ACNE & ROSACEA JULY 2021

A SUPPLEMENT TO

Rosacea phenotypes Erythema and flushing Aggressive treatment of acne Energy-based rosacea therapy Diet and acne

Commentaries by Hilary E. Baldwin, MD

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Moving from subtypes to phenotypes is simplifying rosacea management

By Ted Bosworth symptoms patients find most both- FROM COASTAL DERM ersome. The previous diagnostic crite- hen a new phenotype ap- ria for rosacea, published in 2002, proach to the diagnosis of identified primary and secondary Wrosacea was proposed 2 years symptoms within its four sub- ago, this simpler and more accurate types (J Am Acad Dermatol. 2002 method was accompanied by several Apr;46[4]:584-7). The new diagnos- corollary advantages, including a tic criteria, endorsed by the Nation- Dr. Hilary E. Baldwin more rational approach to treat- al Rosacea Society and published in ment and better methods of mea- 2018, rely on phenotypes defined or the 2021 Acne & Rosacea suring treatment efficacy, according by diagnostic, major, and minor Supplement, Hilary E. Bald- to an expert speaking at the annual symptoms (J Am Acad Dermatol. Fwin, MD, provided commen- Coastal Dermatology Symposium. 2018 Jan;78[1]:148-55). Unlike the taries on a selection of topics, “By looking at rosacea in a more four previous subtypes, which were published in Dermatology News simple way – but a more accurate erythematotelangiectatic, papulo- over the past year, from pub- way – we are able to track what pustular, phymatous, and ocular, the lished studies and meeting pre- happens [to key features] over phenotypes facilitate diagnosis in sentations. time,” explained Jerry Tan, MD, of patients with mixed features. the University of Western Ontario, By replacing “the old thought Dr. Baldwin is a board-certified der- London. process of subtyping” with a newer matologist who is medical director The newer method of diagnosing focus on phenotypes, the updated of the Acne Treatment & Research rosacea, which relies on phenotyp- criteria were “aimed toward accura- Center in New York. She is also clin- ing rather than subtyping, focuses cy, simplicity, and practicality,” Dr. ical associate professor in the depart- on symptoms and their clinical im- Tan said. ment of dermatology, Rutgers Robert pact. With the previous method of Moreover, without squeezing pa- Wood Johnson Medical Center in subtyping, many rosacea patients tients into subgroups where they do New Brunswick, N.J. She was a failed to fit neatly into any of the not neatly fit, the new criteria draw founding board member and second four categories, producing confu- attention to the specific symptoms president of the American Acne & sion and diverting attention from that bring patients to the clinician. Rosacea Society. Dr. Baldwin is on troublesome symptoms. The phenotype approach to the speakers bureau of and is an ad- “Rosacea patients often present treatment strategies was reflected viser to Galderma, Ortho Dermato- with a range of features that span in a systematic review of treat- logics, Vyne Therapeutics, Almirall, multiple subtypes or progress be- ments based on phenotypes that and La Roche–Posay. She is also an tween them,” Dr. Tan explained. was published in 2019, not long adviser to Mayne Pharma, Cassio- The risk is not just a delay in diag- after the new classification system pea, Sol-Gel, and EPI Health. nosis but also a failure to focus on Continued on page 5 

Editor | Elizabeth Mechcatie, BSN, MA Acne & Rosacea is a supplement to Dermatology will not assume responsibility for damages, loss, Group Publisher, Dermatology News | News, an independent newspaper that provides the or claims of any kind arising from or related to the practicing dermatologist with timely and relevant information contained in this publication, including Sally Cioci Fischer: [email protected] news and commentary about clinical developments any claims related to the products, drugs, or services Vice President, Sales | Mike Guire in the field and about the impact of health care mentioned herein. Production Specialist | Valerie Carver policy on the specialty and the physician’s practice. The ideas and opinions expressed in Acne & © Copyright 2021, by Frontline Medical Art Director | Tom C. Lore Rosacea do not necessarily reflect those of the Communications Inc. All rights reserved. Cover image | Aleksandr Zhurilo/Getty Images Publisher. Frontline Medical Communications Inc. Stock photo. Posed by model.

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FOR YOUR PATIENTS WITH ACNE VULGARIS

TAZAROTENE CODE

ARAZLO is the first and only tazarotene lotion, formulated with polymeric emulsion technology, to help deliver the clearance you expect and the tolerability you want1-3

Treatment success* rates were 26% for ARAZLO Lotion vs 13% for vehicle in study 1 and 30% vs 17%, respectively, in study 2 (P<0.001 in both studies)1,4†

Most common adverse events (≥1% of patients and greater than vehicle) at application site were pain (5%), dryness (4%), exfoliation (2%), 1† erythema (2%), and pruritus (1%) T:10.75" B:11" S:10"

SEE WHAT’S POSSIBLE AT ARAZLO.COM

* Treatment success on the Evaluator’s Global Severity Score (EGSS) was defined as at least a 2-grade improvement from baseline and an EGSS score of clear (0) or almost clear (1).1 †Phase 3 study design: The safety and efficacy of ARAZLO Lotion were assessed in 2 multicenter, randomized, double-blind clinical trials of 1,614 subjects aged 9 years and older with facial acne vulgaris. Subjects had a score of moderate (3) or severe (4) on the EGSS, 20 to 50 inflammatory lesions, 25 to 100 noninflammatory lesions, and 2 or fewer facial nodules.1

Indication ARAZLO™ (tazarotene) Lotion, 0.045% is indicated for the topical treatment of acne ARAZLO Lotion. Warn patients with high levels of sun exposure and those with vulgaris in patients 9 years of age and older. inherent sensitivity to sun to exercise caution. Instruct patients to use sunscreen products and protective clothing over treated areas when sun exposure cannot Important Safety Information be avoided. ARAZLO Lotion is for topical use only. Not for oral, ophthalmic, or intravaginal use. ARAZLO Lotion should be administered with caution if the patient is taking drugs Contraindication known to be photosensitizers (eg, thiazides, tetracyclines, fluoroquinolones, ARAZLO Lotion is contraindicated in pregnancy due to the potential harm to the fetus. phenothiazines, sulfonamides) because of the increased possibility of augmented photosensitivity. Warnings and Precautions Weather extremes, such as wind or cold, may be more irritating to patients using Embryofetal Risk Females of childbearing potential should be warned of the ARAZLO Lotion. potential risk and should use adequate birth-control measures when ARAZLO Lotion is used. A negative result for pregnancy should be obtained within 2 weeks prior to Adverse Reactions The most common adverse reactions (in ≥1% of patients ARAZLO Lotion therapy, and therapy begun during a menstrual period. If the patient and greater than vehicle) were: application site pain, dryness, exfoliation, erythema, becomes pregnant while using ARAZLO Lotion, treatment should be discontinued. and pruritus. Skin Irritation Patients using ARAZLO Lotion may experience application site pain, To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at dryness, exfoliation, erythema, and pruritus. Depending upon severity, adjust or 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. interrupt dosing as needed, increasing or resuming treatment as tolerated. Avoid Please see Brief Summary of full Prescribing Information on following page. application of ARAZLO Lotion to eczematous or sunburned skin. Photosensitivity and Risk for Sunburn Minimize unprotected exposure to ultraviolet light, including sunlight, sunlamps and tanning beds, during the use of

