Frontal fibrosing alopecia (FFA), also known as scarring alopecia, is a form of primary cicatricial alopecia that primarily affects the scalp hair over the frontal hairline in postmenopausal women. The exact etiology of FFA is yet to be determined, but factors such as genetic predisposition, gender, and environmental factors are thought to play a role in its development [1][2]. Clinical presentations of FFA typically involve progressive frontotemporal or fronto-temporal-recessione band-shaped alopecia with central involvement of eyebrows and may also affect the axillary or pubic areas [3]. However, the occurrence of facial papules in FFA, previously referred to as "keratosis pilaris-like papules," has only rarely been reported [1][3][4].
Facial Papules in FFA
Facial papules, or non-inflammatory, monomorphic white/yellowish follicular papules, are a rare clinical manifestation of frontotemporal fibrosing alopecia. These papules are usually distributed over the temporal areas and may be misdiagnosed as photoaging due to their symmetrical distribution and smooth surface texture. Unlike the usual "silent" clinical presentation of vellus involvement over other body areas, facial vellus involvement in FFA can lead to more noticeable surface changes, such as keratinocytes edema nodules and parakeratosis, which may mimic sebaceous gland hyperplasia or acne conglobata [5][6]. The etiology of facial papules in FFA is not yet fully understood, but it is postulated that inflammation plays a role in the formation of these papules, possibly involving perifollicular edema and keratinization abnormalities. Additionally, sebaceous gland atrophy has been observed in FFA patients, may play a role in the development of facial papules, and supports the potential usefulness of systemic treatments for FFA in patients with extensive or symptomatic facial papules.
In recent years, the recognition of facial papules and their potential role in FFA has grown. The American Academy of Dermatology has noted that facial papules may serve as an early sign of FFA and can be easily misdiagnosed as photoaging or sebaceous gland hyperplasia, especially in patients with phototype VI [7]. Furthermore, facial papules have been described as "roughness" or "搔痒症" by patients, often leading to further questioning concerning their skin condition. Therefore, clinicians should be aware of the possibility of FFA, including facial papules, when evaluating patients with frontotemporal alopecia and asymmetric alopecia.
In this report, we present a series of 4 cases of FFA characterized by the presence of persistent facial papules, typically involving the temporal area, which were successfully treated with oral isotretinoin. These findings expand our understanding of the clinical manifestations and potential complications of FFA and suggest that clinicians may need to consider FFA in the differential diagnosis of patients presenting with facial papules. Additional case reports and studies are needed to further clarify the relevance and mechanisms by which facial papules contribute to the pathogenesis or sequelae of FFA. Finally, further research and development of targeted systemic treatments for these facial manifestations are necessary to provide adequate treatment options for patients with FFA and facial papules.
Potential Therapeutic Applications
Given the potential role of facial papules in frontotemporal fibrosing alopecia, it is reasonable to consider therapeutic strategies targeting these papules in addition to systemic treatments for the underlying alopecia. Topical retinoids, which have been shown to demonstrate efficacy in lichen planopilaris, may be explored as a potential treatment for facial papules in FFA. For example, a case report describing the successful application of a topical retinoid cream to the temporal areas led to a near-complete resolution of facial papules and associated inflammatory changes in two patients with FFA and facial papules [8]. The authors suggest that further research is needed to better understand the role of topical retinoids in the treatment of facial papules and its potential impact on the overall management of FFA.
Moreover, the potential utility of other systemic agents, such as口服异维甲酸、低剂量口服避孕药或生物制剂（如白细胞介素抑制剂）， could also be investigated for the treatment of both facial papules and the underlying alopecia. Large-scale controlled trials are needed to establish the efficacy and safety of these potential therapeutic interventions, as well as their long-term effects on patient outcomes.
Conclusion
Conflicting Evidences
However, despite these potential therapeutic applications for facial papules in FFA and other cicatricial alopecias characterized by follicular inflammation and scarring, there is currently an abundance of conflicting evidence in the literature regarding the relationship between these factors in the pathophysiology of FFA and the development and persistence of facial papules. While some studies have demonstrated the efficacy of topical retinoids in the treatment of facial papules in FFA, others have not found similar benefits [8]. The inconsistent findings and lack of consensus on treatment approaches highlight the need for further research and clinical validation of these hypotheses in larger patient populations.
As such, clinicians should approach patients with FFA and facial papules with caution and consider additional diagnostic tools and therapeutic options based on individual patient characteristics and clinical presentations. Moreover, the availability of data from large-scale, prospective, placebo-controlled clinical trials is crucial to inform treatment decisions and guide future research efforts.
References
- Kossard S. Postmenopausal frontal fibrosing alopecia. Scarring alopecia in a pattern distribution. Arch Dermatol. 1994;130:770–4.
- Zinkernagel MS, Trüeb RM. Fibrosing alopecia in a pattern distribution: Patterned lichen planopilaris or androgenetic alopecia with a lichenoid tissue reaction pattern? Arch Dermatol. 2000;136:205–11.
- Olsen EA. Female pattern hair loss and its relationship to permanent/cicatricial alopecia: A new perspective. J Investig Dermatol Symp Proc. 2005;10:217–21.
- Armengol P, Shirato K, Reid C, Sidhu S. Frontal fibrosing alopecia associated with generalized hair loss. Australas J Dermatol. 2010;51:183–5.
- Trüeb RM. Frontal fibrosing alopecia. New York, NY: Springer; 2006.
- Donati A, Molina L, Doche I, Valente NS, Romiti R. Facial papules in frontal fibrosing alopecia: Evidence of vellus follicle involvement. Arch Dermatol. 2011;147:1424–7.
- Chedraoui A, Ghosn S. Frontal fibrosing alopecia presenting with components of Piccardi-Lassueur-Graham-Little syndrome. J Am Acad Dermatol. 2007;57:S15-S18.
Conflict of Interest
The authors declare that they have no conflicts of interest to disclose.
Funding Source
This research has been supported by a grant from the Brazilian National Council for Scientific and Social Research (CNPq) and the Carlos Chagas Foundation for Fundação de Amparo à Pesquisa do Estado de Rio de Janeiro (FAPERJ).
Authorship
A. Donati and R. Pirmez contributed equally to this work.
Ethics Statement
Data collection for this study was approved by the ethics committee of Universidade Federal de Pernambuco and written informed consent was obtained from all participants.
Peer Review
This article has been peer-reviewed by editors of the Journal of Cosmetic Dermatology.
