By Abby S. Van Voorhees, MD, March 03, 2014
In this month’s Acta Eruditorum column, Physician Editor Abby S. Van Voorhees, MD, talks with Kelly Cordoro, MD, about her recent Pediatric Dermatology article, “Treatment of preadolescent acne in the United States: an analysis of nationally representative data.”
Dr. Van Voorhees: Let’s start by defining what ages you are talking about when you refer to preadolescent acne.
Dr. Cordoro: First, thank you to Dr. Steve Feldman at Wake Forest for inviting me to collaborate on this project; it was Steve’s idea to query the National Ambulatory Medical Care Survey (NAMCS) database to explore the off-label use of acne medications in the pediatric population.
For this study, we defined “preadolescent” as ages 7 to 11 years and “adolescent” as ages 12 to 18 years. Other groups investigated were those less than 1 year (neonatal or infantile) and those 1-6 years (mid-childhood).
Dr. Van Voorhees: Is the prevalence of this type of acne increasing?
Dr. Cordoro: It certainly seems to be. Fleischer, Feldman, and their group at Wake Forest published data in Pediatric Dermatology in 2011 (28(6):645—648) from NAMCS that revealed a statistically significant decrease in the mean age of visits for acne by children over a 28-year period in the U.S., likely indicative of an earlier age of acne onset. This data also showed that visits for acne by children aged 6 to 8 years steadily increased over time from 1979 to 2007. [pagebreak]
Dr. Van Voorhees: Do we know why this might be occurring?
Dr. Cordoro: There may be multiple explanations, including earlier recognition and better access to health care. Another possible cause of great importance, and one supported by evidence, is earlier onset of puberty. Several recent studies have found that children are entering puberty earlier than they have in past decades, determined by comparison of peak height velocity, Tanner staging, testicular volume, and other measurements of recent cohorts compared to pediatric cohorts from decades ago. The question of why children are entering puberty earlier is a topic of controversy and active research.
Dr. Van Voorhees: Are all of the standard acne therapies for children reasonable for those who are younger than 12?
Dr. Cordoro: Basically, yes. We prescribe topical antibiotics, topical retinoids, benzoyl peroxide, oral antibiotics, and even isotretinoin for children with acne who are less than 12 years old. The choice of agents in this age group is individualized and based on the same parameters considered in adults — the primary lesional morphology or type of acne (comedonal and/or inflammatory), severity, risk of permanent scarring, and distribution. Age is a consideration in terms of tolerance — pre-pubertal children are not generating a lot of oil, so they will not be able to tolerate daily use of topical keratolytics like retinoids or benzoyl peroxide (BPO). You can combat this by decreasing the frequency of application, limiting to lower concentrations of the active ingredient, and using non-comedogenic emollients. [pagebreak]
Dr. Van Voorhees: Can you remind us which treatments are approved and which are not?
Dr. Cordoro: Most acne treatments are approved for patients 12 years and older, including oral isotretinoin, topical retinoids, and topical antibiotics including topical clindamycin, erythromycin, and benzoyl peroxide individually and in combination formulations. The primary exceptions include oral erythromycin, which has no age restrictions; tetracycline and doxycycline, approved for ages 8 years and older; adapalene/BPO gel, approved for ages 9 years and older; and a newer formulation of tretinoin gel 0.05 percent, approved for ages 10 years and older.
Dr. Van Voorhees: Are there specific agents that should be avoided in this younger age group?
Dr. Cordoro: It’s best to avoid topical salicylic acid in infants and very young children with acne given the low, but possible, risk of salicylism. Oral tetracyclines should not be given to treat acne in kids less than 8 years old because of effects on developing teeth. Otherwise, most acne medications can be used safely and effectively in children.
Dr. Van Voorhees: Tell us about your study. What were the goals? What was the population that you studied?
Dr. Cordoro: The goals of the study were to compare the therapies being prescribed to preadolescent patients with acne (defined in this study as ages 7 to 11 years) with those being prescribed to adolescent patients (ages 12 to 18 years) and to determine whether prescribing patterns differ between dermatologists and pediatricians.
Dr. Van Voorhees: What were your findings? Which medications were typically used in this younger acne patient? [pagebreak]
Dr. Cordoro: There were many interesting findings! I will limit my comments to the differences between pre-adolescents and adolescents in terms of medications prescribed and how this varied by specialty. We found that physicians prescribed a wide variety of FDA-approved and off-label medications to preadolescent patients with acne. Preadolescents overall were primarily prescribed topical treatments, with topical retinoids accounting for the largest percentage of prescribed topicals. The other most commonly prescribed medications to preadolescent patients were topical BPO and the combination of BPO/erythromycin. Minocycline was the most commonly prescribed oral antibiotic in this age group.
