Letters

Published Online: October 18, 2017. doi:10.1001/jamadermatol.2017.3668 infection involves the nail matrix, systemic therapy is often Author Contributions: Dr Adotama and Mr Tinker had full access to all of the indicated.2 Terbinafine is the systemic antifungal of choice, data in the study and take responsibility for the integrity of the data and the with cure rates as high as 80%.3 Though terbinafine is well tol- accuracy of the data analysis. erated, hepatotoxic effects have been reported in adults.4 There Study concept and design: Adotama, Glass, Allen. Acquisition, analysis, or interpretation of data: Adotama, Tinker, Mitchell. are fewer risk factors for liver injury in children and consen- Drafting of the manuscript: Adotama, Tinker, Mitchell. sus regarding laboratory surveillance during therapy has not Critical revision of the manuscript for important intellectual content: All authors. been reached, with physician preference varying widely. The Statistical analysis: Adotama, Tinker, Mitchell. Administrative, technical, or material support: Adotama, Tinker, Mitchell. aim of our study was to investigate the prevalence of labora- Study supervision: Adotama, Tinker, Allen. tory monitoring and laboratory abnormalities during sys- Conflict of Interest Disclosures: None reported. temic terbinafine therapy in pediatric patients with onycho- 1. Alexis A, Heath CR, Halder RM. Folliculitis keloidalis nuchae and mycosis. pseudofolliculitis barbae: are prevention and effective treatment within reach? Dermatol Clin. 2014;32(2):183-191. Methods | We conducted an institutional review board- 2. Perry PK, Cook-Bolden FE, Rahman Z, Jones E, Taylor SC. Defining approved retrospective medical record review of patients seen pseudofolliculitis barbae in 2001: a review of the literature and current trends. J Am Acad Dermatol. 2002;46(2)(Suppl Understanding):S113-S119. at Children’s Hospital of Philadelphia for onychomycosis from 3. Olsen EA, Bergfeld WF, Cotsarelis G, et al; Workshop on Cicatricial Alopecia. December 2008 to December 2016. Patients not prescribed sys- Summary of North American Hair Research Society (NAHRS)–sponsored temic terbinafine therapy were excluded. Laboratory abnor- workshop on cicatricial alopecia, Duke University Medical Center, February 10 malities were graded based on The National Cancer Institute and 11, 2001. J Am Acad Dermatol. 2003;48(1):103-110. Common Terminology Criteria for Adverse Events (version 4. Luque JS, Ross L, Gwede CK. Qualitative systematic review of 4.03).5 Statistical analyses were performed using Stata statis- barber-administered health education, promotion, screening and outreach programs in African-American communities. J Community Health. 2014;39(1): tical software (version 14.2, Stata Corp). 