Eyebrow and Eyelash Alopecia A Clinical Review

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American Journal of Clinical Dermatology

https://doi.org/10.1007/s40257-022-00729-5

REVIEW ARTICLE

Eyebrow and Eyelash Alopecia: A Clinical Review


Betty Nguyen1,2   · Jamie Katy Hu1 · Antonella Tosti1

Accepted: 31 August 2022


© The Author(s) 2022

Abstract
Madarosis is characterized by either complete or partial loss of eyebrow or eyelash hair. Etiologies for madarosis are varied,
and accurate diagnosis is the first step in clinical management. Many studies have described findings related to specific
causes of madarosis, but few have summarized the collective literature. The purpose of this review is to provide an updated
overview on the symptomatology, diagnosis, trichoscopy findings, and treatment of eyebrow and eyelash alopecia.

Key Points  treatments. Etiologies of madarosis are varied, and include


autoimmune, endocrinologic, infectious, genetic, neoplas-
Etiologies of eyebrow and eyelash alopecia include auto- tic, nutritional, and traumatic conditions. Madarosis can
immune, endocrinologic, genetic, infectious, neoplastic, be classified as scarring or non-scarring, depending on the
nutritional, and traumatic conditions. cause. Given the extensive breadth of etiology, prompt and
accurate diagnosis is the first step in clinical management.
Trichoscopy is a useful tool to aid in diagnosis of alope-
Unfortunately, few standardized diagnostic pathways and
cia areata, frontal fibrosing alopecia, tinea infection, and
treatment regimens exist in the management of eyebrow
trichotillomania, and treatment is focused on targeting
and eyelash alopecia, further underscoring the importance
the underlying disease.
of early recognition and treatment. In this review, we provide
a summary of the function, anatomy, and life cycle of eye-
brows and eyelashes, in order to comprehensively review the
causes, clinical features, and approach to madarosis.

1 Introduction
2 Anatomy, Life Cycle, Function, and Clinical
Complete or partial eyebrow and eyelash loss can present Significance
as an isolated finding or as the presenting manifestation of
an underlying systemic pathology. Madarosis often refers to 2.1 Anatomy
the loss of eyebrow or eyelashes, whereas milphosis specifi-
cally refers to loss of eyelashes. Due to the many functional Human eyebrows are composed of short, obliquely set hairs
and cosmetic roles of eyebrows and eyelashes, madarosis arranged in arches supra-orbitally. The medial eyebrow hairs
can cause significant distress to patients, necessitating rec- are nearly vertically oriented and become progressively
ognition of potential associated underlying diseases and more horizontal laterally along the brow [1]. The shape and
orientation of eyebrows allows the eyebrows to protect our
eyes from light, sweat, and dust. Although the number of
eyebrow hairs varies widely amongst the population, the
* Betty Nguyen
[email protected] density of eyebrows typically remains stable over time [2].
The eyebrows and nearby glabellar region contain numerous
1
Dr. Phillip Frost Department of Dermatology and Cutaneous sebaceous glands [3].
Surgery, University of Miami Miller School of Medicine, The eyelashes consist of curved sensory hairs originating
1295 NW 14th St, Suite L, Miami, FL 33125, USA
from the eyelid margins. Compared to scalp skin, which is
2
University of California Riverside School of Medicine, comprised of the epidermis, dermis, and hypodermis, the
Riverside, CA, USA

Vol.:(0123456789)
B. Nguyen et al.

skin of eyelids contains a thinner epidermis and no hypo- madarosis has been associated with significant emotional
dermis [4]. Eyelashes are rooted approximately 2 mm deep and psychologic distress. In one study on body image in
into the dermis and lack the arrector pili muscles associated women with breast cancer, 52% of women who experienced
with most other hair follicles [4, 5]. Humans typically have alopecia or loss of eyebrows and eyelashes reported fearing
about 90–160 eyelashes on the upper lids, spread across five what others thought of them and 25% reported newfound
to six rows, and 75–80 eyelashes on the lower lids, dispersed anxiety due to their eyebrow and eyelash alopecia [15]. Loss
between three to four rows [5]. Distribution of eyelashes of eyebrows and eyelashes can also negatively impact self-
among different rows ensures that eyelashes can be shed image, further underscoring the importance of diagnosis and
without leaving unprotected gaps [6]. Eyelash follicles are treatment [16, 17].
maintained by the holocrine glands of Zeis and the apo-
crine glands of Moll, which secrete sebum and immunologic
enzymes to maintain eyelash health [7]. 3 Methods