References: 1. ARAZLO Lotion [prescribing information]. Bridgewater, NJ. Bausch Health US, LLC. 2. Tanghetti EA, Kircik LH, Green LJ, et al. A phase 2, multicenter, double-blind, randomized, vehicle-controlled clinical study to compare the safety and efficacy of a novel tazarotene 0.045% lotion and tazarotene 0.1% cream in the treatment of moderate-to-severe acne vulgaris. J Drugs Dermatol. 2019;18(6):542-548. 3. Food and Drug Administration. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm. Accessed October 20, 2020. ARAZLO is a trademark of Ortho Dermatologics’ affiliated entities. 4. Data on file. © 2020 Ortho Dermatologics’ affiliated entities. ARZ.0140.USA.20

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BRIEF SUMMARY OF PRESCRIBING INFORMATION There are no available data on ARAZLO use in pregnant patients to inform a drug-associated risk of major birth defects, This Brief Summary does not include all the information needed to use ARAZLO safely and effectively. miscarriage or adverse maternal or fetal outcomes. Based on data from animal reproduction studies, retinoid pharmacology, and See full Prescribing Information for ARAZLO. the potential for systemic absorption, ARAZLO may cause fetal harm when administered to a pregnant patient and is ™ contraindicated during pregnancy. The potential risk to the fetus outweighs the potential benefit to the mother; therefore, ARAZLO (tazarotene) Lotion, 0.045% ARAZLO should be discontinued as soon as pregnancy is recognized. For topical use In animal reproduction studies with pregnant rats, reduced fetal body weights and reduced skeletal ossification were observed Initial U.S. Approval: 1997 after topical administration of a tazarotene gel formulation during the period of organogenesis at a dose equivalent to the INDICATIONS AND USAGE maximum recommended human dose (MRHD) (based on AUC comparison). In animal reproduction studies with pregnant ARAZLO™ (tazarotene) Lotion, 0.045% is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older. rabbits, single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies were CONTRAINDICATIONS observed after topical administration of a tazarotene gel formulation at 15 times the MRHD (based on AUC ARAZLO is contraindicated in pregnancy. ARAZLO may cause fetal harm when administered to a pregnant patient [see Warnings comparison) (see Data). and Precautions, Use in Specific Populations]. In animal reproduction studies with pregnant rats and rabbits, malformations, fetal toxicity, developmental delays, and/or WARNINGS AND PRECAUTIONS behavioral delays were observed after oral administration of tazarotene during the period of organogenesis at doses 1 and 30 Embryofetal Toxicity Based on data from animal reproduction studies, retinoid pharmacology and the potential for systemic times, respectively, the MRHD (based on AUC comparison). In pregnant rats, decreased litter size, decreased numbers of live absorption, ARAZLO may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. fetuses, decreased fetal body weights, and increased malformations were observed after oral administration of tazarotene prior Safety in pregnant patients has not been established. The potential risk to the fetus outweighs the potential benefit to the to mating through early gestation at doses 6 times the MRHD (based on AUC comparison) (see Data). mother; therefore, discontinue ARAZLO as soon as pregnancy is recognized. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies Tazarotene elicits malformations and developmental effects associated with retinoids after topical and oral administration to have a background risk of major birth defects, loss, and other adverse outcomes. In the U.S. general population, the estimated pregnant rats and rabbits during organogenesis. However, limited case reports of pregnancy in females enrolled in clinical trials background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. for ARAZLO have not reported a clear association with tazarotene and major birth defects or miscarriage risk [see Data Animal Data In an embryofetal development study in rats, a tazarotene gel formulation, 0.5% (0.25 mg/kg/day tazarotene) Contraindications, Use in Specific Populations]. was topically administered to pregnant rats during gestation days 6 through 17. Reduced fetal body weights and reduced skeletal Systemic exposure to tazarotenic acid is dependent upon the extent of the body surface area treated. In patients treated topically ossification occurred at this dose (equivalent to the MRHD based on AUC comparison). In an embryofetal development study in over sufficient body surface area, exposure could be in the same order of magnitude as in orally treated animals. Tazarotene is a rabbits, a tazarotene gel formulation, 0.5% (0.25 mg/kg/day tazarotene) was topically administered to pregnant rabbits during teratogenic substance in animals, and it is not known what level of exposure is required for teratogenicity in humans. gestation days 6 through 18. Single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart Advise pregnant patients of the potential risk to a fetus. Obtain a pregnancy test within 2 weeks prior to ARAZLO therapy. Initiate anomalies were noted at this dose (15 times the MRHD based on AUC comparison). ARAZLO therapy during a menstrual period. Advise patients of childbearing potential to use effective contraception during When tazarotene was given orally to animals, developmental delays were seen in rats; malformations and post-implantation treatment with ARAZLO [see Dosage and Administration in full Prescribing Information, Use in Specific Populations]. loss were observed in rats and rabbits at doses producing 1 and 30 times, respectively, the MRHD (based on AUC comparison). Skin Irritation Patients using ARAZLO may experience application site pain, dryness, exfoliation, erythema, and pruritus. In female rats orally administered 2 mg/kg/day of tazarotene from 15 days before mating through gestation day 7, classic Depending upon severity of these adverse reactions, instruct patients to use a moisturizer, reduce the frequency of the developmental effects of retinoids including decreased number of implantation sites, decreased litter size, decreased numbers application of ARAZLO, or discontinue use. Therapy can be resumed, or the frequency of application can be increased, as the of live fetuses, and decreased fetal body weights were observed at this dose (6 times the MRHD based on AUC comparison). A patient becomes able to tolerate treatment. low incidence of retinoid-related malformations was observed at this dose. Avoid use of concomitant medications and cosmetics that have a strong drying effect. It is recommended to postpone treatment In a pre- and postnatal development toxicity study, topical administration of a tazarotene gel formulation (0.125 mg/kg/day) to with ARAZLO until the drying effects of these products subside. pregnant female rats from gestation day 16 through lactation day 20 reduced pup survival, but did not affect the reproductive Avoid application of ARAZLO to eczematous or sunburned skin. capacity of the offspring. Based on data from another study, the systemic drug exposure in the rat at this dose would be equivalent to the MRHD (based on AUC comparison). Photosensitivity and Risk for Sunburn Because of heightened burning susceptibility, minimize unprotected exposure to ultraviolet light including sunlight and sunlamps during the use of ARAZLO. Warn patients who normally experience high levels Lactation Risk Summary There are no data on the presence of tazarotene or its metabolites in human milk, the effects on the breastfed of sun exposure and those with inherent sensitivity to sun to exercise caution. Use sunscreen products and protective clothing 14 over treated areas when sun exposure cannot be avoided. Patients with sunburn should be advised not to use ARAZLO infant, or the effects on milk production. After single topical doses of a C-tazarotene gel formulation