Vascular abnormalities in FFA, artificial intelligence, and Winston Churchill

By Warren R. Heymann, MD, FAAD
Aug. 23, 2023
Vol. 5, No. 33

If Winston Churchill were a dermatologist, he would say that frontal fibrosing alopecia (FFA) is “a riddle wrapped in a mystery inside an enigma” (which is how he viewed Russia). Almost 30 years have passed since Kossard described six postmenopausal women who developed a progressive frontal hairline recession associated with perifollicular erythema within the marginal hairline, producing a FFA extending to the temporal and parietal hair margins. The histologic findings were indistinguishable from those in lichen planopilaris (LPP). (1)

In 30 short years, FFA has exploded on the dermatology scene. FFA encounters are a daily occurrence in my practice and probably yours. Once a rare oddity, FFA is now the most common cause of cicatricial alopecia worldwide. (2) Although FFA is most common in postmenopausal white women, it may be observed in patients of color, prior to menopause, in men and children. Astute dermatologists will recognize the “lonely hair sign,” eyebrow hair loss, occasional involvement of other hair-bearing sites (extremities, axillae, pubic), facial papules, facial erythema, glabellar follicular red dots, pigmented macules, and prominent and/or depressed forehead veins. (1) Despite having seen innumerable patients with FFA, I was not familiar with depressed forehead veins as a clinical finding. On a follow-up examination of a 67-year-old woman with FFA treated with clobetasol (see image 2) prominent veins on her left forehead were evident. Befuddled by the striking depression correlating exactly with these veins, I questioned whether this was a function of steroid atrophy, as she also displayed fine telangiectasias. This commentary will focus on this clinical feature of FFA.

The pathogenesis of FFA is unknown, although hormonal factors (decreased estrogen and clinical response to 5 alpha-reductase inhibitors), autoimmunity (associated autoimmune thyroid disease, lichen planus, psoriasis, vitiligo, collagen vascular diseases, inflammatory bowel disease, others), genetics (familial cases of FFA have been reported), and exogenous factors (most famously, sunscreens) have been implicated. (3) According to Robinson et al, “There is insufficient evidence to establish a direct causal relationship between sunscreen and FFA. Further studies are required to better characterize the role of sunscreen and the environment in the pathogenesis of this unique disease.” (4) The jury is still out regarding sunscreen use and FFA; I suspect it will continue to be a hung jury years after I retire.

Vañó-Galván et al reported 11 Caucasian women with histologically confirmed FFA who presented with different grades of depression of the frontal veins at their first visit. The frontal veins were evident due to atrophy of the overlying skin of the forehead. Upon palpation, a marked depression was appreciated. The depression of the frontal veins was more frequently located in the center of the forehead and was not present at other locations. Four patients had not used topical or intralesional steroids in this area. The remainder of the patients indicated that they had noticed this sign during the first months of presenting with a hairline recession, before having applied any topical treatments. Biopsies of two patients demonstrated marked dermal atrophy and dermal fibrosis with a dilated vein in the subcutaneous tissue. (5) González-Guerra reported a 59-year-old woman with FFA treated only with vitamins and anti-hair loss shampoos with notable depression of her frontal veins, suggesting that this sign is helpful diagnostically. (6)

---

Therapy for FFA is suboptimal with a litany of topical agents (steroids, calcineurin inhibitors, minoxidil), intralesional injections (triamcinolone, PRP), oral medications (tetracyclines, 5 alpha-reductase inhibitors (finasteride, dutasteride, pioglitazone, potentially JAK inhibitors), hydroxychloroquine, isotretinoin, minoxidil, immunosuppressants (mycophenolate mofetil, methotrexate, others), surgery (hair transplantation, hairline lowering surgery), and lasers (excimer, CO2), which have been used individually or in combination. (2) Sun et al reported improvement in facial vein prominence utilizing the Nd:YAG laser in five FFA patients. (7)

I am fascinated and mystified by this clinical sign. I agree with Vañó-Galván et al with the hypothesis that scarring produced by FFA may be responsible for skin atrophy and the depression of frontal veins — but why? Steroids may aggravate the process but are not pathogenic. In an effort to gain further insight, I decided to use the popular artificial intelligence tool ChatGPT that has been causing plagiarism tremors in the academic community (see below). I hoped it would actually write my commentary, but it was not particularly helpful. (Chalk one up for humans, for now!) Understanding the pathomechanism underlying depressed frontal veins in FFA will require more research. Winston Churchill’s take would be, “Continuous effort — not strength or intelligence — is the key to unlocking our potential.”

Point to Remember: Dilated, depressed frontal veins are a clinical sign of frontal fibrosing alopecia.