We performed a literature search on PubMed/MEDLINE for


2.2 Life Cycle articles that described trichoscopy and treatment of eyebrow
and eyelash alopecia published before June 2022. The names
The life cycles of the eyebrows and eyelashes differ from of each disease/disorder were queried as search terms, along
other pilosebaceous units on the body, and understanding with the keywords “eyebrow” OR “eyelash” AND “hair loss”
their unique physiology is essential to diagnosis and treat- OR “alopecia” AND “trichoscopy” OR “treatment.” Pub-
ment of associated disease. Contrary to scalp hair follicles, lished, peer-reviewed articles were reviewed and selected.
which have anagen phases of 2–8 years, the anagen phase Two reviewers screened titles and abstracts for relevance,
of eyebrows typically lasts for 2–3 months, catagen for 2–3 and articles that were not in English, presented redundant
weeks, and telogen for 2–3 months [8, 9]. Eyelashes also information, or did not relate to trichoscopy or treatment
have a shorter life cycle of approximately 4–11 months [5]. of eyebrow or eyelash alopecia in humans were excluded.
Eyelashes can grow about 0.12–0.14 mm per day in the ana- Discrepancies were resolved by a third reviewer. We fur-
gen stage [10], which lasts for about 4–10 weeks [5]. The ther searched the references and related articles. Additional
catagen phase of eyelashes is approximately 15 days, and articles on eyebrow and eyelash anatomy, life cycle, func-
the telogen between 4 and 9 months [5]. It is believed that tion, and clinical significance of madarosis were selectively
eyebrow and eyelash length is limited by the short anagen included. A total of 136 articles were included in this review.
phase.
Eyebrow and eyelash thinning and whitening can occur
as a presentation of physiologic aging [11, 12]. However, 4 Etiologies and Trichoscopy Findings
in other individuals, mainly men, advancing age can also
present as eyebrow thickening, rather than thinning. The Eyebrow and eyelash alopecia are often accompanied by
mechanisms of these age-related hair changes are unclear. other affected areas of hair loss, which may assist in diag-
nosis. In cases of isolated eyebrow and eyelash involvement,
2.3 Function and Clinical Significance we recommend trichoscopy as the first best step to distin-
guish among different conditions.
In humans, eyebrows and eyelashes serve multifaceted
purposes, ranging from protection of the eye to emotional 4.1 Autoimmune
expression. Overlying the orbital ridge and eye, the eyebrows
and eyelashes protect these underlying structures from exter- Alopecia areata (AA) involving the eyebrows presents as
nal assault, including sweat, rain, light, dust, microorgan- bilateral, patchy eyebrow loss, whereas eyelash involve-
isms, and other particulate matter [6]. It has been hypoth- ment often presents as bilateral, patchy eyelash loss in the
esized that the density and organization of eyelashes plays upper and lower eyelids (Fig. 1). Although isolated eyelash
a role in the aerodynamic flow of air around the eye and in involvement is rare, eyelash alopecia has been reported as
the protection of the cornea [10]. An essential component the presenting sign of AA, particularly of severe AA [18,
of non-verbal communication, eyebrows are also integral to 19].
the expression of emotions [10]. They are well-documented Trichoscopic features of AA of eyebrows and eyelashes
to serve an important cosmetic function, with their enhance- are often subtle [20]. Exclamation point hairs are not very
ment documented as early as ancient Egypt [13, 14]. numerous, but cadaverized hairs and yellow dots are usually
Due to the varied functional and emotive purposes of eye- visible (Table 1). Severity of the disease can be assessed
brows and eyelashes, as well as the visibility of the hairs, using the clinician-reported outcome (ClinRO) and the
Eyebrow and Eyelash Alopecia: A Clinical Review

