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Cited by 518Acne and Rosacea Treatments and EffectsDermatologic Treatments and ResearchClinical practice guidelines implementation

Guidelines of care for the management of acne vulgaris

Open access
Reynolds, Rachel V., Yeung, Howa, Cheng, Carol E., Cook-Bolden, Fran, Desai, Seemal R., Druby, Kelly M., Freeman, Esther E., Keri, Jonette E. +8 more·2024·Journal of the American Academy of Dermatology
DOI 10.1016/j.jaad.2023.12.017
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Abstract

Background Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older. Objective The objective of this study was to provide evidence-based recommendations for the management of acne. Methods A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. Results This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. Limitations Analysis is based on the best available evidence at the time of the systematic review. Conclusions These guidelines provide evidence-based recommendations for the management of acne vulgaris.

Integrity signals

Registry

Crossref · 10.1016/j.jaad.2023.12.017

Cites

313 of 313 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

37 of 191 cited sources checked · 13 supported · 3 flagged · accuracy not yet measured

  • Findingcitation

    The overall relative risk of inflammatory bowel disease between isotretinoin-exposed and unexposed groups is estimated at 1.13 (95% CI 0.89-1.43).

    “The overall RR of IBD between isotretinoin-exposed and unexposed groups is estimated at 1.13 (95% confidence interval, 0.89, 1.43).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [279] 279. Alhusayen RO, Juurlink DN, Mamdani MM, Morrow RL, Shear NH, Dormuth CR. Isotretinoin use and the risk of inflammatory bowel disease: a population-based cohort study. J Invest Dermatol. 2013;133:907-912. source

      The 'Acne therapy and incident IBD' section reports an overall comparison of isotretinoin-treated and untreated participants, but gives a rate ratio of 1.14 (95% CI 0.92–1.41), not 1.13 (0.89–1.43). No page number is available in our copy. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [280] 280. Bernstein CN, Nugent Z, Longobardi T, Blanchard JF. Isotret- inoin is not associated with inflammatory bowel disease: a population-based case-control study. Am J Gastroenterol. 2009;104:2774-2778. source
    • cites [281] 281. Crockett SD, Porter CQ, Martin CF, Sandler RS, Kappelman MD. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study. Am J Gastroenterol. 2010;105:1986-1993. source

      The Results, under “Results of matched analyses” (page not provided), report an overall IBD odds ratio of 1.68 (95% CI 0.98–2.86) for any isotretinoin use, not the claimed relative risk of 1.13 (95% CI 0.89–1.43). The Methods, under “Statistical analysis,” specify that the study estimated odds ratios rather than relative risks. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Findingcitation

    Low-certainty evidence from seven observational studies with substantial heterogeneity does not support a significant association between isotretinoin use and inflammatory bowel disease incidence, including ulcerative colitis and Crohn's disease.

    “Available low certainty evidence from 7 observational studies with substantial heterogeneity do not support a significant association between isotretinoin use and IBD incidence, including ulcerative colitis and Crohn's disease.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [279] 279. Alhusayen RO, Juurlink DN, Mamdani MM, Morrow RL, Shear NH, Dormuth CR. Isotretinoin use and the risk of inflammatory bowel disease: a population-based cohort study. J Invest Dermatol. 2013;133:907-912. source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [280] 280. Bernstein CN, Nugent Z, Longobardi T, Blanchard JF. Isotret- inoin is not associated with inflammatory bowel disease: a population-based case-control study. Am J Gastroenterol. 2009;104:2774-2778. source
    • cites [281] 281. Crockett SD, Porter CQ, Martin CF, Sandler RS, Kappelman MD. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study. Am J Gastroenterol. 2010;105:1986-1993. source

      Split into 2 atoms — 0 confirmed, 0 partially supported, 2 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Findingcitation

    In four randomized trials, more patients using topical retinoids than vehicle achieved Investigator's Global Assessment success at 12 weeks (risk ratio 1.57, 95% CI 1.21-2.04).

    “Compared to vehicle at 12 weeks, a greater proportion of patients treated with topical retinoids achieved IGA success in 4 RCTs (risk ratio [RR], 1.57 [1.21, 2.04]).59,63,64,71”
    Quote in the paperSubstantial claim2 of 4 sources checked
    • cites [59] 59. Thiboutot D, Pariser DM, Egan N, et al. Adapalene gel 0.3% for the treatment of acne vulgaris: a multicenter, random- ized, double-blind, controlled, phase III trial. J Am Acad Dermatol. 2006;54:242-250. source

      Thiboutot’s paper is a randomized controlled trial of a topical retinoid, so it could be cited as one of the four trials rather than as the source of the pooled estimate. However, paper-scoped searches returned no full-text snippets, and the available evidence does not establish its vehicle comparison, 12-week IGA result, or inclusion in the four-trial analysis. The unscoped searches found no reliable match for the stated risk ratio; they do not establish misattribution. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
    • cites [63] 63. Webster GF, Sugarman J, Levy-Hacham O, Toledano O. Microencapsulated benzoyl peroxide and tretinoin for the treatment of acne vulgaris: results from a phase 2 multicenter, double-blind, randomized, vehicle-controlled study. Skinmed. 2020;18(6):343-351.
    • cites [64] 64. Gollnick HP, Draelos Z, Glenn MJ, et al. Adapalene-benzoyl peroxide, a unique fixed-dose combination topical gel for the treatment of acne vulgaris: a transatlantic, randomized, double-blind, controlled study in 1670 patients. Br J Derma- tol. 2009;161:1180-1189. source

      Gollnick (2009) is identified as a randomized acne trial of adapalene–benzoyl peroxide, so citing it as one of four trials is plausible; the pooled RR need not appear in an individual trial. Two searches of its Semantic Scholar record returned no full-text snippets, however, and the other search results do not establish its vehicle-comparator IGA success result at 12 weeks. The available evidence therefore cannot verify this trial’s contribution to the stated comparison; it does not establish misattribution. (LLM, conf=0.62)

      Experimental — accuracy not yet measured
    • cites [71] 71. Jarratt MT, Brundage T. Efficacy and safety of clindamycin- tretinoin gel versus clindamycin or tretinoin alone in acne vulgaris: a randomized, double-blind, vehicle-controlled study. J Drugs Dermatol. 2012;11:318-326.
  • Interpretationcitation

    For pregnant patients, fetal harm from topical azelaic acid, benzoyl peroxide, erythromycin, and clindamycin is not expected because systemic absorption is expected to be limited.

    “In patients who are pregnant, the risk of fetal harm from topical azelaic acid, BP, erythromycin, and clindamycin are not expected based on limited expected systemic absorption.174,175”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [174] 174. Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation: part I. Pregnancy. J Am Acad Dermatol. 2014;70:401.e1-401.e14; quiz 15. source
    • cites [175] 175. Ly S, Kamal K, Manjaly P, Barbieri JS, Mostaghimi A. Treat- ment of acne vulgaris during pregnancy and lactation: a Narrative review. Dermatol Ther. 2023;13:115-130. source
  • Findingcitation

    In three randomized trials, more patients using combined benzoyl peroxide and topical retinoid than vehicle achieved Investigator's Global Assessment success at 12 weeks (risk ratio 2.19, 95% CI 1.77-2.72).

