreased during the same period by over 40%. That increase, coupled with the welldocumented harms of drug sampling, should galvanize our specialty’s leading professional organizations to guide the practice of dermatology away from the use of drug samples. In the meantime, dermatologists interested in practicing evidencebased medicine should stop giving patients drug samples.

Brian Poligone, MD, PhD

Corresponding Author: Kenneth A. Katz, MD, MSc, MSCE, Department of Dermatology, The Permanente Medical Group Inc, 7601 Stoneridge Dr, Second Floor, S Bldg, Pleasanton, CA 94588 ([email protected]).

Author Affiliation: Department of Dermatology, University of Rochester School of Medicine, Rochester, New York.

Author Affiliations: Department of Dermatology, The Permanente Medical Group Inc, Pleasanton, California (Katz); Department of Dermatology, University of Pennsylvania, Philadelphia (Reid); Department of Dermatology, University of California, San Francisco (Chren); San Francisco Veterans Affairs Medical Center, San Francisco, California (Chren).

Published Online: September 3, 2014. doi:10.1001/jamadermatol.2014.1815.

Corresponding Author: Brian Poligone, MD, PhD, Department of Dermatology, University of Rochester School of Medicine, 601 Elmwood Ave, PO Box 697, Rochester, NY 14642 ([email protected]).

Conflict of Interest Disclosures: Dr Katz is a shareholder in Synta Pharmaceuticals Corp and Arrowhead Research Corp. Dr Chren is a consultant to Genentech. No other disclosures are reported.

Published Online: September 3, 2014. doi:10.1001/jamadermatol.2014.1820.

Disclaimer: The views expressed in this article do not necessarily reflect those of The Permanente Medical Group Inc.

Conflict of Interest Disclosures: Dr Poligone serves as consultant for and is on the speaker’s bureau of Celgene. He is an investigator for Valeant and Kyowa Pharmaceuticals. 1. Hurley MP, Stafford RS, Lane AT. Characterizing the relationship between free drug samples and prescription patterns for acne vulgaris and rosacea. JAMA Dermatol. 2014;150(5):487-493. 2. Katz KA, Reid EE, Chren MM. Drug samples in dermatology: out of the closet, into the dustbin. JAMA Dermatol. 2014;150(5):483-485.

In Reply We agree with Dr Poligone that evidence should guide the practice of medicine. With respect to dispensing free drug samples, existing evidence supports our contention that this practice should be discouraged in dermatology. Although the prescribing practices of Dr Poligone’s colleague are laudable, they are the exception, not the rule, when 1238

Kenneth A. Katz, MD, MSc, MSCE Erika E. Reid, MD Mary-Margaret Chren, MD

1. Boltri JM, Gordon ER, Vogel RL. Effect of antihypertensive samples on physician prescribing patterns. Fam Med. 2002;34(10):729-731. 2. Adair RF, Holmgren LR. Do drug samples influence resident prescribing behavior? A randomized trial. Am J Med. 2005;118(8):881-884. 3. Hurley MP, Stafford RS, Lane AT. Characterizing the relationship between free drug samples and prescription patterns for acne vulgaris and rosacea. JAMA Dermatol. 2014;150(5):487-493. 4. Cutrona SL, Woolhandler S, Lasser KE, et al. Free drug samples in the United States: characteristics of pediatric recipients and safety concerns. Pediatrics. 2008;122(4):736-742. 5. University of Rochester Medical Center. Policy on Industry Interactions: Policy and Guidelines: Interactions between the University of Rochester Medical Center (URMC) and the Pharmaceutical, Biotech, Medical Device, and Hospital Equipment and Supplies Industries (“Industry”): November 8, 2013. Available at: http://www.urmc.rochester.edu/quality/documents/Industry-Interactions -Policy.pdf. Accessed June 12, 2014.

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The good, the bad, and the ugly of free drug samples.

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