of FFA, its frequency varies among different studies and


ethnic groups. In a cohort study of 58 Asian females with
FFA, 69.0% (40/58) had eyebrow loss, and 5.2% (3/58) had
eyelash loss [28]. Eyebrow alopecia was the first symptom
of FFA in 3.4% (2/58) of these patients [28]. Interestingly,
the authors found that 83.3% of patients with linear pattern
FFA experienced eyebrow loss, compared to only 52% of
patients with the pseudo-fringe sign [28]. In a retrospec-
tive analysis of 118 white and 21 black patients with FFA,
eyebrow involvement was observed in 63.6% (75/118) and
52.4% (11/21) and eyelash involvement was observed in
2.5% (3/118) and 9.5% (2/21), respectively, with no sig-
nificant differences in frequency found [29]. Eyebrow loss
preceded loss of scalp hair in 43.7% (66/151) of patients in
one study in Brazil and Italy [30].
Fig. 1  Patient with alopecia areata presenting with patchy eyebrow The most relevant trichoscopy findings of eyebrow FFA
loss and patchy eyelash loss of the upper and lower eyelids include tapered and broken hairs, multiple pinpoint dots,
short thin/vellus hairs, hair growing in different directions,
dystrophic hairs, black dots (cadaverized hairs), red dots
patient-reported outcome (PRO) for eyebrow and eyelash (follicular openings with increased vasculature), and yellow
loss [21]. ClinRO and PRO are based on a scale rating from dots (follicular infundibula with sebum or keratotic mate-
0 (no involvement) to 3 (complete loss). [21]. Other newly rial) (Fig. 2c) [30–32]. In contrast to scalp FFA, affected
developed scales include the Brigham Eyebrow Tool for eyebrows often demonstrate non-scarring features on der-
Alopecia (BETA) and Brigham Eyelash Tool for Alopecia moscopy and histology, including preservation of the folli-
(BELA). The BETA utilizes eyebrow landmarks, surface cular ostia and sebaceous glands, respectively [30, 33]. The
area of involvement, and hair density to calculate an eye- reversibility of some eyebrow loss in FFA could be attrib-
brow score [22], while the BELA utilizes eyelash count, uted to these features. Since the most common findings of
distribution, and prominence of hairs of the upper lashes to eyebrow FFA (yellow dots, multiple pinpoint dots, and short
establish its score [23]. These validated scores may be effec- thin/vellus hairs) are also seen in noncicatricial alopecia,
tive means of quantitatively monitoring progression of AA these findings alone are not enough to reach the diagnosis
of the eyebrows and eyelashes, as well as treatment response [30]. Dystrophic hairs, whitish areas with absent follicular
over time [22, 23]. openings (signifying cicatricial hair loss), and hairs growing
The prevalence of eyebrow and eyelash involvement is in different directions are more specific trichoscopy find-
not precisely known. In a cross-sectional study conducted ings of eyebrow FFA that can assist in diagnosing patients
in Japan of 587 patients with AA, 19.8% (116/587) reported with isolated eyebrow loss [34]. The presence of red dots on
current eyebrow hair loss and 10.1% (59/587) reported cur- eyebrow trichoscopy may be a favorable prognostic factor
rent eyelash hair loss [24]. Prevalence was much higher for eyebrow regrowth [30, 35]. The presence of pili torti
in a Danish cohort study of 1494 patients with AA, with may be a sign of fibrosis and a predictor of poor treatment
approximately 62.8% reporting current eyebrow loss and response [32].
56.4% reporting current eyelash loss [25]. Of these, 36.2% The most common findings on eyelash trichoscopy
of patients reported having no or barely any eyebrow hairs include dystrophic hairs (75%), black dots (50%), visuali-
(PRO score of 3), 10.3% reported having large gaps or thin- zation of hair bulbs (50%) (typically on the upper eyelids),
ning (PRO score of 2), and 16.3% reported minimal gaps or and ingrown hairs (46.9%) [26]. Trichoscopy may be able
thinning (PRO score of 1), whereas 32.2% reported having to detect early eyelash changes in FFA. In one study of 50
no or barely any eyelashes (PRO score of 3), 5.8% reported patients with FFA, eyelash loss was observed clinically in
having large gaps or thinning (PRO score of 2), and 18.4% 17 patients (34%), but in 32 patients (64%) with trichoscopy,
reported minimal gaps or thinning (PRO score of 3) [25]. underscoring its utility for early detection of eyelash involve-
Frontal fibrosing alopecia (FFA) is a cicatricial alopecia ment [26]. Eyelash loss is an independent predictor of FFA
that leads to loss of frontoparietal hair, bilateral eyebrows severity (95% CI 1.74–8.59; P = 0.001) [36].
in up to 96% of patients, and eyelashes in up to 34% of Newly proposed criteria set forth by the International
patients [26]. Eyebrow loss often begins on the lateral eye- FFA Cooperative Group recommend diagnosis based on
brow (Fig. 2a–b), with subsequent thinning, partial, or com- the presence of 4 or more points from a list of clinical and
plete loss [27]. Although eyebrow loss is a common feature pathologic findings typical of FFA [37]. The presence of at

Table 1  Common etiologies, presenting symptoms, trichoscopy, diagnosis, and treatment of eyebrow and eyelash alopecia

Etiology Eyebrow and eyelash presentation Eyebrow trichoscopy Eyelash trichoscopy Treatment

Alopecia areata Patchy eyebrow loss bilaterally Exclamation mark hairs are not very Exclamation mark hairs, cadaverized Eyebrows: no standard treatment. Success-
Bilateral patchy eyelash loss in upper numerous. Cadaverized hairs, yellow hairs, yellow dots ful reported treatments include barici-
and lower lids dots, and black dots [20] are usually tinib 4 mg/day [82], ILTA 2.5 mg/mL
visible (0.5 mg to each eyebrow) [81], topical
tofacitinib 2% gel twice daily [84], oral
tofacitinib 15 mg (case reports) [121,
122], pulsed diode laser at 904 nm (case
report) [87]
Eyelashes: no standard treatment. Suc-
cessful reported treatments include
baricitinib 4 mg/day [82], bimatoprost
0.03% solution once daily [88], topical
tofacitinib 0.005% eye drops once daily
[84]
Frontal fibrosing alopecia Non-scarring alopecia starting on the Tapered and broken hairs, hair growing Dystrophic hairs, black dots, hair bulbs Eyebrows: no standard treatment. Success-
lateral eyebrow in different directions, black, red, or typically on the upper eyelids, and ful reported treatments include light-
Regrowth of eyelash hair in different yellow dots, dystrophic hairs, pili torti, ingrown hairs [26] emitting diodes (630 ± 5 nm) [31], ILTA
directions [26] and white areas of skin lacking follicu- 2.5 mg/mL monthly [96], finasteride
lar openings [31, 32] 2.5 mg/day (case series) [123], topical
bimatoprost 0.03% solution (case series)
[94], low dose oral minoxidil (case
series) 95
Eyelashes: no standard treatment
Keratosis follicularis spinulosa Scarring alopecia of the eyebrows pre- Yellow dots and dystrophic hairs [45] Yellow dots and dystrophic hairs [45] No standard treatment. Successful reported
decalvans senting as sparse eyebrows treatments include dapsone (100 mg/day)
Sparse eyelashes and topical corticosteroids to decrease
inflammation (case report) [124], topical
emollients and keratolytics to improve
skin texture (case report) [45]
Leprosy Loss of eyebrows and eyelashes bilater- Reduced hair density, multiple vellus Not reported Multiple-drug therapy with dapsone,
ally in approximately 9.3–36.5% of hairs, pigment distortion, targetoid rifampin, and clofazimine can be used
patients [47, 48] pigmentation, pinpoint white dots, to treat leprosy, but eyebrow regrowth is
and white-yellowish areas lacking exceptional [50]
structures [49]
Tinea faciei/blepharo-ciliaris Pink to red scaly, inflammatory patches Comma hairs, corkscrew hairs, bent Scaling, broken hairs, bent hairs, and Topical antifungals ± oral terbinafine or
and plaques over eyebrows hairs, morse code hairs, zigzag hairs morse code hairs [57] oral itraconazole (case report) [57]
Itchy erythematous patch involving the [56]
eyelid and broken eyelash hairs [57]
Trichotillomania Isolated eyebrow hair loss without Black dots, broken hairs at different Broken hairs of different length, espe- Psychotherapy [105]
erythema lengths, hook hairs, tulip hairs, and the cially in the longer eyelashes [72, 74]
Isolated alopecia only upper or lower V sign [73]
eyelashes rather than both [74]
B. Nguyen et al.