    “Compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in 3 RCTs (RR, 2.19 [1.77, 2.72]).63,64,109”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [63] 63. Webster GF, Sugarman J, Levy-Hacham O, Toledano O. Microencapsulated benzoyl peroxide and tretinoin for the treatment of acne vulgaris: results from a phase 2 multicenter, double-blind, randomized, vehicle-controlled study. Skinmed. 2020;18(6):343-351.
    • cites [64] 64. Gollnick HP, Draelos Z, Glenn MJ, et al. Adapalene-benzoyl peroxide, a unique fixed-dose combination topical gel for the treatment of acne vulgaris: a transatlantic, randomized, double-blind, controlled study in 1670 patients. Br J Derma- tol. 2009;161:1180-1189. source
    • cites [109] 109. Dreno B, Bissonnette R, Gagne-Henley A, et al. Prevention and reduction of atrophic acne scars with adapalene 0.3%/benzoyl peroxide 2.5% gel in subjects with moderate or severe facial acne: results of a 6-month randomized, vehicle-controlled trial using intra-individual comparison. Am J Clin Dermatol. 2018;19(2):275-286. source
  • May combine two claims. 46
  • Classified as probably not a substantial claim. 8

  • May combine two claims.

    Findingcitation

    Current data show no consistent difference in acne response by combined oral contraceptive formulation or dosage and do not support superiority of one combined oral contraceptive over another for acne.

    “Current data show no consistent difference in acne responses based on COC formulations or dosages and do not support the superiority of one COC over another for acne treatment”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [199] 199. Kelly S, Davies E, Fearns S, et al. Effects of oral contraceptives containing ethinylestradiol with either drospirenone or levo- norgestrel on various parameters associated with well-being in healthy women: a randomized, single-blind, parallel- group, multicentre study. Clin Drug Investig. 2010;30:325-336. source
    • cites [200] 200. Palatsi R, Hirvensalo E, Liukko P, et al. Serum total and unbound testosterone and sex hormone binding globulin (SHBG) in female acne patients treated with two different oral contraceptives. Acta Derm Venereol. 1984;64:517-523. source

      The Improvement of acne section (p. 4) reports that acne responded better to desogestrel/ethinyloestradiol than to levonorgestrel/ethinyloestradiol (p<0.05), contrary to the claim of no formulation difference or superiority. Patients and Methods (p. 2) shows that both groups received the same ethinyloestradiol dose, so this study does not compare dosages. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [201] 201. Rosen MP, Breitkopf DM, Nagamani M. A randomized controlled trial of second-versus third-generation oral contraceptives in the treatment of acne vulgaris. Am J Obstet Gynecol. 2003;188:1158-1160. source

  • May combine two claims.

    Findingcitation

    Use of oral tetracycline-class antibiotics has been linked to inflammatory bowel disease, pharyngitis, Clostridium difficile infection, and Candida vulvovaginitis.

    “In addition to concerns about antibiotic resistance, oral tetracycline-class antibiotic use has been associated with inflammatory bowel disease (IBD), 114 pharyngitis, 179 Clostridium difficile infection, 180,181 and Candida vulvovaginitis.”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [114] 114. Margolis DJ, Fanelli M, Hoffstad O, Lewis JD. Potential association between the oral tetracycline class of antimicro- bials used to treat acne and inflammatory bowel disease. Am J Gastroenterol. 2010;105:2610-2616. source
    • cites [179] source
    • cites [180] 180. Bartlett JG, Chang TW, Gurwith M, Gorbach SL, Onderdonk AB. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N Engl J Med. 1978;298:531-534. source
    • cites [181] 181. Carroll KC, Bartlett JG. Biology of Clostridium difficile: implications for epidemiology and diagnosis. Annu Rev Microbiol. 2011;65:501-521. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The Centers for Disease Control and Prevention recommend that outpatient antibiotic stewardship programs include commitment, implementation, tracking, and access to educational resources.

    “The Centers for Disease Control and Prevention recommend outpatient antibiotic stewardship programs to include (1) commitment to optimizing antibiotic prescribing and patient safety, (2) implementation action for stewardship policy or practice, (3) tracking prescribing practices through clinician feedback or self-assessment, and (4) access to educational resources and expertise.182”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [182] 182. Sanchez GV, Fleming-Dutra KE, Roberts RM, et al. Core elements of outpatient antibiotic stewardship. MMWR Re- comm Rep. 2016;65(6):1-12. 183. 102. Nast A, Dr eno B, Bettoli V, et al. European evidence-based (S3) guideline for the treatment of acne -update 2016 - short version. J Eur Acad Dermatol Venereol. 2016;30: 1261-1268. source

  • May combine two claims.

    Findingcitation

    Menstrual irregularities are commonly reported with spironolactone (40.6% vs 0%; RR 10.89, 95% CI 1.54-77.08), may be dose-dependent, and are less common among those using combined oral contraceptives.

    “Menstrual irregularities were commonly reported (40.6% vs 0%; RR, 10.89 [1.54, 77.08]), 140,141 may be dose-dependent, 232 and are less common among those using COC.233”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [140] 140. Patiyasikunt M, Chancheewa B, Asawanonda P, Noppakun N, Kumtornrut C. Efficacy and tolerability of low-dose spirono- lactone and topical benzoyl peroxide in adult female acne: a randomized, double-blind, placebo-controlled trial. J Derma- tol. 2020;47:1411-1416. source
    • cites [141] 141. Goodfellow A, Alaghband-Zadeh J, Carter G, et al. Oral spironolactone improves acne vulgaris and reduces sebum excretion. Br J Dermatol. 1984;111:209-214. source
    • cites [232] 232. Layton AM, Eady EA, Whitehouse H, Del Rosso JQ, Fedorowicz Z, van Zuuren EJ. Oral spironolactone for acne vulgaris in adult females: a hybrid systematic review. Am J Clin Dermatol. 2017;18:169-191. source

  • May combine two claims.

    Findingcitation

    Systematic reviews associate combined oral contraceptives with small increases in breast and cervical cancer risks and decreases in endometrial, ovarian, and colorectal cancer risks.

    “COCs have been associated with small increases in breast cancer and cervical cancer risks and decreases in endometrial, ovarian, and colorectal cancer risks in systematic reviews.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [212] 212. Gierisch JM, Coeytaux RR, Urrutia RP, et al. Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: a systematic review. Cancer Epidemiol Biomarkers Prev. 2013;22:1931-1943. source
    • cites [213] 213. Havrilesky LJ, Moorman PG, Lowery WJ, et al. Oral contra- ceptive pills as primary prevention for ovarian cancer: a systematic review and meta-analysis. Obstet Gynecol. 2013; 122:139-147. source
    • cites [214] 214. Iversen L, Sivasubramaniam S, Lee AJ, Fielding S, Hannaford PC. Lifetime cancer risk and combined oral contraceptives: the Royal College of general practitioners' oral contraception study. Am J Obstet Gynecol. 2017;216:580.e1-580.e9. source

  • May combine two claims.