to the skin of lactating rats, until fully recovered. radioactivity was detected in rat milk. The developmental and health benefits of breastfeeding should be considered along with ARAZLO should be administered with caution if the patient is taking drugs known to be photosensitizers (e.g., thiazides, the mother’s clinical need for ARAZLO and any potential adverse effects on the breastfed child from ARAZLO. tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the increased possibility of Clinical Considerations To minimize potential exposure to the breastfed infant via breast milk, use ARAZLO for the shortest augmented photosensitivity. duration possible while breastfeeding. Advise breastfeeding patients not to apply ARAZLO directly to the nipple and areola to Weather extremes, such as wind or cold, may be more irritating to patients using ARAZLO. prevent direct infant exposure. ADVERSE REACTIONS Females and Males of Reproductive Potential T:10.75" B:11" The following serious adverse reactions are discussed in more detail in other sections: Pregnancy Testing Pregnancy testing is recommended for patients of childbearing potential within 2 weeks prior to initiating S:10" ARAZLO therapy which should begin during a menstrual period. • Embryofetal toxicity [see Warnings and Precautions] Contraception Advise patients of childbearing potential to use effective contraception during treatment with ARAZLO. • Photosensitivity and Risk of Sunburn [see Warnings and Precautions] Pediatric Use Safety and effectiveness of ARAZLO for the topical treatment of acne vulgaris have been established in pediatric Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed patients age 9 years and older based on evidence from two multicenter, randomized, double-blind, parallel-group, in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the vehicle-controlled, 12-week clinical trials and an open-label pharmacokinetic study. A total of 300 pediatric subjects aged 9 to rates observed in clinical practice. less than 17 years received ARAZLO in the clinical studies [see Clinical Pharmacology and Clinical Studies in full In 2 multicenter, randomized, double-blind, vehicle-controlled clinical trials, subjects age 9 years and older applied ARAZLO or Prescribing Information]. vehicle once daily for 12 weeks. The majority of subjects were White (74%) and female (66%). Approximately 22% were Hispanic/ The safety and effectiveness of ARAZLO in pediatric patients below the age of 9 years have not been established. Latino and 42% were younger than 18 years of age, fourteen of 779 subjects (1.8%) treated with ARAZLO were between 9 years to less than 12 years of age. Adverse reactions reported by ≥1% of subjects treated with ARAZLO and more frequently than subjects Geriatric Use Clinical trials of ARAZLO did not include sufficient numbers of subjects age 65 years and older to determine whether treated with vehicle are summarized in Table 1. Most adverse reactions were mild to moderate in severity. Severe adverse they respond differently from younger subjects. reactions represented 1.3% of the subjects treated. Overall, 2.4% (19/779) of subjects discontinued ARAZLO because of OVERDOSAGE local skin reactions. Oral ingestion of the drug may lead to the same adverse effects as those associated with excessive oral intake of Vitamin A Table 1: Adverse Reactions Reported by ≥1% of the ARAZLO Group and More Frequently than the Vehicle Group (hypervitaminosis A) or other retinoids. If oral ingestion occurs, monitor the patient closely and administer appropriate supportive measures, as necessary. Adverse Reactions N (%) ARAZLO Lotion N=779 Vehicle N=791 NONCLINICAL TOXICOLOGY Application site pain1 41 (5) 2 (<1) Carcinogenesis, Mutagenesis, Impairment of Fertility A long-term study of tazarotene following oral administration of 0.025, 0.050, and 0.125 mg/kg/day to rats showed no indications of increased carcinogenic risks. Based on pharmacokinetic data from a Application site dryness 30 (4) 1 (<1) shorter-term study in rats, the highest dose of 0.125 mg/kg/day was anticipated to give systemic exposure in the rat equivalent Application site exfoliation 16 (2) 0 (0) to the MRHD (based on AUC comparison). Application site erythema 15 (2) 0 (0) A long-term study with topical application of up to 0.1% of tazarotene in a gel formulation in mice terminated at 88 weeks Application site pruritus 10 (1) 0 (0) showed that dose levels of 0.05, 0.125, 0.25, and 1 mg/kg/day (reduced to 0.5 mg/kg/day for males after 41 weeks due to severe 1Application site pain defined as application site stinging, burning, or pain dermal irritation) revealed no apparent carcinogenic effects when compared to vehicle control animals. Tazarotenic acid systemic Skin irritation was evaluated by active assessment of erythema, scaling, itching, burning and stinging, with grades for none, exposures at the highest dose was 7 times the MRHD (based on AUC comparison). mild, moderate, or severe. The maximum severity generally peaked at Week 2 of therapy and decreased thereafter. The Tazarotene was non-mutagenic in the Ames assay and did not produce structural chromosomal aberrations in human percentage of subjects with these signs and symptoms at any post-baseline visit are summarized in Table 2. lymphocytes. Tazarotene was non-mutagenic in CHO/HGPRT mammalian cell forward gene mutation assay and was Table 2: Incidence of Local Cutaneous Irritation at any Post-Baseline Visit non-clastogenic in an in vivo mouse micronucleus test. ARAZLO Lotion Vehicle Lotion No impairment of fertility occurred in rats when male animals were treated for 70 days prior to mating and female animals were N=774 N=789 treated for 14 days prior to mating and continuing through gestation and lactation with topical doses of a tazarotene gel Mild/Moderate/Severe Mild/Moderate/Severe formulation up to 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure in the rat at the highest dose Erythema 49% 38% was equivalent to the MRHD (based on AUC comparison). Scaling 51% 23% No impairment of mating performance or fertility was observed in male rats treated for 70 days prior to mating with oral doses Itching 29% 14% of tazarotene up to 1 mg/kg/day which produced a systemic exposure 4 times the MRHD (based on AUC comparison). Burning 30% 6% No impairment of mating performance or fertility was observed in female rats treated for 15 days prior to mating and continuing Stinging 22% 5% through gestation day 7 with oral doses of tazarotene up to 2 mg/kg/day. However, there was a significant decrease in the number of estrous stages and an increase in developmental effects at that dose which produced a systemic exposure 6 times the DRUG INTERACTIONS MRHD (based on AUC comparison). No formal drug-drug interaction studies were conducted with ARAZLO. Distributed by: Concomitant use with oxidizing agents, as benzoyl peroxide, may cause degradation of tazarotene and may reduce the clinical Bausch Health US, LLC efficacy of tazarotene. Bridgewater, NJ 08807 USA In a trial of 27 healthy female subjects, between the ages of 20–55 years, receiving a combination oral contraceptive tablet containing 1 mg norethindrone and 35 mcg ethinyl estradiol, the concomitant use of tazarotene administered as 1.1 mg orally Manufactured by: Bausch Health Companies Inc. (mean ± SD Cmax and AUC0-24 of tazarotenic acid were 28.9 ± 9.4 ng/mL and 120.6 ± 28.5 ng•hr/mL, respectively) did not affect the pharmacokinetics of norethindrone and ethinyl estradiol over a complete cycle. Laval, Quebec H7L 4A8, Canada The impact of tazarotene on the pharmacokinetics of progestin only oral contraceptives (i.e., minipills) has not been evaluated. U.S. Patent Number: 6,517,847 USE IN SPECIFIC POPULATIONS ARAZLO is a trademark of Bausch Health Companies Inc. or its affiliates. Pregnancy © 2020 Bausch Health Companies Inc. or its affiliates Risk Summary ARAZLO is contraindicated in pregnancy. Based on 9701200 12/2019 ARZ.0106.USA.20 Issued: 07/2020