ILTA intralesional triamcinolone acetonide


Eyebrow and Eyelash Alopecia: A Clinical Review

Fig. 2  a, b Patient with frontal fibrosing alopecia presenting with bilateral eyebrow loss on the lateral eyebrow. c Trichoscopy findings of eye-
brow frontal fibrosing alopecia include hair growing in different directions and yellow dots (arrow)

least 50% eyebrow loss in the absence of AA accounts for reported as an isolated symptom occurring prior to the
1 point, whereas a positive biopsy of the affected anterior onset of erythema, scaly plaques, and scarring alopecia
or temporal scalp or eyebrow contributes 2 points toward of the scalp [42].
the diagnosis (Table 1) [37].
Localized scleroderma is a disorder of excessive col- 4.2 Endocrine
lagen deposition that can present as unilateral atrophy of
the frontoparietal region above the eyebrow. Known as “en Hypothyroidism can present with loss of the lateral third
coup de sabre” (French for “the blow of the sword”) for its of the eyebrow (i.e., Hertoghe sign or Queen Anne’s sign),
resemblance to the scar of a sword wound, linear morphea which is a classic, but nonspecific sign of hypothyroidism.
of the paramedian forehead and scalp can be accompanied Severe hypothyroidism has also been reported to present
by eyebrow depression and hair loss [38]. In a case review with eyelash alopecia [43].
of 50 pediatric patients with localized scleroderma, eye-
brow and eyelash loss occurred in 4% and 12% of patients, 4.3 Genetic
respectively [39].
Discoid lupus erythematosus (DLE) is an autoimmune Keratosis follicularis spinulosa decalvans (KFSD) is an
disorder that can uncommonly present with erythema and X-linked disorder of keratinization that causes follicu-
scaly plaques on the bilateral or, rarely, unilateral eye- lar hyperkeratosis and scarring alopecia of the eyebrows,
lids, with a predilection for the lower and lateral eyelids eyelashes, and scalp. The disease typically begins on the
[40, 41]. In one case report, loss of eyelashes has been face and presents as sparse eyebrows and eyelashes, but can
B. Nguyen et al.