    Premisecitation

    Progestin-only contraceptive pills, intramuscular injections, intrauterine devices, or subcutaneous implants may worsen acne.

    “Progestin-only oral contraceptive pills, intramuscular injections, intrauterine devices, or subcutaneous implants may worsen acne.196,197”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [196] 196. Barbieri JS, Mitra N, Margolis DJ, Harper CC, Mostaghimi A, Abuabara K. Influence of contraception class on incidence and severity of acne vulgaris. Obstet Gynecol. 2020;135:1306-1312. source

      The Results report more acne encounters after switching from combined pills to progestin-only pills, levonorgestrel IUDs, or an etonogestrel implant. The Introduction also reports a prior survey suggesting that injections, implants, and hormonal IUDs worsened acne. However, this paper's new-user analysis found fewer incident acne encounters with DMPA injections and implants, and switching to DMPA was not associated with a significant increase; the blanket claim is therefore not supported by its findings for every listed method. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [197] 197. Lortscher D, Admani S, Satur N, Eichenfield LF. Hormonal contraceptives and acne: a retrospective analysis of 2147 patients. J Drugs Dermatol. 2016;15:670-674.

  • May combine two claims.

    Premisecitation

    Combined oral contraceptives treat acne through anti-androgenic effects: they decrease ovarian androgen production, increase sex hormone-binding globulin, and reduce free testosterone that would activate the androgen receptor.

    “COC treat acne through their overall anti-androgenic properties, which decrease ovarian androgen production, increase sex hormone-binding globulin, and reduce free testosterone that would otherwise activate the androgen receptor.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [192] 192. Arowojolu AO, Gallo MF, Lopez LM, Grimes DA. Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev. 2012;6:CD004425. source
    • cites [193] 193. Arrington EA, Patel NS, Gerancher K, Feldman SR. Combined oral contraceptives for the treatment of acne: a practical guide. Cutis. 2012;90:83-90.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [194] 194. Harper JC. Should dermatologists prescribe hormonal con- traceptives for acne? Dermatol Ther. 2009;22:452-457. source

  • May combine two claims.

    Findingcitation

    Localized skin atrophy, systemic absorption of steroids, and possible adrenal suppression may occur with intralesional corticosteroid injections.

    “Localized skin atrophy, systemic absorption of steroids, and possible adrenal suppression may occur.247”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [247] 247. Kwon HH, Yoon JY, Hong JS, Jung JY, Park MS, Suh DH. Clinical and histological effect of a low glycaemic load diet in treatment of acne vulgaris in Korean patients: a randomized, controlled trial. Acta Derm Venereol. 2012;92:241-246. source

      The Materials and Methods (p. 1) describe a dietary intervention for acne, and the Discussion (pp. 4–5) addresses its effects. Searches for intralesional corticosteroid injections, skin atrophy, systemic steroid absorption, and adrenal suppression found no passage in our copy addressing those risks. (LLM, conf=0.78)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    In two isotretinoin cohort studies, the risk of mild normocytic anemia was 0.4%, abnormal platelet level 1.2% to 2.9%, and abnormal white blood cell count 7.0% to 10.8%.

    “Data from 2 isotretinoin cohort studies estimated the risk of mild normocytic anemia as 0.4%, abnormal platelet level at 1.2% to 2.9%, and abnormal white blood cell count at 7.0% to 10.8%”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [269] 269. Evaristo L, Bagatin E. Use of oral isotretinoin to treat acne in the public system: a hospital-based retrospective cohort. Sao Paulo Med J. 2019;137:363-368. source

      The Results (page unavailable) report one case of mild normocytic anemia among 257 followed patients, approximately 0.4%. They report no leukopenia or thrombocytopenia and do not provide the claimed 1.2%–2.9% platelet or 7.0%–10.8% white-blood-cell abnormality rates. This paper is one cohort, not both studies referred to in the citing sentence. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [270] 270. Barbieri JS, Shin DB, Wang S, Margolis DJ, Takeshita J. The clinical utility of laboratory monitoring during isotretinoin therapy for acne and changes to monitoring practices over time. J Am Acad Dermatol. 2020;82:72-79. source

      The Results (Frequency of laboratory abnormalities; page unavailable) report no significant white blood cell or platelet abnormalities in this cohort, but do not give the claimed rates for mild normocytic anemia, abnormal platelets, or abnormal white blood cell counts. Searches for the percentages and anemia terms found no passage reporting those estimates or combining two cohorts. (LLM, conf=0.77)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Many global acne experts agree that isotretinoin is the most appropriate treatment for patients with severe or scarring acne.

    “Many global acne experts have agreed that isotretinoin is the most appropriate treatment option for those with severe or scarring acne.183,184,[257][258][259][260][261][262]”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [183] source

      In §5.4.4 (pp. 37–38), the guideline says that many experts support isotretinoin as a first-choice treatment for specified severe forms of acne and cites prevention of scarring as a reason. It does not separately recommend isotretinoin as the most appropriate treatment for scarring acne regardless of severity. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [184] 184. Oon HH, Wong SN, Aw DCW, Cheong WK, Goh CL, Tan HH. Acne management guidelines by the Dermatological Society of Singapore. J Clin Aesthet Dermatol. 2019;12:34-50.
    • cites [257] 257. Asai Y, Baibergenova A, Dutil M, et al. Management of acne: Canadian clinical practice guideline. CMAJ. 2016;188: 118-126. source

  • May combine two claims.

    Premisecitation

    Multiple studies indicate that isotretinoin may improve quality of life and reduce anxiety and depression symptoms in patients with moderate to severe acne.

    “Multiple studies indicate that isotretinoin may improve quality of life and decrease symptoms of anxiety and depression in patients with moderate to severe acne”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [292] 292. Secrest AM, Hopkins ZH, Frost ZE, et al. Quality of life assessed using Skindex-16 scores among patients with acne receiving isotretinoin treatment. JAMA Dermatol. 2020;156: 1098-1106. source

      The Results (page not specified) report improved quality-of-life and Emotional domain scores during isotretinoin treatment in patients with moderate to severe acne. The Methods describe these as measures of how skin disease affects quality of life; the paper does not establish a decrease in anxiety or depression symptoms specifically. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [293] 293. Bray AP, Kravvas G, Skevington SM, Lovell CR. Is there an association between isotretinoin therapy and adverse mood changes? A prospective study in a cohort of acne patients. J Dermatolog Treat. 2019;30:796-801. source
    • cites [294] 294. Paljarvi T, McPherson T, Luciano S, Herttua K, Fazel S. Isotretinoin and adverse neuropsychiatric outcomes: retro- spective cohort study using routine data. Br J Dermatol. 2022; 187:64-72. source

      The Discussion (page not provided) says the results add to evidence suggesting improvement in anxiety and depression symptoms, and reports reduced incidence of both compared with patients prescribed oral antibiotics. The paper does not report an improvement in quality of life; its Outcome measurement section lists neuropsychiatric diagnoses and related proxies, not quality-of-life measures. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    Available comparative effectiveness evidence does not show that any topical retinoid is superior to another; efficacy and tolerability vary with concentration and formulation.