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 Continued from page 2 and of matrix metalloproteinases accurate, and more relevant,” Dr. became available (Br J Dermatol. for tissue remodeling are all impli- Tan said. 2019 Jul;181[1]:65-79). In this review, cated in rosacea but drive different This same approach has been ad- coauthored by Dr. Tan, the GRADE types of symptoms. While appropri- vocated by others, including Esther certainty-of-evidence approach ate skin care and efforts to identify J. van Zurren, MD, professor of was employed to identify effective and minimize symptom triggers is dermatology at Leiden University therapies, matching specific symp- appropriate for all patients, pheno- Medical Centre in the Netherlands, toms with specific therapies such as and the lead author of the 2018 sys- low-dose isotretinoin for papules or tematic review article discussed by omega-3 fatty acids for dry eyes. Dr. Tan. In this review article on the Dr. Tan also described a method phenotype approach, specific strate- of documenting the severity of “The move to the gies were recommended for specific major and minor symptoms at each symptoms on the basis of grading visit, based on a patient-centric ap- phenotype approach by an international group of experts proach that emphasizes control of that included Dr. Tan, a coauthor. key symptoms. With this method, is hopefully simpler, “These strategies should be direct- called a rosacea patient tracker, pa- ed toward achieving improvements tients and physicians can determine more accurate, and in general well-being by targeting whether therapies are effective those aspects most bothersome to against the signs and symptoms of more relevant.” the patient,” the article advises. Like disease that they find most burden- Dr. Tan, Dr. van Zurren considers some, according to Dr. Tan, who this phenotype-based approach to was the first author of an article he diagnosis and treatment to be a cited as a reference to this pheno- types provide a guide to the most meaningful clinical advance over the type-based methodology (Br J Der- appropriate therapies. guidelines published in 2002. matol. 2018 Sep;179[3]:741-6). He said he hopes that the focus “Management strategies for peo- Overall, the phenotype approach on phenotypes will draw attention ple with rosacea should include to rosacea “rationalizes treatment,” to differences in these pathophys- phenotype-based treatments,” she he said. iological mechanisms. According agreed, adding that specific choic- Specifically, the heterogeneity of to Dr. Tan, evaluating rosacea es should be made on the basis of symptoms in rosacea is mirrored from the perspective of pheno- these phenotypes “instead of the in the heterogeneity of underlying types has represented an import- previous subtype classification.” pathophysiology. According to Dr. ant paradigm shift that extends MedscapeLIVE! and this news Tan, the upregulation of cytokines beyond diagnosis. organization are owned by the same for inflammation, of angiogenic “The move to the phenotype ap- parent company. pathways for vascular symptoms, proach is hopefully simpler, more [email protected]

COMMENTARY BY DR. BALDWIN: How often is a new characteristic of rosacea; rather, most have multiple findings. concept both more accurate and easier to implement? Additionally, patient symptomatology was omitted from the Such is the case with the changing paradigm for rosacea subtype classification. classification. Over the past 5 years, several expert and Specifying phenotypic characteristics of a patient’s ro- consensus groups have recommended the abandonment of sacea is considerably simpler than subtype classification. the subtype classification of rosacea first published in 2002. In essence, it asks us to consider, separately, the presence At that time, rosacea was viewed as a single entity and new and severity of inflammatory lesions, background erythema, therapies purporting to improve disease did not routinely phymatous changes, telangiectasias, and ocular signs, and identify whether improvement was in erythema, papules or to document the patient’s history of flushing, itch/pain, pustules, or other rosacea characteristics. For the first time, and ocular symptoms. This has several advantages. First, in rosacea patients were categorized as having papulopustular, clinical trials, we more clearly define the patients enrolled. erythematotelangiectatic, phymatous, or ocular disease, and Secondly, in clinical settings, we can track therapeutic therapies were more clearly delineated. improvement over time. Thirdly, it reminds us to evaluate Although it served its purpose at the time of its intro- each manifestation of disease separately when devising a duction, the subtype classification required clinicians and therapeutic approach. Lastly, it simplifies the consultation investigators to squeeze patients into a single category. As as we discuss each aspect of disease with the patient to practitioners, we recognize that few patients have only one devise an overall treatment plan.