also ultimately cause ophthalmic abnormalities including code hairs (Table 1) [57]. With adequate trichoscopy and/or
blepharitis, conjunctivitis, and photophobia [44]. Trichos- clinical findings, empiric treatment with topical and/or oral
copy of eyebrows and eyelashes can show yellow dots and antifungals can be initiated prior to culture results.
dystrophic hairs [45]. Other uncommon genetic causes of Viral infections: Varicella zoster virus (VZV) can infect
madarosis and their presentations are listed in Table 2. the ophthalmic division of the trigeminal nerve, and reacti-
vation of VZV can cause scarring of the eyelid [58]. A few
4.4 Infectious cases have reported unilateral loss of upper lid eyelashes
related to VZV [59, 60]. Though exceedingly rare, madarosis
Lepromatous leprosy may interfere with hair growth, leading has also been reported in HIV [61].
to eyebrow and eyelash loss early in the disease, preceding
the characteristic development of leonine facies [46]. Eye- 4.5 Neoplastic
brow and eyelash loss bilaterally is seen in approximately
9.3–36.5% of patients with lepromatous leprosy [47, 48]. Neoplastic conditions, particularly hematologic malignan-
In a cross sectional study of 23 patients, trichoscopy find- cies, have been associated with eyebrow alopecia, although
ings included reduced hair density, multiple vellus hairs, most of this information is limited to reports of isolated
and distorted pigmentation of skin [49] (Table 1). Treatment cases. One such report describes an adult patient who
did not produce regrowth of eyebrows in these patients, but developed eyebrow alopecia in the setting of mycosis fun-
eyebrow regrowth has been reported in one case report after goides, and histopathology showed a folliculotropic infil-
two months of treatment [50]. trate of atypical lymphocytes sparing the epidermis [62].
Cutaneous syphilis may also result in patchy alopecia of Another report described a 56-year-old female with a history
the scalp, beard, eyebrows, and eyelashes [51]. Eyebrow loss of chronic lymphocytic leukemia (CLL) with infiltrates to
occurs during the secondary stage of syphilis and typically the skin (i.e., leukemia cutis) presenting with erythematous
affects the lateral side of the eyebrows, known as the “omni- papules and bilateral eyebrow alopecia [63]. Rarely, eye-
bus sign” [52, 53]. brow loss may also be secondary to the presence of primary
Tinea faciei, tinea blepharo-ciliaris, and periocular tinea cutaneous tumors, such as one case of madarosis associated
are ringworm infections of the face, eyelids and eyelashes, with pleomorphic adenoma [64].
and eyelids only, respectively. Caused by Microsporum, Chemotherapeutic agents used to treat neoplastic condi-
Trichophyton, or Epidermophyton species, fungal infections tions can also contribute to madarosis. In particular, agents
may result in partial unilateral or bilateral hair loss of the such as taxanes, doxorubicin, and cyclophosphamide have
eyebrows and eyelashes [54, 55]. Trichoscopy of affected been seen to cause hair loss approximately 1 week to 1
eyebrows may show comma hairs (51%), corkscrew hairs month after initiation [65]. In an observational study of
(32%), bent hairs (27%), morse code hairs (22%), and zigzag 68 cancer patients treated with fluorouracil/epirubicin/
hairs (22%) (Table 1) [56]. Trichoscopy of the eyelashes cyclophosphamide (FEC) and taxane, eyebrow and eyelash
reveals widespread scale, broken hairs, bent hairs, and morse loss were reported in 56 patients (82.4%) and 53 patients

Table 2  Uncommon genetic causes of madarosis and their presentations


Disorder Clinical presentation Hair symptoms

T cell immunodeficiency, congenital alopecia, Pitted, curved, or ridged nails Loss of scalp, eyebrow, and eyelash hair
and nail dystrophy (TIDAND) [125–127]
Ectodermal dysplasia [128, 129] Abnormalities in tissues derived from ectoderm Sparse eyebrows
(e.g., hair, teeth, nails, lens or retina of eyes,
inner ears, fingers, and toes)
Graham–Little–Piccardi–Lassueur syndrome Triad of cicatricial scalp alopecia, loss of pubic Non-scarring eyebrow and eyelash thinning
(GLPLS) [130] and axillary hairs, and follicular papules
Hereditary hair loss [131] No other symptoms Thin eyebrows
Inherited biotinidase deficiency [132] Erythroderma of the trunk, face, and scalp Eyebrow alopecia
Lamellar ichthyosis [133] Dark scales with erythema, fissuring, pruritis of Eyebrow and eyelash loss
the skin
(Nonbullous) congenital ichthyosiform erythro- Finer white scale and underlying redness of skin Scarring alopecia of scalp and eyebrows
derma [134]
Vogt–Koyanagi–Harada (VKH) disease [135, Ocular problems (e.g., blurred vision, cho- Depigmentation of the scalp, eyebrows,
136] roiditis, retinal detachment), vertigo, tinnitus, and eyelashes in chronic cases
neurologic symptoms
Eyebrow and Eyelash Alopecia: A Clinical Review