    “Existing comparative effectiveness data do not suggest superiority of one topical retinoid against another, with efficacy and tolerability differing by specific concentrations and formulations.153,[156][157][158][159]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites 153,[156][157][158][159]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingcitation

    Benzoyl peroxide use is limited by burning, stinging, dryness, redness, pain, peeling, irritation, fabric staining and bleaching, and rare contact allergy, with effects depending on concentration and formulation.

    “BP use is limited by concentration and formulation-dependent burning sensation, stinging, dryness, erythema, pain, peeling, irritation, fabric staining and bleaching, and uncommon contact allergy.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The relationship between acne severity and androgen levels is uncertain; some studies report positive associations and others report none.

    “The association between acne severity and androgen levels remains unclear, with some studies showing positive associations while others showed no associations.48,49”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [48] 48. Franik G, Bizo n A, W1och S, Kowalczyk K, Biernacka-Bartnik A, Madej P. Hormonal and metabolic aspects of acne vulgaris in women with polycystic ovary syndrome. Eur Rev Med Pharmacol Sci. 2018;22:4411-4418. source
    • cites [49] 49. Kiayani AJ, Rehman FU. Association of serum testosterone and sex hormone binding globulin levels in females with acne based on its severity. J Ayub Med Coll Abbottabad. 2016; 28:357-359.

  • May combine two claims.

    Findingcitation

    Doxycycline can cause gastrointestinal disturbances, with a higher rate than comparator (15.7% vs 5.9%; RR 2.56, 95% CI 1.05-6.25), including nausea, vomiting, and diarrhea.

    “Doxycycline may cause gastrointestinal disturbances (15.7% vs 5.9%; RR, 2.56 [1.05, 6.25]),”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [115] 115. Skidmore R, Kovach R, Walker C, et al. Effects of subantimicrobial-dose doxycycline in the treatment of mod- erate acne. Arch Dermatol. 2003;139:459-464. source
    • cites [116] 116. Leyden JJ, Bruce S, Lee CS, et al. A randomized, phase 2, dose-ranging study in the treatment of moderate to severe inflammatory facial acne vulgaris with doxycycline calcium. J Drugs Dermatol. 2013;12:658-663.
    • cites [117] 117. Moore A, Ling M, Bucko A, Manna V, Rueda MJ. Efficacy and safety of subantimicrobial dose, modified-release doxycy- cline 40 mg versus doxycycline 100 mg versus placebo for the treatment of inflammatory lesions in moderate and severe acne: a randomized, double-blinded, controlled study. J Drugs Dermatol. 2015;14:581-586.

  • May combine two claims.

    Findingown data

    The evidence is insufficient to recommend topical glycolic acid, sulfur, sodium sulfacetamide, or resorcinol for acne, or to compare topical benzoyl peroxide, retinoids, antibiotics, and their combinations directly.

    “Available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other (Supplementary Tables XXVII-XXXV, available via Mendeley at https://data.mendeley.com/datasets/ z2bmdwwdf9/2)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    Active comparator studies are lacking, so it is not known whether any topical antibiotic is superior to another.

    “There is a lack of active comparator studies to suggest if any one topical antibiotic is superior to another.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    In 2021, dermatologists wrote more oral antibiotic prescriptions per clinician than any other specialty, and most of those antibiotics were for acne.

    “In 2021, dermatologists prescribed more oral antibiotics per clinician than all other specialties, with the majority of antibiotics used for acne treatment.177,178”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [177] 177. Barbieri JS, Bhate K, Hartnett KP, Fleming-Dutra KE, Margolis DJ. Trends in oral antibiotic prescription in dermatology, 2008 to 2016. JAMA Dermatol. 2019;155: 290-297. source
    • cites [178] 178. Centers for Disease Control and Prevention. Outpatient Antibiotic Prescriptions d United States, 2022. Updated November 15, 2025.. Accessed January 18, 2024. https:// www.cdc.gov/antibiotic-use/data/report-2022.html 179. 101. Margolis DJ, Fanelli M, Kupperman E, et al. Association of pharyngitis with oral antibiotic use for the treatment of acne: a cross-sectional and prospective cohort study. Arch Derma- tol. 2012;148:326-332.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingcitation

    In a randomized trial of 925 patients comparing standard isotretinoin with lidose-isotretinoin, 81.0% of standard isotretinoin patients had a 90% reduction in lesion count and 88.9% achieved treatment success after 20 weeks.

    “In a RCT of 925 patients comparing standard isotretinoin with lidoseisotretinoin, 81.0% of patients treated with standard isotretinoin experienced a 90% reduction in lesion count and 88.9% of patients treated with standard isotretinoin achieved treatment success after 20 weeks of treatment.151”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [151] 151. Webster GF, Leyden JJ, Gross JA. Results of a phase III, double-blind, randomized, parallel-group, non-inferiority study evaluating the safety and efficacy of isotretinoin- Lidose in patients with severe recalcitrant nodular acne. J Drugs Dermatol. 2014;13:665-670.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Trimethoprim/sulfamethoxazole may be associated with severe adverse reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis and acute respiratory failure.

    “In addition, TMP-SMX may be associated with severe adverse reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis and acute respiratory failure.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Combined oral contraceptives provide benefits beyond contraception and acne treatment, including regulating menstrual cycles, inducing amenorrhea, preventing menstrual migraines, and treating dysmenorrhea, hirsutism, menorrhagia, endometriosis-associated pelvic pain, and premenstrual syndrome.

    “COC confers benefits beyond contraception and acne treatment, including regulating menstrual cycles, induction of amenorrhea, prevention of menstrual migraines, and treatment of conditions such as dysmenorrhea, hirsutism, menorrhagia, endometriosis-associated pelvic pain, premenstrual syndrome, among others.217”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [217] 217. ACOG practice bulletin no. 110: noncontraceptive uses of hormonal contraceptives. Obstet Gynecol. 2010;115: 206-218. source

  • May combine two claims.

    Findingcitation

    In a small randomized trial of nine patients, most acne cysts injected with triamcinolone resolved within 3-7 days, and triamcinolone-injected cysts resolved faster than saline-injected controls.

    “in a small RCT of 9 patients, most acne cysts injected with triamcinolone resolved within 3-7 days of the treatment, and those injected with triamcinolone resolved faster than those with saline control.239”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [239] 239. Levine RM, Rasmussen JE. Intralesional corticosteroids in the treatment of nodulocystic acne. Arch Dermatol. 1983;119: 480-481. source

  • May combine two claims.