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Treat acne aggressively upfront, expert advises

By Doug Brunk with each patient at every visit so “can definitely increase acne” and is FROM PEDIATRIC DERMATOLOGY 2020 you can determine what their initial seen in patients with polycystic ova- treatment’s going to be and what ry syndrome. n the opinion of Andrea L. their management going forward is For patients with mild acne, initial Zaenglein, MD, the initial assess- going to be.” treatment should consist of a topical Iment of patients who present with According to Dr. Zaenglein, the retinoid and, almost always, benzoyl acne should include five quick steps. best acne treatments are based on peroxide, “unless it’s a pure come- First, determine the types of the pathogenesis of the skin con- donal form of acne,” Dr. Zaenglein lesions they have. “Do they have dition and trying to target as many said. She recommended using the comedones, papules/pustules, and pathogenic factors as possible. The combination of a topical retinoid nodules present?” she asked during four main pathogenic factors in and benzoyl peroxide, noting that, the Pediatric Dermatology 2020: Best acne include hyperkeratinization, while it used to be difficult to find Practices and Innovations Confer- increased sebum production, cuti- benzoyl peroxide, “nowadays there ence. Second, quantify the number bacterium, and inflammation. “This are numerous manufacturers and dif- of lesions that they have. Is it few? is not a stepwise process; there’s ferent formulations of benzoyl per- Several? Many? Third, determine the an interplay between all of those oxide. We also have over-the-counter extent of their acne. “Is it limited to factors,” she said. “All acne is inflam- adapalene now, which is great. So, half the face, or is it generalized to matory, but each of the treatments now we have a complete routine for the face, back, chest, and shoulders?” we have target specific factors. Reti- patients with adapalene and benzoyl added Dr. Zaenglein, professor of noids target hyperkeratinization and peroxide that you can combine to- dermatology and pediatrics at Penn inflammation, whereas the hormon- gether in a cost-effective way.” State University, Hershey. al therapies will address decreased If the initial regimen fails to Fourth, identify postinflamma- sebum production. Antimicrobial improve the patient’s mild acne, a tory changes such as erythema, agents like benzoyl peroxide and second-line treatment would be to hyperpigmentation, and scarring antibiotics will work to decrease change the retinoid and continue “because that’s going to influence cutibacterium acnes. All of these on the existing benzoyl peroxide your management,” she said. “Final- are influenced by the exposome. formulation or to add dapsone gel if ly, you want to give a quick investi- This includes your genetics, external the patient is experiencing skin irri- gative global assessment of the acne factors like pollution, or changes in, tation. The four retinoids currently severity where you quantify them as seasons that can affect your skin and available include adapalene, treti- being clear, almost clear, mild, mod- the severity of your acne.” A state noin, tazarotene, and trifarotene. erate, or severe. You want to do this of hyperandrogenism, she added, “These normalize keratinocyte

COMMENTARY BY DR. BALDWIN: Should we be the turtle side effects. Most of our more efficacious drugs have high- or the hare when it comes to acne therapy? Clearly, since er side-effect profiles, although careful patient counseling acne is a chronic disease, treatment will need to be contin- can overcome this hurdle. Multiple medications may mean uous and lengthy. I have often heard experts refer to it as a multiple side effects that require discussion. This brings us marathon, not a sprint. But that doesn’t mean that we can’t to another consequence of aggressive therapy: More time or shouldn’t, aim for a jackrabbit start. What are the relative will need to be spent by providers/staff in education, prior benefits and risks of an aggressive early approach? authorizations, and patient callbacks. Frankly, shame on us Aggressive starts generally require multiple medications. As if this stops us from doing what is right for our patients, but Dr. Zaenglein discussed in her lecture, acne is best treated it undeniably affects treatment choices. from several directions simultaneously, striving to reduce Aggressive therapy generally means more rapid response. Cutibacterium acnes, follicular hyperkeratinization, sebum This correlates with improved compliance as patients who production, and inflammation whenever possible. Isotretinoin see improvement are encouraged to continue their products is the only drug we have that addresses all four factors as on a regular basis. Lastly, early response has been shown monotherapy, but it obviously is not appropriate for every to decrease the incidence and severity of scarring (Clin Exp patient. Although more effective, multiple medications means Dermatol. 1994 Jul;19[4]:303-8). more copays and the possibility of reduced compliance. But Personally, I think it’s a no-brainer. I’m with Dr. Zaenglein: patients who can pull it off reap the rewards. Early and aggressive therapy is the best approach for acne. Aggressive therapy can mean the increased potential for I’m a hare every time.

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differentiation, reduce keratinocyte Topical dapsone gel (5% and temic symptoms].” proliferation, and decrease expres- 7.5%) is mainly used for patients Sarecycline is the first narrow sion of inflammatory markers,” Dr. with papular-pustular acne. “Its spectrum tetracycline for acne, with Zaenglein noted. “They also prevent mechanism of action for acne is fewer vestibular and phototoxic scarring. Adapalene is considered not known, but presumptively it’s side effects, compared with other to be the most tolerable, whereas anti-inflammatory,” Dr. Zaenglein tetracyclines. “It also has less effect tazarotene may have an edge on said. “It doesn’t require G6PD [glu- on the GI flora,” Dr. Zaenglein said. efficacy. There’s a lot of overlap; cose-6-phosphate dehydrogenase] “It’s a good alternative, but it can head-to-head studies may not al- testing. It can cause some orange be costly, so make sure to check the ways match them up exactly, but discoloration of your skin or fabrics pricing for your patients.” She does generally this is how it’s considered. if you use it with benzoyl peroxide, not use other antibiotics such as Picking the right retinoid for your so you want to apply them at differ- TMP/SMX, penicillins, or cephalo- patient based on efficacy and tolera- ent times of the day. It’s well toler- sporins for acne patients. “The rea- bility is most important.” ated. I tend to use it in patients who son is, the tetracyclines are not only The newest topical retinoid, have problems tolerating any topical antibacterial, but they’re anti-inflam- trifarotene 50 mcg/g cream, is a retinoid or any benzoyl peroxide but matory,” she explained. “They also fourth-generation retinoid that is have mild to moderate acne.” are lipophilic, so they will penetrate retinoic acid receptor gamma selec- For patients with moderate acne, into the sebaceous unit where the tive. Pivotal trials were conducted in consider combination therapy to heart of the acne is.” patients aged 9 years and older with target as many pathogenic factors For patients who don’t want to moderate facial and truncal acne. as possible. “Use a topical reti- take an oral antibiotic, consider With monotherapy, there was a noid plus benzoyl peroxide with minocycline 4% foam, which was success rate of 36% at 12 weeks and or without a systemic antibiotic,” studied in moderate to severe acne 60% at 52 weeks, based on the In- Dr. Zaenglein advised. “I may give in patients aged 9 years and older. vestigator’s Global Assessment. An- them an oral antibiotic if their acne The pooled results from the three other newcomer, tazarotene 0.045% is not responsive to the routine. But studies showed a 47% mean im- lotion, is a third-generation retinoid you wouldn’t want to combine the provement in inflammatory acne, which is retinoic acid receptor alpha systemic antibiotic with a topical an- compared with 37% among those in beta gamma selective. It’s approved tibiotic, like clindamycin with doxy- the vehicle arm. “You wouldn’t use for moderate to severe facial acne in cycline, because you don’t need two this as monotherapy; you’d use this patients 9 years and older. antibiotics. Make sure that you treat in combination with the topical reti- To optimize tolerance to retinoids, aggressively up front. It can take up noid and the benzoyl peroxide,” Dr. Dr. Zaenglein asks patients about to 3 months to see improvement. I Zaenglein said. their typical skin care regimen. “I counsel my patients that we’ll res- Most primary care providers do ask them what they’re washing their cue with the antibiotic and then we not prescribe isotretinoin for pa- face with,” she said. “Are they using maintain, but we’re going to stop tients with severe acne, but they can apricot scrubs or harsh cleansers? that antibiotic after 3 months.” start patients on triple therapy with Make sure they’re applying it to the Systemic antibiotic options for a topical retinoid, benzoyl peroxide, entire face and not spot-treating. You acne include tetracyclines, doxy- and a systemic antibiotic at its full get less irritation when it’s applied cycline, minocycline, and sarecy- dose. “The efficacy of triple thera- to dry skin, so you can recommend cline. “Tetracycline itself we don’t py in patients you would typically that. Make sure that they use a bland use too much because you have deem as isotretinoin worthy is actu- unscented moisturizer in the morn- to take it on an empty stomach, ally pretty good,” she said. “There ing and apply it over top of their and availability is sometimes an have been several studies looking at retinoid. I always warn them that issue,” she said. “Primarily, we use this, and about 70%-80% of patients irritation usually peaks at about 2 doxycycline. You can take it with will respond to triple therapy, where weeks. If they can power through, food, so that helps. The main side they are no longer deemed isotreti- the irritation will improve with con- effects are gastrointestinal upset noin candidates. They still may need tinued use.” and photosensitivity. Alternately, to move on to isotretinoin, but they To optimize adherence to retinoids, you can use minocycline, which is will be improved.” she asks patients how many nights per also okay to take with food. It does Dr. Zaenglein disclosed that week they apply it. If they are using have more potentially worrisome she is a consultant for Cassiopea, it all 7 nights, “they’re good at using side effects, including pseudotumor Novartis, and Pfizer. She has also it,” she said. “If they say 3 nights, then cerebri, blue pigmentation, autoim- received grants or research support they need to work on getting it on mune hepatitis, and DRESS [drug from AbbVie, Incyte, and Pfizer. more frequently.” reaction with eosinophilia and sys- [email protected]