181-190. Results | Over an 8-year period, 1302 patients were diagnosed Laboratory Monitoring During Systemic Terbinafine with onychomycosis. Of these, 269 (21%) were prescribed oral Therapy for Pediatric Onychomycosis terbinafine and were included in analysis (Table 1 and Table 2). Onychomycosis is a fungal infection of the nail resulting in dis- A total of 192 (71.4%) patients were treated by pediatricians and coloration, thickening, and separation from the nail bed. Pe- 77 (28.6%) were treated by pediatric dermatologists. Mean (SD) diatric onychomycosis has a reported incidence of 0.4% to age at initial presentation was 11.5 (3.9) years (range, 2-20 years). 2.6%.1 Topical antifungal therapy has been shown to have some The male to female ratio of the study population was 1.5:1.0, efficacy in children compared with adults; however, when the with 160 (59%) male patients and 109 (41%) female. Diagnosis of onychomycosis was confirmed by nail cul- ture and/or periodic–acid schiff (PAS) stain in 128 (48%) cases Table 1. Demographics of the Study Population and Patients Who Underwent Laboratory Monitoring prior to initiation of treatment. Seventy-two (56%) patients had positive culture results, 44 (34%) patients had positive PAS stain Overall Demographics of Study Population Finding results, and 12 (9%) patients had both. Patients prescribed terbinafine, No. 269 Mean (SD) number of treatment courses was 1.1 (0.3) and Age, mean (SD), y 11.5 (3.9) mean (SD) duration was 11.8 (2.3) weeks. Mean (SD) time to Sex, No. (%) complete resolution was 5.0 (1.9) months. Cure rates were all Female 109 (41) determined clinically. A total of 144 (53.5%) patients under- Male 160 (59) went laboratory monitoring of liver function panels and/or Nail involved, No. (%) complete blood cell counts. Timing of laboratory monitoring Toenail(s) 263 (98) was primarily prior to treatment (34 patients, 23.6%) or prior Fingernail(s) 1 (<1) to treatment and at 6 weeks (102 patients, 70.8%). Whereas Unknown 5 (2) 126 (87.5%) patients had normal laboratory results, 18 (12.5%) Prescribed daily oral terbinafine dose,a No. (%) patients had grade 1 laboratory abnormalities either prior to 62.5 mg (<20 kg) 1 (<1) (12 patients, 8.3%) or during therapy (6 patients, 4.2%). In those 125 mg (20-40 kg) 93 (35) with abnormal results during therapy, 3 patients discontin- 250 mg (>40 kg) 174 (65) ued treatment. Only 1 patient reported an adverse effect (ur- Other (187.5 mg per tinea capitis dosing) 1 (<1) ticaria) at 3 weeks and treatment was stopped. Patients with treatment extended beyond typical course 6 (2) duration,b No. (%) Discussion | The US Food and Drug Administration (FDA) label- Toenail(s) 5 ing for systemic terbinafine specifically states that the safety Fingernail(s) 1 and efficacy in pediatric patients has not been established but a Weight-based dosing used based on prior studies and clinical practice in adults recommends pretreatment serum transaminases although no standard dosing guidelines in pediatric patients per drug insert.4 and laboratory monitoring periodically during therapy.4 Of b Duration of therapy based on adult guidelines of 6 weeks of total therapy for the 144 patients prescribed systemic terbinafine who under- fingernail onychomycosis and 12 weeks of total therapy for toenail went laboratory monitoring, none developed more than a onychomycosis.4 grade 1 laboratory abnormality. In otherwise healthy children,