    Findingcitation

    Estimated venous thromboembolism incidence per 10,000 person-years is about 1-5 in nonpregnant women not using combined oral contraceptives, 3-9 in combined oral contraceptive users, 10 in drospirenone-containing combined oral contraceptive users, 5-20 in pregnancy, and 40-65 in the 12-week postpartum period.

    “Estimated VTE incidence per 10,000 person-years are estimated at approximately 1-5 in nonpregnant women who do not use COCs, 3-9 in COC users, 10 in drospirenone-containing COC users, 5-20 in pregnancy, and 40-65 in the 12-week postpartum period.208,210”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [208] 208. ACOG Committee Opinion Number 540. Risk of Venous Thromboembolism Among Users of Drospirenone- Containing Oral Contraceptive Pills. American College of Obstetricians and Gynecologists; 2012.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [210] 210. Food and Drug Administration. Combined Hormonal Con- traceptives (CHCs) and the Risk of Cardiovascular Disease Endpoints. 2011. Accessed January 18, 2024. https://www. fda.gov/media/82335/download

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingnone given

    Available evidence is insufficient to recommend oral corticosteroids, flutamide, or metformin for acne treatment.

    “Available evidence is insufficient to develop a recommendation on the use of oral corticosteroids, flutamide, or metformin for acne treatment”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Common side effects of spironolactone include diuresis, breast tenderness, breast enlargement, gynecomastia, fatigue, headache, and dizziness.

    “Common side effects also include diuresis, breast tenderness, breast enlargement, gynecomastia, fatigue, headache, and dizziness.234”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [234] 234. Shaw JC, White LE. Long-term safety of spironolactone in acne: results of an 8-year followup study. J Cutan Med Surg. 2002;6:541-545. source

  • May combine two claims.

    Findingnone given

    Sarecycline is generally well tolerated, with low rates of gastrointestinal, photosensitivity, and Candida infection side effects.

    “Sarecycline is dosed by weight at 1.5 mg/kg and is generally well tolerated with low incidence of gastrointestinal, photosensitivity, and Candida infection side effects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In a large cohort of 108,547 acne patients receiving spironolactone for at least 30 days, 0.22% received a hyperkalemia diagnosis and 0.03% discontinued spironolactone within 30 days after hyperkalemia diagnosis.

    “In a large cohort study of 108,547 patients with acne who received spironolactone for $30 days, 0.22% received a hyperkalemia diagnosis and 0.03% discontinued spironolactone within 30 days after hyperkalemia diagnosis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    Despite isotretinoin's remarkable effectiveness in routine dermatology practice, clinical trial data on its efficacy are limited and of low quality.

    “Despite the remarkable effectiveness of isotretinoin observed in routine dermatology practice, clinical trial data regarding its efficacy are limited and of low quality.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In a randomized trial of 33 patients with treatment-resistant cystic and conglobate acne, mean cystic lesion counts decreased by 17% and 33% at 1 and 2 months of isotretinoin, but increased by 33% and 58% at 1 and 2 months of placebo.

    “In a RCT of 33 patients with treatment-resistant cystic and conglobate acne, mean number of cystic lesions decreased by 17% and 33% at 1 and 2 months of isotretinoin treatment, but increased by 33% and 58% at 1 and 2 months of placebo”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [252] 252. Peck GL, Olsen TG, Butkus D, et al. Isotretinoin versus placebo in the treatment of cystic acne. A randomized double-blind study. J Am Acad Dermatol. 1982;6:735-745. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Acne improvement with combined oral contraceptives is usually notable within 3-6 months.

    “Clinicians should counsel patients about expected time to acne improvement with COCs, usually notable within 3-6 months”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In five isotretinoin cohort studies, the risk of liver function test abnormalities above reference limits ranged from 0.8% to 10.4%, and 0.9% to 4.7% of patients required treatment discontinuation.

    “data from 5 isotretinoin cohort studies estimated that risks of abnormal liver function tests above reference limits ranged from 0.8% to 10.4%, with 0.9% to 4.7% requiring treatment discontinuation”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [266] 266. Amichai B, Shemer A, Grunwald MH. Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol. 2006;54: 644-646. source
    • cites [267] 267. Kızılyel O, Metin MS, Elmas € O F, C ¸ayır Y, Aktas ¸A. Effects of oral isotretinoin on lipids and liver enzymes in acne patients. Cutis. 2014;94:234-238.
    • cites [268] 268. Ghaffarpour G, Mazloomi S, Soltani-Arabshahi R, Seyed KS. Oral isotretinoin for acne, adjusting treatment according to patient's response. J Drugs Dermatol. 2006;5:878-882.

  • May combine two claims.

    Findingcitation

    In six isotretinoin cohort studies, the risk of abnormal triglycerides ranged from 7.1% to 39.0% and abnormal cholesterol levels ranged from 6.8% to 27.2%.

    “Data from 6 isotretinoin cohort studies estimated that the risks of abnormal triglycerides ranged from 7.1% to 39.0% and abnormal cholesterol levels ranged from 6.8% to 27.2%”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [266] 266. Amichai B, Shemer A, Grunwald MH. Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol. 2006;54: 644-646. source
    • cites [267] 267. Kızılyel O, Metin MS, Elmas € O F, C ¸ayır Y, Aktas ¸A. Effects of oral isotretinoin on lipids and liver enzymes in acne patients. Cutis. 2014;94:234-238.
    • cites [268] 268. Ghaffarpour G, Mazloomi S, Soltani-Arabshahi R, Seyed KS. Oral isotretinoin for acne, adjusting treatment according to patient's response. J Drugs Dermatol. 2006;5:878-882.

  • May combine two claims.

    Findingcitation

    Common adverse effects of isotretinoin involve the mucocutaneous, musculoskeletal, and ophthalmic systems and generally resolve after isotretinoin discontinuation with standard treatment courses.

    “Common adverse effects associated with isotretinoin involve the mucocutaneous, musculoskeletal, and ophthalmic systems and generally resolve following isotretinoin discontinuation with standard treatment courses. 3”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] 3. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74:945-973.e33. source

  • May combine two claims.

    Findingcitation

    In an RCT of 782 patients, lidose-isotretinoin was non-inferior in reducing facial and truncal nodular lesions and in the proportion of patients achieving ≥90% reduction of total lesions at 20 weeks (76.9% vs 81.0%; RR 0.95 [0.88,1.02]).

    “In an RCT of 782 patients, lidose-isotretinoin showed non-inferiority in reducing facial and truncal nodular lesions and in the proportion of patients achieving $90% reduction of total lesions at 20 weeks (76.9% vs 81.0%; RR, 0.95 [0.88, 1.02]).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [151] 151. Webster GF, Leyden JJ, Gross JA. Results of a phase III, double-blind, randomized, parallel-group, non-inferiority study evaluating the safety and efficacy of isotretinoin- Lidose in patients with severe recalcitrant nodular acne. J Drugs Dermatol. 2014;13:665-670.

  • May combine two claims.

    Findingcitation

    Among sexually active patients who reported non-adherence, 29% did not use condoms consistently and 39% missed one or more contraceptive pills in the previous month.

