Dermatology: Practical and Conceptual Commentary | Dermatol Pract Concept. 2024;14(1):e2024018 1 Is there a Rationale for the Use of Lymecycline for Frontal Fibrosing Alopecia? Flavia Oliveira Xavier de Brito1, Rita Fernanda Cortez de Almeida1, Sidney Frattini2, Carlos Baptista Barcaui1, Michela Starace3,4, Daniel Fernandes Melo1 1 Department of Dermatology, State University of Rio de Janeiro, UERJ, Rio de Janeiro, Rio de Janeiro, Brazil 2 The Mole Clinic, Private Practice, Ancaster, Ontario, Canada 3 Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy 4 Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy Citation: Xavier de Brito F, Cortez de Almeida RF, Frattini S, Barcaui CB, Starace M, Melo DF. Is there a rationale for the Use of Lymecycline for Frontal Fibrosing Alopecia? Dermatol Pract Concept. 2024;14(1):e2024018. DOI: https://doi.org/10.5826/dpc.1401a18 Accepted: May 7, 2023; Published: January 2024 Copyright: ©2024 Xavier de Brito et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Flavia Oliveira Xavier de Brito, Boulevard 28 de Setembro, 77 - Vila Isabel, Rio de Janeiro - RJ, 20551-030, Brazil. Email: flaviaoxb@gmail.com Frontal fibrosing alopecia (FFA) is a primary lymphocytic scarring alopecia considered a variant of lichen planopi- laris. It affects mainly postmenopausal women, and its inci- dence has been increasing worldwide [1-3]. Its pathogenesis remains to be fully appreciated, but it seems related to an autoimmune reaction targeting follicular antigens [2,4]. Clinical manifestations include a recession of the fronto- temporal hairline, loss of body hair and eyebrow, and skin changes such as facial papules and lichen planus pigmento- sus. Pruritus, pain and burning happen in variable degrees [2,5-7]. There is no curative treatment for FFA, so therapy aims to control the symptoms and stop its progress [3]. Tetracycline and doxycycline are effective therapeutic options for some types of alopecia due to their anti-inflammatory properties at various levels of the inflammatory cascade [8,9]. Lymecy- cline has also been cited in a few FFA reports, however its wider recommendation requires further studies [10,11]. This article discusses the theoretical rationale for lymecycline as an alternative for FFA. Lymecycline is the semisynthetic byproduct of the tet- racycline ring combined with the amino acid L-lysine. This combination enhances drug absorption and serum levels, increases tissue penetration, and reduces the biodegrada- tion rate [8,9]. It can thus be administered once a day with less phototoxicity or food interaction. The result is a better cost-effective profile compared to its counterparts [8]. Lyme- cycline is a short-acting tetracycline already well-documented for acne treatment [9]. All tetracyclines have antibacterial and anti-inflammatory properties by inhibiting the synthesis of cytokines and macrophage function [8]. Its most frequent side effects include nausea, diarrhea, and headache [8]. Considering that FFA is in great part related to an in- flammatory attack of CD8 T lymphocytes at the bulge level, lymecycline may be able to control this inflammatory pro- cess, as illustrated in Figure 1 [2,10]. A study with patients affected by neutrophilic cicatricial alopecia suggested a dose of 300 mg per day for approximately 3 months, as it showed a better outcome compared to the use of 45 days [8]. The advantages of this regimen are superior gastrointestinal 2 Commentary | Dermatol Pract Concept. 