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Energy-based therapy plus oxymetazoline found safe for rosacea By Caleb Rans, PHARMD treatment‐emergent adverse events (TEAEs) and seri- FROM LASERS IN SURGERY AND MEDICINE ous adverse events; the exploratory efficacy endpoint was the change in clinician erythema assessment (CEA) nergy-based therapy with adjunctive oxymetazoline score from start of therapy measured over a 6-hour pe- was safe and improved facial erythema for patients riod post treatment. Ewith moderate to severe facial erythema associated Among 43 evaluable patients (who completed the with rosacea, in a phase 4 study. study), CEA score was improved in 39 (90.7%) patients The open-label study included 46 patients with rosacea, 6 hours post treatment on day 56 and in 30 (68.2%) pa- with moderate to severe facial erythema, who received tients pretreatment. On day 31, “one‐grade or greater treatment with one of four energy-based devices: pulsed‐ improvement was observed” in 26 (60.5%) patients be- dye laser Vbeam Perfecta (PDL-Vbeam), pulsed‐dye laser fore application of oxymetazoline and in 38 (88.4%) of Cynergy (PDL-Cynergy), intense pulsed-light therapy patients 6 hours post treatment, reported Emil A. Tang- (IPL), or potassium titanyl phosphate laser (KTP laser), in hetti, MD, of the Center for Dermatology and Laser combination with adjunctive oxymetazoline hydrochlo- Surgery in Sacramento, and coauthors. ride cream (1%). On days 3-27 and 31-56, oxymetazoline, Overall, patient satisfaction increased over the course of an alpha1A adrenoceptor agonist, was applied once daily, the study, with 28 (65.1%) patients reporting they were sat- while energy-based therapy was provided on day 1 and isfied or very satisfied with the treatment on day 56. day 29 (Lasers Surg Med. 2021 Jan;53[1]:55-65). Among 46 patients who received at least one treat- The primary safety endpoints were the incidence of Continued on following page 

COMMENTARY BY DR. BALDWIN: Central-facial erythema porary vasoconstriction that resolves as the drug is metabo- is a common finding in rosacea. In fact, in the most recent lized. Two such agents, brimonidine and oxymetazoline, have paper on the phenotypic categorization of rosacea, central terminal half-lives of about 24 hours, and most patients have facial erythema, along with the presence of phymas, is returned to “baseline” by the next day. In some patients, re- considered diagnostic of the disease (Br J Dermatol. 2017 turn to baseline is accompanied by a temporary worsening of Feb;176[2]:465-71). It always bears repeating that this erythema (I prefer the term rebound erythema). This appears type of erythema (I prefer the term background erythema) to be more common with brimonidine than oxymetazoline, is a distinct entity apart from two other red facial rosacea although there is no head-to-head study. Energy-based thera- findings: perilesional erythema and telangiectasias. Failure pies produce a more durable, sometimes permanent, response to make this distinction has led to considerable confusion after several treatments. However, they may be costly for the in the past, particularly when ascribing efficacy – or lack patient. Immediately following the treatment, there is consid- thereof – to a therapeutic approach. erable redness in the treated area. Although temporary, it is a Perilesional erythema is the small circle of erythema that cause for alarm and dissatisfaction for the patient. often surrounds papules and pustules. In patients with severe So, what does the combination potentially bring to the table? inflammatory disease, there can be such an abundance of Brimonidine had previously been shown to reduce postproce- perilesional erythematous circles that therapeutic reduction dure erythema (Lasers Surg Med. 2018 Dec;50[10]:1002-9). of the lesions is accompanied by an overall impression of Before and between treatments, topical agonists can control improved erythema. However, there are no data demonstrating erythema on a daily basis until the time they are no longer that patients with true background erythema improve with needed. The energy-based therapy will treat telangiectasias as drugs intended for inflammatory disease. well. In patients in whom both severe background erythema Background erythema responds well to alpha-adrenergic and telangiectasias are present, use of the alpha-agonists agonists and energy-based therapy. Telangiectasias do not often results in such good resolution of erythema that the respond to any form of pharmacologic therapy. Since the telangiectasias stand out in stark contrast. So, the patient vascular wall of these vessels is not completely surrounded enjoys the reduction in redness but is now bothered by the by smooth muscle, the alpha-adrenergic agonists are not able telangiectasias. to constrict the vessels or create clinical improvement. Ener- Lastly, alpha-agonists can be used intentionally prior to laser gy-based therapies are currently our only therapeutic option. treatment of telangiectasias to make them more visible and Combining alpha-agonists and energy-based therapies easy to treat. Knowledge provided by Tanghetti et al. that we makes a great deal of sense. The alpha-agonists cause tem- can safely use the two modalities together is a major advance.

