Eyebrow and Eyelash Alopecia A Clinical Review
Eyebrow and Eyelash Alopecia A Clinical Review
Eyebrow and Eyelash Alopecia A Clinical Review
https://doi.org/10.1007/s40257-022-00729-5
REVIEW ARTICLE
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.
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
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.
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
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
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
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-
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6 Conclusion
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