Systemic Comorbidities in Central Centrifugal Cicatricial Alopecia: A Systematic Review and Meta-analysis
DOI:
https://doi.org/10.2340/actadv.v106.adv-2026-0456Keywords:
Central centrifugal cicatricial alopecia, Scarring alopecia, Comorbidity, Cardiometabolic diseases, Gynecologic conditions, Systematic ReviewAbstract
Central centrifugal cicatricial alopecia (CCCA) is the most common scarring alopecia among women of African descent and has been increasingly associated with systemic comorbidities, particularly cardiometabolic and fibroproliferative conditions. We conducted a PRISMA 2020 compliant systematic review and random-effects meta-analysis, prospectively registered in PROSPERO (CRD420250656067), to quantify pooled prevalence estimates and case–control associations for comorbidities in CCCA. MEDLINE and Embase were searched through 18 June 2025 for observational studies reporting comorbidities in CCCA. Twenty three studies, comprising 9,103 patients with CCCA, were eligible. Hypertension (51.9%, 95% CI 33.8–69.6), dyslipidemia (58.4%, 95% CI 29.0 82.8), obesity (37.1%, 95% CI 10.8–74.2) and uterine leiomyomas (28.0%, 95% CI 8.0–64.0) were frequently reported, with substantial heterogeneity across studies. In case–control analyses, CCCA was significantly associated with dyslipidaemia (OR 4.46, 95% CI 1.09–18.25), uterine leiomyomas (OR 2.25, 95% CI 1.10–4.58) and anxiety disorders (OR 3.27, 95% CI 1.22–8.79), whereas hypertension, obesity and thyroid disease were not consistently associated. Most included studies were retrospective and predominantly U.S.-based, contributing to methodological heterogeneity. These findings suggest that CCCA may be accompanied by a substantial burden of medically recorded systemic comorbidities and support holistic, individualized clinical assessment.
Downloads
References
Olsen EA, Bergfeld WF, Cotsarelis G, Price VH, Shapiro J, Sinclair R, et al. Summary of North American Hair Research Society (NAHRS)-sponsored workshop on cicatricial alopecia, Duke University Medical Center, February 10 and 11, 2001. J Am Acad Dermatol 2003; 48: 103–110. DOI: https://doi.org/10.1067/mjd.2003.68
Ogunleye TA, McMichael A, Olsen EA. Central centrifugal cicatricial alopecia: what has been achieved, current clues for future research. Dermatol Clin 2014; 32: 173–181. DOI: https://doi.org/10.1016/j.det.2013.12.005
Gathers RC, Lim HW. Central centrifugal cicatricial alopecia: past, present, and future. J Am Acad Dermatol 2009; 60: 660–668. DOI: https://doi.org/10.1016/j.jaad.2008.09.066
Harries MJ, Trueb RM, Tosti A, Messenger AG, Chaudhry I, Whiting DA, et al. How not to get scar(r)ed: pointers to the correct diagnosis in patients with suspected primary cicatricial alopecia. Br J Dermatol 2009; 160: 482–501. DOI: https://doi.org/10.1111/j.1365-2133.2008.09008.x
Jackson TK, Sow Y, Ayoade KO, Seykora JT, Taylor SC, Ogunleye T. Central centrifugal cicatricial alopecia in males. J Am Acad Dermatol 2023; 89: 1136–1140. DOI: https://doi.org/10.1016/j.jaad.2023.07.1011
Olsen EA, Callender V, McMichael A, Sperling L, Anstrom KJ, Shapiro J, et al. Central hair loss in African American women: incidence and potential risk factors. J Am Acad Dermatol 2011; 64: 245–252. DOI: https://doi.org/10.1016/j.jaad.2009.11.693
Mobini N, Tam S, Kamino H. Possible role of the bulge region in the pathogenesis of inflammatory scarring alopecia: lichen planopilaris as the prototype. J Cutan Pathol 2005; 32: 675–679. DOI: https://doi.org/10.1111/j.0303-6987.2005.00399.x
Cotsarelis G. Epithelial stem cells: a folliculocentric view. J Invest Dermatol 2006; 126: 1459–1468. DOI: https://doi.org/10.1038/sj.jid.5700376
Onamusi T, Larrondo J, McMichael AJ. Clinical factors and hair care practices influencing outcomes in central centrifugal cicatricial alopecia. Arch Dermatol Res 2023; 315: 2375–2381. DOI: https://doi.org/10.1007/s00403-023-02630-5