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Review finds evidence for beta-blockers for some rosacea symptoms By Richard Mark Kirkner ing a meta-analysis. “Erythema and ten missing,” the researchers stated. FROM THE JOURNAL OF THE AMERICAN flushing were assessed by using a “Most studies showed improved ACADEMY OF DERMATOLOGY wide spectrum of mostly subjective erythema and flushing after initiation clinical and patient-based scores, of oral beta-blockers,” they wrote. systematic review of nine stud- and method standardization was of- Continued on following page  ies provided limited evidence A that off-label oral nonselective beta-blockers can be an effective COMMENTARY BY DR. BALDWIN: Not by Logger and colleagues as having a treatment for facial erythema and all manifestations of rosacea are easi- modicum of merit, but the variety of out- flushing in rosacea, while at the ly treated. We have an embarrassment come measures precluded a meta-anal- same time, underscoring the paucity of riches when choosing a medication ysis and usable clinical information. The of evidence supporting their use, for inflammatory lesions: The Food and evidence, such as it was, was highest for investigators reported. Drug Administration–approved topical carvedilol and propranolol. “The evidence was highest for agents and subantibiotic dose doxycy- Recently, Abid and colleagues pub- carvedilol and propranolol, two cline are highly effective. For vascular lished an article suggesting that the nonselective beta-blockers,” wrote disease, the topical alpha-adrenergic long term use of antihypertensive drugs Jade G.M. Logger, MD, of the de- agonists and laser and light therapy with vasodilatory mechanisms of ac- partment of dermatology, Radboud result in excellent responses. Ener- tions might actually protect against University Medical Center in Ni- gy-based therapies improve telangiec- vascular rosacea (J Am Acad Dermatol. jmegen, the Netherlands, and coau- tasias, and phymatous lesions can be 2021 Feb 9; S0190-9622[20]33243- thors (J Am Acad Dermatol. 2020 eradicated with ablative techniques. 6). This is not particularly surprising Oct;83[4]:1088-97). The one sign of rosacea over which as many of the drugs that vasodilate The systematic review included a we have the least therapeutic control centrally vasoconstrict peripheral- case control study of 53,927 patients is flushing and blushing. Behavioral ly. Beta-blockers, for example, cause and an equal number of controls approaches that call for avoidance of vasodilation in the heart by binding that evaluated beta-blockers in gen- triggers are minimally effective and dis- to beta-1 receptors but constrict the eral (Br J Dermatol. 2014;171[1]:130- ruptive and often reduce patient quality cutaneous blood vessels after binding 6), but the remaining studies and of life. Taking aspirin and other NSAIDs, to beta-2 receptors. It is reasonable case reports included only 106 SSRIs, and clonidine, as well as chewing to propose that continuous reduction patients in total. The largest was on ice cubes, have met with limited to no in vascular tone in the skin, such as a prospective cohort study of pro- success. Over the years, beta-blockers that which might occur with daily use pranolol in 63 patients (J Am Acad have been reported in underpowered of a hypertensive agent, might affect Dermatol. 2012;67[3]:491-3). and poorly designed studies to be mar- background erythema in the skin over The studies included patients with ginally effective while accompanied by time. A larger study is needed to assess a history of failed therapies; only a significant side-effect profiles. In a re- this preliminary finding and to see if the small number of beta-blockers were cent systematic review of beta-blocker most elusive of our rosacea findings – evaluated. Outcomes in the studies studies, nine studies were recognized flushing – is reduced. varied widely, which ruled out do-

 Continued from previous page caused inconsistency in the results. ment, five (10.9%) patients had one or more TEAEs “Prospective clinical studies assessing the long‐ (KTP laser, n = 1; PDL-Vbeam, n = 4), and four pa- term safety and efficacy of combined treatment with tients had one or more treatment‐related TEAEs (PDL- oxymetazoline and energy‐based therapies are needed,” Vbeam, n = 4). All TEAEs were considered mild or they concluded. moderate. “Three (6.5%) patients experienced TEAEs The manuscript was funded by oxymetazoline manu- related to oxymetazoline; all led to study discontinua- facturer Aclaris Therapeutics. Several authors disclosed tion,” the researchers reported. being an investigator, consultant, and/or laser manu- The researchers acknowledged that a key limitation facturer. One author was an employee of Aclaris at the of the study was the use of multiple energy-based de- time of the study. vices, delivered by different providers, which could have [email protected]

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High-fat, high-sugar diet may promote adult acne By Heidi Splete related to the occurrence and diagnosis of acne, as well as medical history. Based on their acne status, partic- diet higher in fat, sugar, and milk was associated ipants were identified as falling into the categories of with having acne in a cross-sectional study of ap- never acne, past acne, or current acne, and their dietary A proximately 24,000 adults in France. intake was assessed at baseline and every 6 months us- Acne in adults has been associated with social, emo- ing three nonconsecutive 24-hour dietary records for 2 tional, and psychological consequences similar to those weekdays and 1 weekend day. found with chronic diseases such as asthma, arthritis, In an analysis, after adjustment for confounders, cur- epilepsy, and diabetes, wrote Laetitia Penso, MSc, of the rent acne was significantly associated with consumption University of Paris in Bobigny, France, and colleagues. of fatty and sugary foods (per portion, adjusted odds Although acne patients may believe that eating ratio, 1.54; P = .01), as well as with consumption of certain foods exacerbates acne, data on the effects of sugary drinks (per glass, aOR, 1.18; P = .04) and milk nutrition on acne, including associations between acne (per glass, aOR, 1.12; P = .04). In addition, carbohydrate and a high-glycemic diet, are limited and have produced intake and saturated fatty acid intake were significantly conflicting results, they noted. associated with current acne (aOR, 1.43; P = .02; and In their study, the researchers identified 24,452 adults aOR, 3.90; P = .048, respectively). who participated in the NutriNet-Santé study, an ongo- Three dietary patterns accounted for 42% of the total ing, web-based study in France. Approximately 75% of variability, the researchers said. A healthy pattern of higher the participants were women, the average age was 57 fruit, vegetable, and fish intake accounted for 18%; a fatty years, and 46% reported past or current acne (JAMA and sugary pattern of higher fat and sugar intake (includ- Dermatol. 2020 Aug 1;156[8]:854-62). ing chocolate) accounted for 13%; and an animal product Participants responded to an 11-item questionnaire and cereal pattern of higher intake of meat, milk, and re- between November 2008 and July 2019. Questions were Continued on following page 