2024;14(1):e2024018 tolerance compared to other tetracyclines and better patient adherence due to a single daily dose of the medication. Short- term maintenance treatment of 300 mg every other day may also be considered in refractory FFA, showing signs of active inflammation [8]. FFA is a distressful condition with a profound psycho- social impact. This article discussed the rationale behind the use of oral lymecycline as a therapeutic option for FFA. The biochemical profile of lymecycline seems to support its effec- tiveness, potentially expanding the armamentarium against FFA. While future randomized controlled trials may clarify the therapeutic impact of lymecycline, the discussion above suggests a promising role for this drug in this challenging disease. References 1. Kerkemeyer KLS, Eisman S, Bhoyrul B, Pinczewski J, Sinclair RD. Frontal fibrosing alopecia. Clin Dermatol. 2021;39(2):183-193. DOI: 10.1016/j.clindermatol.2020.10.007. PMID: 34272007. 2. Iorizzo M, Tosti A. Frontal Fibrosing Alopecia: An Update on Pathogenesis, Diagnosis, and Treatment. Am J Clin Derma- tol. 2019;20(3):379-390. DOI: 10.1007/s40257-019-00424-y. PMID: 30659454. 3. Ramos PM, Anzai A, Duque-Estrada B, et al. Risk factors for frontal fibrosing alopecia: A case-control study in a multiracial population. J Am Acad Dermatol. 2021;84(3):712-718. DOI: 10.1016/j.jaad.2020.08.076. PMID: 32835739. 4. Ho A, Shapiro J. Medical therapy for frontal fibrosing alope- cia: A review and clinical approach. J Am Acad Dermatol. 2019;81(2):568-580. DOI: 10.1016/j.jaad.2019.03.079. Epub 2019 Apr 3. PMID: 30953702. 5. Starace M, Orlando G, Iorizzo M, et al. Clinical and Dermo- scopic Approaches to Diagnosis of Frontal Fibrosing Alopecia: Results From a Multicenter Study of the International Dermos- copy Society. Dermatol Pract Concept. 2022;12(1):e2022080. DOI: 10.5826/dpc.1201a80. PMID: 35223189. PMCID: PMC8824238. 6. Vañó-Galván S, Molina-Ruiz AM, Serrano-Falcón C, et al. Frontal fibrosing alopecia: a multicenter review of 355 patients. J  Am Acad Dermatol. 2014;70(4):670-678. DOI: 10.1016/j .jaad.2013.12.003. PMID: 24508293. 7. Melo DF, Barreto TM, Faro GBA, Machado CJ, Donati A. Occip- ital hairline involvement in frontal fibrosing alopecia: frequency, clinical presentation and trichoscopy findings in a series of twenty patients. J Eur Acad Dermatol Venereol. 2020;34(8):e405-e407. DOI: 10.1111/jdv.16337. PMID: 32153060. 8. Melo DF, Jorge Machado C, Bordignon NL, da Silva LL, Ramos  PM. Lymecycline as a treatment option for dis- secting cellulitis and folliculitis decalvans. Dermatol Ther. 2020;33(6):e14051. DOI: 10.1111/dth.14051. PMID: 32705744. 9. Cunliffe WJ, Meynadier J, Alirezai M, et al. Is combined oral and topical therapy better than oral therapy alone in patients with moderate to moderately severe acne vulgaris? A compar- ison of the efficacy and safety of lymecycline plus adapalene gel 0.1%, versus lymecycline plus gel vehicle. J Am Acad Dermatol. 2003;49(3 Suppl):S218-S226. DOI: 10.1067/s0190 -9622(03)01153-8. PMID: 12963898. 10. MacDonald A, Clark C, Holmes S. Frontal fibrosing alopecia: a review of 60 cases. J Am Acad Dermatol. 2012;67(5):955-961. DOI: 10.1016/j.jaad.2011.12.038. PMID: 22503342. 11. Therianou A, Singh S. Facial papules in frontal fibrosing alo- pecia. J Am Acad Dermatol. 2017;76(6 Suppl 1): AB139. DOI: https://DOI.org/10.1016/j.jaad.2017.04.542. Figure 1. (A) Trichoscopy of a frontal fibrosing alopecia patient before treatment with oral lymecycline showing peripilar scaling. (B) Trichos- copy after treatment with oral lymecycline showing reduction of peripilar scaling.