(77.9%), respectively [65]. Younger patients may regrow


hair sooner, suggesting a potential linear association between
the patient’s age and time to recovery from chemotherapy-
induced alopecia of the eyebrow and eyelash [65]. Eyebrow
and eyelash hair loss has been reported to be permanent in
approximately 5% of cases, and patients should be informed
of this risk prior to chemotherapy initiation [66]. Endocrine
therapy-induced hair loss, due to usage of medications such
as selective estrogen receptor modulators and aromatase
inhibitors, can also present with alopecia of eyebrows and
eyelashes. In a retrospective cohort study of women taking
endocrine therapies who developed alopecia, 28.3% (26/92)
had involvement of eyebrows or eyelashes [67].
Additionally, radiation therapy for ocular tumors has also
been reported to cause reversible madarosis by triggering Fig. 3  Patient with trichotillomania presenting with irregular, patchy
alopecia of the eyebrow, with hair shafts of varying lengths, promi-
hair loss in the anagen stage [9, 68]. In a retrospective review nently visible hair follicles, and eyelash alopecia limited to eyelashes
of 63 patients with ocular tumors, madarosis was a compli- of the upper lid
cation in 28.6% (10/35) of eyes treated with proton beam
radiation [68]. At high doses of radiation (typically 50–60
Gy), eyebrow loss may be permanent due to damage to the 4.8 Primary Dermatoses
epithelial stem cells or dermal papilla [9].
Atopic dermatitis can present with loss of the lateral third
4.6 Nutritional of the eyebrows (Hertoghe sign) in up to 39% of patients,
as well as eyelid dermatitis, though involvement of more
Nutrient deficiency of zinc has been reported to cause eye- than just the lateral third of the eyebrow is possible [76].
brow and eyelash alopecia. Sparse eyebrows and hair sec- Although alopecia can be caused by chronic rubbing, eye-
ondary to zinc deficiency has been reported in a patient on brow loss has also occurred in patients without a history of
parenteral nutrition [69]. Acrodermatitis enteropathica, an eyebrow manipulation [77]. It is hypothesized that inflam-
inherited disorder of abnormal zinc absorption, has also mation may itself be responsible for the alopecia.
been shown to cause diffuse eyebrow and eyelash loss [70]. Another primary dermatosis, seborrheic dermatitis, can
cause madarosis that presents as scaling and erythema of the
eyebrows. Eyebrow loss can be a result of repeated scratch-
4.7 Traumatic ing due to pruritis [78]. Trichoscopy often reveals casts sur-
rounding the eyelashes [79].
Causes of eyebrow and eyelash loss from trauma include Psoriasis can cause inflammation of the eyelids (i.e.,
trichotillomania, or hair loss from repetitive pulling or over- blepharitis) and psoriatic plaques, and severe cases of eyelid
plucking of hair. Trichotillomania can present clinically as psoriasis can cause loss of eyelashes [80].
irregular, patchy alopecia of the eyebrows and/or eyelashes,
with hair shafts of varying lengths (Fig. 3) [71]. Eyebrow
and/or eyelash hairs may be nonuniform, tufted, or tortuous, 5 Treatments
and hair follicles may be prominently visible [72]. Trichos-
copy shows broken hairs of different lengths, black dots, 5.1 Autoimmune
hook hairs, tulip hairs, and the V sign [73]. Eyelash alope-
cia is typically limited to the longer eyelashes of the upper AA: Topical and intralesional steroids have long been uti-
eyelid [72, 74]. Patients may state that the eyelashes bother lized for eyebrow alopecia. Intralesional triamcinolone ace-
them when blinking, justifying removal of those eyelashes tonide (ILTA) (2.5 mg/mL; 0.5 mg to each eyebrow) can be
[75]. injected every 4–6 weeks for a maximum of 6 months [81].
Rarely, patients may present with eyebrow alopecia after Moderate potency topical corticosteroids and topical minox-
a burn injury with hot liquids or fire that may lead to forma- idil 5% can also be used on the eyebrows, though studies
tion of scar tissue below the brow. have not been conducted on the efficacy of these treatments.
The JAK inhibitor baricitinib was approved by the US
Food and Drug Administration (FDA) for treatment of
AA. In two randomized controlled phase 3 clinical trials
B. Nguyen et al.