    “Among sexually active patients who reported non-adherence, 29% did not comply with consistent condom use and 39% missed 1 or more contraceptive pills in the previous month.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [277] 277. Collins MK, Moreau JF, Opel D, et al. Compliance with pregnancy prevention measures during isotretinoin therapy. J Am Acad Dermatol. 2014;70:55-59. source

  • May combine two claims.

    Findingcitation

    Population-based studies have not found an increased risk of neuropsychiatric conditions or inflammatory bowel disease in acne patients treated with isotretinoin.

    “Population-based studies have not identified increased risk of neuropsychiatric conditions or IBD in patients with acne undergoing isotretinoin treatment”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Staphylococcus epidermidis, Staphylococcus aureus, and Malassezia species have been found in acne lesions, but their causal role in acne has not been shown.

    “Staphylococcus epidermidis, Staphylococcus aureus, and Malassezia species have also been identified in acne lesions, although causal relationships remain to be demonstrated.[41][42][43][44][45]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41][42][43][44][45]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationnone given

    Topical retinoids can increase sensitivity to sunlight, and daily sunscreen can lower the risk of sunburn.

    “Topical retinoids may cause photosensitivity; concurrent daily sunscreen use can reduce sunburn risks.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Benzoyl peroxide is an over-the-counter topical antimicrobial that releases free oxygen radicals and has mild comedolytic activity.

    “BP is an over-the-counter topical antimicrobial agent that releases free oxygen radicals and is mildly comedolytic.164,165”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [164] 164. Cunliffe WJ, Dodman B, Ead R. Benzoyl peroxide in acne. Practitioner. 1978;220:479-482.
    • cites [165] 165. Fulton JE Jr, Farzad-Bakshandeh A, Bradley S. Studies on the mechanism of action to topical benzoyl peroxide and vitamin A acid in acne vulgaris. J Cutan Pathol. 1974;1:191-200. source

  • May combine two claims.

    Premisecitation

    Clascoterone is a topical antiandrogen that binds the androgen receptor directly and blocks androgen-driven lipid and inflammatory cytokine production by sebocytes.

    “Clascoterone is a topical antiandrogen that directly binds the androgen receptor and inhibits androgen-mediated lipid and inflammatory cytokine synthesis from sebocytes.172”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [172] 172. Rosette C, Agan FJ, Mazzetti A, Moro L, Gerloni M. Cortex- olone 17alpha-propionate (clascoterone) is a novel androgen receptor antagonist that inhibits production of lipids and inflammatory cytokines from sebocytes in vitro. J Drugs Dermatol. 2019;18:412-418.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Tetracycline-class antibiotics have antibacterial effects by binding 16S ribosomal RNA of the bacterial 30S subunit to block protein synthesis, and anti-inflammatory effects by inhibiting neutrophil chemotaxis and matrix metalloproteinases and reducing inflammatory cytokines.

    “Tetracycline-class antibiotics exhibit antibiotic properties by binding the 16S ribosomal RNA of the bacterial ribosome 30S subunit to inhibit protein synthesis, as well as anti-inflammatory properties by inhibiting neutrophil chemotaxis and matrix metalloproteinases and down-regulating inflammatory cytokines.176”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [176] 176. Perret LJ, Tait CP. Non-antibiotic properties of tetracyclines and their clinical application in dermatology. Australas J Dermatol. 2014;55:111-118. source

  • May combine two claims.

    Premisecitation

    Azelaic acid is a topical agent with comedolytic, antibacterial, and anti-inflammatory actions; it may be especially useful for sensitive or darker skin because it lightens dyspigmentation.

    “Azelaic acid is a topical comedolytic, antibacterial, and anti-inflammatory agent, which may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation.96,97,173”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [96] 96. Cunliffe WJ, Holland KT. Clinical and laboratory studies on treatment with 20% azelaic acid cream for acne. Acta Derm Venereol Suppl. 1989;143:31-34.
    • cites [97] 97. Katsambas A, Graupe K, Stratigos J. Clinical studies of 20% azelaic acid cream in the treatment of acne vulgaris. Com- parison with vehicle and topical tretinoin. Acta Derm Venereol Suppl. 1989;143:35-39.
    • cites [173] 173. Kircik LH. Efficacy and safety of azelaic acid (AzA) gel 15% in the treatment of post-inflammatory hyperpigmentation and acne: a 16-week, baseline-controlled study. J Drugs Dermatol. 2011;10:586-590.

  • May combine two claims.

    Premisecitation

    Isotretinoin reduces the size and secretion of sebaceous glands, indirectly decreases surface and ductal sebum-dependent C. acnes, inhibits comedogenesis by normalizing keratinocyte keratinization, and has anti-inflammatory properties.

    “isotretinoin reduces the size and secretion of sebaceous glands, decreases surface and ductal level of sebumdependent C. acnes indirectly, inhibits comedogenesis by normalizing keratinocyte keratinization, and possesses anti-inflammatory properties. 251”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [251] 251. Villani A, Nastro F, Di Vico F, Fabbrocini G, Annunziata MC, Genco L. Oral isotretinoin for acne: a complete overview. Expert Opin Drug Saf. 2022;21:1027-1037. source

  • May combine two claims.

    Premisecitation

    Spironolactone crosses the placenta, and in utero exposure in animal studies may cause feminization of a male fetus.

    “Spironolactone crosses the placenta and exposure in utero in animal studies may cause feminization of a male fetus.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Spironolactone is not FDA-approved for acne treatment.

    “Spironolactone is not FDA-approved for the treatment of acne.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Oral doxycycline, minocycline, and sarecycline are FDA-approved for acne management.

    “Oral doxycycline, minocycline, and sarecycline are FDA-approved for the management of acne.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Prednisone 0.5-1 mg/kg/day has been used to treat acne fulminans, isotretinoin-induced acne fulminans, and to prevent isotretinoin-induced acne flares in at-risk patients.

    “Prednisone 0.5-1 mg/kg/day has been used to treat acne fulminans, isotretinoin-induced acne fulminans and to prevent isotretinoin-induced acne flares in at-risk patients.249,250”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [249] 249. Jansen T, Plewig G. Acne fulminans. Int J Dermatol. 1998;37: 254-257. source
    • cites [250] 250. Karvonen SL. Acne fulminans: report of clinical findings and treatment of twenty-four patients. J Am Acad Dermatol. 1993; 28:572-579. source

  • May combine two claims.

    Premisecitation

    Spironolactone is an aldosterone receptor antagonist that decreases testosterone production and competitively inhibits testosterone and dihydrotestosterone binding to androgen receptors in skin.