 Continued from previous page Jun;82[6]:1501-10). Beta blockers in rosacea patients. “Researchers Treatment of facial erythema and are among the drugs that are some- should further focus on the deter- flushing remains a clinical challenge, times prescribed off label to help mination of the optimal dosage, despite approved therapies for which rosacea-associated flushing, along treatment duration, and long-term poor response and reactivation are with nonsteroidal anti-inflammatory therapeutic effects for adequate common. “Diminishing erythema drugs, antihistamines, and clonidine, treatment of erythema and flushing and flushing in rosacea is challenging according to the update. in rosacea,” they said. because it hardly responds to conven- Dr. Logger and coauthors noted Getting those trials is challenging, tional anti-inflammatory treatment,” that beta-blockers come with risks Dr. Thiboutot said. Nonetheless, they noted. and can aggravate asthma and pso- the studies would be welcome, she “The study adds no new evidence riasis and are contraindicated in pa- said. “If standardized outcome mea- to support the use of beta-block- tients with heart failure, cardiogenic sures for facial erythema were to be ers,” Diane M. Thiboutot, MD, pro- shock, and other cardiovascular dis- developed, a study would be more fessor of dermatology at Penn State eases, along with hyperactive airway feasible.” University, Hershey, said in an inter- and Raynaud’s disease. “It is import- Dr. Logger disclosed financial re- view. “As the authors point out, the ant to monitor patients for adverse lationships with Galderma, AbbVie, nine studies reviewed were of low effects, especially blood pressure and Novartis, Janssen, and LEO Pharma. quality with a variety of outcome heart rate,” they stated. Carvedilol One author disclosed conducting measures that precluded generation and propranolol may have more clinical trials for AbbVie and Novar- of a meta-analysis, which would antioxidant and anti-inflammatory tis. The third author disclosed rela- have represented new information.” properties than other nonselective tionships with Galderma, Cutanea Dr. Thiboutot is lead author of a beta-blockers that may curtail rosa- Life Sciences, AbbVie, Novartis, and 2019 update of management options cea manifestations, they wrote. Janssen, with fees paid to his insti- for rosacea published by the National They called for large, prospective tution. Dr. Thiboutot disclosed a fi- Rosacea Society Expert Commit- clinical trials to more accurately nancial relationship with Galderma. tee (J Am Acad Dermatol. 2020; assess the efficacy of beta-blockers [email protected]

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 Continued from previous page associations given the study design and noted that dietary fined cereals accounted for 11%, they explained. interventions should be implemented with caution be- “The results of our study appear to support the hypoth- cause of the potential for other effects such as reduced esis that the Western diet (rich in animal products and calcium or vitamin D. fatty and sugary foods) is associated with the presence of “Nevertheless, given the potential overall health ben- acne in adulthood,” the researchers efits of a healthy or low–glycemic concluded. Possible explanations for load diet, and two small trials sup- the findings include the effects of a “A low glycemic-load porting its effectiveness in acne, a high–glycemic load diet on circulating low glycemic-load diet is a reasonable IGF-1 and insulin, which ultimately diet is a reasonable recommendation for patients looking increases both oxidative stress and in- for dietary modifications that may flammation that promotes the devel- recommendation for improve their acne,” he said. opment of acne, they noted. Dr. Barbieri said that he was The study findings were limited patients looking encouraged to see that the study by several factors including the use findings reflected previous research of relatively homogeneous younger for dietary identifying an association between and female patient population and acne and high-glycemic load foods, as the reliance on self-reported acne, modifications.” well as milk consumption, but he em- as well as the observational design, phasized that more research is needed which did not allow for identifi- before general recommendations cation of direct, causal associations between diet and about diet and acne can be made. acne, the researchers noted. Larger studies are needed “Trials are needed to evaluate whether dietary in- to examine the relationship between diet and adult acne terventions can improve or prevent acne and how the to inform prevention and treatment, they wrote. effect size of such interventions compares with other “Much of the previous literature on the role of diet standard treatment modalities,” he emphasized. in acne has focused on the association of milk con- The study received no outside funding. The research- sumption and high glycemic-load diet with acne,” John ers had no financial conflicts to disclose. Dr. Barbieri S. Barbieri, MD, of the department of dermatology at disclosed support from the National Institute of Arthri- the University of Pennsylvania, Philadelphia, wrote in tis and Musculoskeletal and Skin Diseases of the Na- an accompanying editorial (JAMA Dermatol. 2020 Aug tional Institutes of Health and from a Pfizer Fellowship 1;156[8]:841-3). grant to the Trustees of the University of Pennsylvania. Dr. Barbieri acknowledged the inability to make causal [email protected]

COMMENTARY BY DR. BALDWIN: I spend a lot of time needs me to add my two cents? with my first-time acne patients. We discuss the anticipated The NutriNet-Santé study adds additional, sorely need- timeline of acne, general pathophysiology, and the role of ed data to help frame our discussion with our patients. medications/procedures, as well as reasonable expectations The finding that dairy consumption and high–glycemic diet for improvement. Together, we arrive at a therapeutic regimen were associated with acne mirrors prior small trials and that fits their lifestyle, is affordable, and is in agreement lends credence to the outcome. However, the authors and with their disease severity, comfort level, and cultural belief commentators all agree, larger trials are needed to assess systems. The one subject I never bring up (and fervently hope causality and to determine if dietary interventions will make a they don’t either), is diet. meaningful clinical impact. I fear that this is easier said than My rationale for this omission has been that I do not done. A prospective trial would need to be very large and of have definitive answers or data-based recommendations. long duration; acne doesn’t alter its course rapidly. Without If I don’t know the answer, why would I pose the question? pharmaceutical support, who will pay for this expensive trial? I have found it to be a pointless, time-consuming rabbit Participants in the NutriNet-Santé trial were older women with hole. If I do it well, the discussion is complicated and murky, acne, a group that can be relied upon for compliant behavior. and I end up recommending a low–glycemic index diet. If I As anyone who has ever tried to switch to a healthier diet or do it poorly, the patient may be unsatisfied, and I end up lose weight can attest, behavioral changes are hard-won and recommending a low–glycemic index diet. Not because I’m short-lived. I find it hard to imagine that a sufficiently large convinced that it would make a difference, but because, in group of teenagers will adhere to a sufficiently low–glycemic the absence of data, I have felt most comfortable defaulting index diet for a sufficiently long period of time to create a to a healthy diet – so does the American Heart Association sufficiently measurable difference in acne. That last piece of and the Centers for Disease Control and Prevention. Who pizza calls ...

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