Dlova NC, Jordaan FH, Sarig O, Sprecher E. Autosomal dominant inheritance of central centrifugal cicatricial alopecia in black South Africans. J Am Acad Dermatol 2014; 70: 679–682. DOI: https://doi.org/10.1016/j.jaad.2013.11.035
Malki L, Sarig O, Romano MT, Méchin MC, Peled A, Pavlovsky M, et al. Variant PADI3 in central centrifugal cicatricial alopecia. N Engl J Med 2019; 380: 833–841. DOI: https://doi.org/10.1056/NEJMoa1816614
Keller-Rosenthal N, Sarig O, Giladi M, Malovitski K, Rubinstein R, Haitin Y, et al. Pathogenic variants affecting peptidyl arginine deiminase 3 and its major substrates underlie central centrifugal cicatricial alopecia. J Invest Dermatol 2026; 146: 1596–1604. DOI: https://doi.org/10.1016/j.jid.2025.10.609
Smith SDB, Woddor N, Cassarino DS, Chen W, Clemetson N, Nava VE. Central centrifugal cicatricial alopecia associated with PDL1 loss and increased expression of caspase 3: a case series. Am J Dermatopathol 2023; 45: 418–422. DOI: https://doi.org/10.1097/DAD.0000000000002428
Gadre A, Dyson T, Lai J, Aguh C. Increased IL-1β in stratum corneum as a marker of inflammation among central centrifugal cicatricial alopecia patients with pruritus: an observational study. JAAD Int 2023; 13: 195–197. DOI: https://doi.org/10.1016/j.jdin.2023.09.005
Roche FC, Hedberg ML, Fischer AS, Ray A, Dentchev T, Rice X, et al. Activation of STAT3 in lymphocytes associated with central centrifugal cicatricial alopecia. J Am Acad Dermatol 2023; 89: 1245–1246. DOI: https://doi.org/10.1016/j.jaad.2023.01.045
Aguh C, Dina Y, Talbot CC Jr, Garza L. Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia. J Am Acad Dermatol 2018; 79: 904–912. DOI: https://doi.org/10.1016/j.jaad.2018.05.1257
Rivera-Ruiz I, Ungar B, Dávila-Flores V, Gay-Mimbrera J, Gómez-Arias PJ, Juan-Cencerrado M, et al. Unravelling the transcriptomic landscape of primary lymphocytic scarring alopecias: systematic review and meta-analysis. Front Immunol 2025; 16: 1651019. DOI: https://doi.org/10.3389/fimmu.2025.1651019
Sundberg JP, Taylor D, Lorch G, Miller J, Silva KA, Sundberg BA, et al. Primary follicular dystrophy with scarring dermatitis in C57BL/6 mouse substrains resembles central centrifugal cicatricial alopecia in humans. Vet Pathol 2011; 48: 513–524. DOI: https://doi.org/10.1177/0300985810379431
Gadre A, Dyson T, Jedrych J, Anhalt G, Byrd AS, Aguh C. Proteomic profiling of central centrifugal cicatricial alopecia reveals role of humoral immune response pathway and metabolic dysregulation. JID Innov 2024; 4: 100263. DOI: https://doi.org/10.1016/j.xjidi.2024.100263
Roche FC, Fischer AS, Williams D, Ogunleye T, Seykora JT, Taylor SC. Central centrifugal cicatricial alopecia: histologic progression correlates with advancing age. J Am Acad Dermatol 2022; 86: 178–179. DOI: https://doi.org/10.1016/j.jaad.2021.01.028
Subash J, Alexander T, Beamer V, McMichael A. A proposed mechanism for central centrifugal cicatricial alopecia. Exp Dermatol 2020; 29: 190–195. DOI: https://doi.org/10.1111/exd.13664
Leung B, Lindley L, Reisch J, Glass DA II, Ayoade K. Comorbidities in patients with central centrifugal cicatricial alopecia: a retrospective chart review of 53 patients. J Am Acad Dermatol 2023; 88: 461–463. DOI: https://doi.org/10.1016/j.jaad.2022.06.013
Roche FC, Harris J, Ogunleye T, Taylor SC. Association of type 2 diabetes with central centrifugal cicatricial alopecia: A follow-up study. J Am Acad Dermatol 2022; 86: 661–662. DOI: https://doi.org/10.1016/j.jaad.2021.02.036
Brown-Korsah JB, Roche FC, Taylor SC. Association of breast and colorectal cancer in patients with central centrifugal cicatricial alopecia: a retrospective, cross-sectional pilot study. J Am Acad Dermatol 2021; 84: 859–860. DOI: https://doi.org/10.1016/j.jaad.2020.10.044