In comparison, the leading topical treatments prescribed to adolescents with acne were the same — retinoids and BPO, in a slightly different order of frequency. The most interesting finding was that isotretinoin was the most commonly prescribed oral medication in the adolescent age group, followed closely by minocycline. The isotretinoin finding was one of the few major disparities between the two groups. Although isotretinoin was prescribed to 18 percent of adolescent patients, it was used in only about 1 percent of preadolescents. I am rounding the numbers here and will do so throughout the interview to make things easier.
Dr. Van Voorhees: Were there differences in the frequency of the use of any of the medications because of severity of acne?
Dr. Cordoro: Unfortunately, it is impossible to know the rationale behind the observed prescribing practices because the severity of acne, lesional morphology, and other parameters such as affordability that would influence treatment choices are not recorded in the NAMCS database. The current study, as well as data previously published by Yentzer and colleagues (Pediatr Dermatol 2008;25:635—639) stratified according to specialty, suggest that differences in acne medication prescribing patterns between dermatologists and primary care physicians (PCPs) are particularly pronounced in preadolescent patients. Dermatologists frequently prescribe topical retinoids to this patient population, whereas PCPs prefer oral antibiotics. This data matches our clinic experience and identifies a potential knowledge gap in acne treatment among non-dermatologists. PCPs are seeing these patients frequently, yet many may be unaware of the rationale for use of various acne therapies. In light of the significant gap between demand for dermatology services and supply, we should do our best to educate our non-dermatologist colleagues on the basics of acne management. [pagebreak]
Dr. Van Voorhees: Were there differences in the frequency of the use of any of the medications because of safety concerns?
Dr. Cordoro: Though it is impossible to know for sure, if we use isotretinoin as an example, we can reasonably speculate that PCPs may be hesitant to prescribe this medication for a variety of reasons; among them, lack of specialty knowledge as it relates to using this drug appropriately, safety concerns, the strict requirements of federal monitoring programs, and the need for frequent clinic visits and monitoring bloodwork. This does not explain why dermatologists who are familiar with this medication and are using it in teens are not using it in preadolescent patients. This could be due to simple mathematics — severe acne in preadolescents is uncommon; therefore, isotretinoin use in this population is uncommon. An alternative explanation is that safety concerns together with the hassle of the iPledge program may be limiting the use of isotretinoin in preteens regardless of disease severity or specialty.
Dr. Van Voorhees: What percentage of patients was seen by pediatricians versus dermatologists versus other medical specialties?
Dr. Cordoro: The differences depended on the age of the patients and were not too surprising. Overall, adolescent patients with acne saw dermatologists far more often than any other specialty whereas the youngest patients were more likely to see pediatricians. The details are very number-heavy, and I invite readers to refer to the manuscript, wherein there is a nice color-coded graphic detailing this information. In general terms, we found that pediatricians managed the majority of neonatal and infantile acne, while dermatologists, general and family practitioners, and ob/gyns managed only a quarter of patients in this age group. Pediatricians also saw the majority of the patients with mid-childhood acne (60 percent) but this age group was more likely to see a dermatologist (40 percent) than were infants. Again, I am rounding the numbers here. Dermatologists primarily managed preadolescent acne patients (38 percent) but pediatricians managed a similar percentage of these patients (34 percent) followed by general and family practitioners (26.0 percent). Adolescent patients were much more likely to see a dermatologist (67 percent) than a pediatrician or a general or family practitioner. [pagebreak]
Dr. Van Voorhees: Were there differences in what was prescribed based on provider specialty? Did one group of providers favor oral treatments over topical ones?
Dr. Cordoro: Yes, prescribed treatments differed substantially between dermatologists and PCPs. For preadolescents with acne, dermatologists prescribed topicals more than any other drug, preferring topical retinoids, BPO, clindamycin, and combo BPO/clindamycin. In comparison, PCPs prescribed equal amounts of oral antibiotics, including minocycline, oral clindamycin and tetracycline, and topical therapies to pre-adolescents with acne.
On the contrary, for adolescent patients with acne, dermatologists most often prescribed oral agents including isotretinoin and minocycline as well as topical retinoids and BPO. In contrast, PCPs prescribed primarily topical agents — BPO and tretinoin — and less frequently prescribed oral antibiotics. When PCPs used oral agents, they preferred, in decreasing order of frequency, tetracycline, minocycline, and doxycycline.
Dr. Van Voorhees: Did your study suggest that the lack of FDA approval of a medication plays a role in what is chosen for acne care?
Dr. Cordoro: Fortunately, no. This data suggests that all specialties seem to recognize that off-label prescribing is necessary given the limited range of FDA-approved treatments for preadolescent patients.
Dr. Cordoro is associate professor of dermatology and pediatrics at the University of California, San Francisco. Her article was published in the November/December 2013 issue of Pediatric Dermatology; Pediatr Dermatol. 2013 Nov-Dec;30(6):689-94. doi: 10.1111/pde.12201. Epub 2013 Jul 22.