of baricitinib for AA (BRAVE-AA1 and BRAVE-AA2), significant eyelash regrowth [89]. A similar lack of efficacy of
researchers randomly assigned a total of 1200 patients to latanoprost was seen in other experimental studies [90, 91].
receive 4 mg baricitinib, 2 mg baricitinib, or placebo for FFA: In a retrospective chart review of FFA cases, ILTA
36 weeks and assessed eyebrow and eyelash outcomes at 10 mg/mL, 0.125 mL per eyebrow, was injected at varying
using the ClinRO [82]. Of 188 and 161 patients taking 4 time intervals and numbers of sessions in ten patients with
mg baricitinib with reported eyebrow outcomes, 35.2% and partial eyebrow loss and one with complete eyebrow loss
38.9% experienced a terminal score of 0–1 (full coverage [92]. Signs of eyebrow regrowth at 2- to 6-month follow-up
or minimal gaps) and a reduction (improvement) in ClinRO visits were found in all patients with partial eyebrow loss (10
eyebrow score of at least 2 points from baseline, compared of 11 patients) [92]. Notably, 20 patients with eyebrow loss
to 4.4% and 5.5% in the placebo group, respectively (p < related to FFA who did not receive ILTA injections did not
0.001) [82]. In 167 and 140 patients taking 4 mg baricitinib experience eyebrow regrowth [92]. A single case report also
compared to placebo for 36 weeks with reported eyelash found eyebrow regrowth with oral dutasteride (0.5 mg/day)
outcomes, 36.2% and 36.8% experienced a terminal score and pimecrolimus 1% cream twice a day [93]. Other possible
of 0–1 and a reduction in ClinRO eyelash score of at least 2 treatments of eyebrow loss in FFA include topical prosta-
points from baseline, compared to 4.4% and 6.9% in the pla- glandin analogs and oral minoxidil. In one study of three
cebo group, respectively (p < 0.001) [82]. Although results patients with eyebrow loss refractory to topical minoxidil and
suggest that baricitinib holds promise in treating eyebrow clobetasol lotion, application of topical bimatoprost ophthal-
and eyelash AA, these clinical trials excluded patients who mic solution 0.03% twice daily for 9 months resulted in eye-
previously had an inadequate response to oral JAK inhibitors brow regrowth in two of three patients who had non-scarring
and patients who had an episode of at least 8 years without features on dermoscopy [94]. In a case series of seven FFA
hair regrowth, limiting the generalizability of results [82]. patients treated with oral minoxidil (0.5–2.5 mg/day) for 6
Use of other JAK inhibitors have also shown promising months, partial eyebrow regrowth was observed in five of
results for eyebrow and eyelashes. In a retrospective study seven and almost complete regrowth in two of seven [95].
including 119 patients treated with tofacitinib for AA, complete Usage of laser therapy has been reported to effectively
eyebrow and eyelash regrowth were achieved in 34.5% (41/119) result in eyebrow regrowth, though studies with high-quality
and 38.7% (46/119) of patients, respectively, after treatment for evidence are lacking. In one study of 16 patients with FFA,
≥ 6 months [83]. Topical tofacitinib 2% gel twice daily for the there was a significant increase in total eyebrow hair count
eyebrows and 0.005% eye drops once daily for eyelashes have after ten treatments with light-emitting diodes (LEDs) at
also been shown to be efficacious, resulting in partial or com- 630 ± 5 nm [31]. Treatment should be initiated as early as
plete regrowth of 66.7% (12/18) of cases of eyebrow AA and possible, as results range from diminished response to no
100% (4/4) of cases with eyelash AA [84]. Complete regrowth response in patients with complete eyebrow loss [96, 97].
of upper eyelashes in localized AA have also been achieved Patients with severe scarring alopecia of the eyebrow may
with tofacitinib 2% solution applied to the upper eyelid once require hair transplantation, although the presence of scar
to twice daily for 7 months [85]. Fewer studies have been con- tissue may impair graft uptake and hair growth. In a cohort
ducted on ruxolitinib, though one patient has been reported study, eight out of ten patients with FFA showed initial
to experience complete eyebrow regrowth after 12 weeks of hair growth and satisfactory results after hair transplanta-
treatment with topical 0.6% ruxolitinib cream [86]. tion using unaffected follicles harvested from the occipital
Successful use of other novel treatments has been region, but transplanted hairs were lost after 3–4 years in all
reported in small uncontrolled studies, though these treat- but one patient [98].
ments are not standard of care. In a clinical trial of three In localized scleroderma, one successful case of eyebrow
patients with recalcitrant eyebrow AA, four sessions of treat- reconstruction using follicular unit transplantation has been
ment with a pulsed diode laser at 904 nm resulted in com- reported [99].
plete eyebrow regrowth of five out of six eyebrow patches In DLE, early diagnosis and treatment with oral hydroxy-
[87]. Although excimer lasers (308 nm) have successfully chloroquine are important to prevent scarring and permanent
resolved scalp patches of AA, no studies have been con- eyelash loss [41].
ducted on eyebrows or eyelashes.
Of the prostaglandin analogs, bimatoprost is a commonly 5.2 Endocrine
utilized treatment. In one study of 41 subjects with alopecia
universalis (AU), application of topical 0.03% bimatoprost to Hypothyroidism: Adequate treatment of hypothyroidism has
the eyelid margin once daily for a year led to slight, moder- been reported to restore normal telogen-anagen hair propor-
ate, or complete eyelash growth in about 70.3% of patients tions in one small study of nine patients [100], though the
[88]. However, in another study of 26 AA patients, application response of eyebrow alopecia to thyroxine treatment has not
of topical latanoprost for 4 months did not show statistically been well documented.
Eyebrow and Eyelash Alopecia: A Clinical Review