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Table 2. Demographics of Patients With Laboratory Monitoringa

Normal Laboratory Results Laboratory or Laboratory Abnormality Abnormality Characteristic Overall Prior to Therapy During Therapy P Value Patients with laboratory 144 (54) 138 (96) 6 (4) monitoring, No. (%) Sex, No. (%) Female 68 (47) 65 (96) 3 (4) .89 a Demographics of the study Male 76 (53) 73 (96) 3 (4) population and patients who Age, No. (%), y underwent laboratory monitoring. <12 71 (49) 68 (96) 3 (4) χ2 tests were performed to evaluate .97 covariates of sex and age assuming ≥12 73 (51) 70 (96) 3 (4) a .05 significance level.

mild liver enzyme elevations are common postinfection. 1. Philpot CM, Shuttleworth D. Dermatophyte onychomycosis in children. Clin Clinically apparent liver injury from terbinafine treatment Exp Dermatol. 1989;14(3):203-205. occurs in 1 per 50 000 to 120 000 cases.6 Asymptomatic 2. Friedlander SF, Chan YC, Chan YH, Eichenfield LF. Onychomycosis does not always require systemic treatment for cure: a trial using topical therapy. Pediatr elevations in serum aminotransferases are found in less than Dermatol. 2013;30(3):316-322. 1% of patients, which typically self-resolve without discon- 3. Gupta AK, Paquet M. Systemic antifungals to treat onychomycosis in tinuing therapy. children: a systematic review. Pediatr Dermatol. 2013;30(3):294-302. We recommend baseline transaminase monitoring. How- 4. Terbinafine hydrochloride [package insert]. East Hanover, NJ: Novartis ever, routine laboratory monitoring during systemic therapy Pharmaceuticals Corporation; 2017. (12 weeks or less) for onychomycosis in healthy children may 5. National Cancer Institute. Common Terminology Criteria for Adverse Events be unnecessary owing to low incidence of clinically signifi- v4.03(CTCAE). https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14 _QuickReference_5x7.pdf. Accessed May 15, 2017. cant adverse effects, costs of laboratory tests, workup of spu- rious laboratory abnormalities, and patient discomfort. This 6. National Library of Medicine, National Institute of Diabetes and Digestive and Kidney Disease. Clinical and research information on drug-induced liver study is limited by its generalizability, small sample size, and injury: drug record: terbinafine. https://livertox.nlm.nih.gov/Terbinafine.htm. retrospective nature. Larger, prospective studies evaluating the Accessed May 15, 2017. safety profile in pediatric patients are needed to detect the rare but serious adverse effects that could occur during therapy and work toward FDA label changes for a pediatric onychomyco- The Most Beautiful People: sis indication. Evolving Standards of Beauty Not merely an aberration of modern culture, societal obses- Deepa Patel, BS sion with beauty is deeply engrained in the past, with the ap- Leslie A. Castelo-Soccio, MD, PhD preciation of human aesthetics dating back to early Greek civi- Adam I. Rubin, MD lization. Although ideas on beauty vary with personal Jenna L. Streicher, MD preferences and cultural standards, in a society at any given time, there is substantial agreement as to what constitutes hu- Author Affiliations: University of Louisville, School of Medicine, Louisville, man beauty.1 This study uses People magazine to compare stan- Kentucky (Patel); Department of Pediatrics, Section of Dermatology, Children’s dards of beauty in 1990 with present day standards. Hospital of Philadelphia, Philadelphia, Pennsylvania (Castelo-Soccio, Rubin, Streicher); Perelman School of Medicine, University of Pennsylvania, Philadelphia, (Castelo-Soccio, Rubin, Streicher); Department of Pathology and Methods | Published by Time Inc, People has the largest audi- Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, ence of any US magazine, with a readership of 43.6 million Pennsylvania (Rubin). adults.2 We compared People magazine’s World’s Most Beau- Corresponding Author: Jenna L. Streicher, MD, Section of Dermatology, tiful (WMB) list in the first issue (1990) with that in the 2017 Department of Pediatrics, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Wood Center, third Floor, Philadelphia, PA 19104 ([email protected] issue, hypothesizing that beauty standards have not changed. .edu). From the 1990 (50 celebrities) and 2017 (135 celebrities) is- Accepted for Publication: September 16, 2017. sues of People magazine’s WMB list, we extracted the follow- Published Online: November 29, 2017. doi:10.1001/jamadermatol.2017.4483 ing information: age at the time of the specific issue, sex, race, Author Contributions: Ms Patel and Dr Streicher had full access to all of the skin type, hair color, eye color, and visible dermatologic con- data in the study and take responsibility for the integrity of the data and the ditions. Characteristics with dichotomous and categorical vari- accuracy of the data analysis. ables were reported as numbers (percentages) and continu- Study concept and design: All authors. Acquisition, analysis, or interpretation of data: All authors. ous variables as means (SDs). Between-group differences were Drafting of the manuscript: Patel, Streicher. assessed using the Fisher exact text or χ2 tests for categorical Critical revision of the manuscript for important intellectual content: Castelo- variables and t tests for continuous variables. Results were con- Soccio, Rubin, Streicher. sidered to be significant at P<.05 in the 2-sided hypothesis. In- Statistical analysis: Patel. Administrative, technical, or material support: Castelo-Soccio, Rubin. stitutional review board approval was waived by the Boston Study supervision: Castelo-Soccio, Rubin, Streicher. University Institutional Review Board. Because no patients were Conflict of Interest Disclosures: None reported. involved in this study, informed consent was not required.

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