    “Spironolactone is an aldosterone receptor antagonist that decreases testosterone production and competitively inhibits testosterone and dihydrotestosterone binding to androgen receptors in the skin.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [225] 225. Boisselle A, Dionne FT, Tremblay RR. Interaction of spirono- lactone with rat skin androgen receptor. Can J Biochem. 1979; 57:1042-1046. source
    • cites [226] 226. Menard RH, Martin HF, Stripp B, Gillette JR, Bartter FC. Spironolactone and cytochrome P-450: impairment of steroid hydroxylation in the adrenal cortex. Life Sci. 1974;15:1639- 1648. source
    • cites [227] 227. Menard RH, Stripp B, Gillette JR. Spironolactone and testic- ular cytochrome P-450: decreased testosterone formation in several species and changes in hepatic drug metabolism. Endocrinology. 1974;94:1628-1636. source

  • May combine two claims.

    Premisecitation

    A recent Delphi consensus study of 22 acne experts agreed on checking alanine aminotransferase and triglycerides before initiation and at peak isotretinoin dose, and on not checking complete blood count, low-density lipoprotein, or high-density lipoprotein.

    “A recent Delphi consensus study of 22 acne experts reached agreement on checking alanine aminotransferase and triglycerides prior to initiation and at peak isotretinoin dose and on not checking complete blood count, low-density lipoprotein or highdensity lipoprotein.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [273] 273. Xia E, Han J, Faletsky A, et al. Isotretinoin laboratory monitoring in acne treatment: a Delphi consensus study. JAMA Dermatol. 2022;158:942-948. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The US Preventive Services Task Force recommends depression screening in adults and adolescents aged 12-18 years and anxiety screening in adolescents aged 8-18 years, regardless of isotretinoin exposure, each with grade B recommendations concluding with moderate certainty of moderate net benefit.

    “Notably, the US Preventive Service Task Force recommends screening for depression in adults 291 and in adolescents aged 12-18 years 295 and recommends screening for anxiety in adolescents aged 8-18 years, 296 regardless of exposure to isotretinoin, each with grade B recommendations that concludes with moderate certainty that such screening yields moderate net benefits.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [291] 291. Siu AL, , US Preventive Services Task Force (USPSTF), Bibbins- Domingo K, Grossman DC, et al. Screening for depression in adults: US preventive services task force recommendation statement. JAMA. 2016;315:380-387. source
    • cites [295] 295. US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, et al. Screening for depression and suicide risk in children and adolescents: US preventive services task force recommendation statement. JAMA. 2022;328:1534-1542. source
    • cites [296] 296. US Preventive Services Task Force, Mangione CM, Barry MJ, Nicholson WK, et al. Screening for anxiety in children and adolescents: US preventive services task force recommenda- tion statement. JAMA. 2022;328:1438-1444. source

  • May combine two claims.

    Premisecitation

    Full-face dermabrasion, mechanical dermabrasion with rotary devices, and ablative laser treatment of the entire face or non-facial regions within 6 months of isotretinoin use are associated with increased risks of adverse events.

    “Full-face dermabrasion, mechanical dermabrasion with rotary devices, and ablative laser treatment of the entire face or non-facial regions are not recommended within 6 months of isotretinoin use due to increased risks of adverse events.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [298] 298. Waldman A, Bolotin D, Arndt KA, et al. ASDS guidelines task force: consensus recommendations regarding the safety of lasers, dermabrasion, chemical peels, Energy devices, and skin surgery during and after isotretinoin use. Dermatol Surg. 2017;43:1249-1262. source

  • Classified as probably not a substantial claim.

    Premisecitation

    Expert consensus from the American Society of Dermatologic Surgery concluded that there is insufficient evidence to justify delaying superficial chemical peels and nonablative lasers, including hair removal lasers and lights, vascular lasers, and nonablative fractional devices, for patients currently receiving or recently having received isotretinoin.

    “Expert consensus from the American Society of Dermatologic Surgery concluded that there is insufficient evidence to justify delaying treatment with superficial chemical peels and nonablative lasers, including hair removal lasers and lights, vascular lasers, and nonablative fractional devices for patients currently receiving or recently received isotretinoin.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [298] 298. Waldman A, Bolotin D, Arndt KA, et al. ASDS guidelines task force: consensus recommendations regarding the safety of lasers, dermabrasion, chemical peels, Energy devices, and skin surgery during and after isotretinoin use. Dermatol Surg. 2017;43:1249-1262. source

  • May combine two claims.

    Premisecitation

    Long-acting reversible contraceptives, including intrauterine devices and contraceptive implants, are more effective than combined oral contraceptives and condoms at reducing unintended pregnancy risk and do not depend on ongoing patient effort.

    “Long-acting reversible contraceptives, including intrauterine devices and contraceptive implants, should be considered as the primary contraceptive method whenever clinically appropriate since they have higher effectiveness than COCs and condoms in reducing the risk of unintended pregnancy and do not depend on ongoing patient efforts.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [278] 278. Committee on Practice Bulletins-Gynecology, Long-Acting Reversible Contraception Work Group. Practice bulletin No. 186: long-acting reversible contraception: implants and intrauterine devices. Obstet Gynecol. 2017;130:e251-e269.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

53 of 53

  • The paper relies on this without support.

    Cutibacterium acnes has specific culture requirements that prevent growth in routine bacterial culture.

    “C. acnes has specific culture requirements that prevent growth in routine bacterial culture.”

  • The paper relies on this without support.

    Routine microbiologic and/or antibiotic susceptibility testing does not affect acne management.

    “routine microbiologic and/or antibiotic susceptibility testing is not indicated for patients with acne since it does not affect management.”

  • The paper relies on this without support.

    Androgens such as testosterone and dehydroepiandrosterone sulfate have central roles in acne pathogenesis.

    “Androgens, such as testosterone and dehydroepiandrosterone sulfate, have central roles in the pathogenesis of acne.”

  • The paper relies on this without support.

    Polycystic ovarian syndrome is a common cause of hyperandrogenism, characterized by ovulatory dysfunction or polycystic ovaries on ultrasonography.

    “Polycystic ovarian syndrome is a common cause of hyperandrogenism, characterized by ovulatory dysfunction or polycystic ovaries on ultrasonography.”

  • The paper relies on this without support.

    Topical retinoids are comedolytic and anti-inflammatory, improve dyspigmentation, and enable maintenance of acne clearance.

    “Topical retinoids are vitamin A derivatives and serve as the cornerstone of acne treatment since they are comedolytic and anti-inflammatory, improve dyspigmentation, and enable maintenance of acne clearance.”

  • The paper relies on this without support.

    Each retinoid binds to a different set of retinoic acid receptors and confers modest differences in activity, tolerability and efficacy.

    “Each retinoid binds to a different set of retinoic acid receptors and confers modest differences in activity, tolerability and efficacy.”

  • The paper relies on this without support.

    Combining topical antibiotics with benzoyl peroxide enhances efficacy and may prevent antibiotic resistance development.

    “Combining topical antibiotics with BP enhances efficacy and may prevent antibiotic resistance development.”

  • The paper relies on this without support.

    Potential adverse effect profiles of fixed-dose combinations generally reflect those of the individual agents in summation.

    “Potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation.”

  • The paper relies on this without support.

    Salicylic acid is a topical comedolytic agent available over the counter, with concentration ranging in 0.5% to 2%.