5.3 Genetic micrograft using FUE technique, with eyebrow hairs as the


donor site, has also been successfully conducted for trau-
There are no specific treatments for eyebrow or eyelash alo- matic madarosis of the upper and lower eyelid in one case
pecia from KFSD. Ophthalmologic referral is important to report [108].
prevent eye complications.
5.8 Primary Dermatoses
5.4 Infectious
In atopic dermatitis, treatment with emollients and topi-
Treatment of infectious diseases results in varying outcomes cal corticosteroids have been reported to result in partial
for eyebrow and eyelash alopecia, though current data relies eyebrow regrowth in one case report [77]. Partial eyebrow
on smaller uncontrolled studies. Treatment of lepromatous regrowth was also observed in one patient treated with sub-
leprosy has not been reported to result in eyebrow regrowth cutaneous dupilumab [109].
[49] except in an isolated case report with one patient who Seborrheic dermatitis is associated with colonization
was treated with dapsone, rifampin, and clofazimine for 2 with Malasezzia spp., and treatment with a topical antifun-
months [50]. Patients with leprosy should be treated with gal, low-potency corticosteroid cream, or topical calcineurin
this standard-of-care regimen regardless of eyebrow involve- inhibitor to the eyebrows has been found to be both safe and
ment. In syphilis, timely treatment with benzathine penicillin effective [110, 111].
G has been reported to result in complete eyebrow regrowth
in two case reports [51, 101]. Eyebrow and eyelash alopecia 5.9 Other
due to tinea faciei has been reported to be reversible after
treatment with topical and/or oral antifungals in two case Because eyelash follicles express prostaglandin F2α recep-
reports [54, 102]. tors, prostaglandin analogs can affect their growth.
­LATISSE® (bimatoprost ophthalmic solution 0.03%) once
5.5 Neoplastic daily was approved by the US FDA in 2008 for eyelash
hypotrichosis and has been shown to increase eyelash pig-
The most promising treatment for chemotherapy-induced mentation, length, and thickness [112].
eyelash alopecia is topical bimatoprost. In a clinical trial In one randomized controlled trial including 357 patients
of 96 patients who were treated with chemotherapy, usage with idiopathic or unspecified eyebrow loss, the efficacy of
of topical bimatoprost 0.03% on the eyelashes for 6 months topical bimatoprost 0.03% applied once or twice daily was
after chemotherapy resulted in significantly longer upper compared to a non-medicated control [113]. Improvements
eyelash length, thickness, and darkness (p = 0.02, < 0.01, in eyebrow fullness and thickness were noted in both bimato-
and < 0.01, respectively) [103]. prost groups when compared to the control (p < 0.001)
[113]. Another randomized trial with 39 participants used
5.6 Nutritional 2% minoxidil lotion applied to the eyebrows twice daily for
16 weeks and found significant improvement in both global
In a patient with chronic diarrhea due to sucrase deficiency, photographic scores and hair count with the use of minoxidil
supplementation with oral zinc was reported to result in when compared to vehicle [114].
growth of thicker and more pigmented eyebrow and eye- Cosmetic treatments for eyebrow and eyelash alopecia
lashes in one case report [104]. include topicals to help regrow hairs such as copper pep-
tides, as well as techniques to camouflage hair loss such as
5.7 Traumatic microblading, microshading, and tattooing. In a cohort study
of six patients, daily application of a peptide solution to the
As no pharmacologic therapy has been FDA-approved for eyebrows and eyelashes for 12 weeks significantly increased
trichotillomania, the mainstay treatment remains psycho- eyelash length (p = 0.014) and clinically improved eyebrow
therapy [105]. N-acetylcysteine (NAC), a glutathione and thickness on digital photography [115].
glutamate modulator, at a dosage of 1200–1800 mg/day has Microblading is a semi-permanent tattooing technique
been used to treat scalp trichotillomania, but there are no that utilizes small needles to deposit pigment superficially
reports of its efficacy in treating eyebrow and eyelash tri- in the epidermis and papillary dermis to create an illusion of
chotillomania [106]. eyebrow hairs [116]. Using a similar technique, microshad-
Hair transplantation by follicular unit extraction (FUE) ing is the process of depositing pigmented dots throughout
has been successfully performed for eyebrow alopecia from the eyebrow to create the appearance of eyebrow makeup.
burn injury using pretreatment with combined non-ablative Microblading and microshading result in fuller-appearing
fractional laser (NAFL) and microfat injection [107]. A strip eyebrows for 12–18 months. Due to loss of superficially
B. Nguyen et al.

deposited pigment over time, the procedure needs to be Author contributions  All authors contributed to the study concep-
repeated at regular time intervals [116]. tion and design. Data collection was performed by all authors. All
authors contributed to writing the manuscript and have approved the
Eyebrow tattooing presents more permanent effects by final manuscript.
depositing tattoo ink deeper into the dermis [117]. Due to
deposition of foreign bodies, tattooing causes an inflamma- Data availability  The data supporting the findings of this study are
tory reaction that can be seen as lymphocytic infiltrate in the available from the corresponding author upon reasonable request.
dermis on histopathology [118]. In a study of 28 patients Ethics approval  Not applicable.
undergoing blepharoplasty, histopathologic analysis of
excised upper eyelid tissue revealed significant dermal fibro- Consent to participate  Not applicable.
sis in patients with eyebrow tattoos compared to those with-
Code availability  Not applicable.
out (p = 0.02) [119]. Ultrasonography of this tissue before
excision also revealed increased soft tissue thickness in
patients with eyebrow tattoos (p < 0.001) [119]. In addition Open Access  This article is licensed under a Creative Commons Attri-
bution-NonCommercial 4.0 International License, which permits any
to these local skin reactions, other risks are involved. The non-commercial use, sharing, adaptation, distribution and reproduction
US FDA has investigated the safety of permanent tattooing in any medium or format, as long as you give appropriate credit to the
and has found complications including infections, allergic original author(s) and the source, provide a link to the Creative Com-
reactions, and formation of granulomas and keloids [120]. mons licence, and indicate if changes were made. The images or other
third party material in this article are included in the article's Creative
Although permanent tattooing is an option for camouflaging Commons licence, unless indicated otherwise in a credit line to the
eyebrow madarosis, patients should be properly counseled material. If material is not included in the article's Creative Commons
on risks associated with this treatment. licence and your intended use is not permitted by statutory regula-
tion or exceeds the permitted use, you will need to obtain permission
directly from the copyright holder. To view a copy of this licence, visit
http://​creat​iveco​mmons.​org/​licen​ses/​by-​nc/4.​0/.
6 Conclusion

Eyebrow and eyelash alopecia have many different etiolo-


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