Collins MS, Ali S, Wiss IP, Senna MM. Increased risk of vitamin D deficiency and insufficiency in Black patients with central centrifugal cicatricial alopecia. J Am Acad Dermatol 2022; 87: 689–691. DOI: https://doi.org/10.1016/j.jaad.2022.02.018
Hagigeorges D, Manatis-Lornell A, Marks DH, Okhovat JP, Senna MM. Patients with central centrifugal cicatricial alopecia: identifying gynecologic comorbidities. J Am Acad Dermatol 2019; 81: AB101. DOI: https://doi.org/10.1016/j.jaad.2019.06.389
Ayandibu G, Bergfeld W. Retrospective cohort study to assess the prevalence of different factors of metabolic syndrome in central centrifugal cicatricial alopecia patients. J Am Acad Dermatol 2018; 79: AB246. DOI: https://doi.org/10.1016/j.jaad.2018.05.979
Ali S, Collins M, Taylor SC, Kelley K, Stratton E, Senna M. Type 2 diabetes mellitus and central centrifugal cicatricial alopecia severity. J Am Acad Dermatol 2022; 87: 1418–1419. DOI: https://doi.org/10.1016/j.jaad.2022.08.031
Jafari AJ, Brown C, Echuri H, Murina AT. Lack of association between comorbidities and central centrifugal cicatricial alopecia: a retrospective cohort study of 153 patients. J Am Acad Dermatol 2023; 88: e101–e103. DOI: https://doi.org/10.1016/j.jaad.2022.09.056
Joshi TP, Duruewuru A, Garcia D, Mireles N, Truong P, Cockerell CJ. Comorbidities in patients with central centrifugal cicatricial alopecia: a case-control study. Int J Dermatol 2024; 63: e37–e39. DOI: https://doi.org/10.1111/ijd.16932
Bao A, Bordone LA, Aguh C. A review of metabolic dysregulation in lymphocytic cicatricial alopecia: exploring the connections and therapeutic implications. J Invest Dermatol 2025; 145: 2153–2161. DOI: https://doi.org/10.1016/j.jid.2025.01.036
Dina Y, Okoye GA, Aguh C. Association of uterine leiomyomas with central centrifugal cicatricial alopecia. JAMA Dermatol 2018; 154: 213–214. DOI: https://doi.org/10.1001/jamadermatol.2017.5163
Samrao A, Lyon L, Mirmirani P. Evaluating the association of central centrifugal cicatricial alopecia (CCCA) and fibroproliferative disorders. Dermatol Online J 2021; 27: 27. DOI: https://doi.org/10.5070/D327854688
Narasimman M, De Bedout V, Castillo DE, Miteva MI. Increased association between previous pregnancies and use of chemical relaxers in 74 women with central centrifugal cicatricial alopecia. Int J Trichology 2020; 12: 176–181. DOI: https://doi.org/10.4103/ijt.ijt_37_20
Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol 2003; 188: 100–107. DOI: https://doi.org/10.1067/mob.2003.99
Jamerson TA, Talbot CC Jr, Dina Y, Aguh C. Presence of uterine leiomyomas has no significant impact on gene expression profile in the scalp of patients with central centrifugal cicatricial alopecia. JID Innov 2022; 2: 100060. DOI: https://doi.org/10.1016/j.xjidi.2021.100060
McKenzie SA, Roche FC, Onyekaba G, Williams DM, Ogunleye TA, Taylor SC. Comorbid anxiety and depression among black women with central centrifugal cicatricial alopecia: a retrospective study. J Dermatol 2021; 48: e19. DOI: https://doi.org/10.1111/1346-8138.15595
Kershaw KN, Osypuk TL, Do DP, De Chavez PJ, Diez Roux AV. Neighborhood-level racial/ethnic residential segregation and incident cardiovascular disease: the multi-ethnic study of atherosclerosis. Circulation 2015; 131: 141–148. DOI: https://doi.org/10.1161/CIRCULATIONAHA.114.011345
Additional Files
Published
How to Cite
License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All digitalized ActaDV contents is available freely online. The Society for Publication of Acta Dermato-Venereologica owns the copyright for all material published until volume 88 (2008) and as from volume 89 (2009) the journal has been published fully Open Access, meaning the authors retain copyright to their work.
Unless otherwise specified, all Open Access articles are published under CC-BY-NC licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.