    “Salicylic acid is a topical comedolytic agent that is available over the counter, with concentration ranging in 0.5% to 2%.”

  • The paper relies on this without support.

    Tetracycline-class antibiotics are contraindicated in pregnancy, lactation, and childhood below age 9 years during tooth development, since repeated exposure may cause permanent teeth enamel hypoplasia or discoloration.

    “Notably, tetracycline-class antibiotics are contraindicated in pregnancy, lactation, and childhood below age 9 years during tooth development, since repeated exposure may cause permanent teeth enamel hypoplasia or discoloration.”

  • The paper relies on this without support.

    Increasing azithromycin use could increase antibiotic resistance.

    “increasing azithromycin use could increase antibiotic resistance.”

  • The paper relies on this without support.

    Tetracycline-class antibiotics can cause permanent teeth discoloration and inhibit bone growth in a fetus or nursing infant.

    “tetracyclineclass antibiotics should be avoided due to potential for permanent teeth discoloration and bone growth inhibition in the fetus or nursing infant.”

  • The paper relies on this without support.

    The high current cost of sarecycline may affect equitable access to acne treatment.

    “concerns about the high current cost of sarecycline treatment that may impact equitable acne treatment access.”

  • The paper relies on this without support.

    Rare potential adverse effects of minocycline, including vertigo, autoimmune hepatitis, skin hyperpigmentation, drug-induced lupus, and hypersensitivity syndrome, are concerns that justify a conditional recommendation.

    “concerns about rare potential adverse effects of minocycline, which include vertigo, autoimmune hepatitis, skin hyperpigmentation, drug-induced lupus, and hypersensitivity syndrome.”

  • The paper relies on this without support.

    Patient values and preferences regarding contraception vary.

    “variability in patient values and preferences related to contraception”

  • The paper relies on this without support.

    Broad use of antibiotics for acne can select for antibiotic-resistant bacteria.

    “broad use for acne should be discouraged to avoid selection of antibiotic-resistant bacteria.”

  • The paper relies on this without support.

    Depression, anxiety, and suicidal ideation/suicide are highly prevalent in the general population, especially among adolescents who may be candidates for isotretinoin therapy.

    “given high prevalence of depression, anxiety and suicidal ideation/suicide in the general population, and especially the adolescent population who may be candidates for isotretinoin therapy”

  • The paper relies on this without support.

    Standard isotretinoin has better bioavailability when taken with a high-fat meal, whereas lidose-isotretinoin bioavailability is less affected by food intake.

    “Standard isotretinoin has better bioavailability when taken with a high fat meal, whereas the bioavailability of lidose-isotretinoin is less affected by whether it is taken with food.”
18 of 18

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Salicylic-acid evidence is graded two ways

    Major

    The treatment section calls the evidence moderate certainty, while Table III grades the same recommendation as low certainty.

  • COC effect estimate falls outside its confidence interval

    Major

    The reported noninflammatory-lesion estimate is −19.45%, but its stated interval runs from −9.9% to −9.0%. The interval's midpoint is −9.45%, so it cannot contain the reported estimate.

    Reported -19.45 · recomputed -9.45

2 of 2

Cites

Flagged first, then by citations

45 of the 358 references couldn’t be matched to a known paper.

Research works printed but not linked: 5

  1. Paracha, 2020, Efficacy and safety of short term use of 0.1% tazarotene gel in the treatment of mild to moderate acne vulgaris: a randomized-vehicle controlled trial, J Postgrad Med Inst, 34, 134
  2. Eichenfield, 2016, Efficacy and safety of once-daily dapsone gel, 7.5% for treatment of adolescents and adults with acne vulgaris: second of two identically designed, large, multicenter, randomized, vehicle-controlled trials, J Drugs Dermatol, 15, 962
  3. Alexis, 2018, BPX-01 minocycline topical gel shows promise for the treatment of moderate-tosevere inflammatory acne vulgaris, J Clin Aesthet Dermatol, 11, 25
  4. Mazzetti, 2019, A phase 2b, randomized, double-blind vehicle controlled, dose escalation study evaluating clascoterone 0.1%, 0.5%, and 1% topical cream in subjects with facial, Acne, 1, 570
  5. Rosette, 2019, Cortexolone 17alpha-propionate (clascoterone) is a novel androgen receptor antagonist that inhibits production of lipids and inflammatory cytokines from sebocytes in vitro, J Drugs Dermatol, 18, 412

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Authors
Reynolds, R. V., Yeung, H., Cheng, C. E., Cook-Bolden, F., Desai, S. R., Druby, K. M., Freeman, E. E., Keri, J. E., Stein Gold, L. F., Tan, J. K. L., Tollefson, M. M., Weiss, J. S., Wu, P. A., Zaenglein, A. L., Han, J. M., & Barbieri, J. S.
Affiliations
  • Beth Israel Deaconess Medical Center (US)
  • Emory University (US)
  • University of California, Los Angeles (US)
  • Weill Cornell Medicine (US)
  • The University of Texas Southwestern Medical Center (US)
  • Pennsylvania State University (US)
  • Massachusetts General Hospital (US)
  • University of Miami (US)
  • Western University (CA)
  • Mayo Clinic (US)
  • University of California Davis Medical Center (US)
  • American Academy of Dermatology (US)
  • Brigham and Women's Hospital (US)
Corresponding author
Han, Jung Min
ORCID
Venue
Journal of the American Academy of Dermatology
Publisher
Elsevier BV
Published
2024-05
Volume
90
Issue
5
Pages
1006.e1-1006.e30
ISSN
0190-9622 (ISSN-L)
DOI
10.1016/j.jaad.2023.12.017
OpenAlex
W4391339756
Cited by
518
References
358
Citations by year
2026: 224 · 2025: 211 · 2024: 82 · 2022: 1
FWCI
209.33
Type
journal article
Language
en
Update notices
Open access
Licence
Locations
  • Journal of the American Academy of Dermatology (publishedVersion)
  • PubMed (publishedVersion)
Funders
American Academy of Dermatology
Topics
  • Health Sciences › Medicine › Dermatology › Acne and Rosacea Treatments and Effects
  • Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Clinical practice guidelines implementation
Keywords
acne, acne treatment, benzoyl peroxide, topical retinoids, topical antibiotics, oral doxycycline, oral isotretinoin, clascoterone, salicylic acid, azelaic acid, minocycline, sarecycline, combined oral contraceptives, spironolactone, intralesional corticosteroids, scar formation, psychosocial burden
MeSH terms
Acne Vulgaris, Administration, Cutaneous, Administration, Oral, Adrenal Cortex Hormones, Anti-Bacterial Agents, Benzoyl Peroxide, Contraceptives, Oral, Combined, Cortodoxone, Dermatologic Agents, Dicarboxylic Acids, Doxycycline, Drug Therapy, Combination, Humans, Minocycline, Propionates, Retinoids, Spironolactone, Tetracyclines, Isotretinoin, Injections, Intralesional, Evidence-Based Medicine, Salicylic Acid

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-09-30.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-30.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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