Our expert’s viewpoint

Steven Kossard, FACD, PhD, FAAD
Director, Kossard/Laverty Dermatopathologists
Macquarie Park, NSW Australia

The observation of dilated, depressed frontal veins as a clinical sign is puzzling as the primary process in FFA is targeted destruction of follicles expressed as LPP. In LPP destroyed follicles are replaced by vertical orientated small diameter fibrous tracts. The process is a concentric perifollicular fibrosis culminating in fibrous tracts. Interfollicular scarring is absent. It is possible that the fibrous tracts undergo progressive vertical contraction leading to dermal constriction which is more marked around veins leading to depressed veins.

I have struggled with the pathogenesis of FFA for 30 years and the challenge of formulating a conceptual framework to accommodate the main genetic, epidemiological, clinical, and histopathological aspects. The model I have proposed is linked to the difference between female pattern hair loss (FPHL) and male pattern alopecia (MPA) with the preservation of the frontal hairline in women. In comparison, MPA has a variant of progressive frontal alopecia clinically resembling marked FFA and not driven by LPP. In contrast to frontal MPA, FFA is driven by LPP as a late senescent hormonally related progressive pattern alopecia.

Initially, I considered FFA to be a longstanding but uncommon form of hair loss that had not been recognized by dermatologists but clearly this is not the case and there is an additional catalyst apart from the change in hormonal profile in menopause. Women developing FFA may have a genetic trait shared with progressive frontal MPA but the frontal hairline is protected by hormones. (8) The preserved immune privilege in this site is lost but the process inducing LPP as a driving force needs to have a catalyst. This may include a variety of topically derived triggers including still-to-be-defined ingredients in sunscreens, cosmetics, and moisturizers introduced in recent decades.

ChatGPT accessed Jan. 17, 2023

What vascular changes occur in patients with frontal fibrosing alopecia?

Frontal fibrosing alopecia is a type of scarring alopecia, which is a type of hair loss caused by inflammation of the hair follicles. In frontal fibrosing alopecia, the inflammation causes the hair follicles to shrink and eventually disappear. This leads to permanent hair loss in the frontal and temporal areas of the scalp. The vascular changes associated with frontal fibrosing alopecia include increased vascularity in the affected areas, as well as increased vascular permeability, which can lead to further hair loss.

1. ZKossard S. Postmenopausal frontal fibrosing alopecia. Scarring alopecia in a pattern distribution. Arch Dermatol. 1994 Jun;130(6):770-4. Erratum in: Arch Dermatol 1994 Nov;130(11):1407. PMID: 8002649.

2. Kerkemeyer KLS, Eisman S, Bhoyrul B, Pinczewski J, Sinclair RD. Frontal fibrosing alopecia. Clin Dermatol. 2021 Mar-Apr;39(2):183-193. doi: 10.1016/j.clindermatol.2020.10.007. Epub 2020 Oct 17. PMID: 34272007.

3. Porriño-Bustamante ML, Fernández-Pugnaire MA, Arias-Santiago S. Frontal Fibrosing Alopecia: A Review. J Clin Med. 2021 Apr 21;10(9):1805. doi: 10.3390/jcm10091805. PMID: 33919069; PMCID: PMC8122646.

4. Robinson G, McMichael A, Wang SQ, Lim HW. Sunscreen and frontal fibrosing alopecia: A review. J Am Acad Dermatol. 2020 Mar;82(3):723-728. doi: 10.1016/j.jaad.2019.09.085. Epub 2019 Oct 22. PMID: 31654665.

5. Vañó-Galván S, Rodrigues-Barata AR, Urech M, Jiménez-Gómez N, Saceda-Corralo D, Paoli J, Cuevas J, Jaén P. Depression of the frontal veins: A new clinical sign of frontal fibrosing alopecia. J Am Acad Dermatol. 2015 Jun;72(6):1087-8. doi: 10.1016/j.jaad.2015.02.1129. PMID: 25981009.

6. González-Guerra E. Depression of the Frontal Veins in Frontal Fibrosing Alopecia. Actas Dermosifiliogr (Engl Ed). 2018 Oct;109(8):748. English, Spanish. doi: 10.1016/j.ad.2017.09.028. Epub 2018 Jun 11. PMID: 29903465.

7. Sun L, Mehrabi S, Khetarpal S, Piliang M. Characterization and treatment of prominent facial vasculature in the setting of frontal fibrosing alopecia. J Am Acad Dermatol. 2023 Jan;88(1):174-176. doi: 10.1016/j.jaad.2021.12.051. Epub 2022 Jan 6. PMID: 34998963.

8. Kossard S. Frontal fibrosing alopecia, just lichen planopilaris? J Am Acad Dermatol 2019Aug;81:e51.doi:10.1016

---